Sclerosing Paragangliomas: Correlations of Histological Features with Patients ’ Genotype and Vesicular Monoamine Transporter Expression

AbstractParagangliomas and pheochromocytomas are rare neuroendocrine tumors, carrying a germ-line mutation in 40% patients. Sclerosis is a rare histological feature in these tumors. We investigated the possible correlations between histological findings, first sclerosis, immunoreactivity for vesicular catecholamine transporters (VMAT1/VMAT2) and patients ’ genotype in a consecutive series of 57 tumors (30 paragangliomas and 27 pheochromocytomas) from 55 patients. The M-GAPP grading system, sclerosis (0–3 scale) and VMAT1/VMAT2 (0–6 scale) immunoreactivity scores were assessed. Germ-line mutations of Succinate Dehydrogenase genes, RET proto-onc ogene and Von Hippel Lindau tumor suppressor gene were searched. A germ-line mutation was found in 25/55 (45.5%) patients, mainly with paraganglioma (N = 14/30, 46,66%). Significant (score ≥ 2) tumor sclerosis was found in 9 (16.1%) tumors, i.e., 7 paragangliomas and 2 pheochromocytomas, most of them (8/9) from patients with a germ-line mutation. M-GAPP score was higher in the mutation status (in 76% of patients involving theSDHx genes, in 12% the RET gene and in the remaining 12% the VHL gene) and in tumors with sclerosis (p  <  0.05). Spearman’s rank correlation showed a strong correlation of germ-line mutations with M-GAPP (p <  0.0001) and sclerosis (p = 0.0027) scores; a significant correlation was also found between sclerosis and M-GAPP scores (p = 0.029). VMAT1 expression was higher in para...
Source: Head and Neck Pathology - Category: Pathology Source Type: research