Malignant melanoma is a cancer of melanocytes. The cancer incidence is on the rise, afflicting over 68,000 people in the United States annually and causing 8000 annual deaths.8 It is the fifth most frequently diagnosed cancer in men (lifetime risk of 2.67%) and the sixth most common in women (lifetime risk of 1.79%).8 Malignant melanoma attracts a great amount of publicity, because it is one of the most common potentially lethal malignancies of young adults. From 1970 to 2009 in Olmsted County, Minnesota, the incidence of melanoma increased by 8-fold among young women and 4-fold among young men (although there was no increase in mortality).9 It is the easiest malignancy to diagnose early, and there are national educational campaigns in most countries emphasizing the importance of self-examination of the skin.
Melanoma can occur at any age but is rare in childhood. Lifetime risk factors (in roughly decreasing risk) include genotypes with specific risk enhancement (eg, CDKN2A), atypical nevus syndrome (especially if two immediate family members have a melanoma history), family history of melanoma in first-order relatives, prior personal history of melanoma, one or more atypical nevi, large numbers of common nevi, advancing age, outdoor occupations or aviation flight occupation, fair skin, history of blistering sunburn, and a history of commercial tanning.3
Most melanomas begin as de novo lesions, although some authors state up to 30% arise in preexisting nevi. The cancer genetics for melanoma are complex, but certain oncogenes have become important because of their frequencies and because of potential therapeutic implications for targeted therapy (eg, vemurafenib for BRAF mutation). Other mutations in addition to BRAF (most common in superficial spreading melanoma) include KIT (most common in lentigo maligna melanoma and acral-lentiginous melanoma), NRAS, and CDKN2A (the most common specific mutation in familial melanoma).10 About 20% to 40% of familial melanoma cases are associated with a CDKN2A mutation.
Patients often have a history of a change in size, shape or color or pruritus in a new or existing nevus.
Melanoma can occur on any skin surface irrespective of sun exposure. The most common locations in men are the trunk (55%), especially the upper back, followed by the legs, arms, and face; in women, the most common location is the legs (42%), followed by the trunk, arms, and face.8
Melanomas typically have the features as listed in Table 18-1. Figure 18-9 demonstrates many of these features.
Melanoma. Demonstrating the ABCD rule with asymmetry, irregular border, variable color, and diameter >6 mm.
Superficial spreading melanoma can occur in sun-exposed or nonexposed skin. It is characterized by a superficial radial growth phase that occurs before an invasive vertical growth phase (Figure 18-10). These melanomas account for about 70% of melanomas and have an excellent prognosis when detected early.
Lentigo maligna melanoma occurs most commonly in sun-damaged skin of the head and neck of elderly patients (Figure 18-11). These account for 10% to 30% of melanomas, depending on the patients' age demographics and latitude.11 These are very often diagnosed as in situ lesions.
Nodular melanoma: These melanomas, representing 10% to 15% of melanomas, lack a radial growth phase (Figure 18-12). They grow rapidly over months and are often advanced at the time of diagnosis.
Acral lentiginous melanoma occurs on the palms and soles (Figure 18-13). It accounts for only about 5% of melanomas in Caucasians, but is the most common cause of melanomas in Asians and Blacks. It is often advanced at diagnosis because of patients' inattentiveness to the sole of the foot.
Superficial spreading melanoma. Dark brown plaque with variable colors and irregular borders on temple.
Lentigo maligna melanoma. Four centimeter lentigo maligna on cheek with indistinct and irregular borders and variable colors with an invasive melanoma component on medial border. A benign lentigo is above the melanoma.
Nodular melanoma. Black–dark grey papule with crust and superficial ulcer on earlobe.
Acral lentiginous melanoma. Dark brown patch with variable colors and irregular border with crust and superficial ulceration on the plantar and lateral aspect of the foot.
Other Presentations of Melanoma
Melanoma in situ (MIS) is a proliferation of malignant melanocytes confined to the epidermis. The American Cancer Society estimated that 46,770 cases of MIS occurred in the United States in 2010. The most common subtype of MIS is lentigo maligna which occurs in sun-exposed skin and accounts for 80% of MIS.11
Metastatic melanoma from an unknown primary: This occurs in about 3% to 5% of all melanoma patients. If the metastasis is limited to skin or lymph nodes, the prognosis is actually better than patients with visceral metastases from a known primary.
Primary mucosal melanoma of the head and neck: This rare subtype occurs in about 1% of melanomas.
Vulvo/vaginal melanoma: These account for a small number of melanomas. However, melanoma in this location is important because the detection is often delayed.
Subungual melanoma: Subungual melanoma accounts for up to 3% of melanomas. It most commonly presents with pigmentary changes of the nail bed. The diagnosis is aided by dermoscopy. Early diagnosis is essential as the prognosis is otherwise poor compared to other melanoma locations.
Primary ocular melanoma: Ocular melanoma is extremely rare. Lesions may be uveal, ciliary, or choroidal and are not amenable to biopsy. Patients usually present with visual loss or pain. The diagnosis is based on physical findings.
Pediatric melanoma: Accounts for 1% to 4% of melanoma. Thirty percent of pediatric melanomas arise in association with a giant congenital melanocytic nevus.12 In two-thirds of the cases the melanomas develop within the congenital nevus.13
Amelanotic melanoma is a variant of melanoma. It usually presents as a pink lesion (Figure 18-14). Dermoscopy will sometimes show a pigment network or globules not apparent on clinical examination. These lesions usually are outliers (ugly ducklings) but sometimes are masked by other pink lesions, particularly in patients with atypical nevus syndrome. They are often nodular and may be confused with pyogenic granulomas.
Desmoplastic melanomas account for 1% of melanoma. These most commonly present as flesh-colored or pink papules or nodules, most commonly on the head, neck, palms, and soles. Although often invasive at the time of diagnosis, the prognosis is better than for comparably thick nodular melanomas. The cell of origin is controversial and this tumor may in fact be a soft tissue sarcoma.
Familial melanoma: 5% to 10% of melanomas occur in familial clusters. Up to 40% of patients with familial melanoma have a gene mutation in the CDKN2A suppressor gene. These patients also are at increased risk for pancreatic cancer. Indications for genetic screening include individuals with three or more primary melanomas or family members affected by two melanomas or two pancreatic cancers.10
Amelanotic melanoma. Pink dome-shaped nodule on temple. The lesion has scale on the surface and crust on the periphery.
The histopathological findings of a melanoma include an irregular distribution of atypical cells in nests and individually with disruption of normal architecture, violation of boundaries, and a host response evident by an inflammatory infiltrate.
A report of melanoma should include the Breslow depth, which is a measurement of thickness of the tumor measured from the surface of the skin to the deepest level of tumor invasion. Tumor staging is based on the Breslow depth, with 1.0, 2.0, and 4.0 mm being thresholds for T category staging.14 Other features important for staging include the number of mitoses and the presence of ulceration. Additional prognostic factors not incorporated into the current American Joint Committee on Cancer (AJCC) staging classification, which have shown prognostic significance in some studies, include radial and vertical growth phases, regression, angiolymphatic invasion, angiotropism, perineural invasion, and tumor-infiltrating lymphocytes. The Clark classification, which is an older measurement of tumor invasion, is not used any more. Atypical melanocytic hyperplasia is a term that describes lesions that are ambiguous histopathologically and may be difficult to distinguish from melanoma. Most experts treat these lesions as MIS.
Most melanomas present with one of more features as listed in the ABCDE rule (Table 18-1).
Dermoscopy is of limited usefulness in patients with nevi that have borderline dermoscopic features or are completely featureless structurally. In these patients if there is clinical uncertainty one is obligated to remove the lesion. An alternative is to follow the patient with serial photography,5 an approach that many experts suggest as standard of care for patients with atypical nevus syndrome.
The first step in management of a suspected melanoma is confirmation of the diagnosis with a skin biopsy. The purpose of the biopsy for a suspected melanoma is to make the diagnosis and to provide staging information. The most important staging information is thickness.14 Ideally a suspicious lesion should be excised in its entirety with at least 2 mm of normal appearing skin at the margin (allowing the pathologist to examine the lesion margin).15
Partial biopsies are subject to sampling error and should be avoided except in limited circumstances such as in a large facial lesion in which a total excision may result in an unacceptable scar. Even in that circumstance best practice would be to obtain multiple biopsies from several parts of the lesion.
Shave biopsies are acceptable if the lesion is suspected to be thin (less than 1 mm in thickness) and the biopsy method can remove the entire lesion to a depth of more than 1 mm and include at least 2 mm of normal skin at the margin. This results, in effect, in more of a saucerization biopsy than a shave biopsy.
Melanoma in situ: This is typically treated with surgical excision. Lentigo maligna (the most common subtype of melanoma in situ) should be excised with a wide local excision with 5 to 7 mm margins after verifying margins using a Wood's lamp or dermoscopy. Mohs micrographic surgery is often used for ill-defined or large lesions of lentigo maligna. The advantage of Moh's surgery is that 100% of the peripheral margin is examined following the excision. Disadvantages are unique technical problems resulting from freeze artifacts and the presence of benign melanocytic hyperplasia common to sun-damaged skin. Alternative therapies for lentigo maligna include radiotherapy, cryosurgery, and topical treatment with imiquimod, or long-term close observation.16
Invasive melanoma: In areas where there are cosmetic or anatomic limitations, the margin of excision may deviate from the standard resection margins. The National Comprehensive Cancer Center guidelines stipulate surgical margins based on tumor thickness (Table 18-5).15 The depth of excision is typically down to fat, but preserving muscular fascia.
Primary surgical management of melanoma.
||Download (.pdf) Table 18-5.
Primary surgical management of melanoma.
|Breslow Depth (Thickness) ||Indications for a Sentinel Node Biopsy ||Clinical Surgical Margin (cm) |
|Melanoma in situ ||No ||0.5-1.0 |
|Less than 0.76 mm ||No ||1.0 |
|0.76-1.0 ||If poor prognostic features are present age, eg, <40 years of age, ulceration, mitotic rate >1/mm2, angiolymphatic invasion ||1.0 |
|1.0-2.0 mm ||Yes ||1-2 |
|>2 mm ||Yes ||2.0 |
Sentinel node biopsy: The AJCC Melanoma Staging Committee has recommended that patients with more advanced stages of melanoma (Table 18-5) and with clinically uninvolved regional nodes have sentinel node biopsy performed.14 The sentinel node status is of prognostic value, even if only microscopic metastases are seen.14 However, at the time of this writing, there is no proven therapeutic benefit from sentinel node biopsy, and there is potential morbidity and opportunities for misdiagnosis and therapeutic misadventures.
Monitoring of Patients with Asymptomatic Melanoma
There are no clear data to guide clinicians regarding follow up and laboratory testing.15 It is reasonable to recommend an annual history and physical examination with attention to skin and lymph nodes. In addition, patients should be educated on the importance of interval self-examination of skin and lymph nodes. Baseline laboratory tests and imaging studies are not recommended, nor is there a clear role for surveillance laboratory testing or imaging studies.
Melanoma survival depends on early diagnosis. Most melanomas begin as thin lesions and early diagnosed melanoma with a thickness of less than 0.75 mm has a 5-year survival prognosis exceeding 98%.17 Patients with melanomas with thicknesses between 1 mm and 2 mm have 10-year survival rates of less than 70% and those with melanomas greater than 4 mm in thickness have 10-year survival rates of less than 20%. The web site www.melanomaprognosis.org has more detailed information for prognosis based on the AJCC melanoma data base.
Primary Prevention and Detection
Ultraviolet radiation exposure, including radiation from commercial tanning beds, increases the risk of malignant melanoma. For this reason as well as for primary prevention of other skin cancers patients should be counseled on the value of sun safe behavior, including sun protective clothing, shade, and use of sun screens.
Indications for Consultation
Patients with melanoma who are candidates for sentinel node lymph biopsies should be referred to a surgeon that has expertise in the procedure. Patients should also be referred to dermatology for a total body examination and follow-up examinations. Patients with positive sentinel lymph nodes or with melanomas with a poor prognosis should be referred to oncology.