1.2.1. Embryological classification

The classification of tumors is based on the embryonic origin of tissues and their histological structure. Thus, there are:

• – tumors originating from the ectoderm and endoderm: epithelial tumors or carcinomas;
• – neuroectodermal tumors: tumors of the nervous system and of the APUD (Amine Precursor Uptake and Decarboxylation) system or DES (diffuse endocrine system) tumors;
• – tumors originating from the mesoderm: tumors of the hematopoietic system and connective sarcomas.

A histogenetic classification, taking into account practical reality, is proposed by GHILEZAN (1992), including the following types of malignant tumors:

1. epithelial tumors (carcinomas, epitheliomas) which include basal cell tumors, pavement tumors, transitional tumors, adenocarcinomas;
2. connective tumors (sarcomas) with bone, cartilaginous and soft tissue tumors;
3. hematopoietic tissue tumors, with: lymphomas, leukemias, plasmacytic neoplasms, histiocytosis;
4. nerve tissue tumors;
5. multiple tissue tumors;
6. rare or difficult to classify tumors.

This book aims to be accessible, and especially, to be a practical guide for veterinary oncologists and researchers in the field. The different forms and types of tumors will be described by systems and large tissue groups.

The classification used is that proposed by WHO, and in certain cases, new and/or practical classifications will be adopted for different tumor forms, which are abundant in the literature.

1.2.2. Anatomical classification

The great majority of anatomical classifications proposed refer to dog and cat tumors but, with small adjustments, they can be used for all species. A short characterization is required for each location:

• – description of the tumor location or region;
• – strict definition of the region, regional and juxtaregional lymph nodes for each location;
• – depending on the case, clinical and surgical methods recommended for the evaluation of TNM categories.

Classification according to anatomical location:

1. skin, without lymphosarcoma and mastocytoma;
2. skin, mastocytoma;
3. mammary gland;
4. head and neck;
5. digestive tract, including the pancreas and liver;
6. urinary system;
7. genital system;
8. bones and joints;
9. lymphatic and hematopoietic system, including malignant skin lymphoma;
10. respiratory system;
11. endocrine glands (the thyroid and adrenal glands).

The tumors of the eye, central nervous system, heart and other endocrine glands are not included, as they are difficult to classify and many of these tumors show only a local invasion.

1.2.3. Histological classification

The quantified assessment of architectural and especially cytological parameters (cell differentiation grade, mitotic index, etc.) allows to establish a hierarchy of malignancy and to assign the studied tumor to a certain category. The notion of grade is intended to define histoprognosis.

Histological categories have been established for humans, then they have been adapted or modified, becoming totally specific for animals. According to their histological structure, tumors can be grouped in the following main categories: epithelial tumors, of ectodermal and endodermal embryonic origin; mesenchymal or connective tumors, of mesodermal origin; neuroectodermal tumors and tumors of unknown origin.

Examples of benign and malignant tumors, according to their histological structure:

• – covering epithelium, at skin level; benign tumor: keratoacanthoma; malignant tumor: squamous cell carcinoma;
• – covering epithelium, at intestinal level; benign tumor: papillary adenoma; malignant tumor: papillary carcinoma;
• – glandular epithelium, in the pancreas; benign tumor: adenoma; malignant tumor: adenocarcinoma;
• – glandular epithelium, in the liver; benign tumor: hepatoma; malignant tumor: hepatocellular carcinoma;
• – connective tissue, in the oral cavity; benign tumor: fibroma; malignant tumor: fibrosarcoma;
• – connective tissue, in the subcutaneous tissue; benign tumor: lipoma; malignant tumor: liposarcoma;
• – nerve tissue in the brain; benign tumor: astrocytoma; malignant tumor: malignant astrocytoma.

1.2.4. Tumor-lymph node-metastasis (TNM) classification

In 1980, OWEN adapted the TNM classification used in human oncology for domestic animals. The author justified the need for a unique classification of human and animal tumors, given the progress achieved since 1975, when the World Health Organization made the first classification of animal tumors.

The TNM system for the tumors of domestic animals raises the accuracy standard for diagnosis, clinical evolution and prediction. The main objective of the international agreement regarding the classification of cancer cases, after the extension of the disease, is to ensure a method that could allow for a unique and clear professional language. The task of the veterinary clinician is to make a provisional diagnosis and to make a decision regarding the most efficient therapeutic approach.

The objectives of tumor staging in animals are:

• – to assist the veterinary clinician in planning treatment;
• – to assist in the evaluation of treatment results;
• – to facilitate the information exchange between veterinary oncologists;
• – to contribute to the development of cancer investigations in animals;
• – to contribute to the information exchange between human and animal oncology.

These objectives can be achieved through the TNM classification system, in which the basic principles can be applied for all locations, regardless of treatment, with the advantage that it can be subsequently completed with the findings obtained from histopathological and surgical investigations.

The TNM system concerns: the extension of the primary tumor (T); the condition of lymph nodes (N); the absence or presence of distant metastases (M). In order to increase the accuracy of these parameters, numbers are added, which indicate the extension of the malignant tumor.

OWEN (1980) establishes some general rules that can be applied to all tumors, regardless of their location.

In all cases, malignancy should be confirmed by histological and/or cytological examination. The cases in which this confirmation is not possible will be recorded separately. In some locations, several types of cancer may appear, which differ not only by their histological appearance, but also by their clinical behavior. Such an example is mammary gland carcinoma in female dogs: in the case of a well differentiated tubular adenocarcinoma, prognosis is favorable after mastectomy, in contrast with anaplastic carcinoma, when prognosis is reserved or even unfavorable.

All cases will be classified using TNM categories and they will be classified and recorded before the initiation of treatment. In the case of an animal with a poor clinical condition, which excludes surgical intervention, the case will not be recorded through the TNM system. The clinical TNM classification performed before treatment is of maximum importance in the reporting and evaluation of the tumor. Detailed histological information is a decisive supplement to clinical diagnosis.

The clinical diagnosing of a tumor in an animal requires multiple investigations. Compulsory investigations will be associated with complementary ones, in order to establish the grade of malignancy. The TNM classification includes a minimum number of categories, among which the regional lymph nodes for each location.

The determining of the extension degree by TNM categories facilitates the grouping of certain tumors at different clinical stages. Due to their location, some tumors are more accessible to a complete clinical examination. Thus, mammary gland, skin and bone tumors, esophageal and laryngeal tumors can be seen, palpated and measured directly, and regional lymph nodes are also accessible. At the same time, other locations such as visceral tumors (stomach, colon, kidney, ovarian tumors), situated at a greater depth, are less accessible to clinical examination, which requires additional investigations in order to complete the data of the TNM classification.

In veterinary oncology, postsurgical TNM classification, pTNM, which also includes histopathological classification, is less used. However, the postsurgical histopathological examination of both the excised tumor and the removed regional lymph nodes is extremely useful in certain cases.

Primary tumors (T) are classified according to their grade in four categories: T₁, T₂, T₃ and T₄. There are peculiarities depending on the location, but each tumor should be examined clinically, if possible, in order to define its limits, size, whether it is mobile or fixed and adherent to the adjacent tissues.

An extremely accurate, simple and stereographic record is necessary, which allows cancer specialists to establish, based on a common language, certain criteria for a positive diagnosis and an adequate therapeutic approach. For this purpose, the following definitions are given for primary tumors (T):

T₀ – means a clinically undetectable tumor, which is evidenced through adenopathies or metastases;

T₁ – refers to a small, strictly circumscribed tumor, which does not reach the organ limits;

T₂ – in this case the tumor reaches the organ limits;

T₃ – the tumor is fixed to the neighboring organs;

T₄ – refers to a tumor that has invaded the neighboring organs.

An in situ tumor is noted IST.

According to their location and possibilities of investigation, primary tumors can be grouped into three categories for the TNM classification:

1. Tumors that appear in a single organ and are the easiest to classify. Such an example can be mammary gland tumors in dogs, whose dimensions, relation to the skin and the deep tissues can be established accurately. The T growth grade and clinical assessment are synthetically shown in the following table:

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   Size	T1	T2	T3	T4
   	<3 cm	3–5 cm	>5 cm
   Skin	Minor invasion			Major invasion
   Fascia, muscle, thoracic wall	With or without fascia or muscle fixation			Tumor fixation to the thoracic or abdominal wall

2. Less circumscribed or completely uncircumscribed tumors, whose size and extension cannot be established, such as bladder tumors that are evaluated by cystoscopy, radiography, local examination under anesthesia and the assessment of tumor penetration into the bladder wall.
3. Tumors that cannot be completely diagnosed without taking into consideration the surgical findings. An example can be ovarian tumors, evaluated through laparotomy; colon and bone tumors, assessed postoperatively.

Multiple primary tumors will be evaluated as follows:

• – tumors found simultaneously in pair organs, such as the mammary gland chain, which will be classified independently;
• – tumors found simultaneously in the skin, when the tumor with the highest T category is first identified, and the number of tumors is indicated between brackets: T₂ (5);
• – tumors found in cavitary viscera or tubular organs, such as: bladder, vagina, penis, for which the number of tumors is not important and which are defined by adding the “m” suffix: T₃ (m).

In order to define the local tumor extension, the grades of the T category should be completed by the following symbols:

• – T₀, for a tumor that cannot be evidenced, such as the cases in which metastases are produced by lymphatic or hematogenous route, while the primary tumor remains occult;
• – T_x, for a primary tumor whose extension is impossible to appreciate; this category is reserved exclusively for the in situ carcinoma, a preinvasive carcinoma, with locations in the sclera, cornea, eyelid, nose, etc.

Regional lymph nodes (N) are catalogued using indices, N₀, N₁, N₂ and N₃, depending on the characteristics of the examination by palpation, lymphangiography and other procedures. For each index of lymph node changing, the following are considered:

• – N₀ means palpable lymph nodes;
• – N₁ is used for palpable, mobile lymph nodes, without pathognomonic characteristics;
• – N₂, for large, hard, still mobile, or with bilateral metastasis in lymph nodes;
• – N₃, for adherent and fixed, uni- or bilateral metastasis in lymph nodes.

If the presence of cancer cells is histologically confirmed, N⁺ is noted, and if no cancer cells are detected, N⁻ is noted.

Distant metastases (M) are codified as follows:

• – M₀, no metastases have been clinically and radiologically identified;
• – M₁, metastases are clinically and radiologically present in organs or tissues, and the metastatic organ (liver, lung, bones, etc.) can be mentioned.

Histopathological extension (P) and grading (G) can offer additional information. The P symbol refers to the depth of the tumor infiltration in an organ or tissue, and the G symbol to the grade of tumor malignancy. For example, in the case of some cavitary organs, histopathological extension is expressed by four P grades:

• – P₁, tumor limited to the mucosa;
• – P_2; the tumor involves the mucosa and submucosa, extending to the serous membrane but without penetrating it;
• – P₃, the tumor penetrates through the serous membrane, with or without the invasion of adjacent structures;
• – P_4; the tumor diffusely and completely invades the organ wall, without the evidencing of limits.

The malignancy grade (G) is expressed by three categories:

1. G₁, low malignancy grade;
2. G₂, moderate malignancy grade;
3. G₃, high malignancy grade.

1.2.5. Clinical classification

The combination of the three elements of the TNM classification allows to establish the clinical stage, with the possibility of prognostic evaluation. An example:

• – clinical stage I: T₁ N₀, M₀ or T₂, N₀, M₀;
• – clinical stage II: T₂, N₁, M₀ or T₂, N₁, M₀;
• – clinical stage III: T₁, N_2,3, M₀ or T₂, N_2,3, M₀;
• – clinical stage IV: T₃, N₀,₁,₂,₃, M₀ or T₄, N₀,₁,₂,₃, M₀ or any TN + M₁.

Survival at one year in the first group can be 60%, while in the last group this can be only 15%. The TNM classification is more practical than the classification by clinical stages.

1.3.1. Tumor incidence in animals

Production animals have a short life or, to put it differently, they have an “economic life”, which is why old age diseases, including cancer, are not expressed. In addition, animal populations fluctuate considerably from year to year, making almost impossible the definition of the populations exposed to the disease. The same problem, but to a smaller extent, occurs in the case of companion animals.

The data obtained for small populations and geographical areas are difficult to extrapolate to humans, and generalizations can be highly biased.

The literature offers fragmentary data regarding the morbidity of cancer disease in animals. We consider that the citation of studies investigating the incidence rate or/and the prevalence of neoplasms in different animal species, in smaller or larger populations, is useful.

1.3.2. Tumor incidence by age

The epidemiological study performed by MIALOT and LAGADIC (1990) includes precise references to the age of dogs and cats, correlated with tumor incidence. A positive correlation of all tumor types with the age of animals is remarked. The increase in tumor incidence is correlated until the age of 10 years with animal age, in both dogs and cats. Tumor frequency remains high until the age of 12 years in dogs and 13 years in cats, then it gradually diminishes, because of the life duration of these species. This distribution of tumor incidence depending on age is mentioned by other authors as well [32, 40, 149].

In dogs, the percentage of benign tumors is significantly higher than that of malignant tumors until the age of three years (p< 0.02), while the percentage of malignant tumors is significantly higher than that of benign tumors, starting with the age of 7 years (p < 0.001).

In cats, tumors are infrequent before the age of three years, being predominantly benign, and the difference between benign and malignant tumors is insignificant. In contrast, the percentage of malignant tumors is significantly higher than that of benign tumors, starting with the age of three years (p < 0.001) and remains significantly high for the studied age group [119].

Cancer seems to appear or can potentially appear in direct relation to life duration; in this sense, the following hierarchy is estimated in decreasing order: man, dog, horse, cat and cattle [89]. There are tumors that occur in both humans and animals, at a young age. Thus, the study of hemolymphatic neoplasms in young animals, under two years of age, shows that cats are the most exposed to this category of tumors, followed in decreasing order by cattle, dogs and horses.

1.3.3. Tumor incidence by sex

The global distribution of tumors in the two sex groups shows a higher frequency of tumors in females, in both dogs and cats, with the predominance of mammary tumors. Mammary tumors in males have a low incidence, less than 1% of mammary tumors in dogs and 1.3% of mammary tumors in cats [146].

In dogs, malignant and benign orodental salivary tumors are more frequent in males than in females (p > 0.001) [119]. DORN and PRIESTER (1976) have shown that there is an increased risk for the appearance of fibrosarcomas and oral melanomas in male dogs.

The frequency of malignant digestive tract tumors is also significantly higher in males compared to females (p > 0.001), while the difference regarding the benign tumors of this system is not significant in dogs [119].

Highly significant differences are found in the frequency of skin tumors in male and female dogs (p > 0.001). The considerable difference of these tumors in males is due to the high proportion of hepatoid gland tumors. These tumors are constant in males, but can also be found in females, with an extremely low percentage, representing 5.5% of all skin tumors, compared to 88.0% in males.

In cats, the malignant tumors of the oral cavity and digestive tract are more frequent in males (p > 0.001) than in females. Male cats have an extremely high frequency (p > 0.001) of bone cancer.

1.3.4. Tumor incidence by breed

In general, no breed has a predisposition to cancer, although the Boxer breed has a higher risk for the development of tumors in certain organs [40, 61, 145]. The literature emphasizes the fact that certain dog breeds have a higher or lower incidence of a certain tumor type.

MIALOT and LAGADIC (1990) were able to test the incidence of tumors in 60 breeds. PARODI’s conclusions (1977) concerning the breed predisposition to certain tumors are classical. The predisposition of dolichocephalic breeds to the tumors of the nasal cavity and sinuses, associated with a lower frequency of these tumors in brachycephalic breeds is well known. The predisposition of large size breeds to skeletal tumors is also known, while small dog breeds have a frequency of these tumors significantly lower than the mean.

The Boxer breed has been proved to have a predisposition to skin tumors, as well as endocrine, testicular and mesenchymal tumors.

The breeds: Teckel, Bichon, Caniche, Yorkshire and Pincher have a predisposition to female genital tumors.

The frequency of oral tumors is related to the presence of melanoma, which predominantly affects the breeds with pigmented mucosae (Scottish, Chow-Chow) or mucosae that can be pigmented (Cocker). The problem of the relation between the tumors of the melanogenic system and natural skin or mucosal pigmentation is posed.

Skin tumors are more frequent in certain breeds, without the predominance of a certain tumor type (epidermoid or basal cell carcinoma, melanoma, tumors of the skin adnexal glands). In the Boxer breed, skin mastocytoma has the highest frequency. A particular aspect is represented by the predisposition of the Briard and Schnauzer breeds to skin tumors, especially epidermoid carcinomas located in the phalanges.

The predisposition of different animal breeds to certain skin neoplasms seems to be more related to skin pigmentation and exposure to solar radiation. Thus, squamous cell carcinoma is 13.4 times more frequent in white cats, compared to cats of other colors. Ocular cancer in Hereford cattle is associated to the white face color and exposure to sun rays. Horse melanoma is associated with hair depigmentation with age, in breeds or/and half-breeds of gray color.

Mesenchymal tissue tumors are more frequent in German Shepherd, Briard, Collie and Belgium Shepherd breeds. The predisposition of the Boxer breed to mesenchymal tumors can be the result of a predisposition to mastocytomas, with subcutaneous location, as well as to hemangiomas and hemangiopericytomas.

There is a real breed predisposition to the tumors of the male genital system and of the hemolymphopoietic system. For the first, the Pincher, Chow-Chow, Collie, Fox Terrier, Basset and Boxer breeds are cited. The Beauceron, German Shepherd, Afghan greyhound and Scottish breeds are predisposed to hemolymphopoietic tumors.

For experimental studies, it is important to identify the breed with a higher incidence of a certain tumor type or carcinoma (chemical, physical, viral). Sometimes, the breed predisposition to a neoplasm can be easily identified: for example, the direct relation between pigmentation and the development of melanomas or the higher frequency of osteosarcomas in large size dog breeds.

Due to the small number of some tumor types (urinary, endocrine, digestive, of digestive tract adnexal glands), a direct relation could not be established between incidence and certain breeds.

The particular aspects regarding the epidemiology of a certain tumor type will be mentioned in the chapters treating the tumor in cause.

1.3.5. Tumor incidence in the human-animal correlation

The risk for cancer of people living close to animals is controversial, and it cannot be excluded, but it is also difficult to prove. A series of other risk factors should be discussed, and in the first place the cohabitation of man and animals, especially companion animals, the same area being under the influence of the same environmental factors (pollution and stress).

Taking data from studies performed in USA, DORN and PRIESTER (1987) show a lymphoid cancer incidence increased by 80%, in a sample of 19 000 veterinary doctors aged over 45 years, compared to human doctors and the general population. In another study, in California, an excessive risk for melanomas was found in veterinary doctors. The same authors cite BLAIR and HAYES (1980), finding an excessive incidence of leukemia and Hodgkin disease in veterinary doctors.

Epidemiological studies, also performed in the USA, reveal the presence of a higher risk for lymphatic and lymphopoietic cancer in the rural population, compared to urban residents. Farmers have a risk for exposure to the bovine leukosis virus, as well as to chemical agents used in agriculture, insecticides in the first place.

In Los Angeles, in a retrospective study of exposure to infections by cohabitation with companion animals, 684 families, in which people with neoplasms were diagnosed, and 1042 control families were inquired. The conclusion was that there were no significant differences regarding the risk of cohabitation with companion animals (dogs, cats and parrots) between families with cancer and controls.

VAN HOOSIER et al. (1968) inquired 100 children with leukemia, 48 lymphoma children and 141 healthy children, without finding significant differences between the children who cohabited with or were bitten by dogs and the other children.

According to BROSS and GIBSON (1970) [63], the cat was the only one of 15 animal species that exceeded by far the risk of association with leukemia cases. Thus, 7.3% of the children with leukemia aged less than 14 years were exposed to ill or dead cats, compared to 4% of the controls.

According to the California Register for Neoplasms in Animals (CRNA), over a period of 5 years, in 675 households with cats affected by neoplasms and 675 control households with normal cats, there were no differences regarding the risk of malignancy in humans, dogs or cats. A subsequent study on feline leukemia-lymphoma cases recorded by CRNA did not confirm the hypothesis that human or feline leukemia would be contagious. There were no significant differences regarding the frequency of human neoplasms in 221 households with affected cats and 221 control households. Additional problems such as allergic reactions, animal and insect bites, scratches were studied.

Human immunoepidemiological studies of feline leukemia virus antibodies were conducted by HARDY (1981), results being negative [63].

1.3.6. Tumor incidence in correlation with environmental factors

HIGGINSON and MUR (1979) from the International Cancer Research Agency (ICRA) affirm that “the majority of cancers are associated to a certain extent with environmental factors” [63].

In the study of the role of environmental factors in the etiology of human cancer, important data can offer companion animals (dogs, cats) that live in the same habitat as man. Epidemiological studies on spontaneous tumors in pets are a real “sentinel model” for the identification of environmental conditions as risk factors in human oncogenesis. Regional variation in the incidence and morphological forms of cancer depends in the first place on quantitative and qualitative fluctuations of carcinogenic agents from the environment of a given geographical area, and in the second place, on specific and individual differences, according to species, breed, age, etc., in the reactivity to environmental carcinogenic agents.

Over the course of millennia, our planet's environment has changed, and man has contributed in a decisive way to its pollution with carcinogenic agents. It can be assumed that primitive man was in contact with chemical substances or physical carcinogenic factors, existing in nature. Gradually, especially over the past 100 years, man has changed natural environment essentially, with disturbing intensity, due to the effects of rapid industrialization and alarmingly increased environmental chemical contamination with synthetic substances. Man has added to the spectrum of natural carcinogens an increasing number of various artificial chemical and physical carcinogenic agents. Air, water, soil and food products are contaminated with these carcinogens, which act on both humans and domestic and wild animals.

HUEPER's conclusions (1963), formulated more than 40 years ago, are not only extremely actual, but they also reveal an increased risk of environmental contamination with carcinogenic agents. The author mentions the fact that mankind has few chances to avoid environmental carcinogens, as it cannot avoid exposure to pathogenic microorganisms. But, if over the past century new means for the reduction and/or control of the impact of carcinogenic agents were discovered, the activity of protection against the increasing number of carcinogenic agents was insignificant. The carcinogens produced and disseminated by man were and still are a serious threat to human and animal health and life.

At present, experimental research has undeniably proved that a great number of synthesis substances, chemical and physical residues, have a carcinogenic action. The knowledge of scientific, practical and ecological aspects of neoplastic diseases requires further epidemiological studies on the general and regional incidence of cancer in animals, and the data thus obtained can be used as a warning system for the potential appearance of cancer in humans. This will allow the institution of rational and efficient control measures for the protection of man and animals.

The first observations on oncogenesis due to environmental pollution date back to 1939, when NIEBERLE reported the appearance of ethmoid tumors in sheep living in the proximity of arsenic gas and dust emission plants [50].

In dogs, epidemiological studies have shown that there is a statistical significant association between the occurrence of mesothelioma and asbestos pollution of the animal's environment.

There is a positive correlation between bladder cancer and the general level of industrial activity, as shown by epidemiological studies performed in veterinary clinics from USA and Canada.

The relatively high incidence of tonsillar carcinoma in dogs from urban environment is associated with industrial or vehicle gas pollution. COTCHIN (1984) found a decreased incidence of tonsillar carcinoma in dogs, in London, after the initiation of measures for the limitation of pollution in this big metropolis.

The great majority of environmental polluting agents have been identified, but modern activities of contemporary society permanently produce new polluting agents, which are risk factors in carcinogenesis.

We consider useful to review the main carcinogenic factors existing in nature, which pollute the environment through the modern activities of human society.

Medical and epidemiological observations have established beyond any doubt that the exposure of humans or animals to certain chemical substances, such as aromatic compounds (alpha- and beta-naphthylamine, benzidine and their derivatives) and azo-colorants, causes an increase in the incidence of cancer at the level of the urinary system and especially of the bladder. Chemical industries, rubber, cosmetic or food colorant industries spread in nature (air, water, food products) potentially carcinogenic chemical products and residues.

Tar coming from the incomplete burning of coal and its derivatives (creosote, anthracene oil, etc.) is the most common polluting agent, being a carcinogenic factor responsible for skin and lung neoplasms.

Oil and its derivatives, mineral oils, lignite and its subproducts represent another important source of environmental pollution in the development of skin, laryngeal, pulmonary and intestinal cancer.

The pollution of drinking water and plant food products, especially vegetables, with detergents derived from industrial leakage and urban sewerage represents another source of carcinogenic factors, for both man and animals. Detergents definitely facilitate the penetration of carcinogens into tissues, in addition to their action as carcinogenic agents.

Companion animals, dogs and cats, are exposed in the context of urban life to the same polluting agents as man. Air carcinogens, coming from vehicle combustion gases, the soot and smoke of coal and oil, have all a neoplastic action on the respiratory system. Our observations, as well as those of the literature, show a constant increase of pulmonary cancer in dogs over the past years. Epidemiological evidence and histological structures of pulmonary neoplasms in dogs and cats can offer prediction regarding pulmonary cancer in man.

Arsenic, one of the oldest carcinogens known, has become particularly common and polluting with the extensive use of pesticides and herbicides. Arsenic causes skin, pulmonary, laryngeal, sinus, esophageal, hepatic neoplasms. Arsenic pollutants from the soil, water and plants are responsible for the development of cancer in domestic and wild animals. Studies, which are rarely systematic, are focused more on arsenic intoxication episodes, and less on the incidence of neoplasms induced by pollutants with pesticides and herbicides.

Radioactive substances can determine the development of carcinomas and sarcomas. Radioactive energy, with direct action on skin or internal organs, is followed by the appearance of skin or bone sarcomas, carcinomas and leukemia. The contamination of the environment with radioactive carcinogens derived from polluting industrial activities results in neoplasms in both man and domestic and wild animals.

Ultraviolet radiation is responsible for the appearance of skin neoplasms, in both man and animals. Thus, squamous cell carcinoma episodes have been described in sheep exposed for a prolonged time to ultraviolet radiation. The location of these neoplasms was on the ear, periorbital, mouth and eyelid skin, in the areas with rare pilosity. Observations on spontaneous neoplasms and experimental studies have demonstrated the higher incidence of neoplasms induced by ultraviolet rays, in the poor pigmented or unpigmented skin areas.

Chloride hydrocarbons, other pesticides and herbicides have been incriminated and proved to be carcinogenic. These chemical substances can induce hepatic, pulmonary neoplasms and leukemia. Some hydrocarbons (tri-ß-anisyl chloroethylene; methoxy chloride) have estrogenic activity, also having carcinogenic properties, and they can develop mammary, uterine, renal, bladder, testicular and hematopoietic tissue neoplasms. The use for 30 years of DDT proves that all aspects of the undesired biological aspects of a chemical product should be studied before its use. The decision to forbid DDT was made only after the negative action of this product on man and animals was demonstrated by epidemiological observations.

Carbamate derivatives (ethyl carbamate; isopropyl-N-phenyl carbamate) are used as insecticides and herbicides. These products have carcinogenic properties, developing pulmonary and epidermal cancer.

Goitrogenic chemicals, thiouracyl derivatives, possess tumorigenic properties on the thyroid and other organs. Strumal changes are considered as premalignant lesions.

Food rations, through contaminated additives and deficiencies, are potentially carcinogenic, which is proved by both epidemiological and experimental studies. Chemical products (colorants, preserving agents, etc.) that were not adequately tested were introduced in human food industry. Later, these were demonstrated to be carcinogenic. Mycetes contamination of human and animal foods causes the appearance of hepatic or/and other carcinomas.

Epidemiological and environmental pollution studies, correlated with the risk of cancer in man and animals, have demonstrated the role of natural agents or agents due to human activities (physical and chemical factors), in the initiation and evolution of neoplasms. These studies provide evidence on the spreading of these dangers through the environment both indirectly, by water, air and plant contamination with carcinogens, and by the direct action of carcinogens on humans and animals. The extension of carcinogens in the surrounding environment explains the role of these factors in the significantly increased risk for man and animals in the appearance of cancer.

We consider the study of carcinogens and neoplasms influenced by environmental factors as extremely useful. In this sense, we mention:

• – the rapid spread of a great number of particularly diverse oncogenic agents, coming from the activities of the overindustrialized human society;
• – unlimited possibilities of a great number of subjects, humans and animals, to come into contact with environmental carcinogenic factors;
• – the hidden or undetected presence of carcinogens that can act since a young age or even transplacentally;
• – difficulties, sometimes hard to overcome, in the obtaining and study of potential carcinogens, due to economic interests and, implicitly, difficulties regarding the dissemination of required information and measures.

HUEPER's warning from 1963 is more actual, because some of his predictions have come true ...the non-discriminated, irrational, superficial and irresponsible contamination of current practices can or will probably cause the appearance of uncontrollable disasters, for man and animals, taking the form of severe epidemic cancers, similar to those that have affected the whole trout population from American fish farms.

In the next chapters, related to tissue and organ tumors, risk factors specific for certain neoplasm types will be mentioned.

1.3.7. Viral epidemiology, immunoepidemiology and molecular epidemiology

DORN and PRIESTER (1987) propose the use of the terms “immunoepidemiology” or “molecular epidemiology”, instead of the term “seroepidemiology”, which is to restrictive, as modern laboratory methodologies use both serum and cells in leukemia detecting tests.

The identification of the feline leukemia virus, bovine leukemia virus and human leukemia virus using T cells has facilitated epidemiological studies of the natural history of leukemia and associated diseases, in the species concerned.

Classical seroepidemiological studies of feline leukemia have shown that antibodies to feline oncornavirus associated cell membrane antigen develop after feline leukemia virus infection and that these antibodies are protective.

In order to offer realistic data, comparable to those of human oncology, epidemiological studies in veterinary oncology should be conducted skillfully, by investigating well defined parameters, but especially in precisely defined animal populations, and the data obtained should be finally corroborated with the results of laboratory investigations. Of special interest is the knowledge and adaptation of human oncology methodologies for investigations in veterinary medicine, so that results can be finally compared.