SDHB expression in paraganglioma-pheochromocytoma syndromes: advantages and limits

Objective: Pheochromocytoma and paraganglioma are rare tumors arising from chromaffin cells. Almost 10% of them are part of typical familial syndromes: Von Hippel–Lindau disease (VHL), neurofibromatosis type 1 (NF1), multiple endocrine neoplasia type 2 (MEN2) and type 1 (MEN1), pheocromocytoma–paraganglioma syndromes (PGLs; SDHB, SDHC, and SDHD) and a newly described syndrome related to TMEM127 gene mutations. Recently, SDHB immunohistochemical analysis has been proposed as a promising molecular marker for succinate dehydrogenase mutation-related neoplasms (i.e. PGLs). Method: All cases of reported pheochromocytomas (n = 160) and paragangliomas (n = 57) between 1988 and 2009 were retrieved from the archives of the Department of Pathology of Padova University. FFPE specimens were genetically characterized for familial syndromes. Syndromic cases and a control group were semiquantitatively (0, 1+, 2+) evaluated for SDHB immunohistochemical expression. Results: Out of 217 cases, 21 cases showed SDHD (n = 3), TMEM127 (n = 3), RET (n = 6), MEN1 (n = 2), VHL (n = 4), or NF1 (n = 3) germline mutations. The other six sporadic cases were evaluated as control. The three SDHD-mutated cases showed either negative (n = 1) or 1+ (n = 2) SDHB immunostaining. Completely negative staining was also observed in a sporadic case. A strong SDHB immunoreaction was observed in 19 and a weak immunoreaction in four of the remaining cases. Conclusion: SDHB immunohistochemical analysis, even not PGL-specific, can be used to triage genetic testing in pheochromocytoma/paraganglioma patients. Further multi-institutional studies should investigate the diagnostic power of this remarkable novel diagnostic tool.