Clinicopathological analysis of fumarate hydratase-deficient renal cell carcinoma and literature review

Abstract

Objective To investigate the clinicopathological characteristics of fumarate hydratase-deficient renal cell carcinoma (FH-d RCC) so as to further understand this rare tumor. Methods Two cases with FH-d RCC diagnosed in our hospital from 2010 to 2020 were studied by histopathological observation, immunohistochemical staining (IHC), fluorescence in situ hybridization (FISH) and next generation sequencing (NGS), respectively. A literature review was also performed. Results Both patients were males and aged 34 and 35 years respectively. In case 1, the tumor affected bilateral kidneys with renal hilar lymph node metastasis, whose tumor cells displayed papillary and glandular patterns with high-grade morphology. In case 2, the tumor was located in the upper pole of the kidney and afflicted the adrenal gland; the tumor cells in most areas were well differentiated, presenting tubular and cystic arrangement in varying sizes, and were surrounded by focal areas of low differentiation. Eosinophilic viral inclusion-like macronucleoli and perinucleolar halos are observed in some tumor nuclei of both cases. Besides positive staining for epithelial and renal markers by IHC, both tumors showed negative for CK7 and focal positive for CA9 (CK7-/CA9+). FH expression was absent in case 1 while retained in case 2, but somatic FH gene mutations were detected in both cases by NGS. Moreover, no rearrangement of TFE3 gene was found by FISH. Conclusion FH-d RCC is a rare high-grade renal cell carcinoma with FH gene mutation, often showing highly aggressive behavior and poor prognosis, whose typical histopathologic features include the papillary arrangement of tumor cells, eosinophilic viral inclusion-like macronucleoli and perinucleolar halos.

Keywords

• fumarate hydratase
• renal cell carcinoma
• diagnosis
• histopathology