The Arteria Lymphatica and Lymphatic Microperforators: A Dedicated Blood Supply to Collecting Lymphatics and Their Potential Implications in Lymphedema: Anatomical Description

Abstract

Background: Lymphedema is common after lymphatic damage in cancer treatment, with negative impacts on function and quality of life. Evidence suggests that blood vessel microvasculature is sensitive to irradiation and trauma; however, despite knowledge regarding dedicated mural blood supply to arteries and veins (vasa vasorum), equivalent blood vessels supplying lymphatics have not been characterized. We studied collecting lymphatics for dedicated mural blood vessels in our series of 500 lymphaticovenous anastomosis procedures for lymphedema, and equivalent controls.

Methods: Microscopic images of lymphatics from lymphedema and control patients were analyzed for lymphatic wall vascular density. Collecting lymphatics from 20 patients with lymphedema and 10 control patients were sampled for more detailed analysis (podoplanin immunostaining, light/confocal microscopy, microcomputed tomography, and transmission electron microscopy) to assess lymphatic wall ultrastructure and blood supply.

Results: Analysis revealed elaborate, dense blood microvessel networks associating with lymphatic walls in lymphedema patients and smaller equivalent vessels in controls. These vasa vasora or "arteria lymphatica" were supplied by regular axial blood vessels, parallel to lymphatic microperforators linking dermal and collecting lymphatics. Lymphatic walls were thicker in lymphedema patients than controls, with immunohistochemistry, computed tomography, transmission electron microscopy, and confocal microscopy characterizing abnormal blood vessels (altered appearance, thickened walls, elastin loss, narrow lumina, and fewer red blood cells) on these lymphatic walls.

Conclusions: Dedicated blood vessels on lymphatics are significantly altered in lymphedema. A better understanding of the role of these vessels may reveal mechanistic clues into lymphedema pathophysiology and technical aspects of lymphedema microsurgery, and suggest potential novel therapeutic targets.

Fig. 1.

Operating microscopy of collecting lymphatic. Microscopic view of an LVA in a lymphedema patient, demonstrating a “meshwork” of BVs (arrows) on the collecting lymphatic (LV) wall, contrasting with the low density of BVs seen on the wall of the adjacent vein (V).

Fig. 2.

Confocal microscopy of whole immunostained lower limb lymphatic from a female patient with chronic lymphedema. External view of lymphatic wall demonstrating “meshwork” of vWF+, BVs (red), overlying the D2–40 (podoplanin)+ staining lymphatic (green) (A); with alternative angle viewed (B); and internal view from within the lymphatic lumen (C).

Fig. 3.

Micro-CT and TEM images of lower limb lymphatic in lymphedema. A, Micro-CT in a transverse plane showing gross morphology of a thickened lymphatic wall with a narrowed lumen. B, TEM of region 1 showing three BVs (arrows) associated with the lymphatic wall, and the ultrastructure of the adjacent lymphatic media with abnormal, “spiky” SMCs (closed arrows). TEM of region 2 demonstrating a single BV with a narrow lumen and vascular endothelial cell nucleus (arrow). C, Abnormal SMCs (closed arrows) are seen in the adjacent lymphatic media.

Fig. 4.

Micro-CT and TEM images of leg lymphatic in lymphedema. A, Micro-CT section through a lymphatic showing mural structure (arrow) of 4–6 SMC layers, connective tissue and associated blood vessels. B, TEM of region 3 demonstrating an abnormal BV adjacent to the lymphatic wall, with a narrow lumen (arrow) containing a permeabilized RBC (closed arrow and label). C, TEM of region 4, showing an associated BV devoid of RBCs.

Fig. 5.

Micro-CT and TEM images of upper limb lymphatic in lymphedema. A, Micro-CT image of a transverse section through the lymphatic showing a thickened smooth muscle layer in the lymphatic wall. B, TEM demonstrating associated blood microvasculature in region 1, with a single BV with a narrow lumen (arrow and label) that is devoid of RBCs. C, TEM of associated microvasculature in region 2 showing a BV comprised of an endothelial cell (nucleus arrowed and labeled) and a RBC in the lumen (closed arrow and label). D, TEM of the lymphatic wall in region 3 showing a normal lymphatic SMC morphology and no evidence of lumen narrowing.

Fig. 6.

Micro-CT and TEM images of control tissues from the lower limb. A, Micro-CT image of a transverse section demonstrating two veins (arrows and labels), and thin-walled lymphatics with associated blood microvasculature (regions 1–4). B, TEM imaging showing the features of the normal BV in region 1, with a rounded morphology, no luminal constriction, and circulating RBC (closed arrow). C, TEM of a normal BV in region 2 containing multiple RBCs (closed arrow). TEM of region 3 and 4 demonstrating a thin-walled lymphatic with only 1–2 SMC layers and a normal lumen (arrows) (D) and two small BVs (E).

Fig. 7.

Three-dimensional reconstructed micro-CT image of lower limb lymphatic in Figure 4. Transverse section in Figure 4 is indicated by the superimposed orthoslice. Lymphatic endothelium is depicted in light blue, showing the outline of the lymphatic lumen (arrow and label). The course of the BVs associated with the lymphatic wall (arrow and label) are shown green.