Unmasking the enigma: A case of Fumarate Hydratase-deficient renal cell carcinoma

Document Type

Case Report




Introduction: Fumarate Hydratase-deficient-renal cell carcinoma (FH-dRCC) is an uncommon and extremely aggressive variant of renal cell carcinoma (RCC) resulting from inactivating mutations in the tumor suppressor gene, fumarate hydratase (FH).
Case presentation: We report a case of a young male who presented with the complaint of painless hematuria. Upon workup, he was found to have a renal mass with bony metastases. The histopathology was consistent with renal cell carcinoma with features of FH-deficient variant. Germline testing showed a pathogenic mutation in the FH gene. He was started on a treatment combination of Pembrolizumab and Axitinib along with Zoledronate for bone metastasis. His response to the combination therapy was short with early progression of disease. He was switched to a second-line treatment Bevacizumab and Erlotinib, which achieved significant disease response.
Discussion: Systemic therapy is the mainstay of treatment for metastatic disease. Although the novel agents approved for other subsets of RCC have been used, the responses are grim. There is no consensus on the sequence of further lines of treatment for FH-dRCC and is based on the physician's choice, availability of the drugs, cost, toxicity, and tolerance of the patient.
Conclusion: This case report emphasizes the occurrence, presentation, management and prognosis of FH-dRCC, which is an aggressive entity, presenting at a young age with early distant metastases, not diagnosed appropriately due to its poorly characterized cytologic features. Being an infrequent neoplasm, it is an area that warrants oncological exploration to improve outcomes in these individuals. The combination of Erlotinib and Bevacizumab provides promising outcomes in terms of progression-free survival.


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Publication (Name of Journal)

International Journal of Surgery Case Reports