This 85-year-old male with prior history of colorectal cancer and MGUS presented with multiple spinal and pelvic bone lesions. The cytomorphologic features were not consistent with multiple myeloma, one of the highest differentials in this clinical scenario. Instead, CT-guided needle biopsy revealed metastatic carcinoma with squamous and glandular differentiation. Two weeks after the bony lesion biopsy, a biopsy was performed of the patient’s rapidly enlarging right facial lesion. This showed a high-grade, malignant neoplasm with epidermoid morphology and rare keratinization. A few poorly formed lumens with intraluminal mucin were present. Immunohistochemistry for p63 was positive in the epidermoid cells, while CK7 highlighted mucin-producing cells. The neoplasm was diagnosed as mucoepidermoid carcinoma. An excision of the mass and parotidectomy confirmed the mass originated in the parotid gland.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor overall, representing approximately 10-15% of all salivary gland neoplasms. MEC arises most frequently in the parotid gland, but it may arise in both the major and minor salivary glands. The age distribution is wide and includes pediatric patients as well as older adults; while the mean age of presentation is in the 5th to 6th decades of life, MEC is the most common salivary gland malignancy in children [1-3]. Low-grade MEC typically presents as a slowly growing, painless mass, whereas high-grade MEC typically presents as a rapidly growing mass with or without pain. High-grade MEC recurs more readily than low-grade and is associated with a worse prognosis. Low- and intermediate-grade tumors both show a greater than 90% 5-year survival rate, whereas for high-grade tumors this figure is less than 60%. Nodal metastasis to cervical or regional lymph nodes is more common in high-grade than low-grade MEC, occurring in 30-50% of high-grade tumors. MEC of the submandibular gland is more prone to recurrence and metastasis than MEC in other locations. Complete surgical excision is the treatment of choice, and adjuvant radiotherapy may be indicated in high-grade or high-stage tumors at increased risk of recurrence [1-4]. Distant metastases are rare and are associated with a poor prognosis. Reported sites of metastasis include the lung (most common), liver, skin, brain, and bone [5-6].

Microscopically, MEC is composed of epidermoid, intermediate, and mucous cells in a cystic, solid, or mixed pattern. Low-grade tumors tend to be more cystic and well-circumscribed, whereas high-grade tumors are more solid and infiltrative. The epidermoid cells are polygonal in shape with abundant eosinophilic cytoplasm. Keratinization is uncommon but may be seen in the form of single-cell keratinization or rare keratin pearls. Mucous cells are characterized by clear or foamy cytoplasm or cytoplasmic mucin vacuoles. Intermediate cells range from small basal cells with little cytoplasm to larger cells with features of epidermoid cells (moderate eosinophilic cytoplasm) or mucous cells (foamy cytoplasm or mucin vacuoles). Cytologic preparations of MEC show a background of extracellular mucin. However, in high-grade tumors, epidermoid cells predominate and mucous cells may not be readily evident; in these tumors, the mucinous background may be less prominent [1-3]. Multiple grading schemes for MEC exist, the two most common of which are the Armed Forces Institute of Pathology (AFIP) and the Brandwein schemes. Both divide MEC into low, intermediate, and high grades based on increasing point values, and both assign points based on low percentage of cystic component, presence of perineural invasion, presence of necrosis, greater than 4 mitoses per 10 high-powered fields, and severe nuclear atypia or anaplasia. The Brandwein scheme additionally incorporates lymphovascular invasion and bony invasion, and it assigns points if the tumor front invades in small nests and islands [1-3].

While morphology is the mainstay of diagnosis, immunohistochemistry and special stains can aid in characterizing the tumor and ruling out differentials. A mucicarmine special stain or a CK7 stain can be used to highlight mucous cells in high-grade tumors where these cells are rare, favoring MEC over squamous cell carcinoma. Meanwhile, p63 or p40 will highlight epidermoid cells in tumors where mucous cells predominate [1-3].

Approximately half to two-thirds of MECs are positive for a t (11;19) chromosomal translocation resulting in the fusion of the genes CRTC1 and MAML2. This fusion is less commonly identified in high-grade tumors [1].