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Division of Surgical Pathology


Email jepstein@jhmi.edu
Phone (410) 955-5043

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Division of Surgical Pathology


Jonathan I. Epstein, M.D.

Director, Division of Genitourinary Pathology
Director, Division of Surgical Pathology
Primary Appointment in Pathology; Secondary Appointments in Oncology and Urology


Carcinoma of the prostate can vary from extremely indolent lesions such as those found incidentally at autopsy to aggressive tumors responsible for the second leading cause of cancer death in men. We have the largest number of completely studied radical prostatectomy specimens in the world and the largest anatomic pathology consult service of genitourinary specimens (>60/day). We are involved in multiple clinico-pathologic studies using a wide range of techniques on both biopsy and prostatectomy specimens to enhance our prognostic capabilities. Tissue microarrays are available for bladder and prostate cancer projects. The consult material also provides the unique opportunity to identify and describe new entities in genitourinary pathology.

Publications
Epstein JI, Walsh PC, CarMichael M, Brendler CB. Pathological and clinical findings to predict tumor extent of non-palpable (stage T1c) prostate cancer JAMA 271:368-374, 1994. Epstein JI, Allsbrook Jr. WC, Amin MB, Egevad LL & The ISUP grading committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 29: 1228-42, 2005.

Epstein JI, Amin MB, Reuter VR, Mostofi FK, and the Bladder Consensus Conference Committee. The World Health Organization/International Society of Urological Pathology Consensus Classification of Urothelial (Transitional Cell) Neoplasms of the Urinary Bladder. Am J Surg Pathol 22:1435-1448, 1998.

Pan C-C, Potter SR, Partin AW, Epstein, JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system Am J Surg Pathol 24:563-569, 2000.

Duffield A, Epstein JI. Detection of cancer in radical prostatectomy specimens with no residual carcinoma in the initial specimen. Am J Surg Pathol (January) 33:120-125,2009.




Email ganhalt@jhmi.edu
Phone (410) 955-3865
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Grant J. Anhalt, M.D.

Primary Appointment in Dermatology; Secondary Appointment in Pathology
Member, Graduate Program in Cellular and Molecular Medicine


In autoimmune blistering skin diseases, skin and mucosal lesions result from autoantibody binding to functionally important adhesion molecules found in stratified squamous epithelia. In many of these diseases, passive transfer of antigen specific antibodies to these molecules will reproduce epithelial blistering in mice and provides an in vivo model to define pathogenetic mechanisms. The use of patient autoantibodies as probes for identification of functionally important adhesion molecules is a major thrust of this laboratory. This approach has led to the identification of the protein antigen and its gene in the following diseases - desmogleins I & III in pemphigus vulgaris and foliaceus, the hemidesmosome protein BP 180 inbullous pemphigoid, and desmoplakins I & II in paraneoplastic pemphigus. Current studies focus on the following: identification of additional adhesion molecules recognized by human autoantibodies but not yet cloned, the mechanisms by which antibody - protein interactions down-regulate their function in vivo, and exploring mechanisms operative in the induction of autoimmunity by lymphoreticular malignancies in paraneoplastic pemphigus.

Publications
Amagai M, Nishikawa T, Nousari HC, Anhalt GJ, Hashimoto T. Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. J Clin Invest 102:775-782, 1998.

Cohen SS, Hemdier BG, Anhalt GJ, Blauvelt A. No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris or pemphigus foliaceus. J Invest Dermatol 111:781-783,1998.

Nousari HC, Kimyai-Asadi A, Caeiro JP, Anhalt GJ. Clinical, demographic and immunohistologic features of vancomycin-induced linear IgAbullous disease. Medicine (Baltimore) 78:1-8, 1999.

Nousari HC, Deterding R, Wojtczack H, Aho S, Uitto J, Hashimoto T, Anhalt GJ. The mechanism of respiratory failure in paraneoplastic pemphigus. New Engl J Med 40:1406-1410, 1999.




Email pargani@jhmi.edu
Phone (410) 614-2428

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Biliary Cancer

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Pedram Argani, M.D.

Primary Appointment in Pathology; Secondary Appointment in Oncology


My research interests span several broad areas of surgical pathology. First, as the Director of the Breast Pathology Program, I am currently involved in studies applying knowledge gained from global genetic analysis of breast carcinoma (such as SAGE and Microarray analysis) to well-defined histopathologic precursor lesions. Many of the new tumor suppressor genes identified have proven to be inactivated by methylation. We hope to be able to use these new markers to improve early detection and treatment of breast cancer.

Second, I am also interested in the molecular pathogenesis of biliary tract carcinomas, which are rare but highly lethal. Again, in this area we apply global genetic analysis to identify novel markers of disease which are of value in diagnosis, and potentially in imaging and therapy. Finally, I am active in the field of pediatric renal neoplasia where we have been able to define rare but morphologically and molecularly distinctive neoplasms.

Publications

Argani P, Antonescu CR, Illei P, Timmons CF, Lui MY, Newbury R, Reuter VE,Garvin AJ, Perez-Atayde A, Fletcher JA, Beckwith JB, Bridge JA, and Ladanyi M. Primary Renal Neoplasms with the ASPL-TFE3 Gene Fusion of Alveolar Soft Part Sarcoma: A Distinctive Tumor Entity Previously Included among Renal Cell Carcinomas of Young People. Am J Pathol 2001; 159: 179-192.

Argani P, Rosty C, Reiter RE, Wilentz RE, Murugesan SR, Leach SR, Ryu B,Skinner HG, Goggins M, Jaffee EM, Yeo CJ, Cameron JL, Kern SE, and Hruban RH. Discovery of New Markers of Cancer Through Serial Analysis of GeneExpression (SAGE): Prostate Stem Cell Antigen (PSCA) is overexpressed in Pancreatic Adenocarcinoma. Cancer Research 2001;61: 4320-4324.

Argani P, Shaukat A, Kaushal M, Wilentz RE, Su GH, Sohn TA, Yeo CJ,Cameron JL, Kern SE, Hruban RH. Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts: evidence for a biologic distinction. Cancer 2001;91: 1332-1341.

Argani P, Beckwith JB. Metanephric Stromal Tumor: Report of 31 cases of adistinctive pediatric renal neoplasm. Am J Surg Pathol 2000;24: 917-926.




Email faskin@jhmi.edu
Phone (410) 550-4841
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Frederic B. Askin, M.D.

Primary Appointment in Pathology


My research efforts are basically clinicopathologic studies of neoplasms and other disease processes seen by the surgical pathologist. Electron microscopy, immunocytochemistry, flow cytometry and molecular biologic techniques are often used in these studies but light microscopy and the clinical history remain important. Radiologic-pathologic correlation is also a valuable area of study. My particular fields of interest are adult and pediatric lung disease and the study of pediatric neoplasms. We also see material from a wide spectrum of non-neoplastic interstitial lung diseases. Lung carcinomas collected in our SPORE study are used in molecular oncologic and clinico-pathologic studies.

Publications
Silver SA, Askin FB. True papillary carcinoma of the lung-A distinct clinicopathologic entity. Am J Surg Pathol 21:43-51, 1997.

Morotti RA, Gutierrez MC, Askin FB, et al. Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of the lung. Pediatr Dev Pathol 3(5): 455-61, 2000.

Nogee LM, Dunbar,III AE, Wert SE, Askin FB et al. A mutation in the surfactant protein C Gene associatedwith familial interstitial lung disease. N Engl J Med 344:573-579, 2001.

Iannone R, Luznik L, Engstrom L, Casella J, Askin F, et al. Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia. Blood 97: 3960-5, 2001.




Email sbegum1@jhmi.edu
Phone (410) 502-5759
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Shahnaz Begum, M.B.B.S., Ph.D.

Primary Appointment in Pathology

Member, Graduate Program in Pathobiology


The overall theme of my research is to develop and validate genetic and epigenetic approach for early cancer diagnosis, cancer risk assessment and cancer prognosis. Our studies are aimed at elucidating the pathogenesis of a variety of neoplasms in lung and head & neck. We are particularly interested in the morphologic and molecular alterations associated with the early events in carcinogenesis. One of our specific interests is to elucidate molecular alterations in lung adenocarcinoma and correlate it with environmental exposure. Our approach also aimed to identify molecular pathways involved in the initiation and progression of lung adenocarcinoma. We are using verity of high throughput genetic and epigenetic approach to this endeavor.

Publications
Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH. Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res.2003 Dec 15;9 (17):6469-75.

*Hoque MO, *Begum S, , Topaloglu O, Jeronimo C, Mambo E, Westra WH, Califano JA, Sidransky D.Quantitative detection of promoter hypermethylation of multiple genes in the tumor, urine, and serum DNA of patients with renal cancer. Cancer Res. 2004 Aug 1;64(15):5511-7. (*Equal Contribution)

Begum S, Cao D, Gillison M, Zahurak M, Westra WH. Tissue distribution of HPV 16 DNA integration in patients with tonsillar carcinoma. Clin Cancer Res. 2005 Aug 15;11(16):5694-9

Hoque MO, Begum S, Topaloglu O, Chatterjee A, Rosenbaum E, Van Criekinge W, Westra WH,Schoenberg M, Zahurak M, Goodman SN, Sidransky D. Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst. 2006 Jul 19;98 (14):996-1004.

Begum S, Gillison ML, Nicol TL, Westra WH. Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2007 Feb 15; 13 (4):1186-91.




Email dbelchi1@jhmi.edu
Phone (410) 550-0671
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Deborah A. Belchis, M.D.

Visiting Associate Professor, Pathology


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Publications
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Email jbishop@jhmi.edu
Phone (410) 955-8116

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Head and Neck Pathology

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Justin Bishop, M.D.

Primary Appointment in Pathology; Secondary Appointment in Otolaryngology-Head and Neck Surgery


Although the head and neck is a relatively small anatomic region, it gives rise to an incredibly large and diverse group of neoplasms. My research is focused on clinicopathologic studies of head and neck tumors, with a focus on new diagnostic tools (e.g., immunohistochemistry, chromogenic or fluorescence in situ hybridization) to assist the surgical pathologist in solving diagnostic dilemmas. Moreover, we have an active consult practice that allows for the characterization of novel entities in head and neck pathology.

Publications
Human papillomavirus-related small cell carcinoma of the oropharynx. JA Bishop, WH Westra, The American journal of surgical pathology 35 (11), 1679

Human papillomavirus-related carcinomas of the sinonasal tract. JA Bishop, TW Guo, DF Smith, H Wang, T Ogawa, SI Pai, WH Westra, The American journal of surgical pathology 37 (2), 185

Detection of transcriptionally active high risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method. JA Bishop, XJ Ma, H Wang, Y Luo, PB Illei, S Begum, JM Taube, Wayne M Koch, William H Westra, The American journal of surgical pathology 36 (12), 1874

Human papillomavirus-related carcinoma with adenoid cystic-like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. JA Bishop, T Ogawa, EB Stelow, CA Moskaluk, WM Koch, SI Pai, William H Westra, The American journal of surgical pathology 37 (6), 836

SMARCB1 (INI-1)-deficient Carcinomas of the Sinonasal Tract. JA Bishop, CR Antonescu, WH Westra, The American journal of surgical pathology 38 (9), 1282-1289




Email acimino1@jhmi.edu
Phone (410) 614-6753

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Breast Cancer and Breast Pathology

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Ashley M. Cimino-Mathews, M.D.

Primary Appointment in Pathology; Secondary Appointment in Oncology


My primary research aim is to characterize the pathogenesis of breast cancer metastasis by studying the changes seen between a patientÂ’s primary and matched metastatic breast carcinoma. Metastatic breast carcinoma carries a poor prognosis, and a better understanding of the molecular steps underlying the progression of metastases will allow for more specialized, targeted therapy in both the early and late stages of metastasis. To date, we have studied the expression of molecules such as the epithelial cell adhesion molecule (EpCAM), the androgen receptor, Sox10, and GATA3. In addition, we are studying the role of the patientÂ’s own immunologic response in mediating breast cancer development and metastasis. Our goal is to characterize the immune infiltrates in primary and metastatic human breast cancers. My secondary research aim is to study the genetic and phenotypic differences of stromal tumors of the breast. Spindle cell proliferations of the breast encompass a range of benign to malignant neoplasms, including fibromatosis, phyllodes tumors, and sarcomatoid (metaplastic) carcinomas. These lesions have overlapping clinicoradiologic and pathologic features but vastly different implications for prognosis.

Publications
Cimino A, Halushka M, Illei P, Wu X, Sukumar S, Argani P. Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases. Breast Cancer Res Treat. 2010;123(3):701-708.

Cimino-Mathews A, Hicks J, Illei PB, Halushka MK, Fetting JH, De Marzo A, Park BH, Argani P. Androgen receptor expression is usually maintained in initial surgically-resected breast cancer metastases, but often lost in terminal metastases found at autopsy. Human Pathology. 2012;43(7):1003-11.

Cimino-Mathews A, Subhawong AP, Elwood H, Nassar Warzecha H, Sharma R, Park BH, Taube JM, Illei PB, Argani PA. Neural crest transcription factor Sox10 is preferentially expressed in triple negative and metaplastic breast carcinomas. Human Pathol. 2013 Jun;44(6):959-65.

Cimino-Mathews A, Ye X, Meeker A, Argani P, Emens LA. Metastatic Triple Negative Breast Cancers at First Relapse Have Fewer Tumor-Infiltrating Lymphocytes Than Their Matched Primary Breast Tumors: A Pilot Study. Human Pathol. 2013 Oct;44:2055-63.

Cimino-Mathews A, Sharma R, Illei PB, Vang R, Argani P. A Subset of Malignant Phyllodes Tumors Express p63 and p40: A Diagnostic Pitfall in Breast Core Needle Biopsies. Amer J Surg Pathol. In press.




Email pillei1@jhmi.edu
Phone (410) 502-5160
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Peter B. Illei, M.D.

Primary Appointment in Pathology


1. The role of CDKN2A deletion, MTAP co-deletion and SV40 in the oncogenesis and treatment of malignant mesothelioma. 2. Development of novel FISH tests and real time PCR protocols for the diagnosis of solid tissue cancer cells in cytology specimens and formalin fixed and paraffin embedded tissue sections. Applications of laser-capture micro dissection coupled with gene expression profiling for the diagnosis of malignancies in cytology preparations and small routinely processed biopsy specimens. 3. The use of DNA profiling (fingerprinting) and laser capture micro-dissection in genotyping neoplasms in solid organ transplants recipients. 4. Detection of C-kit signalling mechanisms in thymic carcinomas.

Publications
Illei P, Feiner H, Yin H, Chan W, Symmans F, Perle MA: Interphase cytogenetic study of chromosomes 7, 18 and X in tissue scrapes of proliferative fibrocystic disease and ductal carcinoma in situ of the breast. The Breast Journal, 4(4):252-7, 1998.

Illei PB, Ladanyi M, Rusch V, Zakowski M: The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. Cancer. 2003 Feb 25;99(1):51-6.

Illei PB, Rusch V, Zakowski MF, Ladanyi M: Homozygous Deletion of CDKN2A and Co-Deletion of the Methylthioadenosine Phosphorylase Gene in the Majority of Pleural Mesotheliomas. Clin Can Res, 2003 Jun;9(6):2108-13.

Huang HY*, Illei PB*, Zhao Z, Mazumdar M, Huvos AG, Healye JH, Gorlick R, Meyers P, and Ladanyi M. Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol. 2005 Jan 20;23(3):548-58.

Lopez-Rios F, Illei PB, Rusch V, Ladanyi M: Multiple lines of evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive SV40 PCR results due to presence of SV40 sequences in common laboratory plasmids. Lancet, 2004 Sep 25, 364: 1157-1166.




Email emccarth@jhmi.edu
Phone (410) 614-3653

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Bone Histomorphometry Laboratory

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Edward F. McCarthy, M.D.

Primary Appointment in Pathology; Secondary Appointment in Orthopedic Surgery


We have a bone biopsy histomorphology laboratory which is available for diagnostic problems and research. Our lab is able to process and cut undecalcified bone specimens. We are interested in metabolic bone disease and, in collaboration with other researchers, are studying the causes and response to treatment of metabolic bone diseases such as osteogenesis imperfecta and renal osteodystrophy. We are also interested in primary and secondary bone tumors. We are studying certain bone tumors, particularly cartilage tumors, with respect to rate of turnover as depicted in immunochemical techniques.

Publications
McCarthy, E.F., Tyler, W.K. Distinguishing enchondromas from central low-grade chondrosarcoma. Pathology Case Reviews 6:8-13, 2001.

Durant, D., Riley, L.H., Burger, P., McCarthy, E.F. Tumoral calcinosis of the spine. A study of 21 cases. Spine 15:1673-1679, 2001.

Tortolani, P.J., Sponseller, P.D., McCarthy, E.F. Decreased bone density in children. J Am Academy of Orthopaedic Surgeons 10:57-66, 2002.




Email wwestra@jhmi.edu
Phone (410) 614-3964
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William H. Westra, M.D.

Co-Director, Division of Surgical Pathology
Primary Appointment in Pathology; Secondary Appointments in Otolaryngology-Head and Neck Surgery, Oncology, and Dermatology


My research activities have centered on the molecular mechanisms of neoplastic transformation. My specific interest in cardiovascular-respiratory pathology has focused on the molecular pathways involved in the development and progression of neoplasms of the lung and head and neck. Our work has identified the earliest morphologic stages of lung tumorigenesis (i.e. adenocarcinoma in situ), and the molecular mechanisms driving the early stages and progression of carcinomas of the lung and head and neck. A particular emphasis of this work has been the utilization of specific genetic alterations as a novel means of early cancer detection and tumor surveillance.

Publications
Westra WH, Baas IO, Hruban RH, Offerhaus GJA, Askin FB, Slebos RJC. K-ras oncogene activation in atypical alveolar hyperplasias of the lung: evidence that K-ras mutations are present at an early stage in the development of lung adenocarcinomas. Cancer Res 56:2224-8, 1996..

Leong PP, Rezai B, Roch WM, Reed A, Eisele D, Lee D-J, Sidransky D, Jen J,Westra WH. Distinguishing Second Primary Tumors from Lung Metastases in Patients with Head and Neck Squamous Cell Carcinoma. J Natl Cancer Inst 90:972-977, 1998.

Califano J, Westra WH, Koch WM, Meininger G, Reed A, Yip L, Boyle JO, Lonardo F, Sidransky D. Unknown primary head and neck squamous cell carcinoma: Molecular identification of the site of origin. J Natl Cancer Inst 91:599-604, 1999.

Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH. Detection of Human Papillomavirus in Cervical Lymph Nodes: A highly effective strategy for localizing site of tumor origin. Clin Cancer Res 15:6469-6475, 2003.

Cohen Y, Rosenbaum E, Clark DP, Zeiger MA, Umbricht CB, Tufano RP, Sidransky S, Westra WH. Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: A potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res 10:2761-2765, 2004.



 


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