The clinical significance and mechanism of DCIS-like morphology of lymph node metastasis in breast cancer.

Abstract

Background: During the practice of diagnostic pathology, we identified a case of invasive ductal carcinoma (IDC) of the breast with lung metastases exhibiting a ductal carcinoma in situ (DCIS)-like morphology. Immunohistochemistry confirmed the presence of CK5/6, P40 and P63-positive tumor cells at the periphery of the metastatic nests. Subsequent expansion of our sample revealed similar DCIS-like morphology in lymph node metastases of other IDC cases. This study aimed to preliminarily characterize the pathological features, significance, and mechanisms of this phenomenon.

Methods: We collected 101 lymph node metastasis specimens of breast IDC. (1) DCIS-like metastases were identified, and their correlation with clinicopathological parameters was analyzed. (2) Immunohistochemistry for basal/myoepithelial markers (CK5/6, P63, SMA, Calponin) was performed to assess their expression in relation to DCIS-like morphology. (3) Stemness markers (ALDH1A1, CD44, SOX2) were detected, and their expression was correlated with clinicopathological parameters, DCIS-like morphology, and basal/myoepithelial differentiation.

Results: (1) DCIS-like morphology was observed in 24.8% (25/101) of lymph node metastases. Its presence correlated with higher nodal burden and non-luminal molecular subtypes (HER2-enriched and triple-negative). The recurrence rate of the DCIS-like metastasis group was higher than that of the non-DCIS-like metastasis group. (2) A subset of cases showed tumor cell expression of P63, CK5/6, or SMA in metastases, while none expressed Calponin. The proportion of cases expressing basal/myoepithelial markers was higher in the DCIS-like metastasis group, with a significant correlation between DCIS-like morphology and CK5/6 expression. (3) High stemness marker expression correlated significantly with higher histological grade, increased numbers of lymph node metastases, advanced pTNM stage, the presence of DCIS-like morphology, and basal/myoepithelial differentiation.

Conclusion: The presence of DCIS-like morphology and basal/myoepithelial marker expression in lymph node metastases of breast IDC is associated with enhanced tumor stemness. DCIS-like metastases may serve as a valuable morphological indicator of higher tumor aggressiveness and increased recurrence risk.