Appraisal of clinicopathological prognosticators in advanced acral lentiginous melanoma with characterization of PD-L1 and CD8/CD4 immunoprofiles.

Acral lentiginous melanoma is the most common subtype of cutaneous melanoma in Asian countries. This study aims to clarify the associations between certain histologic and immunohistochemical parameters, and identify their prognostic values. We assessed several histologic features and conducted immunohistochemical study of programmed cell death ligand 1 (clone 22C3) and CD8/CD4 in 61 Taiwanese patients with Stage III/IV, non-BRAF acral lentiginous melanomas. A total of 41 males and 20 females were included, with a median age of 74 years. The majority of tumors occurred at nonungual locations (86.9%), with 'foot' being the most frequently affected site (85.2%). Positive programmed cell death ligand 1 staining (combined positive score ≥ 10) was significantly associated with the status of tumor-infiltrating lymphocytes (P = 0.036). Lack of skin ulceration was linked to the immunoexpression of CD8/CD4-high (P = 0.004). A superior clinical outcome was found in the tumor-infiltrating lymphocytes-present group (P = 0.011), and among which, CD8/CD4-high was significantly correlated with better survival (P < 0.001). Combined survival analysis revealed that the PD-L1(-) TIL(+) CD8/CD4-high subgroup was associated with favorable prognosis, and cases with PD-L1(+) TIL(-) showed the worst disease specific survival (P < 0.001). In the univariate analysis, lymphovascular invasion (P = 0.002), skin ulceration (P = 0.002), tumor-infiltrating lymphocytes (P = 0.015) and CD8/CD4 status (P < 0.001) were significant prognostic factors. At the multivariate level, the statuses of CD8/CD4-low (P < 0.001) and lymphovascular invasion (P = 0.014) represented the independent poor prognosticators. For advanced, non-BRAF acral lentiginous melanomas, comprehensive assessments of these microscopic traits, along with CD8/CD4 and PD-L1 immunoprofiles, may help guide the clinicians and patients through treatment decisions.