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 set in an acellular hyalinized stroma with focal dystrophic calcifications. The tumor cells have abundant pink cytoplasm. In areas, individual tumor cells are enveloped by the hyalinized stroma. The tumor cells have nuclei that 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 (HTN), as the name indicates, is a thyroid neoplasm characterized by a trabecular growth and prominent extracellular and intracellular deposition of collagen. Some have questioned the legitimacy of this tumor as a distinct tumor entity as trabecular growth can be encountered in various benign (e.g. follicular adenoma) and malignant (e.g. trabecular variant of papillary carcinoma) thyroid neoplasms. What appears to separate this tumor apart from other tumors with trabecular architecture is the distinct hyalinized stroma enveloping individual tumor cells. There is also considerable confusion surrounding the malignant potential of this neoplasm. Once considered a peculiar variant of a follicular adenoma, some now believe that the HTA is more closely related to a low-grade papillary carcinoma. This shifting perspective is based on the following observations:

1) a number of cases have been reported of conventional papillary carcinoma arising from a HTA.

2) Papillary carcinoma and HTN share several key morphologic characteristics including the presence of psammoma bodies, and nuclei that are elongated, grooved, and optically clear with inclusions. And

3), at the genetic level papillary thyroid cancer and HTA also share a common alteration (i.e. activating RET/PTC gene rearrangements). Whatever their relationship to papillary carcinoma, tumors showing classic features of HTA do not appear to have any metastatic potential and should be regarded as clinically benign.

Because of the tremendous morphologic overlap, HTN may be confused with papillary carcinoma, particularly on fine needle aspirates. HTN lacks the papillary architecture of conventional papillary carcinoma, and its nuclei are less crowded and non-overlapping. The nested pattern of growth may cause confusion with medullary carcinoma the rare thyroid paraganglioma, but the origin of HTA from the follicular epithelium is readily confirmed by TTF-1 and thyroglobulin immunohistochemistry.