Aggressive cribriform-morular variant of papillary thyroid carcinoma: Report of an unusual case with pulmonary metastasis displaying poorly differentiated features

Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is usually an inherited malignancy and may be a presenting indicator of familial adenomatous polyposis syndrome although it may occasionally be sporadic. Known CMVPTC mutations include adenomatous polyposis coli ( APC) and β-catenin ( CTNNB1) genes. Despite its malignant classification, CMVPTC is considered to be a well-differentiated thyroid tumor with a generally good behavior. In contrast, poorly differentiated thyroid carcinoma is an aggressive tumor. We report a case of CMVPTC with poorly differentiated features in a young female without phenotypic features of familial adenomatous polyposis but with known germline alterations of the APC gene. High throughput sequencing showed germline chromosome 5q deletion encompassing the APC gene in all components with additional unique genetic alterations in the somatic components. A single nucleotide substitution (c.1548+1G>A, NM_000038.5) located one base pair downstream of exon 12 of the APC gene was identified in the CMVPTC component, and a pathogenic frameshift deletion in exon 14 of APC (c.3642del, p.Ser1214Argfs*51, NM_000038.5) was identified in the poorly differentiated thyroid carcinoma component. No other cancer-associated genes were identified by our techniques. Our case represents a rare phenomenon of poorly differentiated features in association with CMVPTC. To our knowledge, ours is the only such report of poorly differentiated features arising in association with an inherited CMVPTC.

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Cribriform-morular variant of papillary thyroid carcinoma with poorly differentiated features: report of a case and review of the literature

Surgical and Experimental Pathology ◽

10.1186/s42047-021-00103-5 ◽

2022 ◽

Vol 5 (1) ◽

Author(s):

Kusum L. Sharma ◽

Ravi B. Singh ◽

Nisreen Fidda ◽

Ricardo V. Lloyd

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Differentiated Thyroid Carcinoma ◽

Disease Spread ◽

Beta Catenin ◽

Papillary Thyroid ◽

Ki 67 ◽

History Of ◽

Poorly Differentiated ◽

Cribriform Morular Variant

Abstract Introduction Cribrifrom-morular variant of papillary thyroid carcinoma (CMVPTC) is an uncommon thyroid neoplasm that occurs predominantly in women and is sometime associated with familial adenomatous polyposis (FAP). Some of these tumors may undergo dedifferentiation to poorly differentiated thyroid carcinoma (PDTC). We describe a rare case of this carcinoma in a women without a history of FAP. Case presentation A 49-year-old woman with a history of breast carcinoma presented with a thyroid mass. A CMVPTC was diagnosed after excision. There was no history of FAP. Histological examination showed classical features of CMVPTC in most areas, but about 20% of the carcinoma showed features of a poorly differentiated carcinoma with a solid pattern of growth, increase mitotic activity and a high Ki-67 proliferative index (25%). Immunohistochemical stains were positive for nuclear and cytoplasmic beta catenin staining. These special studies supported the diagnosis. Conclusion CMVPTC with dedifferentiation to PDTC is a rare carcinoma with only 4 previous documented cases in the literature. This aggressive variant of thyroid carcinoma is more common in females, as is CMVPTC, and is often associated with an aggressive biological course. The cases usually express nuclear beta catenin and estrogen, progesterone and androgen receptors have been reported in some cases. Some cases may have somatic alterations of the APC gene and TERT promoter mutations. These carcinomas may metastasize to lung, bones and lymph nodes. Because of its aggressive behavior, patient with this diagnosis should be treated aggressively to control disease spread and mortality from the carcinoma.

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