XXVI

EL CARCINOMA RENAL EN REVISIÓNNuevas directrices y propuestas de la ISUP

Comentario crítico

F. AlgabaUnidad de Patología Universitat Autónoma de Barcelona

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

2013 International Society of Urologic Pathology Baltimore Conference on

Best Practices : Recommendations in the Applicationof Immunohistochemistry in Diagnostic Urologic Pathology.

2012 International Society of Urologic Pathology Vancouver Conference on

Renal cell carcinoma.

XXVIEL CARCINOMA RENAL EN REVISIÓN

Nuevas directrices y propuestas de la ISUP

SUBTIPOS HISTOLÓGICOSClásicosNuevos y Emergentes

RELECTURA DE LA GRADACIÓN

VALORACIÓN EXTENSIÓN

PANEL INMUNOHISTOQUÍMICA

XXVISUBTIPOS 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

1 2 3 4 5

34%

64%

1%0%1%

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

Carcinoma renal células claras tipo multilocular

Carcinoma renal papilar

TIPO I TIPO II

TIPO I TIPO IIONCOCITOIDE

Should Oncocytic Papillary-RCC be recognized as a separate entity at this time?

1 2 3 4

14%

2%4%

80%

1. Yes2. No3. Uncertain even with personal

experience/ knowledge4. Not enough personal

experience/knowledge

How do you subtype papillary renal cell carcinoma?

1 2 3 4 5

14%

2%

75%

8%

0%

1. type1 vs type 22. 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 grading5. Other GRADO S

EGÚN EL N

UCLEOLO

Carcinoma renal papilar

Translocación t(6;11)(p21;q12)Translocación Xp11

• MiTF, TFE3, TFEB, TFEC

Subfamilia de factores de transcripción MiT

• Marcadores melanocíticos: HMB45, MELAN A• Cathepsina K

Martignoni G et al. Mod Pathol 2009;22: 1016-1022

CARCINOMA RENAL DE TRANSLOCACIÓNFamilia MiT

Carcinoma renal híbrido

1 2 3 4 5

20%

73%

1%0%6%

1.Subcategory of oncocytoma2. Subcategory of chromophobe3. As a distinctive entity4. Should not be recognized5. I’m not sure

?

XXVINUEVOS SUBTIPOS CARCINOMA RENAL

NO INCLUIDOS EN LA OMS 2004

• EN LEIOMIOMATOSIS HEREDITARIA

• TÚBULO-QUÍSTICO

• EN ENFERMEDAD QUÍSTICA ADQUIRIDA• (TÚBULO) PAPILAR DE CÉLULAS CLARAS

Dra. Merino

Carcinoma renal en leiomiomatosis hereditaria

1 2 3 4

79%

14%

2%5%

1. Yes2. No3. Uncertain even with personal

experience/ knowledge4. Not enough personal

experience/knowledge

?

Should HLRCC be Recognized as a Distinctive Entity at this time?

AMACR

Carcinoma renal túbulo-quístico

Carcinoma renal en enfermedad quística adquirida

Carcinoma renal (túbulo) papilar de células claras

1 2 3 4

80%

13%

3%5%

Asociado a enfermedadquística adquirida

1 2 3 4

85%

3%2%10%

Túbulo-papilar deCélulas claras

1 2 3 4

73%

14%7%5%

Túbulo-quístico

1. Yes2. No3. Uncertain even with

personal experience 4. Not personal

experience

• CARCINOMA RENAL FOLICULAR (TIROIDEO)

• CARCINOMA RENAL ASOCIADO A LA MUTACIÓN GERMINAL SUCCINATO DESHIDROGENASA B

• CARCINOMA RENAL CON TRANSLOCACIÓN ALK

XXVISUBTIPOS EMERGENTES CARCINOMA

RENAL, NO INCLUIDOS EN LA OMS 2004

Carcinoma folicular Carcinoma translocacion ALK

Carcinoma renal mutación SDHB

1 2 3 4

25%

14%13%

48%

1. Yes2. No3. Uncertain even with

personal experience 4. Not personal

experience

Foliculartiroideo

SDHB

1 2 3 4

35%31%

6%

28%

1 2 3 4

9%

42%

3%

46%

Translocación ALK

RENAL EPITHELIAL NEOPLASMS 2012 ISUP modification of WHO classification

Benign

• 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

Malignant (continued)

• 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

XXVIRELECTURA DE LA GRADACIÓN

DEL CARCINOMA RENAL

1 2

78%

22%

1. Fuhrman

2. Nucleolar

Células claras

1 2 3

9% 8%

84%

1. Fuhrman

2. Nucleolar

3. Other

Papilar

1 2 3 4

78%

14%8%

0%

1. None

2. Fuhrman

3. Chromophobe grade (Paner et al)4. Nucleolar

Cromófobo

CRITERIOS PARA LA DETERMINACIÓN DE LOS GRADOS DE FUHRMAN

TAMANO NUCLEARIRREGULARIDADPROMINENCIA NUCLEOLAR

Am. J. Surg. Pathol 1982 ;6:655-63

EVOLUCIÓN DE LA GRADACIÓN DE FUHRMAN

Grade 1 Small (approximately 10 mm) Round Absent inconspicuousGrade 2 Larger (approximately 15 mm) Irregularities Visible at 400Grade 3 Even larger (approximately 20 mm) Obvious irregular Visible at 100Grade 4 As for grade 3 Bizarre multilobed nuclei±spindle cells

Nuclear diameter Shape Nucleoli

100x

1 2

3 4

400x

1 2

3 4

Grade 1 tumors were defined as having inconspicuousor 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 withrhabdoid, sarcomatoid differentiationor extreme nuclear pleomorphism

PROPUESTA DE LA ISUP PARA LA GRADACIÓN DEL CARCINOMA RENAL

Fuhrman nucleolar

HACIA UN GRADO COMPUESTOPARA EL CARCINOMA RENAL

All histological subtypes (841 patients 30% with necrosis)

No necrosis

Necrosis ≥ 50%

Disease specific survival

Katz MD et al. J. Urol. 2010; 183: 909-914

Multivariate analysis independent prognostic significance disease specific survival

Grado nucleolar+necrosis tumoral

1 2 3

2%

72%

27%

Should the presence or absenceof tumor necrosis be routinely

included as a componentof a RCC pathology report evaluation?

1 2

14%

86%

1. Yes

2. No

1. MACROSCOPIC

2. MICROSCOPIC3. BOTH

Should any assessment of amount(percentage) of necrosis be derived by:

A PESAR D

EL CONSENSO

SE DECID

IÓESPERAR U

NA

AMPLIA V

ALIDACIÓ

N

XXVIVALORACIÓN DE LA EXTENSIÓN

EN EL CARCINOMA RENAL

EL SIGNIFICADO DE LA INVASIÓN DE

LOS OTROS VASOS

Dall´Oglio BJI. 2007; 100: 552

Invasión microvascular

10-year Cancer Specific SurvivalMVI (+) 85.1% MVI (-) 96.5%

Shindo et al BJI. 2013; Jan 25.

Should reporting of MVIin RCC be obligatory?

1 2

41%

59% 1. Yes

2. No

Should MVI be includedin the TNM staging of RCC?

1 2

87%

13%

1. Yes

2. No

?

19% 30%25.9%Sinus.

7% 28%50.9%Perinephric

LN Met Met5y survivalSite fat tissueinvasion

J. Urol 2005; 174: 1218-1221 AJSP 2004; 28: 1594-16001 2

10%

90%

1. Yes

2. No