**Abstract**

Mucosal melanomas of the head and neck are very rare malignancies that present with aggressive behavior and poor prognosis. Usually diagnosed at advanced stages, thus presenting macroscopically as aggressive nodular neoplasms arising from the mucosa; few cases are detected in situ. Tumor staging for mucosal melanoma remains a challenge. Several staging systems have been suggested, including tumornodal-metastases (TNM) staging systems, but none are frequently used. There is no clear consensus on the management of head and neck mucosal melanoma, which reflects the rare nature of the disease and complexity of the anatomic site. The late diagnosis, frequently presenting at an advanced stage, denotes the aggressive nature of the disease. Currently, early detection and surgical excision is considered the primary method of treatment. The multidisciplinary team approach can help reduce morbidity and mortality once optimize treatment, reduce costs and minimize adverse events, while maximizing the chances of recovery.

**Keywords:** mucosal, melanoma, head and neck

## **1. Introduction**

Mucosal melanomas of the head and neck are very rare malignancies that present with aggressive behavior, including frequent local recurrence, and poor prognosis. First described by Weber in 1859 [1] and classified as its own distinct disease by Lucke et al. in 1869 [2], they represent a small fraction of all head and neck melanomas.

Unlike cutaneous melanomas, which incidence is believed to be rising over the years, the incidence of mucosal melanomas seems to remain stable [2]. Its annual incidence rate in Europe was estimated in 1.5 per million, with slight female predominance (1.2 vs. 1.0 per million) and in people aged over of 65 years [3], with median age at diagnosis ranging around 70 years old – developing at more advanced ages when compared to cutaneous melanomas. Significant variation between races is observed, with the Japanese more likely to be affected (8%) when compared to Caucasians [4], especially regarding oral cavity mucosal melanoma, suggesting association of this particular subtype with common hereditary or environmental factors, still not identified [5]. Mucosal melanomas represent 0.8 to 3.7% of all melanomas, 0.03% of all neoplasms [6] and occur most commonly in the head and neck (55%) [7], mainly in the nasal cavity (lateral wall and septum) and paranasal sinuses (ethmoid and maxillary sinuses) [6], followed by the oral cavity – approximately 80% in the mucosa of the upper jaws (maxillary anterior gingiva), in the keratinizing mucosa of the palate and alveolar gingivae [8] -, pharynx, larynx, and upper esophagus [3, 9].

To date there are no clearly established risk factors for the mucosal melanoma development [5]. Cigarette smoking seems to be a risk factor for the oral tumor, while exposure to formaldehyde has been suggested as risk factor for the sinonasal malignancy. Association with viruses, such as human papilloma viruses, human herpes viruses or polymavirus is unlikely. Although sun radiation is a well-established risk factor for cutaneous melanoma, there is no evidence of its implication in mucosal melanoma pathogenesis, since its common locations preclude exposure to UV light [3].

Another particularity of mucosal melanomas, divergent from the cutaneous ones, is the more hostile behavior and frequent neoplastic dissemination, which results in greater death rate [10]. The mucosal melanoma aggressive clinical course results in very poor prognosis, especially among old male patients, likely due to little understanding of this rare malignancy and delayed detection, given the lack of specific clinical features for diagnosis, a challenging scenario for clinicians and pathologists [4]. Studies made on European cases diagnosed between 2000 and 2007 showed survival rates in 1, 3 and 5 years of 63%, 30% and 20%, respectively, as well as high rates of locoregional recurrence and distant metastasis [3, 11].

Tumor arising from the respiratory mucosa (such as the nasal cavity) have different clinical and pathological features when compared to those involving oral mucosa, as melanomas originating from non-squamous mucosa behave differently than those originating from multilayered squamous mucosa [11], but still they share similar adverse outcomes and prognosis and, therefore, will be discussed further in this chapter [1].
