Abstract
We report a case of a 22-year-old female patient who was diagnosed with a cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC). While at early ages this thyroid cancer variant is highly suggestive for familial adenomatous polyposis (FAP), there was no family history of FAP. In the tumor biallelic, inactivating APC variants were identified. The patient tested negative for germline variants based on analysis of genomic DNA from peripheral blood leukocytes. Somatic mosaicism was excluded by subsequent deep sequencing of leukocyte and normal thyroid DNA using next generation sequencing (NGS). This report presents a rare sporadic case of CMV-PTC, and to the best of our knowledge the first featuring two somatic APC mutations underlying the disease, with an overview of CMV-PTC cases with detected APC and CTNNB1 pathogenic variants from the literature.
Highlights
The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare subtype of differentiated thyroid cancer and generally has a good prognosis [1]
CMV-PTC has a distinctive histologic morphology featuring morules and a cribriform growth pattern, which is related to the permanent activation of the Wnt pathway, and reflected by nuclear β-catenin staining on immunohistochemistry (IHC) [1, 8]
As the APC gene acts as a negative regulator of the Wnt pathway, mutated APC may result in a truncated protein lacking the majority of β-catenin binding sites, consequentially being unable to degrade β-catenin along with cytoplasmic and nuclear storage, while regulation of the latter is critical to the tumor suppressive effect of APC [14]
Summary
The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare subtype of differentiated thyroid cancer and generally has a good prognosis [1]. CMV-PTC has a distinctive histologic morphology featuring morules and a cribriform growth pattern, which is related to the permanent activation of the Wnt pathway, and reflected by nuclear β-catenin staining on immunohistochemistry (IHC) [1, 8]. The latter may result from biallelic APC gene inactivation, or from somatic mutations of the β-catenin (CTNNB1) [8,9,10,11,12] or AXIN1 gene (or combinations of gene variants), that are functionally similar [1, 13]. The patient had a total remission and no recurrence was noted during follow up
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