Tumour-infiltrating lymphocytes, tertiary lymphoid structures and myxoid stroma predict upstaging of ductal carcinoma in situ in breast biopsies.

Aims: We aimed to evaluate tumour-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLSs) and myxoid stroma in breast biopsies diagnosed with atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). We hypothesized that these stromal features may help identify patients at high risk for upstaging to invasive carcinoma.

Methods and results: Analysis included 592 patients diagnosed with ADH or DCIS via breast biopsy. TILs, TLSs and myxoid stroma were correlated with high-risk features, including larger lesion size, higher BIRADS scores, higher nuclear grade, comedonecrosis, oestrogen receptor (ER) negativity and HER2 overexpression, and were associated with an increased risk of upstaging. In a multivariate logistic regression model incorporating stromal TILs or TLSs, myxoid stroma and basic pathological factors, both stromal TILs or TLSs and myxoid stroma showed independent predictive value, with an AUC of 0.77. The AUC further increased to 0.87 when clinical factors and immunohistochemistry (ER and HER2) were included. Both stromal TILs or TLSs and myxoid stroma demonstrated predictive power exceeding that of comedonecrosis and comparable with nuclear grade. The two pathologists showed moderate to high interobserver agreement in evaluating these stromal and immune features. A simplified scoring system based on six clinicopathological variables retained strong discriminative ability (AUC 0.84).

Conclusions: Stromal TILs, TLSs and myxoid stroma are robust predictors of upstaging to invasive carcinoma in patients diagnosed with ADH/DCIS on biopsy. These features can be readily assessed by pathologists using only H&E staining and should be considered in future risk stratification models to inform clinical decision-making.