Renal carcinoma with giant mitochondria associated with germ‐line mutation and somatic loss of the succinate dehydrogenase B gene

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

“…In addition, LOH seems to constitute the main mechanism of inactivation of the WT allele in these tumors as observed in SDHx-related tumorigenesis (40,53). Taking into consideration: i) the rarity of SDHB-related RCC cases (8,11,14,16,21,22,23,25,26,27,28,29,30,31,32,35,54); ii) the broad distribution of various germline mutations (missense, nonsense, frameshift, and splice site) and large deletions throughout the SDHB gene ( Supplementary Fig. 3, see section on supplementary data given at the end of this article); and iii) the fact that mutations within the same codon can generate variable phenotypes (current study, SDHB c.3GOA p.Met1Ile; PCC/PGL and/or RCC), previous challenges in establishing genotype-phenotype correlations become conceivable (22).…”

“…Biallelic inactivation of SDHx genes has only been reported in six RCC cases (8,16,20,21), two PAs (5,6), one NBL (14), and one testicular seminoma (15) but was not identified in a PA (7), PTC (16), or small-cell lung carcinoma (8). Despite the fact that SDHx inactivation may contribute to these particular phenotypes, the significance of this contribution remains unclear given the relative lack of studies displaying an increased lifetime risk for these tumors arising in the context of an SDH-deficient state (22).…”

Succinate dehydrogenase-deficient renal cell carcinoma: detailed characterization of 11 tumors defining a unique subtype of renal cell carcinoma

“…[1][2][3] In addition to paraganglioma and GIST, there is increasing evidence that patients with germline mutation of SDH subunit genes also develop renal tumors, 4 which, similar to paragangliomas and GISTs in such patients, lack immunohistochemical labeling for SDHB in the neoplastic cells. 5,6 Many of the renal tumors that have been recognized to date in these patients exhibit distinctive morphology, characterized by sheets of uniform cells with eosinophilic or oncocytic cytoplasm that contain cytoplasmic vacuoles or flocculent inclusions. [5][6][7][8] However, renal cell carcinomas (RCCs) with other histologic appearances have been reported in patients with germline mutations of SDH subunit genes, 4,9 and a few RCCs of other histologic types have been found to be SDH-deficient in the absence of known germline gene mutation.…”

“…5,6 Many of the renal tumors that have been recognized to date in these patients exhibit distinctive morphology, characterized by sheets of uniform cells with eosinophilic or oncocytic cytoplasm that contain cytoplasmic vacuoles or flocculent inclusions. [5][6][7][8] However, renal cell carcinomas (RCCs) with other histologic appearances have been reported in patients with germline mutations of SDH subunit genes, 4,9 and a few RCCs of other histologic types have been found to be SDH-deficient in the absence of known germline gene mutation. 8,10 Nonetheless, experience with SDH-deficient RCC demonstrating this unique oncocytic histology remains very limited.…”

“…11 Detailed pathologic features and immunohistochemical staining results for renal tumor antigens have been reported in only four tumors with this unique morphology. 5,6 Therefore, the precise constellation of features that differentiates these neoplasms from other subtypes of renal tumors remains poorly understood. To facilitate discrimination of these SDH-deficient oncocytic renal tumors from other benign and malignant renal neoplasms and to elaborate the spectrum of their pathologic features, we performed a detailed analysis of clinicopathologic, immunohistochemical, and genetic features of SDH-deficient RCCs.…”