Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy

PLoS One. 2012;7(7):e41126. doi: 10.1371/journal.pone.0041126. Epub 2012 Jul 24.

Abstract

Introduction: To date, an electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema. However, such histological studies could be useful for elucidating the mechanism of lymphedema onset. The aim of this study was to clarify the changes occurring in collecting lymphatic vessels after lymphadenectomy.

Methods: The study was conducted on 114 specimens from 37 patients who developed lymphedema of the lower limbs after receiving surgical treatment for gynecologic cancers and who consulted the University of Tokyo Hospital and affiliated hospitals from April 2009 to March 2011. Lymphatic vessels that were not needed for lymphatico venous anastomosis surgery were trimmed and subsequently examined using electron microscopy and light microscopy.

Results: Based on macroscopic findings, the histochemical changes in the collecting lymphatic vessels were defined as follows: normal, ectasis, contraction, and sclerosis type (NECST). In the ectasis type, an increase in endolymphatic pressure was accompanied by a flattening of the lymphatic vessel endothelial cells. In the contraction type, smooth muscle cells were transformed into synthetic cells and promoted the growth of collagen fibers. In the sclerosis type, fibrous elements accounted for the majority of the components, the lymphatic vessels lost their transport and concentrating abilities, and the lumen was either narrowed or completely obstructed.

Conclusions: The increase in pressure inside the collecting lymphatic vessels after lymphadenectomy was accompanied by histological changes that began before the onset of lymphedema.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Desmosomes / pathology
  • Desmosomes / ultrastructure
  • Endothelial Cells / pathology
  • Endothelial Cells / ultrastructure
  • Female
  • Fibrillar Collagens / ultrastructure
  • Humans
  • Lymph Node Excision
  • Lymphatic Vessels / pathology*
  • Lymphedema / etiology*
  • Lymphedema / pathology*
  • Middle Aged
  • Myocytes, Smooth Muscle / pathology
  • Myocytes, Smooth Muscle / ultrastructure
  • Neoplasms / complications*
  • Neoplasms / surgery

Substances

  • Fibrillar Collagens

Grants and funding

The grant was provided by a Japanese funding program for next generation world-leading researchers (NEXT program, LS039). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.