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

• Type of Material: Article
• Authors: Chisato Ohe, Cedars-Sinai Medical Center; Steven C Smith, VCU School of Medicine, Richmond; Deepika Sirohi, Cedars-Sinai Medical Center; Mukul Divatia, Cornell University; Mariza de Peralta-Venturina, Cedars-Sinai Medical Center; Gladell P Paner, University of Chicago; Abbas Agaimy, Friedrich Alexander University; Mitual B Amin, William Beaumont Hosp; Pedram Argani, Johns Hopkins Hospital; Ying-Bei Chen, Memorial Sloan Kettering Cancer Center; Liang Cheng, Indiana University School of Medicine; Maurizio Colecchia, Fondazione IRCCS Istituto Nazionale dei Tumori; Eva Compérat, Université Pierre et Marie Curie; Isabela Werneck da Cunha, AC Camargo Cancer Center; Jonathan I Epstein, Johns Hopkins Hospital; Anthony J Gill, Royal North Shore Hospital; Ondřej Hes, Charles University Hospital; Michelle S Hirsch, Brigham & Womens Hospital; Wolfram Jochum, Kantonsspital St Gallen; Lakshmi P Kunju, University of Michigan; Fiona Maclean, Douglass Hanly Moir Pathology; Cristina Magi-Galluzzi, Cleveland Clinic; Jesse K McKenney, Cleveland Clinic; Rohit Mehra, University of Michigan; Gabriella Nesi, University of Florence; Adeboye Osunkoya, Emory University; Maria M Picken, Loyola University; Priya Rao, MD Anderson Cancer Centr; Victor E Reuter, Memorial Sloan Kettering Cancer; Paulo Guilherme de Oliveira Salles, Hospital Luxemburgo; Luciana Schultz, Instituto de Anatomia Patologica; Satish K Tickoo, Memorial Sloan Kettering Cancer Centre; Scott A Tomlins, University of Michigan, Ann Arbor; Kiril Trpkov, University of Calgary; Mahul B Amin, Cedars-Sinai Medical Center
• Language: English
• Date: 2018-03-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Wolters Kluwer Health, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/PAS.0000000000001000
• Title of Journal or Parent Work: AMERICAN JOURNAL OF SURGICAL PATHOLOGY
• Volume: 42
• Issue: 3
• Start Page: 279
• End Page: 292
• Grant/Funding Information: S.A.T is supported by the A. Alfred Taubman Medical Research Institute. O.H. acknowledges support of the Charles University Research Fund (project number P36) and by the project CZ.1.05/2.1.00/03.0076 from European Regional Development Fund. C.O. received research fellowship training support from the Uehara Memorial Foundation. Presented in part at the annual meeting of the United States and Canadian Academy of Pathology, Seattle, March, 2016.
• Keywords: MUTATIONS; Surgery; Pathology; HEREDITARY LEIOMYOMATOSIS; EXPRESSION; Science & Technology; FH; CANCER; KIDNEY TUMORS; INTERNATIONAL-SOCIETY; Life Sciences & Biomedicine; morphology; collecting duct carcinoma; UTERINE LEIOMYOMAS; IMMUNOHISTOCHEMISTRY; PAX8; renal medullary carcinoma; FH-deficient renal cell carcinoma; hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma

Abstract

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.