A Case Report of Aggressive Fumarate Hydrase-deficient Renal Cell Carcinoma With Loss of HLA Antigens

Cancer Diagn Progn. 2023 Jul 3;3(4):522-527. doi: 10.21873/cdp.10249. eCollection 2023 Jul-Aug.


Background: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype, and FH-deficient RCC may be misdiagnosed as another type of RCC, such as type 2 papillary RCC or collecting duct carcinoma. FH and 2-succinocysteine (2SC) are useful diagnostic markers for FH-deficient RCC and can be measured using immunohistochemistry (IHC).

Case report: A 30-year-old female with 3-month history of fatigue and left-flank mass was diagnosed with a 20×13×10 cm left-side renal mass with massive inferior vena cava (IVC) tumor thrombus that extended into the right atrium. She underwent nephrectomy and IVC thrombectomy, and a pathological diagnosis of type 2 papillary RCC was made. Four months after the surgery, computed tomography scan showed multiple liver metastases not observed immediately after surgery. Systemic treatment with sorafenib was initiated; however, she did not respond and died 3 months after treatment. Subsequent re-review of hematoxylin and eosin-stained sections indicated morphologic characteristics consistent with FH-deficient RCC, and IHC staining was negative for FH but positive for 2SC, indicating a diagnosis of FH-deficient RCC. Further immunological analyses revealed the loss of HLA-class I, b2 microglobulin, and HLA-DR antigens in cancer cells. In addition, a few CD8-positive cytotoxic T cells and CD163-positive tumor-associated macrophages were noted.

Conclusion: An immunosuppressive tumor microenvironment that facilitates cancer immune evasion might be associated with the rapid progression and poor prognosis in our patient. Further investigation of the tumor immune microenvironment in patients with FH-deficient RCC is warranted.

Keywords: 2SC; HLA loss; Renal cell carcinoma; cold tumor; fumarate hydrase deficiency.