1、Classification of Renal CarcinomaZhe WangDepartment of Pathology, Xijing HospitalFourth Military Medical UniversityRenal UnitCK19THPCD10、RCCUEA-1Renal CarcinomaClear Cell CarcinomaGranular cell carcinomaClear Cell CarcinomaChromophobeCarcinomaPapillary CarcinomaType I Type IICollecting duct carcinom

2、aOncocytomaMetanephric Adenoma、AdenofibromaUnclassified and unusual carcinomaCase 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 Mult

3、ifocal unilateral or bilateral tumors Family history of renal cancer or other VHL related tumor Germline mutation analysis Missense mutation of VHL gene on 3p25-26Diagnostic Criteria for VHL Syndrome No family history Hemangioblastoma of CNS or retina + VHL associated extraneural tumors With family

4、history Hemangioblastoma of CNS or retina or VHL associated extraneural tumorsCase 1Diagnosis VHL associated clear cell renal cell carcinomaVHL subtypeHBRCCPCCMutationType 1+-deletion/truncationType 2A+-+Tyr98His/Tyr112HisType 2B+MissenseType 2C-+Leu188ValSer80LeuHB：Hemangioblastoma；RCC：Renal cell c

5、arcinoma；PCC：PheochromocytomaPathogenesisCohen H and McGovern FJ, N Engl J Med, 2005; 353:23pVHL in tumor initiationSporadic Clear Cell CarcinomaPathogenesisCohen H and McGovern FJ, N Engl J Med, 2005; 353:23Fuhrman Nuclear Grade（4 tiered）Note：Apply in clear cell carcinoma and papillary carcinomaGra

6、deDiameter of NucleiNucleiNucleoliOther Features110mRoundAbsence or inconspicuous215mFinely granular open chromatininconspicuous400320mirregularlarge100420+mPleomorphismlargeClump chromatin, spindle cellMultilocular Cystic Renal Cell CarcinomaMultilocular Cystic Renal Cell CarcinomaModern Pathol 201

7、0 23, 931936Most of the cases showed chromosome 3p deletion.Very good survivalHereditary RCC Hereditary leiomyomatosis and RCC Birt-Hogg-Dub syndrome Hyperparathyroidism-Jaw tumor syndrome Familial Papillary Thyroid Cancer Constitutional chromosome 3 translocations Hereditary papillary renal cancerH

8、ereditary leiomyomatosis and RCC Leomyoma or leomyosarcoma of skin or uterus Unilateral papillary renal carcinoma Fumarate Hydratase（FH）mutation 1q42Birt-Hogg-Dub Syndrome Facial fibrofolliculoma and tricodiscoma Lung cyst with risk of spontaneous pneumothorax Colonic polyps Renal tumors: oncocytoma

9、 or chromophobe carcinoma Folliculin（BHD）gene mutation 17p11.2Birt-Hogg-Dub SyndromeHyperparathyroidism-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

10、carcinoma HPT-JT（parafibromin）mutation 1q21q32 J Intern Med, 2003 253(6):634Familial Papillary Thyroid Cancer Familial PTC Associated with Renal Cell Neoplasia 1q21 Not c-Met associated Hereditary renal papillary cacinoma Not Cowden syndrome Not MEN2ACase 2 45 yr male Right kidney massPapillary Rena

11、l 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 1Type 2Case 2Diagnosis Papillary Renal Cell Carcinoma, Type IPrognosis of

12、PRCC Conventional papillary renal carcinoma 75% with duplication of chromosome 7, proto-oncogene METCohen H and McGovern FJ, N Engl J Med, 2005; 353:23Papillary Renal Cancer involved in Hereditary Syndromes Hereditary papillary renal cancer Hereditary leiomyomatosis and RCC Birt-Hogg-Dub syndrome Hy

13、perparathyroidism-Jaw tumor syndrome Familial Papillary Thyroid CancerPapillary 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 smalle

14、r Papillary epithelial neoplasm of low malignant potential Grade 1 papillary tumors between 0.5-2cm are strictly defined as carcinomaTumor Diameters and Metastasis at Autopsy (871 patients)Max tumor diameternM1 or N11-3 cm2087 (3.4%)1-2.5 cm1774 (2.2%)1-2.0 cm1542 (1.3%)1.0 cm3960Grignon and Eble. S

15、emin Diag Pathol. 1998; 15: 41Proposed Developmental Steps of PRCCKL Wang, et al. Hum Pathol 2007 38(3):239Case 3 33 yr, female Right kidney mass, 2X1.5X0.5cm,surface yellowClear-Cell Papillary Renal Cell Carcinoma Clear-cell tubulopapillary renal cell carcinoma Renal angiomyoadenomatous tumor Renal

16、 cell carcinoma with prominent leiomyomatous proliferation Clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivityClear-Cell Papillary Renal Cell Carcinoma Cytokeratin 7+, carbonic anhydrase IX (CA9)+, HIF-1+, GLUT-1+ CD10-, P504S-, TFE3- Absence of VHL gene alterationCase 4 25 y

17、ears old female CT revealed a mass in right kidney Nephrectomy was performed TFE-3Renal carcinomas associated with Xp11.2 translocations Papillary architecture comprised of clear cells Nested architecture Cells with voluminous granular eosinophilic cytoplasm Psammoma bodiesXp11 Translocation Carcino

18、ma 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

19、Diagnosis Renal carcinomas associated with Xp11.2 translocationsMicrophthalmia 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 2005t (6;11)(p21;q12) Renal Carcin

20、oma 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 factorDiagnostic Use of MiTF/TFE Family ProteinGenesIHC AssaysNeoplasmsMiTFYesMalignant melanomaTFE3YesAlv

21、eolar soft part sarcomaXp11 translocation carcinomaTFEBYest (6;11)(p21;q12) Renal CarcinomaTFECNo?Chromophobe Renal Cell Carcinoma Large pale cells with prominent cell membranes Perinuclear halos Eosinophilic variantMucinous tubular and spindle cell carcinoma Tightly packed, small, elongated tubules

22、 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 CarcinomaCollecting Duct Carcinoma Arises in the principal

23、cells of the collecting ducts of Bellini Complex tubulopapillary architecture Pronounced stromal desmoplasia Complex interanastomosing structures CK19、34bE12、UEA-1 + , CD10、Villin - CK19Low Grade Collecting Duct Carcinoma - Tubulocystic carcinoma MacLennan GT, et al. Low-grade collecting duct carcin

24、oma 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. M

25、od 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

26、 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, top