Cribriform-Morular Variant of Papillary Thyroid Carcinoma With Poorly Differentiated Features: A Case Report With Immunohistochemical and Molecular Genetic Analysis

Abstract

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.

The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review

“…[ 146 ]. This is also depicted in our review, where few patients went disease-free [ 36 , 39 , 45 , 52 , 53 , 54 , 56 , 58 , 59 , 64 , 65 , 68 , 71 , 72 , 87 , 96 , 99 , 103 , 104 , 106 , 108 , 117 , 118 ]. Distant metastases represent the most significant cause of death in PDTC, with the majority of patients succumbing to the disease.…”

“…Since cytological diagnosis of PDTC based on FNAC is challenging, our review has shown that some patients underwent a hemithyroidectomy or subtotal thyroidectomy with a completion thyroidectomy after histological diagnosis [ 38 , 44 , 52 , 54 , 59 , 65 , 69 , 85 , 103 , 104 , 107 , 108 , 115 , 117 ], but the majority of them were submitted to a total thyroidectomy as the initial operation [ 40 , 41 , 42 , 43 , 46 , 48 , 49 , 50 , 51 , 53 , 54 , 55 , 56 , 58 , 60 , 61 , 62 , 64 , 67 , 68 , 69 , 72 , 73 , 75 , 79 , 80 , 81 , 82 , 85 , 86 , 88 , 89 , 90 , 91 , 92 , 93 , 95 , 96 , 100 , 101 ,…”

“…However, it remains debatable whether the cut-off value for the poorly differentiated area should be reported in PDTC tumors. Based on our review, several cases had a multiconstituent histology of well-differentiated (mostly PTC and FTC) with poorly differentiated areas without elaborating on their extent [ 49 , 50 , 55 , 56 , 58 , 69 , 71 , 72 , 73 , 91 , 100 , 103 , 107 , 109 , 112 , 113 ]. Interestingly, the Japanese society of thyroid surgery emphasizes that the presence of a poorly differentiated component should be acknowledged as a distinct entity from DTC, independent of its histological extent within the tumor [ 128 ].…”

A Case of Cribriform-Morular Thyroid Carcinoma Presenting Without Thyroid Nodule

“…Cribriform-morular thyroid carcinoma is a rare cancer that can present as an extracolonic manifestation of FAP syndrome. Case reports of cribriform-morular thyroid carcinoma typically have demonstrated evidence of thyroid nodules or a thyroid mass on ultrasound imaging ( 4‐7 ). A retrospective review of ultrasonographic and clinical characteristics of 5 patients with cribriform-morular variant thyroid carcinoma showed that all had either palpable discrete lesions or nodules on ultrasound.…”

Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review)

“…According to the criteria of the new edition of the WHO classification of thyroid tumors ( 1 , 6 ), rare cases of ‘high-grade CMTC’ with necrosis and/or high proliferative activity have also been reported ( 7 , 9 , 46 , 50 – 52 ).…”