Cribriform-Morular Variant (C-MV) of PTC is a rare morphologic entity. It was first described by Harach et al. 1
in association with FAP as a distinctive tumor. A total of 44 cases have been documented so far (See Table ). We describe three cases, in two of which the patients have FAP. Case 2 was lost to follow-up.
Two cases were women in their 30's and the third was a 14 year old. The lesions ranged from 1.5 to 2 cm and were associated with several satellite nodules. There was no lymph node metastasis, capsular or vascular invasion. Our cases are similar to that described by Cameselle-Teijeiro et al. 2
who first proposed the term and did a study on nine cases. All the cases were seen in women between ages of 16-30 years (mean: 21.3). The lesions were predominantly solitary and ranged from 1.5-5.6 cm. All except one showed vascular invasion. Two cases also showed lymph node metastasis. In that study, immunohistochemical stains were positive for thyroglobulin, epithelial membrane antigen, cytokeratin, vimentin, estrogen and progesterone receptors, bcl-2 and Rb proteins. Calcitonin and carcinoembryonic antigen were negative. Follow-up showed seven cases with no recurrences.
C-MV of PTC is commonly seen in young females usually less than 30 years of age. The lesions are encapsulated or well-circumscribed. While sporadic forms usually appear as an isolated tumors, the cases associated with FAP are often multifocal due to different somatic mutations added to the germline mutations 3
. They display the characteristic histologic pattern of cribriforming akin that seen in breast cancer with morules. Morules appear squamous with no keratinization or cellular bridges. There are also follicles showing papillary, trabecular and solid patterns.
There have been several cases showing germline mutations in the APC gene which have also been found in the colonic polyps. Hot spots on codons 1061, 1039 and 698 of the APC gene on exon 15 are frequently identified. It has been proposed that β-catenin immunohistochemistry is a feasible screening method to identify occult FAP in young patients with thyroid tumors 4
. Recently Xu B 5
suggested that accumulation of mutant β-catenin contributes to the development of C-MV of PTC. A handful of sporadic cases have also been documented 6
. Table summarizes all the cases in the literature. Molecular studies were performed in all our cases and they did not show the hot spots of the APC gene.
C-MV carries a better prognosis than the other aggressive variants of PTC (tall cell, columnar, diffuse sclerosing and diffuse follicular) and poorly differentiated carcinoma. Tall cell variant lacks morular, cribriform and spindle cell areas. Columnar cell variant presents in older males. The encapsulated form of columnar cell variant is common in females and histologically shows greater overlap with C-MV but does not have the morules and cribriform pattern. Hyalinizing trabecular tumor shows a zellballen pattern in a hyalinized amyloid-like background. Poorly differentiated (insular) carcinoma shows areas mimicking cribriform structures but lacks morules and is associated with a higher proliferation index and necrosis.
This morphologic variant should be borne in mind by pathologists because of its characteristic pattern. The clinician should be alerted to exclude FAP along with appropriate family screening. In 25-30% of cases, this might provide the first indicator of an underlying FAP syndrome.