An international workshop of toxicologic pathologists reviewed cystic keratinizing squamous lesions of the rat lung. These lesions develop in response to the chronic inhalation of diverse particulate materials. Controversy exists over the biological significance of these changes and their relevance to humans. For the first time, in one place, a group of pathologists analyzed slides from all available studies. The workshop reached a consensus as to classification of these unique pulmonary tissue responses and offers diagnostic criteria for application. Although additional research is needed, this working classification scheme should serve as a practical interim approach for pathologists and regulatory agencies.
Bennett WP, Colby TV, Travis WD, Borkowski A., Jones RT, Lane DP, Metcalf RA, Samet JM, Takeshima Y., Gu JR, et al (1993). p53 protein accumulates frequently in early bronchial neoplasia. Cancer Res. 53: 4817-4822.
2.
Boorman GA and Eustis SL (1990). Lung. In: Pathology of the Fischer Rat, GA Boorman et al (eds). Academic Press, San Diego, pp. 339-367.
3.
Carlton WW (1994). "Proliferative keratin cyst", a lesion in the lungs of rats following chronic exposure to para-aramid fibrils. Fund. Appl. Toxicol. 23: 304-307.
4.
Dungworth DL, et al (1994). Pathologic effects of inhaled particles in rat lungs: Associations between inflammatory and neoplastic processes. In: Toxic and Carcinogenic Effects of Solid Particles in the Respiratory Tract, U Mohr, DL Dungworth, JL Mauderly, and G Oberdorster (eds). ILSI Press, Washington, D.C., pp. 75-98.
5.
Herbert RA, Gillett NA, Rebar AH, Lundgren DL, Hoover MD, Chang IY, Carlton WW, and Hahn FF (1993). Sequential analysis of the pathogenesis of plutonium-induced pulmonary neoplasms in the rat: Morphology, morphometry, and cytokinetics . Radiat. Res. 134: 29-42.
6.
Hirano T., Franzen B., Kato H., Ebihara Y., and Auer G. (1994). Genesis of squamous cell lung carcinoma. Sequential changes of proliferation, DNA ploidy, and p53 expression. Am. J. Pathol. 11: 296-302.
7.
Kelly G., Stegelmeier BL, and Hahn FF (1996). p53 alterations in plutonium-induced rat lung tumors. Radiat. Res. (in press).
8.
Kittel B., et al (1993). Morphological comparison between benign keratinizing cystic squamous cell tumors of the lung and squamous lesions in rats. Exp. Toxicol. Pathol. 45: 257-267.
9.
Klonne D., et al (1985). Two-year inhalation toxicity study of petroleum coke (delayed process) in rats and monkeys. Toxikologist5: 180.
10.
Kuschner M. and Laskins S. (1970). Pulmonary epithedial tumors and tumor like proliferation in the rat. Morphology of experimental respiratory carcinogenesis. In: Proceedings of Biology Division Conference. Oak Ridge National Laboratory, Gatlinburg, Tennessee , May 13-16, 1970, pp. 203-255.
11.
Lee KP (1989). Lung response to particulates. In: Encyclopedia of Environmental Control Technology, Vol. II: Air Pollution Control, PN Cheremisinoff (ed). Gulf Publishing , Houston, Texas, pp. 835-882.
12.
Mohr U., et al (1990). Tumors of the lower respiratory tract and plura in the rat. In: Pathology of Tumors in Laboratory Animals: Tumors of the Rat, V. Turusov and U. Mohr (eds). IARC Scientific Publications , Lyon, France, pp. 275-299.
13.
National Toxicology Program ( 1993). National P. Toxicology and Carcinogenesis Studies of Talc (CAS NO. 14807-96-6) in F344/N Rats and B6C3F1 Mice (Inhalation Studies) . Technical Report No. 421, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, North Carolina.
14.
National Toxicology Program (1995). National P. Toxicology and Carcinogenesis Studies of Nickel Oxide (CAS NO. 1313-99-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). Technical Report No. 451, U.S. Department of Helath and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park , North Carolina.
15.
Nickell-Brady C., Hahn FF, Finch GL, and Belinsky SA (1994). Analysis of K-ras, p53 and c-raf-1 mutations in beryllium-induced rat lung tumors. Carcinogenesis15: 257-262.
16.
Nolte T. and Thiedemann K-U. (1994). Histological and ultrastructural alterations of the bronchioloalvelar region in the rat lung after chronic exposure to a pyrolized condensate or carbon black, alone or in combination. Inhal. Toxicol. 6: 459-483.
17.
Nuorva K., Soini Y., Kamel D., Autio HH, Risteli L., Risteli J., Vahakangas K., and Paakko P. (1993). Concurrent p53 expression in bronchial dysplasia and squamous cell lung carcinomas. Am. J. Pathol. 142: 725-732.
18.
Ohgaki H., Furukawa F., Takahashi M., and Kleihues P. (1993). K-ras mutations are frequent in pulmonary squamous cell carcinomas but not in adenocarcinomas of WBN/Kob rats induced by N-nitrosobis (2-oxopropyl)amine. Carcinogenesis14: 1471-1473.
19.
Schwartz LW, Hahn FF, Keenan KP, Brown HR, and Mann PC (1991) Guides for Toxicologic Pathology. Society of Toxicologic Pathology, AFIP, Washington, D.C.
20.
Stegelmeier BL, Gillette NA, Rebar AH, and Kelly G. (1991). The molecular progression of plutonium-239-induced rat lung carcinogenesis: K-ras expression and activation . Mol. Carcinogen. 4: 43-51.
21.
Suo Z., Holm R., and Nesland JM (1993). Squamous cell carcinomas. An immunohistochemical study of cytokeratins and involucrin in primary and metastatic tumors. Histopathology23 : 45-54.
22.
Swafford DS , Nikula KJ, Mitchell CE, and Belinsky SA (1995). Low frequency of alterations in p53, K-ras and mdm2 in rat lung neoplasms induced by diesel exhaust or carbon black. Carcinogenesis (in press).
23.
Usui Y., Takabe K., Takayama S., Miura H., and Kimula Y. (1991). Minute squamous cell carcinoma arising in the wall of a congenital lung cyst. Chest99: 235-236.
24.
Volm M., Drings P., and Wodrich W. (1993). Prognostic significance of the expression of c-fos, c-jun and c-erbB-1 oncogene products in human squamous cell lung carcinomas . J. Cancer Res. Clin. Oncol. 119: 507-510.
25.
Vosame AI (1979). Carcinogenicity studies of estronian oil soots . Environ. Health Perspect. 30: 173-176.
26.
Zheng J., Shu Q., Shi-Hua L., Tsao J., Weiss LM, and Shibata D. (1994). Patterns of p53 mutations in squamous cell carcinoma of the lung. Am. J. Pathol.145: 1444-1449.
