Losses in the succinate dehydrogenase (SDH) complex characterize 20–30%
of extra-adrenal paragangliomas and 7–8% of gastric GISTs, and rare renal cell
carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression
of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of
the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other
epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258
epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell
carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%) including a patient with an
SDHB-deficient GIST. Histologically the SDHB-negative renal carcinomas varied. There was one clear
cell carcinoma with a high nuclear grade, one papillary carcinoma type 2, one unclassified carcinoma
with a glandular pattern, and one oncocytoid low-grade carcinoma as previously described for
SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss
of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the
adrenal, one in the retroperitoneal lymph nodes). There were no cases with SDHB-loss among 64 renal
oncocytomas. SDHB-losses were not seen in other carcinomas, except in one prostatic adenocarcinoma
(1/57), one lymphoepithelial carcinoma of the stomach, and one (1/40) seminoma. Based on this study,
SDHB-losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas.
Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular
genetics of these SDHB-negative tumors requires further study.