The lymphatic system is known as one of the most important pathways in the disease progression of breast cancer. In this study, we investigated lymphatic systems intra-tumorally, and found a unique structure displaying lymphoendothelial immunoreactivity. These incomplete vessel-like structures that formed sinusoids and specifically reacted with the D2-40 antibody, were found in the tumor stroma and were often infiltrated by cancer cells. To show the clinical significance of these intra-tumoral sinusoidal structures (ISS), we examined 113 specimens of surgically resected breast cancer. In multivariate logistic regression analysis, lymph node status (p=0.024) and disease recurrence (p=0.008) were the independent factors that correlated with the existence of ISS. Positive ISS detection in the tumor correlated more strongly with lymph node metastases than positive lymphovascular invasion by cancer cells. Furthermore, a significant correlation with frequent recurrence and poorer survival were recognized in patients with ISS (p<0.001, log-rank test). The evaluation of ISS by needle-biopsied specimens was as accurate as that with surgical specimens, and a significant correlation between the positive ISS evaluated by biopsy and positive lymph node status (p=0.020) was found. In conclusion, ISS are unique structures which play a crucial role in disease progression through lymphatic systems in breast cancer. In a clinical setting, the detection of ISS by biopsy specimen should be considered as a method for determining prognosis instead of a whole tumor examination.

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