Comparison of primary and metastatic FH-deficient renal cell carcinomas documents morphologic divergence and potential diagnostic pitfall with peritoneal mesothelioma.

cancer biomarkers diagnostic pitfall differential diagnosis fumarate hydratase intratumoral heterogeneity renal cell carcinoma

Journal

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605

Informations de publication

Date de publication:
10 Jul 2024
Historique:
received: 23 02 2024
revised: 05 06 2024
accepted: 01 07 2024
medline: 13 7 2024
pubmed: 13 7 2024
entrez: 12 7 2024
Statut: aheadofprint

Résumé

Fumarate hydratase (FH)-deficient renal cell carcinomas are rare neoplasms characterized by a wide morphological heterogeneity and pathogenetic mutations in the FH gene. They often show aggressive behavior with rapid diffusion to distant organs, so novel therapeutic scenarios have been explored, including EGFR inhibitors and PD-L1 expression for targeted immunotherapy. Herein, we investigated a series of eleven primary FH-deficient renal cell carcinomas and seven distant metastases to evaluate tumor heterogeneity even in metastatic sites and estimate the specific spread rates to various organs. Furthermore, the tumors were tested for immunohistochemical PD-L1 expression and EGFR mutations. Most metastatic cases involved the abdominal lymph nodes (4/7, 57%), followed by the peritoneum (3/7, 42%), the liver (2/7, 29%), and the lungs (1/7, 14%). Six metastatic localizations were histologically documented, revealing morphological heterogeneous architecture often differing from the corresponding primary renal tumor. Peritoneal involvement morphologically resembled a benign reactive mesothelial process or primary peritoneal mesothelioma, thus advocating to perform an accurate immunohistochemical panel, including PAX 8 and FH, to reach the proper diagnosis. A pure low-grade SDH-looking primary FH-deficient renal cell carcinoma was also recorded. As for therapy, significant PD-L1 labeling was found in 60% of primary renal tumors, while none of them carried pathogenetic EGFR mutations. Our data show that FH-deficient renal cell carcinoma may be morphologically heterogeneous in metastases as well, which involve the lymph nodes, the liver, and the peritoneum more frequently than other renal tumors. Due to the high frequency of this latter (42%), pathologists should always be concerned about ruling out mesothelial-derived mimickers, and the occurrence of rarer primary low-grade-looking types. Finally, contrary to EGFR mutations, PD-L1 expression could be a possible predictive biomarker for the therapy of these tumors.

Identifiants

pubmed: 38996839
pii: S0893-3952(24)00141-8
doi: 10.1016/j.modpat.2024.100561
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100561

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Anna Caliò (A)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Stefano Marletta (S)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy; Division of Pathology, Humanitas Istituto Clinico Catanese, Catania, Italy.

Lavinia Stefanizzi (L)

Department of Pathology and Laboratory Medicine, Pederzoli Hospital, Peschiera, Verona, Italy.

Lisa Marcolini (L)

Department of Pathology and Laboratory Medicine, Pederzoli Hospital, Peschiera, Verona, Italy.

Matteo Rotellini (M)

Anatomia Patologica Massa Carrara Azienda Toscana Nord Ovest, Italy.

Gabriella Serio (G)

Department of Precision and Regenerative Medicine and Ionian Area, Pathology Unit, University of Bari, Italy.

Elena Bariani (E)

Unit of Anatomic Pathology, Department of Oncology, Bellaria Hospital, Bologna, Italy.

Caterina Vicentini (C)

Department of Pathology and Laboratory Medicine, Pederzoli Hospital, Peschiera, Verona, Italy.

Serena Pedron (S)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Filippo Maria Martelli (FM)

Department of Pathology and Laboratory Medicine, Pederzoli Hospital, Peschiera, Verona, Italy.

Pietro Antonini (P)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Matteo Brunelli (M)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Guido Martignoni (G)

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy; Department of Pathology and Laboratory Medicine, Pederzoli Hospital, Peschiera, Verona, Italy. Electronic address: guido.martignoni@univr.it.

Classifications MeSH