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Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
40 year-old female with a thyroid mass
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Clinical history: 40 year-old female with a thyroid mass
Choose the correct diagnosis:Correct
Diagnosis: B. Cribriform morular variant of papillary thyroid carcinoma
Histology: This lesion is centered in the thyroid and the background thyroid parenchyma lacks any significant abnormalities (i.e., no inflammation or no signs of Grave’s disease). Low power examination of the lesion reveals varying growth patterns, with some areas of papillary architecture and some areas of cribriform architecture, with areas of admixed squamous morules. High power examination confirms the presence of nuclear atypia in keeping with papillary thyroid carcinoma, including nuclear elongation, overlap, clearing and grooves. Immunostains show the lesion to have nuclear beta-catenin labeling, as well as diffuse ER positivity in the non-squamous areas.
Discussion: These findings all support the diagnosis of cribriform morular variant of papillary thyroid carcinoma (PTC). The cribriform morular variant of PTC can occur sporadically, or in association with familial adenomatous polyposis (FAP), a syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. APC gene mutations lead to abnormal nuclear accumulation of the beta-catenin protein, which can be detected with immunohistochemistry for beta-catenin. Nuclear labeling for beta-catenin can be detected in any tumor type that has mutations or aberrations in the APC pathway, whether the aberrations are germline/syndromic or sporadic. Other lesions that can be seen in patients with FAP include intestinal adenomas and carcinomas, desmoid tumors (fibromatoses), retinal pigmentation, gastric fundic gland polyps, hepatoblastomas, medulloblastomas and glioma, osteomas, fibromas and others. Diagnosis of cribriform morular variant of PTC should prompt clinical evaluation for FAP in any patient. The differential diagnosis of the cribriform morular variant of PTC includes the other variants of PTC; however, the immunoprofile of nuclear beta-catenin labeling is specific for the diagnosis.
1. Hizawa K, Iida M, Yao T, et al. Association between thyroid cancer of cribriform variant and familial adenomatous polyposis. J Clin Pathol. 1996 Jul;49(7):611-3.
2. Xu B, Yoshimoto K, Miyauchi A, et al. Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol. 2003 Jan;199(1):58-67.Incorrect