common in women. Within the upper aerodigestive tract, the tumors most commonly develop in the palate, likely secondary to the large number of seromucinous glands present at this site.
TABLE 6.1 2017 WHO Classification of Epithelial Tumors of the Salivary Glands
glandular structures with lumens (Fig. 6.1; eFig. 6.2). The architecture, however, can be complex and numerous anastomosing trabeculae, small tubular glands, nests, and single epithelioid cells can be present (eFig. 6.3). The epithelial cells may be columnar, cuboidal, squamous, plasmacytoid, oncocytoid, basaloid, clear, or spindled (eFig. 6.4). Most tumors have more than one epithelial cell type scattered throughout the lesion. The stromal elements may by myxoid, hyaline, chondroid, or even osseous (Fig. 6.2; eFig. 6.5). Both the mesenchymal and epithelial elements generally show bland cytology, and mitotic figures are rare. Pleomorphic adenomas of the seromucinous glands typically show a more cellular, myoepithelial phenotype than their counterparts in the major salivary glands and have less stromal elements.5 Furthermore, in our experience, they often contain more prominent squamous differentiation.
FIGURE 6.1 Glandular structures and groups of myoepithelial cells are usually seen with pleomorphic adenomas.
tumor shows mostly epithelial, myoepithelial, or mesenchymal differentiation.7 Most of the epithelial components will express various cytokeratins and show variable degrees of myoepithelial differentiation with expression of smooth muscle actin (SMA), calponin, S100, and glial fibrillary acidic protein (GFAP), CD10 and p63 (eFig. 6.6).6,7,8,9
FIGURE 6.2 The stromal components of pleomorphic adenomas of the upper aerodigestive tract are less abundant than in pleomorphic adenomas of the major salivary glands.
malignancy is usually determined by overall infiltration with these neoplasms and that the unequivocal diagnosis of benignancy cannot always be made based on small biopsies.
sometimes not seen, especially with the plasmacytoid variant (Fig. 6.6; eFigs. 6.12-6.14).8,22,23,24,25,26 A minority of tumors have been shown to harbor EWSR1 translocation similar to soft tissue myoepithliomas and clear cell carcinomas.27 Surgical resection should attempt to achieve free margins and the tumors only rarely recur.21,23
FIGURE 6.4 Fragments of a myoepithelioma seen on biopsy. Infiltration cannot be excluded with such a sample.
FIGURE 6.6 Strong immunoreactivity with antibodies to S100 protein was seen with this myoepithelioma myoepitheliomas.
6.15 and 6.16).6,30,31,32,33 A variable amount of moderately cellular stroma is present between the aggregates of basaloid cells. The basaloid cells themselves are bland cytologically and have scant cytoplasm (Fig. 6.8). Nuclear palisading is usually noted at the periphery of the epithelial structures, and some cells may have more abundant, eosinophilic cytoplasm and show overt squamous differentiation. Lumens may be seen within the epithelial nests and trabeculae and are often lined by columnar ductal cells. Some cases may have hyaline material surrounding the groups of basaloid cells (membranous-type or dermal analogue tumor). Immunohistochemically, all the cells will show immunoreactivity with antibodies to keratins; however, cells lining the apparent lumina stain most intensely.34 Conversely, antibodies to S100 protein, SMA, and p63 highlight the peripheral cells that are juxtaposed to the connective tissues (eFig. 6.17). p63 will also highlight areas of squamous differentiation. c-kit expression can be seen with both basal cell adenomas and adenocarcinomas.35 Immunostaining with antibodies to beta-catenin will show nuclear localization in most basal cell adenomas as the tumors often harbor CTNNB1 mutations.36
are infiltrative, typically have perineural invasion, and many have higher grade cytology. Furthermore, a cribriform growth pattern is not often seen with basal cell adenomas. Aside from the membranous type, basal cell adenomas do very well and almost never recur after adequate resection.6
FIGURE 6.9 Inverted papillomas are well circumscribed and composed of maturing, stratified squamous epithelium.
oncocytic and squamous epithelia have all been described. The cytologically bland epithelium varies in thickness and papilla can often be found. Some cystadenomas have been noted to involve the larynx. Here, they have been noted to have a bland oncocytic epithelium often with papillae.42,43
FIGURE 6.10 Numerous papillae lined by a stratified squamous epithelium are seen with this sialadenoma papilliferum.
found within the cystic spaces that is believed to be basal lamina. The individual neoplastic cells are small with angulated nuclei (eFig. 6.25). Cytoplasm is usually scant and may vary from basophilic to eosinophilic to clear. Small nucleoli may be present, and apoptotic and mitotic figures are
usually infrequent. Rare ductal structures may be seen with all histologic patterns and are lined by epithelial cells. The tubular pattern of growth often is composed of cells that tend to show more distinct epithelial or myoepithelial differentiation, and the tubules will contain the same materials noted previously. Finally, the solid pattern is composed of variably sized nests of basaloid cells with no or very few cystic spaces (Fig. 6.14). This pattern is considered to be higher grade than the others, and apoptotic figures, mitotic figures, and even comedo-type necrosis may be seen (some tumors that have been described as such may actually be other tumors, however, e.g., basaloid squamous cell carcinoma and salivary duct carcinoma).47 All patterns typically infiltrate the surrounding stroma and perineural invasion can almost always be identified (Fig. 6.15; eFig. 6.26).
FIGURE 6.13 Adenoid cystic carcinomas often have a cribriform architecture with frothy basophilic or dense eosinophilic material within the cystic spaces.
adenoid cystic carcinoma and can show squamous differentiation (Fig. 6.16). This can be demonstrated with immunohistochemistry as myoepithelial staining is typically lost. The high-grade component most frequently grows as solid sheets or nests, although cribriform, and micropapillary
growth has been described. Individual cells are enlarged and pleomorphic with atypical nuclei that have vesicular chromatin and prominent nucleoli. Numerous mitotic figures are present with necrosis, including comedoform necrosis within the large nests of neoplastic cells. Unlike with conventional adenoid cystic carcinoma, lymph node metastases develop in half the cases showing high-grade transformation; thus, some suggest lymph node dissections may be warranted for these patients.
FIGURE 6.16 Areas of conventional cribriform adenoid cystic carcinoma (bottom) contrast with the transformed high-grade carcinoma (top).
FIGURE 6.17 c-kit immunoreactivity is usually limited to the more epithelial cells in adenoid cystic carcinoma.