Associations of polymorphisms in the cytokine genes IL1ß (rs16944), IL6 (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with anthracosilicosis in coal miners in Russia and related genotoxic effects.

Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners, results from the accumulation of carbon and silica in the lungs from inhaled coal dust. This study investigated genotoxic effects and certain cytokine genes polymorphic variants in Russian coal miners with АS. Peripheral leukocytes were sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from 164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped in the extracted DNA samples: IL1ß T-511C (rs16944), IL6 C-174G (rs1800795), IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were assessed by the analysis of chromosome aberrations in cultured peripheral lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and 0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82) and 0.09 (95% CI, 0.03-0.15)], respectively. IL1ß gene T/T genotype (rs16944) was associated with AS [17.83% in AS patients against 4.35% in healthy donors, odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of certain chromosome interchanges among AS donors is of interest because such effects are typical for radiation damage and caused by acute oxidative stress. IL1ß T allele probably may be considered as an AS susceptibility factor among coal miners.

Rapid Growth of Lung Nodules due to Combined Pulmonary Vasculitis, Silicoanthracosis, and Chondrocalcinosis.

Background. Silicoanthracosis is a pneumoconiosis due to occupational inhalation of silica and carbon dusts. Clinically, it can be associated with vasculitis or rheumatoid arthritis. In association with these diseases, silicoanthracosis can present within the lung with multiple pulmonary nodules which, as a differential diagnosis, can mimic metastatic disease or multiple abscesses. Case Presentation. We present the case of a 62-year old former pit worker with pulmonary nodules, chondrocalcinosis due to calcium pyrophosphate deposition (CPPD), and a history of renal cancer. Within a short period of time, pulmonary nodules grew rapidly. Thoracoscopically, the resected lung specimen revealed silicoanthracosis associated with small-to-medium-size vasculitis in the presence of antineutrophil cytoplasmatic autoantibodies (c-ANCA). Conclusion. Pulmonary silicoanthracotic lesions on the base of ANCA-associated vasculitis and CPPD arthritis can rapidly grow. A mutual correlation between silicoanthracosis, ANCA-associated vasculitis, and CPPD seems possible. Apart from this, consideration of metastatic disease should be obligatory in patients with a history of cancer at the same time being immunosuppressed.

Specificity of morphologic changes in target organs, associated with exposure to coal rock dust and fluorine compounds.

The studies revealed specificity of morphologic changes in target organs, depending on acting occupational hazard. Evidences are that inhalation of coal rock dust causes irreversible sclerotic and degenerative changes mostly in lungs and bronchi even on 6th week of the experiment. In liver, changes in parenchyma and stroma are controlled by reparative processes by 9th week. Accumulation of sodium fluoride in the body causes irreversible necrotic changes mostly in liver, on 6th week of the intoxication. With that, morphologic changes in lungs and bronchi are minor, characterized by immune inflammation with degenerative changes only after the 9th week. Irrespective of the acting hazard, vascular changes are characterized by media and intima hypertrophy with endothelial dystrophy and hyalinosis since the 6th week of the experiment.

Experimental Study of the Mechanisms of Intracellular Defense in Cardiomyocytes Associated with Stages of Anthracosilicosis Development.

Mechanisms of intracellular defense of rat cardiomyocytes were studied in dynamics of anthracosilicosis development induced by long-term inhalation of coal and rock dust. It was shown that synthesis of transcription factor HIF-1α and protective proteins increased in the heart at the early stages of coal and rock dust inhalation (1-3 weeks), and these changes limited the development of free radical oxidation and activated metabolism of glucose and fatty acids. Exposure to coal and rock dust for 6-12 weeks activated free radical oxidation and decreased basal metabolism in cardiomyocytes.

Calcareous concretions and psammoma bodies in sputum smears: do these similar structures have different clinical significance?

Different noncellular elements, such as round concentric calcified laminated structures, may be found in sputum smears. If these structures appear isolated on the background of the smear, the term usually used to describe them is "calcareous concretions" (CC). On the contrary, when the structures are part of epithelial cell groups or small tissue fragments, the term used to describe them is "Psammoma bodies" (PB). The aim of this work is to establish the relationship between these structures and pulmonary disease, especially lung carcinoma, by searching for the presence of CC and/or PB in sputum smears. Our study has taken as a basis 16.716 sputum smears from 696 patients obtained during a 7-year period (2003-2009). After reviewing them, it was found that from the total, 66 cases (0.39%) contained round calcified structures, 57 of them (0.34%) corresponding to CC, and the remaining 9 ones (0.05%) corresponding to PB. From these 57 CC cases, 56 corresponded to benign entities, and only one was found with lung carcinoma. On the other hand, from the 9 PB cases all of them (100%) were related to lung adenocarcinoma. We conclude that, even having a similar morphological structure, these aforementioned calcified structures we have observed in sputum smears have different and relevant clinical significance.

[Quantitative characteristics of pathomorphologic changes in bronchi and pulmonary artery branches in miners with preroentgenologic stage of anthrasilicosis].

Morphometric studies covered lung tissue of 10 miners exposed to dusty work conditions over 1 to 30 (13.4 +/- 3.6) years, who were considered apparently healthy according to follow-up examinations and died in technogenic accident. Findings are that dysregeneration, hypertrophic and sclerotic changes in respiratory part of lungs, in bronchi and in pulmonary circuit arteries develop simultaneously--that proves common pathogenetic concept of these changes and systemic character of the pneumoconiosis. The results necessitate improved methods to evaluate health state of workers, refined criteria for nosologic diagnosis of respiratory diseases related to dust.

[Charcoal smoke causes bronchial anthracosis and COPD]. / Holzkohlefeuer als Ursache von bronchialer Anthrakose und COPD.

BACKGROUND: Bronchopulmonary disease due to inhalation of smoke from open woodfires represents a major health problem in developing countries. Due to increasing migration such patients also present to medical services in Europe. CASE REPORT AND DISCUSSION: An 84-year-old Afghan housewife who never smoked nor has a history of exposure to inorganic dusts, presents with chronic obstructive pulmonary disease (COPD) in association with bronchial anthracosis and stenosis of a bronchus. The complaints are found to be caused by chronic inhalation of smoke from an open woodfire which was used for cooking. The main complaints of "woodsmoke-associated lung disease" are cough und dyspnea with bronchial obstruction. Radiology and bronchoscopy usually reveal changes which are similar to pneumoconiosis of miners but without patients' relevant exposure. There is a frequent association of anthracotic bronchial stenosis and infection with tuberculosis. CONCLUSION: Since patients rarely recognize the risks of woodsmoke inhalation, they hardly report their exposure. Thus, the anamnesis is crucial to establish the right diagnosis and guide the patient to the appropriate diagnostic and therapeutic procedures.

[A clinicopathological study of 16 autopsy cases of anthracosilicosis with lung cancer].

OBJECTIVE: To investigate the clinicopathological characteristics of anthracosilicosis complicated with lung cancer. METHODS: Tissue specimens from 16 autopsy cases of 0(+) anthracosilicosis complicated with lung cancer were retrospectively studied by hematoxylin-eosin, histochemical, and immunohistochemical staining. RESULTS: All of 16 patients were male. The patient's age ranged from 46 to 57 years (average: 52.8 years). The dust-exposure time were over 25 years. The pneumoconiosis and dust fibrosis of different degrees in the lung were found. The positive detected rate of coal silicotic nodules was 93.75% (15/16). Among 16 cases of lung cancer, there were 5 cases of squamous cell carcinoma, and 5 cases of small cell undifferentiated carcinoma, 3 cases of bronchioloalveolar carcinoma, 2 cases of adenocarcinoma and 1 case of adenosquamous carcinoma. The typical pathological changes of anthracosilicosis complicated with lung cancer were: the cancer tissue was located at the side of coal dust fibrous focus and fibrosis lesion, or mixte with silicotic lesion. CK, EMA and CEA were positively expressed in most of the tumor cells, while vimentin was positive in the fibrocyte of dust fibrosis. CONCLUSIONS: The occurrence of some lung cancer may be related with fibrosis. The dust-exposed workers can suffer from lung cancer which is histologically identical to the general lung tumor. PCNA and Ki67 may be a prognostic index for anthracosilicosis with lung cancer, while vimentin may be a marker for the examination of dust fibrosis in anthracosilicosis.

A case report of anthracosilicotic spindle-cell pseudotumor of mediastinal lymph node: cytologic diagnosis by endoscopic ultrasound-guided fine-needle aspiration.

Pigmented spindle-cell tumors of the lymph nodes have a broad differential diagnosis, including both benign and malignant neoplasms. Here, we report a case of a pigmented spindle-cell lesion in a mediastinal lymph node mimicking a spindle-cell melanoma on fine-needle aspiration cytology. Smears showed atypical polygonal and spindle cells with bland nuclear features and abundant cytoplasmic anthracotic pigment. Immunohistochemistry was negative for melanoma markers, but showed positivity for histiocyte markers. Polarization microscopy revealed minute birefringent intracellular crystals consistent with silica. Electron microscopy was confirmatory and a diagnosis of anthracosilicotic spindle-cell pseudotumor was made. To the best of our knowledge, fine-needle aspiration cytology findings of this lesion have not been reported.

The implication of background anthracosis in the development and progression of pulmonary adenocarcinoma.

In order to characterize the relationship between background anthracosis and pulmonary adenocarcinogenesis, surgically resected tissues of 66 cases of stage I pulmonary adenocarcinoma, 4 cm or less at their greatest dimension, were examined. These cases were diagnosed based on the classification of small-sized adenocarcinoma of the lung (Noguchi et al., Cancer 75, 1995). Thirteen cases were diagnosed as types A (localized bronchioloalveolar adenocarcinoma, LBAC) and B (LBAC with alveolar collapse), 40 cases as type C (LBAC with a focus of fibroblastic proliferation), 8 as type D (poorly differentiated adenocarcinoma) and 5 as types E (bronchial gland type adenocarcinoma) and F (true papillary adenocarcinoma). The 5-year survival rate of types A and B cases was 100%, while those of type C, type D and types E and F were 52%, 48% and 39%, respectively. Nuclear accumulation of abnormal p53 protein in non-replacement type adenocarcinomas (types D, E and F) was detected more frequently than that in replacement type adenocarcinomas (types A, B and C) (P < 0.05). In each case, black dusty material was extracted from tumorous lesions and non-tumorous regions and blotted onto a nitrocellulose membrane. The anthracotic index (AI) was calculated with a densitometer. AIs of non-tumorous regions in early and replacement type adenocarcinomas (types A and B) were significantly less than in relatively advanced (type C) and poorly differentiated (type D) adenocarcinomas (P < 0.05). These results indicated that adenocarcinoma developing in heavily anthracotic lungs readily progresses to an advanced stage, or that adenocarcinoma with a less favorable prognosis tends to develop in severely anthracotic lungs.

Localised obliterative bronchitis due to non-occupational mineral dust inhalation.

We present a 56-year-old woman with an infiltrate in the right middle lobe secondary to obstruction of the right middle lobe bronchus by extensive submucosal fibrosis. This unique stenotic lesion of a central bronchus was caused by a domestically acquired localised central obstructive bronchitis due to the inhalation of mixed dust fibers, in the absence of advanced silicosis. This complication is a rare presentation of the myriad of pulmonary diseases associated with mineral dust inhalation.

[Clinical value of endoscopic ultrasound-guided transesophageal fine needle puncture of mediastinal lesions]. / Zum klinischen Stellenwert der endosonographisch gesteuerten transösophagealen Feinnadelpunktion von Mediastinalprozessen.

BACKGROUND AND OBJECTIVE: As the mediastinum has been a region difficult to access for biopsy, mediastinoscopy has been required in most cases. In a prospective study the value of transoesophageal endoscopic ultrasound (TEUS) guided aspiration biopsy was assessed as an alternative. PATIENTS AND METHODS: TEUS-guided fine-needle aspirations were performed between May 1995 and March 1998 in 35 patients with mediastinal space-occupying lesions. In all cases the conventional endoscopic method or percutaneous puncture-sonography had been impossible or had failed. In one patient it had been performed after a negative mediastinoscopy. RESULTS: In 34 patients (97%) the aspirated tissue cylinder could be evaluated histologically. There were no complications. Malignancy was demonstrated in 24 patients, and there were one case each of sarcoidosis, silicoanthracosis and two cases of retrosternal goitre. In four of seven patients the negative preoperative diagnosis was confirmed at operation or by follow-up. There were two false-negative results and in one patient there has been no definitive diagnosis. The accuracy of the method was thus 91.4%, the positive predictive value for malignancy 88.9% and the negative predictive value for malignancy 72.7%. Ultrasound alone was a poor predictor of malignancy in lymph node enlargement. CONCLUSION: TEUS-guided fine-needle aspiration of space-occupying mediastinal lesions is an effective and low-risk method that can in selected cases shorten the diagnostic process and avoid methods that are expensive or lead to complications such as transpulmonary biopsy guided by computed tomography or mediastinoscopy.

Anthracotic and anthracosilicotic spindle cell pseudotumors of mediastinal lymph nodes: report of five cases of a reactive lesion that stimulates malignancy.

We report five cases of reactive mediastinal spindle cell proliferations associated with anthracosis and anthracosilicosis that simulated a malignant process both on clinical and morphological grounds. Clinically, the lesions formed radiographically evident masses or were infiltrative. Microscopically, a prominent storiform pattern of intertwining spindle cells was found in four cases. This proliferation extended outside of the lymph node capsule in three cases and surrounded nerves in two. Because of this combination of features, the submitted diagnoses included a malignant neoplasm in four cases. The spindle cells were immunoreactive for histiocytic markers and focally contained fine anthracotic pigment. All cases featured nodular hyaline scars and contained polarizable material suggestive of silica, although a history of industrial exposure was obtained in only two cases. No lesion has enlarged or otherwise progressed during follow-up ranging from 6 to 48 months. The differential diagnosis includes a variety of spindle cell neoplasms, including malignant fibrous histiocytoma, follicular dendritic cell tumor, spindle cell melanoma, and Kaposi's sarcoma.

[Discontinuous lymph node metastases ("skipping") in malignant lung tumors]. / Diskontinuierliche Lymphknotenmetastasen ("skipping") bei bösartigen Lungentumoren.

In 50 lung cancers (25 small cell lung cancers, 17 squamous cell carcinomas, 8 adenocarcinomas) pulmonary, mediastinal and cervical lymph node-metastases were analyzed. Lymph-node "skipping" was demonstrated in 46% of the investigated tumors. In seven of these cases the lymph nodes were skipped, which showed complete hyalinization as a consequence of preexisting anthracosilicosis. In 5 other tumors additional lymph nodes with preserved structure were skipped by the metastatic process. Fibrosis of lymphatic tissue after tuberculosis or exposure to ionizing radiation were further reasons for lymph-node skipping. The skipping of intact lymph nodes can be explained by anatomically demonstrable intra- and perinodal short circuit connections. Apart from that, preexisting lymph node changes (silicosis, fibrosis) play an important part.

Pulmonary endocrine cells in anthracosilicotic lungs.

It has been suggested by some studies of human and animal lungs that the products of pulmonary endocrine cells, particularly gastrin-releasing peptide, might play a role in fibrogenesis, but more recent detailed studies of fibrotic human lungs have failed to confirm this. We have made a detailed quantitative examination of a series of fibrotic human lungs to see if we could determine whether there was any relationship between endocrine cells and fibrosis. Using immunocytochemistry, we investigated the morphology, content, distribution and number of pulmonary endocrine cells in 15 pairs of fibrotic lungs from coal miners, and compared their features with those of equivalent cells in age-matched controls. Proliferation of endocrine cells was seen in the lungs of just two miners, in which it was focal and associated with acute bronchitis and bronchopneumonia. There was no difference between the miners and controls in the appearance (mostly solitary cells), content (predominantly gastrin-releasing peptide and calcitonin), distribution (mainly in small bronchi and bronchioles), or number (4.5 vs 4.1 cells per 10,000 epithelial cells, respectively) of endocrine cells. It seems unlikely that the substances secreted by these cells play any role in stimulating fibrosis in human lungs, but rather that they have a function in the inflammatory response to pulmonary injury.

[Comparative characteristics of intrathoracic lymph node coniotuberculosis of occupational and non-occupational etiology]. / Sravnitel'naia kharakteristika koniotuberkuleza vnutrigrudnykh limfaticheskikh uzlov professional'nogo i bytovogo geneza.

263 patients with coniotuberculosis of the intrathoracic lymph nodes were compared clinically according to whether they were or not at 0ccupational risk of silicosis. Patients exposed to quartz dust had some special morphological picture of affected lymph nodes: periadenitis, dust caseosis and tubercula in the presence anthracosilicosis sclerosis. Silicotuberculous broncho-adenitis in silicosis patients is characterized by solitary lesions of the lymph nodes, bronchi, rare dissemination to the lungs. Coniotuberculous broncho-adenitis in elderly subjects arises in the result of occupation-unrelated accumulation in the lymph nodes of coal and quartz dust and runs chronically. Unless the disease is controlled early and actively, it may generalize and aggravate with perforation in the bronchi, vessels and esophagus. Profuse hemorrhage, caverns, atelectasis are also possible.

N-acetyl-beta-D-glucosaminidase activity within BAL from macaques exposed to generic coal dusts.

N-acetyl-beta(beta)-D-glucosaminidase is a lysosomal enzyme secreted by alveolar macrophages in response to phagocytosis of particulate material. Alveolar macrophages participate in the degradation and fibrosis of pulmonary tissue that results in pneumoconiosis. Known quantities of four characterized respirable dusts were bronchoscopically placed into the right caudal lung lobe of macaque monkeys. Bronchoalveolar lavage (BAL) samples were collected from dust-exposed right lung and unexposed left lung of the same individuals at 2-week intervals for 12 weeks after dust instillation. The samples were tested for N-acetyl-beta-D-glucosaminidase activity to determine if the enzyme levels could serve as an indicator of pulmonary injury induced by generic coal dusts when compared to known fibrogenic and nuisance dusts. Installation of generic quartz, anthracite, or TiO2 dusts produced significant elevations of enzyme activity and increased numbers of macrophages in the dust-exposed lobes. Elevations in enzymatic activity and macrophage numbers were greatest in response to generic quartz dust. These results suggest that quantitative levels of N-acetyl-beta-D-glucosaminidase activity may be a useful indicator of acute and chronic lung injury following exposure to fibrogenic and nonfibrogenic dusts.