Harold L. Stewart

Comparative Aspects of Certain Cancers

Descriptions of the relative frequency, age distribution, site, histological appearance, and spread of tumors of man and lower animals are numerous. Many of the sources of information detail wide differences among species. To collect all the specific details of this information in one publication would amount to an encyclopedic task. I have therefore selected a few examples of common human neoplasms of specific sites and compared them with neoplasms of similar sites in other species. These are tumors of the lung, liver, mammary gland, and soft tissues, and, because of their recent appearance in employees of the plastics industry, malignant hemangioendotheliomas induced by exposure to vinyl chloride. While there are some similarities, there are many differences among species. A point of view that many writers on comparative oncology have adopted is to overemphasize the resemblance between neoplasms of lower animals, particularly rodents, and those of man. A stated aim of these authors has been to adopt, whenever possible, the classification and terminology proposed by the WHO International Reference Centers for the histological classification of human tumors. To stress the resemblances without pointing up the differences in structural appearances and known behavior is likely to mislead investigators to believe that many animal tumors are suitable models for the human tumors. What are needed are a series of workshops and studies by collaborative committees. These would bring together pathologists with their slides and their clinical, biological, and behavioral data in order to confer and to work out acceptable definitions of cancer types in different species of lower animals.

Mammary Gland Tumors in Irradiated Untreated Guinea Pigs

This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or 2) as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently-exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.

Primary Tumors of the Spleen in Guinea Pigs

A classification and morphologic description of primary splenic tumors of guinea pigs is presented for the first time. Twenty glomerate vascular tumors, 15 sinusoidal hemangioendotheliomas, 4 hemangiosarcomas, 2 chondromatous and 5 lipomatous tumors with or without fibrous or vascular components were encountered in the spleen of male and female guinea pigs of 2 inbred strains and one noninbred stock. Foci of cellular arrangements distinctive for splenic tissues were observed in every tumor. In 2 additional guinea pigs, hemangiosarcomas were found disseminated in the spleen, liver, lung and kidney; since the splenic origin of these tumors was uncertain, they were not included in this group of primary splenic tumors. At all levels used, whole body irradiation with X-or gamma rays increased the rate of occurrence and the number of splenic tumors. A significantly greater number of splenic tumors developed in the irradiated than in the untreated inbred guinea pigs after the age of 30 months. In the irradiated noninbred guinea pigs significantly fewer splenic tumors occurred than in the guinea pigs of the inbred strains.

Experimental Cancer of the Glandular Stomach. A Review

Genuine progress has been made in the experimental induction of adenocarcinoma of the glandular stomach during the 6 years that have elapsed since the interim meeting of the International Union Against Cancer in Tokyo in 1960. At that meeting I gave a preliminary report of the induction of this neoplasm in rats by the administration of a fluorenamine compound, N,N′-2,7fluorenylenebisacetamide (2,7-FAA) in the diet. Since then, other chemical agents of different classes have also been found that induce this neoplasm when administered orally, intragastrically, intraperitoneally or intravenously. This report reviews the various regimens that have been employed to induce adenocarcinoma and related lesions of the glandular stomach and the possible mechanisms involved. A number of studies have also revealed information on the precancerous changes that occur in the glandular stomach of animals treated with gastric carcinogens and these are reviewed.

The Harold Dorn Memorial Lecture

Cancer of the alimentary tract takes a heavy toll of lives in many countries of the world. It is perhaps important in considering etiology that the frequencies of certain site specific cancers of this tract may vary as much on a geographic basis as do cancers of any other system of the body. Clinical investigations have disclosed next to nothing about etiology and, although certain associations have been proposed, these are often ill-defined and presumptive. We know the cause of relatively few cancers in human beings and most of those that are recognized are in persons exposed to chemicals used in industry. None of these industrial cancers involve the alimentary tract. We cannot select a cancer of any site in the alimentary tract and say with assurance that this cancer was caused by a particular agent. Over the past 30 years, much information has accumulated on experimental cancer of the alimentary tract in animals. Many new carcinogens have been discovered and much new information on the mechanism of carcinogenesis has been revealed. Studies with animals indicate that the etiologies of cancer of each segment of the tract may be highly specific, albeit the emergence of cancer at these sites may be influenced by the genetic or hormonal composition of the test animal. The information that we have acquired from laboratory animals warrants the assumption that the varying site frequencies of alimentary tract cancers in human beings who live in different population groups and geographic areas reflect specific etiologies that are linked to the environment.