FINAL DIAGNOSIS: MALIGNANT MELANOMA
Primary mucosal melanomas of the head and neck are very rare, occurring much less frequently than their cutaneous counterparts. Approximately 1% of all malignant melanomas arise from the mucosa surfaces of the head and neck. Of all head and neck melanomas, 5-10% are primary to the mucous membranes. To date, approximately 1000 cases of primary mucosal melanomas of the head and neck have been reported in the literature.
The etiology of mucosal melanomas is unclear. Factors such as tobacco use and chemical exposure (formaldehyde for example) have been implicated but are not proven to be significant contributing factors. Some authors report an association of oral mucosal melanomas with preexisting "melanosis." There seems to be racial influences on the incidence of mucosal melanomas as well. Mucosal melanoma of the oral cavity made up 7.5% of all reported melanomas among the Japanese, compared with less than 1% for Caucasians. Similarly, mucosal melanomas of the head and neck comprise 10% of all melanomas in residents of Uganda.
Mucosal melanomas of the head and neck most commonly arise in the oral cavity or the sinonasal tract. Of those in the oral cavity, approximately 42% arise in the hard palate and 32% in the maxillary alveolus. In the sinonasal tract, it is often difficult to pinpoint the exact site of origin due to anatomic limitations and a tendency to present with extensive growth. However, the majority are presumed to arise in the nasal cavity rather than the sinuses. Rare cases in the larynx have been reported, mostly in the supraglottic region.
Patients with mucosal melanomas tend to present at a later age than those with cutaneous melanomas and are usually older than 50 years of age. Most patients with sinonasal tumors present with epistaxis and/or obstruction due to the polypoid nature of the lesions, and occasionally complain of pain, facial deformity, or diplopia. In contrast, those with oral melanomas present with flat, irregular shaped pigmented lesions or mucosal ulcers.
Histologically, mucosal melanomas are similar to the cutaneous melanomas. The neoplastic cells are usually polygonal with eosinophilic cytoplasm. The nuclei are enlarged with prominent red nucleoli. Melanin pigment may be identified. If the overlying mucosa is intact, junctional activity and epidermal migration of melanocytes may be seen. However, since the majority of these lesions present with surface ulceration, this important diagnostic feature is often absent. Some melanomas may be composed predominantly of spindled cells or small blue cells. Diagnosis is confirmed by demonstration of intracellular melanin. Melanin can be demonstrated in 71 to 100% of the lesions with immunohistochemical stains for S-100 protein, HMB-45, Mart-1/Melan-A, and tyrosinase. A recent study by Prasad et al demonstrated that all sinonasal mucosal melanomas were reactive for tyrosinase and Mart-1/Melan-A, 98% reactive for HMB-45, and 95% reactive for S-100 protein. For oral mucosal melanoma, Prasad et al found 97% reactivity for S-100 protein, 85% and 84% reactivity with tyrosinase and Mart-1/Melan-A respectively, and 71% for HMB-45. The differential diagnosis of amelanotic melanocytic lesions includes poorly differentiated carcinoma, lymphoma, and "round cell tumors," such as olfactory neuroblastoma, extramedullary plasmacytoma, sinonasal undifferentiated carcinoma, rhabdomyosarcoma, to mention a few. A full body skin exam should be carried out to exclude a metastasis from a cutaneous melanoma.
Review of the literature reveals 75% of patients present with localized disease (Stage I), 18% with metastases to regional lymph nodes (Stage II), and 7% with distant metastasis (Stage III). Mean 5 year survival rate is about ranges from 20 to 40% as reported in the literature. Surgery remains the cornerstone of treatment for mucosal melanomas of the head and neck, with radiation and chemotherapy providing inconsistent results.
Contributed by Melissa Halpern, M.D and Leon E Barnes, MD