Pathological Steps of Cancer-Related Lymphedema: Histological Changes in the Collecting Lymphatic Vessels after Lymphadenectomy

Makoto Mihara,Isao Koshima,Takumi Yamamoto,Kazuki Kikuchi,Taro Okitsu,Naoya Sawamoto,Takuya Iida,Noriyuki Murai,Mitsunaga Narushima,Yohei Hayashi,Jun Araki,Hisako Hara,Iori Kisu,Takeshi Todokoro,Arin Greene

doi:10.1371/journal.pone.0041126

Makoto Mihara, Isao Koshima + Show 13 more

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https://doi.org/10.1371/journal.pone.0041126

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Abstract

IntroductionTo 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.MethodsThe 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.ResultsBased 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.ConclusionsThe increase in pressure inside the collecting lymphatic vessels after lymphadenectomy was accompanied by histological changes that began before the onset of lymphedema.

Highlights

To date, an electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema
Limb lymphedema, which develops after lymphadenectomy for cancer treatment, is an increase in the volume of the diseased limb caused by the subcutaneous accumulation of a protein-rich fluid [1,2]
We investigated the changes occurring in collecting lymphatic vessels after lymphadenectomy by performing electron and light microscopic studies of collecting lymphatic vessels in the human body

Summary

Introduction

An electron microscopy study of the collecting lymphatic vessels has not been conducted to examine the early stages of lymphedema. Such histological studies could be useful for elucidating the mechanism of lymphedema onset. Once lymphedema has become established, complex physical therapy is said to be the gold standard for its treatment [8,9,10,11]. Surgical treatments such as lymphatic venous anastomosis (LVA) [12,13] and lymph node transplantation [14] have recently been developed, expanding the treatment options for those cases in which complex physical therapy alone is insufficient. The indications and non-indications of surgical treatment have not been well defined [15]

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