Pathology of the Head and Neck

Major and Minor Salivary Glands Chapter 5 153Fig. 5.45. Myoepithelial carcinoma, solid growth pattern withcentral necrosis in one of the nodules. This finding may mimicsalivary duct carcinoma with comedo-like necrosisFig. 5.47. Myoepithelial carcinoma: focal squamous metaplasiawith keratin pearl formationFig. 5.46. Myoepithelial carcinoma. The spindle cell componentshows nuclear pleomorphism resembling a soft tissue sarcoma. Ahelpful diagnostic pointer is that other types of myoepithelial cellare usually identified elsewhereinates, but there is usually a minor component of othercell types. No true glands or lumina are seen in pure,malignant myoepitheliomas, but as with their benigncounterparts, occasional small ducts in a neoplasm withotherwise typical features should not preclude the diagnosis[183]. The nuclei can vary from relatively uniform,small with finely distributed chromatin, lacking obviousnucleoli, to markedly enlarged and pleomorphic, showingchromatin clumping and large nucleoli. Mitotic figuresmay be plentiful (range 3 to 51 per 10 high powerfields) and include atypical forms [168]. Multinucleate[33] and bizarre tumour giant cells may occasionally bepresent. The tumour-related matrix is generally prominentand is hyalinised or myxoid.Special stains in tumours without any ductal differentiationshow no mucicarmine-positive mucus,but plentiful glycogen is found in clear cells and themyxoid matrix is positive with Alcian Blue. Metaplasticchanges are frequent and include areas showingsquamous differentiation, often with keratinisation(Fig. 5.47). Perineural invasion is seen in 44% and vascularinvasion in 16%. In one series, 40% of tumourswere categorised as high grade and 60% as low grade[168]. All tumours show some positivity for S-100 protein,vimentin and broad-spectrum cytokeratin (e.g.AE1-AE3 or MNF116). Other cytokeratin antisera(CAM 5.2 and LP34) show some reactivity in most tumours,and about half display some expression of cytokeratin[13]. Of the more specific myoepithelial markers,approximately 75% of tumours including thosecomposed of plasmacytoid cells, express calponin andabout 50% are positive with αSMA; p63 was positivein 60% [166]. Amongst other markers, glial fibrillaryacidic protein (GFAP) is positive in 31% and epithelialmembrane antigen (EMA) in 20%, in addition tohighlighting any true small ducts, but carcino-embryonicantigen (CEA) is usually negative. CD117 (c-kit)was positive in the few cases studied [112]. The meanMIB1 (Ki-67) index in one series was 35% (range 15–65), with any count above 10% said to be diagnostic ofmalignancy in a myoepithelial neoplasm [151].Electron microscopy shows that some tumour cellscontain small desmosomes, but actin filaments are few[168]. It has been shown that malignant myoepitheliomassecrete matrix-degrading proteinases, as well asproteinase inhibitors [215], and this appears to be associatedwith demonstrated inhibition of angiogenesis.These features indicate an anti-invasive effect, and althoughas yet poorly understood, this is likely to have