Thyroid lesions of neuroendocrine origin? Thinking of a “polka‐dotted” zebra! Case series from three Italian referral centers and review of the literature

Background: Neuroendocrine neoplasms (NENs) may metastasize very rarely to the thyroid. The current paper aims at identifying peculiar thyroid nodule's features that could prompt their diagnosis and analyzing therapeutic approach and patient's outcome. Materials and Methods: A case series of three patients have been collected from three Italian referral centers. Moreover, we performed a keyword based PUBMED search, using relevant keywords. Results: We included in the review 27 papers and 33 cases have been identified. Patients’ age ranged from 17 to 85 years (mean age: 55.8 ± 14.2 years), 14 males, 42.4%. The majority of cases (48.5%) originated from a thoracic NEN. Median time to diagnosis from the primary tumor was 48 months (range 1–252 months). At ultrasound, they were generally hypoechoic nodules with irregular margins. The diagnosis was made by fine-niddle aspiration in the majority of cases, followed by nuclear medicine imaging. At immunohistochemistry, chromogranin A and synaptophysin were expressed in almost all of them, with negative calcitonin and thyroid transcription factor-1. Surgery or systemic treatment were needed according to primary tumor, disease stage, and patients’ general condition. Prognosis was variable, better if primary tumor origin was thoracic. Conclusions: Thyroid metastases from NENs should be considered in the diagnostic work-up of suspicious thyroid nodules in patients with a positive medical history of previous NEN, mainly of thoracic origin. Immunohistochemistry is the key diagnostic tool for their identification. A prompt and correct diagnosis is mandatory because of its crucial prognostic and therapeutic implications.