THU540 Cribriform Morular Thyroid Carcinoma In A Young Female With Prior Exposure To Whole-Body Radiation For Metastatic Wilms’ Tumor
Authors: Caesario Darell , Richardson Mary S , Carneiro-Pla Denise , Kanwar Fernandes Jyotika 
Published: October 2023

Disclosure: D. Caesario: None. M.S. Richardson: None. D. Carneiro-Pla: None. J.K. Fernandes: None.

Introduction: Cribriform morular thyroid carcinoma (CMTC) is a rare thyroid cancer that is classically associated with familial adenomatous polyposis (FAP), but can also occur sporadically. We report a case of CMTC in a young female with history of whole-body radiation therapy (WBRT). Case Report: A 19-year-old female with past medical history of Wilms’ tumor (WT) with lung metastasis status post left nephrectomy and WBRT at the age of 6 was seen for newly diagnosed thyroid nodules. Physical exam was remarkable for thyromegaly. Thyroid function tests were normal. Thyroid ultrasound revealed 2 dominant TI-RADS 4 nodules measuring 1.9 x 1.7 x 2.1 cm on the left lobe and 0.9 x 0.8 x 0.8 cm on the right lobe. No suspicious lymphadenopathy. Fine needle aspiration biopsy on both nodules showed findings consistent with papillary thyroid carcinoma (PTC). No family history of thyroid disorders, malignancies, or FAP. She underwent total thyroidectomy with central neck node sampling. Thyroid gland surgical pathology result revealed CMTC positive for thyroid transcription factor-1 (TTF-1), β-catenin, and cytokeratins 5 and 6. It was negative for calcitonin. There was no evidence of invasion, extension, or lymph node metastasis. Genetic tests are currently pending. Discussion: CMTC was previously considered a variant of PTC, accounting for 0.2 to 6% of PTC cases. However, recent observations have challenged this view, and latest WHO update reclassified it as a distinct form of thyroid cancer. It is associated with an indolent clinical course and good prognosis. It almost exclusively affects young women. Both familial and sporadic cases are associated with mutations in the adenomatous polyposis coli (APC) gene. The APC protein is a negative regulator that controls β-catenin concentrations, which is involved in cell adhesion. Mutations in the APC gene may result in FAP and colorectal cancers. In cases associated with FAP, the tumors are usually multifocal and/or bilateral, while sporadic cases usually appear as single nodule. Tumor cells are always positive for TTF-1 and negative for calcitonin. They can also be positive for multiple cytokeratins, but strong nuclear and cytoplasmic staining for β-catenin is the hallmark of this tumor type. The case above occurred in a young female with no significant family history, but who underwent WBRT for WT as a child. Radiation is a known predisposing factor for thyroid cancer, and limited studies on early exposure to radiation revealed higher incidence of sporadic CMTC. However, even among FAP associated cases, CMTC diagnosis preceded that of FAP in up to 40% of the cases. Additionally, up to 20% of WT cases have mutations of the WT1 gene, and among these, at least half also carry acquired somatic mutations in CTNNB1, the gene encoding β-catenin. So far, there has been no reported case of CMTC in the background of WT. It will be interesting to see if she has these underlying mutations.

Presentation: Thursday, June 15, 2023