Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma.
OBJECTIVE
To determine whether density and distribution of tumor-infiltrating lymphocytes (TILs; TIL grade) is an independent predictor of sentinel lymph node (SLN) status and survival in patients with clinically localized primary cutaneous melanoma.


METHODS
From the Melanoma Institute Australia database, 1,865 patients with a single primary melanoma ≥ 0.75 mm in thickness were identified. The associations of clinical and pathologic factors with SLN status, recurrence-free survival (RFS), and melanoma-specific 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 < .001). SLN biopsy was performed in 1,138 patients (61.0%) and was positive in 252 (22.1%). 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 < .001). Predictors of SLN positivity were decreasing age (P < .001), decreasing TIL grade (P < .001), ulceration (P = .003), increasing tumor thickness (P = .01), satellitosis (P = .03), and increasing mitoses (P = .03). The 5-year MSS and RFS rates were 83% and 76%, respectively (median follow-up, 43 months). Tumor thickness (P < .001), ulceration (P < .001), satellitosis (P < .001), mitotic rate (P = .003), TIL grade (P < .001), and sex (P = .01) were independent predictors of MSS. Patients with TIL grade 3 tumors had 100% survival.


CONCLUSIONS
TIL grade is an independent predictor of survival and SLN status in patients with melanoma. Patients with a pronounced TIL infiltrate have an excellent prognosis.
Melanoma Institute Australia, 40 Rocklands Rd, North Sydney NSW 2060, Australia.
Farhad
F
Azimi
Richard A
RA
Scolyer
Pavlina
P
Rumcheva
Marc
M
Moncrieff
Rajmohan
R
Murali
Stanley W
SW
McCarthy
Robyn P
RP
Saw
John F
JF
Thompson
D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology*