A Narrative Review of the Evolution of Diagnostic Techniques and Treatment Strategies for Acral Lentiginous Melanoma

Abstract

Acral melanoma (AM) is a subtype of cutaneous melanoma located on the palms, soles, and nails. The pathogenesis of AM involves mechanical stimulation and characteristic tumor-promoting mutations, such as those in the KIT proto-oncogene. Dermoscopy is useful for diagnosing AM, which is characterized by parallel ridge patterns and irregular diffuse pigmentation. Although histopathological confirmation is the gold standard for diagnosing AM, lesions showing minimal histopathological changes should be considered early-stage AM if they clinically resemble it. Recently, immunohistochemical staining of preferentially expressed antigen in melanoma has been recognized as a useful method to distinguish benign from malignant melanocytic tumors. Research reveals that AM is associated with an immunosuppressive microenvironment characterized by increased numbers of M2 macrophages and regulatory T cells, alongside a decreased number of tumor-infiltrating lymphocytes. Mohs micrographic surgery or digit-sparing wide local excision has been explored to improve quality of life and replace wide local excision or proximal amputation. AM has a worse prognosis than other subtypes, even in the early stages, indicating its inherent aggressiveness.

Keywords: acral lentiginous melanoma; dermoscopy; pathogenesis; preferentially expressed antigen in melanoma; prognosis; surgery; tumor microenvironment.

Figure 1

Clinical, histopathological, and immunohistochemical features of acral melanoma. (A–C) Clinical features of acral melanoma on the soles and palm. Clinical features of subungual melanoma presenting as melanonychia (D) and amelanotic nodule (E). (F,G) Acral melanoma showing asymmetry, border irregularity, multiple colors, and diameter > 6 mm. (H,I) Dermoscopic findings of acral melanoma showing parallel ridge patterns and irregular diffuse pigmentation. (J) Skin biopsy reveals non-equidistant single melanocytes. Malignant melanocytes are positive to HMB-45 (K) and PRAME (L) staining. (M,N) Clinical and dermoscopic features of early acral melanoma showing mild asymmetry and multiple colors. (O) Irregular and confluent nests are observed in skin biopsy (P) Melanocytes are positive to PRAME staining (scale bar = 100 μm; (J) H&E, (K) HMB-45, (L) PRAME, (O) H7E, and (P) PRAME; ×400).

Figure 2

Summary of acral melanoma. Acral melanoma is associated with higher rates of KIT and NF-1 mutations. The general “ABCDE” rule and the “CUBED” rule are used for clinical assessment. Common dermoscopic patterns include the parallel ridge pattern and irregular diffuse pigmentation. Diagnosis relies on histopathological and immunohistochemical findings, with PRAME immunohistochemical staining being a recent area of investigation. Acral melanoma is characterized by an immunosuppressive microenvironment, and surgical approaches have evolved to include slow Mohs microscopic surgery and digit-sparing wide local excision, enhancing quality of life. Overall, the prognosis of acral melanoma is poorer than that of other melanoma subtypes. (Upward pointing arrow in this figure means increased while downward pointing arrow means decreased).

Figure 3

Summary of subungual melanoma. Subungual melanoma has a distinct pathogenesis compared with acral melanoma at other sites. The “ABCDEF” rule is utilized to raise awareness for subungual melanoma. Diagnosis is based on histopathological findings, and the prognosis of subungual melanoma is worse than that of acral melanoma at other sites.