Section 2 -

Matrix-Containing Salivary Gland Tumors (Dr. Powers) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: A 31 year-old woman with a 1.5 cm non-tender right parotid mass that has been slowly enlarging over the past year. Cytologic Findings: The smears are hypocellular with abundant myxoid background material and scatted cytologically bland cells singly and in clusters. The cells have uniform oval nuclei with evenly dispersed chromatin and indistinct nucleoli. Some cells have a plasmacytoid appearance, others are epithelioid, and most cells have a moderate amount of delicate cytoplasm. The groups of cells have a haphazard arrangement. The most notable feature of the smears is the abundant wispy background myxoid material that in the Papanicolaou-stained smears is pale blue, and in the air-dried Romanowsky-stained smears is bright magenta (metachromatic) with a fibrillary appearance. The single cells described above are admixed with the myxoid matrix material. Based upon these findings, a cytologic diagnosis of a "pleomorphic adenoma" was made. The lesion was subsequently surgically excised by superficial parotidectomy, confirming the diagnosis of pleomorphic adenoma. Section 2 - Figure 1 Section 2 - Figure 2 Discussion: Pleomorphic Adenoma Pleomorphic adenoma is the most common salivary gland tumor in children and adults. Two-thirds of parotid tumors and 50% of all salivary gland tumors are pleomorphic adenomas. The most common site is the superficial parotid, often the tail of the gland at the angle of the jaw. Cytologic features of pleomorphic adenoma: Cohesive epithelial cells in honeycomb groups Myoepithelial cells, often plasmacytoid or spindled Chondromyxoid matrix - fibrillary and bright magenta using Romanowsky stains Pleomorphic adenomas are characterized by an admixture of cohesive epithelial cells, usually in a honeycomb pattern, and myoepithelial cells, that can have a variety of appearances including epithelioid, clear, spindled, and plasmacytoid. Unlike epithelial cells, myoepithelial cells are commonly found individually, embedded within matrix material, in loose clusters, or in larger, haphazardly arranged clusters. In our experience, pleomorphic adenomas are more often composed predominantly of myoepithelial cells, but epithelial-predominant lesions do occur. In addition to the cellular component, there is a characteristic matrix material, best appreciated in air-dried Romanowsky-stained preparations where it has a fibrillary or "chondromyxoid" appearance. It stains pale green in Papanicolaou-stained preparations, and it has an intense magenta (metachromatic) color in Romanowsky stained smears. The distinctive fibrillary nature of the matrix material with its frayed, indistinct margins and embedded myoepithelial cells is characteristic enough to distinguish a pleomorphic adenoma from other lesions that may mimic it, especially adenoid cystic carcinoma. Section 2 - Figure 3 Pleomorphic adenoma - Pap Stain Section 2 - Figure 4 Pleomorphic adenoma - Diff-Quik Stain Pitfalls in diagnosing pleomorphic adenomas include: Cellular specimens with sparse or absent matrix material Lesions with focal adenoid cystic-like areas Lesions with cytologic atypia Lesions with metaplastic changes, especially squamous or mucinous features Histologic Features of Pleomorphic Adenoma: Histologically, pleomorphic adenomas are circumscribed biphasic lesions comprised of myoepithelium, ductal epithelium, and myxochondroid stroma. Many histologic patterns including glands, tubules, trabeculae, solid nests, and single cells can be seen. The ratio of ductal and myoepithelial cells is variable, as is the overall cellularity of the lesion. Importantly, infiltrative features, diffuse atypia, mitotic activity, and necrosis are not present. The myoepithelial component is often the dominant cell type, and spindled and plasmacytoid types are frequently seen. The stroma may be abundant or sparse, and consists of a mixture of mucoid, myxoid, chondroid, and hyaline tissue. A range of metaplastic changes can be seen including squamous and mucinous changes. Section 2 - Figure 5 Section 2 - Figure 6 Conventional (left) and cellular (right) pleomorphic adenomas. Note the admixture of myoepithelial cells (spindled to plasmacytoid shaped) and ductal cells. The abundant myxoid stroma with embedded single myoepithelial cells on the left is classic. Differential Diagnosis: The differential diagnosis of pleomorphic adenomas varies depending upon whether the lesion contains abundant matrix material or whether the lesion is cellular. Among the lesions to exclude in the differential diagnosis, adenoid cystic carcinoma is the most important since the clinical implications of this diagnosis are critical. Differential diagnosis of pleomorphic adenoma: Adenoid cystic carcinoma Myoepithelioma Basal cell tumors Carcinoma-ex-pleomorphic adenoma Mucoepidermoid carcinoma Adenoid Cystic Carcinoma: Adenoid cystic carcinomas represent 4-10% of all salivary gland neoplasms, most often occurring in middle-age women. Although the clinical course of adenoid cystic carcinoma is often protracted, long-term (15-20 year) survival is poor. Three variants are recognized and often present in combination: tubular, cribriform, and solid. Recognition of the solid pattern is important because of its more aggressive clinical course. The tendency of these tumors to invade nerves manifests itself clinically as a painful mass or as pain during the FNAB, which should increase the clinical suspicion of malignancy. Cytologic features of adenoid cystic carcinoma: Variably sized, often large, three-dimensional hyaline matrix spheres and linear branching structures Matrix is acellular with sharp borders Surrounding basaloid cells with dark angulated nuclei and variable nuclear atypia Section 2 - Figure 7 Adenoid cystic carcinoma -Diff-Quik stain Section 2 - Figure 8 Adenoid cystic carcinoma - Pap stain The primary way that pleomorphic adenomas and adenoid cystic carcinomas are distinguished is based upon differences in their stroma. Romanowsky-stained preparations are essential for helping to make this distinction since it highlights the stromal features! Pleomorphic adenoma has fibrillar stroma with embedded cells, while adenoid cystic carcinoma has homogeneous acellular stroma in spheres and cylindrical shapes. The differential diagnosis of adenoid cystic carcinoma also includes other basaloid neoplasms (see basaloid tumors below) with the solid variant of adenoid cystic carcinoma causing the most diagnostic difficulty due to scant stroma. Histologic Features of Adenoid Cystic Carcinoma: Adenoid cystic carcinoma can exhibit a cribriform, tubular, or solid pattern in histologic sections. The cribriform pattern is the most classic and easily recognized by its "Swiss-cheese" appearance. The cells of adenoid cystic carcinoma are small, round, and basaloid with dark angulated nuclei, scant cytoplasm, and indistinct intercellular borders. The stroma is present as cylinders of myxoid material that is homogeneous and lacks the embedded cells of pleomorphic adenoma. The basaloid epithelial cells surround the stroma with a well demarcated interface. Infiltration and perineural invasion are commonly seen in all types of adenoid cystic carcinoma. Section 2 - Figure 9 Adenoid cystic carcinoma exhibiting the classic cribriform pattern. Section 2 - Figure 10 Adenoid cystic carcinoma exhibiting the classic tubular pattern.