title: Cribriform-morular variant of papillary thyroid carcinoma: a study of 3 cases featuring the PIK3CA mutation.
abstract: The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an unusual neoplasm with a considerably important association with familial adenomatous polyposis in young women, characterized by a peculiar histologic morphology with mixed cribriform, papillary, solid, tall columnar, and morular patterns. However, it can also occur sporadically. The molecular pathogenesis of sporadic CMV-PTC is not completely understood. We report cases of 3 patients with sporadic CMV-PTC with PIK3CA mutations. Using sequencing analyses and immunohistochemistry, we examined KRAS, BRAF, PIK3CA, and CTNNB1 mutations and related proteins, including β-catenin, PTEN, CD10, estrogen receptor, progesterone receptor, cytokeratin 19, and cyclin D1 in 3 CMV-PTCs. The 3 patients were teenaged girls. The tumors were solitary and encapsulated without cervical lymph node metastasis. They showed no recurrence for more than 6 years after the operation. Three tumors were diffusely positive for β-catenin, cyclin D1, and PTEN. The biphasic immunohistochemical patterns between the morular and nonmorular components were identified; the nonmorular components were positive for estrogen receptor, progesterone receptor, and cytokeratin 19, whereas the morular components showed CD10 positivity. All tumors harbored the same mutation in exon 9, codon 545 of the PIK3CA gene (p.E545A), whereas the KRAS, BRAF, and CTNNB1 mutations were not detected. This is the first study identifying the PIK3CA mutation specifically in sporadic CMV-PTC. The presence of the PIK3CA mutation and the wild-type KRAS, BRAF, CTNNB1 genes, and the intact PTEN expression in 3 sporadic CMV-PTCs may suggest the possible contribution of the PIK3CA mutation in its tumorigenesis.
authors.affiliation: Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Gyeonggi-do, 431-070, Republic of Korea.
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Ilsong Memorial Institute of Head and Neck Cancer, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Rho
authors.affiliation: Department of Surgery, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Jin Cheol
authors.initials: JC
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea.
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Surgery, Hando General Hospital, Danwon-gu, Ansan, Gyeonggi-do, 425-141, Republic of Korea.
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea. Electronic address: apilas@hallym.or.kr.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 134-701, Republic of Korea. Electronic address: esnam2003@yahoo.co.kr.
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Nam
mesh_terms: D000293:Adolescent; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: Cribriform-morular variant; Mutation; PIK3CA gene; Papillary carcinoma; Thyroid