Functional Lymphatic Anatomy for Sentinel Node Biopsy in Breast Cancer

Abstract

The lessons learned from this study provide a functional concept of the breast lymphatic system and its role in metastasis. Anatomical and clinical investigations from the past strongly support these views, as do recent sentinel node studies. Periareolar blue dye injection appears ideally suited to identify the principal (axillary) metastasis route in early breast cancer. Awareness of the targeting mechanism and inherent technical restrictions remain crucial to the ultimate success of sentinel node biopsy and may prevent disaster.

Sentinel lymph node biopsy in early breast cancer surgery – Working with the risks of vital blue dye to reap the benefits

“…Despite the different injection protocols, the precise position of the vital dye injection may be immaterial given the embryology of breast lymphatic tissue; studies have shown that the lymphatics of breast parenchyma and those of its overlying skin and are connected by a common subareolar lymphatic plexus (Sappey's complex) 26 . The presence of this plexus supports the hypothesis that a mammary gland and its overlying skin share the same lymphatic channels to the draining sentinel node 16,27 .…”

“…The uptake kinetics of each mapping agent are different, but the function of both is to localise the sentinel node. It is thought that nanocolloids become entrapped within the sentinel lymph nodes either through a function of their particulate size 13,14 (the larger hydrodynamic diameter of 50-100nm for colloid requires a transit time of usually more than 1 hour 15 ) or because of phagocytosis by leukocytes which migrate to and are retained within the draining lymph nodes 16 . These entrapment processes are unlikely to be mutually exclusive, and other mechanisms may also exist, but the end result is localisation of the nanocolloid within the sentinel nodes rather than its diffuse spread to secondary nodes.…”

“…In contrast, patent blue dyes bind to interstitial albumin and are taken up by local lymphatic tissue 17 . The efficiency with which the lymphatics are converted to bright blue channels by the vital dyes reflects their smaller hydrodynamic diameter, their ability to disperse quickly and even their capacity to readily progress through and beyond the sentinel nodes 15,16,18 . The different properties of the nanocolloids and the vital dyes act synergistically in SLNB; injection of the radio-isotope between 2 and 24 hours before surgery optimises its localisation in the sentinel nodes and intra-operative injection of the vital dye directs the surgeon to the lymphatics that track to the sentinel node.…”

“…These sulphonamide complexes facilitate localisation of the patent blue dyes within the lymphatics and the sentinel lymph nodes 67 , but they are also implicated in the type 1 hypersensitivity reactions. The inability Methylene blue to form these sulphonamide complexes contributes to its safety profile, but this vital dye is not without its side effects; intradermal and subdermal injections of Methylene blue can cause erythematous skin lesions, superficial ulceration and tissue necrosis 16,68,69 . These side effects are thought to be caused by the oxidisation of Methylene blue to substances such as formaldehyde which excites an intense inflammatory response hence the erythematous lesions and ulceration 68,70 .…”

Will early detection of non-axillary sentinel nodes affect treatment decisions?

“…A peritumoural injection technique visualises IM lymph nodes in about 15 -30% of women, whereas subdermal or subareolar injection of isotope does not seem to identify IM nodes (Kett et al, 1993;Borgstein et al, 1997Borgstein et al, , 2000Roumen et al, 1999;Cserni and Szekeres, 2001;Shen et al, 2001;Tanis et al, 2001). The mammary gland and the overlying skin clearly show a common lymphatic pathway to the axilla and the same axillary sentinel node in most cases (Dupont et al, 2001), but they do not appear to both drain to the IM chain.…”