Phoebe Meredith Hammer

All Publications

• Clinicopathologic and Molecular Features of Tubo-Ovarian Carcinosarcomas with an Emphasis on p53 Wild-Type, KRAS-Mutated Tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Hammer, P. M., Kingsley, L. G., Sasse, S. A., Howitt, B. E. 2026: 100971

  Abstract

  Tubo-ovarian carcinosarcomas (OCS) are uncommon, aggressive tumors. Recent literature in uterine carcinosarcomas (UCS) has shown prognostic differences by the molecular classification established by The Cancer Genome Atlas (TCGA). Our aim was to delineate the molecular subtypes within OCS and associated clinicopathologic, immunohistochemical, and additional molecular features. A total of 57 OCS were identified at our institution. Overall median follow-up was 32.3 months, and 5-year survival rates were 71% (Stage I/II), 42% (Stage III), and 17% (stage IV). Fifty-one tumors (89%) were p53-abnormal (p53abn) molecular subtype. Five (9%) were no specific molecular subtype (NSMP) and all 5 of these tumors harbored canonical mutations in KRAS (codon 12). We also identified the first reported primary POLE-mutated OCS in a patient with Lynch Syndrome; this case was assigned as double-classifier POLE-mutated/mismatch repair deficient molecular subtype. No tumors were single-classifier mismatch repair deficient or POLE-mutated molecular subtype. Compared to p53abn tumors, KRAS-mutated tumors occurred in younger women at lower stages, but did recur in 2/5 (40%) patients. They always showed endometrioid rather than high-grade serous morphology, and were usually ER, PR and WT1 negative. Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.

  View details for DOI 10.1016/j.modpat.2026.100971

  View details for PubMedID 41638575

• Mammary small cell neuroendocrine carcinomas that showed excellent pathologic response following etoposide-based neoadjuvant chemotherapy. Breast cancer research and treatment Hammer, P. M., Enamandram, S., Ikeda, D. M., Lam, M. M., Wapnir, I. L., Chamberlain, E. D., Shaheen, S., Caswell-Jin, J. L., Itakura, H., Bean, G. R. 2025; 215 (1): 10

  Abstract

  Small cell neuroendocrine carcinoma (SCNEC) is a very rare, highly aggressive subtype of breast cancer. There are no standard recommendations for the management of mammary SCNEC, and the use and response to neoadjuvant chemotherapy are not well studied. Etoposide is an agent not included in guidelines for the management of breast cancer but traditionally used in the treatment of small cell carcinoma of the lung.We searched for institutional and consultation cases of breast SCNEC and identified those treated with neoadjuvant chemotherapy. Clinical, pathologic, and genetic findings of two patients with SCNEC of the breast treated with etoposide are described. Additionally, we performed a literature review of all known cases of mammary SCNEC treated with neoadjuvant chemotherapy to date.These two women were the sole patients who underwent neoadjuvant etoposide-based chemotherapy followed by surgery for breast SCNEC at our institution in the past 25 years. Both patients achieved excellent imaging and pathologic responses, with no evidence of residual carcinoma in the subsequent breast excisions.Etoposide may be considered as a therapeutic option in the neoadjuvant setting of breast SCNEC. More reports on this very rare breast cancer subtype and response to treatment are needed.

  View details for DOI 10.1007/s10549-025-07854-9

  View details for PubMedID 41269341

  View details for PubMedCentralID 9514991

• Educational case: Estrogen-receptor positive breast cancer: Diagnosis, response to therapy, and prognosis. Academic pathology Afifi, A., Hammer, P., Ernst, K. 2025; 12 (3): 100210

  View details for DOI 10.1016/j.acpath.2025.100210

  View details for PubMedID 40831739

  View details for PubMedCentralID PMC12359217

• Folate receptor alpha (FRα/FOLR1) and HER2 immunohistochemical staining in high-grade endometrial carcinoma with aberrant p53 expression. Histopathology McHenry, A., Liang, B., Libert, D., Hammer, P. M., Tokuyama, M., Tenney, T., Zhang, X., Folkins, A., Longacre, T. A., Howitt, B. E. 2025

  Abstract

  Mirvetuximab soravtansine is an anti-FOLR1 (folate receptor 1/alpha) antibody-drug conjugate with a companion diagnostic immunohistochemical (IHC) biomarker for platinum-resistant ovarian, fallopian tube and primary peritoneal carcinoma. Its effectiveness has sparked interest in FOLR1 expression in endometrial carcinoma. We evaluate the relationship of FOLR1 and HER2-IHC expression in high-grade p53-aberrantly expressed endometrial carcinomas, as overexpression of both is associated with high-grade histologic features and aggressiveness.Carcinomas were scored for HER2-IHC by both gastric and endometrial serous criteria and FOLR1-IHC by Ventana package insert on tissue microarray cores. Intratumoral heterogeneity was quantified for HER2 and FOLR1 expression across multiple cores from the same tumour. A total of 291 cores (226 endometrial serous, 47 high-grade endometrioid and 18 high-grade Müllerian carcinoma, nos) were collected from 66 cases (discrete accession dates) from 62 patients. When stratified by two-category HER2-IHC status (0/1+ vs. 2+/3+, either criteria), significantly more HER2 2+/3+ cores (16/133, 12%) were FOLR1-positive by a ≥75% cut-off than HER2 0/1+ specimens (8/158, 5%, P = 0.031). Results were similar by a ≥25% cut-off (49/133, 37% vs. 38/158, 24%; P = 0.018). More cases with high HER2-IHC heterogeneity (2-3-pt difference) also demonstrated FOLR1-IHC heterogeneity (≥50% score difference between cores from the same case) than cases with no or low (1-pt) HER2-IHC heterogeneity, though most cases did not show high HER2 or FOLR1 intratumoral heterogeneity (16.7%-18.2% 2-3-pt difference and 12.1% ≥50% score difference).A positive correlation between HER2 and FOLR1 overexpression may be seen in high-grade endometrial carcinomas with aberrant p53 expression, which may extend to intratumoral heterogeneity of biomarker expression.

  View details for DOI 10.1111/his.15533

  View details for PubMedID 40769949

• Dominant Negative PTEN Alterations in Endometrial Carcinoma Are Associated With Retained Immunohistochemical PTEN Expression. The American journal of surgical pathology Keyhanian, K., Busca, A., Howitt, B., Hammer, P., Kingsley, L., Lo, B. 2025

  Abstract

  PTEN immunohistochemistry (IHC) is considered complimentary for assessment of PTEN abnormality in endometrial carcinoma (EC), since PTEN IHC staining pattern does not entirely correlate with the presence and absence of mutations on sequencing. A set of functionally defective PTEN variants with stable protein levels are known to act in a dominant-negative manner to suppress wild-type PTEN activity. Our objective was to evaluate PTEN IHC patterns in ECs with dominant-negative (DN) PTEN mutations. ECs with next-generation sequencing (NGS, using Oncomine Comprehensive Assay v3) over a 3-year period were enrolled. PTEN IHC was scored as loss, subclonal loss, reduced, and intact (the last 3 considered retained). Of 182 EC cases, 114 (62.6%) were identified to have PTEN mutation(s), the majority of endometrioid histotype (87.7%) from all EC molecular classes. Forty-seven cases (41.2%) harbored DN mutations which were of endometrioid (FIGO 1 [n=15, 31.9%], FIGO 2 [n=23, 48.9%], FIGO 3 [n=3, 6.4%]), dedifferentiated (n=2, 4%), carcinosarcoma (n=3, 6%), mixed endometrioid and clear cell carcinoma (n=1, 2%) histotype; with representatives from all molecular classes. PTEN IHC showed retained expression in 95.8% (45/47) of DN-mutated cases (intact staining in 36 [76.6%], reduced staining in 6 [12.5%], and subclonal loss in 3 [6.4%]) cases. Two cases showed loss of expression (4.2%). In the PTEN wild-type group, loss and subclonal loss of expression were seen in 12.5% and 9.4%, respectively. Our results indicate that DN PTEN mutations are common in EC, and are associated with retained IHC staining (intact, reduced, or subclonal loss). These results highlight that IHC and NGS are both required in capturing the full spectrum of PTEN-abnormal EC.

  View details for DOI 10.1097/PAS.0000000000002412

  View details for PubMedID 40401766

• Comparison of Endometrial Serous and Gastric HER2 Immunohistochemistry Scoring Schemes in Endometrial Carcinomas With Aberrant p53 Expression: Reproducibility and In Situ Hybridization Correlation. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists McHenry, A., Liang, B., Hammer, P. M., Libert, D., Mack, T., Tokuyama, M., Tenney, T., Zhang, X., Folkins, A., Longacre, T. A., Howitt, B. E. 2025

  Abstract

  In 2023, the College of American Pathologists (CAP) supported histotype-specific scoring for HER2 testing in endometrial serous carcinoma based on enrollment criteria for trastuzumab eligibility in the NCT01367002 clinical trial. However, in 2024, the DESTINY-PanTumor02 trial showed the benefit of trastuzumab-deruxtecan in patients with HER2-IHC 2+ and 3+ tumors using CAP gastric scoring, resulting in confusion about how these criteria relate. We compare the results of these scoring schemes by interobserver agreement and correlation with HER2/Chromosome 17 dual in situ hybridization (DISH). Six observers scored 44 HER2-IHC stained p53-abnormal endometrial carcinoma specimens in tissue microarray (TMA) format by endometrial serous (NCT01367002) and gastric systems. Interobserver agreement for HER2 scores (0, 1+, 2+, and 3+) was 81.5% (kappa=0.75) for endometrial serous and 84.6% (kappa=0.79) for gastric scoring. Eight specimens showed discordant HER2 endometrial serous and gastric scores: 4 endometrial serous 1+/gastric 0 and 4 endometrial serous 2+/gastric 3+. HER2-IHC-DISH discordance occurred in 4 specimens by gastric criteria (IHC 3+/DISH negative) and 1 specimen by endometrial serous criteria (IHC 3+/DISH negative). Endometrial serous and gastric HER2-IHC scoring schemes show similar interobserver agreement. In instances of minimal, faint HER2 staining, the endometrial serous score may be 1+ when the gastric score is 0. In instances of limited, strong HER2 staining, the endometrial serous score may be 2+ when the gastric score is 3+. The endometrial serous scheme appears more concordant with DISH results than the gastric scheme, which shows non-infrequent IHC 3+ cases without HER2-DISH amplification. We emphasize recognition of HER2-IHC therapy-specific scoring in endometrial carcinomas, as these scoring systems are similar but not identical.

  View details for DOI 10.1097/PGP.0000000000001115

  View details for PubMedID 40637410

• Corrigendum to "POLE-Mutated Uterine Carcinosarcomas: A Clinicopathologic and Molecular Study of 11 Cases": [Modern Pathology 38 (2025) 100676]. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Hammer, P. M., Momeni-Boroujeni, A., Kolin, D. L., Kingsley, L., Folkins, A., Geisick, R. L., Ho, C., Suarez, C. J., Howitt, B. E. 2025: 100784

  View details for DOI 10.1016/j.modpat.2025.100784

  View details for PubMedID 40377507

• So-called "Infiltrating Epitheliosis" Shows a Spectrum of Morphologic and Molecular Features: Is It a Precursor for Malignancy? Hammer, P., Winters, C., Dussaq, A., Rutland, C., Allison, K., Bean, G. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.102383

  View details for Web of Science ID 001461690600008

• Clinicopathologic and Molecular Features of Ovarian Carcinosarcomas Hammer, P., Kingsley, L., Sasse, S., Howitt, B. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103223

  View details for Web of Science ID 001464114700056

• Low-Risk HPV-Associated Squamous Cell Carcinomas Comprise a Subset of High-Risk HPV-Independent Squamous Cell Carcinomas of the Uterine Cervix Liang, B., Hammer, P., Gedallovich, J., Mack, T., Yang, E., Kong, C., Longacre, T. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103258

  View details for Web of Science ID 001464114700007

• Molecular Insights into the "Estrogenic Link" between Sex Cord-Stromal Tumors and Endometrial Carcinomas Cataldas, Y., Hammer, P., Donthi, D., Falzarano, S., Gars, E., Kolin, D., Mahadik, J., Neil, A., Parra-Herran, C., Rivera-Zengotita, M., Sharma, A., Nucci, M., Rabban, J., Howitt, B., Ordulu, Z. ELSEVIER SCIENCE INC. 2025

  View details for DOI 10.1016/j.labinv.2024.103301

  View details for Web of Science ID 001460372500036

• POLE-mutated uterine carcinosarcomas: a clinicopathologic and molecular study of 11 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Hammer, P. M., Momeni-Boroujeni, A., Kolin, D. L., Kingsley, L., Folkins, A., Geisick, R. L., Ho, C., Suarez, C. J., Howitt, B. E. 2024: 100676

  Abstract

  Uterine carcinosarcomas (UCS) are high-grade biphasic neoplasms with generally poor outcomes. Based on TCGA molecular classification of endometrial carcinomas, the majority of UCS are classified as copy-number high/serous-like (p53 abnormal); however, a small subset represent other molecular subtypes, including those that harbor POLE mutations. We identified 11 POLE-mutated (POLEmut) UCS across three institutions and assessed the clinical, histopathologic, immunohistochemical and molecular features of these tumors. POLEmut UCS occurred in adult women (median age 64 years, range 48 to 79 years) and usually presented as FIGO (2009) clinical stage IA (n = 4) or IB (n=3). Almost all tumors were predominantly carcinomatous (n =10), with most showing endometrioid morphology (n = 7), followed by ambiguous (n=4) and serous (n = 3) histotypes. By immunohistochemistry, 7 tumors showed aberrant or subclonally aberrant expression of p53, 6 of which harbored pathogenic mutations in TP53 by sequencing. Other frequent mutations included PIK3CA (10/11), PTEN (8/11), RB1 (7/11), ARID1A (7/11), ATM (6/11), PIK3RA (5/11) and FBXW7 (4/11). Two tumors demonstrated loss of mismatch repair protein expression and one had subclonal loss. Heterologous differentiation was uncommon and only chondrosarcomatous type (n = 2) was observed. Mean and median follow-up were 24.3 and 14.1 months, respectively (range 1.4 to 61.1 months). Ten patients (91%) had no recurrences or death from disease, though 3 of these had follow-up periods <1 year. One patient, with the subclonal POLE variant, presented with stage IV disease and died 1.4 months after surgery. In conclusion, POLEmut UCS demonstrate unique morphologic and immunohistochemical features compared to their p53-abnormal counterparts and may have significant prognostic differences. Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.

  View details for DOI 10.1016/j.modpat.2024.100676

  View details for PubMedID 39615841

• Prognostic performance of FIGO 2023 endometrial carcinoma staging: a comparison to FIGO 2009 staging in the setting of known and unknown molecular classification. Histopathology Libert, D., Hammer, P. M., Hui, C., Kidd, E. A., Folkins, A. K., Longacre, T., Yang, E. J., Charu, V., Howitt, B. E. 2024

  Abstract

  The 2023 FIGO staging criteria for endometrial cancer (EC) introduced marked changes from the 2009 version. The full implication of these changes for patient diagnosis and treatment is unknown. We evaluate the differences in staging and prognostication between the two systems, with and without inclusion of molecular classification.We assigned (1) FIGO 2009, (2) 2023 molecular-agnostic and (3) 2023 molecular-informed stages to 404 fully staged and molecularly classified patients with EC. Disease-specific and progression/relapse-free survival were analysed via the Kaplan-Meier method and compared with log-rank testing; 118 of 252 (47%) FIGO 2009 stage I patients were upstaged based on histopathological findings alone. Stage I/II subgroup survival distribution analysis showed a worse prognosis in FIGO 2023 IIB and IIC patients. In the molecular-informed FIGO 2023 system, three of 15 (20%) POLE-mutated stage I/II cases were downstaged from FIGO 2009 and eight (53%) were downstaged from molecular-agnostic FIGO 2023. Fifty-one of 60 (85%) p53-abnormal tumours were upstaged from the FIGO 2009, whereas 13 of 60 (22%) were upstaged from the 2023 molecular-agnostic stage. Molecular classification improved prognostic stratification for both 2009 and 2023 FIGO systems.Downstaging based on POLE mutation more accurately represents patient outcomes. However, in the absence of known POLE status, applying molecular-agnostic FIGO 2023 criteria for stage I/II disease should be conducted with caution. For aggressive histotypes, additionally reporting FIGO 2009 stage should be considered. Upstaging based on substantial lymphovascular space invasion, aggressive histotype with any myometrial invasion and abnormal p53 improves prognostic discernment. Further subdivisions within stage I/II provide minimal additional prognostic information.

  View details for DOI 10.1111/his.15302

  View details for PubMedID 39209547

• Molecular Classification Outperforms Histologic Classification in Prognostication of High-grade Endometrial Carcinomas With Undifferentiated and Sarcomatous Components. The American journal of surgical pathology Hammer, P. M., Wang, A., Vermij, L., Zdravkovic, S., Heilbroner, L., Ryan, E., Geisick, R. L., Charu, V., Longacre, T. A., Suarez, C. J., Ho, C., Jenkins, T. M., Mills, A. M., Bosse, T., Howitt, B. E. 2024

  Abstract

  Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE-mutated (POLEmut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS (P=0.008) and P≤0.0001). POLEmut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.

  View details for DOI 10.1097/PAS.0000000000002250

  View details for PubMedID 38780000

• Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients. Clinical cancer research : an official journal of the American Association for Cancer Research Nief, C. A., Hammer, P. M., Wang, A., Charu, V., Tanweer, A., Litkouhi, B., Kidd, E., Gentles, A. J., Howitt, B. E. 2024

  Abstract

  PURPOSE: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing.EXPERIMENTAL DESIGN: We collected a 105-patient case-control cohort of stage I EEC comprised of 45 patients who experienced recurrence less than 6 years after excision, and 60 FIGO grade matched controls without recurrence. We first utilized two RNA based, previously validated machine learning approaches, namely EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI) which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 stage I EEC patients.RESULTS: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI 4.1-23.8, P <0.001).CONCLUSIONS: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.

  View details for DOI 10.1158/1078-0432.CCR-23-3158

  View details for PubMedID 38669067

• Perivascular Epithelioid Cell-Family Tumors in Children, Adolescents and Young Adults:Clinicopathologic Features in 70 Cases. Archives of pathology & laboratory medicine Hammer, P. M., Toland, A., Shaheen, M., Shenoy, A., Esnakula, A., Hicks, M. J., Warran, M., Al-Ibraheemi, A., Davis, J. L., Tan, S. Y. 2024

  Abstract

  Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.To describe a multi-institutional series of PEComas in children, adolescents, and young adults.PEComas, not otherwise specified (NOS); angiomyolipomas (AMLs); lymphangioleiomyomatosis; and clear cell sugar tumors were retrospectively identified from 6 institutions and authors' files.Seventy PEComas in 64 patients (median age, 15 years) were identified. They were more common in females (45 of 64 patients), occurring predominately in kidney (53 of 70), followed by liver (6 of 70). Thirty-four patients had confirmed tuberous sclerosis complex (TSC), 3 suspected TSC mosaicism, 2 Li-Fraumeni syndrome (LFS) and 1 neurofibromatosis type 1. Most common variants were classic (49 of 70) and epithelioid (8 of 70) AML. Among patients with AMLs, most (34 of 47) had TSC, and more TSC patients had multiple AMLs (15 of 36) than non-TSC patients (2 of 13). Two TSC patients developed malignant transformation of classic AMLs: 1 angiosarcomatous and 1 malignant epithelioid. Lymphangioleiomyomatosis (5 of 70) occurred in females only, usually in the TSC context (4 of 5). PEComas-NOS (6 of 70) occurred exclusively in non-TSC patients, 2 of whom had LFS (2 of 6). Three were malignant, 1 had uncertain malignant potential, and 2 were benign. All 4 PEComas-NOS in non-LFS patients had TFE3 rearrangements.Compared to the general population, TSC was more prevalent in our cohort; PEComas-NOS showed more frequent TFE3 rearrangements and possible association with LFS. This series expands the spectrum of PEComas in young patients and demonstrates molecular features and germline contexts that set them apart from older patients.

  View details for DOI 10.5858/arpa.2023-0552-OA

  View details for PubMedID 38547914

• Soft Tissue Perivascular Epithelioid Cell Tumors. Surgical pathology clinics Hammer, P. M., Tan, S. Y. 2024; 17 (1): 105-118

  Abstract

  Perivascular epithelioid cell tumors (PEComas) are a heterogenous group of mesenchymal neoplasms with a mixed myomelanocytic immunophenotype. PEComa-family tumors include angiomyolipoma, lymphangioleiomyomatosis, and a large category of rare neoplasms throughout the body that are now classified under the umbrella term "PEComa." This review focuses on recent advances in the clinicopathological and molecular features of PEComas, with an emphasis on PEComas that originate in soft tissue.

  View details for DOI 10.1016/j.path.2023.06.002

  View details for PubMedID 38278600

• A Picture is Worth 1000 Pathological Learning Points: Creating Visual Pathology Teaching Materials Appropriate for Pre-Clerkship Medical Student Learning Afifi, A., Cobos, J., Hammer, P., Gilbert, A., Bharani, K., Wang, C., Kuhlmann, R., Ernst, K. ELSEVIER SCIENCE INC. 2024: S1978-S1979

  View details for Web of Science ID 001302363407082

• Characterization of folate receptor alpha expression in non-high-grade serous gynecologic tumors Liang, B., Tenney, T., Tokuyama, M., Hammer, P., Zdravkovic, S., Howitt, B. BMJ PUBLISHING GROUP. 2023: A158-A159

  View details for DOI 10.1136/ijgc-2023-IGCS.285

  View details for Web of Science ID 001262421600295

• Does lymph node assessment change the prognostic significance of substantial LVSI and p53 status in endometrial endometrioid carcinoma? Gynecologic oncology Hui, C., Mendoza, M. G., von Eyben, R., Dorigo, O., Litkouhi, B., Renz, M., Karam, A., Hammer, P. M., Howitt, B. E., Kidd, E. 2023; 177: 150-156

  Abstract

  The PORTEC-2 update suggested that substantial lymphovascular space invasion (LVSI) and abnormal p53 expression (p53abnl) predict for poorer outcomes and that these patients should be treated with external beam radiation therapy (EBRT). We aim to determine if patients with these risk factors who undergo a lymph node (LN) assessment show similar outcomes.We retrospectively reviewed 126 patients with FIGO 2009 stage IA grade 3, stage IB grade 1-2, and stage IIIC (positive LN but no other stage II/III risk factors) endometrioid endometrial cancer who underwent LN assessment. Local (LR), regional recurrences (RR), and distant metastases were analyzed using competing risk methods, and overall survival (OS) was analyzed using Kaplan-Meier.Median follow-up time was 37.2 months. OS was significantly different between patients with and without p53abnl expression (16.7% versus 3.1% deceased), and between patients with and without LVSI (11.1% versus 1.5% deceased; p < 0.01 for both). The 2-year cumulative incidence of LR for patients with p53abnl versus wild type p53 and LVSI versus no LVSI was 11.1% (95% CI 0-25.6) versus 2.2% (95% CI 0-5.25; p = 0.04), and 11.4% (95% CI 2.0-20.9) versus 0%, respectively (p < 0.01). The 2-year cumulative RR in patients with LVSI versus no LVSI was 6.9% (95% CI 0-14.4) versus 0% (p = 0.05). No patients who completed pelvic RT experienced an in-field recurrence.Despite LN assessment, patients with high-intermediate risk early-stage or stage IIIC (with positive lymph nodes only but no other stage II or III risk factors) endometrial cancer with p53abnl expression and/or LVSI have worse outcomes. These patients may derive benefit from intensification with EBRT to improve local and pelvic control.

  View details for DOI 10.1016/j.ygyno.2023.09.001

  View details for PubMedID 37696217

• Detection of FOXL2 C134W Mutation Status by a Novel BaseScope-ISH Assay is Highly Sensitive and Specific for Adult Granulosa Cell Tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc Hammer, P. M., Wang, A., Beard, C., Zdravkovic, S., Tenney, T., Liang, B., Das, I., Bremer, R., Wang, L. C., McCluggage, W. G., Stewart, C. J., Howitt, B. E. 2023: 100318

  Abstract

  Adult granulosa cell tumors (AGCT) are a molecularly distinct group of malignant ovarian sex cord-stromal tumors (SCST) characterized by a nearly ubiquitous c.402C>G/p.C134W mutation in FOXL2 (hereafter referred to as "C134W"). In some cases, AGCT exhibits marked morphological overlap with other SCSTs, and have an identical immunophenotype, and molecular testing may be necessary to help confirm the diagnosis. However, molecular testing is time-consuming, relatively expensive, and unavailable in many pathology laboratories. We describe the development and validation of an in situ hybridization (ISH) custom BaseScope assay for the detection of the FOXL2 C134W mutation. We evaluated 106 ovarian SCSTs, including 78 AGCT, 9 juvenile granulosa cell tumors, 18 fibromas (cellular and conventional), and 1 SCST, not otherwise specified (NOS), as well as 53 epithelial ovarian tumors (42 endometrioid carcinomas and 11 carcinosarcomas) and 1 STK11 adnexal tumor for the presence or absence of FOXL2 wild-type and FOXL2 C134W RNA expression via Basescope-ISH. Fifty-one tumors had previously undergone DNA sequencing of the FOXL2 gene. Across the entire cohort, the FOXL2 C134W probe staining was positive in 77/78 (98.7%) AGCTs. 2/81 (2.5%) non-AGCT also showed positive staining, both of which were epithelial ovarian tumors. The assay worked in tissue blocks >20 years old. There was 100% concordance between the FOXL2 sequencing and Basescope-ISH results. Overall, assessment of FOXL2 mutation status by custom Basescope-ISH demonstrated 98.7% sensitivity and 97.5% specificity for the diagnosis of AGCT. Basescope-ISH for FOXL2 C134W represents a reasonable alternative to sequencing, is quicker and less expensive, and is more easily incorporated than molecular testing into many pathology laboratories. It also has the advantage of requiring less tissue, and the neoplastic cells can be directly visualized on stained sections.

  View details for DOI 10.1016/j.modpat.2023.100318

  View details for PubMedID 37634867

• Polarization of Endothelial and Epithelial Cell States Predicts Recurrence in Endometrial Endometrioid Carcinoma Nief, C., Hammer, P., Wang, A., Gentles, A., Howitt, B. ELSEVIER SCIENCE INC. 2023: S962-S963

  View details for Web of Science ID 000990969802103

• TCGA Molecular Subgroup Shows Greater Prognostic Significance Than Histologic Diagnosis in High-Grade Endometrial Carcinomas with Spindled, Undifferentiated and Sarcomatous Components Hammer, P., Wang, A., Zdravkovic, S., Heilbroner, L., Ryan, E., Mills, A., Jenkins, T., Howitt, B. ELSEVIER SCIENCE INC. 2023: S913-S914

  View details for Web of Science ID 000990969802055

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms Express Germ Cell Markers. Histopathology Hammer, P. M., Kolin, D. L., Charville, G. W., McCluggage, W. G., Howitt, B. E. 2022

  Abstract

  SMARCB1 (INI-1) deficient vulvar neoplasms comprise a group of rare tumors that include epithelioid sarcoma (ES), myoepithelial carcinoma (MEC), the recently described myoepithelioma-like tumor of the vulvar region (MELTVR), and sarcomas which are difficult to classify. It has been suggested that so-called vulvar yolk sac tumors (YST) may represent morphologic variants of SMARCB1-deficient tumors; thus we investigated the immunoreactivity of germ cell markers in SMARCB1-deficient vulvar neoplasms.Ten SMARCB1-deficient vulvar neoplasms were stained with germ cell tumor markers (SALL4, glypican-3, OCT3/4, and AFP) and re-reviewed for morphologic features. The tumors occurred in adult females (median age 41 years) and included ES (n=7), MELTVR (n=2), and MEC (n=1). All cases showed loss of SMARCB1 expression. Four cases (40%) were focally positive for SALL4 in areas with morphology of typical-appearing ES. One of these cases also showed focal staining for OCT3/4. One ES showed a transition from typical-appearing ES to YST-like morphology, with diffuse expression of SALL4 and glypican-3, and focal expression of AFP, in these latter areas. All other tested cases were negative for AFP.Our study reveals that SALL4, glypican-3, and OCT3/4 are positive in a subset of SMARCB1-deficient vulvar neoplasms, which may pose a diagnostic challenge and result in consideration of a germ cell tumor. We also highlight a case with transition from ES to YST-like morphology, lending further support that YSTs of the vulva are somatically derived SMARCB1-deficient neoplasms and do not represent true germ-cell neoplasia.

  View details for DOI 10.1111/his.14709

  View details for PubMedID 35758187

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms are Positive for Germ Cell Markers Hammer, P., McCluggage, W., Kolin, D., Howitt, B. SPRINGERNATURE. 2022: 755-756

  View details for Web of Science ID 000770360202043

• A Subset of SMARCB1 (INI-1) Deficient Vulvar Neoplasms are Positive for Germ Cell Markers Hammer, P., McCluggage, W., Kolin, D., Howitt, B. SPRINGERNATURE. 2022: 755-756

  View details for Web of Science ID 000770361802043

• Intravascular adenomyomatosis: a morphologic variant of intravenous leiomyomatosis associated with endometriosis and potential for misdiagnosis. Human pathology Fitzpatrick, M. B., Hammer, P. M., Yang, E. J., Howitt, B. E. 2021

  Abstract

  Intravenous leiomyomatosis (IVL) is a quasi-malignant smooth muscle tumor involving lymphatic and venous spaces of the myometrium. Rare cases of IVL with admixed endometrial glands and stroma have been described, termed intravascular adenomyomatosis. We report four additional cases of intravascular adenomyomatosis and expand the clinicopathologic features of these rare tumors. Patients were 39-45 years old and presented with symptoms of dysmenorrhea, postmenopausal bleeding, or pelvic mass. All cases were associated with endometriosis. Three cases comprised intravascular bland smooth muscle tumors with plexiform features, and in some foci the intravascular tumor contained endometrial type glands and stroma. In one case there was extensive (>10) foci of intravascular adenomyomatosis without evidence of associated smooth muscle neoplasm but did have an endometrial polyp with adenomyomatous features. None of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. The endometrial stromal components were positive for CD10 and negative or weakly positive for desmin by immunohistochemistry. Two cases underwent molecular testing for JAZF1 and PHF1 rearrangements with negative results. Three patients had no evidence of disease at the time of last follow-up, and one had persistent but stable disease 7 years after incomplete surgical removal and megestrol acetate treatment. Intravascular adenomyomatosis is a variant morphology rarely seen in IVL that lacks characteristic morphologic and molecular features of endometrial stromal sarcoma. Like IVL, prognosis is likely linked to completeness of surgical resection. In this study we found that intravascular adenomyomatosis is frequently associated with endometriosis, a novel finding to add to the literature on this rare IVL variant.

  View details for DOI 10.1016/j.humpath.2021.11.009

  View details for PubMedID 34856302

• Black and Blue: Eyes and Dyes Sobel, R., Nirschl, J., Hammer, P., Sanchez, R., Pershing, S., Louie, C., Lin, J. OXFORD UNIV PRESS INC. 2021: 579

  View details for Web of Science ID 000671021700089

• Molecular Classification of Endometrial Carcinomas with Long-Term Follow-up Hammer, P., Albro, J., Squires, C., Peters-Schulze, G., Sharp, B., Charu, V., Cessna, M., Howitt, B. SPRINGERNATURE. 2021: 691–93

  View details for Web of Science ID 000629690900575

• 100 Years of the Pathology Medical Student Fellowship: Impacts on Undergraduate Education and Career Choices Hammer, P., Ireland, K., Houghton, D., Jaggers, A., Coleman, A., Snir, O., Troxell, M., Andeen, N. SPRINGERNATURE. 2021: 332–33

  View details for Web of Science ID 000629694100282

• Well-differentiated lipomatous neoplasms with p53 alterations: A clinicopathologic and molecular study of eight cases with features of atypical pleomorphic lipomatous tumor. Histopathology Hammer, P. M., Kunder, C. A., Howitt, B. E., Charville, G. W. 2021

  Abstract

  Well-differentiated lipomatous neoplasms encompass a broad spectrum of benign and malignant tumors, many of which are characterized by recurrent genetic abnormalities. Although a key regulator of p53 signaling, MDM2, is characteristically amplified in well-differentiated liposarcoma, recurrent abnormalities of p53 itself have not been reported in well-differentiated adipocytic neoplasms. Here, we present a series of well-differentiated lipomatous tumors characterized by p53 alterations and histologic features in keeping with atypical pleomorphic lipomatous tumor (APLT).We reviewed the morphologic, immunohistochemical, and molecular genetic features of eight lipomatous tumors with p53 alterations. Four tumors arose in the thigh, and one case each arose in the shoulder, calf, upper back, and subclavicular regions; six tumors were deep/subfascial and two were subcutaneous. Relevant clinical history included two patients with Li-Fraumeni syndrome. Morphologically, all cases demonstrated well-differentiated adipocytes with prominent nuclear pleomorphism, limited mitotic activity, and no tumor cell necrosis. All cases were negative for MDM2 overexpression and amplification by immunohistochemistry and fluorescence in situ hybridization, respectively. By immunohistochemistry, p16 was diffusely overexpressed in all cases; seven tumors (88%) showed abnormal loss of Rb and p53. TP53 mutation or deletion was identified in 4 of 6 tumors evaluated by exon-targeted hybrid capture-based massively parallel sequencing; RB1 mutation or deletion was present in 5 of 6 cases.We present a series of eight well-differentiated lipomatous neoplasms characterized by p53 alterations in addition to Rb loss and histologic features of APLT. These findings suggest that impaired p53 signaling may contribute to the pathogenesis of APLT in a subset of cases.

  View details for DOI 10.1111/his.14593

  View details for PubMedID 34725851

• One Hundred Years of the Pathology Medical Student Fellowship. Archives of pathology & laboratory medicine Hammer, P., Ireland, K., Houghton, D. C., Jaggers, A., Coleman, A., Snir, O. L., Troxell, M. L., Andeen, N. K. 2021

  Abstract

  The Pathology Medical Student Fellowship (PSF) is a unique, year-long immersive educational experience. Review of institutional archives describes a medical student "Fellowship in Pathology" founded in 1919.To characterize the impacts of this 100-year-old program.We determined subsequent medical specialty of each PSF graduate in our department and surveyed those with available contact information.Of 145 pathology student fellows graduating between 1924 and 2020, a total of 50 (34.4%) matched into pathology; medical, surgical, and radiology subspecialties were also well-represented career choices. Between 2001 and 2020, of 36 students who matched into pathology from our institution, 19 (52.8%) had completed the fellowship. Survey respondents (n = 42) indicated that before the PSF, 11 of 42 students (26.2 %) were undecided in specialty, with only 6 (14.3%) identifying pathology as their primary field of interest. Of survey respondents who had completed training, 26 (61.9%) practice in academic settings. Nonpathology physicians reported frequent utilization of skills gained during the PSF year, with 5 of 23 (21.7%) responding "daily," and 9 (39.1%) responding "weekly." The most useful skills included knowledge of pathophysiology of disease and anatomy, improved communication with multidisciplinary teams, and/or interpretation of pathology results (each selected by 17 to 20 students, 73.9%-87.0%). Free-text responses on impacts of the PSF described enhanced knowledge of disease pathobiology and diagnostic complexity and increased confidence and autonomy.We describe the program structure, educational benefits, graduate specialty choices, and career impacts of 100 years of the PSF at our institution. Although undecided before pathology exposure, many PSF graduates subsequently enter pathology careers. Regardless of specialty choice, PSF graduates have a high rate of subsequently pursuing academic medical careers.

  View details for DOI 10.5858/arpa.2021-0220-OA

  View details for PubMedID 34784414

• Differential Diagnosis of a Unique Vulvar Mass in an Adolescent. Obstetrics and gynecology Chow, S., Doyle, A., Hammer, P., Tyson, N. A. 2021

  Abstract

  Vulvar masses in adolescents have a broad differential diagnosis, yet few reports exist detailing masses of mammary origin.A nulliparous, healthy 16-year-old adolescent presented with a longstanding, ulcerated, 17-cm vulvar mass of unknown origin and pronounced inguinal lymphadenopathy. The patient underwent a left radical partial vulvectomy, with pathology revealing terminal duct lobular units consistent with polymastia.Differential diagnosis of a vulvar mass in an adolescent should include polymastia.

  View details for DOI 10.1097/AOG.0000000000004563

  View details for PubMedID 34735404

• The utility and challenges of histopathologic evaluation in the diagnosis of nonmalignant skin ulcers. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society Hammer, P., Latour, E., Bohnett, M. C., McKenzie, F., Korcheva, V. B., Mengden, S., White, K. P., Ortega-Loayza, A. G. 2020; 28 (2): 219-223

  Abstract

  Histopathologic evaluation of cutaneous ulcers is indicated when the clinical diagnosis is unclear or when ulcers have not responded to standard of care. Many nonmalignant skin ulcers lack specific histologic findings on biopsy and pose a diagnostic challenge. While the usefulness of skin biopsies to diagnose underlying malignancy in ulcerated lesions has been demonstrated in previous studies, their utility in the diagnosis of ulcers of other etiologies has not been reported. We conducted a retrospective study of 45 nonmalignant ulcer biopsies in a 3-year period to compare the histologic diagnosis with the final diagnosis. Additionally, we assessed the diagnostic concordance among three blinded dermatopathologists when reviewing these cases. The leading histologic diagnosis from each of the three observers agreed with the final clinical diagnosis, on average, for 29.6% of the cases (average pairwise kappa = 0.15). Inflammatory ulcers had the lowest concordance between the observers and final diagnosis with an average of 26.0% of cases (average pairwise kappa = 0.06). The observers agreed with each other for 35.6% of the cases (Fleiss' kappa = 0.32). The highest agreement among observers was in the vascular/vasculopathic category (50%, Fleiss' kappa = 0.44). Our results indicate that skin biopsies alone are useful in the evaluation of nonmalignant ulcers to rule out other conditions (e.g. neoplasm) but frequently not sufficient to establish a definitive diagnosis. Additional clinicopathologic correlation is necessary in the final assessment of nonmalignant ulcers to determine the diagnosis. Future research endeavors should explore alternative approaches to more efficiently diagnose nonmalignant skin ulcers.

  View details for DOI 10.1111/wrr.12780

  View details for PubMedID 31705777

• Characterisation and diagnosis of ulcers in inpatient dermatology consultation services: A multi-centre study. International wound journal Haynes, D., Hammer, P., Malachowski, S. J., Kaffenberger, B., Yi, J. S., Vera, N., Calhoun, C., Shinohara, M. M., Seminario-Vidal, L., Trinidad, J. C., Keller, J. J., Ortega-Loayza, A. G. 2019; 16 (6): 1440-1444

  Abstract

  Accurate and prompt diagnosis of skin ulcers is critical to optimise management; however, studies in hospitalised patients are limited. This retrospective review of dermatologic consultations included 272 inpatients with skin ulcers between July 2015 and July 2018 in four U.S. academic hospitals. The median age was 54 years and 45% were male. In 49.3% of the patients, skin ulcers were considered the primary reason for admission. Ulcers of 62% were chronic and 49.6% were located on the lower extremities. Pyoderma gangrenosum (17.3%), infection (12.5%), and exogenous causes (11.8%) were the leading aetiologies; 12% remained diagnostically inconclusive after consultation. Diagnostic agreements pre-dermatology and post-dermatology consult ranged from 0.104 (n = 77, 95% CI 0.051-0.194) to 0.553 (n = 76, 95% CI 0.440-0.659), indicating poor-modest agreement. This study highlights the diagnostic complexity and relative incidences of skin ulcers in the inpatient setting.

  View details for DOI 10.1111/iwj.13211

  View details for PubMedID 31475449

• Nipple leiomyoma: A rare neoplasm with a broad spectrum of histologic appearances. Journal of cutaneous pathology Hammer, P., White, K., Mengden, S., Korcheva, V., Raess, P. W. 2019; 46 (5): 343-346

  Abstract

  Cutaneous leiomyomas are rare benign smooth-muscle tumors. These lesions are distinguished based on their cell of origin and are subclassified as pilar leiomyoma, angioleiomyoma, and genital-type leiomyoma. Nipple leiomyoma is the least common genital-type leiomyoma, arising from the dartoic muscle cell of the nipple. Histologic examination of the lesion is necessary for definitive diagnosis, and these uncommon tumors can pose a diagnostic challenge. We describe herein a series of six nipple leiomyomas with a spectrum of histologic appearances.

  View details for DOI 10.1111/cup.13423

  View details for PubMedID 30663114