Abstract
Disclosure: D. Diaz Ruiz: None. R.V. Chemitiganti: None. D. Suravajjala: None. J. Case: None. Mrs. CS is a 69-year-old female with a medical history of Hashimoto thyroiditis evaluated for incidentally detected thyroid nodules. She was euthyroid and was found to have multiple nodules on thyroid sonography - Two TI-RADS 5 (TR5) nodules in the right mid pole(3cm) and inferior pole(1.8cm) and a third TR2 nodule in the in the inferior pole (<1 cm). She declined a biopsy and was lost to follow-up during the Covid pandemic. She returned for new pressure symptoms in the neck and now had a large palpable right thyroid mass. A repeat sonogram now showed a TR5 thyroid nodule (4.4 cm) of the right lower pole. The other two TR5 nodules were unchanged. Thyroid FNA biopsy indicated - malignant, poorly differentiated carcinoma of thyroid origin (Bethesda stage VI). The cytology and cell block preparations were cellular and showed sheets of epithelial cells with crowded round to ovoid nuclei. The nuclei showed rare intranuclear inclusions. Immunohistochemical stains were positive for both TTF-1 and PAX-8. BRAF p.V600E c.1799T>A were negative. RET/PTC1, RET/PTC3 were not detected. She underwent an uneventful total thyroidectomy; the surgical pathology report revealed a Cribriform Thyroid Cancer (CTC) with vascular invasion. Post Thyroidectomy I-131 whole body scan was positive for only focal uptake on the right thyroid bed extending into the right lower neck. Bone scan, Head and chest CT were negative for metastases. Cancer genome sequencing studies identified Serine/threonine kinase 11 (STK11) and Kelch-like ECH-associated protein 1 (KEAP1) mutations. Adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) mutations were absent. Cribriform Thyroid Cancer is proposed as a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells. It is an extremely uncommon malignancy that usually affects younger women (18-59 yrs; mean age 33). They were initially described as cribriform variant of papillary thyroid cancer associated with familial adenomatous polyposis (FAP) syndrome. Sporadic forms are known to occur due to somatic alterations in the Wnt/beta-catenin pathway. Germline or somatic mutations of Adenomatous polyposis coli (APC) gene and somatic mutations of the beta-catenin (CTNNB1) gene are usually present in CTC. Inherited mutations in the STK11 gene are associated with Peutz-Jeghers syndrome and an increased risk of developing other cancers. While KEAP1 somatic mutations disproportionately occur in non-small-cell lung, liver, endometrial, bladder and squamous cell cancers. Human germline mutations in KEAP1 are rare. One report in a five-generation multinodular goiter family identified the first KEAP1 mutation, none are yet to be reported in a sporadic form of CTC. This case showcases and adds to our knowledge of unique mutations associated with sporadic form of CTC. Presentation: 6/3/2024