Fumarate hydratase-deficient renal cell carcinoma: A clinicopathological study of seven cases including hereditary and sporadic forms

Naoto Kuroda, Miho Tsutsui, Mitsuko Iguchi, Emi Nobuoka, Takeshi Uehara, Yuta Sonobe, Yukiko Morinaga, Shinsuke Shibuya, Wakako Oda, Hiroyuki Yanai, Chiaki Kawada, Takashi Karashima, Ichiro Yamasaki, Keiji Inoue, Yoji Nagashima

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) has been incorporated into the recent international histological classification of renal tumors. However, to date, there are limited studies describing the clinicopathological features of fumarate hydratase (FH)-deficient RCC, including the hereditary (HLRCC) and sporadic forms. Herein, we present a clinicopathological study of seven cases with FH-deficient RCC. The age of patients ranged from 26 to 70 years with mean and median age of 51.7 and 57 years, respectively. The follow-up data of all patients were available. One patient was alive without the disease and five patients were alive with active disease. One patient died of the disease. Family history of RCC, or skin or uterine smooth muscle tumor within second degree of kinship was present in four of seven patients. Metastasis was observed in all tumors. Metastatic sites included bone, lungs, liver, peritoneum, ovaries, tonsils, or lymph nodes. Grossly, the cut surface of the tumor usually showed light brown, brown, or whitish color. Microscopically, the cytoplasm of the tumor cells was predominantly eosinophilic and all tumors displayed various architectural patterns such as papillary, tubular, solid, or microcystic patterns. Furthermore, two tumors demonstrated a tubulocystic pattern. Sarcomatoid change and rhabdoid features were seen in five tumors and two tumors, respectively. Large cytomegaloviral (CMV) inclusion-like eosinophilic nucleoli surrounded by a clear halo were identified in all tumors. All tumors showed negative immunohistochemical reaction for FH protein. False positive results of TFE3 protein were observed in three tumors. Furthermore, a germline mutation of FH gene was identified in one patient with family history of the disease. In conclusion, FH-deficient RCC includes hereditary and sporadic forms. Grossly, this tumor is solitary and occurs unilaterally. Histologically, the tumor is characterized by various patterns such as papillary, tubular, solid, tubulocystic, or microcystic, has eosinophilic cytoplasm and CMV-like high-grade nuclei. FH-deficient RCCs frequently metastasize to other anatomic sites. TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene.

Original languageEnglish
Article number151599
JournalAnnals of Diagnostic Pathology
Volume49
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Fumarate hydratase
  • Pathology
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Fumarate hydratase-deficient renal cell carcinoma: A clinicopathological study of seven cases including hereditary and sporadic forms'. Together they form a unique fingerprint.

Cite this