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Apparent Alveolar Bronchiolar Tumors Arising in the Mediastinum of F344 Rats

¹ Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina, USA
² MDS Pharma Services, Les Oncins, France
³ Experimental Pathology Laboratories, Inc., National Toxicology Program Archives, Research Triangle Park, North Carolina, USA
⁴ Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Correspondence: Neil Allison, Experimental Pathology Laboratories, Inc., National Toxicology Program Archives, P.O. Box 13566, Research Triangle Park, NC 27709; e-mail:nallison{at}epl-inc.com.

Rare tumors were observed in chronic studies in F-344 rats that were purely or largely free in the mediastinal cavity, yet had the histological architecture of alveolar bronchiolar tumors. They had originally been diagnosed as either pulmonary alveolar bronchiolar tumors, mediastinal mesotheliomas, or thymomas. The authors described these tumors, estimated the fraction of thoracic tumors that they represented, and carried out a preliminary immunohistochemical investigation of whether they were of pulmonary or mesothelial origin. Sections of 715 thoracic tumors originally diagnosed as alveolar bronchiolar tumors, mesotheliomas, or thymomas from control or treated F-344 rats in NTP two-year studies were reviewed. Thirty (4%) were found to be purely or largely mediastinal, yet to have an alveolar bronchiolar histological pattern. A subset of these tumors and some typical intrapulmonary alveolar bronchiolar carcinomas and pleural mesotheliomas were immunostained for Clara cell secretory protein (CCSP), β-tubulin IV, and Wilm’s tumor 1 susceptibility gene products (WT1). The tumors with the histological architecture of alveolar bronchiolar tumors immunostained positive for CCSP and negative for WT1, implying they might have been of alveolar bronchiolar origin, despite their predominantly mediastinal location, although more certain identification would require the use of a larger panel of antibodies.

Key Words: rat • carcinogenicity • lung • mediastinum • alveolar bronchiolar carcinoma • mesothelioma • immunohistochemistry

Abbreviations: CCSP (CC-10), Clara cell secretory 10-kd protein • CEA, carcinoembryonic antigen • NTP, National Toxicology Program • SP-A, surfactant protein A • WT-1, Wilm’s tumor 1 susceptibility gene products

Toxicologic Pathology, Vol. 37, No. 3, 351-358 (2009)
DOI: 10.1177/0192623309332988


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