Clinicopathologic Features and Immune Cell Subtypes Analysis of Tumor-infiltrating Lymphocytes Rich Invasive Breast Carcinoma of No Special Type

Tumor-infiltrating lymphocytes (TILs) rich invasive breast carcinoma no special type (IBC-NST) is an updated name introduced in the fifth edition WHO classification of breast tumors. Typical medullary breast carcinoma (MBC) represents one end of the spectrum of TILs-rich IBC-NST rather than a distinct morphologic subtype in the new category. A total of 42 cases of MBC and 180 cases of high-grade triple-negative breast cancer (TNBC) without medullary features were included. All samples were stained for CD20, CD4, CD8, and FoxP3 by immunohistochemistry staining. TILs infiltration was more prominent in the MBC tumor nests and in the stroma of high-grade TNBC without medullary features. The average stromal TILs percentage was 78.10% and 61.33%. MBC showed significantly lower numbers of lymphocytes expressing FoxP3 (P < 0.001), no significant difference in the number of CD4 (P = 0.154), CD8 (P = 0.199), and a significantly higher CD8/FoxP3 ratio (P < 0.001) than the other high-grade TNBC. MBC cases demonstrated less aggressive features such as lower TNM stage (P = 0.031), smaller tumor size (P = 0.010), and negative lymph node status (P = 0.021) than the other high-grade TNBC. The 5-year disease-free survival and overall survival were significantly higher for MBC 82.50% and 85.00% compared with the other high-grade TNBC(54.49% and 58.68%). MBC is mostly triple-negative with higher nuclear atypia. Despite advanced staging based on cell morphology, it has low malignancy and a good prognosis. Differences in biological features and prognosis between MBC and high-grade TNBC without medullary features may be associated with the composition and function of TILs. Immune cell subtypes are complex in TILs-rich IBC-NST and deserve further investigation.