Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma

Publication

Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma

Journal Paper/Review - Mar 1, 2018

Ohe Chisato, Kunju Lakshmi P, Maclean Fiona, Magi-Galluzzi Cristina, McKenney Jesse K, Mehra Rohit, Nesi Gabriella, Osunkoya Adeboye O, Picken Maria M, Rao Priya, Reuter Victor E, de Oliveira Salles Paulo Guilherme, Schultz Luciana, Tickoo Satish K, Tomlins Scott A, Trpkov Kiril, Jochum Wolfram, Hirsch Michelle S, Hes Ondrej, Smith Steven C, Sirohi Deepika, Divatia Mukul, de Peralta-Venturina Mariza, Paner Gladell P, Agaimy Abbas, Amin Mitual B, Argani Pedram, Chen Ying-Bei, Cheng Liang, Colecchia Maurizio, Compérat Eva, Werneck da Cunha Isabela, Epstein Jonathan I, Gill Anthony J, Amin Mahul B

Citation

Ohe C, Kunju L, Maclean F, Magi-Galluzzi C, McKenney J, Mehra R, Nesi G, Osunkoya A, Picken M, Rao P, Reuter V, de Oliveira Salles P, Schultz L, Tickoo S, Tomlins S, Trpkov K, Jochum W, Hirsch M, Hes O, Smith S, Sirohi D, Divatia M, de Peralta-Venturina M, Paner G, Agaimy A, Amin M, Argani P, Chen Y, Cheng L, Colecchia M, Compérat E, Werneck da Cunha I, Epstein J, Gill A, Amin M. Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma. Am J Surg Pathol 2018; 42:279-292.

Type

Journal Paper/Review (English)

Journal

Am J Surg Pathol 2018; 42

Publication Date

Mar 1, 2018

Issn Electronic

1532-0979

Pages

279-292

Brief description/objective

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.