Despite an overall modest decrease in cancer incidence and cancer-related deaths over the past 20 years (largely related to lung, colon, breast, and prostate cancers), melanoma incidence rates and deaths continue to rise yearly. In the United States alone for 2013, it is estimated that 76,690 new melanoma cases will be diagnosed, and 9,480 deaths will be attributed to melanoma (1). While melanoma accounts for roughly 4% of all skin cancers, it is responsible for more than 77% of skin cancer deaths.

The major risk factors for development of cutaneous melanoma include fair complexion, tendency to sunburn easily, large congenital nevi (greater than 20 cm), presence of atypical/dysplastic nevi (2,3), a personal history of skin cancer (melanoma or otherwise) (4,5,6,7), genetic predisposition (8), and immunosuppression (9). Head and neck melanomas occur more commonly in men (2:1), with a median age at diagnosis of 55 years, and a range of 12 to 92 years (10).

Epidemiologic studies demonstrate higher rates of melanoma in those living in geographic areas that are exposed to intense sunlight (i.e., Australia). This finding and investigations in the laboratory demonstrate that exposure to ultraviolet light plays a major role in the pathogenesis of melanoma, and UV-A and UV-B radiation have both been implicated. This is further supported by the lower rates of melanoma reported in people whose skin natively has more pigmentation, and the incidence of melanoma is approximately 10 times higher in whites than in blacks in the same geographic region (11).

Although the combined head and neck region accounts for only 9% of body surface area, 15% to 30% of all melanomas arise within the head and neck (12,13). Multiple factors may contribute to this anatomic predilection for the skin of the head and neck, including higher levels of sun exposure and melanocyte content of the skin that is two- to threefold higher than other regions (14). Of note, melanomas arising on the face and scalp are associated with higher rates of local recurrence and regional lymph node disease than melanomas arising in other parts of the body.

Melanoma is divided into four distinct clinicopathologic subtypes: lentigo maligna melanoma (LMM), superficial spreading, nodular, and acral lentiginous melanoma. These lesions demonstrate either a radial (intraepithelial) or vertical (intradermal) growth phase or a combination of the two. Radial growth is circumferential in nature and confined to the dermal-epidermal junction. The vertical growth phase (intradermal) demonstrates invasion through the dermal-epidermal junction. The radial growth phase may indicate a lesion’s capacity for growth and invasion into the papillary dermis. These lesions may lack metastatic potential. Conversely, cells in the vertical growth phase may represent a clonal change in cells with a growth advantage over neighboring cells, resulting in the clone’s ability to invade and metastasize.

Cutaneous melanomas may mimic a host of other pathologic cutaneous lesions.

Differential diagnosis includes seborrheic keratosis, benign nevi (including junctional, compound, and dermal), hemangioma, blue nevi, pyogenic granuloma, and pigmented basal cell carcinoma.

Lentigo maligna (LM), also known as melanoma in situ, is a premalignant pigmented lesion that frequently develops in the head and neck region of elderly patients (Fig. 114.1A). Known historically as Hutchinson melanotic freckle, these lesions are associated with solar skin damage and feature atypical melanocytes, which spread radially along the dermal-epidermal junction, exhibit focal nesting, and occasionally extend along skin appendages into the dermis. Up to 5% of LMs or melanomas in situ progress to invasive LMM. LMM lesions should be excised with 0.5- to 1.0-cm margins, although prediction of tumor margins can prove difficult. This is the least common type of cutaneous melanoma and accounts for between 6% and 10% of melanoma lesions. Its growth is characterized by a slow radial phase that may take up to 10 years to progress. At first, they are quite slow to invade deeply, and affected patients have a better prognosis when compared with those with other forms of melanoma.

Superficial spreading melanoma represents the most common type of melanoma and comprises between 65% and 75% of cases (Fig. 114.1B). These lesions may demonstrate a wide variety of colors, including pink, blue-gray, brown, tan, and black. They also may demonstrate radial growth for 5 to 7 years and then become invasive, an event frequently heralded by ulceration and bleeding. High cure rates have been reported when these lesions are clinically detected in the radial growth phase. Spontaneous regression of superficial spreading melanomas also has been reported.

Acral lentiginous is the most common type of melanoma seen in the African American population. Because these lesions commonly occur on the soles of the feet, surfaces of the hand, and oral/anogenital mucosa, head and neck surgeons less commonly encounter them.

Nodular melanoma comprises between 10% and 15% of all melanomas and may affect areas of both exposed and non-sun-exposed areas of the skin (Fig. 114.1C). They tend to develop in patients older than 50 years. Nodular melanoma is considered to be the most invasive of the cutaneous melanomas, and affected patients have the poorest prognosis.

Desmoplastic melanoma is a histologic variant of melanoma that accounts for fewer than 1% of melanoma cases overall (Fig. 114.1D). However, as many as 75% of these tumors occur in the head and neck region. Clinically, desmoplastic melanomas may be amelanotic, a feature that impedes early recognition and often leads to significant delays in diagnosis and treatment. Another important characteristic feature of these lesions is their neurotropism.
This predisposes them to perineural invasion and spread that often accounts for local recurrence despite histologically “negative margins” with recurrence rates reported between 23% and 48% (17,18,19,20,21,22). Therefore, it is suggested that wider resection margins be taken around a desmoplastic tumor and that adjuvant radiation is often recommended after definitive excision. Multiple studies have demonstrated a lower rate of regional nodal spread in patients with desmoplastic melanoma as compared to other histologic subtypes of melanoma (23,24,25,26,27). The lower rate of positive sentinel lymph nodes has made the role of SLNB in this population less widely recommended (25). However, a distinction needs to be made between those lesions which are purely desmoplastic and are associated with a low rate of nodal metastasis and those that have a combination of desmoplastic and a more conventional melanoma histology which spread to lymph nodes at the higher frequency associated with the nondesmoplastic histology (25,26). Therefore, SLNB can be recommended in the combined desmoplastic cases, which meet other criteria for performing the biopsy such as depth of invasion, number of mitoses, and/or ulceration.

A relatively rare entity, mucosal melanoma deserves special mention. Primary melanoma may arise in the mucosa of the respiratory, alimentary, and genitourinary tracts, as they all contain melanocytes. Mucosal melanoma accounts for 1% to 2% of all melanomas, with the majority being found in the head and neck region (28). More than 50% of reported cases arise within the nasal cavity. Other affected areas include the paranasal sinuses, nasopharynx, oral cavity, and oropharynx. Esophageal mucosa can also be affected. Nasal obstruction is the most common presenting symptom for sinonasal lesions. However, a significant number of mucosal melanomas may be asymptomatic until they have progressed to an advanced stage, which contributes to the poor prognosis of patients with this diagnosis. Stern and colleagues (29) at the M.D. Anderson Cancer Center found an average of 9 months between the first onset of symptoms and physician intervention. In addition to delay in diagnosis, the poorer prognosis associated with mucosal melanomas may also be related to an inherently more aggressive behavior of mucosal melanomas, or earlier dissemination, because of the rich lymphatic and vascular supply of the mucosa.

The differential diagnosis includes vascular lesions, angiomas, and dental amalgam tattoos. It is not uncommon for the characteristic melanosis to be absent in mucosal melanoma lesions. Biopsy is usually confirmatory, and immunohistochemistry may be used to assist in diagnosis. Desmoplastic variants of mucosal melanoma have been described in the head and neck (30). No studies have conclusively demonstrated that depth of invasion is of prognostic importance in mucosal melanoma.

The majority of these patients have a poor prognosis. These tumors have a high rate of local recurrence, which is typically a harbinger of disseminated disease, and most of these patients die from complications related to distant metastases.

Anatomic constraints frequently preclude the use of excisional biopsy techniques in most patients with mucosal melanoma. Although wide local excision is the mainstay of therapy, radiation therapy has been used as a primary modality and postoperative adjuvant therapy with unclear benefit (31,32,33). It should especially be considered in situations when adequate resection margin is not possible, where it may help prevent local recurrence (34).

Patients may experience multiple local recurrences and ultimately die of a combination of uncontrolled local and distant disease. Five-year survival rates for mucosal melanoma range between 10% and 45% (35,36,37,38,39).

The staging of malignant melanoma has evolved over the past half century in efforts to more reliably determine prognosis and to identify the most appropriate treatment schemes. Clark and Breslow made significant contributions to the microscopic grading of primary cutaneous melanoma. Clark (40) described five levels of anatomic invasion through the layers of the skin. In the Breslow system (41), the maximum thickness of melanomas is used as a prognostic indicator.

The current staging system for melanoma developed by the American Joint Committee on Cancer (AJCC) and adopted by the International Union for Cancer Control, relies upon assessment of the primary tumor (T), regional lymph nodes (N), and distant metastatic sites (M). The seventh, and most recent, edition of this staging system is based upon long-term analysis of over 38,900 patients with cutaneous melanoma (42) (Table 114.1).

As stated previously, the most powerful predictor of survival is lymph node status. In patients with lesions less than 0.75 mm in depth, lymph node observation is appropriate. Patients with lesions between 0.76-1.0 mm in depth, without ulceration and less than 1 mitosis per mm²
should consider lymph node evaluation. Patients with lesions between 0.76-1.0 mm in depth with ulceration or ≥1 mitosis per mm² or with lesions >1 mm with any characteristic should be offered lymph node evaluation. Of the two main ways of evaluating for occult lymph node metastases, SLNB has supplanted elective lymph node dissection (ELND) as the preferred method.

The rationale for determination of nodal status is to appropriately stage patients and to identify patients who may benefit from regional therapy with surgery, radiation, or both to improve locoregional control. The goal is to also identify patients at greater risk for systemic recurrence who could potentially benefit from systemic adjuvant therapy.