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Pathology of tumours in laboratory animals
ENVIRONMENTAL
RESEARCH
9,94-98
(1975)
Book
PATHOLOGYOF
TUMOURS
Reviews
ANIMALS. Volumel: Tumours oftheRat, Publications No. 5) (in English) Edited by V. S. Agency for Research on Cancer, Lyon, 1973,
IN LABORATORY
Part 1 (IARC Scientific Turusov. International 212 pp. $15.00.
The International Agency for Research on Cancer has undertaken to issue a series of publications on the pathology of tumors in laboratory animals, starting with tumors of the rat, mouse, and hamster-the species most commonly used in cancer research. Part 1 of Volume 1 dealing with rat tumors is now available. It contains chapters on tumors of the skin, auditory sebaceous glands, mammary glands, salivary glands, oesophagus, stomach, intestines, pancreas, soft tissues, bones, and hematopoietic system. In general, the following scheme has been adopted by the various contributors: normal structure of the organ concerned, morphology and classification of tumors, spontaneous tumors, principal methods of tumor induction, and comparative aspects. Each paper is accompanied by a number of illustrations. Two chapters are contributed by a single author but each of the others is by a different author or group of authors, and authors from the following 5 countries contributed to this publication: Japan, the Netherlands, the United Kingdom, U.S.A. and U.S.S.R. The stated purpose is to form a common ground in the understanding and nomenclature of neoplasia in experimental animals so that better communication among investigators can be achieved. The test of this purpose will depend upon the extent to which these definitions of tumor types are accepted. Like all multiauthored volumes, the quality varies. In general, however, this first attempt to bring together the existing knowledge of the pathology of tumors of laboratory animals is excellent and highly commendable. The preface emphasizes the aim to keep information comprehensible, complete, and current. This latter is obviously needed, for there are omissions in several of the present chapters. For example, the salivary gland neoplasms induced by the fluorenamine compounds are not mentioned. Since future editions are already in the planning stages, it behooves all who study the different chapters to offer criticisms and contributions to further editions by transmitting material to the technical editor, Dr. Walter Davis at the International Agency for Research on Cancer, 150 tours Albert Thomas, 69008 Lyon, France. This series of volumes promises to be an excellent compendium of our knowledge of the pathology of rodent neoplasms written especially for experimental pathologists. If the technical format of the subsequent volumes can be improved, the work should receive wide and 94
BOOK
REVIEWS
95
enthusiastic acceptance in the areas of experimental carcinogenesis, carcinogenicity testing and cancer therapy. The chapter on mammary tumors contains, in addition to pathologic descriptions, excellent accounts of the embryological and later development of the rat mammary glands of males and females, the functional capabilities of the tissues, how they synthesize protein, lipids and lactose, the appearance of the structures in electron micrographs, and the histochemical reactions of the different cellular components. ‘The last chapter on hematopoietic neoplasms is also of high quality; it is concise, informative, well annotated and carefully illustrated. One wishes that the other chapters had contained comparable detailed information about the tissue sites from which the neoplasms develop. The authors wisely solicited illustrations from their colleagues in order to supplement their own and to reproduce the best possible figures. Numerically, qualitatively, and quantitatively the book is abundantly illustrated and the photomicrographs are accurately reproduced, Objections are the dark background and, moreover, none of the illustrations are in color. One wonders why? Certainly not for lack of money. Above billions in the form of yen, francs, marks, kroner, pounds, and like currencies from state and private organizations of many countries of the world are annually available for the support of cancer research from which a small sum could have been siphoned off to provide improved illustrations for this very important publication. The WHO publications of the International Reference Centers (IRC) are elegantly illustrated in color and the illustrations are exceedingly accurate. The value of the Pathology of Tumours in Laboratory AnimaZs could have been enhanced by the addition of some color illustrations. Unfortunate features also are that all of the illustrations are placed at the end of each chapter and the legends are printed in numerical order one after the other on a page or two immediately following the references and preceding the illustrations. This necessitates thumbing back and forth through several pages to locate a figure to which the text refers and to compare the illustration with the description in the legend. It would have been more convenient for the reader had the illustrations been approximated more closely to the text that refers to them and the legend for the corresponding illustration printed beneath the figure or on the facing page. Moreover, the legends could have been more detailed and explanatory to give the illustrations more prominence and to have made the publication more of an atlas. Benign and malignant are two words the meaning and characteristics of which every experimental pathologist should define clearly as he intends them to be understood when he uses them and writes about them. Nowadays, to make a decision that a given neoplasm is benign or malignant carries a legal implication in the area of carcinogenicity testing. In this country, if a malignant neoplasm develops from the administration of a potential food additive, the agent is banned, whereas if the neoplasm so induced is diagnosed benign, the agent is permitted. This present publication is full of specious decisions about benign and malignant neoplasms. To give a few examples, benign soft tissue neoplasms such as fibroma and lipoma are described separately from malignant ones but some experimental pathologists have never encountered neoplasms of this type or any induced soft
96
BOOK
REVIEWS
tissue neoplasm in a rat that they were convinced was entirely benign. A benign form of hemangioendothelioma is listed, a neoplasm that most pathologists would designate hemangioma, reserving the term hemangioendothelioma for the malignant neoplasms of blood vessels. The author of the chapter on auditory sebaceous gland tumors has skirted this problem by designating one of the neoplasms of this site as “malignant adenoma,” an obvious contradiction in terms. With mammary gland tumors, many of those that the authors of this chapter describe and illustrate as benign are indistinguishable from those that have been successfully transplanted serially to syngeneic rats in which the neoplasm grows, spreads, metastasizes and kills the animal like any malignant neoplasm. The authors state that differentiating adenoma from adenocarcinoma of the mammary gland of the rat may be difficult. This is certainly an understatement. One wonders if such attempts are not futile in view of the close intermingling of the two patterns described in the same mammary tumor and the likelihood that the two simply represent different stages of progression. Comparable histologic patterns at different stages of progression are manifested by bladder tumors in man and uterine tumors in the rabbit. This is likely the case with rat mammary tumors. With the epithelial tumors of the glandular stomach also, pathologists are advised to diagnose carcinoma on the basis of the histologic appearances of the tissue. However, it is well known that non-neoplastic proliferative lesions of the glandular stomach of rodents may exhibit histologically abnormal appearing glandular formations and yet the process does not spread locally, metastasize or grow upon transplantation. Advice of this nature is likely to introduce a shifting denominator which has the effect of raising or lowering the incidence of cancers induced by the same compound in rats of the same strain but evaluated by different observers with different standards. In part these criticisms are due to the inadequate state of our knowledge about the biology of rodent neoplasms and the lack of agreement about the significance of criteria. In earlier years the same uncertainty about the benign or malignant nature of many neoplasms of man existed and it was only as a result of comparing their morphological characteristics with their behavior that the accuracy of the diagnosis of clinical cancer has reached the high level that it enjoys today. A stated aim of this publication has been to adopt, whenever possible, the classification and terminology proposed by WHO’s International Reference Centers for human tumors. One wonders if this isn’t a mistake and if it had been wiser to introduce a terminology for rodent tumors more fitting to the correlation of their structural appearance and known behavior. On several pages (31, 43,49) the structural resemblance between rat and human mammary neoplasms is emphasized. This is likely to mislead investigators inexperienced in pathology to believe that rat mammary tumors are suitable laboratory models for human breast cancer. Mammary cancers in man invariably metastasize if untreated, whereas in rats as stated in the text, spontaneous and carcinogen induced mammary tumors do not usually metastasize. Some rat mammary tumors having the histologic appearance of “cancer” regress upon the removal of the initiating agent. Regression of mammary cancer in man happens so infrequently that when it does the host becomes a candidate for canonization for surely this is evidence of divine
97
BOOK REVIEWS
intervention. Should the same name be applied to neoplasms that behave so differently in two species. 2 In several different chapters of this publication, the section on comparative pathology emphasizes more the similarities between rodent and human neoplasms rather than their dissimilarities. Obviously what is needed in experimental pathology is a series of workshops and studies by collaborative committees similar to those that WHO International Reference Centers have instituted to bring together pathologists with their slides and clinical, biological and behavioral data to confer and to work out acceptible definitions of cancer types. The same should be done for rodent neoplasms. The authors of this volume cannot be held responsible for misstatements about the biology of neoplasms about which there is a lack of general agreement. MEARL F. STANTON
Lal7oratory
of Pathology
HAHOLD L. STEWART
Registry of Experimental Cancers National Cancer Institute Bethesda. Alaryland 20014
THER~~AL COMFORT AND MODERATE HEAT STRESS.Building ResearchEstablishment (U. K.), Report No. 2. Proceedings of the CIB (International Building Research Council) Commission W45 (Human Requirements) Symposium, 13-15 September, 1972. Her Majesty’s Stationary Office, London. 283 pp., g3.25. After more than 25 years of “needling” by his erstwhile colleagues, the reviewer still has to admit that very little attention is being given in the U. S. to the thermal aspects of housing. Apart from limited academic studies supported by the American Society of Heating, Refrigerating and Air Conditioning Engineers, house design in relation to comfort has been almost entirely neglected here. The stock answer to repeated questions on the subject has been, in substance, “put on a bigger air conditioner ( and/ or heater) !” Such attitudes never made much sense in economies other than the North American, and it no longer makes sense there. In the meantime, generations of neglect have saddled us with structures seemingly designed to make life difficult without the expenditure of excessive and costly amounts of fuel. This casual attitude is underlined by the fact that, out of 75 participants, including 33 non-British nationals, in the symposium here reported. just three were from the U. S. Of those, two were from academia, and one from the National Bureau of Standards, which is hardly the governmental agency that one associates with housing. Now that the inescapable has focussed attention upon the inevitable, it is hoped that a belated interest in the economic aspects of house design will drive a goodly number to seek out the principles invoIved and to bring themselves abreast with available knowledge. For such as these, and it is hoped that
RESEARCH
9,94-98
(1975)
Book
PATHOLOGYOF
TUMOURS
Reviews
ANIMALS. Volumel: Tumours oftheRat, Publications No. 5) (in English) Edited by V. S. Agency for Research on Cancer, Lyon, 1973,
IN LABORATORY
Part 1 (IARC Scientific Turusov. International 212 pp. $15.00.
The International Agency for Research on Cancer has undertaken to issue a series of publications on the pathology of tumors in laboratory animals, starting with tumors of the rat, mouse, and hamster-the species most commonly used in cancer research. Part 1 of Volume 1 dealing with rat tumors is now available. It contains chapters on tumors of the skin, auditory sebaceous glands, mammary glands, salivary glands, oesophagus, stomach, intestines, pancreas, soft tissues, bones, and hematopoietic system. In general, the following scheme has been adopted by the various contributors: normal structure of the organ concerned, morphology and classification of tumors, spontaneous tumors, principal methods of tumor induction, and comparative aspects. Each paper is accompanied by a number of illustrations. Two chapters are contributed by a single author but each of the others is by a different author or group of authors, and authors from the following 5 countries contributed to this publication: Japan, the Netherlands, the United Kingdom, U.S.A. and U.S.S.R. The stated purpose is to form a common ground in the understanding and nomenclature of neoplasia in experimental animals so that better communication among investigators can be achieved. The test of this purpose will depend upon the extent to which these definitions of tumor types are accepted. Like all multiauthored volumes, the quality varies. In general, however, this first attempt to bring together the existing knowledge of the pathology of tumors of laboratory animals is excellent and highly commendable. The preface emphasizes the aim to keep information comprehensible, complete, and current. This latter is obviously needed, for there are omissions in several of the present chapters. For example, the salivary gland neoplasms induced by the fluorenamine compounds are not mentioned. Since future editions are already in the planning stages, it behooves all who study the different chapters to offer criticisms and contributions to further editions by transmitting material to the technical editor, Dr. Walter Davis at the International Agency for Research on Cancer, 150 tours Albert Thomas, 69008 Lyon, France. This series of volumes promises to be an excellent compendium of our knowledge of the pathology of rodent neoplasms written especially for experimental pathologists. If the technical format of the subsequent volumes can be improved, the work should receive wide and 94
BOOK
REVIEWS
95
enthusiastic acceptance in the areas of experimental carcinogenesis, carcinogenicity testing and cancer therapy. The chapter on mammary tumors contains, in addition to pathologic descriptions, excellent accounts of the embryological and later development of the rat mammary glands of males and females, the functional capabilities of the tissues, how they synthesize protein, lipids and lactose, the appearance of the structures in electron micrographs, and the histochemical reactions of the different cellular components. ‘The last chapter on hematopoietic neoplasms is also of high quality; it is concise, informative, well annotated and carefully illustrated. One wishes that the other chapters had contained comparable detailed information about the tissue sites from which the neoplasms develop. The authors wisely solicited illustrations from their colleagues in order to supplement their own and to reproduce the best possible figures. Numerically, qualitatively, and quantitatively the book is abundantly illustrated and the photomicrographs are accurately reproduced, Objections are the dark background and, moreover, none of the illustrations are in color. One wonders why? Certainly not for lack of money. Above billions in the form of yen, francs, marks, kroner, pounds, and like currencies from state and private organizations of many countries of the world are annually available for the support of cancer research from which a small sum could have been siphoned off to provide improved illustrations for this very important publication. The WHO publications of the International Reference Centers (IRC) are elegantly illustrated in color and the illustrations are exceedingly accurate. The value of the Pathology of Tumours in Laboratory AnimaZs could have been enhanced by the addition of some color illustrations. Unfortunate features also are that all of the illustrations are placed at the end of each chapter and the legends are printed in numerical order one after the other on a page or two immediately following the references and preceding the illustrations. This necessitates thumbing back and forth through several pages to locate a figure to which the text refers and to compare the illustration with the description in the legend. It would have been more convenient for the reader had the illustrations been approximated more closely to the text that refers to them and the legend for the corresponding illustration printed beneath the figure or on the facing page. Moreover, the legends could have been more detailed and explanatory to give the illustrations more prominence and to have made the publication more of an atlas. Benign and malignant are two words the meaning and characteristics of which every experimental pathologist should define clearly as he intends them to be understood when he uses them and writes about them. Nowadays, to make a decision that a given neoplasm is benign or malignant carries a legal implication in the area of carcinogenicity testing. In this country, if a malignant neoplasm develops from the administration of a potential food additive, the agent is banned, whereas if the neoplasm so induced is diagnosed benign, the agent is permitted. This present publication is full of specious decisions about benign and malignant neoplasms. To give a few examples, benign soft tissue neoplasms such as fibroma and lipoma are described separately from malignant ones but some experimental pathologists have never encountered neoplasms of this type or any induced soft
96
BOOK
REVIEWS
tissue neoplasm in a rat that they were convinced was entirely benign. A benign form of hemangioendothelioma is listed, a neoplasm that most pathologists would designate hemangioma, reserving the term hemangioendothelioma for the malignant neoplasms of blood vessels. The author of the chapter on auditory sebaceous gland tumors has skirted this problem by designating one of the neoplasms of this site as “malignant adenoma,” an obvious contradiction in terms. With mammary gland tumors, many of those that the authors of this chapter describe and illustrate as benign are indistinguishable from those that have been successfully transplanted serially to syngeneic rats in which the neoplasm grows, spreads, metastasizes and kills the animal like any malignant neoplasm. The authors state that differentiating adenoma from adenocarcinoma of the mammary gland of the rat may be difficult. This is certainly an understatement. One wonders if such attempts are not futile in view of the close intermingling of the two patterns described in the same mammary tumor and the likelihood that the two simply represent different stages of progression. Comparable histologic patterns at different stages of progression are manifested by bladder tumors in man and uterine tumors in the rabbit. This is likely the case with rat mammary tumors. With the epithelial tumors of the glandular stomach also, pathologists are advised to diagnose carcinoma on the basis of the histologic appearances of the tissue. However, it is well known that non-neoplastic proliferative lesions of the glandular stomach of rodents may exhibit histologically abnormal appearing glandular formations and yet the process does not spread locally, metastasize or grow upon transplantation. Advice of this nature is likely to introduce a shifting denominator which has the effect of raising or lowering the incidence of cancers induced by the same compound in rats of the same strain but evaluated by different observers with different standards. In part these criticisms are due to the inadequate state of our knowledge about the biology of rodent neoplasms and the lack of agreement about the significance of criteria. In earlier years the same uncertainty about the benign or malignant nature of many neoplasms of man existed and it was only as a result of comparing their morphological characteristics with their behavior that the accuracy of the diagnosis of clinical cancer has reached the high level that it enjoys today. A stated aim of this publication has been to adopt, whenever possible, the classification and terminology proposed by WHO’s International Reference Centers for human tumors. One wonders if this isn’t a mistake and if it had been wiser to introduce a terminology for rodent tumors more fitting to the correlation of their structural appearance and known behavior. On several pages (31, 43,49) the structural resemblance between rat and human mammary neoplasms is emphasized. This is likely to mislead investigators inexperienced in pathology to believe that rat mammary tumors are suitable laboratory models for human breast cancer. Mammary cancers in man invariably metastasize if untreated, whereas in rats as stated in the text, spontaneous and carcinogen induced mammary tumors do not usually metastasize. Some rat mammary tumors having the histologic appearance of “cancer” regress upon the removal of the initiating agent. Regression of mammary cancer in man happens so infrequently that when it does the host becomes a candidate for canonization for surely this is evidence of divine
97
BOOK REVIEWS
intervention. Should the same name be applied to neoplasms that behave so differently in two species. 2 In several different chapters of this publication, the section on comparative pathology emphasizes more the similarities between rodent and human neoplasms rather than their dissimilarities. Obviously what is needed in experimental pathology is a series of workshops and studies by collaborative committees similar to those that WHO International Reference Centers have instituted to bring together pathologists with their slides and clinical, biological and behavioral data to confer and to work out acceptible definitions of cancer types. The same should be done for rodent neoplasms. The authors of this volume cannot be held responsible for misstatements about the biology of neoplasms about which there is a lack of general agreement. MEARL F. STANTON
Lal7oratory
of Pathology
HAHOLD L. STEWART
Registry of Experimental Cancers National Cancer Institute Bethesda. Alaryland 20014
THER~~AL COMFORT AND MODERATE HEAT STRESS.Building ResearchEstablishment (U. K.), Report No. 2. Proceedings of the CIB (International Building Research Council) Commission W45 (Human Requirements) Symposium, 13-15 September, 1972. Her Majesty’s Stationary Office, London. 283 pp., g3.25. After more than 25 years of “needling” by his erstwhile colleagues, the reviewer still has to admit that very little attention is being given in the U. S. to the thermal aspects of housing. Apart from limited academic studies supported by the American Society of Heating, Refrigerating and Air Conditioning Engineers, house design in relation to comfort has been almost entirely neglected here. The stock answer to repeated questions on the subject has been, in substance, “put on a bigger air conditioner ( and/ or heater) !” Such attitudes never made much sense in economies other than the North American, and it no longer makes sense there. In the meantime, generations of neglect have saddled us with structures seemingly designed to make life difficult without the expenditure of excessive and costly amounts of fuel. This casual attitude is underlined by the fact that, out of 75 participants, including 33 non-British nationals, in the symposium here reported. just three were from the U. S. Of those, two were from academia, and one from the National Bureau of Standards, which is hardly the governmental agency that one associates with housing. Now that the inescapable has focussed attention upon the inevitable, it is hoped that a belated interest in the economic aspects of house design will drive a goodly number to seek out the principles invoIved and to bring themselves abreast with available knowledge. For such as these, and it is hoped that