A Novel Adenomatous Polyposis Coli Gene Mutation of Cribriform-Morular Variant Papillary Thyroid Carcinoma: A Case Report / 대한이비인후과학회지

Cribriform-morular variant papillary thyroid carcinoma (CMV-PTC) is a rare cancer that may arise in patients with familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) gene mutation is associated with FAP, which is known as a premalignant lesion of colon cancer. In this report, we report a 16 years old patient of CMV-PTC comorbid with FAP, which was related with a new type of APC gene mutation.

Cytohistology of morule in cribriform-morular variant of papillary thyroid carcinoma

@#Introduction: Cribriform-morular variant (CMV) is a rare variant of papillary thyroid carcinoma. It frequently occurs in association with familial adenomatous polyposis (FAP), although some cases are sporadic. Herein, we report a case of CMV and analyse morule cytohistology. Case Report: The patient was a 47-year-old woman with no familial history of FAP. A 3.0-cm unifocal mass was identified in the left thyroidal lobe. Fine-needle aspiration cytology revealed papillary clusters of atypical cells with nuclear grooves, which was suspected to be conventional papillary thyroid carcinoma. Histologically, the tumour comprised a papillary and cribriform growth of atypical cells with cytoplasmic accumulation and nuclear translocation of b-catenin. In addition, frequent morule formation was identified. Discussion: In this case, we performed morule analysis through correlative light and electron microscopy (CLEM), and revealed its ultrastructure. Although CMV is a rare form of thyroid carcinoma, it should be considered along with its distinct clinicopathological characteristics.

Clinicopathologic and molecular features of cribriform morular variant of papillary thyroid carcinoma / 中华病理学杂志

Objective@#To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC).@*Methods@#The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed.@*Results@#All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected.@*Conclusions@#CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma Associated with Familial Adenomatous Polyposis / 대한이비인후과학회지

We report a case of cribriform-morular variant of papillary thyroid carcinoma associated with familial adenomatous polyposis. A 21-year-old woman presented with multiple, well-defined, oval shaped thyroid nodules, which showed hypo-echoic and solid mixed with some cystic components by ultrasound, and poorly enhancing and low dense by CT scan. Cytological finding was compatible with papillary carcinoma. Total thyroidectomy was performed and nodules were palated soft. Histologic analysis confirmed the diagnosis of cribriform-morular variant of papillary thyroid carcinoma. Familial adenomatous polyposis, thereafter, was diagnosed by family history and colonoscopy, and preventive colectomy was performed.

Cribriform-morular Variant Papillary Carcinoma associated with Familial Adenomatous Polyposis / 대한내분비외과학회지

Cribriform-morular variant (CMV) is a rare histologic subtype of papillary thyroid carcinoma (PTC). Patients with familial adenomatous polyposis (FAP) could be associated with several comorbid diseases including thyroid cancer. Most thyroid cancers in them are PTCs, but infrequently CMV types can occur. The FAP concomitant CMV-PTCs are found predominantly in young women and reveals lower recurrence rate. Moreover, this variant shows circumscribed morphology and rarely metastasizes to node. Because the incidence of thyroid carcinoma is higher than that in general population, comprehensive evaluation of thyroid gland should be performed for the patients with FAP. Because thyroid cancer could be first manifestation of FAP, colonic screening should be considered in CMV-PTC patient. We report two cases of CMV-PTCs concurrent with FAP.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: A Report of Two Cases

Cribriform-morular variant of papillary thyroid carcinoma is an unusual and peculiar subtype of papillary thyroid carcinomas. It occurs both sporadically and in association with familial adenomatous polyposis. We report here on two cases of cribriform-morular variant of papillary thyroid carcinoma in a 33-year-old woman and in a 21-year-old woman. On gross examination, both cases were multicentric. The first case showed two well-encapsulated yellow solid masses in the right (2.0 cm) and the left lobes of the thyroid gland (0.5 cm). The second case showed four well-encapsulated gray-white solid lobulating masses and nodules in the right (4.5 and 1.2 cm) and the left lobes (1.1 and 0.8 cm) of the thyroid gland. Microscopically, both cases exhibited an intricate blending of papillary, cribriform, trabecular, spindle, and solid patterns of growth with morular areas. Typical nuclear features of papillary carcinomas were focally seen. Immunohistochemically, the tumor cells were positive for thyroglobulin, thyroid transcription factor-1 (TTF-1), and beta-catenin, but were negative for calcitonin.