Tumor-infiltrating lymphocyte grade (TIL grade) is an independent predictor of sentinel lymph node status and survival in cutaneous melanoma patients

Abstract

Purpose: To determine whether density and distribution of tumor-infiltrating lymphocytes (TIL) (TIL grade) is an independent predictor of sentinel node (SLN) status and survival in patients with clinically localized primary cutaneous melanoma. Methods: From the Melanoma Institute Australia database, 1865 patients with a single primary melanoma >0.75mm in thickness were identified. The associations of clinical and pathologic factors with SLN status, recurrence-free survival (RFS) and melanomaspecific survival (MSS) were analyzed. Results: The majority of patients had either no (TIL grade 0, 35.4%) or few (TIL grade 1, 45.1%) TILs, with a minority showing moderate (TIL grade 2, 16.3%) or marked (TIL grade 3, 3.2%) TILs. Tumor thickness, mitotic rate and Clark level were inversely correlated with TIL grade (each p<0.0001). SLN biopsy was performed in 1138 (61%) patients and was positive in 237 (21%). There was a significant inverse association between SLN status and TIL grade (SLN positivity rates for each TIL grade: 0=27.8%, 1=20.1%, 2=18.3%, 3=5.6%; p<0.0001). Predictors of SLN positivity were decreasing age (p<0.0001), decreasing TIL grade (p<0.0001), ulceration (p=0.003), increasing tumor thickness (p=0.01)satellitosis (p=0.03) and increasing mitoses (p=0.03). 5-year MSS and RFS rates were 83% and 76%, respectively (median follow-up 43 months). Tumor thickness (p<0.0001), ulceration (p<0.0001), satellitosis (p<0.0001), mitotic rate (p=0.003), TIL grade (p<0.0001) and gender (p=0.01) were independent predictors of MSS. Patients with TIL grade 3 tumors had 100% survival. Conclusion: TIL grade is an independent predictor of survival and SLN status in melanoma patients. Patients with a pronounced TIL infiltrate have an excellent prognosis.