The asbestos fibre burden in human lungs: new insights into the chrysotile debate.

The traceability of asbestos fibres in human lungs is a matter of discussion especially for chrysotile. This issue is of high significance for differential diagnosis, risk assessment and occupational compensation. At present no intra-individual longitudinal information is available. This study addresses the question whether the asbestos fibre burden in human lungs decreases with time after exposure cessation.The database of the German Mesothelioma Register was screened for patients with asbestos body counts of at least 500 fibres per gram of wet lung, which had been analysed twice from different tissue excisions at minimum intervals of 4 years.Twelve datasets with individual longitudinal information were discovered with a median interval of about 8 years (range 4-21 years). Both examinations were performed after exposure cessation (median: surgery, 9.5 years; autopsy, 22 years). Pulmonary asbestos fibre burden was stable between both examinations (median 1623/4269 asbestos bodies per gram wet lung). Electron microscopy demonstrated a preponderance of chrysotile (median 80%).This study is the first to present longitudinal intra-individual data about the asbestos fibre burden in living human lungs. The high biopersistence of amphiboles, but also of chrysotile, offers mechanistic explanations for fibre toxicity, especially the long latency period of asbestos-related diseases.

[Benign mesothelial tumors]. / Benigne Tumoren des Mesothels.

Benign mesothelial tumors are rarer than malignant mesotheliomas and are often found in the peritoneum as incidental findings in women. They include the adenomatoid tumor (AT), the well-differentiated mesothelial tumor (WDPMT), the mesothelioma in situ (MIS), and the solid papillary mesothelial tumor (SPMT). ATs are always benign and predominantly manifest in the genital tract. WDPMTs can develop multifocally and are prone to recurrence, particularly in the case of incomplete resection. Only MISs are considered a confirmed precursor lesion of malignant mesothelioma according to the currently valid World Health Organization (WHO) classifications. As with malignant mesothelioma, alterations of BAP1, MTAP, and p16 are detectable for MIS in contrast to the other three tumors. SPMTs cannot be clearly assigned to the other mesothelial tumors and have so far only been described in the peritoneum in women with a benign course.

Intravascular large B-cell lymphoma presenting as dementia and hemolytic anemia.

BACKGROUND: Intravascular lymphoma (IVL) is an uncommon disease characterized by atypical lymphoid cells growing inside the lumina of small vessels. The diversity of clinical presentation due to possible involvement of multiple organs often complicates its diagnosis. CASE REPORT: Here, we report on a case of IVL with rapidly progressive dementia and Coombs-negative hemolytic anemia. Interestingly, the erythrocytes exhibited a decreased osmotic resistance. Bone marrow histopathology revealed increased erythropoiesis and, finally, a small monoclonal B lymphocyte population. Cerebral magnetic resonance imaging (MRI) demonstrated few micro-bleedings. Computed tomography (CT) showed bilateral ground-glass opacity of the lungs. Within a few days, the patient developed respiratory failure and died. On post-mortem examination, intravascular large B-cell lymphoma with almost complete infiltration of the brain and lungs was diagnosed. CONCLUSION: IVL should be considered early in situations of unexplained neuropsychiatric disease along with markedly elevated levels of lactic dehydrogenase, anemia, and hemolysis.

Histological findings and lung dust analysis as the basis for occupational disease compensation in asbestos-related lung cancer in Germany.

OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease. MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings. RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated. CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.

[Prognosis, staging and therapy of malignant pleural mesothelioma]. / Prognose, Staging und Therapie des malignen Pleuramesothelioms.

PROGNOSIS: Prognosis of pleural mesothelioma remains dismal. Regardless of the modality employed median survival ranges between 6 and 12 months, only 20% of patients survive 1 year. In 1996 the International Mesothelioma Interest Group (IMIG) published a widely accepted staging system. So far there is no effective standard therapy. Even very aggressive therapies do not basically influence the course of the disease. THERAPEUTICAL STUDIES: Despite numerous single-agent and combination chemotherapy trials no standard regimen could be found. Few agents yield reproducible response rates above 20%. The majority of the trials are inconclusive according to statistical criteria, as subject numbers are insufficient to prove or deny effectiveness. It also remains obscure in which stage of the disease patients may benefit from chemotherapy because of a lack of analysis of response rates within different stages. Striking is the lack of sufficient studies analyzing patients' quality of life treated with often very toxic regimens. DRUG TREATMENT: Systemic administration of interferons alone or in combination with chemotherapeutic agents did not result in higher response rates or prolonged median survival. In very early stages of the disease patients may have limited benefit from intracavitary, local administration of gamma-interferon. MULTIMODALITY APPROACHES: Mere surgical procedures as extrapleural pneumonectomy or pleurectomy/decortication have been left in favor of multimodality approaches. Due to careful patient selection and improved operation techniques mortality could be reduced. Neither chemotherapy, radiotherapy nor photodynamic therapy can prevent local relapse which occurs in the majority of patients. RADIOTHERAPY: The effectiveness of primary radiation therapy remains controversial. Even very high doses of radiation cannot control tumor growth. It remains unclear whether radiation therapy may palliate tumor associated symptoms. Prophylactic radiation of puncture channels and thoracotomy scars is effective to prevent tumor growth caused by seeding of mesothelioma cells. PERSPECTIVES: Research of the biological behavior of mesothelioma resulted in first phase I gene therapy trials. The results of the few promising approaches tested in phase II and III trials with sufficient patient numbers have to be awaited until we have learned whether and in which stage of the disease patients may benefit from therapy.

Subarachnoid-pleural fistula as a complication of malignant pleural mesothelioma.

We report a 62-year-old male patient with asbestos-related malignant pleural mesothelioma who developed recurrent pleural effusions after surgical resection of paravertebral tumour masses. Pleural effusions were drained on several occasions with the patient suffering severe headaches and vascular dysregulation. Cytological studies of the pleural fluid showed no evidence of inflammatory or malignant cells. The fluid was interpreted as seroma despite its unusual transparency until magnetic resonance imaging was suggestive of a subarachnoid-pleural fistula; its presence was confirmed when beta-trace protein--a specific marker for cerebrospinal fluid--was added to the standard laboratory testing of the pleural effusion. A subarachnoid-pleural fistula has to be included in the differential diagnosis of patients with recurrent pleural effusions after surgical debulkment of malignant pleural mesothelioma. The beta-trace protein may help to establish this diagnosis especially in cases where important therapeutic consequences may need to be drawn.