A newly identified type of renal carcinoma that is associated with succinate dehydrogenase deficiency should become more recognizable now that its distinctive clinical and morphologic features are beginning to be characterized, according to a report published online in the Journal of Clinical Oncology.
A case report of a 27-year-old man who presented with left shoulder pain and on imaging was found to have a destructive lesion in the humerus, widespread skeletal metastases, and bilateral renal tumors was reported by Dr. Julie Y. Paik of Royal North Shore Hospital, Sydney, Australia, and her associates.
Although a biopsy of the humerus clearly revealed carcinoma, the neoplastic cells were not typical for conventional clear-cell renal carcinoma. Some contained distinctive, prominent cytoplasmic inclusions filled with clear or pale eosinophilic or vacuolated material, but it was not until 2 years later that this feature was recognized as representing the newly described entity of succinate dehydrogenase–deficient renal carcinoma.
As part of the screening process for a clinical trial 2 years after presentation, succinate dehydrogenase–deficient renal carcinoma was confirmed by simple succinate dehydrogenase B (SDHB) immunohistochemistry. Genetic testing was recommended. A detailed family history revealed that a male cousin had died at age 37 years from metastatic renal cancer, and germline mutation testing confirmed that the patient and his mother both carried a mutation in the succinate dehydrogenase B gene. Despite the correct diagnosis and an initial response to treatment with pazopanib, the patient soon died from metastatic disease at the age of 29.
"With awareness, this disease entity can be recognized prospectively, primarily on the basis of morphology alone, and confirmed with immunohistochemistry," the authors wrote. Succinate dehydrogenase is necessary for respiration, and the most important morphologic clue to the diagnosis is the prominent cytoplasmic inclusions that are either clear or contain pale eosinophilic material, indicative of giant mitochondria.
Additional microscopic features of SDH-deficient renal carcinoma include well-circumscribed or lobulated borders with entrapment of nonneoplastic parenchyma at the periphery; cuboidal tumor cells with indistinct borders arranged in trabeculae or "nests" supported by a fine fibrovascular network, resulting in an architecture reminiscent of paraganglioma/pheochromocytoma; and abundant cytoplasm with a granular or bubbly quality, reported Dr. Paik and her associates (J. Clin. Oncol. 2014 Jan. 6 [doi:10.1200/JCO.2012.47.2647]).
"We recommend that immunohistochemistry for SDHB be performed on renal tumors with this distinctive histology or with clinical features that suggest syndromic disease," such as a family history of renal carcinoma, young age at onset, and bilateral or multifocal disease, the authors said.
Dr. Paik reported no financial conflicts of interest; her associates reported ties to Pfizer, Cook Medical, Novartis, and Roche.