Publications

Authors:

Caliò, Anna; Marletta, Stefano; Stefanizzi, Lavinia; Marcolini, Lisa; Rotellini, Matteo; Serio, Gabriella; Bariani, Elena; Vicentini, Caterina; Pedron, Serena; Martelli, Filippo Maria; Antonini, Pietro; Brunelli, Matteo; Martignoni, Guido

Title:

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

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

Modern Pathology

ISSN of journal:

0893-3952

N° Volume:

37

Number or Folder:

9

Page numbers:

1-1

Keyword:

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

Short description of contents:

: 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.

Note:

These Authors contributed equally to this work: Caliò Anna, Marletta Stefano

Product ID:

140507

Handle IRIS:

11562/1131287

Last Modified:

August 22, 2024

Bibliographic citation:

Caliò, Anna; Marletta, Stefano; Stefanizzi, Lavinia; Marcolini, Lisa; Rotellini, Matteo; Serio, Gabriella; Bariani, Elena; Vicentini, Caterina; Pedron, Serena; Martelli, Filippo Maria; Antonini, Pietro; Brunelli, Matteo; Martignoni, Guido, Comparison of primary and metastatic FH-deficient renal cell carcinomas documents morphologic divergence and potential diagnostic pitfall with peritoneal mesothelioma «Modern Pathology» , vol. 37 , n. 9 , 2024 , pp. 1-1

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