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The term neoplasia literally means new growth and the mass of cells that composes the new growth is known as a neoplasm. Neoplasms represent growth disturbances in which the regulatory mechanisms of cell contact inhibition, differentiation, and mitosis are defective. As discussed in section B and K, hyperplasia, metaplasia, and dysplasia represent the three distinctive patterns of controlled non-neoplastic growth.
11.4.1 Definitions
Before embarking on the study of neoplasia, some of the commonly used terms should be clearly understood. In addition to the terms listed below, other terms are introduced throughout the section.
11.4.1.1 Oncology
Refers to the study of or science of neoplastic growth.
11.4.1.2 Neoplasia
literally means "new growth" and the mass of cells composing the new growth is a neoplasm. (The term "new growth" does not adequately define an neoplasm.)
11.4.1.3 Neoplasm
Refers to a new abnormal growth or mass of tissue whose growth rate exceeds and is uncoordinated with that of normal tissue, which serves no useful purpose, and which persists in the same excessive manner after cessation of the evoking stimuli which caused the change.
11.4.1.4 Tumor
Originally referred to any swelling but currently used almost exclusively to refer to a neoplastic growth.
11.4.1.5 Cancer
The common term used for all malignant neoplasms.
11.4.1.6 Benign neoplasm
A neoplasm that tends to grow slowly, is well differentiated, does not metastasize, and is usually non-life threatening.
11.4.1.7 Malignant neoplasm
A neoplasm that tends to grow rapidly, is poorly differentiated, often metastasizes, and frequently causes death of the host.
11.4.1.8 Metastasis
Refers to the transfer of disease manifestations from one organ to another. It is used mainly to refer to the secondary growth of a malignant neoplasm in an organ or site remote from the primary site.
11.4.1.9 Differentiation
Refers to the process where by one form, typically the immature, develops into another, usually the mature. As it relates to cells, this generally involves the development of immature cells into mature ones.
11.4.1.10 Anaplasia
literally means "to form backwards" but refers to the tendency of a neoplasm to be composed of less differentiated/mature cells.
11.4.2 NOMENCLATURE
Unfortunately, the nomenclature of neoplasms does not follow any single consistent pattern. However, most benign tumors end with the suffix "oma." Malignant neoplasms of connective tissue are generally named by attaching the term "sarcoma" to the name for the essential cell. Malignant neoplasms of epithelial origin end with the term "carcinoma" (there are exceptions). Attaching the suffix "oma" to the cell type constituting the neoplasm works well with mesenchymal benign neoplasm (those arising in muscles, bones, tendons, cartilage, fat, vessels, lymphoid and fibrous tissue) because:
- (1) the cells usually closely resemble their normal counter parts and
- (2) the various adult mesenchymal cells are sufficiently distinctive to be readily differentiated from one another. However, benign neoplasms of epithelial origin defy such easy classification. These neoplasms are variously classified, some on the basis of their cell or origin, others on microscopic architecture and still others on their gross patterns. Adenoma is the term applied to the benign epithelial neoplasm which forms a glandular pattern and/or is derived from glands (but not necessarily reproducing glandular patterns).
EXAMPLE:
A benign epithelial neoplasm that arises from the intestinal lining cell growing in the form of gland-like structures would be termed an adenoma, as would a mass of adrenal cortical cells growing in no distinctive pattern, but merely producing a small benign new growth.
Benign epithelial neoplasms producing microscopically or grossly visible "finger-like" or "wart-like" projections from epithelial surfaces are referred to as papillomas or polyps. Those that form large cystic masses (as in ovaries) are referred to as cystomas or cystadenomas.
The nomenclature for malignant neoplasms essentially follows the same pattern used for benign neoplasms with certain additions. Malignant neoplasms of connective tissue origin are called sarcomas.
EXAMPLE:
A malignant neoplasm of fibroblasts is a fibrosarcoma. One composed of fat cells is a liposarcoma.
Malignant neoplasms of epithelial cell origin (derived from any of the three germ layers) are called carcinomas. A carcinoma with a glandular growth pattern microscopically is termed an adenocarcinoma. One producing recognizable squamous cells (arising from any of the stratified squamous epithelia of the body) is termed a squamous cell carcinoma. Also, it is a common practice to specify, when possible, the organ of origin (e.g., renal adenocarcinoma, bronchogenic squamous cell carcinoma, etc.). A malignant neoplasm may be composed of very primitive, undifferentiated cells and must be designated merely as an undifferentiated malignant tumor or, when possible, undifferentiated carcinoma or undifferentiated sarcoma.
The term teratoma is used to designate a tumor composed of a variety of cell types representative of more than one germ layer.
The chart on the following page lists some of the commonly encountered benign and malignant neoplasms.
The differentiation of benign from malignant is the most important judgement the veterinarian is called upon to make relative to neoplasia (upon this decision are based the treatment of the lesion and the outlook for the animal). Benign and malignant neoplasms are most commonly distinguished on the basis of:
Differentiated neoplastic cells are those that resemble their normal cell of origin and includes the extent to which they achieve their fully mature morphologic and functional characteristics. The closer the resemblance to their normal cell of origin, the better the differentiation. However, the greater the departure from the characteristics of the normal, the poorer the differentiation. The terms undifferentiated or anaplasia refer to poorly differentiated cells.
In general, all benign neoplasms are well-differentiated. However, malignant neoplasms range from well-differentiated to those consisting of primitive appearing undifferentiated cells. Remember, even well-differentiated malignant neoplasms generally have some degree of anaplasia. Anaplastic or undifferentiated neoplasms are invariable malignant, and are composed of cells that have lost some or all resemblance to their normal counterpart. On the other hand, benign neoplasms are extremely well-differentiated and closely resemble the normal cells. Oftentimes, only the massing of these cells into a nodule discloses the neoplastic nature of the lesion (mitosis is extremely scant and such neoplasms never metastasize).
Anaplasia (undifferentiated cells) is characterized by the features listed below:
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The functional capability of neoplastic cells usually correlates with their degree of morphologic differentiation. Well-differentiated neoplastic cells may elaborate the characteristic products of their normal counterparts (e.g., well-differentiated squamous cell carcinomas may form keratin). Undifferentiated neoplastic cells tend to lose their specialized functional characteristics.
In general, benign tumors (well-differentiated) grow slowly over a period of years at a rather steady pace. Most malignant neoplasms grow rapidly, sometimes at an erratic pace, eventually to spread and kill the host. Remember, there are exceptions to this generalization. Benign neoplasms, for example, may enter periods of long dormancy when they apparently do not enlarge. Others may achieve a certain size and apparently cease growing or decrease in size. Although most malignant neoplasms progressively enlarge, some may shrink in size and others may remain dormant for periods of time. However, as a rule of thumb, the more anaplastic the neoplasm, the more numerous the mitoses and the more rapid the growth.
The mode of growth and capacity to spread clearly differentiate malignant from benign neoplasms.
Nearly all benign neoplasms grow as localized expansive masses enclosed within a fibrous capsule. Such neoplasms remain localized to their site of origin and dog not disseminate throughout the body. Although encapsulation is a characteristic of benign neoplasms, the lack of a capsule does not make a neoplasm malignant.
Malignant neoplasms are almost never encapsulated and are characterized by infiltrative, erosive growth which extends into adjacent tissues (normal anatomic boundaries are not recognized).
Metastasis refers to the spread of neoplastic cells from one part of the body to another by way of the bloodstream (hematogenous) or lymph channels (lymphogenous). As neoplastic cells infiltrate, they may erode into blood vessels or lymphatics, become detached and act as emboli. Thus, when these cells become lodged in other tissues, they may grow and develop into secondary tumor nodules (metastases). Neoplastic cells traveling by way of the bloodstream usually lodge in the first capillary bed they encounter. The lungs and liver are probably the most common sites for lodgement. Cells traveling by way of the lymph channels usually lodge in sinuses of the regional lymph nodes. There is a tendency for epithelial neoplasms to metastasize by way of lymphatics and for connective tissue neoplasms to metastasize by way of the bloodstream (there are exceptions).
Metastasis is a "hallmark" of malignancy. All neoplasms that metastasize are malignant, although all malignant neoplasms do not metastasize (for example, malignant glial cell neoplasms of the central nervous system and basal cell carcinomas of the skin are highly invasive neoplasms but they rarely metastasize).
Refers to the transfer of neoplastic cells from one serous or mucous surface to another by direct contact. Body cavities (peritoneal, etc.) are commonly involved. Because of their lack of cohesiveness, neoplastic cells growing on epithelial surfaces are prone to shed into the surrounding spaces. Implantation is a feature of some malignant neoplasms. Transplantation refers to the mechanical transport of neoplastic cells by instruments and gloved hands. This is a significant potential hazard during cancer surgery.
In summary, benign and malignant neoplasms are most commonly distinguished on the basis of:
Benign neoplasms are characterized by:
Malignant neoplasms are characterized by
Anaplasia and metastasis are the "hallmarks" of a malignant neoplasm. Lymphatic channels are the most common pathway for the initial spread of carcinomas, whereas sarcomas tend to spread by way of the bloodstream (there are exceptions).
Significant features of benign and malignant neoplasms are listed in the following tables
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There have been numerous theories advanced to explain the cause of neoplasms. Many of the early theories were speculative without adequate scientific data. Recent research efforts have unmasked the causes of some animal neoplasms and the enormous amount of experimental evidence that exists relative to other neoplasms justify presumptive statements as to their causes. However, the factor or factors responsible for the development of most neoplasms still remains unknown. The numerous agents capable of producing neoplasia naturally and experimentally can be grouped as follows:
In animals, there are various neoplasms in which a viral cause has been definitely established. Viral oncogenesis was actually observed before viruses were known when Ellerman and Bang (1908) demonstrated that a sarcoma of chickens could be passed to other birds in cell-free material. Since then, a great many oncogenic viruses have been identified that can be divided into DNA and RNA viruses. Viruses may influence the development of neoplasia by inserting themselves into the host genome directly or indirectly as DNA sequences, resulting in transformation of cells.
The oncogenic RNA viruses have been demonstrated as the cause of some forms of leukemia or lymphosarcoma in animals. These viruses belong to the retrovirus family and are commonly known as oncornaviruses or leukoviruses. They are widely distributed among vertebrates and have many common physical, chemical and oncogenic properties. All oncogenic RNA viruses contain a means by which viral RNA is transcribed into the DNA of the host cell. These viruses contain an enzyme (RNA-dependent DNA polymerase or reverse transcriptase) which uses the viral RNA genome to make a DNA copy of itself. As now understood, the sequence of events are as follows:
The RNA virus is ingested in phagocytic vacuoles of the cell; uncoating of the virion exposes the 70s RNA of the viral genome. This 70s RNA serves as a template for the transcription of a single strand of DNA through the action of reverse transcriptase. Subsequently, a double-stranded DNA-RNA hybrid is formed. The RNA strand is then degraded and is replaced by another strand of DNA, using the first DNA strand as a template. In this manner, a DNA-RNA provirus is created. The double-stranded DNA is then inserted into the genome of the host cell (the provirus thus becomes incorporated into the genome of the host cell). The host cell is then able to synthesize progeny RNA from the provirus. As a part of the genome of the host cell, the provirus is not recognized as "foreign" by the immune system and is thus protected from immunologic destruction.
Under the electron microscope, the various oncornaviruses appear as either type "C" (centrally position nucleoid) or type "B" (eccentrically positioned nucleoid) particles. Both type "B" and "C" viruses are synthesized by host cells.
The 3 biologic forms of oncornavirus are
Studies on the mode of oncornavirus transmission revealed that both somatic and germ cells of animals may harbor unexpressed type C viral genome (virogene). This suggests that oncornaviruses may remain latent within apparently normal cells. Two major theories have been proposed to explain this finding:
The oncogene theory proposes that a portion of the oncornavirus genome existing as the DNA provirus is part of the normal gene pool of all vertebrates and it is passed vertically by the usual mechanisms of inheritance. This oncogene is normally repressed, but can be activated by carcinogens, radiation, aging, etc. The provirus theory is based on the potential for genetic evolution in cells. It implies that oncogenic viruses arise as mutations in somatic cells. It is proposed that there are regions in cellular DNA that serve as templates for the synthesis of RNA and reverse transcriptase. With mediation of the reverse transcriptase, this RNA can serve as a template for new DNA which is subsequently integrated into the cellular DNA. Thus, in this cyclic formation of DNA to RNA and then back to DNA on a random basis, the genome in a rare somatic cell becomes a provirus containing all of the information needed for the production of oncornaviruses.
There are three groups of DNA viruses known to have strong oncogenic potential in animal systems:
All three groups have the ability to become integrated into the DNA of host cells, causing neoplastic transformation. The papova viruses include the polyoma virus, simian virus 40 and the papilloma viruses. The herpesviruses induce a variety of tumors in several vertebrate species, including Marek's disease in birds, reticulum cell sarcoma in marmosets and owl monkeys and renal adenocarcinomas in frogs.
When a DNA oncogenic virus infects the cells of its normal host, a productive infection occurs and numerous virus particles are released. The cell is usually lysed (the normal host cells are said to be permissive since they permit the virus to complete its life cycle). However, when cells not the natural host of the virus are infected, virus particles are not produced and the cells often undergo neoplastic transformation. Such cells are said to be "nonpermissive" and the infection is "nonproductive" and "transforming." The host cell is the major determinant of the pathway that will be followed. The sequence of events in the "transformation" reaction between DNA viruses and the host cells takes place in two stages, "early" and "late."
The "early" stage includes entry of the virus into the cell and removal of the protein envelope from the DNA. Thereafter, the viral DNA is integrated into the genome of the host cell. In nonpermissive cells, "early" viral genes are expressed, leading to the synthesis of a viral coded protein called tumor or T-antigen. The T-antigen has been shown to bind to DNA and in some way modify expression of the viral genome so as to block the production of virus particles and instead produce alterations in the cell membrane characteristic of neoplastic transformation. The "late" stage of viral infection, involving genes that code for the viral capsid proteins required for the production of infectious virions, is suppressed in cell transformation.
There is no need for reverse transcriptase in neoplastic transformation by DNA viruses (reverse transcriptase is a feature only of the oncogenic RNA viruses). In contrast to the situation with RNA viruses, when DNA viruses induce cellular transformation there is no release of infectious virions.
Chemical carcinogens (compounds capable of producing neoplasms) are numerous, but the best known are hydrocarbons, alkylating agents, azo dyes and aromatic amines. The student should be reminded of the following pertinent facts relative to chemical carcinogens:
The study of chemical carcinogenesis has contributed more to the understanding of neoplasia than any other experimental approach. The following facts are basic to chemical carcinogenesis.
Radiation energy, whatever its source (sunlight, x-ray, nuclear fission, etc.) is a well-documented carcinogen. The mechanisms involved in the induction of neoplasia by radiation is poorly understood. However, the following theories have been advanced.
Ultraviolet light: Studies on such neoplasms as the basal cell carcinoma of the skin of man and squamous cell carcinoma of the eye of Hereford cattle show that incidence is greatest in those parts of the country where the exposure to sunlight is maximum. The "brand cancer" in range cattle is also thought to be associated with ultraviolet light. There is little pigmentation and the skin is therefore more sensitive to light. The possibility exists, however, that the effect of the burning of the skin at the time of branding could influence the development of neoplasms.
In summary, present evidence suggests that there is no single cause of neoplasia in man or animals. Most likely, neoplasia is a common endpoint arrived at through a diversity of pathways. It is entirely possible that several influences act in concert to produce the unwanted results.
Even though present evidence suggests that oncogenic viruses, carcinogenic chemicals and radiation are important factors in inducing neoplasia under natural and/or experimental conditions, there are a number of factors related to both the host and the environment that influences the animal's predisposition.
A. Heredity:
Much of the work attempting to relate heredity to the incidence of neoplasia has been done in mice. Strains of mice have been developed which are highly susceptible to tumors of the skin, mammary gland or liver, while other strains of mice are quite resistant to the same neoplasms. However, some studies indicate that factors other than heredity play a role in these strain differences. For example, if young mice of a susceptible strain are suckled by a dam from a resistant strain, the incidence of neoplasms is less than that encountered if the young are allowed to nurse their own mother. This suggests the presence of a "milk factor" which may be an infectious agent, an endocrine product, or some undescribed factor. It has also been shown that certain strains of chickens are extremely susceptible to the agent causing Marek's disease, while others are extremely resistant.
B. Age:
Tumors are usually more frequent in older individuals, although there are exceptions. As an example of the latter, the canine transmissible venereal tumor is usually seen in relatively young dogs during the years of greatest sexual activity. Also from the standpoint of age, tumors derived from connective tissue are generally more common in young animals, while tumors derived from epithelial tissue are more common in older animals.
C. Sex:
The incidence of neoplasms in the two sexes is approximately the same, but the type of growth varies. This variation is most easily recognized in neoplasms involving the genital organs, but it also applies to others. Neoplasms of the perianal gland of the dog are more common in the male than the female, suggesting a hormonal relationship.
D. Pigmentation:
Pigmentation of the hair or skin sometimes makes individuals more susceptible or resistant to neoplasms. Malignant melanomas are more common in white or gray horses than in horses of other colors. Hereford cattle are more susceptible to neoplasms of the eye and related structures than are most other breeds. This has been attributed to a lack of pigmentation in the skin of the eyelids.
E. Hormones:
The endocrine products may be either intrinsic or extrinsic factors in the etiology of neoplasms. Estrogenic hormones administered in large doses to mice have reported to cause mammary neoplasms and neoplasms of the interstitial cell of the testicle of the male.
F. Chronic Irritation:
Numerous examples of neoplasms thought to be caused by chronic irritation are listed in the text.
G. Parasites:
The text mentions several parasites which are apparently related to the development of neoplasms. The incidence of fibrosarcoma or osteosarcoma in the esophagus of the dog parasitized with Spirocerca lupi is considerable. Some believe that the lesions caused by Eimeria stiedae in the bile duct of the rabbit represent true neoplasia. Most people, however, look upon this change as being merely hyperplasia, rather than neoplasia.
A.Morphology:
Grossly there is wide variation in the appearance of neoplasms. In general the benign neoplasms tend to extend above the surface of the skin or the organ in which they are growing, while malignant neoplasms tend to be very irregular in shape and to infiltrate the underlying tissue.
Microscopically, neoplasms resemble the cells from which the growth arose. That is, neoplasms composed of fibroblasts, lymphocytes, squamous cells, etc., are merely growing in abnormal locations, in abnormal quantities or at an abnormal rate. There are also abnormalities in cell size, shape and growth patterns.
B.Metabolism:
Neoplastic cells differ metabolically from normal cells and the amount of this difference varies directly with the degree of malignancy. Normal cells have a pattern of enzyme activity which is characteristic of that particular tissue or organ. In neoplastic cells, this pattern is less characteristic and there is a tendency for the enzyme activity to converge toward a common pattern in more malignant lesions. This lack of biochemical differentiation is analogous to the lack of morphologic differentiation recognized as anaplasia in malignant cells.
In general, most malignant cells have high rates of both aerobic and anaerobic glycolysis. These rates may be several times that seen in normal cells. The abnormal metabolic patterns of neoplastic cells sometimes make them more susceptible than are normal cells to various chemotherapeutic agents or to influences such as x-rays and other forms of irradiation. Advantage is taken of this fact in treating neoplasms, and the ideal therapeutic regimen would be one which destroyed all neoplastic cells but failed to damage normal cells.
The natural course of malignant neoplasms differs greatly. However, it is usual for an animal with a malignant neoplasm to survive from six months to a year after the lesion becomes apparent. Factors that restrain neoplasms are numerous. In addition to intrinsic properties of the neoplasm (genotype, vascular supply, etc.), there are factors that can be altered in the host such as nutrition, endocrinologic status and immunologic reactivity.
11.12.1 Endocrine-Dependent Neoplasms:
There are few known endocrine-dependent neoplasms in animals. However, in man, neoplasms of the prostate and mammary gland are to varying degrees, endocrine-dependent. For example, prostate carcinomas develops under the influence of testosterone; orchiectomy inhibits growth, as does treatment with estrogens.
11.12.2 Nutrition
There is some evidence to suggest that the nutritive status of an animal may play some role in susceptibility to neoplasia. In general, animals on very high calorie diets have slightly increased incidence of neoplasms.
11.12.3 Chemotherapy
Various chemotherapeutic drugs may alter the course of neoplasia. However, chemotherapy as a method of treatment is largely restricted to human neoplasms (most widely used in neoplasms of the lymphoreticular system). The drugs used include corticosteroids, antimetabolites, radiomimetric drugs and selective toxins. In general, drug-sensitive neoplasms are those in which most cells are in an active mitotic cycle. Also, chemotherapy depends on a well-developed blood supply within the neoplasm (for the drugs must reach the neoplastic cells in concentrations sufficient enough to exert an effect).
11.12.4 Neoplasm Immunity
The development of immunity to artificially produced neoplasms in laboratory animals can be demonstrated. If certain coal tar compounds are applied to the skin, neoplasms develop. If these neoplasms are then removed and the area is allowed to heal, application of the same compound to the area a second time fails to produce neoplasms. This suggests tissue immunity of some description. It also appears that the presence of one tumor in an organ or tissue sometimes provides immunity against the appearance of another neoplasm in the same organ.
Recent evidence suggests that many cells with neoplastic capabilities are produced in the body but that they are suppressed by an immune reaction before they reach macroscopic size. According to this theory, clinical neoplasia represents the remaining small minority of lesions that, for some reason, are able to escape this defense.
The immunity to tumor-specific antigens is mediated by lymphocytes and is analogous to delayed hypersensitivity. There is evidence that circulating antibodies may, on the other hand, protect neoplastic cells from the cell-associated type of immune reaction and enhance tumor growth.
The effect of a neoplasm upon the body depends on such factors as the location of the neoplasm, the essential cell of growth and whether the tumor is benign or malignant. Some of the possible effects are:
1.Atrophy of surrounding cells:
This atrophy is due to direct pressure by the neoplastic cells as well as interference with the blood supply.
2.Obstruction of the lumen or organs:
This obstruction may come about from neoplasms within the lumen or those growing on the outside and putting pressure on the hollow organ.
3.Destruction of blood or lymph supply:
The invasion of blood vessels or lymphatics by neoplastic cells may cause thrombosis or actual blockage by the tumor cells themselves. This may result in such things as passive hyperemia, edema and infarction.
4.Destruction of nerve supply:
This may result from pressure upon the nerve or by the neoplastic cells actually infiltrating the nerve. This is commonly seen in the sciatic nerve of chickens affected with Merek's disease.
5.Bacterial invasion of the neoplasm:
When neoplasms undergo necrosis and other degenerative change, suitable conditions are provided for bacterial growth. It is also possible that infection may spread to other parts of the body from the neoplasm.
6.Emaciation:
This term is used to indicate a wasted condition of the body or excessive leanness. Emaciation may be due to starvation if the gastrointestinal tract itself is involved. Neoplasms in the oral cavity preventing mastication, neoplasms involving the stomach or intestine in which blockage occurs or neoplasms involving such organs as the liver or pancreas and thus interfering with the production of digestive secretions are examples of starvation due to neoplasia. In other instances, emaciation may be due to toxins produced by the degeneration and necrosis of neoplasms or perhaps bacterial toxins if the neoplasm has been invaded by bacteria.
7.Anemia:
Anemia in neoplastic conditions may be due to hemorrhage, tumors of the digestive tract which cause nutritional deficiencies by interfering with absorption, invasion of bone marrow by neoplastic cells and the elaboration of toxins which inhibit hematopoiesis.
8.Excessive production of hormones:
It has been shown that neoplasms of the parathyroid result in decalcification of the skeleton. Neoplasms of the Sertoli cell of the testicle produce excess estrogens and cause feminization in male dogs. Tumors of the anterior pituitary are often associated with the production of excess somatotrophic hormone, resulting in gigantism in children and acromegaly in adults.
9.Death of the individual:
The causes of death in neoplasia are varied and include many of the factors previously mentioned in this list.
10.Spontaneous regression and recovery:
There have been instances in man and animals in which widespread and extensive neoplasms have regressed and eventually disappeared. It is possible that neoplastic cells are susceptible to toxicoses and infectious diseases as are normal cells. It is known that such things as x-rays, radium and radioactive isotopes have more effects on neoplastic cells than on normal cells. It is possible that other unknown factors, perhaps even viruses, may work in a similar way to destroy neoplasms. Unfortunately, spontaneous regression and recovery are rare.
As time goes by, more and better techniques are being developed for the diagnosis of neoplasms. Some of the presently used methods are:
1.Biopsy technique:
The surgical removal of all or a portion of the neoplasm and subsequent examination of the tissue by light microscopy constitutes the most common means of diagnosis. Special stains, histochemistry and electron microscopy are further techniques which may be used on biopsy specimens.
2.Exfoliative cytology:
This is the study of cells obtained from body secretions and excretions. The most widely publicized use of exfoliative cytology is the Papanicolaou technique for the examination of uterine secretions as a screening technique for the diagnosis of neoplasms involving the cervix or uterus in women. Similar techniques may be used in examining secretions from the respiratory tract, gastrointestinal tract, and urinary tract. In the latter case, samples of urine are centrifuged, the supernatant is discarded and smears are made of the remaining material. Exfoliative cytology is also useful in examining ascitic fluid. Neoplasms which have transplanted on the serosal surfaces may often be diagnosed in this way.
3.Radiology:
Radiographic techniques are of value in diagnosing neoplasms which are infiltrating bone and also in neoplasms which have metastasized to such soft tissues as the lung.
4.Chemical analysis:
This technique is of some value in the diagnosis of certain neoplasms. Some neoplastic cells produce enzymes and this may be helpful in diagnosis. As an example, the osteoblast is high in alkaline phosphatase and, in an animal with extensive osteosarcoma, the serum levels of alkaline phosphatase may be quite high.
The following are some of the methods presently being employed in the treatment of neoplasms.
1.Surgery:
Surgery is probably the most common therapeutic measure for neoplasms. It is usually quite successful in benign neoplasms but the degree of success in treating malignancies by means of surgery depends upon how long the neoplasm has been present, how extensively it has infiltrated and whether or not it has metastasized.
2.X-rays:
One of the unique characteristics of x-rays is that they both produce and are useful in the treatment of neoplasms. When x-rays are involved as etiologic factors in neoplasia, there is usually low to moderate exposure over a long period of time, while in treating neoplasms massive doses of irradiation are given over a relatively short period of time. In general, the epithelial neoplasms respond to x-ray treatment more readily than do those of connective tissue origin.
3.Radium and other radioactive materials:
Radium was used many years ago as a treatment for malignancies and in recent years radioactive cobalt has come into prominence as a therapeutic agent. The effect of x-rays and radioactive compounds on neoplasms is thought to be due to at least three factors. The first of these is the direct effect of the irradiation on the neoplastic cells. It appears that rapidly proliferating cells are more susceptible to irradiation than are the normal cells of an organ or tissue. Secondly, irradiation appears to impair the blood supply to an area and thus interferes with the growth of neoplastic cells. The third factor involved is fibrosis and hyalinization of the connective tissue in the stroma of a neoplastic growth. This causes interference with nutritional exchange between the neoplastic cell and the blood vascular system and it also hinders the spread of neoplastic cells.
4.Endocrine products:
Various hormones have been used in the treatment of malignancies of endocrine glands. An example is the use of estrogens in treating prostatic neoplasms in man.
5.Chemicals:
Massive research efforts have been devoted to the development of chemotherapeutic agents capable of destroying or inhibiting the growth of neoplastic cells without seriously affecting normal cells. Nitrogen mustard was one of the early drugs shown to be of benefit in treating various forms of malignant lymphomas. Since that time, many other drugs with varying degrees of efficacy have been developed. As an example of the mode of action of some of these agents, some neoplastic cells require an exogenous source of asparagine, while normal cells do not have such a requirement. The systemic administration of asparaginase is, therefore, of theoretical benefit in treating an individual with an asparagine-dependent tumor. Unfortunately, no agent uniformly effective against all types of neoplasms has been found.
6.Immunotherapy:
The results of research studies have suggested that some forms of immunotherapy may be of value in treating malignancies. It has been shown that nonspecific immunologic stimulation of the body by BCG administration was helpful in treating human patients with some forms of leukemia. Other therapeutic approaches which have received attention have involved the administration of immune lymphocytes of cytotoxic, nonblocking antibodies. Some chemotherapeutic agents effective in treating neoplasms are thought to function by enhancing the body's immunologic capabilities.
The biologic behavior, diagnosis and treatment of individual neoplasms will be included in special pathology as well as in medicine and surgery courses. However, it is important to have an overall view of the general incidence of neoplasms in animals in order to be familiar with those that occur frequently and are important. The incidence of neoplasms in dogs is higher than in all other species. On the other hand, the incidence in sheep and pigs is quite low. The following table (from Thomson, R.G.: General Veterinary Pathology. W.B. Saunders Co., 1978) provides a general indication of the incidence of neoplasms in animals.
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DOG :
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CAT:
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HORSE:
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CATTLE:
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SHEEP :
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PIG: |
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After completing this section, each student should be in a position be provide appropriate answers for the following questions.
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