A 56-year-old woman comes to the office due to a pigmented lesion on her back. She first noted the lesion a year ago and says it has enlarged. Past medical history is unremarkable. The patient has worked as a forest service ranger for the last 30 years and has spent much of her time outdoors. On examination, there is a large irregular pigmented lesion on the upper back, as shown in the exhibit, as well as scattered patches of erythema and telangiectasias. Excisional biopsy of the lesion shows malignant melanoma. Which of the following is associated with the highest risk of metastasis for this patient's lesion?
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Malignant melanoma most often arises in the skin, although it may occur wherever there are pigmented cells, such as the eye and the mucosa of the gastrointestinal tract. Sunlight exposure appears to be an important factor in the pathogenesis of dermal melanoma, as are hereditary factors and a history of preexistent dysplastic nevi. Light-skinned individuals are at greatest risk.
On gross inspection, melanomas are characterized by asymmetric shape, irregular or jagged border, variability of color (brown, black, red, blue, or unpigmented), diameter >0.5 cm, and evolution in size and appearance over time (ABCDE criteria). Histologically, melanoma cells congregate in poorly formed nests and are large with irregular nuclei, clumped chromatin, and prominent nucleoli.
In early development, many melanomas exhibit a radial growth phase. This superficial, horizontal growth within the epidermis and superficial dermis carries a very low risk of metastatic spread (Choice A). In contrast, melanomas in the vertical growth phase contain melanoma cells that travel downward into the deeper dermal layers, increasing metastatic risk. Vertical growth often corresponds to a palpable nodularity of the lesion. The Breslow depth (distance from the epidermal granular cell layer to the deepest visible melanoma cells) is the most important prognostic indicator in malignant melanoma.
(Choice C) A dense lymphocytic infiltration of the tumor suggests a robust immune response and is thought to improve prognosis.
(Choice D) Multinucleated giant melanocytes are a characteristic finding in lentigo maligna melanoma. Lentigo maligna are common pigmented lesions in elderly patients and are considered to be a type of melanoma in-situ. When melanoma develops in lentigo maligna, the prognosis is similar to other melanomas of the same stage.
(Choice E) Prominent cellular atypia is a classic finding of malignant melanoma, but it is not considered the most important risk factor for metastatic disease.
Educational objective:
Melanoma often has an early horizontal growth phase with low metastatic potential followed by a nodular, vertical growth phase with a significantly increased risk of metastasis. Depth of invasion (Breslow thickness) is the most important prognostic indicator in malignant melanoma.