Screening of Renal Cell Neoplasms for Succinate Dehydrogenase Deficiency and Fumarate Hydratase Deficiency Using Immunohistochemistry for SDH-B, FH, and 2-SC: Study from an Indian Oncology Center

Introduction Renal cell carcinoma (RCC) accounts for 2% of all cancers globally. Majority of RCC are sporadic, and only 2%-5% are associated with inherited tumor syndromes. The latest World Health Organization (WHO) classification of renal cell tumors (5th edition) has introduced a new category of molecularly defined renal tumors, which include fumarate hydratase (FH)-deficient RCC and succinate dehydrogenase (SDH)-B-deficient RCC among others. These entities can be screened in tumor tissue using immunohistochemistry (IHC). Ours is the first study from India documenting screening of renal neoplasms for FH and SDH deficiency, using IHC. Materials and Methods In our study, we screened 297 cases of renal cell neoplasms using IHC “SDH-B” for SDH-B deficiency, and “FH” & 2-succino-cysteine (“2-SC”) for FH-deficient RCC. Results We found 0.7% (2/297 cases) of FH-deficient RCC. Both these patients were of young age (20 and 37 years), with stage III disease showing early metastasis. The common feature of vesicular nuclei with conspicuous eosinophilic nucleoli was seen in both cases. We could not perform the mutational analysis in these cases. We did not find any case with SDH-B deficiency. Conclusion One should keep a low threshold in diagnosing the aggressive FH-deficient RCC, and use IHC panel for the same, especially in cases with papillary architecture and grade 3 nuclei. These patients also require germline testing and surveillance of other family members.