Malignant Melanoma

MALIGNANT MELANOMA

A malignant melanoma is a cancerous neoplasm in which atypi-cal melanocytes (ie, pigment cells) are present in the epidermis and the dermis (and sometimes the subcutaneous cells). It is the most lethal of all the skin cancers and is responsible for about 2% of all cancer deaths (Odom et al., 2000).

It can occur in one of several forms: superficial spreading melanoma, lentigo-maligna melanoma, nodular melanoma, and acral-lentiginous melanoma. These types have specific clinical and histologic features as well as different biologic behaviors. Most melanomas arise from cutaneous epidermal melanocytes, but some appear in preexisting nevi (ie, moles) in the skin or de-velop in the uveal tract of the eye. Melanomas occasionally ap-pear simultaneously with cancer of other organs.

The worldwide incidence of melanoma doubles every 10 years, a rise that is probably related to increased recreational sun expo-sure and better methods of early detection. Peak incidence occurs between ages 20 and 45. The incidence of melanoma is increas-ing faster than that of almost any other cancer, and the mortality rate is increasing faster than that of any other cancer except lung cancer. The estimated number of new cases in 2002 is 53,600 and the number of deaths is 7400 (American Cancer Society, 2002).

Risk Factors

The cause of malignant melanoma is unknown, but ultraviolet rays are strongly suspected, based on indirect evidence such as the increased incidence of melanoma in countries near the equator and in people younger than age 30 who have used a tanning bed more than 10 times per year. In general, 1 in 100 Caucasians will get melanoma every year. Up to 10% of melanoma patients are members of melanoma-prone families who have multiple chang-ing moles (ie, dysplastic nevi) that are susceptible to malignant transformation. Patients with dysplastic nevus syndrome have been found to have unusual moles, larger and more numerous moles, lesions with irregular outlines, and pigmentation located all over the skin. Microscopic examination of dysplastic moles shows disordered, faulty growth. Chart 56-7 lists risk factors for malignant melanoma.

Research has identified a gene that resides on chromosome 9p, the absence of which increases the likelihood that potentially mutagenic DNA damage will escape repair before cell division. The absence of this gene can be identified in melanoma-prone families (Piepkorn, 2000).

Clinical Manifestations

Superficial spreading melanoma occurs anywhere on the body and is the most common form of melanoma. It usually affects middle-aged people and occurs most frequently on the trunk and lower extremities. The lesion tends to be circular, with irregular outer portions. The margins of the lesion may be flat or elevated and palpable (Fig. 56-7). This type of melanoma may appear in a combination of colors, with hues of tan, brown, and black mixed with gray, blue-black, or white. Sometimes a dull pink rose color can be seen in a small area within the lesion.

LENTIGO-MALIGNA MELANOMAS

Lentigo-maligna melanomas are slowly evolving, pigmented le-sions that occur on exposed skin areas, especially the dorsum of the hand, the head, and the neck in elderly people. Often, the le-sions are present for many years before they are examined by a physician. They first appear as tan, flat lesions, but in time, they undergo changes in size and color.

NODULAR MELANOMA

Nodular melanoma is a spherical, blueberry-like nodule with a relatively smooth surface and a relatively uniform, blue-black color (see Fig. 56-7). It may be dome shaped with a smooth sur-face. It may have other shadings of red, gray, or purple. Some-times, nodular melanomas appear as irregularly shaped plaques.

The patient may describe this as a blood blister that fails to re-solve. A nodular melanoma invades directly into adjacent dermis (ie, vertical growth) and therefore has a poorer prognosis.

ACRAL-LENTIGINOUS MELANOMA

Acral-lentiginous melanoma occurs in areas not excessively ex-posed to sunlight and where hair follicles are absent. It is found on the palms of the hands, on the soles, in the nail beds, and in the mucous membranes in dark-skinned people. These melanomas appear as irregular, pigmented macules that develop nodules. They may become invasive early.

Assessment and Diagnostic Findings

Biopsy results confirm the diagnosis of melanoma. An excisional biopsy specimen provides histologic information on the type, level of invasion, and thickness of the lesion. An excisional biopsy specimen that includes a 1-cm margin of normal tissue and a por-tion of underlying subcutaneous fatty tissue is sufficient for staging a melanoma in situ or an early, noninvasive melanoma. Incisional biopsy should be performed when the suspicious lesion is too large to be removed safely without extensive scarring. Biopsy spec-imens obtained by shaving, curettage, or needle aspiration are not considered reliable histologic proof of disease.

A thorough history and physical examination should include a meticulous skin examination and palpation of regional lymph nodes that drain the lesional area. Because melanoma occurs in families, a positive family history of melanoma is investigated so that first-degree relatives, who may be at high risk for melanoma, can be evaluated for atypical lesions. After the diagnosis of mel-anoma has been confirmed, a chest x-ray, complete blood cell count, liver function tests, and radionuclide or computed to-mography scans are usually ordered to stage the extent of disease.

Prognosis

The prognosis for long-term (5-year) survival is considered poor when the lesion is more than 1.5 mm thick or there is regional lymph node involvement. A person with a thin lesion and no lymph node involvement has a 3% chance of developing metastases and a 95% chance of surviving 5 years. If regional lymph nodes are in-volved, there is a 20% to 50% chance of surviving 5 years. Patients with melanoma on the hand, foot, or scalp have a better prognosis; those with lesions on the torso have an increased chance of metas-tases to the bone, liver, lungs, spleen, and central nervous system. Men and elderly patients also have poor prognoses (Demis, 1998).

Medical Management

Treatment depends on the level of invasion and the depth of the lesion. Surgical excision is the treatment of choice for small, su-perficial lesions. Deeper lesions require wide local excision, after which skin grafting may be needed. Regional lymph node dis-section is commonly performed to rule out metastasis, although new surgical approaches call for only sentinel node biopsy. This technique is used to sample the nodes nearest the tumor and spares the patient the long-term sequelae of extensive removal of lymph nodes if the sample node is negative (Wagner, 2000).

Immunotherapy has had varied success. Immunotherapy mod-ifies immune function and other biologic responses to cancer. Several forms of immunotherapy (eg, bacillus Calmette-Guérin [BCG] vaccine, Corynebacterium parvum, levamisole) offer en-couraging results. Some investigational therapies include biologic response modifiers (eg, interferon-alpha, interleukin-2), adaptive immunotherapy (ie, lymphokine-activated killer cells), and mono-clonal antibodies directed at melanoma antigens. One of these, proleukin, shows promise in preventing recurrence of melanoma (Demis, 1998). Under investigation is the laboratory assay of ty-rosinase, an enzyme believed to be produced only by melanoma cells (Demis, 1998). Several other studies are attempting to develop autologous immunization against specific tumor cells. These stud-ies are still in the early experimental stage but show promise of pro-ducing a vaccine against melanoma (Piepkorn, 2000).

Current treatments for metastatic melanoma are largely un-successful, with cure generally impossible. Further surgical inter-vention may be performed to debulk the tumor or to remove part of the organ involved (eg, lung, liver, or colon). The rationale for more extensive surgery, however, is for relief of symptoms, not for cure. Chemotherapy for metastatic melanoma may be used; however, only a few agents (eg, dacarbazine, nitrosoureas, cis-platin) have been effective in controlling the disease.

When the melanoma is located in an extremity, regional per-fusion may be used; the chemotherapeutic agent is perfused di-rectly into the area that contains the melanoma. This approach delivers a high concentration of cytotoxic agents while avoiding systemic, toxic side effects. The limb is perfused for 1 hour with high concentrations of the medication at temperatures of 39°C to 40°C (102.2°F to 104°F) with a perfusion pump. Inducing hyperthermia enhances the effect of the chemotherapy so that a smaller total dose can be used. It is hoped that regional perfusion can control the metastasis, especially if it is used in combination with surgical excision of the primary lesion and with regional lymph node dissection.