Answer: Hyalinizing trabecular adenoma

Histology: The tumor is thinly encapsulated throughout. There is no evidence of invasive tumor growth. There is a striking trabecular pattern of growth. Uniform nests of cells are set in an acellular hyalinized stroma. The tumor nests have a zonal appearance: The nuclei are placed at the periphery; while toward the center of the nests the individual tumor cells are enveloped by the hyalinized stroma and their nuclei fade away into this pink background. The tumor cells have abundant pink cytoplasm. The nuclei are enlarged, elongated and grooved; but they are evenly spaced without crowding and overlap. Many of the nuclei contain prominent pink inclusions. The tumor cells are immunoreactive for TTF-1 and thyroglobulin; and they are not immunoreactive for calcitonin (immunohistochemistry not shown).

Discussion: Hyalinizing trabecular adenoma (HTA) is a low grade neoplasm of the thyroid that was first described by Carney in 1987. Its distinguishing morphologic features are its prominent trabecular growth pattern and its striking intra- and extra-cellular hyalinization. It is generally included in the differential diagnosis of other thyroid tumors that exhibit a prominent trabecular pattern of growth including cellular forms of follicular adenoma (e.g. embryonal form of follicular adenoma), medullary carcinoma, paraganglioma and trabecular variant of papillary carcinoma (PTC).

Of these, HTA is notable for ways in which it overlaps with PTC. Morphologically, HTA has nuclei with exaggerated features of PTC including elongation, inclusions, pallor and grooves. Stromal calcifications resembling psammoma bodies are also frequently noted. Biologically, HTAs have been shown to harbor some of the same genetic mutations as PTC (i.e. ret oncogene translocations). HTAs often arise in thyroid glands that harbor foci of PTA, and sometimes there may even be a direct association between HTA and conventional PTC. Because of this overlap, some pathologists argue that the HTA represents a low grade form of PTC and are best classified as hyalinizing trabecular neoplasm – a diagnostic term that leaves some room for uncertainty regarding potential malignant behavior. I have not observed any examples of metastatic HTA, and I am unaware of any convincing examples as published in the literature. For those hyalinizing trabecular neoplasms that do not show any invasive tumor growth, I am comfortable designating these as benign adenomas.

The nested pattern of growth may cause confusion with medullary carcinoma or the rare thyroid paraganglioma, but the origin of HTA from the follicular epithelium is readily confirmed by immunohistochemical staining (i.e. thyroglobulin positive, TTF-1 positive, PAX8 positive, calcitonin negative, chromogranin negative).