MALIGNANT MELANOMA

Malignant melanoma is a neoplasm of melanocytes or of the cells that develop from melanocytes. Although melanoma was once considered an uncommon disease, the annual incidence has increased dramatically over the over the past few decades, as have deaths from melanoma. (See the images of malignant melanoma below.) (See Etiology and Epidemiology.)
A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation. Malignant melanoma. Image courtesy of Hon Pak, MD. Also see Lentigo Maligna Melanoma, Oral Malignant Melanoma, and Head and Neck Mucosal Melanomas.

Growth

Melanomas have 2 growth phases, radial and vertical. During the radial growth phase, malignant cells grow in a radial fashion in the epidermis. With time, most melanomas progress to the vertical growth phase, in which the malignant cells invade the dermis and develop the ability to metastasize. (See Etiology and Workup.)
Clinically, lesions are classified as thin if they are 1 mm or less in depth; moderate if they are 1-4 mm in depth; and thick if they are greater than 4 mm in depth.

Histologic types of melanoma

There are 5 different forms, or histologic types, of melanoma:

• Superficial spreading melanomas
• Nodular melanomas
• Lentigo maligna melanomas
• Acral lentiginous melanomas
• Mucosal lentiginous melanomas

Superficial spreading melanomas

Approximately 70% of cutaneous malignant melanomas are the superficial spreading melanoma (SSM) type and often arise from a pigmented dysplastic nevus. SSMs typically develop after a long-standing stable nevus changes; typical changes include ulceration, enlargement, or color changes. An SSM may be found on any body surface, especially the head, neck, and trunk of males and the lower extremities of females.

Nodular melanomas

Nodular melanomas (NMs) represent approximately 10-15% of melanomas and also are found commonly on all body surfaces, especially the trunk of males. These lesions are the most symmetrical and uniform of the melanomas and are dark brown or black. The radial growth phase may not be evident in NMs; however, if this phase is evident, it is short-lived, because the tumor advances rapidly to the vertical growth phase, thus making the NM a high-risk lesion. Approximately 5% of all NMs are amelanotic melanomas.

Lentigo maligna melanomas

Lentigo maligna melanomas (LMMs) also account for 10-15% of melanomas. They typically are found on sun-exposed areas (eg, hand, neck). LMMs may have areas of hypopigmentation and often are quite large. LMMs arise from a lentigo maligna precursor lesion. (See the image of lentigo maligna melanoma below.)
Lentigo maligna melanoma, right lower cheek. The centrally located erythematous papule represents invasive melanoma with surrounding macular lentigo maligna (melanoma in situ). Image courtesy of Susan M. Swetter, MD.

Acral lentiginous melanomas

Acral lentiginous melanomas (ALMs) are the only melanomas that have an equal frequency among blacks and whites. They occur on the palms, soles, and subungual areas. Subungual melanomas often are mistaken for subungual hematomas (splinter hemorrhages). Like NM, ALM is extremely aggressive, with rapid progression from the radial to vertical growth phase.

Mucosal lentiginous melanomas

Mucosal lentiginous melanomas (MLMs) develop from the mucosal epithelium that lines the respiratory, gastrointestinal, and genitourinary tracts. These lesions account for approximately 3% of the melanomas diagnosed annually and may occur on any mucosal surface, including the conjunctiva, oral cavity, esophagus, vagina, female urethra, penis, and anus. Noncutaneous melanomas commonly are diagnosed in patients of advanced age. MLMs appear to have a more aggressive course than cutaneous melanomas, although this may be because they commonly are diagnosed at a later stage of disease than the more readily apparent cutaneous melanomas.

Sites other than the skin

The majority of melanomas are in the skin, but other sites include the eyes, mucosa, gastrointestinal tract, genitourinary tract, and leptomeninges. Metastatic melanoma with an unknown primary site may be found in lymph nodes only.

Staging

Clark staging is as follows:

• level I - All tumor cells above basement membrane (in situ)
• level II - Tumor extends into papillary dermis
• level III - Tumor extends to interface between papillary and reticular dermis
• level IV - Tumor extends between bundles of collagen of reticular dermis (extends into reticular dermis)
• level V - Tumor invasion of subcutaneous tissue

Breslow classification (thickness) is as follows:

• Less than or equal to 0.75 mm
• 0.76-1.5 mm
• 1.51-4 mm
• Greater than or equal to 4 mm

The staging system for cutaneous melanoma was revised by the American Joint Committee on Cancer (AJCC) in early 2002.^{[1, 2]}
AJCC groupings based on TNM classification are as follows:

• Stage 0 - Tis, N0, M0
• Stage IA - T1a, N0, M0
• Stage IB - T1b, N0, M0; T2b, N0, M0
• Stage IIA - T2b, N0, M0; T3a, N0, M0
• Stage IIB - T3b, N0, M0; T4a, N0, M0
• Stage IIC - T4b, N0, M0
• Stage III - Any T, N 1-3, M0
• Stage IIIA - pT1-4a, N1a, M0; pT1-4a, N2a, M0
• Stage IIIB - pT1-4b, N1a, M0; pT1-4b, N2a, M0; pT1-4a, N1b, M0; pT1-4a, N2b, M0; pT1-4a/b, N2c, M0
• Stage IIIC - pT1-4b, N1b, M0; pT1-4b, N2b, M0; any T, N3, M0
• Stage IV - Any T, Any N, Any M

T classification (thickness) is as follows:

• TX - Primary tumor cannot be assessed (shave biopsy, regressed primary)
• Tis - Melanoma in situ
• T1 - ≤1.0 mm (a: without ulceration, b: with ulceration)
• T2 - 1.01-2.0 mm (a: without ulceration, b: with ulceration)
• T3 - 2.01-4.0 mm (a: without ulceration, b: with ulceration)
• T4 - < 4.0 mm (a: without ulceration, b: with ulceration)

N classification is as follows:

• N1 - 1 lymph node; a: micrometastasis (clinically occult), b: macrometastasis (clinically apparent)
• N2 - 2-3 lymph nodes; a: micrometastasis, b: macrometastasis, c: in transit met(s), satellite(s), without metastatic lymph nodes (N2a: 2-3 nodes positive for micrometastasis; N2b: 2-3 nodes positive for macrometastasis; N2c: In transit met(s) or satellite(s) without metastatic nodes)
• N3 - 4 or more metastatic nodes or matted nodes or in-transit metastases or satellite(s) with metastatic node(s)

Note that micrometastases are diagnosed after elective or sentinel lymphadenectomy. Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.
M classification is as follows:

• M1a - Distant skin, subcutaneous, or nodal metastases, normal lactate dehydrogenase (LDH) level
• M1b - Lung metastases, normal LDH level
• M1c - All other visceral metastases or any distant metastases with an elevated LDH level