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Oncogenic BRAF is expressed in a variety of melanoma subtypes

Historically, the classification of primary melanoma has been determined by site of origin, tumor thickness, and histological subtype. For instance, cutaneous melanoma, a primary site of melanoma, has been subclassified into 4 groups with distinct clinicopathologic features: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma (Figure 2).¹⁷

Ongoing genetic studies using a variety of technologies, including DNA sequencing and immunohistochemistry, are demonstrating specific genotype-phenotype correlations that provide insights into molecular subclassifications of melanoma and the heterogeneous nature of this malignancy.¹⁷

Continuing research into determining whether molecular pathways of tumor progression differ between subtypes of cutaneous melanoma is critical in order to ensure the most appropriate treatments can be offered to the right patient subtype.²⁴

Superficial spreading malignant melanomas and lentigo maligna melanomas

A study by Saldanha et al concluded that while the mutational frequency of BRAF differed between cutaneous melanoma subtypes, BRAF mutations were most frequent in superficial spreading malignant melanomas and lentigo maligna melanomas. Superficial spreading melanoma is commonly associated with sun exposure and comprises 70% of primary cutaneous melanomas. Lentigo maligna melanomas are diagnosed as thin lesions and commonly manifest on the faces of older individuals. Identification of BRAF mutations in these patients suggests that the activation of the RAS-RAF pathway may be an important genetic feature of these melanomas.^15,25

Figure 2

A.

Reprinted with permission from MacMillan Publishers Ltd: Mod Pathol, 2006.

B.

Reprinted with permission from MacMillan Publishers Ltd: Mod Pathol, 2006.

A) Histology of superficial spreading melanoma comprises haphazardly distributed atypical melanocytes present as single cells and/or nests of cells throughout different levels of the epidermis. B) Histology of lentigo maligna. The tumor is typically characterized by confluent single melanocytes aligned along the dermal-epidermal junction and spreading down cutaneous appendages. The cells are small and do not normally exhibit hyperchromatic nuclei and pagetoid extensions. An underlying solar elastosis is common in this subcategory of tumors.^26,27