Squamous Differentiation in the Thyroid: Metaplasia, Neoplasia, or Bystander?

Abstract

Background. Squamous differentiation within the thyroid is seen in a variety of settings. Squamous epithelium is non-native to the thyroid, and its debated origins span reactive metaplasia and developmental/embryologic remnants. Despite a lack of clarity as to its evolution, squamous epithelium may be associated with both neoplastic and non-neoplastic processes. Methods. Thyroid pathology reports spanning a 30-year period were reviewed for terms indicating squamous features. Associated diagnostic and clinical information was collated. Results. Four hundred and twenty seven of 17,452 (2.4%) thyroid surgical pathology cases during this period utilized terminology indicating squamous differentiation including 243 malignant (58%) and 178 benign (42%) diagnoses. There were 111 (26%) primary thyroid malignancies with squamous differentiation, 116 (28%) malignancies of non-thyroid origin including local extension from nearby cancers, and 16 (4%) malignancies of uncertain primary. Most benign lesions were non-neoplastic (84%). The minor subset representing benign neoplasia was interpreted as secondary reactive changes. Conclusion. While squamous differentiation is seen routinely in the thyroid, it is most commonly reported in malignancy. For primary thyroid malignancies reported to demonstrate a squamous component, biologically aggressive tumors were overrepresented. Available evidence suggests that multiple pathways may contribute to the presence of squamous epithelium in the thyroid including metaplasia of mature follicular cells, development from established embryonic remnants, or inception in putative, incompletely characterized stem-like cells. Our retrospective review presents an institutional landscape from which further investigation into the frequency and unique histologic and molecular context of intrathyroidal squamous differentiation as a driver or terminal event in thyroid pathophysiology.

Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach

“…ATC with the squamous cell carcinoma pattern has more frequent BRAF V600E mutation rate and PAX8 immunopositivity than other ATCs [32,33]. Squamous differentiation can be seen not only in ATC, but also in other types of thyroid tumors, including PTC, FTC, PDTC, MTC, mucoepidermoid carcinoma, and intrathyroidal thymic carcinoma [34]. In particular, the histopathologic features of intrathyroidal thymic carcinoma may mimic those of ATC with the squamous cell carcinoma pattern or metastatic squamous cell carcinoma.…”

Primary Squamous Cell Carcinoma of the Thyroid Has a Molecular Genetic Profile Distinct From That of Anaplastic Thyroid Carcinoma

“…The median survival of patients is 6 to 9 months, with a 2-year survival rate of 14% and a passive treatment status. 3 Its biological behavior is very similar to that of anaplastic thyroid carcinoma. 4 Anaplastic thyroid carcinoma (ATC) is a highly aggressive type of thyroid cancer, also known as undifferentiated thyroid cancer.…”

“…Primary SCC of the thyroid progresses rapidly, and its prognosis is extremely poor. The median survival of patients is 6 to 9 months, with a 2-year survival rate of 14% and a passive treatment status 3 . Its biological behavior is very similar to that of anaplastic thyroid carcinoma 4 …”