Diagnosis
Diagnosis
Anaplastic Thyroid Carcinoma
Discussion
Anaplastic Thyroid Carcinoma (ATC) is a highly aggressive and often fatal malignancy originating from the thyroid. It constitutes a minority of thyroid carcinomas and is associated with a rapid and frequently fatal clinical progression1. The current WHO definition notes ATC is a highly aggressive thyroid malignancy composed of undifferentiated follicular thyroid cells which may demonstrate areas of differentiated carcinomas, suggesting evolution from these entities2.
Histologically, three common variants of ATC may be observed either individually or in combined patterns. The epithelial variant, as seen in this case, consists of nests of cohesive tumor cells with squamoid features, which may include frank keratinization. The sarcomatoid variant consists of malignant spindled sarcoma-like cells. The giant cell variant demonstrates pleomorphic cells, including giant cells that may be multinucleated. All forms of ATC may demonstrate a high mitotic count, tumor necrosis, and an infiltrative growth pattern.
Given the anaplastic morphology of the tumor, the histologic differential diagnosis may be broad and include lymphoma, sarcoma, melanoma, and non-thyroidal carcinomas, such as squamous cell carcinoma of the head and neck. Immunostaining can aid in supporting the diagnosis of ATC, including the use of PAX8. PAX8 is a nuclear transcription factor that is expressed in thyroid follicular epithelium. One study of PAX8 staining of ATC demonstrated that the majority of ATCs (76%) expressed PAX8 via immunohistochemistry, with all examined squamoid ATCs demonstrating PAX8 positivity3. In comparison, all 118 examined cases of squamous cell carcinoma of the head and neck were negative for PAX8 immunostaining.
References
Bishop JA, Sharma R, Westra WH. PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Human Pathology. 2011 Dec;42(12):1873-7.
El-Naggar AK, Baloch ZW, Eng C, et al. Anaplastic Thyroid Carcinoma, In: Lyoyd RV, Osamura RY, Kloppel G, Rosai J, editors. WHO Classification of tumors of endocrine organs. Lyons: IARC; 2017. p. 104-6.
Kuhn E, Ragazzi M, Ciarrocchi A, et al. Angiosarcoma and anaplastic carcinoma of the thyroid are two distinct entities: a morphologic, immunohistochemical, and genetic study. Modern Pathology 2019.