Section 8 -

Clear Cell Tumors (Dr. Faquin) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: A 60 year-old woman presented with a slowly enlarging 2 cm non-tender parotid gland mass. An FNAB was performed. Cytologic Findings: The smears were cellular and showed cohesive 3-dimensional clusters of cells with moderate to abundant amounts of pale-staining cytoplasm. In addition, a second population of smaller darker ductal-type cells with only small amounts of dense cytoplasm, were present. The nuclei of the cells were cytologically bland and vesicular. The background contained rare globules of acellular homogeneous matrix material as well as many scattered bland naked nuclei. Based upon these cytologic findings, a diagnosis of low-grade salivary gland neoplasm with prominent clear myoepithelial cells was made. In a note, the differential diagnosis of epithelial-myoepithelial carcinoma and myoepithelial-predominant pleomorphic adenoma was made. The lesion was surgically resected by superficial parotidectomy and showed a biphasic tumor diagnostic of epithelial-myoepithelial carcinoma. Section 8 - Figure 1 Section 8 - Figure 2 Discussion: Epithelial-Myoepithelial Carcinoma Epithelial-myoepithelial carcinoma is a low-grade tumor that represents approximately 1% of all salivary gland neoplasms; it occurs most commonly in the parotid gland where it is locally aggressive. Cytologically and histologically, it consists of a predominant population of myoepithelial cells that have moderate to abundant amounts of delicate pale to clear glycogen-rich cytoplasm. The background contains many naked myoepithelial nuclei as well as single myoepithelial cells. Nuclear atypia is mild with most cells having uniform oval to round vesicular nuclei, and small indistinct nucleoli. A second minor population of small dark bland ductal epithelial cells is also present. A small to moderate amount of acellular proteinaceous material is present adjacent to some cell clusters as well as forming separate spheres within the background. The presence of these protein spheres raises the differential diagnosis of adenoid cystic carcinoma; however, the abundance of myoepithelial cells favors an epithelial-myoepithelial carcinoma. If material is available for making a cell block, it is possible to perform immunohistochemical stains for cytokeratins and calponin (or other myoepithelial markers) which will highlight the characteristic biphasic nature of the tumor. Cytologic features of epithelial-myoepithelial carcinoma: 3-dimensional groups of biphasic cells: Myoepithelial cells with abundant clear cytoplasm and vesicular nuclei Small ductal cells with scant cytoplasm Laminated proteinaceous material Background naked nuclei Section 8 - Figure 3 Histologic Features of Epithelial-Myoepithelial Carcinoma: The classic form of this tumor exhibits a multinodular pattern of well-defined tubules lined by two layers of cells, an inner layer of ductal-type cells and an outer layer of clear myoepithelial cells. A well-defined outer basement membrane is typically seen. Sometimes, the myoepithelial cell component will predominate. Necrosis, marked nuclear atypia, and mitotic activity are not seen. Section 8 - Figure 4 Epithelial-myoepithelial carcinoma showing the uniquely characteristic pattern of clear and ductal cells. Differential Diagnosis of Clear Cell Tumors: A wide range of tumors both primary within the salivary gland and metastatic can exhibit clear cell features. The clear cytoplasm can be due to any of a number of different causes including: mitochondrial condensation, edema, glycogen, mucin, or fat. Distinction between the various clear cell tumors is challenging and depends upon assessing the presence of and degree of nuclear atypia, detection of a secondary cell population admixed with the clear cells, and a careful search for areas of the tumor without the clear cell features. Useful ancillary studies to help in narrowing the differential diagnosis include ultrastructural studies, and cell block material to histochemically assess the nature of the clear cytoplasm. Differential Diagnosis of Clear Cell Tumors: Myoepithelioma/myoepithelial carcinoma Oncocytoma Epithelial-myoepithelial carcinoma Metastatic renal cell carcinoma Lipoma Hyalinizing clear cell carcinoma Sebaceous adenoma/carcinoma Acinic cell carcinoma Mucoepidermoid carcinoma