Mucoepidermoid carcinomas represent a distinct type of tumor. They contain three cellular elements in varying proportions: squamous cells, mucus-secreting cells, and "intermediate" cells. (1) Mucoepidermoid carcinomas were first described by Masson and Berger in 1924. Since then, they have become well recognized as a common salivary gland neoplasm, accounting for approximately 35% of all malignancies of the major and minor salivary glands in general. Mucoepidermoid carcinomas have been reported at distant and atypical sites, including the breast, Eustachian tube of the ear, bronchi of the lungs, and thyroid. Reports of mucoepidermoid carcinomas of the subglottis are not common. Women are more commonly affected than men (3:2), and the mean age at onset is in the 5th decade of life. MEC is also the most common salivary gland malignancy in children.
The tumor usually forms as a painless, fixed, slowly growing swelling of widely varying duration that sometimes goes through a phase of accelerated growth immediately before clinical presentation. Symptoms include tenderness, otorrhea, dysphagia, and trismus. Intraoral tumors are often bluish-red and fluctuant, and they may resemble mucoceles or vascular lesions. They occasionally invade the underlying bone.
MECs may be circumscribed and variably capsulated or infiltrative and fixed; the latter characteristics generally apply to higher-grade tumors. Areas of scarfing are relatively common. Most tumors are smaller than 4 cm in diameter. Cysts of variable sizes are often present, and they usually contain brownish fluid. MEC cells form sheets, islands, duct-like structures, and cysts of various sizes. The cysts may be lined with intermediate, mucous, or epidermoid cells, and they are filled with mucus. Papillary processes may extend into the cyst lumina, and this is occasionally a conspicuous feature.
The tumor is primarily made up of three cell types in widely varying proportions: intermediate, mucous, and epidermoid
- The intermediate cells frequently predominate; their appearance ranges from small basal cells with scanty basophilic cytoplasm to larger and more oval cells with more abundant pale eosinophilic cytoplasm that appears to merge into epidermoid or mucous cells.
- Mucous cells (mucocytes) can occur singly or in clusters, and they have pale and sometimes foamy cytoplasm, a distinct cell boundary, and small, peripherally placed, compressed nuclei. Mucocytes often form the lining of cysts or duct-like structures. Occasionally mucocytes are so scanty that they can be identified with confidence only by using stains such as mucicarmine.
- Epidermoid cells may be uncommon and focally distributed. They have abundant eosinophilic cytoplasm, but they rarely show keratin pearl formation or dyskeratosis. Oncocytic metaplasia is seen occasionally.
Higher-grade tumors show evidence of cytologic atypia, a high mitotic frequency, and areas of necrosis, and they are more likely to show neural invasion. Stromal hyalinization is common and sometimes extensive.
MECs exhibit remarkable variability in their clinical behavior. Several microscopic grading systems based on a numerical score have been advocated as a means of predicting outcome. These systems rely on subjective evaluations of the relative proportions of the various cell types, the degree of cellular atypia, mitotic frequency, presence of necrosis, and invasive characteristics.
MECs must be distinguished from necrotizing sialometaplasia, chronic sialadenitis, cystadenoma, cystadenocarcinoma, squamous cell carcinoma, epithelial-myoepithelial carcinoma, clear cell carcinoma (not otherwise specified), and metastatic tumors.
It has been proposed that mucoepidermoid tumors arise from subepithelial mucus glands that line the upper respiratory and digestive tracts. If so, this might explain why this tumor type is more common at the supraglottis, which is the subsite of the larynx that has the greatest concentration of subepithelial mucous glands.
Mucoepidermoid carcinoma cell types are classified histologically as low, intermediate, and high-grade types. High-grade tumors are poorly differentiated, and they are made up primarily of squamous epithelial and intermediate cells. Low-grade tumors are well differentiated and are made up primarily of mucus-secreting and squamous epithelial cells. The histologic features of intermediate-grade tumors fall in between. Histologic tumor grade is a useful prognostic indicator for mucoepidermoid carcinomas of the major and minor salivary glands. The prognosis is dependent on the clinical stage, site, grading, and adequacy of surgery. Pires et. al. reviewed the literature and reported that overall 5-year survival rates ranged from 0 to 43% for patients with high-grade mucoepidermoid cancers of the salivary glands, 62 to 92% for patients with intermediate-grade tumors, and 92 to 100% for patients with low-grade tumors.
The infrequency of reports of mucoepidermoid carcinoma of the subglottis, and of the larynx in general, may be attributable to the relative difficulty that physicians have in recognizing this tumor type when it occurs outside the salivary glands. In addition to the possibility of sampling errors, interpretative errors during analysis of tumor specimens obtained from atypical locations have been reported. Notably, Binder et al cited the misclassification of high-grade mucoepidermoid carcinomas as adenosquamous carcinomas. Likewise, Ferlito et. al. reported that 10 of 11 patients who were ultimately diagnosed with mucoepidermoid carcinoma of the larynx had been initially diagnosed by histopathology with squamous cell carcinoma. Finally, there is significant variability in the way mucoepidermoid carcinomas are histologically graded, even among pathologists experienced in head and neck cancer.
The appropriate management of mucoepidermoid carcinomas of the larynx is unsettled, but most authors agree that different treatment approaches are indicated for different tumor subsites and histologic grades. High-grade tumors are usually treated in a more aggressive fashion, with surgery as the primary modality, as is the case with high-grade tumors of the major and minor salivary glands. There is less agreement about the appropriate management of low-grade tumors. Some have recommended a partial laryngectomy resection for low-grade supraglottic tumors and a total laryngectomy for subglottic tumors. Others have recommended approaches that preserve laryngeal function provided that tumor-free margins around the resection are achieved.
The issue of treatment with radiotherapy is unsettled. As a primary treatment modality, radiotherapy has met with both success and failure. Results of its use as an adjunctive therapy have also been mixed. Finally, the therapeutic role of cervical lymphadenectomy is also unresolved.
The treatment approach is determined by the tumor grade, the tumor location, and the clinical presentation. The aim is to ensure oncologic safety by leaving tumor-free margins while preserving laryngeal function when this organ is involved.
The relative successes of different treatments for mucoepidermoid carcinoma will become clearer as cases continue to be reported. At this time, however, surgical management of low-grade mucoepidermoid carcinomas is the standard care, and those of the subglottis should be centered on attempts to preserve laryngeal function as long as tumor-free margins can be achieved.