Residual Pure Intralymphatic Breast Carcinoma After Neoadjuvant Therapy: Clinicopathologic Analysis and Comparative Outcomes Across Published Studies

Context.— Residual pure intralymphatic carcinoma (PIC), defined as residual tumor confined exclusively to lymphovascular spaces without stromal invasion after neoadjuvant therapy (NAT), is a rare, residual disease pattern. No standardized staging, pathology reporting protocol, or consensus classification exists within current frameworks. Objective.— To characterize the clinicopathologic features, post-NAT staging, Residual Cancer Burden (RCB) classification, and outcomes of patients with PIC at our institution, and to perform a pooled analysis of all published cohorts. Design.— This is a retrospective cohort study of consecutive patients with breast cancer treated with NAT and surgery at a large academic medical center from January 2015 to September 2025. Identified PIC cases were systematically characterized and compared against 5 previously published cohorts. Results.— Of 2000 patients screened, 13 (0.65%) had PIC (9 of 13 [69%] grade 3; 7 of 13 [54%] human epidermal growth factor receptor 2 [HER2]–positive). All had ypT0 disease (yp denotes pathologic stage after neoadjuvant therapy) on American Joint Committee on Cancer (AJCC) staging, while 8 of 13 node-negative patients (62%) may have an RCB score of RCB-I or higher when intralymphatic tumor dimensions are entered—a framework mismatch rather than true pathologic complete response (pCR). At median follow-up of 59.2 months, overall survival was 100% (13 of 13) and disease-free survival, was 92% (12 of 13). Pooled analysis (N = 60) showed mortality decline from 83% (5 of 6) in the earliest (pre-2018) cohort to 0% to 20% post-2018. Conclusions.— Current staging frameworks may misclassify PIC as pCR, implying incomplete standardization with potential clinical consequences. We propose an AJCC modifier, ypT0(LVI + ), for residual lymphovascular invasion in the absence of residual in situ carcinoma or nodal metastasis, plus a dedicated College of American Pathologists synoptic field to ensure appropriate management.