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Division of Surgical Pathology


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

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Division of Surgical Pathology

Gleason Grading


Jonathan I. Epstein, M.D.

Director, Division of Genitourinary Pathology
Director, Division of Surgical Pathology
Primary Appointment in Pathology; Secondary Appointments in Oncology, 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 (>30/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
Kronz JD, Silberman MA, Allsbrook WC, Jr., Epstein JI. A web-based tutorial improves practicing pathologists' Gleason grading of prostate cancer on needle biopsies: Validation of a new medical education paradigm. Cancer 89:1818-1823, 2000.

Levi AW, Epstein JI. Pseudohyperplastic prostatic adenocarcinoma on needle biopsy & simple prostatectomy. Am J Surg Pathol 24:1039-1046, 2000.

Kronz JD, Allan CH, Shaikh AA, Epstein JI. Predicting cancer following a diagnosis of high grade prostatic intraepithelial neoplasia on needle biopsy: data on men with more than one follow-up biopsy. Am J Surg Pathol25:1079-1085,2001.

Chan TY, Epstein JI. In-situ adenocarcinoma of the bladder. Am J Surg Pathol 25:892-899, 2001.




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


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 wrgreen@jhmi.edu
Phone (410) 955-3455

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Curriculum Vitae

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W. Richard Green, M.D.

Primary Appointment in Ophthalmology; Secondary Appointment in Pathology


My chief interests are clinicopathologic correlative studies of ocular diseases and of ocular manifestations of systemic diseases. Ocular diseases have included various studies of the optic nerve head in glaucoma, branch and central retinal vein occlusion, corneal dystrophies, macular holes, age-related macular degeneration, surgical complications, surgically removed submacular membranes, etc. Ocular manifestations of systemic disease have included genetic-metabolic storage diseases, sickle cell retinopathy, AIDS retinopathy, etc.

Publications
Green WR: Retina. In: Spencer WH (ed), Ophthalmic Pathology. An Atlas andTextbook (4th Edition). Philadelphia, WB Saunders, 1996, vol 2, Ch. 9, pp.667-1331.

GreenWR: The Unveal Tract. In: Spencer WH (ed), Ophthalmic Pathology. An Atlas and Textbook (4th Edition). Philadelphia, WB Saunders, 1996, vol 3,Ch. 10, pp. 1439-2120.

Collaborative Ocular Melanoma Study Group. Histopathologiccharacteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study (COMS). COMS report no. 6. Am J Ophthalmol 125(June): 745-766, 1998.

Green WR, Enger C. Age-related macular degeneration histopathologic studies. The 1993 Lorenz E. Zimmerman Lecture. Ophthalmology100:1519-1535, 1993.




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 hnassar1@jhmi.edu
Phone (410) 955-3580
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Hind Nassar, M.D.

Primary Appointment in Pathology


My primary research interest is breast pathology, including breast cancer and benign breast diseases. In breast cancer, my main focus is on specific types of breast cancer that are very aggressive clinically. Studying the clinicopathologic characteristics and immunohistochemical/ molecular features of these tumors could help in understanding their clinical behavior and in using specific types of treatment. I am also interested in studying benign breast diseases. Specific types of benign breast diseases expose women to an increased risk of breast cancer; this is known however in the Caucasian American population. I am interested in studying the risk of breast cancer in African-American women and in women with a strong family history of breast cancer, diagnosed with benign breast diseases. In addition, I work on racial differences in breast cancer, in particular pre-invasive cancer (DCIS) in African-American women.

Publications
Nassar H, Sharafaldeen B, Visvanathan K, Visscher D. Ductal Carcinoma in Situ in African-American vs.Caucasian-American Women: Analysis of Clinicopathologic features and outcome. Cancer 2009.

Subhawong AP, Subhawong T, Kouprina N, Begum S, Vang R, Nassar H, Westra WH, Argani P. Most Basal-like Breast Carcinomas Demonstrate the Same Rb-/p16+ Immunophenotype as the HPV-related Poorly-differentiated Squamous Carcinomas Which They Resemble Morphologically. American Journal of Surgical Pathology 2009.

Nassar H, Qureshi H, Adsay NV, Visscher D. Clinicopathological features of solid papillary carcinoma of the breast and associated invasive carcinomas. American Journal of Surgical Pathology, 2006.

Nassar H, Pansare V, Zhang H, Kotcher G, Che M, Sakr W, Ali-Fehmi R, Grignon D, Sarkar F, Feng J, Adsay NV. Pathogenesis of invasive micropapillary carcinoma: Role of MUC1 Glycoprotein. Modern Pathology, 2004.

Nassar H, Wallis T, Adsay V, Visscher D. Clinicopathologic analysis of Invasive Micropapillary differentiation in Carcinoma of the Breast. Modern Pathology; 2001.




Email matso@jhmi.edu
Phone (410) 614-0229
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Mark O.M. Tso, M.B.B.S.

Primary Appointment in Ophthalmology; Secondary Appointment in Pathology


My career has been built on my research in experimental and human ophthalmic pathologic studies. Studies on the benign form of retinoblastoma (fleurettes in retinoma), pathology and pathogenesis of papilledema, macula edema, retinal photic injury and photoreceptor degeneration were innovative, creative and original. In recent decades, I have explored a family of antioxidants that will provide neuro-protection to the photoreceptor cells. I have an active U.S. and international patent on the use of astaxanthin for neuroprotection of the photoreceptor cells.

Publications
Wu T., Chen Y., Chiang S.K. S. and Tso, M.O.M. NF-kB activation in light-induced retinal degeneration in a mouse model. Invest Opthal Vis. Sc. 43: 2834-2840, 2002

Chen Y, Zhang C, Chiang KS, Wu TH, and Tso MOM. Increased NF-kB p65 immunoreactivity following retinal ischemia and reperfusion injury in mice. Journal of Neuroscience Research 72:125-131, 2003

Zhang C, Tso MOM, Characterization of Activated Retinal Microglia Following Optic Axotomy. Journal of Neuroscience Research. 73:840-845, 2003

Tso MOM, Abbott R., Spivey B., International Guidelines: All for One and One for All? Arch. Ophthalmol. 122:1090-1091, 2004

Zhang C, Lei B, Lam T, Fang Y, Debasish S, Tso MOM, Neuroprotection of Photoreceptors by Minocycline in Light-induced Retinal Degeneration. Investigative Ophthalmology & Visual Science 45:2753-2759, 2004



 


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