Table Of ContentMonographs on
Pathology of Laboratory Animals
Sponsored by the
International Life Sciences Institute
Editorial Board
J. D. Burek, West Point· J. S. Campbell, Ottawa
C. C. Capen, Columbus . A. Cardesa, Barcelona
RG.Carison, Kalamazoo· D. de Paola, Rio de Janeiro
G. Della Porta, Milan . J. L. Emerson, Atlanta
F. M. Garner, Rockville . L. Golberg, Research Triangle Park
H. C. Grice, N epean . C. C. Harris, Bethesda . R Hess, Basel
C. F. Hollander, Rijswijk· G. H. Hottendorf, Syracuse
RD. Hunt, Southborough . T. C. Jones, Southborough
Y. Konishi, Nara . D. Krewski, Ottawa· R Kroes, Bilthoven
H. Luginbuhl, Bern . U. Mohr, Hannover . P. Olsen, Soborg
J. A. Popp, Research Triangle Park· J. R Schenken, Omaha
R A. Squire, Baltimore· J. Sugar, Budapest
S. Takayama, Tokyo . G. C. Todd, Greenfield
L. Tomatis, Lyon . B. F. Trump, Baltimore· J. M. Ward, Frederick
Officers - ILSI
Alex Malaspina, Atlanta - President
Peter B. Dews, Boston - Vice President
Ulrich Mohr, Hannover - Vice President
Roger D. Middlekauff, Washington - Secretary/Treasurer
Respiratory
System
Edited by
T.e.Jones V.Mohr R.D.Hunt
With 279 Figures and 20 Tables
Springer-Verlag
Berlin Heidelberg New York Tokyo 1985
Thomas Carlyle Jones, D. V. M., D. Sc.
Professor of Comparative Pathology, Emeritus
Harvard Medical School
New England Regional Primate Research Center
One Pine Hill Drive, Southborough, MA 01772, USA
Ulrich Mohr, M. D.
Professor of Experimental Pathology
Medizinische Hochschule Hannover
Institut fur Experimentelle Pathologie
Konstanty-Gutschow-Strasse 8
3000 Hannover 61, Federal Republic of Germany
Ronald Duncan Hunt, D. V. M.
Professor of Comparative Pathology
Harvard Medical School
New England Regional Primate Research Center
One Pine Hill Drive, Southborough, MA 01772, USA
ISBN-13: 978-3-642-96848-8 e-ISBN-13: 978-3-642-96846-4
DOl: 10.1007/978-3-642-96846-4
Library of Congress Cataloging in Publication Data. Main entry under title:
Respiratory system. (Monographs on pathology oflaboratory animals) Bibliography: p.
Includes index. 1. Laboratory animals-Diseases. 2. Respiratory organs-Diseases. 3. Ro-
dents-Diseases. 4. Rodents as laboratory animals. 5. Pathology, Comparative. I. Jones,
Thomas Carlyle. II. Mohr, U. (Ulrich) III. Hunt, Ronald Duncan. IV. Series.
SF996.5.R47 1985 599.32'3 84-14048
This work is subject to copyright. All rights are reserved, whether the whole or part of the
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than private use a fee is payable to 'Verwertungsgesellschaft Wort', Munich.
© Springer-Verlag Berlin Heidelberg 1985
The use of registered names, trademarks, etc. in the publication does not imply, even in
the absence of a specific statement, that such names are exempt from the relevant protec-
tive laws and regulations and therefore free for general use.
Product Liability: The publisher can give no guarantee for information about drug
dosage and application thereof contained in this book. In every individual case the
respective user must check its accuracy by consulting other pharmaceutical literature.
2123/3140-543210
Foreword
The International Life Sciences Institute (ILSI) was creat-
ed to promote cooperative efforts toward solving critical
health and safety questions involving foods, drugs, cosmet-
ics, chemicals, and other aspects of the environment. The
Officers and Trustees believe that questions regarding
health and safety are best resolved when government and
industry rely on scientific investigations, analyses, and re-
views by independent experts. Further, the scientific
aspects of an issue should be examined and discussed on
an international basis, separate from the political concerns
of individual companies.
ILSI is pleased to sponsor this set of monographs on the
pathology of laboratory animals. This project will be use-
ful in improving the scientific basis for the application of
pathologic techniques to health and safety evaluation of
substances in our environment. The world wide distribu-
tion of the authors, editors, and Editorial Board who are
creating these monographs strengthens the expectation
that international communication and cooperation will al-
so be strengthened.
Alex Malaspina
President
International Life Sciences Institute
Preface
This book on the respiratory system is the second volume of a set pre-
pared under the sponsorship of the International Life Sciences Insti-
tute (ILSI). One aim of this set on the Pathology of Laboratory Ani-
mals is to provide information which will be useful to pathologists,
especially those involved in studies on the safety of foods, drugs,
chemicals, and other substances in the environment. It is expected that
this and future volumes will contribute to better communication on an
international basis among people in government, industry, and acade-
mia who are involved in the protection of the public health.
The arrangement of this volume is based, in part, upon the philosophy
that the first step toward understanding a pathologic lesion is its pre-
cise and unambiguous identification. The microscopic and ultrastruc-
tural features of a lesion that are particularly useful to the pathologist
for definitive diagnosis are therefore considered foremost. Diagnostic
terms preferred by the author and editors are used as the subject head-
ing for each pathologic lesion. Synonyms are listed although most are
not preferred and some may have been used erroneously in prior pub-
lications. The problems arising in differential diagnosis of similar le-
sions are considered in detail. The biologic significance of each patho-
logic lesion is considered under such headings as etiology, natural
history, pathogenesis, and frequency of occurrence under natural or
experimental conditions.
Comparison of information available on similar lesions in man and
other species is valuable as a means to gain broader understanding of
the processes involved. Knowledge of this nature is needed to form a
scientific basis for safety evaluations and experimental pathology. Ref-
erences to pertinent literature are provided in close juxtaposition to the
text in order to support conclusions in the text and lead toward addi-
tional information. Illustrations are an especially important means of
non verbal communication, especially among pathologists, and there-
fore constitute important features of each volume.
The subject under each heading is covered in concise terms and is ex-
pected to stand alone, but in some instances it is important to refer to
other parts of the volume. A comprehensive index is provided to en-
hance the use of each volume as a reference.
Some omissions are inevitable and we solicit comments from our col-
leagues to identify parts which need strengthening or correction. We
have endeavored to include important lesions which a pathologist
might encounter in studies involving the rat, mouse, or hamster. Newly
recognized lesions or better understanding of old ones may make
revised editions necessary in the future.
The editors wish to express their deep gratitude to all of the individuals
who have helped with this enterprise. We are indebted to each author
and member of the Editorial Board whose names appear elsewhere in
the volume. We are especially grateful to the Officers and Board of
Trustees of the International Life Sciences Institute for their support
and understanding. Several people have worked directly on important
details in this venture. These include Nina Murray, Executive Secre-
VIII Preface
tary; Beverly Blake, Editorial Assistant; June Armstrong, Medical Il-
lustrator; and Virginia Werwath, Administrative Assistant. Sharon K.
Coleman, ILSI Coordinator for External Affairs, was helpful on many
occasions.
We are particularly grateful to Dr. Dietrich Gotze and his staff at
Springer-Verlag for the quality of the published product.
November 1984 T.C.Jones
V.Mohr
R.D.Hunt
Table of Contents
The Upper Respiratory System (Nares, Larynx, Trachea) . 1
Histology, Ultrastructure, Embryology . . . . . . . . . . . . 3
Macrosopic, Microscopic, and Ultrastructural Anatomy of the
Nasal Cavity, Rat
J. A. POPP and N. A. MONTEIRO-RIVIERE ........... 3
Development of Syrian Golden Hamster Tracheal Epithelium
During Prenatal and Immediate Postnatal Stages
M.EMURA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Epithelial Alterations in Explant Cultures of Fetal Tracheae of
Syrian Golden Hamsters
M.EMURA. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Response to Carcinogens of Respiratory Epithelium, Syrian
Golden Hamster (Mesocricetus Auratus)
H.-B. RICHTER-REICHHELM, W. BONING, and J. ALTHOFF. 33
Polypoid Adenoma, Nasal Mucosa, Rat
W.D.KERNS .................. . 41
Neoplasms, Mucosa, Ethmoid Turbinates, Rat
S. F. STINSON and H. M. REZNIK-SCHOLLER . 47
Squamous Cell Carcinoma, Nasal Mucosa, Rat
W.D.KERNS .................. . 54
Squamous Cell Carcinoma, Upper Respiratory Tract, Syrian
Hamster
P. M. POUR. . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Adenocarcinoma, Anterior Nasal Epithelium, Rat
S. F. STINSON and G. REZNIK ........... . 67
Hemangiosarcoma, Nasal Cavity, Mouse
W. E. GIDDENS Jr. and R. A. RENNE .... 72
Clear Cell Carcinoma, Larynx, Syrian Hamster
P.M. POUR .................... . 75
Lesions Due to Infections. . . . . . . . . . . . . . . . . . . . . .. 78
Murine Respiratory Mycoplasmosis, Upper Respiratory Tract,
Rat
T. R. SCHOEB and J. R. LINDSEY. . . . . . . . . . . . . . . . . 78
Sialodacryoadenitis Virus Infection, Upper Respiratory Tract,
Rat
D. G. BROWNSTEIN ....................... 84
X Table of Contents
The Lung (Bronchi, Bronchioles, Alveolar Ducts, Alveoli, Pleura) . 87
Histology and Ultrastructure . . . . . 89
Structure and Function of the Lung
C. KUHN III ............ . 89
Neoplasms. 99
Bronchiolar/Alveolar Adenoma, Lung, Rat
G. A. BOORMAN ............... . 99
Alveolar Type II Cell Adenoma, Lung, Mouse
S. L. KAUFFMAN and T. SATO ........ . 102
Bronchiolar Adenoma, Lung, Mouse
S. L. KAUFFMAN and T.SATO ..... 107
Bronchiolar/Alveolar Carcinoma, Lung, Rat
G. A. BOORMAN ................ . 112
Squamous Cell Carcinoma, Lung, Syrian Hamster
P. M. POUR and H. M. REZNIK-SCHULLER. 117
Squamous Cell Carcinoma, Lung, Rat
G. A. BOORMAN ............... . 124
Radiation-Induced Squamous Cell Carcinoma, Lung of
Rodents
F. F. HAHN. . . . . . . . . . . . . . . . . . . . . . . . . . 127
Pleural Mesothelioma, Syrian Hamster
A.CARDESAandJ.A.BOMBI ... 133
Metastatic Tumors, Lung, Mouse
B. SASS and A. G. LIEBELT 138
Nonneoplastic Lesions . . . 160
Bleomycin-Induced Injury, Mouse: A Model for Pulmonary
Fibrosis
D. H. BOWDEN .... . . . . . . . . . . . . . . . . . . 160
Endogenous Lipid Pneumonia in Female B6C3Fl Mice
Y. EMI and Y. KONISHI ................. . 166
Pulmonary Lipidosis, Rat
Y. EM I, R. HIGASHIGUCHI, and Y. KONISHI . 169
Alveolar Lipoproteinosis, Rat
W.WELLER .................. . 171
Bronchiolar/Alveolar Hyperplasia, Lung, Rat
G. A. BOORMAN ................ . 177
Fly Ash Pneumoconiosis, Hamster
G. E. DAGLE and A. P. WEHNER 180
Asbestosis, Hamster
G. E. DAGLE and A. P. WEHNER 183
Pulmonary Hair Embolism
A. KAST ............ . 186
Table of Contents XI
Lesions Due to Infection . . . . . . . . . . . . . 195
Sendai Virus Infection, Lung, Mouse and Rat
D. G. BROWNSTEIN ......... . 195
Rat Coronavirus Infection, Lung, Rat
D. G. BROWNSTEIN ......... . 203
Pneumonia Virus of Mice Infection, Lung, Mouse and Rat
D. G. BROWNSTEIN ................. 206
Sialodacryoadenitits Virus Infection, Lung, Mouse
D. G. BROWNSTEIN .............. . 210
Murine Respiratory Mycoplasmosis, Lung, Rat
T. R. SCHOEB and J. R. LINDSEY ........ . 213
Pneumocystosis, Lung, Rat
J. K. FRENKEL ......... . 218
Aspergillosis and Mucormycosis, Lung, Rat
J. K. FRENKEL ............... . 224
Toxoplasmosis, Lung, Mouse and Hamster
J. K. FRENKEL 227
Subject Index . . 231
List of Contributors
llirgen Althoff, M. D.
Professor of Experimental Pathology, Hannover Medical School,
3000 Hannover 61, Federal Republic of Germany
Josep Antoni Bombi, M. D.
Assistant Professor, Department of Pathology,
University of Barcelona, Medical School, Barcelona, Spain
W. Boning, Dr. rer. nat.
Hannover Medical School, Hannover, Federal Republic of Germany
Gary A. Boorman, D. V. M., Ph. D.
Head, Tumor Pathology, Chemical Pathology Branch, NIEHS,
Research Triangle Park, North Carolina, USA
Drummond H. Bowden, M. D.
Professor and Head, Department of Pathology,
University of Manitoba, Manitoba, Canada
David G. Brownstein, D. V. M.
Associate Professor of Comparative Medicine, Yale University School
of Medicine, New Haven, Connecticut, USA
A. Cardesa, M. D.
Patologica Facultad de Medicina, Universidad de Barcelona,
Barcelona, Spain
Gerald E. Dagle, D. V. M., Ph. D.
Staff Pathologist, Battelle, Pacific Northwest Laboratory, Richland,
Washington, USA
Yohko Emi, D.V.M.
Department of Oncological Pathology, Cancer Center,
Nara Medical College, Nara, Japan
Makito Emura, Priv. Doz. Dr. rer. nat.
Head, Tissue Culture Unit, Institute of Experimental Pathology,
Hannover Medical College, Hannover, Federal Republic of Germany
J. K. Frenkel, M. D., Ph. D.
Professor of Pathology and Oncology, Department of Pathology and
Oncology, University of Kansas Medical Center,
Kansas City, Kansas, USA
W. Ellis Giddens, Jr., D. V. M., Ph. D.
Associate Professor, Division of Animal Medicine,
Department of Pathology, School of Medicine,
University of Washington, Seattle, Washington, USA
Fletcher F. Hahn, D. V. M., Ph. D.
Head, Pathology Group, Inhalation Toxicology Research Institute,
Lovelace Biomedical and Environmental Research Institute,
Albuquerque, New Mexico, USA
Ryuichi Higashiguchi, M. D.
Assistant, Department of Oncological Pathology, Cancer Center,
Nara Medical College, Nara, Japan
