Melanoma

A melanoma, frequently called a malignant melanoma, is an aggressively malignant cancer that develops in epithelial cells capable of producing melanin. It appears most often on the skin, but, also, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. Early detection is critical, as localized melanoma usually can be surgically excised, but metastatic disease has a poor prognosis.

It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world.

Pathology

The microstage of malignant melanoma is determined on histologic examination by the vertical thickness of the lesion in millimeters (Breslow classification) and/or the anatomic level of local invasion (Clark classification). The Breslow thickness is more reproducible and more accurately predicts subsequent behavior of malignant melanoma in lesions larger than 1.5 mm in thickness and should always be reported. Accurate microstaging of the primary tumor requires careful histologic evaluation of the entire specimen by an experienced pathologist. Estimates of prognosis should be modified by sex and anatomic site as well as by clinical and histologic evaluation. Clark Classification (Level of Invasion)

• Level I: Lesions involving only the epidermis (in situ melanoma); not an invasive lesion.
• Level II: Invasion of the papillary dermis but does not reach the papillary-reticular dermal interface.
• Level III: Invasion fills and expands the papillary dermis but does not penetrate the reticular dermis.
• Level IV: Invasion into the reticular dermis but not into the subcutaneous tissue.
• Level V: Invasion through the reticular dermis into the subcutaneous tissue.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define melanoma. TNM Definitions

Primary tumor (T) TX: Primary tumor cannot be assessed (e.g., shave biopsy or regressed melanoma) T0: No evidence of primary tumor Tis: Melanoma in situ T1: Tumor 1.0 mm or less in thickness with or without ulceration T1a: Tumor 1.0 mm or less in thickness and Clark level II or III with no ulceration T1b: Tumor 1.0 mm or less in thickness and Clark level IV or V or with ulceration T2: Tumor more than 1.0 mm but 2.0 mm or less in thickness with or without ulceration T2a: Tumor more than 1.0 mm but 2.0 mm or less in thickness with no ulceration T2b: Tumor more than 1.0 mm but 2.0 mm or less in thickness with ulceration T3: Tumor more than 2.0 mm but 4.0 mm or less in thickness with or without ulceration T3a: Tumor more than 2.0 mm but 4.0 mm or less in thickness without ulceration T3b: Tumor more than 2.0 mm but 4.0 mm or less in thickness with ulceration T4: Tumor more than 4.0 mm in thickness with or without ulceration T4a: Tumor more than 4.0 mm in thickness without ulceration T4b: Tumor more than 4.0 mm in thickness with ulceration Regional lymph nodes (N) [Note: Micrometastases are diagnosed after elective or sentinel lymphadenectomy; macrometastases are defined as clinically detectable lymph nodes metastases confirmed by therapeutic lymphadenectomy, or when any lymph node metastasis exhibits gross extracapsular extension.] NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis to one lymph node N1a: Clinically occult (microscopic) metastasis N1b: Clinically apparent (macroscopic) metastasis N2: Metastasis to two or three regional nodes or intralymphatic regional metastasis without nodal metastases N2a: Clinically occult (microscopic) metastasis N2b: Clinically apparent (macroscopic) metastasis N2c: Satellite or in-transit metastasis without nodal metastasis N3: Metastasis in more than four regional nodes, or matted lymph nodes, or in-transit metastasis or satellite(s) with metastatic regional node(s) Distant Metastasis (M) MX: Distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis M1a: Metastasis to skin, subcutaneous tissues, or distant lymph nodes M1b: Metastasis to lung M1c: Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehydrogenase