EL CARCINOMA RENAL EN REVISIÓN Nuevas directrices y propuestas de la ISUP Comentario crítico

XXVI EL CARCINOMA RENAL EN REVISIÓN Nuevas directrices y propuestas de la ISUP Comentario crítico F. Algaba Unidad de Patología Universitat Autónoma de Barcelona

Am J Surg Pathol Volume 29, Number 9, September 2005

2012 International Society of Urologic Pathology Vancouver Conference on Renal cell carcinoma. 2013 International Society of Urologic Pathology Baltimore Conference on Best Practices : Recommendations in the Application of Immunohistochemistry in Diagnostic Urologic Pathology.

XXVI EL CARCINOMA RENAL EN REVISIÓN Nuevas directrices y propuestas de la ISUP SUBTIPOS HISTOLÓGICOS Clásicos Nuevos y Emergentes RELECTURA DE LA GRADACIÓN VALORACIÓN EXTENSIÓN PANEL INMUNOHISTOQUÍMICA

XXVI SUBTIPOS CARCINOMA RENAL OMS 2004 DE CÉLULAS CLARAS Tipo multilocular PAPILAR CROMÓFOBO DE DUCTOS COLECTORES (BELLINI) MEDULAR MUCINOSO TUBULAR Y FUSOCELULAR ASOCIADO CON NEUROBLASTOMA DE TRANSLOCACIÓN Xp11.2 (gen TFE3) INCLASIFICABLE

Carcinoma renal células claras tipo multilocular 1. Multilocular cystic renal cell carcinoma 2. Multilocular cystic renal cell neoplasm of low malignant potential 3. Renal cell carcinoma with extensive cystic change 4. Multicystic renal epithelial neoplasm with focal clear cell change 5. None of the above or Uncertain 64% 34% 1% 0% 1% 1 2 3 4 5

Carcinoma renal papilar TIPO I TIPO II TIPO I ONCOCITOIDE TIPO II

Should Oncocytic Papillary-RCC be recognized as a separate entity at this time? 80% 1. Yes 2. No 3. Uncertain even with personal experience/ knowledge 4. Not enough personal experience/knowledge 14% 4% 2% 1 2 3 4

How do you subtype papillary renal cell carcinoma? 1. type1 vs type 2 2. type 1 vs type 2 vs type 3 [oncocytic] 3. type 1 vs type 2a vs type 2b vs type 2c (based on molecular classification) 4. Fuhrman grading 5. Other 14% 2% 0% 8% GRADO SEGÚN EL NUCLEOLO 75% 1 2 3 4 5

Carcinoma renal papilar

Translocación Xp11 Translocación t(6;11)(p21;q12) Subfamilia de factores de transcripción MiT MiTF, TFE3, TFEB, TFEC Marcadores melanocíticos: HMB45, MELAN A Cathepsina K Martignoni G et al. Mod Pathol 2009;22: 1016-1022 CARCINOMA RENAL DE TRANSLOCACIÓN Familia MiT

Carcinoma renal híbrido 73% 1.Subcategory of oncocytoma 2. Subcategory of chromophobe 3. As a distinctive entity 4. Should not be recognized 5. I m not sure? 20% 6% 0% 1% 1 2 3 4 5

XXVI NUEVOS SUBTIPOS CARCINOMA RENAL NO INCLUIDOS EN LA OMS 2004 EN LEIOMIOMATOSIS HEREDITARIA TÚBULO-QUÍSTICO EN ENFERMEDAD QUÍSTICA ADQUIRIDA (TÚBULO) PAPILAR DE CÉLULAS CLARAS

Carcinoma renal en leiomiomatosis hereditaria Should HLRCC be Recognized as a Distinctive Entity at this time? 79% 1. Yes 2. No 3. Uncertain even with personal experience/ knowledge 4. Not enough personal experience/knowledge? 5% 14% 2% 1 2 3 4 Dra. Merino

Carcinoma renal túbulo-quístico AMACR

Carcinoma renal en enfermedad quística adquirida

Carcinoma renal (túbulo) papilar de células claras

73% Túbulo-quístico 1. Yes 2. No 3. Uncertain even with personal experience 4. Not personal experience 5% 7% 14% 1 2 3 4 80% 85% Asociado a enfermedad quística adquirida Túbulo-papilar de Células claras 5% 3% 13% 10% 2% 3% 1 2 3 4 1 2 3 4

XXVI SUBTIPOS EMERGENTES CARCINOMA RENAL, NO INCLUIDOS EN LA OMS 2004 CARCINOMA RENAL FOLICULAR (TIROIDEO) CARCINOMA RENAL ASOCIADO A LA MUTACIÓN GERMINAL SUCCINATO DESHIDROGENASA B CARCINOMA RENAL CON TRANSLOCACIÓN ALK

Carcinoma folicular Carcinoma translocacion ALK Carcinoma renal mutación SDHB

48% 1. Yes 2. No 3. Uncertain even with personal experience 4. Not personal experience Folicular tiroideo 25% 13% 14% Translocación ALK 46% 42% 1 2 3 4 35% 31% 28% SDHB 9% 3% 6% 1 2 3 4 1 2 3 4

RENAL EPITHELIAL NEOPLASMS 2012 ISUP modification of WHO classification Benign Malignant (continued) papillary adenoma oncocytoma Malignant clear cell carcinoma multicystic renal cell neoplasm of low malignant potential papillary carcinoma chromophobe cell carcinoma hybrid oncocytoma chromophobe tumor collecting duct carcinoma renal medullary carcinoma mucinous, tubular and spindle cell carcinoma carcinoma in neuroblastoma survivors MiT family translocation carcinomas Xp11 translocation carcinoma t(6,11) translocation carcinoma tubulocystic carcinoma acquired cystic disease carcinoma clear cell tubulopapillary carcinoma hereditary leiomyomatosis carcinoma Emerging/provisional carcinomas Thyroid-like follicular RCC SDHB RCC ALK translocation RCC unclassified renal cell carcinoma

XXVI Células claras RELECTURA DE LA GRADACIÓN DEL CARCINOMA RENAL 78% Papilar 84% 1. Fuhrman 2. Nucleolar 22% 1. Fuhrman 2. Nucleolar 3. Other 9% 8% 1 2 78% 1 2 3 1. None 2. Fuhrman Cromófobo 3. Chromophobe grade (Paner et al) 4. Nucleolar 0% 8% 14% 1 2 3 4

EVOLUCIÓN DE LA GRADACIÓN DE FUHRMAN CRITERIOS PARA LA DETERMINACIÓN DE LOS GRADOS DE FUHRMAN TAMANO NUCLEAR IRREGULARIDAD PROMINENCIA NUCLEOLAR Am. J. Surg. Pathol 1982 ;6:655-63 Nuclear diameter Shape Nucleoli Grade 1 Small (approximately 10 mm) Round Absent inconspicuous Grade 2 Larger (approximately 15 mm) Irregularities Visible at 400 Grade 3 Even larger (approximately 20 mm) Obvious irregular Visible at 100 Grade 4 As for grade 3 Bizarre multilobed nuclei±spindle cells

100x 1 2 3 4

400x 1 2 3 4

PROPUESTA DE LA ISUP PARA LA GRADACIÓN DEL CARCINOMA RENAL Fuhrman nucleolar Grade 1 tumors were defined as having inconspicuous or absent nucleoli at 100x magnification; Grade 2 tumors, nucleoli should be distinctly visible at 400x, but inconspicuous or invisible at 100x magnification; Grade 3 tumors, nucleoli should be distinctly visible at 100x magnification. Grade 4 tumors should encompassed tumors with rhabdoid, sarcomatoid differentiation or extreme nuclear pleomorphism

HACIA UN GRADO COMPUESTO PARA EL CARCINOMA RENAL Grado nucleolar+necrosis tumoral Should the presence or absence of tumor necrosis be routinely Should any assessment of amount included All histological as a component subtypes (841 (percentage) patients 30% of with necrosis necrosis) be derived by: of a RCC pathology report evaluation? 86% 1. Yes 2. No Disease specific survival 1. MACROSCOPIC 2. MICROSCOPIC 3. BOTH A PESAR DEL CONSENSO SE DECIDIÓESPERAR UNA AMPLIA VALIDACIÓN 27% 72% No necrosis Necrosis 50% 14% Multivariate analysis independent prognostic significance disease specific survival 1 2 2% Katz MD et al. J. Urol. 2010; 183: 909-914 1 2 3

XXVI VALORACIÓN DE LA EXTENSIÓN EN EL CARCINOMA RENAL EL SIGNIFICADO DE LA INVASIÓN DE LOS OTROS VASOS

Invasión microvascular Dall Oglio BJI. 2007; 100: 552 10-year Cancer Specific Survival MVI (+) 85.1% MVI (-) 96.5% Shindo et al BJI. 2013; Jan 25.

Should reporting of MVI in RCC be obligatory? Should MVI be included in the TNM staging of RCC? 59% 1. Yes 2. No 1. Yes 2. No 87% 41%? 13% 1 2 1 2

90% 1. Yes 2. No Site fat tissue invasion Perinephric Sinus. 5y survival 50.9% 25.9% 10% LN Met Met 7% 28% 19% 30% 1 2 J. Urol 2005; 174: 1218-1221 AJSP 2004; 28: 1594-1600