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      Concomitant medullary thyroid carcinoma with paraganglioma-like pattern and papillary thyroid carcinoma

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          Abstract

          Summary

          A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0–7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors.

          Learning points:
          • Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern.

          • We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary.

          • Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.

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          Most cited references 10

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          Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

          The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates.
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            The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer.

            The diagnostic value of calcitonin measurement in fine-needle aspiration biopsy (FNAB) wash-out fluid (Ct-FNAB) for medullary thyroid cancer (MTC) remains to be determined. This prospective study aimed to assess the diagnostic value of Ct-FNAB in thyroid nodules in comparison with basal serum calcitonin (Ct), pentagastrin-stimulated Ct (Pg-sCt), and cytology.
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              C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

              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.
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                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                06 November 2019
                2019
                : 2019
                Affiliations
                [1 ]Unit of Endocrinology , Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
                [2 ]Unit of Endocrinology , Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
                [3 ]Department of Diagnostic , Clinical Medicine and Public Health, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
                Author notes
                Correspondence should be addressed to G Brigante; Email: giulia.brigante@ 123456unimore.it
                Article
                EDM190094
                10.1530/EDM-19-0094
                6893314
                31778356
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                Categories
                Geriatric
                Male
                White
                Italy
                Thyroid
                Thyroid
                Calcitonin
                TSH
                Medullary Thyroid Cancer
                Papillary Thyroid Cancer
                Goitre (Multinodular)
                Goitre
                Calcitonin
                Thyroid ultrasonography
                Fine needle aspiration biopsy
                Histopathology
                Immunohistochemistry
                Chromogranin A
                Carcinoembryonic antigen
                Thyroid transcription factor-1
                S-100 protein*
                TSH
                Thyroglobulin
                CT scan
                PET scan
                Thyroidectomy
                Lymph node dissection
                Radioiodine
                recombinant human TSH*
                Oncology
                New Disease or Syndrome: Presentations/Diagnosis/Management
                New Disease or Syndrome: Presentations/Diagnosis/Management

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