Long-term outcome of high-grade encapsulated papillary carcinoma of the breast: implications for staging and management

Background: Encapsulated papillary carcinoma (EPC) of the breast is an uncommon tumour with controversial biological behaviour and staging. Emerging evidence suggests that EPC with adverse pathological features (EPC-A) may exhibit invasive potential. The absence of uniform staging criteria contributes to management variability. This study evaluates the clinicopathological characteristics and clinical course of high-grade EPC (HG-EPC), including EPC-A. Materials and methods: This retrospective multicentre study (2000-2025) included 25 HG-EPC cases, irrespectively of ER/PR and HER2 status. Tumours with frank stromal invasion beyond microinvasive foci were excluded. Histopathological re-evaluation was performed in accordance with 2019 WHO classification criteria. Results: Of 38 cases reviewed, 25 fulfilled the inclusion criteria as EPC (mean age 57.2 years, mean tumour size 2.9 cm). Six cases (24%) demonstrated conventional-type microinvasive components. A subset of 16 cases fulfilled criteria for EPC-A, defined by high-grade morphology in combination with ER/PR-negative (or ER <30% positive) and/or HER2-positive status. Staging and management were variable. Initial pathological stage varied: pTis (n = 13) to pT1 (n = 4) or pT2 (n = 7), and pT3 (n = 1). Adjuvant chemotherapy and radiotherapy were administered in 7 and 12 patients respectively. During follow-up, four local recurrences (three invasive and one in situ) were observed. One of the locally recurrent patients subsequently developed distant metastasis, and one breast cancer-related death occurred 200 months after diagnosis. Recurrence or death occurred in 20% (5/25) of patients despite therapy. Microinvasion was seen only in the EPC-A tumours. Conclusion: HG-EPC and EPC-A overlap morphologically and diagnostically with frankly invasive carcinomas and demonstrate a non-negligible risk of recurrence. Clinical outcomes and more frequent microinvasion in EPC-A support the view that EPC-A is more appropriately regarded as an indolent form of invasive carcinoma rather than a purely in situ lesion and demonstrate a non-negligible risk of recurrence and highlight the need for standardized staging criteria.