肾细胞癌的分类-compressedppt课件.ppt

Classification of Renal Carcinoma,Renal Unit,CK19,THP,CD10、RCC,UEA-1,Renal Carcinoma,Clear Cell Carcinoma,Granular cell carcinoma,Clear Cell Carcinoma,Chromophobe Carcinoma,Papillary Carcinoma Type I Type II,Collecting duct carcinoma,Oncocytoma,Metanephric Adenoma、Adenofibroma,Unclassified and unusual carcinoma,Case 1,37 yr male. History of cerebellar hemangioblastoma, renal tumor and cyst Gross：Tumor diameter 5X5X2.5cm，cut surface yellow Some cysts in the tumor,Risk factor for Von Hippel Lindau syndrome Younger than 50 years Multifocal unilateral or bilateral tumors Family history of renal cancer or other VHL related tumor Germline mutation analysis Missense mutation of VHL gene on 3p25-26,Diagnostic Criteria for VHL Syndrome,No family history Hemangioblastoma of CNS or retina + VHL associated extraneural tumors With family history Hemangioblastoma of CNS or retina or VHL associated extraneural tumors,Case 1,Diagnosis VHL associated clear cell renal cell carcinoma,VHL subtype,HB：Hemangioblastoma；RCC：Renal cell carcinoma；PCC：Pheochromocytoma,Pathogenesis,Cohen H and McGovern FJ, N Engl J Med, 2005; 353:23,pVHL in tumor initiation,Sporadic Clear Cell Carcinoma,Pathogenesis,Cohen H and McGovern FJ, N Engl J Med, 2005; 353:23,Fuhrman Nuclear Grade （4 tiered）,Note： Apply in clear cell carcinoma and papillary carcinoma,Multilocular Cystic Renal Cell Carcinoma,Multilocular Cystic Renal Cell Carcinoma,Modern Pathol 2010 23, 931936,Most of the cases showed chromosome 3p deletion. Very good survival,Hereditary RCC,Hereditary leiomyomatosis and RCC Birt-Hogg-Dub syndrome Hyperparathyroidism-Jaw tumor syndrome Familial Papillary Thyroid Cancer Constitutional chromosome 3 translocations Hereditary papillary renal cancer,Hereditary leiomyomatosis and RCC,Leomyoma or leomyosarcoma of skin or uterus Unilateral papillary renal carcinoma Fumarate Hydratase（FH）mutation 1q42,Birt-Hogg-Dub Syndrome,Facial fibrofolliculoma and tricodiscoma Lung cyst with risk of spontaneous pneumothorax Colonic polyps Renal tumors: oncocytoma or chromophobe carcinoma Folliculin（BHD）gene mutation 17p11.2,Birt-Hogg-Dub Syndrome,Hyperparathyroidism-Jaw Tumor Syndrome,Autosomal dominant Parathyroid adenomas (carcinoma)、Ossifying fibroma of the maxilla or mandible、Renal cysts or renal tumor Wilms tumor、mixed epithelial-stromal tumor、papillary carcinoma HPT-JT（parafibromin）mutation 1q21q32,J Intern Med, 2003 253(6):634,Familial Papillary Thyroid Cancer,Familial PTC Associated with Renal Cell Neoplasia 1q21 Not c-Met associated Hereditary renal papillary cacinoma Not Cowden syndrome Not MEN2A,Case 2,45 yr male Right kidney mass,Papillary Renal Carcinoma,Type 1 Papillae covered by small cells with scanty cytoplasm Single layer on the papillary basement membrane. Type 2 Higher nuclear grade with eosinophilic cytoplasm Pseudostratified nuclei on papillary cores.,Type 1,Type 2,Case 2,Diagnosis Papillary Renal Cell Carcinoma, Type I,Prognosis of PRCC,Conventional papillary renal carcinoma 75% with duplication of chromosome 7, proto-oncogene MET,Cohen H and McGovern FJ, N Engl J Med, 2005; 353:23,Papillary Renal Cancer involved in Hereditary Syndromes,Hereditary papillary renal cancer Hereditary leiomyomatosis and RCC Birt-Hogg-Dub syndrome Hyperparathyroidism-Jaw tumor syndrome Familial Papillary Thyroid Cancer,Papillary Adenoma,Grignon DJ, Eble JN. Papillary and metanephric adenomas of the kidney. Semin Diagn Pathol. 1998;15:4153.,Definition,Tumors with papillary or tubular architecture of low nulear grade and 5 mm in diameter or smaller Papillary epithelial neoplasm of low malignant potential Grade 1 papillary tumors between 0.5-2cm are strictly defined as carcinoma,Tumor Diameters and Metastasis at Autopsy (871 patients),Grignon and Eble. Semin Diag Pathol. 1998; 15: 41,Proposed Developmental Steps of PRCC,KL Wang, et al. Hum Pathol 2007 38(3):239,Case 3,33 yr, female Right kidney mass, 2X1.5X0.5cm,surface yellow,Clear-Cell Papillary Renal Cell Carcinoma,Clear-cell tubulopapillary renal cell carcinoma Renal angiomyoadenomatous tumor Renal cell carcinoma with prominent leiomyomatous proliferation Clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity,Clear-Cell Papillary Renal Cell Carcinoma,Cytokeratin 7+, carbonic anhydrase IX (CA9)+, HIF-1+, GLUT-1+ CD10-, P504S-, TFE3- Absence of VHL gene alteration,Case 4,25 years old female CT revealed a mass in right kidney Nephrectomy was performed,TFE-3,Renal carcinomas associated with Xp11.2 translocations,Papillary architecture comprised of clear cells Nested architecture Cells with voluminous granular eosinophilic cytoplasm Psammoma bodies,Xp11 Translocation Carcinoma,Heimann et al. Fusion of a novel gene, RCC17, to the TFE3 gene. Cancer Res 2001; 61: 4130 Argani et al. Primary renal neoplasms with ASPL-TFE3 gene fusion of alveolar soft part sarcoma. Am J Surg Pathol 2001; 159: 179 Argani et al. PRCC-TFE3 renal carcinomas. Am J Surg Pathol 2002; 26:1553,Case 3,Diagnosis Renal carcinomas associated with Xp11.2 translocations,Microphthalmia Transcription Factor / TFE Family,MiTF, TFE3, TFEB, TFEC Homologous DNA binding domain Recognize identical DNA sequences Activate transcription of similar genes in vitro,Am J Surg Pathol 2005,t (6;11)(p21;q12) Renal Carcinoma,Ages 6-53 years (median 18 yr) Morphology Epithelioid cells, predominantly clear cytoplasm IHC Minimal cytokeratins expression All HMB45, Melan-A (+) Aberrant positive of TFEB transcription factor,Diagnostic Use of MiTF/TFE Family Protein,Chromophobe Renal Cell Carcinoma,Large pale cells with prominent cell membranes Perinuclear halos Eosinophilic variant,Mucinous tubular and spindle cell carcinoma,Tightly packed, small, elongated tubules separated by pale mucinous stroma The parallel tubular arrays often have a spindle cell configuration Cuboidal or oval nulear shapes and low-grade features Positive for EMA, AE1/AE3, CK7, CK19, 34E12 and AMACR,MTSCC-Loopoma?,Collecting Duct Carcinoma,Collecting Duct Carcinoma,Arises in the principal cells of the collecting ducts of Bellini Complex tubulopapillary architecture Pronounced stromal desmoplasia Complex interanastomosing structures CK19、34bE12、UEA-1 + , CD10、Villin -,CK19,Low Grade Collecting Duct Carcinoma - Tubulocystic carcinoma,MacLennan GT, et al. Low-grade collecting duct carcinoma of the kidney: report of 13 cases of low-grade mucinous tubulocystic renal carcinoma of possible collecting duct origin. Urology 1997; 50:679-684. Amin MB, et al. Tubulocystic carcinoma of the kidney: Clinicopathologic analysis of 29 cases of a distinctive rare subtype of renal cell carcinoma. Mod Pathol 2004; 17:137A,Tubulocystic carcinoma,Tubules and cystic structures of markedly variable size, separated by delicate septa. “spider web-like” Tubules are lined by a single layer of low cuboidal epithelial cells with hobnail appearance IHC similar to collecting duct carcinoma,Renal Medullary Carcinoma,Strongly associated with sickle cell hemoglobinopathies Typically located in the renal medulla May arise in the terminal collecting ducts and the adjacent papillary epithelium,Reticular or microcystic growth pattern Tubule formation and growth in diffuse sheets or solid nodules Pleomorphic nuclei, prominent nucleoli, and eosinophilic cytoplasm IHC positive for CEA, EMA, CK19, topoisomerase IIa,Renal Medullary Carcinoma,Acquired Cystic Disease-Associated Renal Cell Carcinoma,End-stage renal disease (ESRD)