TY - JOUR
T1 - Reappraisal of Morphologic Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma
AU - Ohe, Chisato
AU - Smith, Steven C.
AU - Sirohi, Deepika
AU - Divatia, Mukul
AU - De Peralta-Venturina, Mariza
AU - Paner, Gladell P.
AU - Agaimy, Abbas
AU - Amin, Mitual B.
AU - Argani, Pedram
AU - Chen, Ying Bei
AU - Cheng, Liang
AU - Colecchia, Maurizio
AU - Compérat, Eva
AU - Da Cunha, Isabela Werneck
AU - Epstein, Jonathan I.
AU - Gill, Anthony J.
AU - Hes, Ondřej
AU - Hirsch, Michelle S.
AU - Jochum, Wolfram
AU - Kunju, Lakshmi P.
AU - MacLean, Fiona
AU - Magi-Galluzzi, Cristina
AU - McKenney, Jesse K.
AU - Mehra, Rohit
AU - Nesi, Gabriella
AU - Osunkoya, Adeboye O.
AU - Picken, Maria M.
AU - Rao, Priya
AU - Reuter, Victor E.
AU - De Oliveira Salles, Paulo Guilherme
AU - Schultz, Luciana
AU - Tickoo, Satish K.
AU - Tomlins, Scott A.
AU - Trpkov, Kiril
AU - Amin, Mahul B.
N1 - Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH-/2SC + or FH ±/2SC + with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.
AB - Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH-/2SC + or FH ±/2SC + with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.
KW - FH-deficient renal cell carcinoma
KW - collecting duct carcinoma
KW - hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma
KW - morphology
KW - renal medullary carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85044528308&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044528308&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000001000
DO - 10.1097/PAS.0000000000001000
M3 - Article
C2 - 29309300
AN - SCOPUS:85044528308
SN - 0147-5185
VL - 42
SP - 279
EP - 292
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 3
ER -