[1779] Unique Ultrastructural Features in Pheochromocytoma from Patients with Mutations in the Succinate Dehydrogenase B and D Genes

JM Osman, SF Fliedner, M Abu-Asab, K Pacak, M Tsokos. National Institutes of Health, Bethesda, MD

Background: Pheochromocytomas (pheos) are rare tumors that arise either from the chromaffin cells of the adrenal medulla, or extra-adrenal paraganglionic tissue. They often produce and secrete catecholamines. Although pheos have been classified according to the site of origin, familial history and mutations, a comprehensive ultrastructural comparison has not been carried out before. Traditionally, pheos have been diagnosed with electron microscopy by the presence of secretory granules in tumor cells. It is of high interest from clinical and research perspectives to find out whether ultrastructural features correlate with familial versus sporadic pheos, or with widely known mutations of the succinate dehydrogenase B and D (SDHB/D) genes.
Design: We performed a retrospective EM analysis on adrenal and extra-adrenal tumors from 23 patients. Evaluated ultrastructural features encompassed morphology and numbers of mitochondria and secretory granules, cell processes and intracytoplasmic inclusions (lipid and glycogen). The tumors occurred in the following clinical settings, which were unkown to us at the time of the ultrastructural evaluation: Group 1: sporadic (n=5); Group 2: familial with SDHB (n=8) and SDHD (n=4) mutations; Group 3: in association with VHL (n=4), or MEN (n=2) syndromes.
Results: Pheos occurring in patients with SDHB/D gene mutations exhibited consistently higher numbers of mitochondria when compared to sporadic, as well as VHL- and MEN-associated pheos. Mitochondrial abnormalities were also more commonly encountered in pheos from patients with mutations. In addition, fewer numbers of secretory granules were observed in pheos from patients with SDHB mutation.
Conclusions: The observed unique ultrastructural characteristics in pheos from patients with SDHB/D mutations, i.e. numerous mitochondria and/or sparse secretory granules, distinguish them from pheos occurring in other clinical settings. Therefore, they may be of diagnostic and/or prognostic significance, since tumors with SDHB are known for their high malignant potential.
Category: Ultrastructural

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 250, Monday Morning