title: C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.
abstract: In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal University of Yamanashi, Yamanashi, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: University of Santiago de Compostela, IDIS, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Cameselle-Teijeiro
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Vinagre
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Medical Faculty of the University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.affiliation: CHMouscron, Mouscron, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rousseau
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Central Hospital of S João, Porto, Portugal University of Porto, Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Eloy
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal Medical Faculty of the University of Porto, Porto, Portugal Central Hospital of S João, Porto, Portugal ssimoes@ipatimup.pt.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000368:Aged; D002116:Calcitonin / Q000096:biosynthesis; D018278:Carcinoma, Neuroendocrine / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D013964:Thyroid Neoplasms / Q000175:diagnosis*
chemical_list: D002116:Calcitonin
keywords: calcitonin; medullary thyroid carcinoma; metastatic carcinoma; neuroendocrine carcinoma; parafollicular cell (C-cell); paraganglioma; thyroid gland