Apocrine encapsulated papillary carcinoma: a comprehensive clinicopathological analysis of 28 cases

Encapsulated papillary carcinoma (EPC) is characterized by neoplastic epithelial cells of low-to-intermediate nuclear grade arranged along fibrovascular cores. Classical EPC typically expresses oestrogen receptor (ER) and usually progesterone receptor (PR), while lacking human epidermal growth factor receptor 2 (HER2) overexpression and gene amplification. In contrast, apocrine encapsulated papillary carcinoma (AEPC), an exceptionally rare tumour with only a few well-characterized cases, exhibits a triple-negative phenotype (ER-, PR-, HER2-). The purpose of this study is to investigate whether the clinicopathological characteristics of AEPC differ from those of classical EPC.

Since 2014, 28 cases of AEPC have been identified at the Department of Pathology, Fudan University Shanghai Cancer Centre. We conducted a comprehensive clinicopathological evaluation and prognostic assessment in this case series.

All 28 patients in our study were female, with a median age at diagnosis of 61.5 years (range: 34-90). Fifteen cases were consultation referrals, while 13 cases were diagnosed and treated at our centre. Histologically, all AEPC cases demonstrated cystic architecture with papillary growth patterns. The papillary structures were lined by cells exhibiting uniform apocrine differentiation. The degree of cellular atypia ranged from mild-to-moderate, with no severe atypia identified. Notably, myoepithelial cells were absent in both the papillary structures and lesion peripheries. Among the 28 AEPC cases, 18 were non-invasive, 8 demonstrated microinvasion (<1 mm), and 2 exhibited frank invasion (1-4 mm). The tumour cells exhibited a triple-negative profile and most cases presented with diffuse positivity for androgen receptor (AR) and gross cystic disease fluid protein 15 (GCDFP15). The median Ki-67 proliferation index was 10% (range: 5%-20%). Among the 28 patients, 19 received no adjuvant therapy, while 9 underwent postoperative radiotherapy and/or chemotherapy. With a median follow-up of 44.3 months (range: 7.4-135.5 months) for 27 patients, no recurrences or metastases were observed.

Classical EPC typically demonstrates favourable prognosis and is managed as ductal carcinoma in situ. In our study, none of the AEPC patients developed recurrence or metastasis, regardless of adjuvant therapy administration. Although AEPC exhibits a triple-negative immunophenotype, it differs biologically from conventional triple-negative breast cancer (TNBC). The indolent behaviour of AEPC aligns more closely with classical EPC rather than TNBC. Therefore, it may be more appropriate to treat AEPC patients using the same strategies applied to classical EPC.