[Bleomycin-induced pulmonary fibrosis following chemotherapy of ovarian granulosa cell tumor].
Bleomycin is used in the cytostatic therapeutical management of a variety of malignant tumours. The development of an interstitially accentuated pulmonary disease is a dreaded complication; this side effect may occur dose-related or not dose-related. We report on a 52-year old female patient with recurrent tumour after adnexectomy because of granulosa cell tumour, surgical re-intervention and subsequent polychemotherapy with cisplatin, etoposid and bleomycin (PEB regimen). Following this, the patient developed rapidly progressing lung fibrosis. There was no improvement in spite of combined high dose antibiotic and corticosteroid therapy. The patient finally died of respiratory insufficiency. Upon autopsy, apart from a circumscribed loco-regional tumour recurrence the clinical diagnosis of well advanced interstitial lung fibrosis presenting as so-called cytostatic pneumopathy was found. Immunohistochemical investigations using so-called proliferation markers revealed a markedly increased, centrifugally accentuated proliferative activity of both mesenchymal cells and of atypical pneumocyte regenerates, originating in areas of advanced parenchymal transformation and proceeding towards areas of supposedly intact lung tissue, a finding seen as an impressive histomorphological correlate of the clinically observed rapid progression of the disease. The development of a so-called bleomycin lung ist demonstrated from the formal pathogenetical point of view and correlated with the clinical course. The comparatively rapid shift of an expression of mediator systems with inflammatory properties towards local pulmonary or mesenchymal cells must be interpreted as the reason for the course of the disease, which in later phases could no longer be influenced by anti-inflammatory medication. These findings underline impressively the importance of early detection of developing pulmonary complications following cytostatic therapy. Apart from imaging techniques such as chest x-rays and HRCT, monitoring by 99mTc-DPTA inhalation is a very promising method for early demonstration of pulmonary alterations caused by cytostatically acting medication. This method registers precisely disturbances in pulmonary membrane permeability by measuring the radio nucleotide absorption rate along the alveolar-capillary membrane. In a therapeutical approach, next to the standard procedure of high-dose administration of corticosteroids, the influence of non-steroidal antiphlogistics and antioxidants is analysed, the growing knowledge on the cellular and molecular level possible leading to future therapeutical strategies, although the complex interactive mechanisms are still not completely understood.
Institut für Pathologie an den Berufsgenossenschaftlichen Kliniken Bergmannsheil, Universitätsklinik, Bochum.
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D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001344:Autopsy; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use*; D017809:Fatal Outcome; D005260:Female; D006106:Granulosa Cell Tumor / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D013902:Radiography, Thoracic
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin