High-grade Mucoepidermoid Carcinoma, Predominantly Composed of Clear Cells Dr. Llúcia Alós Hospital Clinic, University of Barcelona Spain

Clinical History A 65 year-old female presented with a firm and painless right parotid mass lasting six months. No adenopaties were noted on examination. The surgical excision of the tumor was performed. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: - High-grade Mucoepidermoid Carcinoma, Predominantly Composed of Clear Cells Discussion Mucoepidermoid carcinoma is the most common malignant salivary gland tumor. About half of the tumors arise in major salivary glands, and the other half from minor salivary glands, especially in the mouth [1, 2]. It can present in patients of all ages, but mean patient age is approximately 45 years. There is a 3:2 female predominance. Clinical symptoms depend on the site of occurrence. Most tumors present as a firm, fixed and painless swelling. In advanced stages and high-grade tumors symptoms include pain, paraesthesia, facial nerve palsy, and bleeding [1, 2]. Macroscopic features depend on the histological grade of the tumors. Low-grade mucoepidermoid carcinomas are usually cystic; high-grade tumors are solid, firm and show infiltrative margins. Histologically they are usually composed of different cell types, such as mucous, epidermoid, intermediate, clear, and columnar cells. In spite of most tumors presenting different cell types, one cell type can predominate and this makes the diagnosis of mucoepidermoid carcinoma difficult. In these cases, careful examination of the whole tumor is recommended in order to perform a correct diagnosis. The presented case here is mostly composed of clear cells, but scarce mucous cells can be seen in some of the tumoral nests. These cells can be easily found with alcian blue or other mucin stains. Immunohistochemical stains for mucins (MUCs) can also be useful, as mucoepidermoid carcinomas express MUC1 and MUC4; and mucinous differentiated cells are positive for gastric type MUC5AC and intestinal type MUC5B. Conversely, MUC2 and MUC6 are infrequently expressed, and MUC7 should be negative [3]. Mucoepidermoid carcinoma must be classified into three histological grades, following histological characteristics, such as the cystic component of the tumor, cellular anaplasia, necrosis, mitoses, perineural invasion and osseous infiltration [4, 5, 6]. Also the expression with MUCs is related with the histological grade and the prognosis of this neoplasm, as a high expression of MUC1 is related with high-grade tumors and worse prognosis; and high expression of MUC4 is related with low-grade tumors and better prognosis [3]. When a mucoepidermoid carcinoma is predominantly composed of clear cell, as the presented case here, the differential diagnosis must be done with other clear cell malignant tumors originating in salivary glands: Myoepithelial tumors. Myoepithelial cells may present different morphologies, such as epithelioid, spindle, clear and plasmacytoid cell [1, 2, 7]. Myoepithelial tumors are composed of a mixture of these cell types, but one cell type often predominates, especially in myoepithelial carcinomas [7]. Characteristically they have a hyalin or myxoid stroma. In epithelial-myoepithelial carcinomas, myoepithelial cells usually form wide nests of clear cells, but a biphasic pattern, with presence of ductal structures, is always found. The myoepithelial nature of the neoplastic cells must be ruled out with immunohistochemical procedures, as they are always positive for cytokeratins, vimentin and S100 protein, and often express actins, PGAF, caldesmon, and p63. Clear cell carcinoma. This tumor usually arises from minor salivary glands of the palate or tongue, and the presentation from the parotid gland is unusual [2]. Frequently it has a very hyalinized stroma, and it has been named 'hyalinizing clear cell carcinoma'. The clear cells in this tumor have abundant glycogen. [2, 8]. Acinic cell carcinoma . In this tumor several cell types and histomorphological growth patterns are recognized. The cells can be acinar, intercalated ductal, clear and non-specific glandular. Growth patterns can be solid-lobular, microcystic, papillary-cystic and follicular [1, 2]. Clear cells are similar to acinar cells in size and shape but are non-reactive with PAS stain. Clear cells are seen in 6% of acinic cell carcinomas, they are usually focal, so only rarely they can cause diagnostic confusion. Sebaceous carcinoma. This tumor type can originate from salivary glands, commonly from parotid gland. It may have squamous or basaloid differentiated areas. The clear cells have a microvacuolated cytoplasm and marked nuclear atypia [1, 2]. Metastasis of clear cell tumors. Metastasis of a renal clear cell carcinoma should be ruled out, as these tumors may have a predilection to metastatize in head and neck region, through renal vein invasion and thoracic duct. Metastasing renal cell carcinoma usually presents a very vascularised stroma. Immunohistochemically they express cytokeratins, vimentin and show a strong membrane positivity for CD10 [9]. Malignant melanomas with clear cells should also be ruled out. The cells are usually non-cohesive and present nuclear atypia and conspicuous nucleoli. They express s100 protein, HMB45 y MelanA. The elective treatment for mucoepidermoid carcinoma is complete resection of the tumor with free margins. If the tumor is a high grade mucoepidermoid carcinoma, measures more than 2 cms. and there is perineural or vascular invasion a more aggressive treatment is recommended, with regional lymph node removal, radiotherapy and/or chemotherapy. The prognosis of mucoepidermoid carcinomas correlates with the histological grade [4, 5, 6]. Low-grade tumors usually have good prognosis, whereas high-grade tumors can metastatize to regional lymph nodes and may have an unfavourable outcome. References: Ellis,G.L., Auclair,P.L. Tumours of the salivary glands, 3rd edition. Armed Forces Institute of Pathology, Washington, 1996. "Tumors of the salivary glands" Chapter 5. En Head and Neck Tumours, World Health Organization Classification of Tumours, Lyon 2005. Alos L, Lujan B, Castillo M, Nadal A, Carreras M, Caballero M, de Bolos C, Cardesa A. Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands.Am J Surg Pathol 2005; 29:806-813. Auclair,P.L., Goode,R.K., Ellis,G.L., 1992. Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases. Cancer 69, 2021-2030. Evans,H.L., 1984. Mucoepidermoid carcinoma of salivary glands: a study of 69 cases with special attention to histologic grading. Am J Clin Pathol 81, 696-701. Brandwein,M.S., Ivanov,K., Wallace,D.I., Hille,J.J., Wang,B., Fahmy,A., Bodian,C., Urken,M.L., Gnepp,D.R., Huvos,A., Lumerman,H., Mills,S.E., Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol 2001; 25; 835-845. Alos L., Cardesa A., Bombi J.A., Mallofre C., Cuchi A., Traserra J. 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