Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo\[a\]pyrene

Our plain-English summary of Differential diagnosis of malignant tumours in the abdominal cavity of rats after intraperitoneal injection of crocidolite or benzo[a]pyrene, by J. Friemann, M. Varnai, C. Sutter, et al (Experimental and Toxicologic Pathology, 1996).

The study

• Authors: J. Friemann, M. Varnai, C. Sutter, B. Hohr, A. Behrens, G.H. Althoff, H.W. Schilpkoter
• Journal: Experimental and Toxicologic Pathology
• Published: 1996;48(1):13-7
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In our investigation (i.p. test), crocidolite and benzo[a]pyrene, both caused a progression from initially reactive, then autonomously transformed proliferation of myofibroblasts and undifferentiated mesenchymal cells to malignant, multidirectionally differentiated (desmin and ED-1 positive) fibro-histiocytic tumours. Immunohistochemically these tumours showed no morphological characteristics (for example co-expression of vimentin and keratin in spindle-shaped tumour cells) of human asbestos-associated malignant mesotheliomas. On the other hand many tumour cells induced by crocidolite and benzo[a]pyrene had an ultrastructural appearance resembling fibroblasts and myofibroblasts. These have been demonstrated in only a few desmoplastic and sarcomatous mesotheliomas in human beings. None of the tumours revealed the typical ultrastructural features of epitheloid or transitional mesotheliomas. Apparently, both carcinogenic substances induce the transformation of undifferentiated pluripotent mesenchymal cells in rat peritoneum, regardless of their localization in the submesothelial compartment or perivascular connective tissue (preferentially after crocidolite application) or in the connective tissue pseudocapsule of major benzo[a]pyrene containing beeswax/tricaprylin depots in the mesometrium and mesenterial fatty tissue. In this way asbestos fibres in this animal experiment do not seem to induce an arrest in differentiation of intermediate or immature mesothelial cells as supposed formerly, but rather affect undifferentiated mesenchyme cells and myofibroblasts. This is an explanation for the immunohistochemical expression of markers of muscular differentiation in these tumour cells, which is known to occur in human malignant fibro-histiocytic tumours. If supplementary immunohistochemical investigations with different keratin antibodies also fail to confirm the mesothelial differentiation of the tumours induced in our i.p. test, the decision to call them "mesotheliomas" should be reconsidered. Further immuno-transmission-electron microscopical investigations with intermediate filament or macrophage antibodies are needed to clarify whether the term malignant "fibrohistiocytic sarcoma", "mesenchymoma" or "mesothelioblastoma" would be more correct from the morphological point of view.

In plain English

In this animal experiment, 217 female Wistar rats were studied, including 48 untreated comparison animals. The others received injections into the abdominal cavity of crocidolite asbestos (2.0 mg), benzo[a]pyrene (5.0 mg in beeswax/tricaprylin) or soluble glass fibres (25.0 mg). The authors examined tumours by microscopy, antibody staining and electron microscopy. After crocidolite, tumours appeared 11 to 20 months later in 15 of 24 animals that died or were sacrificed. After benzo[a]pyrene, similar tumours were found. The scanned text gives the count as '33 or 37' sacrificed animals, possibly 33 of 37, which the article does not confirm. Most tumours were classified as malignant fibro-histiocytic tumours. Most tumour cells stained for desmin. The tumours lacked the co-expression of vimentin and keratin described in human asbestos-associated malignant mesotheliomas. Electron microscopy of 2 crocidolite and 8 benzo[a]pyrene cases showed many cells resembling fibroblasts and myofibroblasts. Two of 14 glass-fibre animals had genital tract carcinomas. The authors concluded that both substances appeared to transform undifferentiated mesenchymal cells rather than mesothelial cells. They also concluded that calling these tumours 'mesotheliomas' should be reconsidered if further keratin tests also fail to show mesothelial differentiation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (intraperitoneal injection test), part of an ongoing long-term trial, with microscopic, immunohistochemical and electron-microscopic examination of tumours
• Who was studied: 217 female Wistar rats (strain WilWu, Kissleg, Germany) in total, divided into groups. Table 1 lists 48 untreated animals among them. The authors also mention negative controls. The study was done at the Department of Environmental Pathology, Heinrich Heine University, Düsseldorf.
• Exposure: Intraperitoneal injection of crocidolite (2.0 mg), benzo[a]pyrene (5.0 mg in beeswax/tricaprylin) or soluble glass fibres (25.0 mg). Animals were sacrificed from 8 days or 1 month onward, or after visible health impairment.
• Main results:
  • Crocidolite group: tumours occurred between 11 and 20 months after injection in 15 of 24 animals sacrificed or deceased
  • Crocidolite tumours spread mostly as a band beneath a mesothelial layer that was not neoplastically transformed and stained positive for keratin
  • Most tumour cells reacted strongly with the antibody against desmin, and less often with the antibody against alpha-1 muscle actin
  • Electron microscopy of two crocidolite cases showed no typical desmosomes, junctional complexes or basal membrane fragments. Most neoplastic cells resembled fibroblasts, and others resembled myofibroblasts.
  • Benzo[a]pyrene group: malignant fibro-histiocytic tumours similar to those after crocidolite were found 6 to 20 months after injection. The scanned text gives the count as '33 or 37' sacrificed animals. This may be a scanning error for 33 of 37, but the article does not confirm it.
  • Benzo[a]pyrene tumours appeared to arise mainly in the connective tissue capsules around large beeswax deposits in the mesometrium and mesentery
  • The antibody staining pattern of benzo[a]pyrene tumours did not differ from that of crocidolite-associated tumours
  • Electron microscopy of 8 benzo[a]pyrene cases showed mainly fibroblastic and myofibroblastic cells. Only a few cells had desmosomes or microvilli-like processes, and no basal lamina or hyaluronic acid crystals were detected.
  • Soluble glass fibre group: 2 of 14 animals that died or were sacrificed 8 to 20 months after treatment had carcinomas of the internal or external genital tract with metastatic spread
  • The tumours showed none of the features of human asbestos-associated malignant mesotheliomas, such as co-expression of vimentin and keratin in spindle-shaped tumour cells
• The authors' conclusion: The authors concluded that both crocidolite and benzo[a]pyrene appear to transform undifferentiated pluripotent mesenchymal cells in rat peritoneum. In this experiment, asbestos fibres did not seem to arrest the differentiation of mesothelial cells, as had previously been supposed. The authors further concluded that if additional keratin antibody tests also fail to confirm mesothelial differentiation, the decision to call these tumours 'mesotheliomas' should be reconsidered.
• Limitations the authors state:
  • The origin of the benzo[a]pyrene tumours could be judged only as far as possible in advanced tumour stages
  • The authors state that further keratin antibody tests are needed, along with electron-microscopic studies using intermediate filament or macrophage antibodies, to decide the correct name for these tumours

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Differential Diagnosis, Crocidolite, Desmin, Malignant Mesothelioma, Fibroblast, Desmoplastic Mesothelioma, Mesothelioma, Transitional Mesothelioma.

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