Assessment of stromal tumor infiltrating lymphocytes and immunohistochemical features in invasive micropapillary breast carcinoma with long-term outcomes

Abstract

Purpose: We studied the long-term outcomes of invasive micropapillary carcinoma (IMPCs) of the breast in relation to stromal tumor infiltrating lymphocytes (sTILs), prognostic biomarkers and clinico-pathological features.Methods: Stage I-III IMPCs treated with upfront surgery at our institution (January 2000 and December 2016) were included. Central pathology review was performed and sTILs (including zonal distribution and hot spot analysis) and tumor associated plasma cells (TAPC) were evaluated. Expression of P53, BCL2, FOXP3, and WT1, which are variably linked to breast cancer prognosis, was measured by immunohistochemistry using tissue microarrays.Time-to-event endpoints were distant recurrence free interval (DRFI) and breast cancer specific survival (BCSS). Results:We included 111 patients of whom 59% were pure IMPCs. Standard clinicopathological features were comparable between pure and non-pure IMPCs. Overall, the mean sTILs level was 20% with higher proportion of sTILs present at the invasive front. There were no significant differences between pure-and non-pure IMPCs in sTILs levels, nor in the spatial distribution of the hot spot regions or in the distribution of TAPC. Higher sTILs correlated with worse DRFI (HR=1.55; p=0.0172) and BCSS (HR=2.10; p<0.001).Conclusions: Clinico-pathological features, geographical distribution of sTILs and TAPC are similar between pure and non-pure IMPCs. Despite a high proportion of grade 3 tumors and lymph node involvement, we observed a low rate of distant recurrences and breast cancer related death in this cohort of stage I-III IMPCs treated with primary surgery. Caution in interpretation of the observed prognostic correlations is required given the very low number of events, warranting validation in other cohorts.

Intra-Tumour Heterogeneity Is One of the Main Sources of Inter-Observer Variation in Scoring Stromal Tumour Infiltrating Lymphocytes in Triple Negative Breast Cancer

“…Heterogeneity complicates assessment in both core biopsies and excision specimens because the former generally contains multiple separate cores and fragments of tumour. Additionally, the interpretation of sTILs hotspots poses a particular challenge [25]. Current guidance recommends averaging sTILs over the tumour and not focusing on hotspots [12]; however, this is difficult to achieve on core biopsies and the inclusion or exclusion of the hotspot impacts on consistency.…”

Papillary lesions of the breast

“…Despite higher frequency of lymph node metastasis, higher tumor grade, and more frequent lymph vascular invasion compared to NST carcinomas, pure IMPC does not show worse prognosis [16]. A higher level of stromal tumor infiltrating lymphocytes (TILs) seems to be associated with features of dismal prognosis when compared to IMPC with low TILs, being consistent with the predominant luminal phenotype of IMPC [22]. Immunohistochemistry for GATA3, WT1, and PAX8 is useful to exclude metastasis from ovarian serous carcinoma.…”

Micropapillary Breast Carcinoma: From Molecular Pathogenesis to Prognosis

“…PR positivity was more frequent in IDC patients Kim et al (2005) 102 Case–Control Study Positive in 19.4% of the patients Positive in 19.4% of the patients Positive in 38.9% of the patients No observed differences compared to non-IMPC patients Collins et al (2017) 108 Case Series Study Positive in 100% of the patients Positive in 85.7% of the patients Positive in 14.2% of the patients – Yoon et al (2019) 124 Case–Control Study Positive in 79.2% of the patients Positive in 60.7% of the patients Positive in 38% of the patients After propensity score matching, HER-2 positivity was significantly higher in IMPC patients compared to IDC patients. No observed difference in ER or PR positivity Kim et al (2010) 140 Case–Control Study Positive in 77% of the patients Positive in 73.8% of the patients Positive in 39.3% of the patients No observed difference between IMPC and IDC patients Chen et al (2018) 143 Case–Control Study Positive in 83.2% of the patients Positive in 74.7% of the patients Positive in 21.1% of the patients – Li et al (2019) 144 Case–Control Study Positive in 88.69% of the patients Positive in 78.75% of the patients – ER and PR positivity rates were higher in IMPC patients, compared to IDC patients Li et al (2016) 147 Case–Control Study Positive in 81.8% of the patients Positive in 75.8% of the patients Positive in 18.8% of the patients ER positivity rates were signi...…”