Clinicopathological significance of intratumoral and peritumoral lymphocytes and lymphocyte score based on the histologic subtypes of cutaneous melanoma

Abstract

The presence of tumor infiltrating lymphocytes is a favorable prognostic factor in cutaneous melanoma, but their clinicopathological significance in the intratumoral compartment compared to the peritumoral compartment is unclear. We investigated the clinicopathologic significance of tumor-infiltrating lymphocytes and lymphocyte score in intra- and peritumoral compartments in 177 Korean patients who had undergone surgical excision of cutaneous melanoma. No significant correlation was observed between various clinicopathologic factors and the presence of intratumoral lymphocytes. However, high peritumoral lymphocyte scores were associated with lower Clark levels (P = 0.001), shallower Breslow thicknesses (P = 0.006), and fewer mitotic counts (P = 0.01) than tumors with lower scores. There was a trend for longer disease-free survival in cases with peritumoral lymphocytes (P = 0.07) than those without peritumoral lymphocytes. In patients with acral lentiginous melanoma, a strong association between a high peritumoral lymphocyte score and shallow Clark level was apparent (P = 0.03), and the presence of peritumoral lymphocytes (P = 0.02) and a high intratumoral lymphocyte score (P = 0.04) was also associated with longer disease-free survival. Particularly, low intratumoral lymphocyte score remarkably affected tumor recurrence and distant metastasis in a multivariate analysis using Cox regression test (H.R. = 0.304, 95% C.I. = 0.078-1.185, P = 0.09). Thus, the presence of lymphocytes and high lymphocyte scores in the intratumoral and peritumoral compartments are valid prognostic factors in cutaneous melanoma.

Keywords: intratumoral lymphocyte; lymphocytic score; melanoma; peritumoral lymphocyte; tumor infiltrating lymphocyte.

Figure 1. Microscopic examples of low and high lymphocyte scores in the intratumoral and peritumoral compartments of cutaneous melanomas

Representative microphotographs of the intratumoral and peritumoral lymphocyte scores with original magnification ×100 (H&E).

Figure 2. Survival of patients with cutaneous melanoma of different histological subtypes

(A) Disease-free survival. (B) Overall survival. ALM: acral lentiginous melanoma; NM: nodular melanoma; SSM: superficial spreading melanoma.

Figure 3. Kaplan-Meier survival analysis in intratumoral and peritumoral compartments

(A) Disease-free survival of all cases of cutaneous melanomas in the study, in the presence or absence of peritumoral lymphocytes. (B) Disease-free survival of all cases of cutaneous melanoma in the study, compared to the peritumoral lymphocyte scores. (C) Disease-free survival of 80 acral lentiginous melanomas in the presence or absence of peritumoral lymphocytes. (D) Disease-free survival of 80 acral lentiginous melanomas compared to the intratumoral lymphocyte score.