Succinate dehydrogenase-B fluorescence in situ hybridization in pheochromocytoma-paragangliomas

Objective: Preoperative identification of familial pheochromocytoma and paraganglioma (PPGL) is crucial, yet often overlooked, leading to missed diagnoses. Typically, succinate dehydrogenase-B (SDHB) and fumarate hydratase (FH) tests are applied postoperatively to confirm familial links and assess prognosis. However, routine preoperative multidisciplinary collaboration is limited, causing delayed screening requests. Consequently, routine SDHB and FH immunohistochemistry (IHC) testing is not widely practiced. This study introduces SDHB fluorescence in situ hybridization (FISH) as a diagnostic tool, akin to HER2 IHC-FISH testing in gastric carcinomas. Materials and Methods: Succinate dehydrogenase-B and FH IHC were conducted on 43 cases. FISH analysis was performed for 28 cases with suspected familial origin or SDHB IHC loss to determine whether the protein loss was due to chromosomal changes. Results: Complete SDHB IHC loss occurred in 8 cases, partial loss in 4, and preservation in 31. Complete FH loss occurred in 10 cases. FISH analysis revealed chromosomal breaks in 20 cases (71.4%), including those with SDHB/FH IHC loss or positive clinical history. Ten cases (35.7%) showed a “red-signal only” pattern, suggesting further genetic testing. Conclusion: Succinate dehydrogenase-B FISH serves as a cost-effective tool for early PPGL diagnosis, complementing SDHB and FH IHC results. It can help identify cases that need genetic testing, even when IHC results are preserved.