Occult neoplastic cells and malignant micro-aggregates in lymph node sinuses: review and hypothesis

Many studies have shown a close relationship between the detection of occult neoplastic cells (ONCs) freely floating in lymph node sinuses remote from the primary tumor and the recurrence/metastasis of various malignancies. If 5 to 10 circulating ONCs form an aggregate of tumor cells, it may easily escape attack by the host immune system. Since such malignant micro-aggregates cannot pass through the circulation in the liver and lungs, which filter tumor cells from the blood, the aggregates may become anchored in these organs and cause metastasis. A hypothesis is proposed that the most important factor leading to distant metastasis/recurrence of stage I or II cancer without microscopic lymph node metastasis, so-called N0 local disease (N0-LD), is the release of malignant micro-aggregates consisting of many ONCs from the primary tumor. Distant metastasis/recurrence of N0-LD may occur when such infiltrating/proliferating cells enter target organs, especially the liver and lungs, in a viable state during their first pass through the circulation preoperatively and/or intraoperatively.