Published in:
07-05-2022 | Neuroendocrine Tumor | Original Paper
Sclerosing Paragangliomas: Correlations of Histological Features with Patients’ Genotype and Vesicular Monoamine Transporter Expression
Authors:
Angela Pucci, Alessandra Bacca, Ivana Barravecchia, Iosè Di Stefano, Beatrice Belgio, Daniele Lorenzini, Liborio Torregrossa, Serena Chiacchio, Caterina Congregati, Gabriele Materazzi, Mauro Ferrari, Debora Angeloni, Giampaolo Bernini, Fulvio Basolo
Published in:
Head and Neck Pathology
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Issue 4/2022
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Abstract
Paragangliomas 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-oncogene 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 the SDHx 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 paragangliomas than in pheochromocytomas (p = 0.0006), the highest scores being more frequent in mutation-bearing patients’ tumors (p < 0.01). VMAT2 was highly expressed in all but two negative tumors. Sclerosis and VMAT1 expression were higher in
paragangliomas than in pheochromocytomas;
tumor sclerosis, M-GAPP and VMAT1 scores were associated to germ-line
mutations. Sclerosis might represent a histological marker of tumor
susceptibility, prompting to genetic investigations in paragangliomas.