May 2016 - Presented by Dr. Trevor Starnes


D. Low-grade mucoepidermoid carcinoma


Salivary gland tumors are uncommon, comprising 2000-2500 cases in the United States each year. About 25% of parotid gland tumors are malignant, the most frequent of which is mucoepidermoid carcinoma, followed by adenoid cystic carcinoma. Mucoepidermoid carcinoma is characterized by a variable contribution of mixed cell types including mucus cells, intermediate cells, and squamoid or epidermoid cells. In contrast, adenoid cystic carcinoma has epithelial and myoepithelial cells in a range of morphological patterns ranging from tubular to solid.¹

While many patients with mucoepidermoid carcinoma are asymptomatic as in this case, some patients with a parotid mass will present with paralysis of facial muscles through involvement of the facial nerve. This would favor a malignant process like mucoepidermoid carcinoma over the more common and benign pleomorphic adenoma. These cancers are not restricted to the major salivary glands, and can occur in minor salivary glands causing a variety of symptoms depending upon adjacent structures.²

Histological grade is very important in the prognosis of mucoepidermoid carcinoma. Low-grade tumors have a 5-year survival of greater than 90%, while high grade tumors have survivals below 43%. When metastasis occurs from a parotid gland primary, level I and level II cervical lymph nodes will normally be the initial sites of metastasis.²

Grade also affects treatment in that low grade cancers require local excision while high grade requires adjuvant radiation and neck dissection.³  Thus, a careful microscopic examination by the pathologist is especially critical for optimal patient care. Multiple grading systems exist including the Brandwein system, which is points-based. Points are assigned based upon intracystic component <25%, tumor front invading in small nests, pronounced nuclear atypia, lymphovascular invasion, bony invasion, >4 mitoses/10 hpf, perineural invasion, or necrosis. While the points should be tallied, the simplest way to determine grade is to know that fulfilling any of these will result in an intermediate grade, and fulfilling two criteria will result in a high-grade classification unless it is restricted to the first three criteria I listed, in which case three criteria are required.³

Risk factors for this cancer are not well-established. However some studies have demonstrated that it may be caused by human cytomegalovirus (CMV), a highly prevalent and usually asymptomatic infection that has tropism for salivary glands. For example, the study by Melnick et al4 fulfilled Koch’s postulates for causation in their research by finding markers for active CMV in 97% of the mucoepidermoid cancers, not finding these markers in non-neoplastic salivary gland tissue, finding that expression of CMV proteins are correlated with disease severity, and that CMV upregulates the established oncogenic signaling pathway of COX/AREG/EGFR/ERK. However, further research is needed to confirm and elucidate this chain of causation, which could unlock further therapeutic or preventive options for this cancer.


1. Barnes, L., Eveson, J.W., Reichart, P., Sidransky, D. Pathology and Genetics of Head and Neck Tumours. Third edition. Who Classification of Tumors, Volume 9. IARC.

2. Laurie, Scott A. “Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging” UpToDate. <> Mar 17, 2016.

3. Seethala, Raja. “An Update on Grading of Salivary Gland Carcinomas” Head Neck Pathol. 2009 Mar; 3(1): 69–77.

4. Melnick M, Sedghizadeh PP, Allen CM, Jaskoll T. “Human cytomegalovirus and mucoepidermoid carcinoma of salivary glands: cell-specific localization of active viral and oncogenic signaling proteins is confirmatory of a causal relationship.” Exp Mol Pathol. 2012 Feb;92(1):118-25.