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

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.     

Computed tomographic symptomatology of lymphedema of the lower extremities]

CT potentialities in the diagnosis and differential diagnosis of lower limb lymphedema in 40 patients (11 men and 29 women), aged 16 to 56, are illustrated. Eighty studies on the limbs were performed to 20 patients with primary lymphedema, 6 with congenital lymphedema, 26 with secondary lymphedema, and 28 with unaffected limbs. The data were statistically processed according to the following parameters: leg diameter, skin and subcutaneous fat thickness and density, the presence of fibrosis in subcutaneous fat, its localization, shape and spreading, fascial thickness. CT permitted objective assessment of disease and a right choice of a type of surgical intervention.     

Intracytoplasmic inclusions in the peripheral blood lymphocytes of patients with chronic lymphatic leukemia

An ultrastructural survey of peripheral blood lymphocytes in 81 patients with chronic lymphatic leukemia (CLL) demonstrated intracytoplasmic inclusions in 15 of them. These inclusions consisted of round, dense bodies, ferritin deposits, lipid-containing bodies, concentric rings of endoplasmic reticulum, microfibrillar formations and crystalloid inclusions. The variety of these inclusions suggests that cases diagnosed by light microscopy as classical CLL are actually subtypes which may differ in their clinical course and ultimate prognosis.     

The myocytes of the lymphatic vessels]

Histo- and ultrastructure of myocytes of the lymphatic vessels has been studied in some farm animals. Architectonics, amount and interconnection of myocytes in the lymphangion wall have been investigated. Communicational and gap myo-myocytic contacts revealed give a possibility to suppose that there exists a direct connection between myocytes. This is important for conducting electrical stimulation from one cell to another. For the myocytes abundance of myofilaments, and in some--an essential accumulation of mitochondria are specific; they are morphological manifestation of contractile function of myocytes.     

Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD

Background

De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking.

Methods

Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6.

Results

The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01).

Conclusions

This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD.     

Structure of lymphatic vessels in the rat thyroid gland

The lymphatic bed of the thyroid gland has been studied in 24 intact rats. Three techniques facilitating to reveal lymphatic vessels in the organ have been used: preparation of semithin sections, injection of the blood bed with methyl methacrylate with a successive chemical extraction of the preparations, injection of the blood bed with liquid solution of methyl methacrylate with a consecutive study of the preparations in the scanning electron microscope. Methods of electron histochemistry (revealing horseradish peroxidase) and kryofractography have been applied. Construction of the thyroid lymphatic bed, structure of the wall are described, fibroblastic membrane (F-membrane) is revealed and the signs are presented, that allow to differentiate F-membrane from endothelium of the lymphatic capillaries. The pathways of lymph outflow in the rat thyroid gland consist of the following links: interstitial space in the interlobular spaces of the gland, into them the tissue liquor (lymph) is filtered ; plates of the F-membrane regulating direction of excessive albumin-containing liquor in the lymphatic capillaries, surrounding groups of 5-11 follicles, embracing the microlobule of the gland and situating in the interlobular spaces, deferent lymphatic vessels.     

Individual and age-related differences in the anatomy of the main deferent lymphatic vessels of the human heart and their applied significance

One hundred human hearts of various age have been investigated. Structure, size of their main deferent lymphatic vessels are defined by the organ's form, sex and age of the persons. According to the position signs, extreme forms of their topography have been revealed. In the left--the course in the adventitia of the anterior wall of the pulmonary trunk and of the ascending aorta. In the left--the course in the adventitia of the right lateral wall of the ascending aorta and of the pulmonary trunk. The number of the extraorganic vessels, that bring lymph out of the heart, is from 1 up to 3. The anastomoses made between certain parts of the lymph nodes and the extraorganic lymphatic vessels in the transplanted and removed hearts are more economic.