Answer: Undifferentiated (anaplastic) thyroid carcinoma

Histology: The thyroid gland is diffusely infiltrated by tumor. The tumor is growing as loosely cohesive sheets of cells without apparent follicular or papillary formations (Image 1). The tumor cells have a distinct epithelioid appearance. They are polygonal in shape with distinct cell borders, and they have enlarged nuclei with prominent nucleoli. Numerous multinucleated tumor giant cells are present (Image 2). At the center of the tumor is a round nodule (Image 3). The cells forming this nodule are growing in a trabecular arrangement. They have pink granular cytoplasm and round uniform nuclei with central nucleoli (Image 4).

Immunohistochemical analysis was performed. The central nodule was reactive for thyroglobulin and thyroid transcription factor (TTF-1), but the surrounding zone of pleomorphic carcinoma was not immunoreactive.

Discussion: Anaplastic thyroid carcinomas are rare thyroid neoplasms that almost always involve older adults (i.e. older than 50). Their incidence seems to be on the decline, probably as a result of the better recognition and more aggressive surgical management of well differentiated thyroid cancer (from which many of these undifferentiated tumors undoubtedly arise). They tend to present clinically as rapidly expanding neck masses. Because these tumors are histologically undifferentiated, their derivation from thyroid follicular epithelial cells is not apparent at the light microscopic level. Thus, correlation with the clinical and radiographic findings is important in addressing the excluding the possibility of direct local extension into the thyroid by some other poorly differentiated malignancy (e.g. laryngeal carcinoma, soft tissue sarcoma).

Histologically, three different forms of anaplastic thyroid carcinoma are recognized: spindle cell, squamoid, and pleomorphic/giant cell. The differential diagnosis varies depending on the particular form. The spindle cell form, for example, is notoriously difficult to distinguish from a true mesenchymal cell sarcoma. Contrary to popular thought, immunohistochemistry is usually not helpful in establishing the follicular epithelial derivation of these anaplastic carcinomas. The overwhelming majority of these tumors are not immunoreactive for thyroglobulin or thyroid transcription factor (TTF-1). Undifferentiated thyroid carcinoma should not be confused with poorly differentiated thyroid carcinoma. The latter tends to grow in an insular pattern, consistently demonstrates immunoreactivity for thyroglobulin, carries a more favorable prognosis, and is treated differently than anaplastic carcinoma.

When encountering an undifferentiated malignancy in the neck, the most powerful evidence to support its thyroid origin is the presence of a pre-existing well-differentiated thyroid carcinoma. Although this component may be overrun by its anaplastic counterpart, it is present as a minor component in the majority of cases. In the present case, the central nodule was recognized as a residual invasive focus of Hurthle cell carcinoma. This finding was very helpful in excluding the possibility of a metastatic implant or local extension from a laryngeal carcinoma.