Bio

Clinical Focus


  • Pathology
  • Anatomic Pathology

Academic Appointments


  • Assistant Professor - Med Center Line, Pathology

Professional Education


  • Fellowship:Univ of California San Francisco (2005) CA
  • Fellowship:Stanford University Medical Center (2004) CA
  • Internship:Stanford University Medical Center (2000) CA
  • Residency:Stanford University Medical Center (2003) CA
  • Board Certification: Cytopathology, American Board of Pathology (2005)
  • Board Certification: Anatomic Pathology, American Board of Pathology (2003)
  • Board Certification: Hematology, American Board of Pathology (2004)
  • Medical Education:Stanford University School of Medicine (1999) CA

Teaching

2014-15 Courses


Publications

Journal Articles


  • Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips LAB ON A CHIP Earhart, C. M., Hughes, C. E., Gaster, R. S., Ooi, C. C., Wilson, R. J., Zhou, L. Y., Humke, E. W., Xu, L., Wong, D. J., Willingham, S. B., Schwartz, E. J., Weissman, I. L., Jeffrey, S. S., Neal, J. W., Rohatgi, R., Wakeleebe, H. A., Wang, S. X. 2014; 14 (1): 78-88

    View details for DOI 10.1039/c3lc50580d

    View details for Web of Science ID 000327669000008

  • A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk BREAST CANCER RESEARCH AND TREATMENT Vinayak, S., Schwartz, E. J., Jensen, K., Lipson, J., Alli, E., McPherson, L., Fernandez, A. M., Sharma, V. B., Staton, A., Mills, M. A., Schackmann, E. A., Telli, M. L., Kardashian, A., Ford, J. M., Kurian, A. W. 2013; 142 (2): 389-398

    Abstract

    Pre-clinical and epidemiologic studies provide rationale for evaluating lipophilic statins for breast cancer prevention. We conducted a single-arm, biomarker modulation trial of lovastatin among women with increased risk of breast cancer. Eligibility criteria included a deleterious germline mutation in BRCA1, BRCA2, CDH1, or TP53; lifetime breast cancer risk of ≥20 % as estimated by the Claus model; or personal history of estrogen receptor and progesterone receptor-negative breast cancer. Participants received 40 mg of lovastatin orally twice daily for 6 months. We evaluated the following biomarkers before and after lovastatin use: breast duct cytology (primary endpoint), serum lipids, C-reactive protein, insulin-like growth factor-1, IGF binding protein-3, lipid peroxidation, oxidative DNA damage, 3-hydroxy-3-methylglutaryl CoA reductase genotype, and mammographic density. Thirty women were enrolled, and 26 (86.7 %) completed the study. For the primary endpoint of changes in breast duct cytology sampled by random periareolar fine needle aspiration, most participants [57.7 %, 95 % confidence interval (CI) 38.9-74.5 %] showed no change after lovastatin; 19.2 % (CI 8.1-38.3 %) had a favorable change in cytology, 7.7 % (95 % CI 1.0-25.3 %) had an unfavorable change, and 15.4 % (95 % CI 5.5-34.2 %) had equivocal results due to acellular specimens, usually after lovastatin. No significant changes were observed in secondary biomarker endpoints. The study was generally well-tolerated: 4 (13.3 %) participants did not complete the study, and one (3.8 %) required a dose reduction. This trial was technically feasible, but demonstrated no significant biomarker modulation; contributing factors may include insufficient sample size, drug dose and/or duration. The results are inconclusive and do not exclude a favorable effect on breast cancer risk.

    View details for DOI 10.1007/s10549-013-2739-z

    View details for Web of Science ID 000327079800013

    View details for PubMedID 24166281

  • Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients INTERNATIONAL JOURNAL OF CANCER Zuckerman, N. S., Yu, H., Simons, D. L., Bhattacharya, N., Carcamo-Cavazos, V., Yan, N., Dirbas, F. M., Johnson, D. L., Schwartz, E. J., Lee, P. P. 2013; 132 (11): 2537-2547

    Abstract

    Cancer-mediated immune dysfunction contributes to tumor progression and correlates with patient outcome. Metastasis to tumor draining lymph nodes (TDLNs) is an important step in breast cancer progression and is used to predict patient outcome and survival. Although lymph nodes are important immune organs, the role of immune cells in TDLNs has not been thoroughly investigated. We hypothesized that the host immune response in node negative (NN) patients is more intact and thereby can resist tumor invasion compared to node positive (NP) patients. As such, lymph node metastasis requires breakdown of the host immune response in addition to escape of cancer cells from the tumor. To investigate the immunological differences between NN and NP breast cancer patients, we purified and profiled immune cells from the three major compartments where cancer and immune cells interact: tumor, TDLNs and peripheral blood. Significant down-regulation of genes associated with immune-related pathways and up-regulation of genes associated with tumor-promoting pathways was consistently observed in NP patients' TDLNs compared to NN patients. Importantly, these signatures were seen even in NP patients' tumor-free TDLNs, suggesting that such immune changes are not driven solely by local tumor invasion. Furthermore, similar patterns were also observed in NP patients' tumor and blood immune cells, suggesting that immunological differences between NN and NP patients are systemic. Together, these findings suggest that alterations in overall immune function may underlie risk for LN metastasis in breast cancer patients.

    View details for DOI 10.1002/ijc.27933

    View details for Web of Science ID 000316824000009

  • Spatial organization of dendritic cells within tumor draining lymph nodes impacts clinical outcome in breast cancer patients. Journal of translational medicine Chang, A. Y., Bhattacharya, N., Mu, J., Setiadi, A. F., Carcamo-Cavazos, V., Lee, G. H., Simons, D. L., Yadegarynia, S., Hemati, K., Kapelner, A., Ming, Z., Krag, D. N., Schwartz, E. J., Chen, D. Z., Lee, P. P. 2013; 11: 242-?

    Abstract

    Dendritic cells (DCs) are important mediators of anti-tumor immune responses. We hypothesized that an in-depth analysis of dendritic cells and their spatial relationships to each other as well as to other immune cells within tumor draining lymph nodes (TDLNs) could provide a better understanding of immune function and dysregulation in cancer.We analyzed immune cells within TDLNs from 59 breast cancer patients with at least 5 years of clinical follow-up using immunohistochemical staining with a novel quantitative image analysis system. We developed algorithms to analyze spatial distribution patterns of immune cells in cancer versus healthy intra-mammary lymph nodes (HLNs) to derive information about possible mechanisms underlying immune-dysregulation in breast cancer. We used the non-parametric Mann-Whitney test for inter-group comparisons, Wilcoxon Matched-Pairs Signed Ranks test for intra-group comparisons and log-rank (Mantel-Cox) test for Kaplan Maier analyses.Degree of clustering of DCs (in terms of spatial proximity of the cells to each other) was reduced in TDLNs compared to HLNs. While there were more numerous DC clusters in TDLNs compared to HLNs,DC clusters within TDLNs tended to have fewer member DCs and also consisted of fewer cells displaying the DC maturity marker CD83. The average number of T cells within a standardized radius of a clustered DC was increased compared to that of an unclustered DC, suggesting that DC clustering was associated with T cell interaction. Furthermore, the number of T cells within the radius of a clustered DC was reduced in tumor-positive TDLNs compared to HLNs. Importantly, clinical outcome analysis revealed that DC clustering in tumor-positive TDLNs correlated with the duration of disease-free survival in breast cancer patients.These findings are the first to describe the spatial organization of DCs within TDLNs and their association with survival outcome. In addition, we characterized specific changes in number, size, maturity, and T cell co-localization of such clusters. Strategies to enhance DC function in-vivo, including maturation and clustering, may provide additional tools for developing more efficacious DC cancer vaccines.

    View details for DOI 10.1186/1479-5876-11-242

    View details for PubMedID 24088396

  • PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ PLOS ONE Yu, H., Simons, D. L., Segall, I., Carcamo-Cavazos, V., Schwartz, E. J., Yan, N., Zuckerman, N. S., Dirbas, F. M., Johnson, D. L., Holmes, S. P., Lee, P. P. 2012; 7 (12)

    Abstract

    Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression.We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors.This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens up epigenetic drug development possibilities for the treatment and prevention of lymph node metastasis in breast cancer.

    View details for DOI 10.1371/journal.pone.0051239

    View details for Web of Science ID 000312201900057

    View details for PubMedID 23251464

  • Discordant Immunophenotypic Profiles of Adhesion Molecules and Cytokines in Acute Myeloid Leukemia Involving Bone Marrow and Skin AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sachdev, R., George, T. I., Schwartz, E. J., Sundram, U. N. 2012; 138 (2): 290-299

    Abstract

    We investigated the role of adhesion molecules in skin involvement by acute myeloid leukemia (AML) using immunohistochemical analysis. Ten paired cases of skin and bone marrow biopsy specimens from patients with myeloid leukemia cutis (MLC) and 15 bone marrow biopsy specimens from patients without MLC were studied with antibodies directed against CD29, CD34, CD54, CD62-L, CD183, and cutaneous lymphocyte antigen (CLA). CLA was expressed in all cases of leukemia whereas CD54 was negative within blasts. CD62-L was expressed in 4 of 10 specimens of marrow infiltrates with MLC and 6 of 10 specimens of matching skin infiltrates; in marrows without MLC, only 2 of 15 were positive. CD29 was expressed in 1 of 10 marrow infiltrate specimens with MLC and 4 of 10 matching skin infiltrate specimens; in marrows without MLC, only 1 of 15 were positive. CD183 was expressed in 1 of 10 marrow infiltrate specimens with MLC and 4 of 10 matching skin infiltrate specimens; in marrows without MLC, CD183 was negative. The gain of CD62-L, CD29, and CD183 expression in bone marrow and skin infiltrates in leukemia cutis, relative to bone marrow infiltrates of cases without MLC, suggests a role for these markers in AML homing to skin.

    View details for DOI 10.1309/AJCP34YERPZSCYKQ

    View details for Web of Science ID 000306536000017

    View details for PubMedID 22904142

  • ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy. Lung cancer Das, M., Riess, J. W., Frankel, P., Schwartz, E., Bennis, R., Hsieh, H. B., Liu, X., Ly, J. C., Zhou, L., Nieva, J. J., Wakelee, H. A., Bruce, R. H. 2012; 77 (2): 421-426

    Abstract

    To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC).ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation.PFS decreased with increasing ERCC1 expression (p<0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p<0.02) in a Kaplan-Meier analysis using ERCC expression level of 1 as a cutoff (range 0-30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25-14.1, p<0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p<0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging.Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy.

    View details for DOI 10.1016/j.lungcan.2012.04.005

    View details for PubMedID 22555222

  • A Comparative Analysis of Cutaneous Marginal Zone Lymphoma and Cutaneous Chronic Lymphocytic Leukemia AMERICAN JOURNAL OF DERMATOPATHOLOGY Levin, C., Mirzamani, N., Zwerner, J., Kim, Y., Schwartz, E. J., Sundram, U. 2012; 34 (1): 18-23

    Abstract

    The morphologic distinction between cutaneous marginal zone lymphoma (CMZL) and secondary cutaneous involvement by B-cell chronic lymphocytic leukemia (B-CLL) can be difficult. Both entities can show very similar architectural patterns of involvement in the skin and not uncommonly, the skin can be the first site of presentation of B-CLL in the elderly. We reviewed biopsies of 13 patients with cutaneous B-CLL and 14 patients with CMZL to compare their histologic and immunohistochemical features. CMZL and cutaneous B-CLL both predominantly exhibited a nodular pattern of skin involvement (9 of 13 B-CLL, 9 of 14 CMZL) with a minority of cases demonstrating a diffuse pattern (4 of 13 B-CLL, 4 of 14 CMZL). Although reactive germinal centers (12 of 14 cases) and plasma cells (10 of 14 cases) were seen more often in CMZL, plasma cells were also observed in cases of B-CLL (4 of 13). The lesional cells of B-CLL expressed CD79, CD5, CD23, and CD43, although CMZL did not express CD5 or CD43. Although we noted light chain restriction in 13 of 14 cases of CMZL cases, we also observed light chain restriction in 4 of 13 cases of B-CLL. Our results indicate that CMZL and B-CLL can be morphologically similar and both may show light chain restriction. Complete immunophenotyping is necessary to ensure that all cases are correctly classified.

    View details for DOI 10.1097/DAD.0b013e31821528bc

    View details for Web of Science ID 000299325900005

    View details for PubMedID 22257836

  • Cytotoxic T lymphocyte responses against melanocytes and melanoma JOURNAL OF TRANSLATIONAL MEDICINE Chang, G. Y., Kohrt, H. E., Stuge, T. B., Schwartz, E. J., Weber, J. S., Lee, P. P. 2011; 9

    Abstract

    Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs) against melanoma commonly target melanoma-associated antigens (MAAs) which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels.To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines.CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry.Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.

    View details for DOI 10.1186/1479-5876-9-122

    View details for Web of Science ID 000294153500001

    View details for PubMedID 21794122

  • Quantitative, Architectural Analysis of Immune Cell Subsets in Tumor-Draining Lymph Nodes from Breast Cancer Patients and Healthy Lymph Nodes PLOS ONE Setiadi, A. F., Ray, N. C., Kohrt, H. E., Kapelner, A., Carcamo-Cavazos, V., Levic, E. B., Yadegarynia, S., van der Loos, C. M., Schwartz, E. J., Holmes, S., Lee, P. P. 2010; 5 (8)

    Abstract

    To date, pathological examination of specimens remains largely qualitative. Quantitative measures of tissue spatial features are generally not captured. To gain additional mechanistic and prognostic insights, a need for quantitative architectural analysis arises in studying immune cell-cancer interactions within the tumor microenvironment and tumor-draining lymph nodes (TDLNs).We present a novel, quantitative image analysis approach incorporating 1) multi-color tissue staining, 2) high-resolution, automated whole-section imaging, 3) custom image analysis software that identifies cell types and locations, and 4) spatial statistical analysis. As a proof of concept, we applied this approach to study the architectural patterns of T and B cells within tumor-draining lymph nodes from breast cancer patients versus healthy lymph nodes. We found that the spatial grouping patterns of T and B cells differed between healthy and breast cancer lymph nodes, and this could be attributed to the lack of B cell localization in the extrafollicular region of the TDLNs.Our integrative approach has made quantitative analysis of complex visual data possible. Our results highlight spatial alterations of immune cells within lymph nodes from breast cancer patients as an independent variable from numerical changes. This opens up new areas of investigations in research and medicine. Future application of this approach will lead to a better understanding of immune changes in the tumor microenvironment and TDLNs, and how they affect clinical outcomes.

    View details for DOI 10.1371/journal.pone.0012420

    View details for Web of Science ID 000281234700034

    View details for PubMedID 20811638

  • CD163 Expression Is Present in Cutaneous Histiocytomas but Not in Atypical Fibroxanthomas AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sachdev, R., Robbins, J., Kohler, S., Vanchinathan, V., Schwartz, E. J., Surdram, U. N. 2010; 133 (6): 915-921

    Abstract

    CD163, a hemoglobin scavenger receptor, is expressed in monocytes and macrophages. Recent work has shown that this marker is specific for neoplasms of histiocytic differentiation. Our aim was to test the ability of CD163 to separate cutaneous histiocytomas from their morphologic mimics. We tested the expression of CD163 in 78 cases, including 19 xanthogranulomas, 16 atypical fibroxanthomas, 6 reticulohistiocytomas, 8 epithelioid cell histiocytomas, 9 cases of Langerhans cell histiocytosis, 10 xanthomas, and 10 intradermal Spitz nevi. CD163 expression was seen in all xanthogranulomas and reticulohistiocytomas, 4 epithelioid cell histiocytomas, 2 cases of Langerhans cell histiocytosis, and 8 xanthomas but was absent in atypical fibroxanthomas and Spitz nevi. CD163 is an excellent marker for confirming histiocytic differentiation and is useful in eliminating morphologic mimics such as Spitz nevi from the differential diagnosis. The lack of CD163 in atypical fibroxanthomas argues against a histiocytic origin for this tumor.

    View details for DOI 10.1309/AJCP88IRBPXQZYIR

    View details for Web of Science ID 000277846700013

    View details for PubMedID 20472850

  • Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases MODERN PATHOLOGY Sangoi, A. R., McKenney, J. K., Schwartz, E. J., Rouse, R. V., Longacre, T. A. 2009; 22 (9): 1228-1235

    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

  • A Phase II Study of Gefitinib, 5-Fluorouracil, Leucovorin, and Oxaliplatin in Previously Untreated Patients with Metastatic Colorectal Cancer CLINICAL CANCER RESEARCH Fischer, G., Kuo, T., Ramsey, M., Schwartz, E., Rouse, R., Cho, C. D., Halsey, J., Sikic, B. I. 2008; 14 (21): 7074-7079

    Abstract

    We investigated the gefitinib, 5-fluorouracil (5-FU), leucovorin and oxaliplatin (IFOX) regimen as first-line therapy in patients with metastatic colorectal cancer.Eligible patients had stage IV colorectal adenocarcinoma, and had not received prior chemotherapy for metastatic disease. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin, leucovorin, and 5-FU (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg orally daily throughout the 14-day cycle.Forty-five patients were enrolled and were assessable for toxicity. Forty-three patients were assessable for response. Thirty-one of the 43 patients (72%) had either a complete or partial response by the Response Evaluation Criteria in Solid Tumors. Median overall survival was 20.5 months. Median time to progression was 9.3 months. Commonly encountered grade 3 or 4 toxicities included diarrhea in 67% of patients and neutropenia in 60%. Grade 2 acneiform skin rash typical of gefitinib occurred in 60% of patients.IFOX is an active first-line regimen in patients with metastatic colorectal adenocarcinoma, showing higher response rates but also increased toxicities compared with FOLFOX-4 alone in a similar patient population.

    View details for DOI 10.1158/1078-0432.CCR-08-1014

    View details for Web of Science ID 000260732200044

    View details for PubMedID 18981005

  • Immunohistochemical characterization of nasal-type extranodal NK/T-Cell lymphoma using a tissue microarray AMERICAN JOURNAL OF CLINICAL PATHOLOGY Schwartz, E. J., Molina-Kirsch, H., Zhao, S., Marinelli, R. J., Warnke, R. A., Natkunam, Y. 2008; 130 (3): 343-351

    Abstract

    Nasal-type extranodal natural killer (NK)/T-cell lymphoma is an uncommon malignancy. By using a tissue microarray, we characterized 84 cases of extranodal NK/T-cell lymphoma with regard to expression of 18 immunohistochemical markers and the presence of Epstein-Barr virus (EBV) RNA. In our series, CD2 was positive in 69 (93%) of 74 cases, CD3 in 68 (84%) of 81, CD5 in 22 (27%) of 81, CD20 in 0 (0%) of 82, CD29 in 75 (91%) of 82, CD30 in 29 (35%) of 84, CD43 in 81 (96%) of 84, CD54 in 58 (72%) of 81, CD56 in 46 (58%) of 79, CD62L in 23 (28%) of 83, CD183 in 66 (80%) of 83, BCL2 in 33 (39%) of 84, cutaneous lymphocyte antigen in 21 (25%) of 84, granzyme B in 70 (83%) of 84, Ki-67 in 59 (71%) of 83, linker for activation of T cells in 60 (71%) of 84, perforin in 66 (86%) of 77, TIA1 in 76 (90%) of 84, and EBV in 73 (87%) of 84. Hierarchical cluster analysis separated primary cutaneous cases from cases manifesting in other sites based on lower expression of the cell adhesion molecule CD54.

    View details for DOI 10.1309/V561QTM6854W4WAV

    View details for Web of Science ID 000258538900003

    View details for PubMedID 18701406

  • CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells MODERN PATHOLOGY Reichard, K. K., Schwartz, E. J., Higgins, J. P., Narasimhan, B., Warnke, R. A., Natkunam, Y. 2006; 19 (3): 337-343

    Abstract

    CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap. Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13). Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10+ atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10+ peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity. The predominant staining pattern in the CD10+ cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively. This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.

    View details for DOI 10.1038/modpathol.3800536

    View details for Web of Science ID 000235592800001

    View details for PubMedID 16400325

  • Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Troxell, M. L., Schwartz, E. J., van de Ruin, M., Ross, D. T., Warnke, R. A., Higgins, J. P., Natkunam, Y. 2005; 13 (4): 297-303

    Abstract

    Angioimmunoblastic T-cell lymphoma is characterized by a paracortical proliferation of medium to large neoplastic T cells, often with clear cytoplasm, in a background of arborizing high endothelial venules, many surrounded by follicular dendritic cells (FDCs). IHC staining may be applied to highlight these extrafollicular FDCs, traditionally using CD21, or CD23. Several alternative FDC markers have been described, including CNA.42, cystatin A/acid cysteine proteinase inhibitor (ACPI, involved in antigen presentation), and fascin (an actin binding protein). The authors stained a collection of 45 angioimmunoblastic T-cell lymphomas with CD21, CD23, CNA.42, cystatin A, and fascin for direct comparison of FDC staining characteristics in this setting. CD21 highlighted the expected dendritic network of cell processes, within residual follicles and outside of follicles, often adjacent to proliferating vessels. CD23 exhibited similar staining quality but was less sensitive than CD21. CNA.42 showed only diffuse weak labeling of FDCs. Cystatin A stained the cytoplasm of follicular dendritic cells within and outside of follicles; however, staining was often not sharply localized to dendritic cell processes, and scoring was further complicated by reactivity with other cell types in over half of the cases. Likewise, fascin stained a variety of cell types, including strong staining of interdigitating dendritic-like cells, moderate staining of endothelial cells, and only weak staining of follicular dendritic cells within and outside of follicles. Thus, CD21 remains the most reliable marker of follicular dendritic cells in angioimmunoblastic T-cell lymphoma.

    View details for Web of Science ID 000233572700001

    View details for PubMedID 16280657

  • Expression of CD163 (hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely restricted to the monocyte/macrophage lineage AMERICAN JOURNAL OF SURGICAL PATHOLOGY Nguyen, T. D., Schwartz, E. J., West, R. B., Warnke, R. A., Arber, D. A., Natkunam, Y. 2005; 29 (5): 617-624

    Abstract

    CD163, a hemoglobin scavenger receptor, is expressed in monocytes and macrophages. We tested the expression of the CD163 protein in 1,105 human malignancies and normal tissues using tissue microarrays and conventional paraffin-embedded tissue sections. Besides staining nonneoplastic monocytes and histiocytes (tissue macrophages), membranous/cytoplasmic staining for CD163 was primarily limited to neoplasms with monocytic/histiocytic differentiation. CD163 reactivity was not observed in normal tissues, lymphomas, carcinomas, and in a majority of mesenchymal neoplasms, including follicular dendritic cell tumors (0 of 4), although it stained admixed histiocytes. Staining for CD163 was seen in Rosai-Dorfman disease (5 of 6), histiocytic sarcoma (3 of 4), littoral cell angioma (6 of 6), and Langerhans cell histiocytosis (3 of 5). A subset of atypical fibrous histiocytomas (9 of 16), benign fibrous histiocytomas (6 of 9), and atypical fibroxanthomas (1 of 3) also showed CD163 staining. Our studies also confirm earlier work showing that CD163 is expressed in acute myeloid leukemia with monocytic differentiation (AML, FAB subtype M5) (2 of 6), as well as a majority of giant cell tenosynovial tumors (7 of 8). Its limited range of expression and tissue specificity indicate that CD163 may have significant diagnostic utility in separating specific tumors with monocytic and histiocytic derivation from other entities in their differential diagnosis.

    View details for Web of Science ID 000228707200007

    View details for PubMedID 15832085

  • Adenomatoid tumors of the female and male genital tracts express WT1 INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY Schwartz, E. J., Longacre, T. A. 2004; 23 (2): 123-128

    Abstract

    Adenomatoid tumors are benign proliferations most often encountered in the female and male genital tracts. The mesothelial phenotype of these unusual tumors has been established by a variety of ultrastructural and immunohistochemical studies, although their etiology is by no means certain. The expression of the Wilms' tumor suppressor gene, WT1, in normal, hyperplastic, and malignant mesothelial cells prompted us to analyze the expression pattern of WT1 in a series of 24 adenomatoid tumors occurring in the uterus, fallopian tube, ovary, epididymis, scrotum, and testis. Twenty-three of the tumors expressed WT1 protein and the same number expressed calretinin, another marker of mesothelial differentiation. The one tumor that failed to stain with calretinin was positive for WT1. These results provide further support for mesothelial differentiation of adenomatoid tumors and suggest that the presence of WT1 expression may be useful in the differential diagnosis of these uncommon neoplasms, especially when they present in unusual settings or expression of other mesothelial markers is absent.

    View details for DOI 10.1097/01.pgp.0000116625.23685.20

    View details for Web of Science ID 000220452800006

    View details for PubMedID 15084840

  • Human herpesvirus-8 latent nuclear antigen-1 expression in endemic Kaposi sarcoma - An immunohistochemical study of 16 cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Schwartz, E. J., Dorfman, R. F., Kohler, S. 2003; 27 (12): 1546-1550

    Abstract

    Human herpesvirus-8 (HHV-8) infection is considered the initiating factor in all forms of Kaposi sarcoma (KS). Latent nuclear antigen (LNA-1) is constitutively expressed in all HHV-8-infected cells. An antibody to LNA-1 has recently become commercially available. The current study addresses the role of immunohistochemistry in the diagnosis of KS, particularly the endemic form. Seven recent cases of KS, 1 atypical vascular lesion in a patient subsequently diagnosed with KS, and 16 endemic cases collected in South Africa in the early 1960s were stained with an antibody to LNA-1. Nine benign vascular lesions and three angiosarcomas were also stained. All 7 recent cases expressed the antigen as did the atypical vascular lesion. Of particular interest was the finding that 10 of the 16 endemic cases were positive. None of the other vascular lesions showed staining. A subset of the endemic lesions was stained for CD31, an antigen universally expressed in KS. CD31 staining was reduced compared with a positive control suggesting that the current study may underestimate the sensitivity of LNA-1 immunohistochemistry in endemic KS because of poor antigen preservation in the archival tissue. Our results confirm the utility of LNA-1 immunohistochemistry as an aid in the diagnosis of KS.

    View details for Web of Science ID 000186820600007

    View details for PubMedID 14657714

Conference Proceedings


  • Adenomatoid Tumors of the Female and Male Genital Tracts: A Morphological and Immunohistochemical Study of 34 Cases Sangoi, A. R., Schwartz, E. J., McKenney, J. K., Rouse, R. V., Longacre, T. A. NATURE PUBLISHING GROUP. 2009: 235A-236A

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