(15.06) PAX 8 to the rescue: A case of anaplastic thyroid cancer histologically being confused with squamous cell carcinoma

Anaplastic thyroid carcinoma (ATC) are a rare and fatal malignancy accounting for 1-2 percent of all thyroid cancers. Paired Box Gene-8 (PAX 8) is an important transcription factor which is persistently expressed in differentiated thyroid carcinomas, however recent literature suggests up to 76-78 percent expression in patients with ATC indicating possible diagnostic utility. Here we present a case of undifferentiated carcinoma with a pathologic and clinical dilemma of the primary tissue being tracheal versus thyroid, which was answered by the PAX 8 Immunostain. 

 


Case(s) Description : A 76-year-old male presented to the emergency department in September 2023 with worsening shortness of breath, hemoptysis, and hoarseness of voice for several months. Notably, the patient was followed for stable thyroid nodules from 2017 to 2022, with the last thyroid ultrasound demonstrating the greatest nodule on the right lobe measuring 1.6 cm. During this hospitalization, CT with contrast of the neck revealed an enlarged right thyroid lobe mass with calcifications and significant tracheal lumen irregularities. Ultrasound of the thyroid revealed a 3.6 cm right-sided, poorly defined nodule and a 1.9 cm right-side level III cervical lymph node. Initially, interventional radiology guided fine needle aspiration of the right thyroid nodule was reported as possible squamous cell carcinoma with no immunohistochemistry (IHC) due to limited tumor cells. The patient underwent direct laryngoscopy and bronchoscopy. Intraoperatively, the patient was found to have significant intraluminal disease extending 4.5 cm down the trachea. Initial histopathology of the tracheal mass was reported as moderately differentiated invasive squamous cell carcinoma, negative for TTF1, thyroglobulin, and BRAF V600, favoring tracheal in origin. However, after discussion at the head and neck tumor board and imaging more consistent with thyroid origin, PAX 8 IHC was requested and returned positive, consistent with ATC. The patient is now being treated as ATC with chemotherapy and radiation.

Discussion : Histopathologically, ATC is categorized into three variants: squamous, giant cell, and sarcomatoid. Due to loss of differentiation of the thyroid tissue, ATC can be confused with squamous cell carcinomas of the head and neck. Immunohistochemistry becomes critical for the correct diagnosis given different treatment strategies and prognosis. PAX 8 immunostain has been shown to be negative in squamous cell carcinoma of the lung, esophagus, larynx and pharynx. On contrary, literature suggests that PAX 8 expression is retained in ATC (76-79%) indicating a possible diagnostic role in undifferentiated malignancy of the head and neck.