Cribriform adenocarcinoma of minor salivary glands may express galectin-3, cytokeratin 19, and HBME-1 and contains polymorphisms of RET and H-RAS proto-oncogenes

Abstract

The aim of the study was to further elucidate the immunohistochemical and genetic characteristics of cribriform adenocarcinoma of minor salivary glands (CAMSG). The study comprised five CAMSG from two males and three females, aged 21-72 years. Four tumors were localized at the base of tongue and one in the floor of mouth. At the time of diagnosis, four tumors had metastasised to regional lymph nodes. After tumor resection, two patients were treated by radiotherapy and one by chemoradiotherapy. During the follow-up (median 14 months), two patients developed lymph node metastasis. Microscopically, all tumors showed cribriform, papillary, follicular, and microcystic growth patterns. The tumor cells displayed vesicular nuclei with intranuclear grooves. Immunohistochemically, all tumors showed expression of cytokeratin (CK) 7, CK8, CK18, vimentin, smooth muscle actin, calponin, S-100 protein, and p16 protein. In addition, we observed expression of galectin-3, CK19, and HBME-1, but not of thyroglobulin and TTF-1. No mutations of RET, BRAF, K-RAS, H-RAS, and N-RAS proto-oncogenes were detected. However, in RET proto-oncogene, we found polymorphisms Gly691Ser (exon 11) and Ser904Ser (exon 15) in one case, p.Leu769Leu (exon 13) in one case, and variant p.IVS14-24 G/A of intron 14 in two cases, and in H-RAS proto-oncogene we found polymorphism 81 T-C (exon 1) in three cases. Thyroglobulin and TTF-1 are the only useful markers in the differential diagnosis between CAMSG and papillary thyroid carcinoma as both tumors may express galectin-3, CK19, and HBME-1. The RET, H-RAS, and N-RAS proto-oncoogenes are not mutated in CAMSG.

Cribriform Adenocarcinoma of the Tongue and Minor Salivary Glands: A Review

“…More importantly all the tumors are invariably completely devoid of any staining for TTF-1 and thyroglobulin. The Ki-67 proliferation index was generally low [2,7].…”

“…No somatic mutations of BRAF, K-RAS, H-RAS, N-RAS, ckit, and PDGFRa genes were found in any of the analyzable cases in two papers [2,7]. However, in RET protooncogene, heterozygous polymorphism Gly691Ser in exon 11 (1 case), heterozygous polymorphism p.Leu769Leu in exon 13 (1 case), heterozygous polymorphism Ser904Ser in exon 15 (1 case), and intronic variant p.IVS14-24 G/A of exon 14 (2 cases) were found in one study [7].…”

“…Basal and myoepithelial cell markers, such as p63, calponin, CK14, and CK5/6 are positive in all tumors with variable proportions up to 60 % often at the periphery of the tumor nodules, especially marking the palisaded cells surrounding the glomeruloid structures. Expression of CK19 was variable with mild to moderate staining of membranes and cytoplasm in 12 out of 17 cases in two studies [2,7]. EMA, EGFR, HER-2/neu, ER, and PR are usually negative.…”

“…Of the 31 published cases in the literature [2][3][4][5][6][7], 21 tumors were located in the tongue (usually the base), 3 in the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, 1 in the upper lip and 1 in the floor of the mouth. One tumor located in the tongue was described to have a pedunculated configuration [4].…”

“…We and others are convinced, however, that CATMSG is a distinct neoplasm, and that it should be considered separately from PLGA [4][5][6][7][8].…”