ANAPLASTIC THYROID CARCINOMA
Anaplastic thyroid carcinoma comprises approximately 1.7% of all cases of thyroid cancer . Ninety percent of cases occur in patients over the age of 50 [9, 14], with an average age of presentation between 55-65 . The disease exhibits an approximately 1.5-2:1 female to male ratio [2, 3, 14]. It is a very aggressive malignancy with a poor prognosis; the average survival time following diagnosis is typically six months or less [2,14]. The most common site of metastasis is the lungs, with other metastatic sites including bone, skin, and the brain [3, 14, 16].
Clinically, anaplastic thyroid carcinoma often presents as a quickly growing and firm lesion in the neck, and it may be associated with vocal cord paralysis, hoarseness, weight loss, and dyspnea [1,5]. On average, it is typically diagnosed approximated 1.5 months after its initial onset, with an approximate range of 0-8 months [14,18]. According to the AJCC Cancer Staging Manual (7th edition), all anaplastic thyroid carcinomas are classified as Stage 4. T4a classification is given to intrathyroidal tumors, while T4b lesions have gross extrathyroidal extension. This case was staged as a T4b tumor. No (0/9) positive lymph nodes were identified .
Grossly, anaplastic thyroid carcinoma is often tan-white, with areas of hemorrhage and necrosis. It characteristically has an infiltrative appearance . Cytologically, it features spindle or epitheloid shaped tumor cells, pleomorphic and hyperchromatic nuclei, coarse chromatin clumping, and in some cases, giant cells . Similarly, histologic sections of anaplastic thyroid carcinoma may show a spindle cell, giant cell, or squamoid morphology . There are also paucicellular, carcinomosarcomatoid, and lymphoepitheloid variants [1,14]. Typically, a high number of mitotic figures are identified . Most cases immunohistochemically stain for cytokeratin AE1/AE3 and vimentin, and have overexpression of TP53 . In one series of 34 cases of anaplastic thyroid carcinoma, positive PAX8 immunostaining was identified 76% of the time, and has been suggested as an especially useful marker in helping to distinguish the squamoid variants of anaplastic thyroid carcinoma from squamous cell carcinomas of the head and neck. In spite of this, however, only 50% of the spindle variants, as was seen in this case, stained positively for this marker . While anaplastic thyroid carcinoma is typically negative for TTF-1, this stain may still be positive in adjacent areas of well-differentiated thyroid carcinoma . BRAF mutations have been identified in approximately 24% of anaplastic thyroid carcinomas, and may indicate that such tumors are arising from cases of papillary thyroid carcinoma .
The differential diagnosis for anaplastic thyroid carcinoma includes a medullary thyroid carcinoma, metastatic neoplasms to the thyroid, and poorly differentiated thyroid carcinoma. Care must be taken not to diagnose the lymphoepitheloid variant as a lymphoma, or the paucicellular variant as a Reidel's thyroiditis [3,19].
As mentioned above, the prognosis in cases of anaplastic thyroid carcinoma is grim. The five year survival rate for patients is typically 0-14% . Although not universally agreed upon , some have described a younger age (under 60) and a tumor size of 7cm or less as favorable prognostic factors [12,14]. Appropriate patients may undergo surgical resection , although a majority of patients may not be eligible for a complete resection . Chemoradiation therapy has also been used in treatment, although most patients still carry a poor prognosis .
In summary, the lesion in this case has a spindle cell morphology, is juxtaposed to an area of well-differentiated papillary thyroid carcinoma, and stains positively for cytokeratin AE1/AE3 and P53, while only the adjacent papillary thyroid carcinoma stains positively for TTF-1. These features all support the above diagnosis of anaplastic thyroid carcinoma.
Contributed by Tanner Bartholow, MD, MS.