Ankur Sangoi

All Publications

• High-Grade Early-Onset Prostate Cancer: Assessment of TMPRSS2::ERG-Negative Tumors Suggests Low Frequency of Germline Alterations and a Pathogenic Role for HOXB13. The American journal of surgical pathology Maharjan, D., Siegmund, S., Michalova, K., Odintsov, I., Hornick, J. L., Nair, V., Idrees, M. T., Collins, K., Gordetsky, J. B., Osunkoya, A. O., Cheng, L., Miyamoto, H., Sangoi, A. R., Wu, D. J., Ricci, C., Mollica, V., Raspollini, M. R., Contreras, F., Bernal, M. P., Fernandez, I. M., Rodriguez, A., Lobo, A., Mohanty, S. K., Sharma, S., Goksel, M., Acosta, A. M. 2025

  Abstract

  Early onset prostate cancer (EOPC; defined herein as prostate cancer [PCa] affecting men ≤ 55 years-old) tends to show low histologic grade, likely representing early detection of indolent tumors that would otherwise be diagnosed later in life. A small subset of EOPC exhibits Gleason scores consistent with high-risk disease (Grade Groups 4 to 5; high-grade EOPC [HG-EOPC] hereafter). In this study, we assess the clinicopathologic features of HG-EOPC, with genomic analysis of ERG-negative cases. We assessed HG-EOPC using immunohistochemistry for ERG (as a surrogate marker of TMPRSS2::ERG), PMS2 (as a surrogate marker of MLH1/PMS2 inactivation), and MSH6 (as a surrogate marker of MSH2/MSH6 inactivation). Selected ERG negative cases were assessed using Oncopanel, which interrogates 447 genes, including PCa-relevant genes. Ninety-six samples from 96 individual patients (median age: 52 y; range: 40 to 55 y) were included in the study. Immunohistochemical staining with ERG was performed in 95 cases, 52 (54%) of which showed negative staining. PMS2 was performed in 93 cases, being retained in 92 (98.9%) and lost in 1 (1.1%). MSH6 was performed in 96 cases, being retained in 92 (95.8%), lost in 2 (2.1%), and equivocal in 2 (2.1%). Sequencing of 23 ERG-negative primary tumors showed enrichment for alterations that are typically associated with castration resistance, including loss of 8p (>50%), gains of 8q (>50%), and inactivation of CDK12 (n=4). The cohort also showed a relatively high frequency of pathogenic TP53 (n=7) and SPOP (n=4) variants. Pathogenic BRCA2 variants and mismatch repair deficiency were identified in 1 case each. Interestingly, >50% of the tumors showed HOXB13 amplification. In conclusion, TMPRSS2::ERG fusion-negative HG-EOPC shows a high frequency of genomic alterations typically enriched in castration-resistant neoplasms but variants of potential germline origin (including those in mismatch repair genes) are rare. These results demonstrate that HG-EOPC is driven largely by somatic events.

  View details for DOI 10.1097/PAS.0000000000002459

  View details for PubMedID 40745946

• Invasive urothelial carcinoma with chordoid and myxoid features shows increased RAS/RAF pathway alterations. Human pathology Chan, E., Stohr, B. A., Sangoi, A. R., Sirohi, D. 2025: 105882

  Abstract

  Invasive urothelial carcinoma (UCa) with chordoid and myxoid features is an uncommon but previously described subtype of UCa composed of distinctive elongated nests and cords of tumor cells floating within a prominent myxoid stroma. The molecular features of chordoid and myxoid UCa are not known. We identified 9 cases of UCa with chordoid and myxoid features and performed a comprehensive next generation sequencing assay, targeting the chordoid and myxoid component. The cases included 7 TURBT and 2 nephroureterectomies in which chordoid/myxoid component ranged from 10-80% (mean 47%). Available immunohistochemistry in the chordoid and myxoid component showed p63+ (9/9) and GATA3+ (8/9), supporting UCa. All cases were largely negative for SOX10 and CDX2 (one case showed weak CDX2 staining). On molecular analysis, chordoid and myxoid UCa showed a molecular profile typical of conventional UCa, with recurrent alterations in TERTp (7/9), chromatin remodeling genes (8/9) and cell cycle pathway genes (8/9). A high rate of DNA damage repair gene alterations was also seen (6/9). Interestingly, 5/9 cases demonstrated recurring alterations in RAS/RAF genes, typically more frequently seen in primary adenocarcinomas of the urinary bladder and less common in conventional UCa, suggesting possible alternative therapies for these patients. In conclusion, chordoid and myxoid UCa shows a genomic profile with both urothelial and adenocarcinoma features. Furthermore, the molecular profile reveals potentially actionable therapeutic targets in the RAS/RAF and DNA damage repair pathways and high tumor mutational burden.

  View details for DOI 10.1016/j.humpath.2025.105882

  View details for PubMedID 40752735

• Collision of Presumed Primary Urinary Bladder Malignant Melanoma and Invasive Urothelial Carcinoma: A Case Report. International journal of surgical pathology Cheng, A. V., Bardell, J., Sangoi, A. R. 2025: 10668969251358376

  Abstract

  "Collision tumors" are a phenomenon that occur when two neoplasms concomitantly localize next to each other. Malignant melanoma of the bladder is an uncommon entity with less than 40 reported instances and is exceedingly rare to present as a collision tumor. In this report, we present a collision tumor consisting of a primary bladder malignant melanoma and invasive high-grade papillary urothelial carcinoma. The clinical presentation and cytomorphologic, immunophenotypic, and molecular findings of this tumor are depicted. Additionally, we also briefly discuss an overview of cutaneous versus mucosal melanomas, focusing on those reported in the genitourinary tract. To the best of our knowledge, this is the second report in literature of a collision between malignant bladder melanoma and urothelial carcinoma occurring in the bladder and the first to involve an invasive urothelial carcinoma.

  View details for DOI 10.1177/10668969251358376

  View details for PubMedID 40717603

• Interobserver Reproducibility of Pelvicalyceal Invasion in Renal Cell Carcinoma Nephrectomies Among Genitourinary Pathologists. The American journal of surgical pathology Sangoi, A. R., Akgul, M., Mubeen, A., Humble, R., Wu, D. J., Pacheco, R., Acosta, A., Amin, M., Aron, M., Brimo, F., Chan, E., Cheng, L., Cheville, J., Collins, K., Cornejo, K., Dhillon, J., Downes, M. R., Epstein, J. I., Hirsch, M., Kapur, P., Lobo, A., Mehra, R., Mohanty, S., Netto, G., Osunkoya, A. O., Paner, G., Rao, P., Saleeb, R., Shah, R. B., Shen, S., Smith, S., Tickoo, S., Tretiakova, M., Trpkov, K., Wobker, S., Tamboli, P., Zynger, D., Williamson, S. R. 2025

  Abstract

  Pelvicalyceal invasion (PCI) is a relatively novel pT3a staging parameter for renal cell carcinoma (RCC) nephrectomies. While interobserver reproducibility staging studies of sinus/vascular invasion in RCC exist, a similar evaluation for PCI has not been performed. Moreover, in our experience, there is also diagnostic variability in how pathologists interpret PCI. Herein, we explore interobserver reproducibility among genitourinary (GU) pathologists. Twenty hematoxylin and eosin-stained digitized slides from RCCs (all grossly approaching the renal pelvis) were distributed to 31 GU pathologists to classify each as PCI or not PCI based on their respective clinical practices; slides with concomitant sinus/fat/vascular invasion were excluded. Slides were then evaluated for the following 4 morphologic features: tumor abutting renal pelvis, tumor pushing/indenting into the renal pelvis, polypoid configuration of tumor into the renal pelvis, and tumor eroding through renal pelvic urothelium. Interobserver reproducibility was assessed, and the morphologic features were correlated with PCI. Relationships between pathologists' interpretations, morphologic features, and PCI were evaluated using hierarchical clustering. Although the diagnosis of PCI was relatively uniform with a majority agreement (>67%) reached in 16/20 slides, overall interobserver reproducibility was only moderate (kappa=0.601). While all 4 morphologic features were sensitive for PCI, polypoid configuration of the tumor into the renal pelvis and the tumor eroding through the renal pelvic urothelium were most specific (90%, 100%, respectively). Although we show general consensus among genitourinary pathologists on PCI assessment, clarifying the diagnostic guidelines with specific criteria should be included in pathologic staging systems.

  View details for DOI 10.1097/PAS.0000000000002456

  View details for PubMedID 40734292

• Correction to: Succinate dehydrogenase defcient renal cell carcinoma frequently expresses GATA3 and L1CAM. Virchows Archiv : an international journal of pathology Sangoi, A. R., Williamson, S. R., Oktay, M., Gill, A. J., Trpkov, K., Siadat, F., MacLean, F., Galea, L. A., Baydar, D. E., Cakir, C., Karabulut, Y. Y., Baycelebi, D., Coban, G., Sarsik, B., Bayrak, B. Y., Kuthi, L., Posfai, B., Mobeen, A., Mohanty, S. K., Zhang, X., Alghamdi, M. A., Cheng, L., Hirsch, M. S., Akgul, M. 2025

  View details for DOI 10.1007/s00428-025-04194-3

  View details for PubMedID 40711546

• Loss of expression of STK11/LKB1 in intratubular large cell hyalinizing Sertoli cell neoplasm HISTOPATHOLOGY Anderson, W. J., Kolin, D. L., Gonzalez, I. A., Vargas, S. O., Gonzalez-Peramato, P., Cornejo, K. M., Maclean, F., Sangoi, A. R., Colecchia, M., Hirsch, M. S., Ulbright, T. M., Acosta, A. M. 2025

  View details for DOI 10.1111/his.15513

  View details for Web of Science ID 001529840400001

• Interobserver reproducibility of hilar soft tissue invasion in testicular germ cell tumours among genitourinary pathologists. Histopathology Wu, D. J., Akgul, M., Williamson, S. R., Pacheco, R., Acosta, A., Al-Obaidy, K., Amin, M., Berney, D., Brimo, F., Cheng, L., Colecchia, M., Comperat, E., Cornejo, K., Dhillon, J., Downes, M., Epstein, J. I., Hirsch, M. S., Jimenez, R., Kaushal, S., Lobo, A., Lopez-Beltran, A., Mehra, R., Mohanty, S. K., Paner, G., Rao, P., Reuter, V., Shah, R. B., Shen, S., Smith, S., Tretiakova, M., Trpkov, K., Wobker, S. E., Tamboli, P., Zynger, D., Sangoi, A. R. 2025

  Abstract

  AIMS: Compared to lymphovascular invasion (LVI), hilar soft tissue invasion (HSTI) is a relatively novel pT2 staging parameter in testicular germ cell tumours (GCT), associated with metastasis at the time of diagnosis and a risk factor for disease relapse. Given diagnostic variability in how pathologists interpret HSTI, herein we explore interobserver reproducibility among genitourinary (GU) pathologists.METHODS: Twenty haematoxylin and eosin-stained digitized slides from testicular GCTs were distributed to 30 GU pathologists to classify each as HSTI or not HSTI based on their respective clinical practices; slides with concomitant LVI were excluded. Slides were then evaluated for the following morphologic features: tumour invasion beyond prominent hilar vessels, tumour invasion beyond the rete, tumour invasion beyond the level parallel to hilar adipose tissue and tumour within (directly touching) hilar adipose tissue. Interobserver reproducibility was assessed, and the morphological features were correlated with HSTI. Relationships between pathologists' interpretations, morphological features and HSTI were evaluated using hierarchical clustering.RESULTS: Although the diagnosis of HSTI was relatively uniform with a majority agreement (>67%) reached in 17/20 slides, overall interobserver reproducibility was only moderate (kappa=0.50). Morphological features such as invasion beyond the level parallel to hilar adipose tissue and invasion into fat were more sensitive and specific for HSTI, while features such as invasion beyond hilar vessels and invasion beyond rete were less useful.CONCLUSIONS: These findings suggest that more specific defined diagnostic criteria for testicular GCT HSTI are needed.

  View details for DOI 10.1111/his.15504

  View details for PubMedID 40611804

• Myeloid sarcomas of the genitourinary tract: A multi-institutional study of sixteen tumors with review of literature. Pathology, research and practice Shafi, S., Mohanty, S. K., Williamson, S. R., Sharma, S., Akgul, M., Sangoi, A. R., Arora, S., Acosta, A. M., Panda, S. S., Mishra, S. K., Deshwal, A., Jha, S., Mallik, V., Lobo, A., Dixit, M., Kaushal, S., Quiroga-Garza, G., Cheng, L., Shana'ah, A., Parwani, A. V., Jaiswal, A. G., Dhillon, J., Biswas, G., Satturwar, S. 2025; 272: 156106

  Abstract

  Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myelogenous leukemia (AML). Leukemic involvement of the genitourinary (GU) tract is extremely rare with only 2-7 % of the reported MS cases involving the kidney or urinary system. Patients with urinary tract MS can present with signs and symptoms related to urinary tract obstruction, hematuria, or urinary retention. Despite its rarity, MS can be diagnosed correctly with the use of ancillary tests such as immunohistochemical (IHC), flow cytometry and/or molecular testing. Right diagnosis is essential for selection of appropriate therapy. We performed a retrospective multi-institution study of 16 cases of MS of GU tract reported between 2010 and 2024. Clinicopathological, IHC, flow cytometric and molecular data were analyzed. The average age of patients in our cohort was 38 years with a male: female ratio of 5.3:1. Most of the cases were in the bladder (13/16) followed by ureter (2/16) and kidney (1/16). All cases presented as a relapse of AML and hematuria was most common clinical presentation (60 % cases). The average size of tumor was 3.3 cm. Immunohistochemically, CD45, CD34, CD117, MPO were positive in all cases. FLT3- ITD and NRAS mutation was noted in 13.3 % respectively. 8/16 patients died of myeloid sarcoma. Our study provides a comprehensive largest-to-date case series of the extremely rare MS of the GU system. Most common location was bladder. All cases were correctly diagnosed using ancillary testing and showed poor prognosis with a high mortality rate (46.6 %).

  View details for DOI 10.1016/j.prp.2025.156106

  View details for PubMedID 40618426

• Pseudopapillary and micropapillary-like changes in classical renal angiomyolipoma: a multi-institutional series of 60 cases. Virchows Archiv : an international journal of pathology Tannous, E., Baycelebi, D., Sangoi, A. R., Pacheco, R. R., Alghamdi, M. A., Lightle, A. R., Al-Obaidy, K., Williamson, S. R., Cetin, Z., Korentzelos, D., Akgul, M. 2025

  Abstract

  Pseudopapillary- and micropapillary-like changes in classical renal angiomyolipoma (AML) are underappreciated morphologic patterns that in some instances may cause diagnostic confusion with renal cell carcinoma or urothelial carcinoma. To further evaluate the incidence of these morphologies, a multi-institutional cohort of 60 patients with classical AML was retrospectively analyzed by genitourinary pathologists. Clinicopathologic features include tumor characteristics of fat assessment and extent of pseudopapillary/micropapillary-like changes were recorded. Chi-square test was conducted to determine associations with tumor subtype. Most cases were unilateral (56/60; 93%) and solitary (55/60; 92%), with a median tumor size of 3.1cm (range: 0.25 - 19.0cm). Pseudopapillary/micropapillary changes were identified in 19/60 cases (32%), significantly occurring more frequently in fat-poor AML (17/30; 57%) compared to non-fat-poor AML (2/30; 7%; p<0.001). Pseudopapillary/micropapillary growth, mostly in mixed form, within tumors was 20% on average (range: 1 - 60%). No recurrence or tumor-related deaths were observed [44/60 patients; median follow-up=11months (range: 1- 96months)]. Recognizing pseudopapillary/micropapillary features, particularly in fat-poor AML and in a biopsy setting, is critical to avoid misdiagnosis.

  View details for DOI 10.1007/s00428-025-04155-w

  View details for PubMedID 40563034

• Urothelial carcinoma with osteoclast-like giant cells: An expanded immunohistochemical and molecular profile. American journal of clinical pathology Rizkalla, C. N., Tretiakova, M., Suarez, C. J., Williamson, S. R., Al-Obaidy, K. I., Acosta, A. M., Idrees, M. T., Chan, E., Potterveld, S., Sangoi, A. R. 2025

  Abstract

  OBJECTIVE: Osteoclast-rich undifferentiated carcinoma of the urinary tract, herein referred to as urothelial carcinoma with osteoclast-like giant cells (UCOGC), is a rare tumor currently classified under the "poorly differentiated urothelial carcinoma" subtype. This study aimed to evaluate the clinicopathologic, immunophenotypic, and molecular features of UCOGC to better characterize its origin and support its classification as a unique subtype.METHODS: There were 14 UCOGCs studied with immunohistochemistry/in situ hybridization and compared to urothelial carcinomas with trophoblastic differentiation (n = 6) and giant cell urothelial carcinomas (n = 5). Markers were assessed in mononuclear (MN) and giant cell (GC) components. Next-generation sequencing was performed on 4 UCOGCs.RESULTS: The MN cells of UCOGC demonstrated high expression of CD68, CD163, SATB2, cathepsin K, and CSF1 in situ hybridization (ISH), with moderate staining for GATA3, p63, and PU.1 and low staining for pankeratin. The GCs showed high CD68, PU.1, and cathepsin K expression but low CD163, SATB2, and CSF1 ISH, with no staining for urothelial markers or pankeratin. Both MN and GC were negative for H3.G34W and HCG. Next-generation sequencing revealed mutations consistent with conventional urothelial carcinomas.CONCLUSIONS: The distinct biphasic morphology, characteristic immunophenotype, and molecular findings of UCOGC suggest it is of urothelial origin, and we believe it justifies its classification as a unique subtype rather than under "poorly differentiated urothelial carcinoma."

  View details for DOI 10.1093/ajcp/aqaf044

  View details for PubMedID 40512053

• Serous Borderline Tumors of the Testis and Paratestis: A Clinicopathologic Study of 19 Tumors Emphasizing Morphologic Spectrum and Clinical Outcome. The American journal of surgical pathology Shahabi, A., Konstantinov, A., McKenney, J. K., Lane, J., Kao, C. S., Williamson, S. R., Alaghehbandan, R., Cheng, L., Sangoi, A. R., Chan, E., Cornejo, K. M., Przybycin, C. G. 2025

  Abstract

  Serous borderline tumors of the testis and paratestis are rare, and experience with these neoplasms is limited. We report a series of 19 tumors, emphasizing their morphologic spectrum and clinical behavior. Eighteen tumors (95%) had conventional serous borderline tumor morphology identical to ovarian serous borderline tumors, and 1 case (5%) had a pattern resembling the epithelial subtype of noninvasive implants of serous borderline tumor. A component of micropapillary serous borderline tumor was present in 6 tumors (31%), including 1 that was exclusively micropapillary. Five tumors (26%) had associated autoimplants. Microinvasion was identified in 4 tumors (21%). One tumor had associated low-grade serous carcinoma, and 1 tumor had associated high-grade serous carcinoma. Immunohistochemical stains demonstrated diffuse expression of PAX8 in 12 of 12 (100%) cases. Estrogen receptor was diffusely positive in 11 of 12 (92%) cases and progesterone receptor was positive in 8 of 9 (89%) cases. D2-40 was negative in 7 of 9 (78%) cases and calretinin was negative in 11 of 11 cases (100%). Clinical follow-up data were available in 9 patients (47%) with pure serous borderline tumors, of which 4 had micropapillary features (44%), 3 had microinvasion (33%), and 2 had autoimplants (22%). None of these 9 patients experienced adverse outcomes related to serous borderline tumor over the follow-up period (mean: 94 mo, median: 85 mo, range: 17 to 204 mo). Serous borderline tumors of the testis and paratestis are identical morphologically to their ovarian counterparts and can be associated with similar histologic phenomena (microinvasion, autoimplants, and micropapillary features). Although they can develop associated serous carcinoma, we conclude that serous borderline tumors of the testis and paratestis (when pure) appear to show indolent behavior.

  View details for DOI 10.1097/PAS.0000000000002439

  View details for PubMedID 40511957

• Current practices in prostate pathology reporting: results from a survey of genitourinary and general pathologists. Histopathology Nourbakshs, M., Du, L., Acosta, A. M., Alaghehbandan, R., Amin, A., Amin, M. B., Aron, M., Berney, D., Brimo, F., Chan, E., Cheng, L., Colecchia, M., Dhillon, J., Downes, M. R., Evans, A. J., Harik, L. R., Hassan, O., Haider, A., Humphrey, P. A., Jha, S., Kandukuri, S., Kao, C. S., Kaushal, S., Khani, F., Kryvenko, O. N., Kweldam, C., Lal, P., Lobo, A., Maclean, F., Magi-Galluzzi, C., Mehra, R., Miyamoto, H., Mohanty, S. K., Montironi, R., Nesi, G., Netto, G. J., Nguyen, J. K., Nourieh, M., Osunkoya, A. O., Paner, G. P., Sangoi, A. R., Shah, R. B., Srigley, J. R., Tretiakova, M., Troncoso, P., Trpkov, K., Van Der Kwast, T. H., Zhang, M., Zynger, D. L., Williamson, S. R., Giannico, G. A. 2025

  Abstract

  AIMS: Standardizing pathology reporting protocols through peer consensus review is critical for the best quality of care metrics. Reporting heterogeneity due to discrepancies among professional societies and practice patterns may lead to heterogeneous management and treatment approaches. This issue prompted a multi-institutional survey of pathologists to address potential similarities or differences in trends and practice patterns in prostate pathology reporting worldwide.METHODS AND RESULTS: A REDCap survey was distributed among 175 pathologists worldwide, recruited through invitations and social media. The response rate among invited pathologists was 83%. The practice locations were as follows: North America (USA, Canada, and Mexico, 62%), Europe (17%), Australia/New Zealand (3%), Central/South America (2%), Asia (13%), and Africa (2%). Most pathologists practiced for <5years (28%). A genitourinary (GU) pathology fellowship was completed by 37%, 58% practiced in a subspecialized setting, and 43% in academia. Reporting includes (63%) or subtracts (37%) intervening benign tissue. Both Gleason score and Grade Groups (GG)s were reported by 96% of responders, whereas 94% report percent pattern 4 (%4). Aggregate grading and volume estimation in undesignated cores with different grades in the same jar are reported by 73% and 54% for systematic biopsies, and 83% and 62% for targeted biopsies, respectively. Cribriform morphology was reported by 81%. For presumed intraductal carcinoma (IDC), 89% use basal cell markers when isolated (iIDC), 82% with GG1 cancer, and 37% with ≥GG2. iIDC or IDC associated with GG1 or with ≥GG2 was not graded by 90%, 78%, and 70%, respectively. In radical prostatectomies, 90% report %4, but only 53% report it if the overall grade is ≥7. A tumour with Gleason 3+3=6 and <5% pattern 4 was graded as GG2 by 64%. A <5% cutoff for defining tertiary pattern was used by 74%, and 80% report >5% pattern 4 or 5 as a secondary pattern. Grading was assigned based on the dominantnodule by 59%. Finally, reporting practices were significantly associated with demographic characteristics.CONCLUSIONS: Although most issues are agreed upon, significant discordance is identified among societies and pathologists in different practice settings. We hope this survey will serve as the basis for future studies and new collaborative approaches to more standardized reporting practices.

  View details for DOI 10.1111/his.15469

  View details for PubMedID 40364451

• Renal Epithelioid Angiomyolipoma: Prognostic Implications of Targeted Immunohistochemical and Molecular Markers in Conjunction with Clinicopathologic Features. The American journal of surgical pathology Sangoi, A. R., Lobo, A., Jha, S., Kaushal, S., Tiwari, A., Mubeen, A., Humble, R., Potterveld, S. K., Williamson, S. R., Akgul, M., Srinivas, S., Mohanty, S. K. 2025

  Abstract

  Epithelioid angiomyolipoma (eAML) is an uncommon subtype of angiomyolipoma, a subset of which can demonstrate malignant behavior. While some studies have proposed histopathologic features predictive of aggressive behavior in eAML, there is limited data on the use of immunohistochemistry (IHC) and/or next-generation sequencing (NGS) to identify biomarkers for poor clinical outcome. Moreover, there is limited data on the proposed genetic dichotomy (tuberous sclerosis complex [TSC] alteration versus TFE3 rearrangement) of eAML. Clinicopathologic features (including purported histologic features associated with adverse outcome) of 30 eAML were recorded with IHC performed on 1 whole-slide section per tumor for the following markers (interpretations): p16 (positive or negative), p53 (wild type or mutant), TRIM63 ISH (>10% as positive or ≤10% as negative), ATRX (retained or lost), and RB1 (retained or lost). NGS was performed on 23 tumors. The 30 eAML tumors were from 30 patients (23 female, 7 male) of an age range 22 to 77 years (mean=51.9y). Clinical follow-up was available from 27 patients (mean=36mo). The features significantly associated with metastatic disease included ≥70% atypical epithelial cells (P=0.04), ≥2 mitotic figures per 10 high-power fields (P=0.0013), atypical mitotic figures (P=0.0003), and necrosis (P=0.0213). Other features such as local invasion, vascular invasion, tumor size, and immunohistochemical profile (p16, TRIM63, p53, ATRX, and RB1) showed no significant association with the development of metastasis. Interestingly, among the 7 tumors with clinical follow-up showing TFE3 rearrangement, 5 developed metastases (OR=4.50), while 6 of 14 TSC/MTOR mutated tumors with clinical follow-up had metastatic disease (OR=0.222). Notably, TRIM63 ISH showed high sensitivity (100%) for eAML with TFE3 rearrangement but with poor specificity (38%). The genetic dichotomy of eAML comes in the form of TSC/MTOR alterations or TFE3 rearrangement elucidated by NGS, both of which may be associated with poor outcome, and therefore show potential therapeutic implications. As eAML may show overlap with TFE3-rearranged/TFEB-altered renal cell carcinoma, shared TRIM63 ISH positivity for these tumor types represents an important potential diagnostic pitfall.

  View details for DOI 10.1097/PAS.0000000000002411

  View details for PubMedID 40289813

• Adrenal Gland Pathology Reporting Among Genitourinary Pathologists: An Orphan Field Handled by Foster Pathologists? International journal of surgical pathology Sangoi, A. R., Sparger, C. C., Williamson, S. R., Barletta, J., Mohanty, S. K., Akgul, M. 2025: 10668969251333436

  Abstract

  Due to their association with the kidney, adrenal glands are frequently resected by urologists and evaluated by genitourinary (GU) pathologists. However, given the growing complexity of adrenal pathology and advent of a dedicated "endocrine pathology" subspecialty, herein we sought to assess the sentiment regarding adrenal pathology among GU pathologists. One hundred twenty-eight pathologists who handle GU specimens participated in a survey including both junior (40%<10 years in practice) and experienced pathologists (60%>11 years in practice), who work in academic (75%) or private practice settings (25%). Participants reported "on the job" adrenal pathology training (61%) and/or formal training during GU fellowship (36%). While participants felt mainly "comfortable" (36%) or "neutral" (29%) reporting adrenal specimens, some felt "uncomfortable" (15%) or "very uncomfortable" (5%). Most reported that adrenal specimens are handled by GU pathology (56%) versus general surgical pathology (26%) or endocrine pathology (22%; although only 30% reported having formal endocrine pathologists). However, when the participants were asked who they felt should be handling adrenal specimens, participants most strongly endorsed either endocrine pathology (74%) or GU pathology (58%). For workplaces that didn't have a dedicated endocrine pathologist, the main limitations were insufficient number of endocrine pathology specimens for the position (53%; 81% reporting an average of ≤10 per month) or insufficient number of qualified endocrine pathologists (46%). Although adrenal specimens are typically received from urology colleagues, many GU pathologists feel it may be prudent to consider them under the rubric of endocrine pathology services as they become more readily available.

  View details for DOI 10.1177/10668969251333436

  View details for PubMedID 40221989

• MEIS1::NCOA1 Primitive Spindle Cell Sarcoma of the Kidney: Report of 7 Cases of a Distinctive Clinicopathologic Entity. The American journal of surgical pathology Argani, P., Wangsiricharoen, S., Tretiakova, M., Liu, Y. J., Falzarano, S. M., Collins, K., Brimo, F., Gross, J. M., Baraban, E., Matoso, A., Wakeman, K., Corless, C., Neff, T., Smith, B. F., Abdel Satir, A., Agaimy, A., Antonescu, C. R., Charville, G. W., Sangoi, A. R. 2025

  Abstract

  Primitive sarcomas harboring the MEIS1::NCOA2 gene fusion were originally described in the kidney in 2018, and subsequently reported in other organs. These variably cellular neoplasms feature monomorphic primitive plump spindle cells forming nodules and whorls in addition to nondescript fascicular, solid, and storiform patterns. They lack skeletal muscle differentiation in contrast to the primarily intraosseous rhabdomyosarcomas that harbor the same gene fusion. We describe 7 new primary primitive renal sarcomas with MEIS1::NCOA1 gene fusions. Although their morphology overlaps with that described in MEIS1::NCOA2 renal sarcoma, 3 of the 7 cases contained adipose tissue. The majority had intimately admixed entrapped cystic epithelial elements and demonstrated patchy immunoreactivity for estrogen receptor and nuclear labeling for WT1 protein, leading to the differential diagnosis of malignant mixed epithelial stromal tumor (MEST) in 4 cases and metanephric stromal tumor in one. The neoplasms demonstrate a broad spectrum of clinicopathologic features ranging from a bland low-grade neoplasm that metastasized 9 years after diagnosis to a high-grade sarcoma with multiple recurrences, ultimately leading to patient death in under 1 year. In summary, MEIS1::NCOA1 primitive sarcomas overlap with the previously described MEIS1::NCOA2 primitive renal sarcomas and represent a distinctive renal neoplasm that can be mistaken for malignant MEST. Grade ranges from low to high but even low-grade neoplasms require long-term clinical follow-up.

  View details for DOI 10.1097/PAS.0000000000002386

  View details for PubMedID 40160183

• Succinate dehydrogenase deficient renal cell carcinoma frequently expresses GATA3 and L1CAM. Virchows Archiv : an international journal of pathology Sangoi, A. R., Williamson, S. R., Oktay, M., Gill, A. J., Trpkov, K., Siadat, F., MacLean, F., Galea, L. A., Baydar, D. E., Cakir, C., Karabulut, Y. Y., Baycelebi, D., Coban, G., Sarsik, B., Bayrak, B. Y., Kuthi, L., Posfai, B., Mobeen, A., Mohanty, S. K., Zhang, X., Alghamdi, M. A., Cheng, L., Hirsch, M. S., Akgul, M. 2025

  Abstract

  Succinate dehydrogenase deficient renal cell carcinoma (SDH RCC) is an uncommon, familial RCC that has overlapping morphologic features with other low grade eosinophilic tumors of the kidney. Although the diagnosis of SDH RCC relies on loss of SDHB by immunohistochemistry (IHC), not all laboratories have access to this antibody. GATA3 and L1CAM are increasingly utilized in the diagnosis of eosinophilic renal tumors; however, their expression profile has not been studied in SDH RCC. We evaluated clinical parameters and GATA3 and L1CAM reactivity in a large nephrectomy cohort (n = 40) of patients with SDH RCC. The male-to-female ratio was 3:1 and the median age was 48 years (range: 17 to 79 years). Specimens included 20 radical resections, 19 partial resections, and 1 unknown procedure. Tumor laterality was nearly equal (right:left = 18:20; one case was bilateral). Tumors in 4 (10%) patients were multifocal. Median tumor size was 2.0 cm (range 1 - 14.8 cm). Tumor stage distribution was: pT1a (n = 16, 40%), pT1b (n = 7, 18%), pT2a (n = 5, 13%), pT2b (n = 4, 10%), pT3a (n = 6, 15%), and pT4 (n = 1, 3%). Most cases (n = 33, 83%) exhibited classical morphologic features, whereas 2/40 (5%) had sarcomatoid differentiation. GATA3 was positive in 37/39 (95%) tumors, with more than 50% of cells positive in 35/37 (95%), and with moderate-high intensity (2/3 +) in 33/37 (89%). L1CAM was expressed in 13/18 (72%) tumors, with moderate-high intensity (2/3 +) in 10/13 (77%). When both markers were performed, dual GATA3/L1CAM expression was present in 12/17 (71%) tumors. As L1CAM has been postulated to represent a marker of principal cell of the distal nephron, frequent L1CAM expression in SDH RCC suggests that they may originate from the principal cells of the distal nephron.

  View details for DOI 10.1007/s00428-025-04078-6

  View details for PubMedID 40100385

• Renal Epithelioid Angiomyolipomas: Prognostic Implications of Targeted Immunohistochemical and Molecular Markers Sangoi, A., Lobo, A., Jha, S., Kaushal, S., Tiwari, A., Mubeen, A., Humble, R., Mohanty, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103125

  View details for Web of Science ID 001469676500048

• Expanding Horizons: A Deeper Dive into the Morphologic and Genomic Landscape of ALK-Rearranged Renal Cell Carcinomas Lobo, A., Sangoi, A., Al-Obaidy, K., Akgul, M., Acosta, A., Kandukuri, S., Jha, S., Kaushal, S., Satturwar, S., Osunkoya, A., Parwani, A., Dhillon, J., Williamson, S., Shah, R., Cheng, L., Mohanty, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103076

  View details for Web of Science ID 001469676900047

• Genomic Insights and Cell of Origin Concepts Reveal Distal Nephron Origin for SDH-B Deficient Renal Cell Carcinoma Mannan, R., Zhang, Y., Paturu, R., Hu, J., Mahapatra, S., Chinnaiyan, A., Wang, X., Cao, X., Su, F., Wang, R., Picken, M., Palapattu, G., Hafez, K., Vaishampayan, U., Gupta, S., Sangoi, A., Argani, P., Chinnaiyan, A., Dhanasekaran, S., Mehra, R. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103086

  View details for Web of Science ID 001469676900003

• Perivascular Epithelioid Cell Tumors of the Urinary Bladder: A Clinicopathologic and Comprehensive Molecular Analysis including Microsatellite Instability Status and Tumor Mutational Burden in a Contemporary Cohort of 21 cases Lobo, A., Tiwari, A., Agaimy, A., Akgul, M., Sangoi, A., Kandukuri, S., Acosta, A., Al-Obaidy, K., Jha, S., Kaushal, S., Satturwar, S., Dhillon, J., Osunkoya, A., Williamson, S., Pradhan, D., Shah, R., Parwani, A., Cheng, L., Mohanty, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103077

  View details for Web of Science ID 001469676900044

• Post-therapeutic Squamous Cell Transformation of Metastatic Prostatic Adenocarcinoma with Paired Molecular Profiling: A Multi-Institutional Cohort of an Under-reported Kaushal, S., Dhillon, J., Malik, V., Akgul, M., Acosta, A., Lobo, A., Smith, S., Aron, M., Al-Obaidy, K., Williamson, S., Sangoi, A., Cheng, L., Amin, M., Lotan, T., Mohanty, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103054

  View details for Web of Science ID 001469676900012

• Current Reporting Trends, Practices, and Resource Utilization in Penile Cancer: A Survey among Genitourinary Pathologists Dhillon, J., Lobo, A., Akgul, M., Acosta, A., Chumbalkar, V., Vosoughi, A., Xu, H., Al-Ahmadie, H., Al-Obaidy, K., Amin, M., Aron, M., Arora, S., Ayyanar, P., Bakshi, N., Balzer, B., Bardia, A., Baweja, P., Chakrabarti, I., Cheng, L., Cima, L., Colecchia, M., Collins, K., Comperat, E., Das, D., Dixit, M., Downes, M., Elhence, P., Epstein, J., Galea, L., Gandhi, J., Giannico, G., Gordetsky, J., Gupta, G., Gupta, N., Haider, A., Hansel, D., Hartmann, A., Ho-Yen, C., Iczkowski, K., Jain, E., Jain, R., Jha, S., Kao, C., Kaushal, S., van Leenders, G., Lenka, K., Lopez, J., Lopez-Beltran, A., Luthringer, D., Maclean, F., Magi-Galluzzi, C., Malik, V., Manini, C., Martignoni, G., Mehta, B., Menon, S., Misra, S., Mohanty, S., Montironi, R., Nayak, S., Nguyen, J., Ntala, C., Oliveira, P., Osunkoya, A., Patil, S., Picken, M., Dr Prachi, Pradhan, D., Prendeville, S., Queipo, F., Quiroga-Garza, G., Rao, B., Rao, P., Raspollini, M., Sabnis, S., Sancheti, S., Sanchez, D. F., Sarungbam, J., Satarkar, R., Satturwar, S., Sayyed, N., Shah, R., Sharma, I., Sharma, N., Sharma, S., Sirohi, D., Sobti, P., Soni, S., Sreeram, S., Sundaram, S., Tamboli, P., Tanveer, N., Tickoo, S., Tiwari, A., Tomar, R., Tretiakova, M., Trpkov, K., Tsuzuki, T., Warrick, J., Zhou, M., Sangoi, A., Williamson, S., Mohanty, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103023

  View details for Web of Science ID 001465165000010

• Determinants of Oncologic Outcomes in High Grade Organ-Confined Prostate Cancer After Radical Prostatectomy Youssef, R., Saeed, O., Baraban, E., Salimian, M., Iczkowski, K., Chung, L., Baniak, N., Comperat, E., Miyamoto, H., van Leenders, G., Sangoi, A., Wu, D., Osunkoya, A., Kandukuri, S., Michalova, K., Martignoni, G., Marcolini, L., Calio, A., Pecoraro, A., Strakova-Peterikova, A., Wang, Y., Cuber, A., Tsuzuki, T., Acosta, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103155

  View details for Web of Science ID 001469676500004

• Renal Sarcoma with MEIS1::NCOA1 Fusion: A Rare Entity with Pathologic Overlap with Mixed Epithelial and Stromal Tumor and Metanephric Stromal Tumor Smith, B., Argani, P., Wangsiricharoen, S., Wakeman, K., Neff, T., Tretiakova, M., Brimo, F., Collins, K., Falzarano, S., Gross, J., Antonescu, C., Agaimy, A., Charville, G., Sangoi, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103133

  View details for Web of Science ID 001469676500060

• DNA-sequencing Study of Low Grade Urachal Mucinous Cystic Tumors Suggest a KRASindependent Pathogenesis Michalova, K., Gordetsky, J., Sangoi, A., Cornejo, K., Martinek, P., Ptakova, N., Michal, M., Michal, M., Acosta, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103095

  View details for Web of Science ID 001469676900063

• Osteoclast-Rich Undifferentiated Urothelial Carcinoma: An Expanded Immunohistochemical and Molecular Profiling with Classification Reassessment Rizkalla, C., Tretiakova, M., Suarez, C., Williamson, S., Al-Obaidy, K., Acosta, A., Idrees, M., Chan, E., Potterveld, S., Sangoi, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103116

  View details for Web of Science ID 001469676900008

• Aberrant INSM1 Expression in Erythroid Cells: A Potential Diagnostic Pitfall Versus Neuroendocrine Tumors Wu, D., Charville, G., Sangoi, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.102983

  View details for Web of Science ID 001465165000049

• GATA3 is Underexpressed in Penile Neoplasia: Potential Implications in Diagnosis and Pathogenesis Kandiyil, N., Sangoi, A., Kim, J., Rodriguez, C., Tifrea, D., Rahmatpanah, F., Granada, C., Giannico, G. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.102991

  View details for Web of Science ID 001465165000028

• Do Urinary Bladder Smooth Muscle Neoplasms Show Morphologic and Immunophenotypic Features of Their Uterine Fumarate Hydratase-Deficient Counterparts? Gao, H., Ren, D., Giannico, G., Khani, F., Galea, L., Al-Obaidy, K., Falzarano, S., Wobker, S., Barry-Holson, K., Chan, E., Mchenry, A., Sangoi, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103034

  View details for Web of Science ID 001465165000006

• Paraganglioma of The Urinary Bladder: An International Collaborative Study of 59 Tumors Macedo, R., He, H., Magi-Galluzzi, C., Nezami, B., Montiel, D., Shah, R., Smith, S., Ulamec, M., Falzarano, S., Osunkoya, A., Picken, M., Rogala, J., Sangoi, A., Tretiakova, M., Mckenney, J., Nguyen, J., Przybycin, C., Williamson, S., Almassi, N., Alaghehbandan, R. ELSEVIER SCIENCE INC. 2025: 117-118

  View details for DOI 10.1016/j.labinv.2024.103135

  View details for Web of Science ID 001469676500067

• Interobserver Reproducibility of Pelvicalyceal Invasion in Renal Cell Carcinomas Among Genitourinary Pathologists Sangoi, A., Akgul, M., Mubeen, A., Humble, R., Acosta, A., Amin, M., Aron, M., Brimo, F., Chan, E., Cheng, L., Cheville, J., Collins, K., Cornejo, K., Dhillon, J., Downes, M., Epstein, J., Hirsch, M., Kapur, P., Lobo, A., Mehra, R., Mohanty, S., Netto, G., Osunkoya, A., Paner, G., Rao, P., Saleeb, R., Shah, R., Shen, S., Smith, S., Tickoo, S., Tretiakova, M., Trpkov, K., Wobker, S., Tamboli, P., Zynger, D., Williamson, S. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103126

  View details for Web of Science ID 001469676500046

• Interobserver Reproducibility of Hilar Soft Tissue Invasion in Testicular Germ Cell Tumors Among Genitourinary Pathologists Wu, D., Akgul, M., Williamson, S., Acosta, A., Al-Obaidy, K., Amin, M., Berney, D., Brimo, F., Cheng, L., Colecchia, M., Comperat, E., Cornejo, K., Dhillon, J., Downes, M., Epstein, J., Hirsch, M., Jimenez, R., Lobo, A., Kaushal, S., Lopez-Beltran, A., Mohanty, S., Mehra, R., Paner, G., Rao, P., Reuter, V., Shah, R., Shen, S., Smith, S., Tretiakova, M., Trpkov, K., Wobker, S., Tamboli, P., Zynger, D., Sangoi, A. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103150

  View details for Web of Science ID 001469676500005

• Utility of CA9 Immunostain in Margin Assessment of Clear Cell Renal Cell Carcinoma Nephrectomies. International journal of surgical pathology Sparger, C. C., Pacheco, R. R., Sangoi, A. R. 2025: 10668969251323934

  View details for DOI 10.1177/10668969251323934

  View details for PubMedID 40012266

• Artificial Intelligence-Based Classification of Renal Oncocytic Neoplasms: Advancing From a 2-Class Model of Renal Oncocytoma and Low-Grade Oncocytic Tumor to a 3-Class Model Including Chromophobe Renal Cell Carcinoma. Archives of pathology & laboratory medicine Collins, K., Innani, S., Ebare, K., Saad, M., Siegmund, S. E., Williamson, S. R., Maclean, F., Matoso, A., Sangoi, A., Hirsch, M. S., Gondim, D. D., Acosta, A. M., Baheti, B., Bakas, S., Idrees, M. T. 2025

  Abstract

  CONTEXT.: Distinguishing between renal oncocytic tumors, such as renal oncocytoma (RO), and a subset of tumors with overlapping characteristics, including the recently identified low-grade oncocytic tumor (LOT), can present a diagnostic challenge for pathologists owing to shared histopathologic features.OBJECTIVE.: To develop an automatic computational classifier for stratifying whole slide images of biopsy and resection specimens into 2 distinct groups: RO and LOT.DESIGN.: A total of 269 whole slide images from 125 cases across 6 institutions were collected. A weakly supervised attention-based multiple-instance-learning deep learning (DL) model was trained and initially evaluated through 5-fold cross validation with case-level stratification, followed by validation using an independent holdout data set. Quantitative performance evaluation was based on accuracy and the area under the receiver operating characteristic curve (AUC).RESULTS.: The developed model data set yielded generalizable performance, with a 5-fold average testing accuracy of 84% (AUC = 0.78), and a closely aligning accuracy of 83% (AUC = 0.92) on the independent holdout data set.CONCLUSIONS.: The proposed artificial intelligence approach contributes toward a comprehensive solution for addressing commonly encountered renal oncocytic neoplasms, encompassing well-established entities like RO along with the challenging "gray zone" LOT, thereby proving applicable in clinical practice.

  View details for DOI 10.5858/arpa.2024-0374-OA

  View details for PubMedID 39957180

• Incidence and Pitfalls of Intratesticular Adipose Tissue Encountered in Orchiectomy Specimens. International journal of surgical pathology Nguyen, N. J., Gosnell, H., Pacheco, R. R., Akgul, M., Williamson, S. R., Sangoi, A. R. 2025: 10668969241309941

  Abstract

  Based on the eighth edition of the American Joint Committee on Cancer staging system, postpubertal germ cell tumors (GCT) and malignant sex cord-stromal tumors (SCST) of the testis invading hilar soft tissue are of pathologic stage pT2. Adipose tissue is typically used as an anatomical landmark by pathologists for determining hilar soft tissue invasion. Herein, we evaluated for the presence, location, and extent of intratesticular fat in a multi-institutional cohort of orchiectomies. Consecutive orchiectomies from 3 academic institutions were reviewed (n=605), including both benign and malignant specimens. Intratesticular fat was identified by hematoxylin and eosin (H&E) evaluation in 11/605 (1.8%) orchiectomies, including the following diagnoses: mixed non-teratomatous GCT (n=1), mixed GCT with a teratoma component (n=2), pure teratoma (n=2), Leydig cell hyperplasia (n=1), regressed GCT (n=1), hormone therapy effect (n=1), atrophic changes (n=1), fibrosis (n=1), infarction (n=1). Adipose tissue was located within the rete testis stroma (n=2), just below the rete testis (n=4), within nodules of Leydig hyperplasia between the seminiferous tubules (n=1), or within the confines of testicular parenchyma (n=4). Among the 4 specimens containing admixed neoplastic (teratomatous) fat, the extent of adipose tissue ranged from 3.0 to 11.0 mm (mean 6.8 mm). Among the 7 specimens with non-neoplastic adipose tissue within/near the rete, the extent ranged from 0.1 to 12.7 mm (mean 2.3 mm). Although uncommon, intratesticular fat can be found in orchiectomy specimens, which may represent a staging pitfall in GCT and SCST especially when located at the interface between the testicular parenchyma and hilum.

  View details for DOI 10.1177/10668969241309941

  View details for PubMedID 39911022

• Aberrant Cytoplasmic INSM1 Expression in Erythroid Cells: A Potential Diagnostic Pitfall Versus Neuroendocrine Neoplasms. International journal of surgical pathology Wu, D. J., Charville, G. W., Sangoi, A. R. 2025: 10668969241311524

  Abstract

  Insulinoma-associated protein 1 (INSM1) is a relatively new immunostain used in the diagnostic assessment of tumors with neuroendocrine differentiation. While INSM1 positivity has been described in some non-neuroendocrine neoplasms, reactivity in red blood cells (RBCs) has only been anecdotally noted in one prior study without description of the degree/extent of staining. INSM1 staining in nucleated erythroid precursors has not been previously reported. Herein, 100 small biopsy specimens containing RBCs where INSM1 was used for diagnostic workup were reviewed. Additionally, 5 benign bone specimens and 5 adrenal myelolipoma specimens containing nucleated erythroid precursors were stained with INSM1. INSM1 staining intensity (0-3) and staining extent (0-100%) in RBC/erythroid cells was evaluated and an H-score was calculated (0-300). Positive cytoplasmic INSM1 staining in RBCs was observed in 99/100 (99%) specimens, with mean staining intensity of 2.1 (median = 2) and mean staining percent of 59% (median = 70%), with mean H-score of 125 (median = 140). Positive cytoplasmic INSM1 staining was identified in 10/10 (100%) specimens containing nucleated erythroid precursors, with mean staining intensity of 2.7 (median = 3) and mean staining percent of 53% (median = 50%), with mean H-score of 132 (median = 120). INSM1 is frequently positive in RBCs and nucleated erythroid precursors, albeit with variable staining intensity and extent. Although the INSM1 staining is cytoplasmic in RBCs (lacking nuclei) and nucleated erythroid precursors, the morphological features can mimic positive nuclear staining of neuroendocrine neoplasms. Particularly in small biopsy samples, which often contain background RBCs, positive INSM1 staining should be reviewed with caution to avoid misdiagnosis of neuroendocrine differentiation.

  View details for DOI 10.1177/10668969241311524

  View details for PubMedID 39871709

• MAPK1IP1L::TFE3-rearranged renal cell carcinoma: a novel fusion adding to the differential diagnosis of oncocytic renal neoplasms. Virchows Archiv : an international journal of pathology Cheng, A. V., Wu, D. J., Friedman, L. A., Chan, E., Williamson, S. R., Galea, L. A., Sangoi, A. R. 2025

  Abstract

  Beyond the more common TFE3 fusion partners PRCC, ASPSCR1, and SFPQ, additional less common fusion partners of TFE3-rearranged renal cell carcinoma (RCC) have been described. Herein, we present an example of TFE3-rearranged renal cell carcinoma harboring fusion partner MAPK1IP1L, a rare rearrangement with only one other reported tumor found in the literature. The currently reported TFE3-rearranged RCC demonstrates unique histological features compared to the previously reported tumor including dense eosinophilic cytoplasm and nuclear pseudoinclusions (corroborated by electron microscopic evaluation), with features not typically seen in other TFE3-rearranged RCCs. Recognizing this novel fusion may be important in the identification, classification, and development of potential therapeutic agents of kidney tumors in the future.

  View details for DOI 10.1007/s00428-025-04031-7

  View details for PubMedID 39862330

• Gamna-Gandy bodies in renal neoplasms: A multi-institutional clinicopathologic study of 350 consecutive nephrectomies. Annals of diagnostic pathology Mubeen, A., Pacheco, R., Akgul, M., Williamson, S. R., Collins, K., Chan, E., Sangoi, A. R. 2025; 75: 152440

  Abstract

  Gamna-Gandy (GG) bodies are sclerosiderotic nodules composed of iron pigment and calcium, that have been described predominantly in the spleens of patients with sickle cell disease. Their formal depiction in the kidney is mainly limited to case reports and small series. We aimed to investigate the incidence of GG bodies and associated clinicopathologic features in consecutive nephrectomies performed for renal tumors. Slides of consecutive nephrectomies for renal neoplasms at 3 institutions were reviewed by genitourinary pathologists, with detailed clinicopathologic features recorded. The incidence of GG bodies in our nephrectomy cohort was 13% (44/350). The most common tumor exhibiting GG bodies was clear cell renal cell carcinoma (RCC) (40/44), followed by papillary RCC (2/44), chromophobe RCC (1/44), and epithelioid angiomyolipoma (1/44). Most RCCs were pathologic stage pT3a (46%). GG bodies were intratumoral in 77%, peritumoral in 5%, and both in 18% of patients. They were focal in 43% and multifocal in 57%, with the largest focus ranging from 0.2 to 7mm (mean 1.7mm). Background fibrosis and hemosiderin laden macrophages were commonly associated (93% for both). All tumors demonstrated cystic elements. In 2 renal tumor specimens, an extensive fungal workup was performed and was negative; the "structures" were not formally recognized as GG bodies in either specimen. GG bodies are not an uncommon finding in renal tumors, particularly in clear cell RCC. Awareness of the morphologic appearance is crucial to avoid mistaking them for fungal structures or other organisms.

  View details for DOI 10.1016/j.anndiagpath.2025.152440

  View details for PubMedID 39826481

• Primary intrarenal hemangioma - A series of 39 cases. Annals of diagnostic pathology Faraz, M., Rosenzweig, A., Panizo, A., Hajiyeva, S., Subasi, N. B., Alghamdi, M. A., Lightle, A. A., Kuthi, L., Kelemen, D., Sangoi, A. R., Nova-Camacho, L. M., Martos, M. G., Movassaghi, M., Lobo, A., Jha, S., Yörükoğlu, K., Bayrak, B. Y., Williamson, S. R., Bhardwaj, S., Kandukuri, S., Kaushal, S., Mohanty, S. K., Akgul, M. 2025; 75: 152436

  Abstract

  Intrarenal hemangiomas lack concise clinicopathologic information, due to the predominance of single case reports and inclusion of other vascular neoplasms and hemangiomas of perirenal, hilar, and renal vein origin. Herein, in this multi-institutional study we evaluate clinicopathologic features of 39 intrarenal hemangiomas. The median age was 62 years (range = 27-94 years; 2:1 male to female ratio), with left-sided predominance (left = 21, right = 13; one case was bilateral). The median tumor size was 1.5 cm (0.2-10 cm). Two cases arose from transplanted kidneys. Most were asymptomatic (n = 30, 86 %), even though most surgical interventions (19 partial, 19 radical, 1 biopsy) were due to hemangiomas (n = 24, 62 %). Synchronous renal neoplasms were present in 9 (23 %) patients, including clear cell renal cell carcinoma (RCC) (n = 4), angiomyolipoma (n = 2), oncocytoma (n = 2), and chromophobe RCC (n = 1). Multifocal hemangiomas (n = 5) were seen in cases with end stage renal disease. Intrarenal hemangiomas were mostly anastomosing (n = 18; 46 %), followed by capillary (n = 15; 38 %), and cavernous (n = 6; 16 %) subtypes. Fibrin thrombus (n = 9; 23 %) and extramedullary hematopoiesis (n = 4; 10 %) were occasionally present, the latter being only in the anastomosing subtype. Immunohistochemistry was performed on a majority (n = 33, 84 %) of hemangiomas, with vascular markers CD31 and CD34 and lack of PAX8 were most used for diagnosis. 30 patients had follow-up (median 48 months, range 1-241 months), none showed disease progression/recurrence. This study provides comprehensive observation of the largest intrarenal hemangioma cohort, highlighting their frequent cause of surgical intervention when present, predominance of anastomosing subtype, multifocality in end stage kidney disease, and occasional concurrent ipsilateral neoplasms.

  View details for DOI 10.1016/j.anndiagpath.2025.152436

  View details for PubMedID 39793165

• Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations. American journal of clinical pathology Sangoi, A. R., Shahabi, A., Hirsch, M. S., Kao, C. S., Deebajah, M., Barletta, J. A., Paner, G. P., Smith, S. C., Grignon, D. J., Compérat, E., Amin, M. B., Maclean, F., Shah, R. B., Iczkowski, K. A., Delprado, W., Cheng, L., Pan, C. C., McKenney, J. K., Ro, J. Y., Khani, F., Montironi, R., Robinson, B. D., Al-Ahmadie, H., Epstein, J. I., Trpkov, K., Tretiakova, M., Shen, S. S., Alanee, S., Weight, C. J., Akgul, M., Williamson, S. R. 2024

  Abstract

  Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3). Among all 3 groups, group 1 was most likely to diagnose concomitant CIS and PUC in the same specimen but in different tissue fragments (58%). Pagetoid spread was reported to favor CIS predominantly by group 1 (61%). Urologists felt that the term lateral spread/shoulder was unclear (75%) and preferred early PUC (44%) or PUC with early growth (44%). Half (53%) of urologists felt that reporting CIS instead of lateral spread of PUC would change management.Documentation of flat lesions lacks consensus among pathologists and may benefit from standardized terminology. Moreover, the distinction between CIS and early or lateral spread of PUC is not always clear to urologists and can influence disease management.

  View details for DOI 10.1093/ajcp/aqae167

  View details for PubMedID 39720998

• Paneth cell-like differentiation in urothelial carcinoma: A hitherto unreported phenomena? Human pathology Rizkalla, C. N., Friedman, L., Charu, V., Sangoi, A. R. 2024: 105701

  View details for DOI 10.1016/j.humpath.2024.105701

  View details for PubMedID 39613164

• SS18-SSX Expression and Clinicopathologic Profiles in a Contemporary Cohort of Primary Paratesticular Synovial Sarcoma: A Series of Fourteen Patients. The American journal of surgical pathology Lobo, A., Mishra, S. K., Acosta, A. M., Kaushal, S., Akgul, M., Williamson, S. R., Sangoi, A. R., Aron, M., Kandukuri, S. R., Shinde, S., Sharma, S., Jain, E., Dhillon, J., Deshwal, A., Peddinti, K., Jaiswal, S., Das, S., Kapoor, R., Biswas, G., Pradhan, M. R., Osunkoya, A. O., Pradhan, D., Chakrabarti, I., Jha, S., Parwani, A. V., Shah, R. B., Amin, M. B., Cheng, L., Mohanty, S. K. 2024

  Abstract

  Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30 y). The tumor size ranged from 4​​​​​​ to 15 cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10 mo). Four patients died of metastatic disease (range: 5 to 16 mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.

  View details for DOI 10.1097/PAS.0000000000002323

  View details for PubMedID 39449577

• Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors. American journal of clinical pathology Potterveld, S. K., Akgul, M., Pacheco, R., Humble, R. M., Mubeen, A., Williamson, S. R., Gosnell, H., Sangoi, A. R. 2024

  Abstract

  OBJECTIVES: The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology.METHODS: A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded.RESULTS: The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%.CONCLUSIONS: Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.

  View details for DOI 10.1093/ajcp/aqae140

  View details for PubMedID 39437183

• Incidence and Pitfalls of Adipose Tissue Encountered in Urinary Bladder Biopsy/Transurethral Resection Specimens. International journal of surgical pathology Rizkalla, C. N., Srinivas, S., Sangoi, A. R. 2024: 10668969241271957

  Abstract

  Despite the College of American Pathologists' recommendation against diagnosing "fat invasion" in urinary bladder biopsies and transurethral resection of bladder tumor specimens (TURBT), some pathologists still consider this scenario as pathologic stage T3. However, a formal evaluation of fat in biopsies/TURBT has not been performed. Material obtained from TURBT is considered as clinical staging (cT) and that obtained from cystectomy is true pathologic staging (pT). Herein, we analyze adipose tissue incidence/distribution, cancer involving fat, staging ramifications, and clinical outcomes in a large series of biopsies/TURBT. Among 366 biopsies/TURBT specimens, data on adipose tissue presence, location, and quantity were analyzed. An initial analysis of 200 consecutive biopsies/TURBT specimens (including benign/cancer), adipose tissue was identified in 37% of 200 specimens (22% biopsies, 78% TURBT), primarily in the lamina propria (57%) or both lamina propria/muscularis propria (32%). A subsequent analysis of 183 invasive cancer (cT1/cT2) biopsies/TURBT revealed adipose tissue in 40% of specimens, predominantly within both the lamina propria and muscularis propria. Among all cT1/cT2 specimens, 26% (23/88) had cancer involving fat. Clinical follow-up on these putative "cT3" specimens revealed 10 patients who underwent radical cystectomy of which only 1 of 10 remained pT3/pT4 (although 8 patients had neoadjuvant chemotherapy). Adipose tissue is commonly found in biopsies/TURBT, predominantly localized in the lamina propria and sometimes extending into the muscularis propria. Importantly, the presence of tumor "invading" fat on biopsies/TURBT does not necessarily indicate pT3 disease. This underscores the need for standardized reporting practices, emphasizing the importance of reserving pathologic staging for cystectomy specimens.

  View details for DOI 10.1177/10668969241271957

  View details for PubMedID 39300817

• Pure Intertubular Seminoma (PITS) of the Testis: A Multi-institutional Cohort of a Rare Growth Pattern of Seminoma. Human pathology Kaushal, S., Jain, E., Acosta, A. M., Sangoi, A. R., Lobo, A., Jha, S., Sharma, S., Arora, S., Beg, A., Akgul, M., Williamson, S. R., Baisakh, M. R., Pattnaik, N., Satturwar, S., Parwani, A. V., Dixit, M., Malik, V., Osunkoya, A. O., Cheng, L., Amin, M. B., Dhillon, J., Mishra, S. K., Biswas, G., Panda, S. S., Mohanty, S. K. 2024: 105667

  Abstract

  Pure intertubular seminoma (PITS) of the testis is described as the presence of seminoma cells within the interstitium of testis without any evidence of diffuse growth pattern or mass lesion of classical seminoma. These tumors are clinically and grossly inconspicuous and are diagnosed incidentally or during investigations for testicular pain, infertility or other symptoms. Rarely metastasis is the first presentation. Microscopic identification can be difficult and poses a diagnostic challenge in the absence of a mass lesion. Seminomas with exclusive intertubular growth patterns were gathered in an international cohort. Diagnoses were confirmed by fellowship-trained or specialized urologic pathologists. Cases with the presence of a classical diffuse or nested pattern of seminoma or any other germ cell tumor component were excluded. The patient's age, tumor characteristics and additional clinicopathologic features were recorded and analyzed. 15 patients of pure intertubular seminoma (PITS) were collated. The mean age of presentation was 29 years. Patients presented with variable symptoms, including undescended testis (26%, n=4/15), testicular heaviness/pain (20%, n=3/15) infertility (20%, n=3/15) and metastasis (6%, n=1/15); presentation was unknown in 4 patients. Of note, none of the patients presented because of testicular mass. Serum markers were within normal limits in most patients (93%, n=14/15) with available data. No tumors were identified macroscopically; however, an ill-defined, grey-white, firm area was noted in one orchiectomy specimen. Microscopically, tumor cells were seen in intertubular spaces as dispersed individual cells or small clusters. Tumor cells were round to polygonal with large nuclei and prominent nucleoli. Mild to moderate lymphocytic infiltrates were seen admixed with tumor cells in 40% (n=6/15) of the tumors. GCNIS was present in association with most PITS (73%, n=11/15). Tubular atrophy with thickening of the basement membrane and Leydig cell hyperplasia was observed in one tumor. Thirty-three percent (n=5/15) of the tumors showed pagetoid involvement of rete testis, including the tumor with metastasis. All tumors showed the classical immunohistochemical profile of seminoma, with PLAP, c-KIT, OCT3/4, D2-40 and SALL4 positivity. PITS can be clinically & pathologically inconspicuous, difficult to stage and liable to be misdiagnosed especially if presented with metastasis. Despite the inconspicuousness, PITS may represent an aggressive growth pattern of seminoma with the propensity for rete testis invasion.

  View details for DOI 10.1016/j.humpath.2024.105667

  View details for PubMedID 39305965

• Cowper Glands Identified in Prostate and Urethral Specimens: A Comprehensive Immunohistochemical Characterization and Potential Diagnostic Pitfall. International journal of surgical pathology Sangoi, A. R., Al-Obaidy, K. I., Akgul, M., Mehra, R., Chan, E., Williamson, S. R. 2024: 10668969241268375

  Abstract

  Cowper glands recognition remains one of the key histoanatomic benign mimics of prostatic adenocarcinoma. In most instances, these can be identified based on the dimorphic population of lobulated acini and duct(s). However, in the prostate biopsy setting with incomplete/distorted cores, this may not be immediately apparent and may warrant use of immunohistochemistry to argue against prostatic adenocarcinoma. Although immunohistochemical pitfalls in Cowper glands have been described, to our knowledge a comprehensive evaluation of both traditional and purportedly prostate-specific novel markers in Cowper glands has not been previously performed. Herein, we studied the clinicopathological and immunohistochemical features of 21 male patients (age range 39-81 years; mean=63 years), including 15 prostate biopsies (7 of which also had prostate cancer in the same specimen set and 2 of which had both prostate cancer and Cowper glands in the same biopsy core). Immunohistochemistry showed the following results in Cowper glands: 100% positive for NKX3.1, 100% positive (basal cells) for both high molecular weight keratin and p63, 57% positive for PSAP, 25% positive for PSMA, 5% positive for AMACR, and 0% positive for PSA. In conclusion, for specimens lacking appreciable dimorphic morphology, caution should be rendered when using prostate-specific markers (PSA, PSAP, PSMA, and NKX3.1) as these can show considerable staining in Cowper glands and be a pitfall. Instead, findings from this cohort indicate relying on basal markers (high molecular weight keratin/p63; either individually or in a "cocktail" approach) and PSA are most useful in distinguishing Cowper glands (retained basal cell markers staining) from prostatic adenocarcinoma.

  View details for DOI 10.1177/10668969241268375

  View details for PubMedID 39165181

• Incidence and Pitfalls of Adipose Tissue Encountered in Prostatic Transurethral Resections and Related Specimens. International journal of surgical pathology Wu, D. J., Brooks, J. D., Rizkalla, C., Sangoi, A. R. 2024: 10668969241265032

  Abstract

  While the presence of adipose tissue and its involvement by prostatic cancer (extraprostatic extension) is well-recognized in prostate biopsies, adipose tissue in transurethral resections of the prostate (TURP) is largely unexplored. Herein, 200 consecutive TURPs and related specimens were reviewed, including a separate 3-year analysis of specimens containing prostatic cancer, with the following data collected: presence of fat, presence of cancer within fat, and quantity of fat. For specimens with both fat and prostatic cancer, specimen weight and tumor volume were recorded. Within the 200 consecutive TURPs and related specimens, adipose tissue was identified in 20%; 55% had 2.5 mm of adipose tissue; the number of fragments with adipose tissue ranged from 1 to 14. No correlation between specimen weight and measured extent of adipose tissue or number of fragments with adipose tissue was identified. Of all the specimens with prostatic cancer, 15/56 (27%) involved adipose tissue, with two specimens with large cancer volume (>90%) demonstrating extensive involvement of adipose tissue. Adipose tissue is frequently present within TURP and related specimens with variability in extent. The etiology behind encountering adipose tissue is uncertain, and it could represent resection into peri-prostatic fat, intraprostatic fat, or bladder neck fat sampling. Although encountering adipose tissue involved by cancer in TURP and related specimens may imply extraprostatic extension (pT3a), further studies are needed to corroborate these findings as well as to determine if these should be included in reported synoptics.

  View details for DOI 10.1177/10668969241265032

  View details for PubMedID 39090855

• Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature. Histopathology Lobo, A., Collins, K., Kaushal, S., Acosta, A. M., Akgul, M., Adhya, A. K., Al-Ahmadie, H. A., Al-Obaidy, K. I., Amin, A., Amin, M. B., Aron, M., Balzer, B. L., Biswal, R., Mohanty, S., Browning, L., Chakrabarti, I., Cima, L., Cimadamore, A., Desai, S., Dhillon, J., Deshwal, A., Diego, G. G., Diwaker, P., Galea, L. A., Magi-Galluzzi, C., Giannico, G. A., Gupta, N. S., Haider, A., Hirsch, M. S., Iczkowski, K. A., Arora, S., Jain, E., Jain, D., Jha, S., Kandukuri, S., Kao, C., Kryvenko, O. N., Kumar, R. M., Kumari, N., Kunju, L. P., Kuthi, L., Lobo, J., Lopez, J. I., Luthringer, D. J., Maclean, F., Manini, C., Mannan, R., Martos, M. G., Mehra, R., Menon, S., Mishra, P., Moch, H., Montironi, R., Baisakh, M. R., Netto, G. J., Nigam, L. K., Osunkoya, A. O., Pagliuca, F., Paner, G. P., Panizo, A., Parwani, A. V., Picken, M. M., Prendeville, S., Przybycin, C. G., Purkait, S., Queipo, F. J., Rao, B. V., Rao, P., Reuter, V. E., Sancheti, S., Sangoi, A. R., Sardana, R., Satturwar, S., Shah, R. B., Sharma, S., Dixit, M., Verma, M., Sirohi, D., Smith, S. C., Soni, S., Sundaram, S., Swain, M., Tretiakova, M., Trpkov, K., MunizUnamunzaga, G., Zhou, M., Williamson, S. R., Lopez-Beltran, A., Cheng, L., Mohanty, S. K. 2024

  Abstract

  AIMS: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe.METHODS AND RESULTS: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy.CONCLUSION: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.

  View details for DOI 10.1111/his.15287

  View details for PubMedID 39075659

• Immunophenotypical assessment supports that post-chemotherapy glandular tumours of germ cell origin straddle between glandular yolk sac tumour and 'somatic-type' adenocarcinoma. Histopathology Ricci, C., Ambrosi, F., Grillini, A., Grillini, M., Mollica, V., Fiorentino, M., Sangoi, A. R., De Leo, A., Idrees, M. T., Ulbright, T. M., Acosta, A. M. 2024

  View details for DOI 10.1111/his.15277

  View details for PubMedID 38952141

• Expression of L1 Cell Adhesion Molecule (L1CAM), A Nephronal Principal Cell Marker, in Nephrogenic Adenoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Mannan, R., Wang, X., Mahapatra, S., Wang, S., Chinnaiyan, A. K., Skala, S. L., Zhang, Y., McMurray, L. M., Zelenka-Wang, S., Cao, X., Sangoi, A. R., Dadhania, V., Picken, M. M., Menon, S., Ahmadie, H. A., Chinnaiyan, A. M., Dhanasekaran, S. M., Mehra, R. 2024: 100540

  Abstract

  Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or operative history. Its histopathological diversity can create diagnostic dilemmas and pathologists utilize morphological evaluation along with available immunohistochemical markers to navigate these challenges. Immunohistochemical assays currently do not designate or specify nephrogenic adenoma's potential putative cell of origin. Leveraging single-cell RNA sequencing technology, we nominated a principal cell collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for nephrogenic adenoma. Immunohistochemical characterization revealed L1CAM to be positive in all 35 (100%) patient samples of nephrogenic adenoma; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma in situ, prostatic adenocarcinoma, majority of high-grade urothelial carcinoma, and metastatic urothelial carcinoma. In the study, we also utilized single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for proximal tubule, loop of Henle, and distal tubule (including principal and intercalated cells) which can be used to perform nephronal mapping utilizing RNA in situ hybridization and immunohistochemistry technology. Employing this technique on nephrogenic adenoma we found enrichment of both principal cell marker L1CAM and, the proximal tubule types-A and -B cells markers, PDZKI1P1 and PIGR respectively. The cell type markers for the intercalated cell of distal tubules (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in nephrogenic adenoma. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between distal tubule principal cell (P) cells and nephrogenic adenoma. L1CAM expression will be of potential value in assisting surgical pathologists towards a diagnosis of nephrogenic adenoma in challenging patient samples.

  View details for DOI 10.1016/j.modpat.2024.100540

  View details for PubMedID 38901674

• Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases. Histopathology Potterveld, S. K., Mubeen, A., Anderson, W. J., Clay, M. R., Bourgeau, M., Charville, G. W., Sangoi, A. R. 2024

  Abstract

  Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma.This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma. The majority (26 of 30, 87%) of lesions were accurately diagnosed on biopsy sampling, all of which incorporated testing for MDM2 by immunohistochemistry (IHC), fluorescence in-situ hybridisation (FISH) or a combination of the two as part of the diagnostic work-up. Tumour expression of MDM2 by IHC without confirmatory FISH analysis was sometimes (30%) sufficient to reach a diagnosis, but demonstration of MDM2 amplification by FISH was ascertained in the majority (57%) of biopsy samples. A diagnosis of de-differentiated liposarcoma was not definitively established until resection in four (13%) patients, as no MDM2 testing was performed on the corresponding pre-operative biopsies.When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.

  View details for DOI 10.1111/his.15197

  View details for PubMedID 38646791

• Chromophobe Renal Cell Carcinoma With Extensive Retraction Artifact: A Potential Diagnostic Pitfall From Micropapillary Urothelial Carcinoma. International journal of surgical pathology Sangoi, A. R., Pivovarcikova, K., Akgul, M., Williamson, S. R., Ulamec, M., Rogala, J. D., Martinek, P., Vanecek, T., Hes, O., Alaghehbandan, R. 2024: 10668969241239678

  Abstract

  In addition to "classic" and eosinophilic subtype, chromophobe renal cell carcinoma (RCC) is well-known to demonstrate various morphological patterns including adenomatoid, microcystic, pigmented, multicystic, papillary, neuroendocrine-like, and small cell-like, all of which are important to appreciate for accurate diagnosis. Herein, we expand on a unique chromophobe RCC morphology not previously described consisting of tumor cells with extensive stromal retraction, mimicking upper urothelial tract micropapillary carcinoma (MPC). Twelve MPC-like chromophobe RCC nephrectomies were reviewed with clinicopathological features recorded; molecular testing was performed on 7 of 12 tumors. Patients were mostly men (n=10) with a mean age of 65 years. Mean tumor size was 6.4 cm with pathological stage distribution as follows: 4 (33%) T1a, 2 (17%) T1b, 1 (8%) T2b, and 3 (25%) T3a. The extent of MPC-like chromophobe RCC foci ranged from 10% to 40% (mean=26%; there was no correlation between the extent of MPC-like chromophobe RCC foci and tumor stage). Other chromophobe RCC morphological patterns were not identified. When performed, all (100%) tumors depicted prototypic chromophobe RCC staining pattern of KIT positivity/KRT7 positivity. Molecular showed 6 of 7 (86%) with multiple chromosomal losses. Clinically significant mutations were identified in NF1, TP53, FLCN (likely somatic), CHEK2, and ZFHX3 genes. Follow up available in 9 patients showed no evidence of disease (mean=23 months). Although the etiology behind the extensive stromal retraction in our tumors is unknown, this may likely be artifactual in nature. Nonetheless, it is important to include MPC-like chromophobe RCC in the spectrum of "variant" morphologies to avoid diagnostic pitfalls from micropapillary carcinoma.

  View details for DOI 10.1177/10668969241239678

  View details for PubMedID 38567430

• GATA3 Expression in Prostatic Adenosquamous Carcinoma: A Potential Diagnostic Pitfall. International journal of surgical pathology Potterveld, S. K., Williamson, S. R., Al-Obaidy, K. I., Akgul, M., Chan, E., Giannico, G. A., Sangoi, A. R. 2024: 10668969241241640

  Abstract

  Urothelial carcinoma and prostatic adenocarcinoma can have overlapping histologic features and in some instances pose challenges to pathologists. GATA binding protein 3 (GATA3) immunohistochemistry (IHC) is a well-established tool to aid in this specific diagnostic dilemma as it has been shown to be a sensitive marker for urothelial carcinoma and a putatively specific marker in excluding prostatic adenocarcinoma. However, in encountering an index tumor of prostatic adenosquamous carcinoma positive for GATA3, herein we sought to investigate this potential diagnostic pitfall in a larger series of tumors. In this study, we retrospectively reviewed prostatic adenosquamous carcinomas diagnosed in 17 patients across the authors' institutions and personal consult collections in the past 10 years. GATA3 IHC was either reviewed or performed on tumors not previously tested. We also recorded other immunostains that were performed at initial diagnosis. Positivity for GATA3 was found in 9 of 17 (53%) tumors, all within squamous regions (2 tumors also showed concomitant moderate GATA3 positivity within glandular elements). The GATA3 positive tumors were all positive for p63 in the 7 tumors where p63 was also performed. Of all tumors tested, NKX3.1 was positive in 100% (13/13) of the glandular elements (3 tumors also showed NKX3.1 concomitant positivity within squamous regions). In summary, when encountering a carcinoma with mixed glandular/squamous features in which prostatic origin is being considered, awareness of GATA3 immunoreactivity in a subset of prostatic adenosquamous carcinoma is critical to avoid diagnostic pitfalls.

  View details for DOI 10.1177/10668969241241640

  View details for PubMedID 38562047

• Topline/Final Diagnostic Inclusion of Relevant Histologic Findings in Surgical Pathology Reporting of Carcinoma in Prostate Biopsies. International journal of surgical pathology Mullane, P., Williamson, S. R., Prostate Biopsy Reporting Panel *, Sangoi, A. R. 2024: 10668969241231972

  Abstract

  INTRODUCTION: As the list of histologic parameters to include in surgical pathology reports of prostate cancer biopsies grows, some pathologists include this information in the microscopic description or summary sections of the report, whereas others include it in the "topline" or final diagnosis section. This prompted us to develop a multi-institutional survey to assess reporting trends among genitourinary (GU) pathologists.METHODS: A survey instrument was shared among 110 GU pathologists via surveymonkey.com. Anonymized respondent data was analyzed.RESULTS: Eighty-four (76%) participants completed the survey across four continents. Most participants report tumor volume quantitation (88%), number of cores involved (89%), and both Gleason grade and Grade group (93%) in their topline; 71% include percent of pattern 4, with another 16% including it depending on cancer grade; 58% include the presence of cribriform growth pattern 4, with another 11% including it depending on cancer grade. When present, most include extraprostatic extension (90%), prostatic intraductal carcinoma (77%), and perineural invasion (77%). Inclusion of atypical intraductal proliferation (AIP) in the topline diagnosis was cancer grade-dependent, with 74% including AIP in Grade group 1, 61% in Grade group 2, 45% in Grade group 3, 30% in Grade group 4, and 26% in Grade group 5 cancers.CONCLUSION: Certain histologic features such as Gleason grade and tumor volume/cores involved are frequently included in the topline diagnosis, whereas the incorporation of other findings are more variably included. Prostate biopsy reporting remains a dynamic process with stylistic similarities and differences existing among GU pathologists.

  View details for DOI 10.1177/10668969241231972

  View details for PubMedID 38504649

• TRIM63 Overexpression in FISH Negative Renal Cell Carcinoma with TFE3 or TFEB Rearrangement Mannan, R., Chen, Y., Wang, X., Dhanasekaran, S., Zhang, Y., Dadhania, V., Vaishampayan, U., Shao, L., Brown, N., Betz, B., Mahapatra, S., Chinnaiyan, A., Caldwell-Smith, C., McMurry, L., Cao, X., Su, F., Wang, R., Sangoi, A., Acosta, A., Williamson, S., Argani, P., Tickoo, S., Chinnaiyan, A., Reuter, V., Mehra, R. ELSEVIER SCIENCE INC. 2024: S1010-S1012

  View details for Web of Science ID 001302363403097

• GPNMB Expression Pattern in Molecularly characterized Unclassified Low-Grade Oncocytic Renal Epithelial Neoplasms (ULGOREN), A Study of 14 Distinct Tumors Ma, B., Aron, M., Parwani, A., Kaushal, S., Cheng, L., Jha, S., Lobo, A., Arora, S., Acosta, A., Akgul, M., Williamson, S., Sangoi, A., Mohanty, S., Kandukuri, S. ELSEVIER SCIENCE INC. 2024: S1003-S1005

  View details for Web of Science ID 001302363403092

• Recurrent BRAF V600E Mutations and HMGA2::WIF1 Fusions in Ceruminous Adenoma: Does Molecular Evidence Support a Simpler Classification? Rooper, L., Thompson, L., Sangoi, A., Oliver, D., Gagan, J., Bishop, J. ELSEVIER SCIENCE INC. 2024: S1347-S1348

  View details for Web of Science ID 001302363404208

• Primary Intrarenal Hemangiomas: A Review of 38 Cases Faraz, M., Akgul, M., Subasi, N., Alghamdi, M., Sangoi, A., Panizo, A., Nova-Camacho, L., Garcia Martos, M., Lobo, A., Jha, S., Yorukoglu, K., Hajiyeva, S., Williamson, S., Bhardwaj, S., Kandukuri, S., Mohanty, S. ELSEVIER SCIENCE INC. 2024: S943-S945

  View details for Web of Science ID 001302363403046

• Renal Tumors with Fibromyomatous Stroma Represent a Heterogeneous Group of Tumors with Distinct Molecular Alterations Siegmund, S., Maclean, F., Tsai, H., Sangoi, A., Barletta, J., Amin, M., Swarbrick, N., Khani, F., Williamson, S., Dal Cin, P., Hirsch, M. ELSEVIER SCIENCE INC. 2024: S1057-S1058

  View details for Web of Science ID 001302363403138

• GPNMB Immunohistochemistry in Low-Grade Oncocytic Tumor of the Kidney Consistently Recognizes TSC/MTOR Altered Tumors but Not PIK3CA Altered Tumors Williamson, S., Lobo, A., Jha, S., Akgul, M., Sangoi, A., Berney, D., Comperat, E., Hes, O., Trpkov, K., Mohanty, S. ELSEVIER SCIENCE INC. 2024: S1072-S1073

  View details for Web of Science ID 001302363403153

• Evaluating GPNMB Immunostaining as a Surrogate Marker for TSC/MTOR Altered Renal Tumors in a Cohort of Eosinophilic Solid and Cystic Renal Cell Carcinoma Lobo, A., Sangoi, A., Akgul, M., Acosta, A., Arora, S., Jha, S., Kaushal, S., Mishra, S., Baisakh, M., Pattnaik, N., Rao, B., Deshwal, A., Parwani, A., Osunkoya, A., Cheng, L., Williamson, S., Mohanty, S. ELSEVIER SCIENCE INC. 2024: S993-S994

  View details for Web of Science ID 001302363403086

• Expanding the Spectrum of De Novo and Treatment-related Neuroendocrine Prostate Cancer: A Clinicopathologic and Genomic Evaluation in a Contemporary Cohort of 103 Patients Lobo, A., Jha, S., Akgul, M., Sangoi, A., Acosta, A., Mishra, S., Deshwal, A., Baisakh, M., Pattnaik, N., Arora, S., Kaushal, S., Kandukuri, S., Cheng, L., Parwani, A., Osunkoya, A., Williamson, S., Mohanty, S. ELSEVIER SCIENCE INC. 2024: S991-S993

  View details for Web of Science ID 001302363403085

• The Gene's Out of the Bottle: Uncovering Molecularly Defined Renal Carcinomas in The Cancer Genome Atlas (TCGA) Database Pacheco, R., Alghamdi, M., Nezami, B., Sangoi, A., Williamson, S., Akgul, M. ELSEVIER SCIENCE INC. 2024: S1030-S1032

  View details for Web of Science ID 001302363403117

• Paratesticular Clear Cell Papillary Cystadenomas: A Morphologic and Immunohistochemical Comparison with Metastatic Renal Cell Carcinoma Morrison, C., Chan, E., Acosta, A., Panizo, A., Williamson, S., Mubeen, A., Nova-Camacho, L., Sangoi, A. ELSEVIER SCIENCE INC. 2024: S1022-S1023

  View details for Web of Science ID 001302363403107

• Foamy Macrophages in Clear Cell Renal Cell Carcinoma are Highly Associated with BAP1Deficient Tumors Gupta, A., Zalles, N., Sangoi, A., Akgul, M., Al-Obaidy, K., Mohanty, S., Przybycin, C., Myles, J., Gallan, A., Nguyen, J., Alaghehbandan, R., Williamson, S. ELSEVIER SCIENCE INC. 2024: S952-S953

  View details for Web of Science ID 001302363403055

• Diagnostic Discrepancy in The Cancer Genome Atlas Kidney Renal Cell Carcinoma Cohorts Pacheco, R., Alghamdi, M., Nezami, B., George, R., Oktay, M., Yaskiv, O., Friedman, P., Sheuka, N., Bhardwaj, S., Mohanty, S., Sangoi, A., Williamson, S., Akgul, M. ELSEVIER SCIENCE INC. 2024: S1032-S1034

  View details for Web of Science ID 001302363403118

• Invasive Urothelial Carcinoma with Choroid And Myxoid Features Shows Increased Alterations In RAS/RAF Pathway Chan, E., Stohr, B., Sangoi, A., Sirohi, D. ELSEVIER SCIENCE INC. 2024: S918-S919

  View details for Web of Science ID 001302363403025

• Pure Intertubular Seminoma (PITS) of the Testis: A Multi-institutional Cohort of a Rare Growth Pattern of Seminoma Kaushal, S., Acosta, A., Sangoi, A., Lobo, A., Jha, S., Beg, A., Sharma, S., Arora, S., Jain, E., Akgul, M., Williamson, S., Baisakh, M., Pattnaik, N., Parwani, A., Osunkoya, A., Cheng, L., Amin, M., Mohanty, S. ELSEVIER SCIENCE INC. 2024: S967-S969

  View details for Web of Science ID 001302363403067

• Highlighting the Differential Pattern of GPNMB Expression in a Cohort of ELOC-mutated RCC Mohanty, S., Lobo, A., Aron, M., Chan, E., Jha, S., Sangoi, A., Akgul, M., Deshwal, A., Acosta, A., Williamson, S., Kaushal, S., Cheng, L., Rao, B., Parwani, A., Osunkoya, A., Jia, L., Amin, M., Shah, R. ELSEVIER SCIENCE INC. 2024: S1017-S1018

  View details for Web of Science ID 001302363403104

• Vascular, adipose tissue, and/or calyceal invasion in clear cell tubulopapillary renal cell tumour: potentially problematic diagnostic scenarios. Histopathology Sangoi, A. R., Tsai, H., Harik, L., Mahlow, J., Tretiakova, M., Williamson, S. R., Hirsch, M. S. 2024

  Abstract

  AIMS: The 2022 WHO classification for kidney tumours recently downgraded clear cell tubulopapillary (also known as clear cell papillary) renal cell carcinoma (RCC) to a benign neoplasm (i.e. clear cell tubulopapillary renal cell tumour) based on the overwhelmingly banal nature of this neoplasm. However, it has been recognized that some clear cell tubulopapillary renal cell tumours demonstrate vascular, adipose or pelvicalyceal invasion, raising the possibility of more aggressive behaviour. The goal of this study was to determine if these 'high stage' features have an effect on tumour prognosis, warranting a carcinoma designation.METHODS AND RESULTS: After excluding cases with tissue artefact (i.e. prior core biopsy track changes) and other RCC subtypes with next-generation sequencing, nine clear cell tubulopapillary renal cell tumours with these so-called 'high stage' features, and otherwise classic morphologic and immunophenotypic findings, including low-grade cytology and 'cup-like' CA9 expression, were evaluated. Median tumour size was 2.2cm with a range of 0.8 to 6.7cm. Eight cases (89%) demonstrated perinephric or hilar adipose tissue invasion, although most of these cases showed a bulging (in contrast to an infiltrative) growth pattern. One case demonstrated renal vascular invasion in addition to hilar adipose tissue invasion, and one case demonstrated extension into the pelvicalyceal system. There were no recurrences or evidence of metastatic disease.CONCLUSION: These overall findings continue to support the benign designation for clear cell tubulopapillary renal cell tumours, despite morphologic features that might raise the possibility of a 'higher stage' neoplasm.

  View details for DOI 10.1111/his.15166

  View details for PubMedID 38422612

• Biphasic papillary (biphasic squamoid alveolar) renal cell carcinoma: a clinicopathologic and molecular study of 17 renal cell carcinomas including 10 papillary adenomas. Virchows Archiv : an international journal of pathology Nova-Camacho, L. M., Acosta, A. M., Akgul, M., Panizo, A., Galea, L. A., Val-Carreres, A., Talavera, J. A., Guerrero-Setas, D., Martin-Arruti, M., Ruiz, I., Garcia-Martos, M., Sangoi, A. R. 2024

  Abstract

  Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With<70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6cm (range 1.6-8cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.

  View details for DOI 10.1007/s00428-024-03768-x

  View details for PubMedID 38388964

• Are Renal Tumor Diagnostics Becoming Too Advanced for Many Pathology Laboratories? International journal of surgical pathology Akbulut, D., Sangoi, A. R., Williamson, S. R., Akgul, M. 2024: 10668969241231982

  Abstract

  The recent influx of novel renal neoplasms, particularly molecularly-defined renal carcinomas, has introduced new challenges in the daily practice of most pathology laboratories. These tumors are uncommon, they do not always have well-established morphologic features, and the expression profile of most common biomarkers is not well understood. Moreover, the diagnosis of molecularly-defined renal carcinomas requires the documentation of the disease-defining molecular alteration, with molecular studies or surrogate immunohistochemical markers. Unfortunately, most pathology laboratories lack molecular laboratories, or it is not cost-effective to maintain assays of the specific biomarkers in these unusual tumors. Pathologists should have updated knowledge about the recent changes in renal neoplasms and be aware of these limitations.

  View details for DOI 10.1177/10668969241231982

  View details for PubMedID 38378181

• Upper Urothelial Tract Extraosseous Bone Formation: An Unexpected Finding and Differential Diagnostic Considerations. International journal of surgical pathology Potterveld, S. K., Wang, N., Sangoi, A. R. 2024: 10668969231221755

  Abstract

  Extraosseous bone formation of the upper urothelial tract is an unusual phenomenon with limited documentation in the uropathology literature, reported in only 2 clinical series of patients undergoing percutaneous nephrolithotomy for the management of renal stones. While speculations regarding the pathogenesis of this occurrence have been published, heterotopic ossification is still poorly understood. We report the finding of extraosseous bone formation in the renal pelvis of a 30-year-old male patient with a history of kidney stones. Histologic sections of the ureter and renal pelvis showed submucosal nodules of woven bone. Ancillary fluorescence in-situ hybridization studies were negative for MDM2 amplification and USP6 rearrangement.

  View details for DOI 10.1177/10668969231221755

  View details for PubMedID 38298018

• Extramedullary haematopoiesis in renal neoplasms. Histopathology George, R., Akgul, M., Lightle, A., Kuthi, L., Sánta, F., Panizo, A., Queipo Gutiérrez, F. J., Martos, M. G., Kaushal, S., Mohanty, S., Mehra, R., Williamson, S., Sangoi, A. R. 2024

  View details for DOI 10.1111/his.15138

  View details for PubMedID 38192207

• Seminal Vesicle Stromal Lipofuscinosis: A Rare Incidental Finding with Potential for Misdiagnosis. International journal of surgical pathology Potterveld, S. K., Sangoi, A. R. 2023: 10668969231215424

  Abstract

  We report a patient with isolated stromal lipofuscinosis of the seminal vesicle, a rare entity characterized by intracytoplasmic pigmented granules within stromal cells intimately surrounding seminal vesicle epithelium. Only 4 patients with this unusual phenomenon have been previously reported in the literature. Recognizing this incidental and presumably non-pathologic finding is important to prevent misclassification as a more concerning lesion.

  View details for DOI 10.1177/10668969231215424

  View details for PubMedID 38058146

• Adenoid cystic carcinoma metastatic to the kidney: a series of 10 patients emphasizing unilateral presentation and long time interval from primary diagnosis. Virchows Archiv : an international journal of pathology Akgul, M., Cha, J., Williamson, S. R., Arora, K., Celik, M., Rooper, L. M., Zynger, D. L., Sangoi, A. R. 2023

  Abstract

  Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (n = 6). Patients were predominately female (n = 7) with a median age of 48 years (35-62 years). The most common primary location of the AdCC was head and neck (n = 6, among them parotid gland = 4), followed by lung (n = 2), breast (n = 1), and vulva (n = 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1-336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.

  View details for DOI 10.1007/s00428-023-03711-6

  View details for PubMedID 37987868

• Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors. The American journal of surgical pathology Siegmund, S., Ricci, C., Kao, C. S., Sangoi, A. R., Mohanty, S., Fletcher, C. D., Colecchia, M., Acosta, A. M. 2023

  Abstract

  Sertoli cell tumor is a type of testicular sex cord-stromal tumor (TSCST) typically driven by gain-of-function CTNNB1 variants. Recently, molecular studies have identified TSCSTs (including Sertoli cell tumors) with loss-of-function APC variants, raising the possibility that germline APC alterations may predispose to TSCSTs. In this study, we evaluated 4 TSCSTs from 4 individual patients, including 3 APC-mutant neoplasms identified in prior studies (1 in a patient with familial adenomatous polyposis [FAP] and 2 in patients with unknown syndromic status) and 1 tumor of unknown mutational status diagnosed in a patient with known FAP. Three neoplasms were typical Sertoli cell tumors, and 1 was a malignant unclassified TSCT. All neoplasms exhibited diffuse nuclear beta-catenin expression. Non-neoplastic tissue could be obtained for DNA sequencing in the 3 Sertoli cell tumors. Comparative assessment of non-neoplastic and lesional tissue in these cases suggested that germline APC variants with subsequent inactivation of the gene (loss of heterozygosity) were the likely oncogenic driver of these Sertoli cell tumors. In the malignant unclassified TSCSTs, APC inactivation was also interpreted as the most likely driver event, and the germline origin of the variant was inferred using a recently published method. The results of this study suggest that pathogenic germline APC alterations (eg, FAP and variants thereof) may predispose to TSCSTs.

  View details for DOI 10.1097/PAS.0000000000002132

  View details for PubMedID 37811860

• Positive NKX3.1 as a diagnostic pitfall for prostate cancer in extramammary Paget's disease of genitourinary sites. Histopathology Chen, C. V., Francois, R. A., Mully, T. W., Sangoi, A., LeBoit, P. E., Simko, J. P., Chan, E. 2023

  View details for DOI 10.1111/his.15061

  View details for PubMedID 37794658

• IDH1 p.R132C mutation in prostatic carcinoma with psammomatous calcifications: report of two cases. Pathology Galea, L. A., Flynn, M., Jones, V., Harraway, J., Appu, S., Sangoi, A. R. 2023

  View details for DOI 10.1016/j.pathol.2023.06.017

  View details for PubMedID 37716816

• Clear Cell Renal Cell Carcinoma With Syncytial-Type Multinucleated Giant Tumor Cells: A Clinicopathologic Study of 14 Cases. International journal of surgical pathology Nova-Camacho, L. M., Sangoi, A. R. 2023: 10668969231189798

  Abstract

  The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered.

  View details for DOI 10.1177/10668969231189798

  View details for PubMedID 37525565

• IgG4-Related Prostatitis: A Potentially Underappreciated Finding for Pathologists. International journal of surgical pathology Sangoi, A. R., Maclean, F., Myint, E., Chan, E. 2023: 10668969231171659

  View details for DOI 10.1177/10668969231171659

  View details for PubMedID 37143307

• Scars Run Deep: Problematic Morphology and Immunoprofile of Scars in Renal Oncocytomas. International journal of surgical pathology Sangoi, A. R., Nova-Camacho, L. M., Akgul, M., Queipo, F. J., Aisa, G., Garcia-Martos, M., Panizo, A. 2023: 10668969231171683

  Abstract

  In some instances, the central scar of renal oncocytoma can demonstrate entrapped cells with unusual morphology and aberrant immunoprofile creating potential diagnostic confusion. Herein, 100 renal oncocytomas containing scars with embedded epithelial cells were identified from 6 institutions, including nephrectomies (64% partial, 36% radical) of similar laterality (left=51%) and sex distribution (male=56%), with patient ages ranging from 38 to 86 years (mean=64.3years) and tumor sizes ranging from 2 to 16 cm (mean=5.3 cm). Immunohistochemistry was performed on all tumors for KRT7, KIT, vimentin, and CA9 with staining intensity and extensity separately analyzed. Of 4 architectural patterns of cells within the scar, 60% showed tubular pattern. Of 4 cytologies within the scar, flat/elongated (49%) and cuboidal cells (40%) predominated. Within the scar, 62% showed eosinophilic cytoplasm, with 38% showing both cleared and eosinophilic cytoplasm; notably, 79% showed higher grade nuclei than typical oncocytes. A subset of scar cells showed mucinous-like basophilic secretions (19%). Compared to background renal oncocytoma, tumor cells within the scar were more often positive for vimentin, KRT7, and CA9 and more frequently negativity for KIT. Specifically, of the notable "aberrant" immunoprofiles, 79% showed KRT7 positivity/KIT negativity/vimentin positive, 84% showed vimentin positivity/CA9 positivity, and 78% showed KIT negativity/vimentin positivity/CA9 positivity. While encountering scars within renal oncocytomas is not uncommon, what is not well appreciated is the unique morphology and immunohistochemistry of tumor cells within the scar. Comparing tumor morphology and immunoprofile of the scar to the background oncocytoma is helpful to avoid interpretative confusion.

  View details for DOI 10.1177/10668969231171683

  View details for PubMedID 37143313

• Molecular Correlates of Aggressive Behavior and Biologic Progression in Testicular Sertoli Cell Tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Rizzo, N. M., Sholl, L. M., Kao, C. S., Cornejo, K. M., Sangoi, A. R., Hirsch, M. S., Collins, K., Gordetsky, J. B., Reyes Curcio, F. A., Fletcher, C. D., Ulbright, T. M., Acosta, A. M. 2023: 100152

  Abstract

  Sertoli cell tumor (SCT) is the second most common type of sex cord-stromal tumor in men and ∼10% exhibit malignant behavior. Although CTNNB1 variants have been described in SCTs, only a limited number of metastatic cases have been analyzed, and the molecular alterations associated with aggressive behavior remain largely unexplored. This study evaluated a series of nonmetastasizing and metastasizing SCTs using next-generation DNA sequencing to further characterize their genomic landscape. Twenty-two tumors from 21 patients were analyzed. Cases were divided into metastasizing SCTs and nonmetastasizing SCTs. Nonmetastasizing tumors were considered to have aggressive histopathologic features if they exhibited ≥1 of the following: size > 2.4 cm, necrosis, lymphovascular invasion, ≥ 3 mitoses per 10 high-power fields (HPF), severe nuclear atypia or invasive growth. Six patients had metastasizing SCTs and the remaining 15 had nonmetastasizing SCTs; 5 nonmetastasizing tumors had ≥1 aggressive histopathologic feature(s). Gain-of-function CTNNB1 or inactivating APC variants were highly recurrent in nonmetastasizing SCTs (combined frequency >90%), with arm-/chromosomal-level CNVs, loss of 1p and CTNNB1 LOH occurring exclusively in CTNNB1-mutant tumors with aggressive histopathologic features or size >1.5 cm. Nonmetastasizing SCTs were almost invariably driven by WNT pathway activation. In contrast, only 50% of metastasizing SCTs harbored gain-of-function CTNNB1 variants. The remaining 50% of metastasizing SCTs were CTNNB1-wild-type and harbored alterations in TP53, MDM2, CDKN2A/CDKN2B, and TERT pathways. These findings suggest that aggressive SCTs can arise from progression of CTNNB1-mutant benign SCTs, or from CTNNB1-wild type tumors with alterations of TP53, cell cycle regulation, and telomere maintenance pathways.

  View details for DOI 10.1016/j.modpat.2023.100152

  View details for PubMedID 36906070

• Current Practices in Prostate Pathology Reporting: Results From A Survey of Genitourinary Pathologists Williamson, S., Alaghehbandan, R., Amin, A., Amin, M., Aron, M., Brimo, F., Chan, E., Cheng, L., Colecchia, M., Dhillon, J., Downes, M., Evans, A., Harik, L., Hassan, O., Haider, A., Humphrey, P., Jha, S., Kandukuri, S., Kao, C., Kaushal, S., Khani, F., Kryvenko, O., Kweldam, C., Lal, P., Lobo, A., Maclean, F., Magi-Galluzzi, C., Mehra, R., Menon, S., Miyamoto, H., Mohanty, S., Montironi, R., Nesi, G., Netto, G., Nguyen, J., Nourieh, M., Osunkoya, A., Paner, G., Sangoi, A., Shah, R., Srigley, J., Tretiakova, M., Troncoso, P., Trpkov, K., Van Der Kwast, T., Zhang, M., Zynger, D., Giannico, G. ELSEVIER SCIENCE INC. 2023: S826-S827

  View details for Web of Science ID 000990969801345

• Clear Cell Renal Cell Carcinoma with Focal Psammomatous Calcifications: A Rare Occurrence Mimicking Translocation Carcinoma. Histopathology Sangoi, A. R., Al-Obaidy, K. I., Cheng, L., Kao, C., Chan, E., Sadasivan, S., Levin, A. M., Alvarado-Cabrero, I., Kunju, L. P., Mehra, R., Mannan, R., Wang, X., Dhillon, J., Tretiakova, M., Smith, S. C., Hes, O., Williamson, S. R. 2022

  Abstract

  AIMS: Renal cell carcinoma (RCC) with clear cells and psammoma-like calcifications would often raise suspicion for MITF family translocation RCC. However, we have rarely encountered tumors consistent with clear cell RCC that contain focal psammomatous calcifications.METHODS & RESULTS: We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in situ hybridization (FISH and RNA ISH). Twenty-one tumors were identified: 12 men, 9 women, ages 45 to 83years. Tumor size was 2.3 to 14.0 cm (median 6.75 cm). Nucleolar grade was 3 (n=14), 2 (n=4), or 4 (n=3). In addition to clear cell pattern, morphology included eosinophilic (n=12), syncytial giant cell (n=4), rhabdoid (n=2), branched glandular (n=1), early spindle cell (n=1), and poorly differentiated components (n=1). Labeling for CA9 was usually 80-100% of the tumor cells (n=17/21) but was sometimes decreased in areas of eosinophilic cells (n=4). All (19/19) were positive for CD10. Most (19/20) were positive for AMACR (variable staining, 20-100%). Staining was negative for keratin 7, although 4 showed rare positive cells (4/20). Results were negative for cathepsin K (0/19), melan A (0/17), HMB45 (0/17), TFE3 (0/5), TRIM63 RNA-ISH (0/13), and TFE3 (0/19) and TFEB rearrangements (0/12). Seven of 19 (37%) showed chromosome 3p deletion. One (1/19) showed trisomy 7 and 17 without papillary features.CONCLUSIONS: Psammomatous calcifications in RCC with a clear cell pattern suggests a diagnosis of MITF family translocation RCC; however, psammomatous calcifications can rarely be found in true clear cell RCC.

  View details for DOI 10.1111/his.14854

  View details for PubMedID 36564980

• Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis. The American journal of surgical pathology Ladwig, N. R., Bean, G. R., Pekmezci, M., Boscardin, J., Joseph, N. M., Therrien, N., Sangoi, A. R., Piening, B., Rajamanickam, V., Galvin, M., Bernard, B., Zaloudek, C., Rabban, J. T., Garg, K., Umetsu, S. E. 2022

  Abstract

  Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs. In this study, a series of 11 uterine IMTs, 5 of which demonstrated aggressive behavior, were evaluated for clinicopathologic variables and additionally subjected to capture-based next-generation sequencing with or without whole-transcriptome RNA sequencing. In the 6 IMTs without aggressive behavior, ALK fusions were the sole pathogenic alteration. In contrast, all 5 aggressive IMTs harbored pathogenic molecular alterations and numerous copy number changes in addition to ALK fusions, with the majority of the additional alterations present in the primary tumors. We combined our series with cases previously reported in the literature and performed statistical analyses to propose a novel clinicopathologic risk stratification score assigning 1 point each for: age above 45 years, size≥5cm,≥4 mitotic figures per 10 high-power field, and infiltrative borders. No tumors with 0 points had an aggressive outcome, while 21% of tumors with 1 to 2 points and all tumors with ≥3 points had aggressive outcomes. We propose a 2-step classification model that first uses the clinicopathologic risk stratification score to identify low-risk and high-risk tumors, and recommend molecular testing to further classify intermediate-risk tumors.

  View details for DOI 10.1097/PAS.0000000000001987

  View details for PubMedID 36344483

• Clinicopathologic Spectrum of Secondary Solid Tumors of the Prostate of Nonurothelial Origin: Multi-institutional Evaluation of 85 Cases. The American journal of surgical pathology Acosta, A. M., Gordetsky, J. B., Collins, K., Osunkoya, A. O., Sangoi, A. R., Miyamoto, H., Kao, C. S., Trpkov, K., Van Leenders, G. J., Wobker, S. E., Maclean, F., Lal, P., Daniel, R. E., Brimo, F., Wasco, M., Hirsch, M. S., Baniak, N., Diaz-Perez, J. A., Cornejo, K. M., Choy, B., Mehra, R., Williamson, S. R., Epstein, J. I., Matoso, A. 2022

  Abstract

  Secondary involvement of the prostate by urothelial or hematolymphoid neoplasms is relatively common and well-described. In contrast, less is known about the clinicopathologic spectrum of secondary solid tumors of the prostate of nonurothelial origin. This study evaluated a series of secondary nonurothelial solid tumors of the prostate diagnosed at 21 institutions. Eighty-five patients with a median age at diagnosis of 64 years were included. Sixty-two patients had clinically manifest disease (62/85, 73%), 10 were diagnosed incidentally (10/85, 12%), and 13 (13/85, 15%) had no detailed clinical data available about symptomatology at presentation. Among patients with clinically manifest disease, the most common symptoms and signs were lower urinary tract symptoms (either obstructive of irritative; 36/62, 58%), abdominal or pelvic pain or discomfort (16/62, 26%), and hematuria (12/62, 19%). Metastasis and direct invasion occurred at roughly similar frequencies (47% vs. 42%) in this series, and in 11% of the cases, the mechanism of spread to the prostate was unclear/uncertain. Overall, among tumors with confirmed sites of origin, the most common primary sites were gastrointestinal tract (53/85, 62%), lung (9/85, 11%), skin (6/85, 7%), and testis (4/85, 5%). Among metastases, the most common tumor types were lung carcinomas (9/40, 23%), colorectal adenocarcinomas (7/40, 18%), melanoma (6/40, 15%), and germ cell tumors (6/40, 15%). This study demonstrated that secondary involvement of the prostate by solid tumors of nonurothelial origin is commonly symptomatic and that the most frequent sites of origin are the gastrointestinal tract, lung, skin, and testis. These findings are worth considering when lesions with unusual cytomorphology and/or architecture are encountered in prostate specimens.

  View details for DOI 10.1097/PAS.0000000000001907

  View details for PubMedID 35900850

• Granulomas associated with renal neoplasms: A multi-institutional clinicopathological study of 111 cases. Histopathology Sangoi, A. R., Maclean, F., Mohanty, S., Hes, O., Daniel, R., Lal, P., Canete-Portillo, S., Magi-Galluzzi, C., Cornejo, K. M., Collins, K., Hwang, M., Falzarano, S. M., Feely, M. M., Dababneh, M., Harik, L., Tretiakova, M., Akgul, M., Manucha, V., Chan, E., Kao, C., Siadat, F., Arora, K., Barkan, G., Cheng, L., Hirsch, M., Lei, L., Wasco, M., Williamson, S. R., Acosta, A. M. 2022

  Abstract

  AIMS: Formal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort.METHODS AND RESULTS: One hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies. Patient ages ranged from 27 to 85years (average=60.1years; male=61%). Renal neoplasms included clear cell renal cell carcinoma (RCC; 86%), papillary RCC (8%), chromophobe RCC (3%), clear cell papillary RCC (1%), mixed epithelial stromal tumour (1%) and oncocytoma (1%). Granulomas were peritumoral in 36%, intratumoral in 24% andboth in 40% of cases. Total granuloma count per case ranged from one to 300 (median=15) withsizes ranging from 0.15 to 15mm (mean= 1.9mm). Necrotising granulomas were seen in 14%of cases. Histochemical stains for organisms were performed on 45% of cases (all negative). Sixteen cases (14%) had a prior biopsy/procedure performed, and eight patients had neoadjuvant immunotherapy or chemotherapy. Eleven patients (10%) had a confirmed diagnosis of sarcoidosis, including five in whom sarcoidosis was diagnosed after nephrectomy.CONCLUSION: Based on this largest case-series to date, peri-/intratumoral granulomas associated with renal neoplasms may be more common than initially perceived. The extent of granulomatous inflammation can vary widely and may or may not have necrosis with possible aetiologies, including prior procedure or immunotherapy/chemotherapy.Although a clinical association with sarcoidosisis infrequent it can still occur, and the presence of granulomas warrants mention in pathology reports.

  View details for DOI 10.1111/his.14633

  View details for PubMedID 35347739

• Molecular Characterization of Urachal Neoplasms Khan, O., Kunder, C., Kao, C., Sangoi, A. SPRINGERNATURE. 2022: 614-615

  View details for Web of Science ID 000770361801201

• Clear Cell Renal Cell Carcinoma with Psammomatous Calcifications: A Rare Occurrence Mimicking Translocation Carcinoma Sangoi, A., Al-Obaidy, K., Cheng, L., Kao, C., Chan, E., Sadasivan, S., Alvarado-Cabrero, I., Kunju, L., Dhillon, J., Tretiakova, M., Smith, S., Hes, O., Williamson, S. SPRINGERNATURE. 2022: 664

  View details for Web of Science ID 000770361801245

• Molecular Characterization of Urachal Neoplasms Khan, O., Kunder, C., Kao, C., Sangoi, A. SPRINGERNATURE. 2022: 614-615

  View details for Web of Science ID 000770360201201

• Clear Cell Renal Cell Carcinoma with Psammomatous Calcifications: A Rare Occurrence Mimicking Translocation Carcinoma Sangoi, A., Al-Obaidy, K., Cheng, L., Kao, C., Chan, E., Sadasivan, S., Alvarado-Cabrero, I., Kunju, L., Dhillon, J., Tretiakova, M., Smith, S., Hes, O., Williamson, S. SPRINGERNATURE. 2022: 664

  View details for Web of Science ID 000770360201245

• Magnifying Power: New Endoscopic Tools for the Diagnosis of Krukenberg Tumor. Digestive diseases and sciences Ramrakhiani, H., Thaker, A. K., Pisani, A., Sangoi, A., Triadafilopoulos, G. 2021

  View details for DOI 10.1007/s10620-020-06799-x

  View details for PubMedID 33433803

• Non-Invasive Papillary Urothelial Carcinoma with "Micropapillary" Architecture: Clinicopathologic Study of 18 Patients Emphasizing Clinical Outcomes. Histopathology Sangoi, A. R., Cox, R. M., Higgins, J. P., Quick, C. M., McKenney, J. K. 2020

  Abstract

  AIM: Invasive micropapillary carcinoma is a recognized aggressive urothelial carcinoma variant. One prior study focusing on non-invasive (pTa) high grade papillary urothelial carcinoma with micropapillary architecture has been reported.METHODS AND RESULTS: We collected bladder transurethral resection specimens showing non-invasive high grade papillary urothelial carcinoma with non-hierarchical secondary papillae lacking fibrovascular cores (i.e. micropapillary architecture). Cases with any invasive component or any prior history of invasive urothelial carcinoma were excluded. 20 cases were identified from 16 male and 2 female patients (ages 55-86 years). Micropapillary architecture comprised from 10%-95% (mean 31%), but non-invasive cribriform [15 cases (comprising 5-60%, mean 19%) and villoglandular patterns [9 cases (comprising 5-60%, mean 24%) were commonly admixed. Treatment data were available for 16 patients: surveillance (n=13), cystoprostatectomy (n=1), BCG plus mitomycin (n=1), and BCG (n=1). Follow-up data was available from 16 patients (range 1-128 months, mean 50 months): 13 patients had no new occurrences to date (81%), 2 had stage progression to pT1 papillary urothelial carcinoma (13%) with one dieing of other causes, and 1 died of other causes with no evidence of disease (6%).CONCLUSION: Non-invasive urothelial carcinomas with micropapillary architecture are often admixed with non-invasive cribriform and villoglandular patterns. Stage progression to lamina propria invasion in only 2 of 16 patients (13%) is not higher than expected for otherwise typical pTa high grade urothelial carcinomas and no progression to invasive micropapillary carcinoma was identified, adding further support to the current World Health Organization recommendation excluding use of the term "micropapillary" for pTa urothelial carcinoma.

  View details for DOI 10.1111/his.14161

  View details for PubMedID 32443178

• A Deep Learning System with Subspecialist-Level Accuracy for Gleason Grading Prostate Biopsies Nagpal, K., Foote, D., Tan, F., Liu, Y., Chen, P., Steiner, D., Manoj, N., Olson, N., Smith, J., Mohtashamian, A., Peterson, B., Amin, M., Evans, A., Sweet, J., Cheung, C., Van der Kwast, T., Sangoi, A., Zhou, M., Allan, R., Humphrey, P., Hipp, J., Gadepalli, K., Corrado, G., Peng, L., Stumpe, M., Mermel, C. NATURE PUBLISHING GROUP. 2020: 943–45

  View details for Web of Science ID 000518328802122

• A Deep Learning System with Subspecialist-Level Accuracy for Gleason Grading Prostate Biopsies Nagpal, K., Foote, D., Tan, F., Liu, Y., Chen, P., Steiner, D., Manoj, N., Olson, N., Smith, J., Mohtashamian, A., Peterson, B., Amin, M., Evans, A., Sweet, J., Cheung, C., Van der Kwast, T., Sangoi, A., Zhou, M., Allan, R., Humphrey, P., Hipp, J., Gadepalli, K., Corrado, G., Peng, L., Stumpe, M., Mermel, C. NATURE PUBLISHING GROUP. 2020: 943–45

  View details for Web of Science ID 000518328902122

• Urothelial Carcinoma in Situ Versus Early High-Grade Papillary Urothelial Carcinoma: A Survey of Pathologist and Urologist Interpretations Williamson, S., Sangoi, A., Kao, C., Deebajah, M., Barletta, J., Paner, G., Smith, S., Grignon, D., Comperat, E., Amin, M., Maclean, F., Shah, R., Iczkowski, K., Delprado, W., Cheng, L., Pan, C., McKenney, J., Ro, J., Khani, F., Montironi, R., Robinson, B., Al-Ahmadie, H., Epstein, J., Trpkov, K., Tretiakova, M., Shen, S., Alanee, S., Hirsch, M. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478081101448

• Urothelial Carcinoma in Situ Versus Early High-Grade Papillary Urothelial Carcinoma: A Survey of Pathologist and Urologist Interpretations Williamson, S., Sangoi, A., Kao, C., Deebajah, M., Barletta, J., Paner, G., Smith, S., Grignon, D., Comperat, E., Amin, M., Maclean, F., Shah, R., Iczkowski, K., Delprado, W., Cheng, L., Pan, C., McKenney, J., Ro, J., Khani, F., Montironi, R., Robinson, B., Al-Ahmadie, H., Epstein, J., Trpkov, K., Tretiakova, M., Shen, S., Alanee, S., Hirsch, M. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915502407

• Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas. International journal of gynecological pathology Sangoi, A. R., Kshirsagar, M., Roma, A. A., Horvai, A. E., Chivukula, M., Ellenson, L. H., Fadare, O., Folkins, A. K., Garg, K., Hanley, K., Longacre, T. A., Haas, J., McCluggage, W. G., McKenney, J. K., Nucci, M. R., Oliva, E., Park, K. J., Parkash, V., Quick, C. M., Rabban, J. T., Rutgers, J. K., Soslow, R., Vang, R., Yemelyanova, A., Zaloudek, C., Beck, A. H. 2017

  Abstract

  Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci. Digital H&E images from 20 gynecologic tract carcinosarcomas were reviewed by 22 gynecologic pathologists with a request to determine the presence or absence of an osteosarcomatous component. The 20 preselected cases included areas of classic heterologous osteosarcoma (malignant cells producing osteoid; n=10) and osteosarcoma mimics (malignant cells with admixed nonosteoid matrix; n=10). Interobserver agreement was evaluated and SATB2 scored on all 20 cases and compared with the original diagnoses. Moderate agreement (Fleiss' κ=0.483) was identified for the 22 raters scoring the 20 cases with a median sensitivity of 7/10 and a median specificity of 9/10 for the diagnosis of osteosarcoma. SATB2 showed 100% sensitivity (10/10) and 60% (6/10) specificity in discriminating classic osteosarcoma from osteosarcoma mimics. Utilizing negative SATB2 as a surrogate marker to exclude osteosarcoma, 73% (16/22) of the reviewers would have downgraded at least 1 case to not contain an osteosarcomatous component (range, 1-6 cases, median 1 case). Gynecologic pathologists demonstrate only a moderate level of agreement in the diagnosis of heterologous osteosarcoma based on morphologic grounds. In such instances, a negative SATB2 staining may assist in increasing accuracy in the diagnosis of an osteosarcomatous component.

  View details for DOI 10.1097/PGP.0000000000000329

  View details for PubMedID 28221217

• Mellow Yellow: Diagnosis and Management of Multifactorial Postoperative Jaundice DIGESTIVE DISEASES AND SCIENCES Tandon, A., Roorda, A. K., Legha, P., Sangoi, A., Triadafilopoulos, G. 2016; 61 (8): 2226-2230

  View details for DOI 10.1007/s10620-015-3946-8

  View details for PubMedID 26518416

• Eosinophilic, Solid, and Cystic Renal Cell Carcinoma Clinicopathologic Study of 16 Unique, Sporadic Neoplasms Occurring in Women AMERICAN JOURNAL OF SURGICAL PATHOLOGY Trpkov, K., Hes, O., Bonert, M., Lopez, J. I., Bonsib, S. M., Nesi, G., Comperat, E., Sibony, M., Berney, D. M., Martinek, P., Bulimbasic, S., Suster, S., Sangoi, A., Yilmaz, A., Higgins, J. P., Zhou, M., Gill, A. J., Przybycin, C. G., Magi-Galluzzi, C., McKenney, J. K. 2016; 40 (1): 60-71

  Abstract

  A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and cystic growth was recently reported in patients with tuberous sclerosis complex (TSC). We searched multiple institutional archives and consult files in an attempt to identify a sporadic counterpart. We identified 16 morphologically identical cases, all in women, without clinical features of TSC. The median age was 57 years (range, 31 to 75 y). Macroscopically, tumors were tan and had a solid and macrocystic (12) or only solid appearance (4). Average tumor size was 50 mm (median, 38.5 mm; range, 15 to 135 mm). Microscopically, the tumors showed solid areas admixed with variably sized macrocysts and microcysts that were lined by cells with a pronounced hobnail arrangement. The cells had voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to oval nuclei with prominent nucleoli. Scattered histiocytes and lymphocytes were invariably present. Thirteen of 16 patients were stage pT1; 2 were pT2, and 1 was pT3a. The cells demonstrated a distinct immunoprofile: nuclear PAX8 expression, predominant CK20-positive/CK7-negative phenotype, patchy AMACR staining, but no CD117 reactivity. Thirteen of 14 patients with follow-up were alive and without disease progression after 2 to 138 months (mean: 53 mo; median: 37.5 mo); 1 patient died of other causes. Although similar to a subset of renal cell carcinomas (RCCs) seen in TSC, we propose that sporadic "eosinophilic, solid, and cystic RCC," which occurs predominantly in female individuals and is characterized by distinct morphologic features, predominant CK20-positive/CK7-negative immunophenotype, and indolent behavior, represents a novel subtype of RCC.

  View details for Web of Science ID 000367135400008

  View details for PubMedID 26414221

• Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms PATHOLOGY RESEARCH AND PRACTICE Bonsib, S. M., Boils, C., Gokden, N., Grignon, D., Gu, X., Higgins, J. P., Leroy, X., McKenney, J. K., Nasr, S. H., Phillips, C., Sangoi, A. R., Wilson, J., Zhang, P. L. 2016; 212 (11): 972-979

  Abstract

  Tuberous sclerosis complex (TSC) results from mutation of TSC1 or TSC2 that encode for hamartin and tuberin. It affects the kidneys often in advance of extra-renal stigmata. We studied 14 TSC cases, and 4 possible TSC cases with multiple angiomyolipomas (AMLs) for hamartin and tuberin protein expression to determine if the staining profile could predict mutation status or likelihood of TSC with renal-limited disease. The 18 cases included 15 nephrectomies and 1 section of 6 TSC-associated renal cell carcinomas (RCC). Controls included the non-neoplastic kidney in 5 tumor nephrectomies, 4 sporadic cases of AML and 6 clear cell RCCs. In the 14 TSC cases, 9 had AMLs, 9 had RCCs, 5 had polycystic kidney disease and 8 had eosinophilic cysts (EC) lined by large eosinophilic cells. The controls and study cases showed luminal staining of proximal tubules (PT) and peripheral membrane staining in distal tubules/collecting ducts for hamartin and cytoplasmic staining for tuberin. Eosinophilic cysts had a luminal PT-like stain with hamartin and a cytoplasmic reaction for tuberin. Hamartin stained myoid cells in all AMLs. Tuberin was negative in all but 1AML, an epithelioid AML. All but 1 RCC were positive for tuberin; 13 RCCs (7 TSC/6 non-TSC) were negative for hamartin and 4 showed a weak reaction. We conclude that the ECs of TSC are proximal tubule-derived. The hamartin and tuberin staining profiles of AMLs and most RCCs are reciprocal precluding prediction of the mutation in TSC, and fail to predict if a patient with multifocal AML has TSC.

  View details for DOI 10.1016/j.prp.2016.04.005

  View details for Web of Science ID 000389159500003

  View details for PubMedID 27640314

• Androgen receptor immunohistochemistry in genitourinary neoplasms INTERNATIONAL UROLOGY AND NEPHROLOGY Williams, E. M., Higgins, J. P., Sangoi, A. R., McKenney, J. K., Troxell, M. L. 2015; 47 (1): 81-85

  Abstract

  Androgen receptor (AR) is a recognized immunohistochemical marker of prostate cancer. However, the sensitivity and specificity of AR for prostate cancer in the setting of other genitourinary neoplasms has not been rigorously studied.We employed tissue microarrays containing prostate carcinomas, urothelial carcinomas, renal cell carcinomas, and testicular neoplasms. Slides were stained immunohistochemically for AR.Androgen receptor was positive in 95% of prostate carcinomas (n=230), but 19% of invasive urothelial carcinomas of the bladder (n=190) and 33% of non-invasive bladder urothelial carcinomas were also AR positive (N=107). Furthermore, 16% of renal pelvis urothelial carcinomas (n=43) were positive. Of primary renal cell carcinomas, 19% were AR positive (n=307). From a metastatic renal cell carcinoma cohort, 28% of metastases were AR positive (N=126). Six percent of non-teratomatous testicular germ cell tumors stained for AR (n=103).Our data show that the sensitivity of AR immunohistochemistry for prostate cancer is 94.8%. However, the specificity of AR is only 81.4%, among our cohort of invasive genitourinary tumors. Thus, we find the specificity of AR suboptimal, yet AR may remain useful as a component of an immunostain panel.

  View details for DOI 10.1007/s11255-014-0834-7

  View details for PubMedID 25218615

• Tuberous Sclerosis-associated Renal Cell Carcinoma A Clinicopathologic Study of 57 Separate Carcinomas in 18 Patients AMERICAN JOURNAL OF SURGICAL PATHOLOGY Guo, J., Tretiakova, M. S., Troxell, M. L., Osunkoya, A. O., Fadare, O., Sangoi, A. R., Shen, S. S., Lopez-Beltran, A., Mehra, R., Heider, A., Higgins, J. P., Harik, L. R., Leroy, X., Gill, A. J., Trpkov, K., Campbell, S. C., Przybycin, C., Magi-Galluzzi, C., McKenney, J. K. 2014; 38 (11): 1457-1467

  Abstract

  Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with characteristic tumors involving multiple organ systems. Whereas renal angiomyolipoma (AML) is common in TSC, renal cell carcinoma (RCC) is rarely reported. Fifty-seven RCCs from 13 female and 5 male TSC patients were reviewed. Age at surgery ranged from 7 to 65 years (mean: 42 y). Nine patients (50%) had multiple synchronous and/or metachronous RCCs (range of 2 to 20 RCCs) and 5 had bilateral RCCs (28%). Seventeen patients (94%) had histologically confirmed concurrent renal AMLs, including 15 with multiple AMLs (88%) and 9 (50%) with AMLs with epithelial cysts. None of the 15 patients with available clinical follow-up information had evidence of distant metastatic disease from 6 to 198 months after their initial surgery (mean: 52 mo). The 57 RCCs exhibited 3 major distinct morphologies: (1) 17 RCCs (30%) had features similar to tumors previously described as "renal angiomyoadenomatous tumor" or "RCC with smooth muscle stroma"; (2) 34 RCCs (59%) showed features similar to chromophobe RCC; and (3) 6 RCCs (11%) showed a granular eosinophilic-macrocystic morphology. Distinct histologic changes were also commonly present in the background kidney parenchyma and included cysts or renal tubules lined by epithelial cells with prominent eosinophilic cytoplasm, nucleomegaly, and nucleoli. Immunohistochemically, all RCCs tested showed strong nuclear reactivity for PAX8 and HMB45 negativity. Compared with sporadic RCCs, TSC-associated RCCs have unique clinicopathologic features including female predominance, younger age at diagnosis, multiplicity, association with AMLs, 3 recurring histologic patterns, and an indolent clinical course. Awareness of the morphologic and clinicopathologic spectrum of RCC in this setting will allow surgical pathologists to better recognize clinically unsuspected TSC patients.

  View details for PubMedID 25093518

• Evaluation of SF-1 Expression in Testicular Germ Cell Tumors: A Tissue Microarray Study of 127 Cases. Applied immunohistochemistry & molecular morphology Sangoi, A. R., McKenney, J. K., Brooks, J. D., Higgins, J. P. 2013; 21 (4): 318-321

  Abstract

  Differentiating testicular germ cell tumors from sex-cord stromal tumors can be difficult in certain cases because of overlapping morphologic features and/or an absence of clinically apparent hormonal symptoms. Immunohistochemistry may be needed as an ancillary diagnostic tool in this differential diagnostic setting. Steroidogenic factor-1 (SF-1) is a nuclear transcription factor controlling steroidogenesis and is expressed in developing Sertoli and Leydig cells. Although 1 recent study has reported SF-1 nuclear immunoreactivity in testicular sex-cord stromal tumors, the specificity for this marker in germ cell tumors has not been evaluated. After encountering several problematic cases (including some on testicular biopsy), we sought to determine the diagnostic specificity of SF-1 in a large series of germ cell tumors. Nuclear immunohistochemical expression of SF-1 was evaluated in 127 germ cell tumors using tissue microarray technology with 23 non-germ cell tumor tissues as positive internal controls. No nuclear SF-1 expression was identified in any of the 127 germ cell tumors [including choriocarcinoma (3), embryonal carcinoma (25), epidermal inclusion cyst (1), intratubular germ cell neoplasia unclassified (4), seminoma (72), spermatocytic seminoma (2), teratoma (8), and yolk sac tumor (12)]. All 23 non-germ cell tumor tissues showed strong nuclear SF-1 expression in Sertoli and/or Leydig cells [including testicular atrophy (10), cryptorchidism (2), normal testis (4), hypospermatogenesis (1), immature testis (1), intratubular large cell calcifying Sertoli cell tumor (1), Leydig cell tumor (3), and Sertoli only (1)]. This study documents the absence of SF-1 expression in testicular germ cell tumors and supports its specificity for sex-cord stromal lesions in this diagnostic context.

  View details for DOI 10.1097/PAI.0b013e318277cf5a

  View details for PubMedID 23165333

• Evaluation of Putative Renal Cell Carcinoma Markers PAX-2, PAX-8, and hKIM-1 in Germ Cell Tumors: A Tissue Microarray Study of 100 Cases APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Sangoi, A. R., McKenney, J. K., Brooks, J. D., Bonventre, J. V., Higgins, J. P. 2012; 20 (5): 451-453

  Abstract

  In a subset of cases, metastatic renal cell carcinoma can demonstrate significant morphologic overlap with germ cell neoplasms, making accurate diagnosis challenging. In such cases, immunohistochemistry is often used as an adjunct diagnostic tool. Expression of the putative renal cell carcinoma markers PAX-2, PAX-8, and hKIM-1 has been reported in a small series of certain germ cell tumors, raising doubt about their specificity for renal cell carcinoma. To further characterize these markers, we evaluated PAX-2, PAX-8, and hKIM-1 staining in 100 germ cell tumors using tissue microarrays. PAX-2 and PAX-8 staining was identified in 50% and 25% of yolk sac tumors (respectively), with hKIM-1 staining identified in 48% of embryonal carcinomas and 50% of yolk sac tumors. All other germ tumor cells (notably including 62 seminomas) were negative for all 3 markers, in contrast to prior reports of PAX-8 reactivity in seminoma. This study indicates that PAX-2, PAX-8, and hKIM-1 should be used cautiously in distinguishing renal cell carcinoma from nonseminomatous germ cell neoplasia and also adds to the growing list of nonrenal tumors that express these 3 markers.

  View details for DOI 10.1097/PAI.0b013e31824bb404

  View details for Web of Science ID 000309551700003

  View details for PubMedID 22495365

• Evaluation of SF-1 Expression in Testicular Germ Cell Tumors: A Tissue Microarray Study of 100 Cases Sangoi, A. R., McKenney, J. K., Brooks, J. D., Higgins, J. P. OXFORD UNIV PRESS INC. 2012: A355

  View details for DOI 10.1093/ajcp/138.suppl1.331

  View details for Web of Science ID 000209848700315

• Plasmacytoid carcinoma of the bladder: a urothelial carcinoma variant with a predilection for intraperitoneal spread. journal of urology Ricardo-Gonzalez, R. R., Nguyen, M., Gokden, N., Sangoi, A. R., Presti, J. C., McKenney, J. K. 2012; 187 (3): 852-855

  Abstract

  Bladder plasmacytoid carcinoma is an invasive urothelial carcinoma subtype that is emphasized for its morphological overlap with plasma cells and metastatic carcinoma. Our experience suggests frequent intraperitoneal spread that is not typical of conventional urothelial carcinoma.We identified cases of plasmacytoid urothelial carcinoma diagnosed on radical cystectomy. Patient age, gender, American Joint Committee on Cancer (7th edition) stage, metastatic spread/recurrence sites and clinical disease status at last followup were recorded.A total of 10 male and 5 female patients 42 to 81 years old were identified. One tumor was pT2, 11 pT3 and 3 pT4. Six of 15 patients (40%) presented with lymph node metastasis and 5 (33%) had intraperitoneal metastasis at cystectomy. These initial sites of metastatic spread included the prerectal space, ovary and vagina, ovary and fallopian tube, bowel serosa, and omentum and bowel serosa in 1 case each. Three patients had subsequent metastasis involving the prerectal space, pleural fluid and small bowel serosa, and bowel serosa in 1 each. Eight patients had followup information available, including 3 who died of disease, 3 with disease and 2 with no evidence of disease.Of the patients 33% with the plasmacytoid variant of urothelial carcinoma presented with intraperitoneal disease spread and 20% had subsequent metastasis involving serosal surfaces. The possibility of noncontiguous intraperitoneal spread involving serosal surfaces should be recognized to ensure proper intraoperative staging and clinical followup for patients with plasmacytoid carcinoma.

  View details for DOI 10.1016/j.juro.2011.10.145

  View details for PubMedID 22245324

• In reply. Advances in anatomic pathology Sangoi, A. R., McKenney, J. K. 2012; 19 (2): 128-?

  View details for DOI 10.1097/PAP.0b013e31824dafb3

  View details for PubMedID 22313841

• Systematic Analysis of Breast Cancer Morphology Uncovers Stromal Features Associated with Survival SCIENCE TRANSLATIONAL MEDICINE Beck, A. H., Sangoi, A. R., Leung, S., Marinelli, R. J., Nielsen, T. O., van de Vijver, M. J., West, R. B., van de Rijn, M., Koller, D. 2011; 3 (108)

  Abstract

  The morphological interpretation of histologic sections forms the basis of diagnosis and prognostication for cancer. In the diagnosis of carcinomas, pathologists perform a semiquantitative analysis of a small set of morphological features to determine the cancer's histologic grade. Physicians use histologic grade to inform their assessment of a carcinoma's aggressiveness and a patient's prognosis. Nevertheless, the determination of grade in breast cancer examines only a small set of morphological features of breast cancer epithelial cells, which has been largely unchanged since the 1920s. A comprehensive analysis of automatically quantitated morphological features could identify characteristics of prognostic relevance and provide an accurate and reproducible means for assessing prognosis from microscopic image data. We developed the C-Path (Computational Pathologist) system to measure a rich quantitative feature set from the breast cancer epithelium and stroma (6642 features), including both standard morphometric descriptors of image objects and higher-level contextual, relational, and global image features. These measurements were used to construct a prognostic model. We applied the C-Path system to microscopic images from two independent cohorts of breast cancer patients [from the Netherlands Cancer Institute (NKI) cohort, n = 248, and the Vancouver General Hospital (VGH) cohort, n = 328]. The prognostic model score generated by our system was strongly associated with overall survival in both the NKI and the VGH cohorts (both log-rank P ≤ 0.001). This association was independent of clinical, pathological, and molecular factors. Three stromal features were significantly associated with survival, and this association was stronger than the association of survival with epithelial characteristics in the model. These findings implicate stromal morphologic structure as a previously unrecognized prognostic determinant for breast cancer.

  View details for DOI 10.1126/scitranslmed.3002564

  View details for PubMedID 22072638

• PAX8 Is Expressed in Pancreatic Well-Differentiated Neuroendocrine Tumors and in Extrapancreatic Poorly Differentiated Neuroendocrine Carcinomas in Fine-Needle Aspiration Biopsy Specimens CANCER CYTOPATHOLOGY Haynes, C. M., Sangoi, A. R., Pai, R. K. 2011; 119 (3): 193-201

  Abstract

  PAX (paired box) genes encode a family of transcription factors important for organogenesis. Recently, PAX8 has been recognized as a potential immunohistochemical marker of pancreatic neuroendocrine tumors. The authors evaluated PAX8 expression in fine-needle aspiration biopsies of neuroendocrine tumors to establish whether PAX8 immunohistochemistry can be used as an ancillary marker of pancreatic origin for neuroendocrine tumors.Fine-needle aspiration biopsies from 72 neuroendocrine tumors were evaluated for PAX8 expression: 32 primary and 23 metastatic well-differentiated neuroendocrine tumors (25 pancreatic, 13 pulmonary, 3 ileal, 2 duodenal, 1 rectal, 1 ovarian, and 10 primary site unknown) and 17 poorly differentiated neuroendocrine carcinomas (11 pulmonary, 1 pancreas, 1 breast, 1 thymus, and 3 primary site unknown).Among well-differentiated neuroendocrine tumors, only tumors from the pancreas were PAX8 positive (14 of 25, 56%) whereas no cases of pulmonary (0 of 13), ileal (0 of 3), duodenal (0 of 2), rectal (0 of 1), or ovarian (0 of 1) well-differentiated neuroendocrine tumors were positive for PAX8. One of 10 (10%) well-differentiated neuroendocrine tumors of unknown primary origin was PAX8 positive. Among poorly differentiated neuroendocrine carcinomas, PAX8 expression was identified in 1 of 1 (100%) pancreatic, 1 of 1 (100%) thymic, 4 of 11 (36%) pulmonary, and 0 of 1 (0%) breast carcinomas. One of 3 (33%) poorly differentiated neuroendocrine carcinomas of unknown primary origin was PAX8 positive.Pancreatic well-differentiated neuroendocrine tumors frequently express PAX8, which can help distinguish pancreatic primary tumors from tumors of other anatomic sites. In contrast, PAX8 expression in poorly differentiated neuroendocrine carcinomas is not specific for pancreatic origin and can be seen in extrapancreatic poorly differentiated neuroendocrine carcinomas.

  View details for DOI 10.1002/cncy.20136

  View details for Web of Science ID 000291756200009

  View details for PubMedID 21328566

• Immunohistochemical Distinction of Primary Adrenal Cortical Lesions From Metastatic Clear Cell Renal Cell Carcinoma: A Study of 248 Cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Sangoi, A. R., Fujiwara, M., West, R. B., Montgomery, K. D., Bonventre, J. V., Higgins, J. P., Rouse, R. V., Gokden, N., McKenney, J. K. 2011; 35 (5): 678-686

  Abstract

  The diagnosis of metastatic clear cell renal cell carcinoma (CC-RCC) can be difficult because of its morphologic heterogeneity and the increasing use of small image-guided biopsies that yield scant diagnostic material. This is further complicated by the degree of morphologic and immunophenotypic overlap with nonrenal neoplasms and tissues, such as adrenal cortex. In this study, a detailed immunoprofile of 63 adrenal cortical lesions, which included 54 cortical neoplasms, was compared with 185 metastatic CC-RCCs using traditional [anticalretinin, CD10, antichromogranin, antiepithelial membrane antigen, anti-inhibin, antimelanA, anticytokeratins (AE1/AE3 and AE1/CAM5.2), antirenal cell carcinoma marker, and antisynaptophysin)] and novel [anticarbonic anhydrase-IX, antihepatocyte nuclear factor-1b, antihuman kidney injury molecule-1 (hKIM-1), anti-PAX-2, anti-PAX-8, antisteroidogenic factor-1 (SF-1), and anti-T-cell immunoglobulin mucin-1] antibodies. Tissue microarray methodology was used to simulate small image-guided biopsies. Staining extent and intensity were scored semiquantitatively for each antibody. In comparing different intensity thresholds required for a "positive" result, a value of ≥2+ was identified as optimal for diagnostic sensitivity/specificity. For the distinction of adrenal cortical lesions from metastatic CC-RCCs, immunoreactivity for the adrenal cortical antigens SF-1 (86% adrenal; 0% CC-RCC), calretinin (89% adrenal; 10% CC-RCC), inhibin (86% adrenal; 9% CC-RCC), and melanA (86% adrenal; 10% CC-RCC) and for the renal epithelial antigens hKIM-1 (0% adrenal; 83% CC-RCC), PAX-8 (0% adrenal; 83% CC-RCC), hepatocyte nuclear factor-1b (0% adrenal; 76% CC-RCC), epithelial membrane antigen (0% adrenal; 78% CC-RCC), and carbonic anhydrase-IX (3% adrenal; 87% CC-RCC) had the most potential use. Use of novel renal epithelial markers hKIM-1 (clone AKG7) and/or PAX-8 and the adrenocortical marker SF-1 in an immunohistochemical panel for distinguishing adrenal cortical lesions from metastatic CC-RCC offers improved diagnostic sensitivity and specificity.

  View details for DOI 10.1097/PAS.0b013e3182152629

  View details for Web of Science ID 000289506600007

  View details for PubMedID 21490444

• PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from Heal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma MODERN PATHOLOGY Sangoi, A. R., Ohgami, R. S., Pai, R. K., Beck, A. H., McKenney, J. K., Pai, R. K. 2011; 24 (3): 412-424

  Abstract

  PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.

  View details for DOI 10.1038/modpathol.2010.176

  View details for Web of Science ID 000287986600009

  View details for PubMedID 20890270

• Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases MODERN PATHOLOGY Sangoi, A. R., Karamchandani, J., Lane, B., Higgins, J. P., Rouse, R. V., Brooks, J. D., McKenney, J. K. 2011; 24 (3): 425-429

  Abstract

  Brachyury is recognized as a specific marker for notochord-derived tissues and neoplasms, and has become a defining immunohistochemical feature of chordoma. The main differential diagnostic consideration for chordoma is chondrosarcoma, which is known to lack brachyury expression. However, within the spectrum of genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell carcinoma may also be close morphological mimics of chordoma, particularly given the increasing prevalence of small tissue samples from image-guided biopsies. Although immunoreactivity for brachyury has been reported in a few germ cell tumors, a thorough characterization of staining by specific subtype has not been performed in a large series. Additionally, brachyury expression in clear cell renal cell carcinoma has not been well studied. In this study, immunohistochemical expression with the brachyury antibody was evaluated in 111 germ cell tumors, 30 non-neoplastic and neoplastic (non-germ cell) testicular tissues, and 184 metastatic clear cell renal cell carcinomas using tissue microarray technology. In addition, immunoreactivity for PAX-8 and SALL-4 was evaluated in 12 chordomas on whole section. No nuclear brachyury expression was identified in any of the 101 germ cell tumors within the tissue microarray (including choriocarcinoma (1), embryonal carcinoma (20), intratubular germ cell neoplasia unclassified (2), seminoma (64), spermatocytic seminoma (1), teratoma (5) and yolk sac tumor (8)), in any of the 30 non-neoplastic and neoplastic (non-germ cell) testicular tissues, or in any of the 10 whole-section seminomas. All 184 metastatic clear cell renal cell carcinomas were also non-reactive for brachyury. All 12 chordomas showed strong nuclear immunoreactivity for brachyury, but no expression of SALL-4. In all, 1 of 12 chordoma cases showed patchy, 1+ nuclear immunoreactivity for PAX-8. This study confirms the specificity of brachyury for chordoma in the differential diagnostic distinction from the potential genitourinary mimics, germ cell tumors and metastatic clear cell renal cell carcinoma.

  View details for DOI 10.1038/modpathol.2010.196

  View details for Web of Science ID 000287986600010

  View details for PubMedID 21102418

• Invasive Micropapillary Carcinoma: Beyond the Borders Reply AMERICAN JOURNAL OF SURGICAL PATHOLOGY McKenney, J. K., Sangoi, A. R. 2011; 35 (2): 312

  View details for DOI 10.1097/PAS.0b013e318204c952

  View details for Web of Science ID 000286581700020

• The Use of Immunohistochemistry in the Diagnosis of Metastatic Clear Cell Renal Cell Carcinoma A Review of PAX-8, PAX-2, hKIM-1, RCCma, and CD10 ADVANCES IN ANATOMIC PATHOLOGY Sangoi, A. R., Karamchandani, J., Kim, J., Pai, R. K., McKenney, J. K. 2010; 17 (6): 377-393

  Abstract

  The diagnosis of metastatic clear cell renal cell carcinoma may be difficult in some cases, particularly in the small image-guided biopsies that are becoming more common. As targeted therapies for renal cell carcinoma are now standard treatment, the recognition and diagnosis of renal cell carcinoma has become even more critical. Many adjunctive immunohistochemical markers of renal epithelial lineage such as CD10 and RCCma have been proposed as aids in the diagnosis of metastatic renal cell carcinoma, but low specificities often limit their utility. More recently described markers (PAX-2, PAX-8, human kidney injury molecule-1, hepatocyte nuclear factor-1-β, and carbonic anhydrase-IX) offer the potential for greater sensitivity and specificity in this diagnostic setting; however, knowledge of their expected staining in other neoplasms and tissues is critical for appropriate use. In this review, we discuss the most widely used immunohistochemical markers of renal lineage with an emphasis on their sensitivity and specificity for metastatic clear cell renal cell carcinoma. Subsequently, we present a variety of organ-specific differential diagnostic scenarios in which metastatic clear cell renal cell carcinoma might be considered and we propose immunopanels for use in each situation.

  View details for DOI 10.1097/PAP.0b013e3181f89400

  View details for Web of Science ID 000283328100001

  View details for PubMedID 20966644

• Interobserver Reproducibility in the Diagnosis of Invasive Micropapillary Carcinoma of the Urinary Tract Among Urologic Pathologists AMERICAN JOURNAL OF SURGICAL PATHOLOGY Sangoi, A. R., Beck, A. H., Amin, M. B., Cheng, L., Epstein, J. I., Hansel, D. E., Iczkowski, K. A., Lopez-Beltran, A., Oliva, E., Paner, G. P., Reuter, V. E., Ro, J. Y., Shah, R. B., Shen, S. S., Tamboli, P., McKenney, J. K. 2010; 34 (9): 1367-1376

  Abstract

  Invasive micropapillary carcinoma (IMPC) of the urinary tract is a well-described variant of the urothelial carcinoma with aggressive clinical behavior. Recent studies have proposed that patients with IMPC on transurethral resection should be treated with radical cystectomy regardless of the pathologic stage. Despite the potentially important therapeutic implications of this diagnosis, interobserver variation in the diagnosis of IMPC has not been studied. Sixty digital images, each from hematoxylin and eosin-stained slides, representing 30 invasive urothelial carcinomas (2 images per case), were distributed to 14 genitourinary subspecialists and each pathologist was requested to classify cases as IMPC or not. These cases included "classic" IMPC (n=10) and urothelial carcinoma with retraction and variably sized nests that might potentially be regarded as IMPC (n=20). The following 13 morphologic features were recorded as positive/negative for all cases independent of the reviewers' diagnoses: columnar cells, elongate nests or processes, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial ring forms, intracytoplasmic vacuolization, multiple nests within the same lacunar space, back-to-back lacunar spaces, epithelial nest anastomosis/confluence, marked nuclear pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, and tumor nest size. In addition, a mean tumor nest size was calculated for each image based on the number of nuclei spanning the width of the nests. Interobserver reproducibility was assessed and the morphologic features were correlated with the classic IMPC and nonclassic/potential IMPC groups. In addition, the relationships between morphologic features, pathologists' interpretations, and case type (classic IMPC vs. nonclassic/potential IMPC) were evaluated using unsupervised hierarchical clustering analysis. Interobserver reproducibility for a diagnosis of IMPC in the 30 study cases was moderate (kappa: 0.54). Although classification as IMPC among the 10 "classic" IMPC cases was relatively uniform (93% agreement), the classification in the subset of 20 invasive urothelial carcinomas with extensive retraction and varying sized tumor nests was more variable. Multiple nests within the same lacunar space had the highest association with a diagnosis of classic IMPC. These findings suggest that more study of IMPC is needed to identify the individual pathologic features that might potentially correlate with an aggressive outcome and response to intravesical therapy.

  View details for Web of Science ID 000281579800017

  View details for PubMedID 20717002

• The distribution of PAX-2 immunoreactivity in the prostate gland, seminal vesicle, and ejaculatory duct: comparison with prostatic adenocarcinoma and discussion of prostatic zonal embryogenesis HUMAN PATHOLOGY Quick, C. M., Gokden, N., Sangoi, A. R., Brooks, J. D., McKenney, J. K. 2010; 41 (8): 1145-1149

  Abstract

  PAX-2 is a homeogene strongly expressed during development of the genitourinary tract, including the kidney and both wolffian- and müllerian-derived tissues. Expression of PAX-2 by immunohistochemistry has been studied mainly in renal epithelial neoplasms with little attention to the lower male genitourinary tract. We studied PAX-2 expression in epithelium of normal seminal vesicle, normal ejaculatory duct, normal prostatic secretory epithelium, and prostatic adenocarcinoma to define its immunoreactivity pattern throughout the prostate gland and to evaluate its potential diagnostic role in the discrimination of seminal vesicle/ejaculatory duct epithelium from prostatic adenocarcinoma. In addition, given that PAX-2 is highly expressed in tissues of wolffian duct embryologic origin, we also sought to confirm the divergent embryogenesis of the central zone, seminal vesicle, and ejaculatory duct from other regions of the prostate. Prostatectomy specimens from 12 patients were reviewed to identify blocks containing seminal vesicle, ejaculatory duct, periurethral glands, benign prostatic glands, and prostatic acinar adenocarcinoma. A total of 35 blocks from the 12 patients were evaluated. In addition, 2 tissue microarrays representing 15 additional seminal vesicles and 45 prostatic adenocarcinomas, 7 whole sections from prostatic adenocarcinomas of the central zone, and 5 core needle biopsies of seminal vesicle were also evaluated with anti-PAX-2 antibody. In the 12 radical prostatectomy whole sections, nuclear reactivity for PAX-2 was identified in 12 (100%) of 12 of the seminal vesicle epithelium, 9 (90%) of 10 of the ejaculatory duct epithelium, 0 of 12 of the prostatic adenocarcinoma, and 0 of 6 of the high-grade prostatic intraepithelial neoplasia. All 20 total additional seminal vesicles were positive for PAX-2 in the tissue microarray and biopsies; and all 52 additional prostatic adenocarcinomas were negative, including 7 of central zone origin. The staining intensity and percentage of immunoreactive cells in seminal vesicle were both 3+ in all cases. Although the ejaculatory ducts also showed diffuse staining, their staining intensity was less (2+) than that in the seminal vesicles, particularly in the ejaculatory ducts in the periurethral area (1-2+intensity). The smaller glands surrounding the main seminal vesicle duct also showed less intense staining than the luminal cells of the main duct. Of the 19 total cases with evaluable central zone glands, 2 (10.5%) had focal nuclear reactivity in normal, benign prostatic secretory cells. All other benign prostatic secretory epithelia from the peripheral and transition zones were negative for PAX-2. In conclusion, nuclear PAX-2 immunoreactivity is typical in epithelium of the seminal vesicle and ejaculatory duct; but the intensity of staining is less in the ejaculatory duct. No reactivity for PAX-2 was seen in prostatic adenocarcinoma or high-grade prostatic intraepithelial neoplasia. PAX-2 has diagnostic utility as a positive immunohistochemical marker of seminal vesicle and ejaculatory duct epithelium. In addition, these data add further support to the proposed embryogenesis of the prostatic central zone, seminal vesicle, and ejaculatory ducts from the wolffian system.

  View details for DOI 10.1016/j.humpath.2010.01.010

  View details for Web of Science ID 000280128300011

  View details for PubMedID 20413145

• A Tissue Microarray-based Comparative Analysis of Novel and Traditional Immunohistochemical Markers in the Distinction Between Adrenal Cortical Lesions and Pheochromocytoma AMERICAN JOURNAL OF SURGICAL PATHOLOGY Sangoi, A. R., McKenney, J. K. 2010; 34 (3): 423-432

  Abstract

  We have encountered an increasing number of image-guided adrenal mass biopsies in which the differential diagnosis is adrenal cortical lesion versus pheochromocytoma. This distinction is sometimes difficult because of confounding clinical presentations, overlapping morphologies, and some degree of immunophenotypic overlap including focal staining with markers of purported lineage specificity. Interventional radiologists commonly use narrow gauge biopsy needles in this setting, which yield scant diagnostic tissue and further complicate pathologic evaluation. In this study, a detailed immunoprofile of 63 adrenal cortical lesions (3 adrenal rests, 6 adrenal cortical hyperplasias, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, and 7 adrenal cortical carcinomas) was compared with 35 pheochromocytomas using traditional (calretinin, chromogranin, inhibin, melanA, and synaptophysin) and novel [steroidogenic factor-1 (SF-1), microtubule-associated protein 2, and mammalian achaete-scute homolog-1] antibodies, using tissue microarray technology to simulate small image-guided biopsies. Staining extent and intensity were each scored semiquantitatively for each antibody. A comparison of sensitivity and specificity using different intensity thresholds required for a "positive" result (> or = 1+ vs. > or = 2+) was performed. Staining results based on a > or = 1+ and (> or = 2+) intensity threshold were as follows: calretinin-95% (89%) in adrenal cortical lesions and 14% (0%) in pheochromocytomas; chromogranin-0% in adrenal cortical lesions and 100% in pheochromocytomas; inhibin-97% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; microtubule-associated protein 2-29% (16%) in adrenal cortical lesions and 100% (89%) in pheochromocytomas; mammalian achaete-scute homolog-1-0% in both adrenal cortical lesions and pheochromocytomas; melanA-94% (86%) in adrenal cortical lesions and 6% (0%) in pheochromocytomas; SF-1-87% (86%) in adrenal cortical lesions and 0% in pheochromocytomas; synaptophysin-67% (59%) in adrenal cortical lesions and 100% in pheochromocytomas. Using an antibody panel consisting of chromogranin plus the nuclear antibody SF-1 and either calretinin or inhibin, while requiring a high-staining intensity threshold, helps to eliminate interpretative issues of artifactual or background reactivity, improves diagnostic sensitivity/specificity, and makes for an effective immunohistochemical approach in distinguishing adrenal cortical lesions from pheochromocytomas.

  View details for DOI 10.1097/PAS.0b013e3181cfb506

  View details for Web of Science ID 000275697000015

  View details for PubMedID 20154585

• Evaluation of patients with clinically detected recurrence of rectal carcinoma: Current practice patterns of colorectal surgeons ONCOLOGY LETTERS Sangoi, A., Patel, U., Ode, K., Audisio, R., Virgo, K. S., Johnson, F. E. 2010; 1 (2): 355-359

  Abstract

  The optimal evaluation of patients with clinically suspected recurrence of rectal carcinoma following initial treatment has yet to be determined. We documented the intensity of the extent-of-disease workup conducted by colorectal surgeons when their patients with rectal carcinoma develop clinical evidence of metastases. A custom-designed questionnaire was mailed to all 1,795 members of the American Society of Colon and Rectal Surgeons. Subjects were asked which laboratory tests and imaging studies they would order for one of their own generally healthy patients with a suspicious abnormality found during surveillance testing. The tests most frequently recommended were computed tomography and serum carcinoembryonic antigen level. Few tests were recommended by >90% of respondents. There is no consensus among experts in this common situation.

  View details for DOI 10.3892/ol_00000063

  View details for Web of Science ID 000284800100024

  View details for PubMedID 22966308

  View details for PubMedCentralID PMC3436337

• Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases 98th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology Sangoi, A. R., McKenney, J. K., Schwartz, E. J., Rouse, R. V., Longacre, T. A. NATURE PUBLISHING GROUP. 2009: 1228–35

  Abstract

  Adenomatoid tumors of the female and male genital tracts are well characterized as mesothelial in origin, but a detailed histological and immunohistochemical analysis comparing both traditional and newer mesothelial markers across gender and site has not been formally conducted. A variety of morphologic features previously described as characteristic of adenomatoid tumors were evaluated in 44 adenomatoid tumors from the male and female genital tracts. Immunohistochemical analysis with pankeratin (AE1/CAM5.2), WT-1, calretinin, CK5/6, D2-40, and caldesmon was also performed. The extent and intensity of staining were scored semiquantitatively on one representative section per case and mean value for each parameter was calculated. All (n=44) the adenomatoid tumors from both the female and male genital tracts demonstrated a distinctive thread-like bridging strand pattern. Lymphoid aggregates were seen in all 12 adenomatoid tumors of male patients, but in only 4 of 32 (13%) tumors in female patients (P<0.0001). The remaining morphologic features were variably present with no clear sex predilection. Pankeratin, calretinin, and D2-40 reactivity were identified in all female (n=32) and male (n=12) genital tract adenomatoid tumors. Adenomatoid tumors expressed WT-1 in 11/12 (92%) male patients and in 31/32 (97%) female patients. In male patients, reactivity for CK5/6 and caldesmon was found in 1/12 (8%) and 0/12 (0%) adenomatoid tumors (respectively), whereas reactivity in female patients was found in 5/32 (16%) and 1/32 (3%); respectively. Female tumors differ from their male counterparts by the frequent absence of lymphoid aggregates and the presence of a circumscribed margin when occurring in the fallopian tube. Of the putative mesothelial markers evaluated, calretinin, D2-40, and WT-1 show a similar immunoprofile and have a higher sensitivity than CK5/6 and caldesmon in genital tract adenomatoid tumors. However, the presence of additional, often strong expression of WT-1 in normal tissues of the female genital tract limits the utility of WT-1 in this setting.

  View details for DOI 10.1038/modpathol.2009.90

  View details for Web of Science ID 000269448700012

  View details for PubMedID 19543245

• Invasive Urothelial Carcinoma With Chordoid Features A Report of 12 Distinct Cases Characterized by Prominent Myxoid Stroma and Cordlike Epithelial Architecture AMERICAN JOURNAL OF SURGICAL PATHOLOGY Cox, R. M., Schneider, A. G., Sangoi, A. R., Clingan, W. J., Gokden, N., McKenney, J. K. 2009; 33 (8): 1213-1219

  Abstract

  Urothelial carcinoma is morphologically heterogeneous and many variant forms have been described. We have encountered several invasive urothelial carcinomas with a unique chordoid morphology characterized by prominent cellular cording and associated myxoid stromal matrix, a pattern closely resembling extraskeletal myxoid chondrosarcoma. This morphologic appearance, to our knowledge, has not been formally described in urothelial carcinoma. A series of 166 consecutive invasive urothelial carcinomas were reviewed to identify cases with cellular cording and myxoid stroma. The patient age, sex, tumor stage, morphologic features, association with typical urothelial carcinoma, and clinical outcome were recorded. Immunostains for p63, cytokeratin (CK) 34BE12, CK20, calponin, glial fibrillary acidic protein, S-100 protein, oncofetal protein glypican-3, and brachyury were performed on 7 cases. Mucin histochemistry was performed on 8 cases to evaluate the extracellular myxoid material. Eleven of the 166 (7%) consecutive invasive urothelial carcinomas had areas with a chordoid appearance. A total of 12 cases were analyzed including the addition of a consult case. The patients' ages ranged from 50 to 85 years (mean: 68 y); there were 8 males and 4 females. The specimens consisted of 5 cystectomies, 6 transurethral resections, and 1 anterior exenteration with right nephroureterectomy. Morphologically, each case had at least focal areas in which acellular myxoid stroma was associated with the carcinoma cells. When well developed, the neoplastic cells had scant eosinophilic cytoplasm and were arranged into cords closely mimicking extraskeletal myxoid chondrosarcoma, chordoma, mixed tumor/myoepithelioma of soft tissue, and yolk sac tumor. The percentage of tumor with a chordoid appearance ranged from 5% to 95% (mean: 39%; median: 25%). No conventional sarcomatous differentiation, no intracytoplasmic mucin, and no glandular formation were present in any case. All 12 cases had foci of typical urothelial carcinoma present at least focally and a gradual transition to the chordoid pattern was commonly seen. Immunophenotypically, all 7 cases evaluated showed strong immunoreactivity for p63 (nuclear) and CK34BE12 (cytoplasmic). Immunostains for CK20, calponin, glial fibrillary acidic protein, oncofetal protein glypican-3, and brachyury and were negative in the 7 cases studied (0 out of 7), whereas S-100 protein had focal staining (<5%) in 1 case. The myxoid stromal component was diffusely colloidal iron and Alcian blue positive in all 8 cases examined; periodic acid Schiff was negative in all 8 cases, whereas mucicarmine was only focally positive in 2 of 8 cases. Most cases were high stage (pT4: 5, pT3: 4, pT2: 2, and pT1: 1), and 6 of 8 cases (75%) with nodal sampling had metastatic disease. In 1 case, the lymph node metastasis had areas with chordoid morphology. Nine of 12 patients had available follow-up: 2 were dead of disease (1 and 10 mo), 4 were alive with disease (5 to 8 mo) with distant metastasis in 3, and 3 had no evidence of disease at last follow-up (2 to 120 mo). In summary, we describe a morphologic pattern of urothelial carcinoma with a distinct chordoid appearance that may potentially mimic a spectrum of primary vesical and nonvesical neoplasms with myxoid or mucinous components. These carcinomas maintain an immunophenotype characteristic of urothelial carcinoma and usually present with high stage disease.

  View details for Web of Science ID 000268850300013

  View details for PubMedID 19542871

• Distinguishing Chordoid Meningiomas From Their Histologic Mimics An Immunohistochemical Evaluation 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology Sangoi, A. R., Dulai, M. S., Beck, A. H., Brat, D. J., Vogel, H. LIPPINCOTT WILLIAMS & WILKINS. 2009: 669–81

  Abstract

  Chordoid meningioma, World Health Organization grade II, is an uncommon variant of meningioma with a propensity for aggressive behavior and increased likelihood of recurrence. As such, recognition of this entity is important in cases that show similar morphologic overlap with other chondroid/myxoid neoplasms that can arise within or near the central nervous system. A formal comparison of the immunohistochemical features of chordoid meningioma versus tumors with significant histologic overlap has not been previously reported. In this study, immunohistochemical staining was performed with antibodies against D2-40, S100, pankeratin, epithelial membrane antigen (EMA), brachyury, and glial fibrillary acidic protein (GFAP) in 4 cases of chordoid glioma, 6 skeletal myxoid chondrosarcomas, 10 chordoid meningiomas, 16 extraskeletal myxoid chondrosarcoma, 18 chordomas, 22 low-grade chondrosarcomas, and 27 enchondromas. Staining extent and intensity were evaluated semiquantitatively and mean values for each parameter were calculated. Immunostaining with D2-40 showed positivity in 100% of skeletal myxoid chondrosarcomas, 96% of enchondromas, 95% of low-grade chondrosarcomas, 80% of chordoid meningiomas, and 75% of chordoid gliomas. Staining with S100 demonstrated diffuse, strong positivity in all (100%) chordoid gliomas, skeletal myxoid chondrosarcomas, low-grade chondrosarcomas, and enchondromas, 94% of chordomas, and 81% of extraskeletal myxoid chondrosarcomas, with focal, moderate staining in 40% of chordoid meningiomas. Pankeratin highlighted 100% of chordoid gliomas and chordomas, 38% of extraskeletal myxoid chondrosarcomas, and 20% of chordoid meningiomas. EMA staining was positive in 100% of chordoid gliomas, 94% of chordomas, 90% of chordoid meningiomas, and 25% of extraskeletal myxoid chondrosarcomas. Brachyury was positive only in the chordomas (100%), whereas GFAP was positive only in the chordoid gliomas (100%). EMA was the most effective antibody for differentiating chordoid meningioma from skeletal myxoid chondrosarcoma, low-grade chondrosarcoma, and enchondroma, whereas D2-40 was the most effective antibody for differentiating chordoid meningioma from extraskeletal myxoid chondrosarcoma and chordoma. Our findings demonstrate that in conjunction with clinical and radiographic findings, immunohistochemical evaluation with a panel of D2-40, EMA, brachyury, and GFAP is most useful in distinguishing chordoid meningioma from chordoid glioma, skeletal myxoid chondrosarcoma, extraskeletal myxoid chondrosarcoma, chordoma, low-grade chondrosarcoma, and enchondroma. A lack of strong, diffuse S100 reactivity may also be useful in excluding chordoid meningioma. Among the neoplasms evaluated, brachyury and GFAP proved to be both sensitive and specific markers for chordoma and chordoid glioma, respectively. Of note, this study is the first to characterize the D2-40 immunoprofile in extraskeletal myxoid chondrosarcoma, results that could be of utility in differential diagnostic assessment.

  View details for PubMedID 19194275

• Immunohistochemical comparison of MUC1, CA125, and Her2Neu in invasive micropapillary carcinoma of the urinary tract and typical invasive urothelial carcinoma with retraction artifact MODERN PATHOLOGY Sangoi, A. R., Higgins, J. P., Rouse, R. V., Schneider, A. G., McKenney, J. K. 2009; 22 (5): 660-667

  Abstract

  On the basis of recent clinical studies, some urologic oncologists do not offer bladder-sparing therapy for patients diagnosed with micropapillary carcinoma of the urinary bladder, even in the setting superficially invasive disease. Unfortunately, the distinction of invasive micropapillary carcinoma from typical invasive urothelial carcinoma with prominent retraction artifact may be difficult in some cases. In this study, we compared the immunophenotype of invasive micropapillary carcinoma to invasive urothelial carcinoma with retraction artifact using antibodies previously reported as specific for micropapillary carcinoma. Immunohistochemical staining was performed on 24 invasive micropapillary carcinomas of the urinary tract and 24 case controls of invasive urothelial carcinoma with retraction artifact using monoclonal antibodies MUC1, CA125, and Her2Neu. The staining extent and intensity for MUC1 and CA125 were scored on one representative section per case. Immunostaining for Her2Neu was scored based on the 2007 CAP/ASCO guidelines for breast carcinoma. Basal ('reverse-apical') MUC1 staining was identified in 23 of the 24 (96%) invasive micropapillary carcinomas and in 15 of the 24 (63%) invasive urothelial carcinomas with retraction artifact (P=0.0102). Membranous reactivity with CA125 was seen in 8 of the 24 (33%) invasive micropapillary carcinomas and in 3 of the 24 (13%) invasive urothelial carcinomas with retraction artifact (P=0.1681). Positive (3+) membranous Her2Neu staining was present in 6 of 24 (25%) invasive micropapillary carcinomas and in 2 of the 24 (8%) invasive urothelial carcinomas with retraction artifact (P=0.2448). The specificity for invasive micropapillary carcinoma vs invasive urothelial carcinoma with retraction artifact using antibodies MUC1, CA125, and Her2Neu was 37, 87, and 92%, respectively. Invasive micropapillary carcinoma more commonly showed immunoreactivity for MUC1, CA125, and Her2Neu compared to invasive urothelial carcinoma with retraction artifact, but only MUC1 reached statistical significance. The lack of specificity of these evaluated markers for invasive micropapillary carcinoma limits their utility in the distinction from invasive urothelial carcinoma with retraction artifact, especially given the potentially significant therapeutic implications.

  View details for DOI 10.1038/modpathol.2009.16

  View details for Web of Science ID 000265640200007

  View details for PubMedID 19270645

• Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens A Ten-Year Retrospective Review at a Single Institution AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sangoi, A. R., Rogers, W. M., Longacre, T. A., Montoya, J. G., Baron, E. J., Banaei, N. 2009; 131 (3): 364-375

  Abstract

  Despite the advantages of providing an early presumptive diagnosis, fungal classification by histopathology can be difficult and may lead to diagnostic error. To assess the accuracy of histologic diagnosis of fungal infections vs culture ("gold standard"), we performed a 10-year retrospective review at our institution. Of the 47 of 338 positive mold and yeast cultures with concurrent surgical pathology evaluation without known history of a fungal infection, 37 (79%) were correctly identified based on morphologic features in histologic and/or cytologic specimens. The 10 discrepant diagnoses (21%) included misidentification of septate and nonseptate hyphal organisms and yeast forms. Errors resulted from morphologic mimics, use of inappropriate terminology, and incomplete knowledge in mycology. The accuracy did not correlate with preceding antifungal therapy (P = .14) or use of special stains (P = .34) and was not operator-dependent. Among 8 discrepancies with clinical follow-up available, 2 potential adverse clinical consequences resulted. While histopathologic identification of fungi in tissue sections and cytologic preparations is prone to error, implementation of a standardized reporting format should improve diagnostic accuracy and prevent adverse outcomes.

  View details for DOI 10.1309/AJCP99OOOZSNISCZ

  View details for PubMedID 19228642

• Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens A Ten-Year Retrospective Review at a Single Institution AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sangoi, A. R. R., Rogers, W. M. M., Longacre, T. A. A., Montoya, J. G. G., Baron, E., Banaei, N. 2009; 131 (3): 364-375

  View details for DOI 10.1309/AJCP99OOOZSNISCZ

  View details for Web of Science ID 000917985800008

• Suprasellar giant cell ependymoma: a rare neoplasm in a unique location HUMAN PATHOLOGY Sangoi, A. R., Lim, M., Dulai, M. S., Vogel, H., Chang, S. D. 2008; 39 (9): 1396-1401

  Abstract

  Ependymomas are glial tumors that usually present in the posterior fossa in children and in the spinal cord in adults. Giant cell ependymoma, a rare ependymal subtype only recently recognized as a diagnostic entity in the last decade, demonstrates pleomorphic giant cells admixed with features of typical ependymoma. Although only 8 giant cell ependymomas have been reported to date, none have been reported in the suprasellar space. Moreover, as these neoplasms demonstrate a high incidence of anaplastic grade, recognition of this ependymal subtype is paramount. We describe the presentation and pertinent radiologic, histologic, immunologic, and ultrastructural findings in conjunction with relevant clinical implications of the first reported case of a suprasellar giant cell ependymoma occurring in a 34-year-old female 7 years after an initial diagnosis of a medullary ependymoma with rare atypical giant cells, a potential tumor seeding culprit.

  View details for DOI 10.1016/j.humpath.2008.01.007

  View details for PubMedID 18602668

• Lymphatic vascular invasion in ovarian serous tumors of low malignant potential with stromal microinvasion - A case control study 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology Sangoi, A. R., McKenney, J. K., Dadras, S. S., Longacre, T. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 261–68

  Abstract

  Stromal microinvasion in ovarian serous tumors of low malignant potential (S-LMP) stratifies patients at long-term risk for disease progression independent of stage and primary ovarian histology. Despite the histologic impression and often-quoted incidence of lymphatic vascular invasion (LVI) in S-LMP with stromal microinvasion, there has been no formal evaluation in a case control series of S-LMP. The presence and extent of (LVI) was assessed in 20 S-LMP with stromal microinvasion and 20 S-LMP case controls without stromal microinvasion and compared with a series of low-grade and high-grade serous carcinomas using D2-40 monoclonal antibody recognizing podoplanin, a novel lymphatic endothelial marker. S-LMP case controls were matched for primary ovarian histology (usual vs. micropapillary), International Federation of Gynecology and Obstetrics (FIGO) stage, and age (best possible match). The patterns of stromal microinvasion included individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, and inverted macropapillae. Immunohistologic staining with D2-40 monoclonal antibody clearly identified intratumoral LVI in 12/20 (60%) S-LMP with stromal microinvasion and 0/20 S-LMP without stromal microinvasion. Although only 4/13 (31%) low-grade serous carcinomas and 7/20 (35%) high-grade serous carcinomas had intratumoral LVI, hilar LVI was more common in the carcinomas (15% low-grade; 69% high-grade). Intratumoral LVI in S-LMP ranged from focal (6 cases) to multifocal (6 cases, maximum of 5 discrete foci) in any 1 section and included isolated single cells, simple papillae, and in 1 case, cribriform glands. Multifocal LVI was identified in 1 study patient who was pregnant. One of the 12 S-LMP patients with LVI had an intra-abdominal recurrence with high-grade disease at 16 months; whereas all other patients with follow-up were free of disease. LVI in ovarian S-LMP was significantly associated with the presence of stromal microinvasion (P<0.0001) and is independent of age, stage, primary ovarian histology, and pattern or extent of microinvasion. The presence of LVI in microinvasive S-LMP corroborates the view that microinvasion represents an early, but very low risk, invasive process that morphologically links S-LMP and low-grade serous carcinoma.

  View details for Web of Science ID 000252759900011

  View details for PubMedID 18223329

• Ovarian clear cell carcinoma with papillary features: A potential mimic of serous tumor of low malignant potential 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology Sangoi, A. R., Soslow, R. A., Teng, N. N., Longacre, T. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 269–74

  Abstract

  The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.

  View details for Web of Science ID 000252759900012

  View details for PubMedID 18223330

• Bilateral mixed epithelial stromal tumor in an end-stage renal disease patient: the first case report HUMAN PATHOLOGY Sangoi, A. R., Higgins, J. P. 2008; 39 (1): 142-146

  Abstract

  Although first intimated in the 1970s, mixed epithelial stromal tumor has been recognized as a diagnostic entity for less than 10 years, with an identity that has been challenged by overlap between other cystic renal neoplasms, most notably with cystic nephroma. We report the first case of a bilateral mixed epithelial stromal tumor occurring in a 41-year-old dialysis-dependent woman, notably also the first case reported in a patient with end-stage renal disease. The neoplasms occurred 5 years apart and were diagnosed as mixed epithelial stromal tumor in both instances. We describe the presentation and pertinent radiologic, histologic, and immunophenotypic findings of these neoplasms with a review of the current debate regarding mixed epithelial stromal tumor and cystic nephroma taxonomy.

  View details for DOI 10.1016/j.humpath.2007.08.001

  View details for Web of Science ID 000251895500019

  View details for PubMedID 18070633

• Respiratory epithelial adenomatoid hamartoma: Diagnostic pitfalls with emphasis on differential diagnosis ADVANCES IN ANATOMIC PATHOLOGY Sangoi, A. R., Berry, G. 2007; 14 (1): 11-16

  Abstract

  In the upper aerodigestive tract, respiratory epithelial adenomatoid hamartoma (REAH) is described as a polypoid proliferation of glands lined by ciliated respiratory epithelium that seem to invaginate downward into the submucosa while maintaining direct continuity with the surface mucosa. The lesion can be confused with a variety of benign and malignant entities, including inflammatory polyp, inverted schneiderian papilloma, and low-grade sinonasal adenocarcinoma. In reviewing the historical, clinical, gross, and histopathologic features of REAH and its subtypes, we elucidate how the distinction of REAH with florid mucinous metaplasia from low-grade adenocarcinoma can be challenging particularly in the setting of small biopsy samples. Diagnostic criteria are reviewed with emphasis on key distinguishing characteristics. The significance of this distinction is paramount in preventing unwarranted surgery and untoward consequences for the patient.

  View details for Web of Science ID 000243573000002

  View details for PubMedID 17198306