A 50-year-old man presented with an incidentally diagnosed calcified goiter on imaging procedures intended to evaluate rib fractures from a auto roll-over accident. The thyroid was enlarged (90 mm×70 mm×27 mm), plunging retrosternally into the mediastinum. The patient had also experienced generalized tonic-clonic seizures 13 and 3 years previously, and had been undergoing treatment with levetiracetam (2×500 g/day) for the past 3 years. The patient’s serum calcium, as well as the prothrombin time and activated cephalin time, fell within normal range. Thyroidectomy was performed, and the microscopic diagnosis was nodular goiter with fibrosis and dystrophic calcifications. A 3-mm encapsulated nodule was incidentally identified in the left lobe of the resected thyroid gland with extensive calcification comprising 75%-90% of the nodule surface on different tissue sections (supplementary Fig. 1). The tumor cells showed a vesicular arrangement, nuclear incisions, and inclusion, and they also diffusely expressed cytokeratin 19 (CK19). Several tumoral vesicles were directly surrounded by a calcified matrix, which also contained isolated nuclei. One focus of invasion was seen in the relatively thick capsule of the nodule. Dystrophic calcification was seen in a perinodular fibrous tract and in the colloid, as well as in a perithyroid blood vessel wall (von Monckeberg type). Postoperatively, calcemia was normal and a substitutive thyroid hormone treatment was started.

The origin of the dystrophic calcification in the thyroid microcarcinoma we report was difficult to precisely determine. The presence of a nodular carcinoma-specific microenvironment, characterized by the diffuse expression of the acid cytokeratin CK19 (OMIM 148020) in tumor cells, could be implicated in the genesis of the extensive, pan-nodular dystrophic calcifications. Moreover, several dystrophic nuclei were observed in the calcified matrix, suggestive of necrosis, also considered a pro-calcification microenvironment [5]. Hemorrhagia and hematoma are also considered procalcification microenvironments. In the case we present, both acute and chronic hemorrhagia-related lesions, such as fibrosis and pigmented macrophages, were present in the resected thyroid, including at the proximity of the calcified nodule. Moreover, a large malformed cavitary intrathyroid blood vessel, the origin of abnormal oxygenation and possible hemorrhage, was observed 4 mm from the calcified microcarcinoma. We concluded that dystrophic macrocalcifications may occur in thyroid microcarcinomas, more likely as a result of the tumor microenvironment than of systemic abnormal calcium metabolism.