Clinical Focus


  • Anatomic Pathology
  • Surgical Pathology
  • Urological Pathology
  • Soft Tissue Pathology
  • Molecular Pathology

Academic Appointments


Administrative Appointments


  • Assistant Medical Director, Molecular Pathology Laboratory (2015 - 2018)
  • Associate Medical Director, Molecular Pathology Laboratory (2018 - Present)

Professional Education


  • Fellowship:Stanford University Molecular Genetic Pathology Fellowship (2015) CA
  • Board Certification: Molecular Genetic Pathology, American Board of Pathology (2015)
  • Board Certification, American Board of Pathology, Molecular Genetic Pathology (2015)
  • Fellowship, Stanford Health Care, Molecular Genetic Pathology (2015)
  • Board Certification, American Board of Pathology, Hematology (2014)
  • Fellowship, Stanford Health Care, Hematopathology (2014)
  • Board Certification, American Board of Pathology, Anatomic Pathology (2013)
  • Fellowship, Stanford Health Care, Surgical Pathology (2013)
  • Residency, Stanford Health Care, Anatomic Pathology (2013)
  • Medical Education:Duke University School of Medicine (2010) NC

Current Research and Scholarly Interests


My main interest is in understanding the biology of human neoplasms, using traditional histopathology, molecular genetic techniques, and other modalities. In particular, I am interested in soft tissue and genitourinary neoplasms, especially prostate cancer.

I am also interested in the classification and nomenclature of neoplasms and in practical research that helps us refine these, using a variety of techniques but still principally guided by histopathology.

I also work on developing next generation sequencing-based tests for genotyping tumors and in expanding the scope of this testing with the goal of identifying patients eligible for novel targeting therapies.

All Publications


  • Structural. Variation Detection by Proximity Ligation from Formalin-Fixed, Paraffin-Embedded Tumor Tissue JOURNAL OF MOLECULAR DIAGNOSTICS Troll, C. J., Putnam, N. H., Hartley, P. D., Rice, B., Blanchette, M., Siddiqui, S., Ganbat, J., Powers, M. P., Ramakrishnan, R., Kunder, C. A., Bustamante, C. D., Zehnder, J. L., Green, R. E., Costa, H. A. 2019; 21 (3): 375–83
  • Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. Anti-cancer drugs Wang, S. X., Zhang, B. M., Wakelee, H. A., Koontz, M. Z., Pan, M., Diehn, M., Kunder, C. A., Neal, J. W. 2019

    Abstract

    The mesenchymal-to-epithelial transition (MET) gene is altered and becomes a driver mutation in up to 5% of non-small-cell lung cancer (NSCLC). We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib. We identified cases of NSCLC with METex14 mutations using an institutionally developed or commercial next-generation sequencing assay. We assessed patient and disease characteristics by retrospective chart review. Some patients were treated off-label by the physician with crizotinib or cabozantinib, and tumor responses to these agents were assessed. A total of 15 patients with METex14-mutated NSCLC were identified, predominantly male (n=10) with a smoking history (60%) and a median age of 74.0 years. No other actionable somatic mutations were detected. Stage distribution included 26.7% stage I, 6.7% stage II, 6.7% stage III, and 60.0% stage IV. Among patients treated with crizotinib or cabozantinib (n=6), three patients showed partial response and one patient showed stable disease on the basis of RECIST criteria. Four patients experienced side effects requiring drug holiday, reduction, or cessation. Our findings highlight the diversity in presentation and histology of NSCLC with METex14 mutations, which were found in the absence of other actionable driver mutations. We observed evidence of tumor response to crizotinib and cabozantinib, supporting the previous reports that METex14 mutations in NSCLC are actionable driver events.

    View details for PubMedID 30762593

  • A Case of Disseminated Pneumocystis Jiroveci in a Non-Human Immunodeficiency Virus Infected Patient Siddiqi, A. E., Sacha, J., Saenz, R., Liu, A., Kunder, C., Uzel, G., Martin, B., Lewis, D. B., Gernez-Goldhammer, Y. SPRINGER/PLENUM PUBLISHERS. 2019: S73–S74
  • A Case Report of Pediatric Clear Cell Carcinoma of the Urinary Bladder Associated With Polyomavirus AJSP-REVIEWS AND REPORTS Saleem, A., Brown, R. A., Higgins, J. T., Troxell, M. L., Kunder, C. A., Pinsky, B. A., Zambrano, E., Kao, C. 2018; 23 (6): 291–95
  • Circulating tumor DNA (ctDNA) in B-cell lymphoma Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. M., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Green, M. R., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Davis, R., Levy, R., Ohgami, R. S., Kunder, C. A., Rossi, D., Westin, J., Diehn, M., Alizadeh, A. A. WILEY. 2018: 16–17
  • Synchronous primary lung adenocarcinomas harboring distinct MET Exon 14 splice site mutations. Lung cancer (Amsterdam, Netherlands) Wang, S. X., Lei, L., Guo, H. H., Shrager, J., Kunder, C. A., Neal, J. W. 2018; 122: 187–91

    Abstract

    When a patient is found to have multiple lung tumors, distinguishing whether they represent metastatic nodules or separate primary cancers is crucial for staging and therapy. We report the case of a 79-year-old patient with two surgically resected synchronous left upper lobe adenocarcinomas initially pathologically staged as T3 (IIB), indicating adjuvant chemotherapy should be recommended. However, the tumors appeared radiographically distinct, so next-generation sequencing was performed on each nodule. Each tumor harbored a different mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation, an emerging targetable mutation, suggestive of distinct clonality. While the in frame protein deletion was the same in each tumor, the nucleotide base substitutions were different. Thus, the patient was down-staged to having two separate IA tumors, spared of adjuvant chemotherapy, and routine surveillance was recommended. This case highlights the utility of using molecular analysis in diagnosing and treating multifocal lung tumors, and the process of convergent molecular evolution toward a common oncogenic driver mutation. This is the first case of multiple synchronous lung tumors each harboring a distinct MET exon 14 splice site mutation.

    View details for PubMedID 30032829

  • Methionine aminopeptidase II (MetAP2) activated in situ self-assembly of small-molecule probes for imaging prostate cancer. Xie, J., Rice, M., Cheng, Y., Song, G., Kunder, C., Brooks, J. D., Stoyanova, T., Rao, J. AMER ASSOC CANCER RESEARCH. 2018: 115–16
  • Defining new drivers of castration- resistant prostate cancer Hsu, E., Rice, M., Nolley, R., Bermudez, A., Huang, J., Peehl, D., Kunder, C., Pitteri, S., Brooks, J., Stoyanova, T. AMER ASSOC CANCER RESEARCH. 2018: 90
  • Adrenal Myelolipomas Involved by Plasma Cell Myeloma. American journal of clinical pathology Lin, C., Levy, D., Higgins, J. P., Kunder, C. A., Kao, C. 2018

    Abstract

    Objectives: To report the presence and evaluate the frequency of plasma cell neoplasms within adrenal myelolipomas.Methods: Adrenal myelolipomas within our institution were reviewed for the presence of hematologic neoplasia, and a review of the literature was performed.Results: Two (9%) of 23 adrenal myelolipomas were involved by plasma cell myeloma. The patients were 71 and 81 years old, one woman and one man, with tumors measuring 7 cm and 8.5 cm, respectively. Both tumors contained large aggregates of dysplastic plasma cells occupying at least one *10 field and demonstrated light chain restriction. Neither had an established diagnosis of plasma cell neoplasm previously. After receiving therapy, one patient exhibited a stable clinical course 1 year after diagnosis while the other died of disease 3 years later.Conclusions: We report the first two cases of adrenal myelolipoma involved by plasma cell myeloma, a rare and subtle finding that has significant clinical implications.

    View details for PubMedID 30052719

  • ALK-rearranged Tumors are Highly Enriched in the STUMP Subcategory of Uterine Tumors. The American journal of surgical pathology Devereaux, K. A., Kunder, C. A., Longacre, T. A. 2018

    Abstract

    Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogenous. Recent data suggest uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as STUMPs, but the extent to which this occurs has not been examined. We identified 60 female patients with tumors previously diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid features, although limited in some cases, were present in all 6 ALK IHC positive tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3' ALK signals, an unusual FISH pattern not previously described in uterine IMTs. Two patients developed recurrent disease and were treated with ALK-targeted therapy with initial response. Our data demonstrate that a significant proportion of uterine and cervical tumors considered to be STUMPs are ALK-positive by IHC and FISH. Future screening of all uterine and cervical mesenchymal tumors under consideration for the diagnosis of STUMP, particularly those with myxoid features, is recommended to identify ALK-rearranged IMTs that could potentially be treated with targeted therapy using tyrosine kinase inhibitors.

    View details for PubMedID 29794871

  • Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology Park, S. Y., Zacharias, C., Harrison, C., Fan, R. E., Kunder, C., Hatami, N., Giesel, F., Ghanouni, P., Daniel, B., Loening, A. M., Sonn, G. A., Iagaru, A. 2018: 172232

    Abstract

    Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi ± 0.7 (151.7 MBq ± 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

    View details for PubMedID 29786490

  • Serum miR371a Quantitation for Assessing Tumor Burden in Testicular Germ Cell Tumors Kunder, C., Imae, Y., Srinivas, S., Fan, A. C. NATURE PUBLISHING GROUP. 2018: 703
  • Clinicopathologic Characteristics of Fumarate Hydratase-Deficient and Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Series of 10 Cases Lau, H., Williamson, S. R., Kunder, C., Fan, A. C., Kao, C. NATURE PUBLISHING GROUP. 2018: 358
  • Validation and Application of Predicted Tumor Mutational Burden (pTMB) Using a 130-Gene Sequencing Panel in Lung Adenocarcinoma Yang, S., Steiner, D., Stehr, H., Berry, G., Zehnder, J. L., Kunder, C. NATURE PUBLISHING GROUP. 2018: 758–59
  • Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival CLINICAL LUNG CANCER Berry, M. F., Gao, R., Kunder, C. A., Backhus, L., Khuong, A., Kadoch, M., Leung, A., Shrager, J. 2018; 19 (1): E47–E51

    Abstract

    While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas.The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses.A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01).Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies.

    View details for PubMedID 28743420

  • Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy. Research and reports in urology Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B. I., Sonn, G. A. 2018; 10: 233–35

    Abstract

    Utilization of pre-biopsy multiparametric MRI (mpMRI) is increasing. To optimize the usefulness of mpMRI, physicians should accurately quote patients a numerical risk of cancer based on their MRI. The Prostate Imaging Reporting and Data System (PIRADS) standardizes interpretation of mpMRI; however, reported rates of clinically significant prostate cancer (CSC) stratified by PIRADS score vary widely. While some publications use radical prostatectomy (RP) specimens as gold standard, others use biopsy. We hypothesized that much of the variation in CSC stems from differences in cancer prevalence in RP cohorts (100% prevalence) vs biopsy cohorts. To quantify the impact of this selection bias on cancer yield according to PIRADS score, we analyzed data from 614 men with 854 lesions who underwent targeted biopsy from 2014 to 2018. Of these, 125 men underwent RP. We compared the PIRADS detection rates of CSC (Gleason ≥7) on targeted biopsy between the biopsy-only and RP cohorts. For all PIRADS scores, CSC yield was much greater in patients who underwent RP. For example, CSC was found in 30% of PIRADS 3 lesions in men who underwent RP vs 7.6% in men who underwent biopsy. Our results show that mpMRI performance appears to be better in men who undergo RP compared with those who only receive biopsy. Physicians should understand the effect of this selection bias and its magnitude when discussing mpMRI results with patients considering biopsy, and take great caution in quoting CSC yields from publications using RP as gold standard.

    View details for PubMedID 30538970

  • Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy RESEARCH AND REPORTS IN UROLOGY Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B., Sonn, G. A. 2018; 10: 233–35
  • Survival and risk factors for progression after resection of the dominant tumor in multifocal, lepidic-type pulmonary adenocarcinoma Gao, R. W., Berry, M. F., Kunder, C. A., Khuong, A. A., Wakelee, H., Neal, J. W., Backhus, L. M., Shrager, J. B. MOSBY-ELSEVIER. 2017: 2092-+

    Abstract

    It remains unclear whether a dominant lung adenocarcinoma that presents with multifocal ground glass opacities (GGOs) should be treated by local therapy. We sought to address survival in this setting and to identify risk factors for progression of unresected GGOs.Retrospective review of 70 patients who underwent resection of a pN0, lepidic adenocarcinoma, who harbored at least 1 additional GGO. Features associated with GGO progression were determined using logistic regression and survival was evaluated using the Kaplan-Meier method.Subjects harbored 1 to 7 GGOs beyond their dominant tumor (DT). Mean follow-up was 4.1 ± 2.8 years. At least 1 GGO progressed after DT resection in 21 patients (30%). In 11 patients (15.7%), this progression prompted resection (n = 5) or stereotactic radiotherapy (n = 6) at mean 2.8 ± 2.3 years. Several measures of the overall tumor burden were associated with GGO progression (all P values < .03) and with progression prompting intervention (all P values < .01). In logistic regression, greater DT size (odds ratio, 1.07; 95% confidence interval, 1.01-1.14) and an initial GGO > 1 cm (odds ratio, 4.98; 95% confidence interval, 1.15-21.28) were the only factors independently associated with GGO progression. Survival was not negatively influenced by GGO progression (100% with vs 80.7% without; P = .1) or by progression-prompting intervention (P = .4).At 4.1-year mean follow-up, 15.7% of patients with unresected GGOs after resection of a pN0 DT underwent subsequent intervention for a progressing GGO. Some features correlated with GGO growth, but neither growth, nor need for an intervention, negatively influenced survival. Thus, even those at highest risk for GGO progression should not be denied resection of a DT.

    View details for PubMedID 28863952

  • KLHL6 Is Preferentially Expressed in Germinal Center-Derived B-Cell Lymphomas AMERICAN JOURNAL OF CLINICAL PATHOLOGY Kunder, C. A., Roncador, G., Advani, R. H., Gualco, G., Bacchi, C. E., Sabile, J. M., Lossos, I. S., Nie, K., Tibshirani, R., Green, M. R., Alizadeh, A. A., Natkunam, Y. 2017; 148 (6): 465–76

    Abstract

    KLHL6 is a recently described BTB-Kelch protein with selective expression in lymphoid tissues and is most strongly expressed in germinal center B cells.Using gene expression profiling as well as immunohistochemistry with an anti-KLHL6 monoclonal antibody, we have characterized the expression of this molecule in normal and neoplastic tissues. Protein expression was evaluated in 1,058 hematopoietic neoplasms.Consistent with its discovery as a germinal center marker, KLHL6 was positive mainly in B-cell neoplasms of germinal center derivation, including 95% of follicular lymphomas (106/112). B-cell lymphomas of non-germinal center derivation were generally negative (0/33 chronic lymphocytic leukemias/small lymphocytic lymphomas, 3/49 marginal zone lymphomas, and 2/66 mantle cell lymphomas).In addition to other germinal center markers, including BCL6, CD10, HGAL, and LMO2, KLHL6 immunohistochemistry may prove a useful adjunct in the diagnosis and future classification of B-cell lymphomas.

    View details for PubMedID 29140403

  • Predominance of CD4+ T Cells in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma and Identification of a Subset of Patients With Peripheral B-Cell Lymphopenia. American journal of clinical pathology Kunder, C., Cascio, M. J., Bakke, A., Venkataraman, G., O'Malley, D. P., Ohgami, R. S. 2017; 147 (6): 596-603

    Abstract

    T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a morphologic variant of large B-cell lymphoma whose flow cytometry findings are not well characterized.Nineteen cases with flow cytometric immunophenotyping were identified from the case records of four institutions between 2001 and 2016.In most cases, neoplastic B cells were not detected by flow cytometry. Overall, cases showed a predominance of CD4+ T cells, which in some cases was marked. Significant coexpression of CD57 was seen on CD4+ T cells where this marker was analyzed, which correlated with PD-1 expression. Two cases also showed a profound systemic B-cell lymphopenia, which was associated in one case with hypogammaglobulinemia.Overall, our work challenges previous findings that cases of THRLBCL are rich in CD8+ T cells and highlights parallels between THRLBCL and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Also, an association of THRLBCL with systemic B-cell lymphopenia has not been previously reported but may represent an underrecognized manifestation.

    View details for DOI 10.1093/ajcp/aqx034

    View details for PubMedID 28575178

  • Case Series of MET Exon 14 Skipping Mutation-positive Non-Small Cell Lung Cancers and Response to Crizotinib. International journal of radiation oncology, biology, physics Wang, S. X., Zhang, B., Wakelee, H. A., Diehn, M., Kunder, C., Neal, J. W. 2017; 98 (1): 239-?

    View details for DOI 10.1016/j.ijrobp.2017.01.170

    View details for PubMedID 28587017

  • Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Banerjee, S., Zare, R. N., Tibshirani, R. J., Kunder, C. A., Nolley, R., Fan, R., Brooks, J. D., Sonn, G. A. 2017; 114 (13): 3334-3339

    Abstract

    Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.

    View details for DOI 10.1073/pnas.1700677114

    View details for Web of Science ID 000397607300049

    View details for PubMedID 28292895

    View details for PubMedCentralID PMC5380053

  • Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy. Journal of cutaneous pathology Dai, J., Kunder, C. A., Chu, E. Y., Chan, E. F., Egan, C. L., Novoa, R. A. 2017

    Abstract

    Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma 6 months after initiation of vemurafenib therapy. Next-generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.

    View details for PubMedID 28796396

  • Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

    Abstract

    Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

    View details for PubMedID 28761389

  • Mycosis fungoides presenting as symmetric concentric patches mimicking figurate erythema. JAAD case reports Notay, M., Petukhova, T. A., Kiuru, M., Kunder, C. A., Hwang, S. T. 2017; 3 (4): 288–90

    View details for PubMedID 28702497

    View details for PubMedCentralID PMC5484965

  • Indolent thyroid cancer: knowns and unknowns. Cancers of the head & neck Hahn, L. D., Kunder, C. A., Chen, M. M., Orloff, L. A., Desser, T. S. 2017; 2: 1

    Abstract

    Thyroid cancer incidence is rapidly increasing due to increased detection and diagnosis of indolent thyroid cancer, i.e. cancer that is likely to be clinically insignificant. Clinical, radiologic, and pathologic features predicting indolent behavior of thyroid cancer are still largely unknown and unstudied. Existing clinicopathologic staging systems are useful for providing prognosis in the context of treated thyroid cancer but are not designed for and are inadequate for predicting indolent behavior. Ultrasound studies have primarily focused on discrimination between malignant and benign nodules; some studies show promising data on using sonographic features for predicting indolence but are still in their early stages. Similarly, molecular studies are being developed to better characterize thyroid cancer and improve the yield of fine needle aspiration biopsy, but definite markers of indolent thyroid cancer have yet to be identified. Nonetheless, active surveillance has been introduced as an alternative to surgery in the case of indolent thyroid microcarcinoma, and protocols for safe surveillance are in development. As increased detection of thyroid cancer is all but inevitable, increased research on predicting indolent behavior is needed to avoid an epidemic of overtreatment.

    View details for PubMedID 31093348

    View details for PubMedCentralID PMC6460732

  • Comprehensive Genomic Profiling of Malignant Effusions in Patients with Metastatic Lung Adenocarcinoma. The Journal of molecular diagnostics : JMD Yang, S. R., Lin, C. Y., Stehr, H., Long, S. R., Kong, C. S., Berry, G. J., Zehnder, J. L., Kunder, C. A. 2017

    Abstract

    Cytology samples are being increasingly utilized for comprehensive molecular testing. Although fine-needle aspirates are adequate substrates for high-throughput sequencing, the suitability of malignant body fluids remains largely unexplored. Herein, we investigated the adequacy and utility of performing targeted next-generation sequencing (NGS) on malignant effusions from patients with metastatic lung adenocarcinoma. Thirty-two effusion samples that were submitted for hybrid capture-based NGS using a clinically validated solid tumor genotyping panel were examined. All cases showed ≥5% tumor cellularity; however, 28 (88%) provided sufficient DNA for NGS (≥1 ng/μL). The sequencing reads showed satisfactory quality control statistics, and the variant allele frequencies were correlated with tumor cellularity. Furthermore, pathogenic or likely pathogenic genomic alterations were identified in 26/28 samples (93%), whereas clinically actionable alterations were present in 18 (64%). Notably, nine patients had additional molecular testing performed on preceding/subsequent biopsies, and the results across multiple samples were compared. In two patients, the NGS-based fluid analysis identified clinically actionable alterations that were not detected by other hotspot testing. In four patients treated with tyrosine kinase inhibitors, malignant fluid sequencing confirmed driver alterations from prior testing and revealed new resistance mechanisms. Hence, given adequate DNA input and tumor cellularity, comprehensive genomic profiling of malignant effusions may be used to establish mutational status at diagnosis and inform treatment resistance during targeted therapy.

    View details for PubMedID 29269277

  • Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA SCIENCE TRANSLATIONAL MEDICINE Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. F., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Kunder, C. A., Diehn, M., Alizadeh, A. A. 2016; 8 (364)

    Abstract

    Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.

    View details for DOI 10.1126/scitranslmed.aai8545

    View details for PubMedID 27831904

  • PS01.67: Case Series of MET Exon 14 Skipping Mutation-Positive Non-Small Cell Lung Cancers and Response to Crizotinib: Topic: Medical Oncology. Journal of thoracic oncology Wang, S. X., Zhang, B. M., Wakelee, H., Diehn, M., Kunder, C. A., Neal, J. W. 2016; 11 (11S): S312-S313

    View details for DOI 10.1016/j.jtho.2016.09.102

    View details for PubMedID 27969534

  • Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood Kurtz, D. M., Green, M. R., Bratman, S. V., Scherer, F., Liu, C. L., Kunder, C. A., Takahashi, K., Glover, C., Keane, C., Kihira, S., Visser, B., Callahan, J., Kong, K. A., Faham, M., Corbelli, K. S., Miklos, D., Advani, R. H., Levy, R., Hicks, R. J., Hertzberg, M., Ohgami, R. S., Gandhi, M. K., Diehn, M., Alizadeh, A. A. 2015; 125 (24): 3679-3687

    Abstract

    Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and (18)fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT; n = 173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, compared with circulating leukocytes, was more abundant and better correlated with radiographic disease burden. Before treatment, molecular disease was detected in the plasma of 82% of patients compared with 71% in circulating cells (P = .68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs 30%; P = .001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time points before relapse, plasma Ig-HTS demonstrated improved specificity (100% vs 56%, P < .0001) and similar sensitivity (31% vs 55%, P = .4) compared with PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission.

    View details for DOI 10.1182/blood-2015-03-635169

    View details for PubMedID 25887775

  • Refractory warm IgM-mediated autoimmune hemolytic anemia associated with Churg-Strauss syndrome responsive to eculizumab and rituximab AMERICAN JOURNAL OF HEMATOLOGY Chao, M. P., Hong, J., Kunder, C., Lester, L., Schrier, S. L., Majeti, R. 2015; 90 (1): 78-81

    View details for DOI 10.1002/ajh.23791

    View details for Web of Science ID 000346771400022

    View details for PubMedID 24942207

  • Anterolateral congenital diaphragmatic hernia with omphalocele: A case report and literature review AMERICAN JOURNAL OF MEDICAL GENETICS PART A Scahill, M. D., Maak, P., Kunder, C., Halamek, L. P. 2013; 161A (3): 585-588

    Abstract

    The combination of congenital diaphragmatic hernia (CDH) and omphalocele is quite rare but can be seen in several syndromes. We report on a female newborn with this combination that had not been diagnosed prenatally. The patient suffered respiratory failure that persisted despite intensive care support, suggesting severe secondary pulmonary hypoplasia. Autopsy revealed the combination of an anterolateral CDH and omphalocele in the absence of other anomalies. We believe this to be the first such case to be reported in the literature.

    View details for DOI 10.1002/ajmg.a.35703

    View details for Web of Science ID 000315341700025

  • Pediatric plastic bronchitis: case report and retrospective comparative analysis of epidemiology and pathology. Case reports in pulmonology Kunder, R., Kunder, C., Sun, H. Y., Berry, G., Messner, A., Frankovich, J., Roth, S., Mark, J. 2013; 2013: 649365-?

    Abstract

    Plastic bronchitis (PB) is a pathologic condition in which airway casts develop in the tracheobronchial tree causing airway obstruction. There is no standard treatment strategy for this uncommon condition. We report an index patient treated using an emerging multimodal strategy of directly instilled and inhaled tissue plasminogen activator (t-PA) as well as 13 other cases of PB at our institution between 2000 and 2012. The majority of cases (n = 8) occurred in patients with congenital heart disease. Clinical presentations, treatments used, histopathology of the casts, and patient outcomes are reviewed. Further discussion is focused on the epidemiology of plastic bronchitis and a systematic approach to the histologic classification of casts. Comorbid conditions identified in this study included congenital heart disease (8), pneumonia (3), and asthma (2). Our institutional prevalence rate was 6.8 per 100,000 patients, and our case fatality rate was 7%.

    View details for DOI 10.1155/2013/649365

    View details for PubMedID 23662235

  • Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation NATURE COMMUNICATIONS Romero-Camarero, I., Jiang, X., Natkunam, Y., Lu, X., Vicente-Duenas, C., Gonzalez-Herrero, I., Flores, T., Luis Garcia, J., McNamara, G., Kunder, C., Zhao, S., Segura, V., Fontan, L., Martinez-Climent, J. A., Javier Garcia-Criado, F., Theis, J. D., Dogan, A., Campos-Sanchez, E., Green, M. R., Alizadeh, A. A., Cobaleda, C., Sanchez-Garcia, I., Lossos, I. S. 2013; 4

    Abstract

    The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

    View details for DOI 10.1038/ncomms2334

    View details for Web of Science ID 000316614600008

    View details for PubMedID 23299888

    View details for PubMedCentralID PMC3545406

  • Anterolateral congenital diaphragmatic hernia with omphalocele: a case report and literature review. American journal of medical genetics. Part A Scahill, M. D., Maak, P., Kunder, C., Halamek, L. P. 2013; 161 (3): 585–88

    Abstract

    The combination of congenital diaphragmatic hernia (CDH) and omphalocele is quite rare but can be seen in several syndromes. We report on a female newborn with this combination that had not been diagnosed prenatally. The patient suffered respiratory failure that persisted despite intensive care support, suggesting severe secondary pulmonary hypoplasia. Autopsy revealed the combination of an anterolateral CDH and omphalocele in the absence of other anomalies. We believe this to be the first such case to be reported in the literature.

    View details for PubMedID 23401132