Secretory Carcinoma of the Thyroid Gland: Report of a Highly Aggressive Case Clinically Mimicking Undifferentiated Carcinoma and Review of the Literature

Abstract

After being described in the salivary glands as a malignancy with features essentially identical to those of the breast, secretory carcinoma (SC) (formerly mammary analogue SC) has now been identified in other sites including the skin, lung, and thyroid gland. In the breast, SC has a relatively favorable prognosis. Likewise when arising in the salivary glands, it is generally considered to be a low to intermediate grade carcinoma; however, there is a range of clinical behavior with occasional patients dying of progressive disease. SCs of the thyroid gland are rare, and reports suggest a relatively aggressive behavior, at least relative to well differentiated carcinomas such as papillary carcinoma and minimally invasive follicular carcinoma. We present a patient with a highly aggressive thyroid gland SC that mimicked undifferentiated carcinoma clinically. The patient had widespread metastatic disease and died rapidly from airway compromise. We also review the literature for reported cases of thyroid gland SC in order to better establish the clinical features and expected clinical course of such tumors occurring at this site.

Keywords: Anaplastic carcinoma; ETV6 gene rearrangement; Mammary analogue secretory carcinoma; Papillary carcinoma; Thyroid.

Fig. 1

a Coronal post-contrast computed tomography neck image through the trachea (endotracheal tube in place) showing massive bilateral enlargement of the thyroid gland (T), extending inferiorly to the aortic arch and superiorly to the top of the thyroid cartilage. Bulky right middle and inferior lateral neck adenopathy (*). b Axial computed tomography chest maximum intensity projection image (15 mm thickness) showing multiple, bilateral, rounded lung metastases

Fig. 2

a, b Fine needle aspiration smear is hypercellular with cohesive sheets and clusters of monomorphic cells with vaguely acinar and pseudopapillary structures (‘tentacular nubbins’). c, d The tumor cells show dispersed chromatin with variably prominent, centrally-placed nucleoli, occasional grooves, and abundant, vacuolated, eosinophilic cytoplasm. Eosinophilic colloid-like secretions are present

Fig. 3

a–d Hematoxylin and eosin-stained sections of the thyroidectomy specimen demonstrating lobules of tumor separated by hyalinized stroma, composed of cells arranged in various architectural patterns ranging from solid to trabecular to micropapillary to cribriform. Large areas of necrosis are present (indicated by N). Intraluminal eosinophilic secretions are present with peripheral vacuolization. The tumor cells have large, round to ovoid nuclei with vesicular chromatin, central nucleoli, and abundant granular, eosinophilic cytoplasm. e The secretions are positive on periodic acid Schiff (PAS) staining. f Immunohistochemistry for GATA-3 showed strong diffuse nuclear staining. g Immunohistochemistry for GCDFP-15 showed patchy positive cytoplasmic staining. h Immunohistochemistry for S-100 showed extensive, but moderate intensity, nuclear and cytoplasmic staining

Fig. 4

Fluorescence in situ hybridization using ETV6 dual color, break apart rearrangement probes demonstrates ETV6 rearrangement in 100% of tumor cells. 22% of cells have the typical pattern of one intact gene (red and green signals together) and one rearranged gene (separate red and green signals). 78% of cells have a unique pattern of one intact gene and one rearranged gene with two red signals (ie; gain of red signal)