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

Chisato Ohe, Steven C. Smith, Deepika Sirohi, Mukul Divatia, Mariza De Peralta-Venturina, Gladell P. Paner, Abbas Agaimy, Mitual B. Amin, Pedram Argani, Ying Bei Chen, Liang Cheng, Maurizio Colecchia, Eva Compérat, Isabela Werneck Da Cunha, Jonathan I. Epstein, Anthony J. Gill, Ondřej Hes, Michelle S. Hirsch, Wolfram Jochum, Lakshmi P. Kunju & 15 others Fiona MacLean, Cristina Magi-Galluzzi, Jesse K. McKenney, Rohit Mehra, Gabriella Nesi, Adeboye O. Osunkoya, Maria M. Picken, Priya Rao, Victor E. Reuter, Paulo Guilherme De Oliveira Salles, Luciana Schultz, Satish K. Tickoo, Scott A. Tomlins, Kiril Trpkov, Mahul B. Amin

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)279-292
Number of pages14
JournalAmerican Journal of Surgical Pathology
Volume42
Issue number3
DOIs
StatePublished - Jan 1 2018

Fingerprint

Fumarate Hydratase
Medullary Carcinoma
Renal Cell Carcinoma
Kidney
Leiomyomatosis
Endodermal Sinus Tumor
Christianity
Hemoglobinopathies
Nephrons
Neoplasms
Adenocarcinoma

Keywords

  • collecting duct carcinoma
  • FH-deficient renal cell carcinoma
  • hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma
  • morphology
  • renal medullary carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Reappraisal of Morphologic Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma. / Ohe, Chisato; 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; Da Cunha, Isabela Werneck; Epstein, Jonathan I.; Gill, Anthony J.; Hes, Ondřej; Hirsch, Michelle S.; Jochum, Wolfram; 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; Amin, Mahul B.

In: American Journal of Surgical Pathology, Vol. 42, No. 3, 01.01.2018, p. 279-292.

Research output: Contribution to journalArticle

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, Da Cunha, IW, 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 & Amin, MB 2018, 'Reappraisal of Morphologic Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma', American Journal of Surgical Pathology, vol. 42, no. 3, pp. 279-292. https://doi.org/10.1097/PAS.0000000000001000
Ohe, Chisato ; 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 ; Da Cunha, Isabela Werneck ; Epstein, Jonathan I. ; Gill, Anthony J. ; Hes, Ondřej ; Hirsch, Michelle S. ; Jochum, Wolfram ; 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 ; Amin, Mahul B. / Reappraisal of Morphologic Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma. In: American Journal of Surgical Pathology. 2018 ; Vol. 42, No. 3. pp. 279-292.
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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

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AU - Mehra, Rohit

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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.

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AU - Trpkov, Kiril

AU - Amin, Mahul B.

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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.

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KW - FH-deficient renal cell carcinoma

KW - hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma

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KW - renal medullary carcinoma

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