1. Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma.
- Author
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Ohe C, Smith SC, Sirohi D, Divatia M, de Peralta-Venturina M, Paner GP, Agaimy A, Amin MB, Argani P, Chen YB, Cheng L, Colecchia M, Compérat E, Werneck da Cunha I, Epstein JI, Gill AJ, Hes O, Hirsch MS, Jochum W, Kunju LP, Maclean F, Magi-Galluzzi C, McKenney JK, Mehra R, Nesi G, Osunkoya AO, Picken MM, Rao P, Reuter VE, de Oliveira Salles PG, Schultz L, Tickoo SK, Tomlins SA, Trpkov K, and Amin MB
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Australia, Biomarkers, Tumor genetics, Biopsy, Brazil, Canada, Carcinoma, Renal Cell classification, Carcinoma, Renal Cell enzymology, Carcinoma, Renal Cell genetics, Child, DNA Mutational Analysis, Diagnosis, Differential, Europe, Female, Fumarate Hydratase genetics, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Kidney Medulla enzymology, Kidney Neoplasms classification, Kidney Neoplasms enzymology, Kidney Neoplasms genetics, Kidney Tubules, Collecting enzymology, Male, Middle Aged, Mutation, Neoplasm Grading, Phenotype, Predictive Value of Tests, Retrospective Studies, United States, Young Adult, Biomarkers, Tumor deficiency, Carcinoma, Renal Cell pathology, Fumarate Hydratase deficiency, Kidney Medulla pathology, Kidney Neoplasms pathology, Kidney Tubules, Collecting pathology
- 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.
- Published
- 2018
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