Peribronchial Lymphatics Research Articles

Congenital Pulmonary Lymphangiectasia: A Disorder not only of Fetoneonates.

Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9β1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema. In infancy, the diagnosis seems to be more difficult due to the nonspecific respiratory symptoms like persistent tachypnea, cough and wheeze. Lung biopsy with subsequent histological and immunohistochemical studies is the golden diagnostic method of CPL. Immunohistochemical staining for endothelial cell markers CD31, CD34 and D2-40 confirms lymphatic origin. Therapeutic strategies include supportive, nutritional, investigational, aggressively interventional and surgical regimens, most of which have shown promising outcomes. Although CPL was once regarded as a disorder of very poor prognosis in neonatal onset cases, teenager and adult patients have shown good outcomes upon long-term follow-up.Die angeborene pulmonale Lymphangiektasie (CPL) ist eine seltene Entwicklungsstörung der Lunge, die durch eine Dilatation der pulmonalen subpleuralen, interlobären, perivaskulären und peribronchialen Lymphgefäße charakterisiert ist. Die Inzidenz der CPL bei Totgeburten und Neugeborenen wird <1% geschätzt. Die Ätiologie der CPL ist unbekannt. Allerdings wird ein genetischer Hintergrund vermutet. Neuere Grundlagenstudien zeigten, dass die CPL durch FOXC2, Vegfr-3 und Integrin α9β1-Genmutationen verursacht sein könnte. Die klinische Diagnose der CPL ist sehr viel einfacher in Reifgeborenen zu stellen, die Atemnot, Pleuraergüsse (vor allem chylöse) mit und ohne generalisiertem Ödem aufweisen. In der frühen Kindheit ist die Diagnose aufgrund der unspezifischen respiratorischen Symptomatik wie persistierende Tachypnoen, Husten oder Röcheln schwerer zu stellen. Die Lungenbiopsie mit anschließenden histologischen und immunhistochemischen Untersuchungen ist der Goldstandard für die Diagnose der CPL. Die immunhistochemische Färbung der Endothelzellmarker CD31, CD34 und D2-40 bestätigt den lymphatischen Ursprung. Die Behandlungsstrategien umfassen unterstützende, alimentäre, in Erprobung befindliche, aggressiv-interventionelle und chirurgische Behandlungspläne, von denen die meisten ermutigende Ergebnisse zeigten. Obwohl die CPL einst bei Fällen mit Ausbruch im Neugeborenenalter als Erkrankung mit sehr schlechter Prognose galt, zeigen Teenager und erwachsene Patienten in der Langzeit-Nachbeobachtung gute Verläufe.

Electron microscopical findings with special reference to cancer in rats caused by inhalation of nickel oxide

A special exposure system was used for the inhalation of nickel oxide (NiO) aerosol by Wistar male rats. The median aerodynamic diameter and the geometric standard deviation were 1.2 μm and 2.2, respectively. A histopathological study of the rats was performed immediately, and at intervals of 12 and 20 mo after a 1-mo expsoure to NiO. Electron microscopy showed that localization of NiO particles was restricted to the lungs and that each particle had been engulfed by the alveolar macrophages. Type II pneumocytes and nonciliated bronchiolar epithelial cells (Clara cells), as well as numerous tubular myelin (surfactant) in the alveoli were prominent. In rats dissected after 12 mo, clusters of NiO particles were still present within the terminal bronchioli, alveolar walls, and lysosomes of the alveolar macrophages. Pools of tubular myelin were observed in the peribron-chial lymphatics. The Clara cells, which project into the lumen of bronchioli, showed active secretion and were filled with smooth en-doplasmic reticulum (SER) in the apical cytoplasm. In the experimental group sacrificed after 20 mo, one rat had papillary adenocarcinoma and two rats showed adenomatosis in the peripheral portion of the lung, but none in the upper respiratory tract.

Transmigration of titanium dioxide (TiO2) particles in rats after inhalation exposure

Titanium dioxide (TiO2) has been used extensively in the manufacturing of white pigment and has generally been regarded as a nuisance dust in animals and man. After inhalation exposure, little is known about transmigration routes and potential toxic effects of translocated particles in other organs. In order to answer these questions, rats were exposed to TiO2 by inhalation exposure at concentrations of 0, 10, 50, and 250 mg/m3 for 2 years. A few free particles were retained in the nasal and tracheobronchial epithelium without any cellular damage, but aggregates of dust-laden macrophages (dust cells) were found in the lymphoid tissue of the submucosa. Inhaled particles were mostly engulfed by alveolar macrophages and confined sharply to the alveolar duct region at 10 and 50 mg/m3, while dust cells were scattered throughout alveoli at 250 mg/m3. A fraction of the inhaled particles was retained in the membranous pneumocytes and interstitial macrophages. A dense accumulation of dust cells was found in the perivascular and peribronchial lymphoid tissue. Some dust cells entered peribronchial lymphatics or pulmonary blood vessels and the general circulation. Dust cells in the hyperplastic peribronchial lymphoid tissue were exposed directly in the luminal surface of the airways and were subsequently eliminated via airways. Massive dust deposition was observed in the tracheobronchial lymph nodes. Dust transmigration was markedly reduced in the cervical lymph nodes, and only a trace amount of dust particles was found in the mesenteric lymph nodes. Some dust cells entered either blood or lymphatic vessels in the lymph nodes and then migrated into the general circulation. The incidence of extrapulmonary dust deposition in the liver or spleen was increased in a dose-related fashion similar to the lung dust burden. Since there was no tissue response to translocated particles in the lymph nodes, spleen, or liver, potential adverse health effects appear to be negligible.

Lymphangitic carcinomatosis of the lung in metastatic breast carcinoma

The lungs of 34 patients who had died of carcinoma of the breast and pulmonary lymphangitis carcinomatosa were prepared by air insufflation and then examined radiologically and histologically. The results were compared with x-ray examination performed just before death. The interstitial pattern of lymphangitis is due to tumour cell infiltration of septal, peri-vasal and peri-bronchial lymphatics, and to fibrosis. Pleural effusions developed in 17 patients and were twice as frequent on the side of the breast tumour. Hilar lymph node enlargement was found in only five cases, although histological involvement was proven in 19. Theories concerning the mode of propagation of pulmonary lymphangitis carcinomatosa are discussed.

Survival with residual tumor on the bronchial margin after resection for bronchogenic carcinoma

Sixty-four (14.7 percent) of 434 consecutive patients having pulmonary resection for bronchogenic carcinoma were found to have microscopic residual tumor on the cut margins of the resected specimens. These subjects were further subdivided histologically into those with direct extension of the tumor (34 patients), lymphatic permeation (14 patients), clumps of cancer cells in parabronchial tissues (six patients), and the presence of carcinoma in situ change (10 patients). Bronchopleural fistulas developed in eight (12.5 percent) of 64 patients. The operative mortality rate was 15.6 percent, with four of the deaths occurring as the result of bronchopleural fistulas. Thirty-two patients (50 percent) survived 1 year, 21 (32.8 percent) survived 3 years, and 15 (23.4 percent) lived for 5 years or more. The patients with tumor in the submucosal and peribronchial lymphatics had the worst prognosis. 78.6 percent having died within 1 year and the remainder within 3 years. All 5-year survivors were men with squamous cell carcinoma and had relatively small tumors (mean diameter 2.9 cm). No direct relationship between the length of the resected bronchial stump and survival could be established; a short stump did not preclude long survival. The possible factors involved in the relatively high 5 year survival rate in this group of patients and the therapeutic implications of these factors are discussed.

Chylous reflux in the lungs and pleurae.

Lymphangiectasis of varying extent may be present in some cases of chronic pulmonary disease. Often the dilated lymphatic channels are not identified because pulmonary fibrosis and emphysema together with secondary inflammatory changes obscure the lymph vessel pathology. When chylothorax is associated with such chronic pulmonary pathology, attention may be drawn to the lymphatic system. The presence of a chylothorax is usually attributed to obstruction or injury of the thoracic duct, whereas in some cases chylous reflux into the lungs and pleurae via abnormal lymph channels in the lungs and pleurae as well as in the mediastinum may cause the chylothorax. In rare instances a patient may actually expectorate chylous fluid which seeps into the bronchi from the abnormal peribronchial lymphatics. A detailed analysis of reported cases together with some personal experience has demonstrated that pathological changes in the pulmonary and pleural lymphatic vessels are more common than is usually appreciated. The normal remarkable regenerative potential which is usually evident after experimental interruption of the lymphatics apparently is lacking in some humans due to genetic and other factors. Thus pathological changes, difficult to simulate experimentally, may be encountered. Lymphangiectasis is often found not to be limited to a single organ if complete studies of the lymphatic system are made.

Hodgkin's disease of the lung; roentgen appearance and therapeutic management.

Although the involvement of the pulmonary parenchyma in Hodgkin's disease is well known, the subject remains of considerable interest to radiologists. In this communication, a series of 35 cases of Hodgkin's disease of the lung, selected from a survey of 140 histologically proved cases followed in the Radiotherapy Department of the Veterans Administration Hospital (Bronx, N. Y.), is presented to demonstrate the striking variability of the roentgen appearance. The series includes essentially every known pulmonary manifestation of the disease and affords evidence of the challenging complexity of this type of complication, especially from the standpoint of differential diagnosis. Onset with predominantly pulmonary manifestations may lead to erroneous diagnoses such as tuberculosis, pulmonary abscess, sarcoidosis, mycotic infection, or bronchogenic carcinoma, with consequent mismanagement. The prompt diagnosis of the disease is therefore a matter of considerable practical importance. In addition, it is felt that some therapeutic considerations merit emphasis. Historical Review The history of pulmonary Hodgkin's disease has been traced in detail by Wessler and Greene (24), Falconer and Leonard (7), Vieta and Craver (23), and Hoster and Dratman (11) in this country, and by Versé (22), Uehlinger (21), and Perrier (16) abroad. The incidence of involvement of the lung parenchyma has been variously reported, as follows: There is essentially universal agreement as regards the various modes of spread of the disease to the lung. Uehlinger, Versé, Vieta and Craver, and Hoster and Dratman are agreed that the three chief modes of extension of the disease are (a) lymphogenous and (b) hematogenous dissemination from more distant foci and (c) propagation by direct contiguity from a pre-existing focus of involvement in the mediastinal nodal structures. Still another mode of dissemination is that originally described by Wessler and Greene, namely, autochthonous foci developing spontaneously in the lymphoid tissue of the lung. Hoster et al. indicate that the roentgen appearance of the pulmonary lesions may vary according to their origin. Thus, the hematogenous dissemination of the disease would result in diffusely scattered nodules and the lymphatic spread in linear or feathery densities corresponding to the distribution of the peribronchial lymphatics. Those lesions which develop as a result of direct extension would radiate from the hilar area to involve a variable segment of pulmonary parenchyma. Perrier postulates that ultimately Hodgkin's disease is featured by successive episodes of generalization and that the pulmonary lesions closely mirror the occurrence and degree of dissemination. A corollary opinion is expressed by Vieta and Craver, who state that the entire lymphatic system seems to react as a whole to the exciting agent responsible for the disease.

The Detection of Crystalline Silica in Lung Tissue by X-ray Diffraction Analysis

THE subject of pneumonoconiosis includes a wide range of disease conditions resulting from the inhalation of some type of dust. It has been known for many years that the clinical findings, as well as the pathology, vary roughly according to the particular irritants, and that the conditions resulting from their inhalation may be sharply divided into two groups, viz.: those that produce a specific fibrosis in the peribronchial lymphatics and the parenchyma of the lung, and those that do not produce this “exuberant granulation tissue” but cause detriment more slowly as a foreign body that interferes with the lymph drainage and cleaning facilities of the lung. In the former, there is a gradual impairment of the total alveolar surface of the lung, together with an encroachment upon the lymph drainage; in the latter, there is only encroachment upon the lymph drainage. The former is much more serious as a disease process per se, as well as a soil for the growth of the tubercle bacillus which causes tuberculosis. These two conditions (the former is best represented by silicosis and the latter by pure anthracosis) may be combined in varying proportions, with or without an accompanying infection, such as tuberculosis. Practically all types of pneumonoconiosis are described in the report of Sweany, Porsche, and Douglass (1). A rough relationship was established between the pathology and the amount of silica found by chemical analyses of lungs and lymph nodes. In the majority of cases the amount of specific fibrosis corresponded roughly to the silica content; in others there seemed to be little or no positive correlation. In those cases wherein a high silica content was not accompanied by a specific fibrosis, it was thought that the condition might be attributed to one or more of the following factors: (1) The dampening effect of inert dusts such as coal and iron. There seems to be but little doubt that inert dusts delay the action of silica, if they do not actually dampen it completely. This conclusion is supported by the findings in coal miners reported by Sampson (2), Cummins (3), and others. (2) A time interval following exposure that is not sufficiently long to permit the development of fibrosis. (3) The presence of non-toxic silicates. In some instances the quantity of silica indicated by chemical analysis was too large to fail to produce fibrosis, irrespective of circumstances. In view of the above considerations, it is evident that there is great need in industrial medicine for a method which will enable us to distinguish the detrimental type of silica (usually thought to be quartz) from silicates, which yield silica upon chemical analysis. Chemical methods thus permit only the estimation of total silica; they do not make it possible to differentiate between free and combined silica, or between crystalline and amorphous silica.