(14.08) A Mass that Would Not Stop: The Rapid Growth of a Papillary Thyroid Cancer into an Invasive Anaplastic Cancer with Squamous Differentiation

Squamous epithelium is not a tissue native to the thyroid, and its origins are hypothesized to be reactive metaplasia to remnants of the thyroglossal duct and branchial pouch. Squamous differentiation (SD) in the thyroid can be seen in many diseases, from benign conditions such as chronic lymphocytic thyroiditis, to malignancies such as anaplastic thyroid carcinoma (ATC), including the squamous cell carcinoma (SCC) subtype. Squamous differentiation however is reported more commonly in malignant cases than benign.

Case(s) Description :

A 42-year-old Hispanic male with no significant past medical history presented to the emergency department with a four-month history of a progressively enlarging right-sided neck mass. Associated compressive symptoms included odynophagia (to solids and liquids), right-sided neck pain, voice changes, and a recurrent right-sided headache that started concurrently with the onset of the neck mass. On CT he was found to have a complex mass arising from the right lobe of the thyroid gland, measuring 10 x 9.4 cm axially, with multiple calcifications. MRI of the brain showed a 9 x 8 mm heterogeneous ring enhancing lesion in the posterior aspect of the right frontal lobe . On bloodwork, his TSH was 0.886 (0.35 - 5.5 UIU/mL) and free T4 1.12 (0.9 - 1.8 ng/dL). Thyroid FNA showed a Bethesda Category VI carcinoma with squamous differentiation and necrosis. Molecular testing was positive for a BRAF V600E mutation.

He underwent a total thyroidectomy and radical lymph node dissection, with pathology positive for ATC with squamous differentiation, transformed from papillary thyroid carcinoma (PTC), classic subtype. Histologic sections of the neck dissection showed a partially encapsulated and invasive well-differentiated PTC. Staining on the PTC was strong for CK7, PAX-8, and TTF1.The mass measured over 11cm and extended anteriorly in the subcutaneous fat, and laterally and posteriorly into the right piriform sinus, with positive lymph nodes (3/35). Despite efforts to remove the tumor in completion, a one-centimeter focus of gross disease at the thoracic inlet between the trachea and the carotid takeoff was left behind. Given the extent of the tumor infiltration, the patient underwent a right pharyngectomy. After surgery, he was started on radiation therapy to the neck and combined chemotherapy with carboplatin and paclitaxel.

Discussion :

Previously, SCC of the thyroid was listed as separate tumor classification by the World Health Organization (WHO), however now it is classified as a subtype of ATC. ATC often have a BRAF V600E mutation along with history of concurrent PTC or other differentiated thyroid carcinomas, with BRAF considered an early driver mutation. Staining for CK5/6, P63, and TTF1 suggest development from PTC to squamous cell differentiation. Other cases have found that PTC with squamous differentiation are more aggressive tumors with a poor prognosis. These findings may suggest that patients with thyroid markers or pathology concerning for squamous features may have a more aggressive cancer subtype with worse prognosis than without squamous differentiation.