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Published on: June 1, 2019
Histiocyte Quantity in Tumor-Negative Sentinel Lymph Nodes Predicts 10-Year Disease-Free Survival in Patients With
Sabine Dieleman1, Loes F S Kooreman2, Michiel T H M Henkens3
1Department of Pathology, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Surgery, GROW - Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Background And Aim:
The sentinel lymph node (SLN) play a key role in the host antitumor immune response. Microarchitectural patterns in tumor-negative SLNs (SLNneg) may provide important clinical information about the host's antitumor immune response against breast cancer.
Methods:
This retrospective cohort study included SLNneg from 339 breast cancer patients. SLNneg microarchitectural features (percentage (%) SLNneg area occupied by histiocytes, germinal centers, lymphocytes outside germinal centers, adipocytes, vessels or connective tissue) were quantified morphometrically. The relationship with 10-year disease-free survival (DFS) was investigated using Cox regression analyses. Variables showing a nonlinear relationship with survival, cubic spline analysis was used to identify distinct groups.
Results:
SLNnegs were predominantly occupied by lymphocytes (median % SLNneg area: 60%) followed by histiocytes (14%), vessels (7%), connective tissue (5%), adipocytes (5%) and germinal centers (0.4%). Histiocyte quantity was related to survival in a nonlinear fashion with 9% and 21% as relevant cutoffs. Patients with < 9% or > 21% SLNneg area occupied by histiocytes had poorer survival compared to patients with 9% to 21% SLNneg area occupied by histiocytes (< 9% SLNneg area Hazard Ratio (HR) 2.5 (95% CI, 1.4-4.5), P = .001; > 21% SLNneg area HR 2.7 (1.5;4.7), P < .001; 9% to 21% SLNneg area = ref.), remaining significant in multivariable analysis. The other microarchitectural features were not related to survival.
Conclusion:
This is the first study showing that quantity of histiocytes in SLNneg is associated with 10-year DFS in breast cancer in a nonlinear manner. This suggests that cell type specific morphological changes within the SLNneg reflect the host's antitumor immune response providing clinically relevant information in breast cancer patients.
