Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

Abstract

Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.

Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation

“…2,3,6,10 This immune reaction is believed to be beneficial, leading to the overall improved survival in these patients, 2,3,6,10 such as seen in some other lymphoid-rich neoplasms of both thymic 2 and nonthymic origin. [11][12][13][14][15] It is not clear what mechanism initially triggers such immune reaction, or why this type of reaction only occurs in a subset of thymic epithelial neoplasms. In addition, it is not certain whether the mechanism is a localized or more of a systemic process.…”

Targeted agents and immunotherapies: optimizing outcomes in melanoma

“…In the largest available population-based analysis of primary invasive melanomas 36 , 15% of primary lesions had 'brisk' infiltration (lymphocytes throughout the tumour and/or along almost its entire base), 64% 'non-brisk' , while 20% had no lymphocytic infiltration. Using this classification scheme, a dose-response relationship between an increasing density of lymphocytes and protection from melanoma fatality was observed 36 . Comparatively less evidence is available regarding the influence of lymphocytic infiltration into metastatic lesions on patient prognosis.…”

Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

“…Ис-следование показало, что группы пациентов с умеренной и выраженной лимфоидной инфильтрацией ассоциирова-лись с более низкой стадией меланомы по American Joint Committee on Cancer (AJCC) по сравнению с группой паци-ентов с отсутствием лимфоидной инфильтрации. Смерт-ность от меланомы была ниже на 30% и 50% у пациентов с умеренной и выраженной лимфоидной инфильтрацией соответственно, по сравнению с пациентами без призна-ков лимфоидной инфильтрации [5]. В другом исследова- .…”