Proceedings of the 2017 National Toxicology Program Satellite Symposium

Our plain-English summary of Proceedings of the 2017 National Toxicology Program Satellite Symposium, by S.A. Elmore, F. Aeffner, D.S. Bangari, et al (Toxicologic Pathology, 2017).

The study

• Authors: S.A. Elmore, F. Aeffner, D.S. Bangari, T.A. Crabbs, S. Fossey, S.C. Gad, W.M. Haschek, J.S. Hoane, K. Janardhan, R.C. Kovi, G. Pearse, L.M. Wancket, E.M. Quist
• Journal: Toxicologic Pathology
• Published: 2017;45(7):799-833
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The 2017 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Montreal, Quebec, Canada at the Society of Toxicologic Pathology's 36th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and other topics covered during the symposium included renal papillary degeneration in perinatally exposed animals, an atriocaval mesothelioma, an unusual presentation of an alveolar-bronchiolar carcinoma, a paraganglioma of the organ of Zuckerkandl (also called an extra-adrenal pheochromocytoma), the use of human muscle samples to illustrate the challenges of manual scoring of fluorescent staining, intertubular spermatocytic seminomas, medical device pathology assessment and discussion of the approval process, collagen-induced arthritis, incisor denticles, ameloblast degeneration and poorly mineralized enamel matrix, connective tissue paragangliomas, microcystin-LR toxicity, perivascular mast cells in the forebrain thalamus unrelated to treatment, and 2 cases that provided a review of the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) bone nomenclature and recommended application of the terminology in routine nonclinical toxicity studies.

In plain English

This article is the written record of a one-day rodent pathology teaching symposium held in 2017, not a study of asbestos. Speakers showed difficult cases for audience voting. Two cases raised mesothelioma as a possible diagnosis. In the first, a male Sprague Dawley rat from a 1-year oral gavage study had a tumor in the right atrium of the heart. The presenter's preferred diagnosis was atriocaval mesothelioma, and the tumor cells stained for cytokeratin only. Across roughly 500 two-year studies of F344 and HSD rats run by the National Toxicology Program, the incidence of heart mesothelioma was 0.028% (56 tumors: 47 in males, 9 in females). In the second, 72% of the audience voted that a chest tumor in another rat was malignant mesothelioma. The presenter concluded from staining results that it was a lung carcinoma, though not everyone in the audience was convinced. Asbestos appeared only in a cited passage naming oxidative stress as a proposed mechanism for asbestos-induced testicular-lining mesothelioma in rats. The authors said further work is needed to find where atriocaval tumors come from.

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: Conference proceedings: summaries of case presentations and teaching talks from the 2017 National Toxicology Program Satellite Symposium, with audience voting on diagnoses. Not an original epidemiological or asbestos study.
• Who was studied: Individual animal cases, mostly rats from toxicity and carcinogenicity studies. Topics also included mice, a rabbit and human muscle biopsies. The mesothelioma-related cases were one male Sprague Dawley (NCTR) rat with a right atrial mass and one male SD (NCTR) rat with a chest tumor.
• Exposure: No asbestos exposure was studied. The rats came from studies of various unnamed test compounds. Asbestos is mentioned only once, in a cited background passage that names oxidative stress as a proposed mechanism of action for asbestos-induced tunica vaginalis mesothelioma in rats.
• Main results:
  • In the rat with the right atrial mass, the presenter's preferred diagnosis was atriocaval mesothelioma. The audience vote had favored hemangiosarcoma (39%) over mesothelioma (15%). The tumor cells stained for cytokeratin only.
  • Across about 500 National Toxicology Program two-year studies in F344 and HSD rats, the incidence of heart mesothelioma was 0.028% (56 heart mesotheliomas).
  • Of these 56 heart mesotheliomas in rats, 47 were in males and 9 in females.
  • A chest tumor in a male SD rat, voted malignant mesothelioma by most of the audience, was diagnosed by the presenter as alveolar–bronchiolar (lung) carcinoma based on immunohistochemical staining.
  • After discussion of the chest tumor, the audience did not reach full agreement with the lung carcinoma diagnosis.
• The authors' conclusion: The presenter of the heart case concluded that atriocaval tumors should be told apart from mesothelioma of the pericardial surface, metastatic adenocarcinoma and primary cardiac hemangiosarcoma, based on location and microscopic features.
• Limitations the authors state:
  • The cell of origin of atriocaval mesothelioma in the rat is not known.
  • Not all images shown for voting are included in the article.

Topics

Medical terms in this study, explained in our Lexicon: Pathology, Mesothelioma, Carcinoma, Collagen.

Related studies

• Diffuse mesothelioma and exposure to asbestos dust in the Merseyside area — W.G. Owen (1964)
• Talc pneumoconiosis: a report of six patients with postmortem findings — M. Kleinfeld, C.P. Giel, et al. (1963)
• Exposure to asbestos and mesothelioma of the pleura — P.B. Fowler, J.C. Sloper, et al. (1964)
• Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma — M.T. Siddiqui, F. Schmitt, et al. (2019)
• Particle toxicology: from coal mining to nanotechnology — P.J. Borm (2002)
• Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference — H.O. Adami, S.C. Berry, et al. (2011)

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