11.1. CARCINOMA

Carcinoma in dogs and cats is characterized by different stromal reactions depending on the subject. A simpler classification that can allow histopathologists to establish rapid diagnosis and, to a certain extent, prediction, includes in the group of epithelial tumors: papillary, tubular, solid and anaplastic carcinomas. Precancerous lobules and ductal hyperplasia are found at the periphery of carcinogenic nodules, in adjacent tissues, in both dogs (73.6%) and cats (56.3%) [4].

Macroscopically, carcinoma is characterized by rapid growth, doubling its volume in a short time, with local invasion, infiltrating the surrounding normal tissue. Sometimes, mammary neoplasms are delimited, a capsule appearing on palpation, but they present fibrous adhesions to the epidermis and the muscle fasciae or the neighboring muscles, and they cannot be freely moved. The skin is frequently ulcerated and the tumor invades the lymphatic vessels and lymph nodes, skin and the adjacent gland on the same side.

Mammary neoplasms can have diameters between 2 and 20 cm, and round, ovoid, discoid, fungiform or poorly defined shapes. The tumor extends rapidly and occupies the whole gland, as well as adjacent glands, and carcinomas can coexist with benign tumors in the same gland and/or the neighboring glands.

Adenocarcinomas are usually soft, and in section, a diffuse or lobular structure of homogeneous tissue of white-cream color appears. Papillary carcinomas have a firm or soft-bloody structure. Scirrhous carcinomas have irregular shapes, they are poorly delimited and occasionally invade adjacent mammary glands. They are of a dense-ligneous, even hard consistency, white-gray or brown-yellow color, and they adhere to skin or the basic musculature. Solid carcinomas are soft and in section they have a lobular structure, of white or gray color. Squamous cell carcinomas are of irregular shapes, hard, in section their structure is lobular, color being gray or white, with yellow spots [37].

Carcinomas generally develop rapidly, and they are detected by the owner in 2–6 months. If, following diagnosis, the mammary tumor is not removed, tumor growth lasts for a longer time before the dog’s death. Carcinomas may develop over a period of 3 months to 6 years. The conclusions drawn by FOWLER et al. (1974), based on a large number of mammary neoplasms in bitches, regarding the behavior of carcinomas after diagnosis and treatment, are extremely interesting. The mean survival time after the diagnosis of infiltrating papillary carcinomas was 5.6 months, less than for other carcinomas. The mean duration after the diagnosis of infiltrating solid carcinoma was 7.3 months. Scirrhous carcinoma had a longer duration than non-scirrhous carcinoma, 9.7 months. Most dogs with infiltrating papillary carcinoma died following metastases. The behavior of scirrhous carcinoma was similar to that of papillary carcinoma.

Epithelial carcinomas may develop from intralobular ductal or alveolar epithelium, appearing as non-infiltrating or infiltrating tumor structures. The evolution duration of non-infiltrating carcinomas was 36 months and that of infiltrating carcinomas 13 months.

Metastases of mammary carcinomas occur in 25% of cases. The metastatic process is facilitated by both blood flow and lymphatic flow, distributed in the mammary parenchyma.

11.1.1. Adenocarcinoma

Simple tubular adenocarcinoma is a relatively frequent tumor in dogs, the tubular type being predominant. The microscopic structure is dominated by tubular epithelial cells, in which pleomorphism and mitotic activity is estimated from low to high, and necrotic foci are frequent. The connective stroma can be in limited or moderate amounts. Tumor proliferation is surrounded by variable lymphocytic infiltration. The histological differentiation between tubular adenocarcinoma and benign lesion forms is difficult. Benign lesions can have in some cases a high mitotic activity or they can stimulate local invasive growth. In cats, these tumors represent the most frequent type. Tubular adenocarcinoma has in 70% of cases an invasive character, or expansive nodular character in 30%. The lymphocytic infiltration of the tumor is frequent, in approximately 50% of cases (Fig. 11.1, 11.2, 11.4, 11.5, 11.6, 11.30).

Fig. 11.1

Tubular adenocarcinoma, simple type.

Fig. 11.2

Tubular adenocarcinoma, scirrhous type.

Fig. 11.4

Tubular adenocarcinoma, simple type.

Fig. 11.5

Tubular adenocarcinoma, simple type.

Fig. 11.6

Tubular adenocarcinoma, simple type.

Fig. 11.30

Tubular adenocarcinoma, cat.

Complex tubular carcinoma in dogs has a predominantly tubular cell arrangement. Microscopically, tubular epithelial cells and myoepithelial cells form tumors of this type. Cuboid or fusiform cells, the latter with frequently vacuolated cytoplasm, line tumor tubules. Sometimes, the surrounding neoplastic myoepithelial cells are arranged more or less in a mass of stellate reticular cells. Tumor growth may be expansive, nodular or lobular. The histological difference between the highly differentiated carcinoma of this type and complex adenoma is extremely difficult. Malignancy is characterized by numerous mitoses, cellularity and large necrotic foci. Complex tubular adenocarcinoma has not been diagnosed in cats [19] (Fig. 11.7. and 11.8).

Fig. 11.7

Tubular adenocarcinoma, complex type.

Fig. 11.8

Tubular adenocarcinoma, complex type.

Papillary adenocarcinomas arise de novo or by the evolution towards malignization of the benign form, papillary adenoma. Papillary adenocarcinomas are usually multicentric, with simultaneous neoplastic changes in distinct and unrelated parts of the mammary gland. Papillary carcinomas can develop: when an alveolar structure or a canaliculus dilates and forms intraluminal papillae; when multiple mammary ducts dilate, thin stromal septa break, transforming the lobe into a cystic mass, in which papillae develop; when interlobular ducts become papillomatous. Approximately 18% of papillary carcinomas develop from mammary lobules, the rest from interlobular ducts [37].

Simple papillary adenocarcinoma is formed by columnar or cuboid cells, arranged in tubules under a sessile papillary form, or with a pedunculated structure, with scant connective stroma. The tumor is found in particular in dogs (Fig. 11.3, 11.9–11.12). These tumor types are almost exclusively papillary, but solid areas may also appear. About 80% of these neoplasms have infiltrative extension in the skin and the surrounding tissues, also invading the lymphatic system. A high pleomorphism and numerous mitoses are noted. Differential diagnosis is made with certain difficulty compared to benign papilliferous proliferation lesions.

Fig. 11.3

Papillary adenocarcinoma, simple type.

Fig. 11.9

Papillary adenocarcinoma, simple type.

Fig. 11.10

Papillary adenocarcinoma, simple type, pulmonary metastasis.

Fig. 11.11

Cystic papillary adenocarcinoma, simple type.

Fig. 11.12

Papillary adenocarcinoma and chondroma.

In addition to cell pleomorphism and a high mitotic index, necrotic foci, lymphocytic and plasmacytic infiltration is found in the tumor mass, and granulocytes are present in the duct lumen.

Complex papillary adenocarcinoma in dogs has a low incidence. The cells of neoplastic ducts are arranged in sessile or pedunculated papillary structures. Extensive areas of myoepithelial cells surround cuboid or columnar epithelial cells. The tumor is well delimited, without lymphocytic infiltration.

Simple cystic papillary adenocarcinoma is common in bitches, appearing as papillary or cystic structures, formed by cuboid epithelial cells, with low to moderate pleomorphism and mitotic activity.

Papillary cystadenocarcinoma is well differentiated, which makes difficult differential diagnosis from papillary cystadenoma and cystadenopapillomatosis. In cats, this tumor type has invasive growth, with lymphocytic infiltration. Pleomorphism and the mitotic index can be considered as moderate.

Complex cystic papillary adenocarcinoma has a low incidence in dogs, a papillary and cystic structure. The tumor is formed by epithelial and myoepithelial cells, which makes it extremely similar to simple cystic papillary adenocarcinoma, the difference consisting in the presence of microfoci of fusiform myoepithelial cells with cytoplasmic vacuoles. This type of neoplasm produces metastases, although it shows a high differentiation, which makes difficult differential diagnosis from the benign form. The tumor has not been diagnosed in cats.

11.1.2. Solid carcinoma

Solid carcinomas may arise through an extensive intralobular invasion in adenocarcinomas, in which lobules are changed into solid tumor cell masses with a reduced glandular structure and inapparent stroma; epithelial excrescences can form and invasion may occur in the papillary carcinoma, with papillary projections transformed into solid cellular masses, or from diffuse infiltrating carcinomas, with invading cell bundles, so compact that they form solid cellular masses.

Solid carcinoma is probably a more advanced form of other types of carcinoma, being found much more frequently when the neoplasm has developed over a long time period, without the intervention of surgery or other therapeutic form.

Simple solid carcinoma is frequently found in dogs and is formed by epithelial or myoepithelial cells. Cells are arranged in solid foci, cords or masses, forming tubes or other structures with a lumen. Sometimes there are few solid foci, along with differentiated adenomatous formations. Pleomorphism and the mitotic index are moderate to high, and the connective stroma is in a moderate amount. This type of solid carcinoma has an infiltrative growth and a 60% penetration rate in the regional lymph nodes.

Some solid carcinomas are formed by cells with vacuolated cytoplasm, being similar to myoepithelial cells, which indicates an exclusive extension of poorly differentiated myopithelial carcinoma (Fig. 11.13).

Fig. 11.13

Solid carcinoma, simple type.

In cats, solid carcinoma appears almost exclusively, which develops with intense infiltrative growth and penetration in lymphatic vessels. The presence of lymphocytic and plasmacytic infiltration can be evaluated as moderate to intense.

Complex solid carcinoma has only been diagnosed in bitches. Microscopically, it is formed by epithelial and myoepithelial cells. Epithelial cells have vacuolated cytoplasm, they are arranged as tubes and apparently with squamous metaplasia. In most cases, neoplastic cells are structured under the form of layers, cords or masses that present a lumen. The growth of this carcinoma is frequently expansive, and penetration in lymphatic vessels and lymph nodes is exceptional (Fig. 11.14).

Fig. 11.14

Solid carcinoma, complex type.

Differential diagnosis between complex solid carcinoma and complex adenoma is extremely difficult.

11.1.4. Anaplastic carcinoma

Anaplastic carcinoma is a neoplasm that cannot be classified in one of the following types: adenocarcinoma, solid carcinoma, squamous cell carcinoma or mucinous carcinoma. Anaplastic carcinoma appears as an infiltrative neoplasm, formed by large pleomorphic cells, frequently with bizarre chromatin-rich nuclei, with the presence of multinucleated cells. Anaplastic giant cell mammary carcinoma is not frequent and has only been reported in female dogs and cats [34]. By special histochemical methods, antibodies and ultrastructural examination, the origin of canine mammary tumors has been proved to be in the stem cell [22, 47]. The authors mention the possibility of the coexistence of malignant epithelium and giant cells in anaplastic carcinoma. SALDA et al. (1993) have electron microscopically identified the presence of disseminated tonofibril bundles, but not of lysosomal formations. The conclusion is that canine mammary tumors originate from the stem cell. Mitoses are present in a considerable number. Cells have eosinophilic and vacuolated cytoplasm, sometimes being extremely small, poorly defined, with tubular structures or extremely small solid cords. Polynuclear granulocytes are present among tumor cells and in the stroma of most anaplastic carcinomas. This will be taken into consideration, as there is a risk for confusion with mastitis. The collagenous stroma is abundant, the carcinoma is scirrhous and contains lymphocytic foci. The infiltration of neoplastic cells in the lymphatic system is frequent. Some anaplastic carcinomas can be recognized as epithelial tumors (Fig. 11.17).

Fig. 11.17

Anaplastic carcinoma.

11.1.5. Squamous cell carcinoma

Squamous cell carcinoma is formed by stratified squamous epithelium, spinous and/or keratinized cells. This neoplasm can be simple or complex, with the presence of extremely varied histological structures. Approximately half of squamous cell carcinomas appear as adenomatous structures, with the presence of keratohyalin granules and keratin lamellae. Other squamous cell carcinomas appear as solid layers and cords with cornified areas. Basal cells are dominant at the periphery of the neoplasm, and keratohyalin granules are absent or rare. In the central area, non-lamellar keratin is mixed with necrosis, and the neoplasm is frequently abundantly infiltrated with lymphocytes. Primary squamous cell mammary carcinoma should be differentiated from primary squamous cell tumors derived from the skin, dermal adnexae and epidermal cysts. Squamous cell mammary carcinoma has not been diagnosed in cats (Fig. 11.18).

Fig. 11.18

Squamous carcinoma.

11.1.6. Mucinous carcinoma

Mucinous carcinoma, in its typical form, is rarely found in female dogs and cats. Microscopically, the predominance of myoepithelial cells has been found, without these being related to mucus secretion. Three types can be theoretically identified: mucin that can arise from secretory epithelial cells, from connective tissue cells or myoepithelial cells. Cystic adenoid carcinoma can be included in this category. Few mucinous carcinomas have been reported in dogs and cats (Fig. 11.15, 11.16).

Fig. 11.15

Mucinous carcinoma.

Fig. 11.16

Mucinous carcinoma.

11.2. SARCOMA

Mammary sarcomas are relatively frequent in bitches, but not in cats. Sarcoma metastases have only been diagnosed in dogs.

11.2.2. Osteosarcoma

Cells that only produce osteoid and/or bone form osteosarcoma. Bone and osteoid trabeculae appear in various proportions in the structure of the tumor, in different areas of the neoplastic mass. The tumor center is occupied by a dense compact mass, while the cellular area is at the periphery. Necrotic cysts and hemorrhagic foci frequently appear. Neoplastic cells are pleomorphic and frequently polyhedral, while in other tumors, fusiform cells predominate. In the majority of tumors, the mitotic index is high, as well as the number of multinucleated cells similar to osteoclasts, situated in the proximity of neoplastic bone tissue (Fig. 11.19, 11.20).

Fig. 11.19

Osteoblastic osteosarcoma.

Fig. 11.20

Chondroblastic osteosarcoma.

11.3. CARCINOSARCOMA

Carcinosarcoma is a malignant mixed tumor, formed by epithelium-like cells (epithelial, myoepithelial or both cells type) and connective tissue-like cells. Histological structure varies widely, from one tumor to another. A high percentage (30%) of mixed tumors contains fusiform cells, which are considered to originate in myoepithelial cells or connective tissue. The osteosarcomatous component is considered to originate from enchondral ossification (secondary bone) and from fibrous cells, primary bone.

Infiltrative growth and lymphatic metastases occur more rarely; it seems that these aspects only involve the carcinomatous component, less the sarcomatous component. Histological differentiation of carcinosarcoma is required from benign mixed tumors, and is sometimes difficult (Fig. 11.24.).

Fig. 11.24

Fibroadenoma.

Malignant mixed tumors grow more slowly than carcinomas, with limits from 1 month to 1 year or more, the majority during of at least 6 months. Some of the mixed tumors histologically diagnosed as benign can be potentially and evolutionally malignant.

Metastases in malignant mixed tumors usually appear under the form of carcinomas and exceptionally as osteosarcomas, chondrosarcomas or myoepitheliomas. Metastases have been found in the lymph nodes, lungs, liver, kidneys and exceptionally in other organs.

11.4. BENIGN TUMORS

Benign tumors have been classified according to the classification known in women. In most cases, in female dogs and cats, these lesions do not evolve independently, but some of them correspond to those described in women. Benign mammary tumors, of adenoma type, are difficult to differentiate histologically from the physiological hyperplasia of the mammary gland. In both cases, large mammary lobules appear, with the dilation of acini and mammary ducts, papillary concretions being occasionally present, both in benign and malignant forms. This lesion is extremely rare in dogs and cats. Nodules formed by fusiform cells with little stroma may be found, being considered as solid myoepithelial adenoma.

Complex adenomas are extremely frequent in dogs and cats and are formed by the proliferation of secretory epithelial cells, myoepithelial cells and insignificant stroma. These tumors partially correspond to cellular fibroadenomas, benign mixed tumors, and sometimes to complex (non-tumoral) lobular hyperplasia. Inflammation and metaplastic changes are described as non-tumoral inflammatory nodular hyperplasia.

Differential diagnosis between complex adenoma and complex adenocarcinoma is difficult.

11.4.1. Papilloma

Duct papilloma is infrequent in dogs and cats, but it can frequently be identified in a complex tumor, especially in the complex type.

Duct papillomatosis. Papillary duct covering and cysts should be differentiated from duct papilloma. The presence of adenosis in the duct lumen with ectasia and the appearance of secondary papillary formations have led to the term duct papillomatosis. The differentiation between duct papillomatosis and papillary adenocarcinoma is difficult, especially in cats. Papillary proliferations develop in both acinar lobules and the intralobular duct system, in the sinus of the mammary glands, by duct dilation or septal breaking and formation of cysts, in which papilliferous proliferations develop. Papilliferous expansions can be sessile, pedunculated or polypous. The epithelium that covers these proliferations is mono-or pluristratified, flat and atrophied, simple cuboid or columnar. The lumen of the duct or cyst contains homogeneous acidophilic fluid. Papillary proliferations develop from well vascularized connective tissue filaments, covered by cuboid or columnar cells (Fig. 11.27).

Fig. 11.27

Duct papilloma, dog.

11.4.2. Fibroadenoma

Fibroadenoma can be pericanalicular and intracanalicular, the latter being of either non-cellular or cellular type.

Pericanalicular fibroadenoma is characterized by the dominance of fusiform, myoepithelial cells and/or stromal tissue.

Benign mixed tumors appear as cartilage, bone and fat tissue. It is difficult, sometimes impossible, to differentiate the tumor stroma from cartilaginous metaplasia or the myoepithelial component. Benign mixed tumors originate in several germ layers, including a wide variety of tissues, for example epithelial cells, fibrous connective tissue, cartilage and bone. Myoepithelial cells can be identified in all tumor forms. The origin of cartilaginous and bone tissue can be metaplastic, by the transformation of epithelial cells, but more likely, it is in the stromal connective tissue. Cartilaginous tissue is supposed to be derived from myoepithelial cell metaplasia.

Macroscopically, mixed tumors have sizes that range from several millimeters to 20 cm, firm and frequently cartilaginous or of bone consistency. In section, they appear lobulated, of white-gray color, and cysts with unclear or red-brown liquid are frequent. Papillary changes frequently occur on the internal side of cysts. The tumor has a spherical, ovoid shape, or appears as a pendulous mass, affecting one or more mammary glands, sometimes with the involvement of the whole gland. Mixed tumors are well encapsulated, being non-adherent to neighboring tissues, and more rarely to skin.

Microscopically, the aspects of the development of a mixed tumor are preceded by myoepithelial cell changes and cartilage formation. In the early proliferation stage, a separation of myoepithelial cells is found in the basal layer of the ducts. In this stage, the basal membrane is intact, myoepithelial cells are grouped in spherical masses of stellate or elongated cells, separated by a colorless or slightly basophilic substance. These myoepithelial cell masses penetrate the stroma, causing a severe disorganization of epithelial elements, compressing the canaliculi and the acinar structure in thin structures. Myoepithelial cells, being at the same time a precursor of hyaline cartilage, secrete the intercellular substance. In order to differentiate myoepithelial cells from fibroblasts and from epithelial cells, the alkaline phosphatase reaction is performed, which is positive in the cytoplasm of myoepithelial cells and negative in the other cells (Fig. 11.25).

Fig. 11.25

Benign mixed tumor.

Electron microscopically, the dominant aspect of neoplastic myoepithelial cells is the high number of cytoplasmic filaments. These filaments are more separated, larger and more rectilinear in tumor cells than in normal cells and are much easier to distinguish. An extensive Golgi apparatus that frequently occupies a large cytoplasm area represents another characteristic of neoplastic myoepithelial cells. As myoepithelial cells proliferate and organize into neoplasms, the tissue resembles more and more hyaline cartilage, the Golgi apparatus extends, while the number of cytoplasmic filaments diminishes [44].

The cartilage formed in mixed tumors appears as nodules or plaques of various sizes. Osteoblasts actively participate in bone formation, under the form of osteoid or well mineralized bone tissue. The connective stroma is frequently hyalinized.

Benign mixed tumors that reach large sizes may become infected and/or ulcerated, having foci and diffuse collections that contain fluids and tissue debris, and hyalinization and calcification are usual aspects.

Total fibroadenomatous change may appear in one or all mammary glands, in young cats, being considered a dysplastic benign lesion. It is difficult to establish a equivalence with andromastosis in women, considered as a bilateral juvenile pseudohypertrophy (Fig. 11.32).

Fig. 11.32

Fibroadenomatous change, cat.

Benign soft tissue tumors. The group of these tumors includes lipomas and hemangiomas, to which benign mixed tumors that mimic chondroma, osteoma or fibroma are added.

Unclassified tumors. This group includes benign and malignant tumors that cannot be included in the previously described categories.

11.5. BENIGN DYSPLASIAS

Non-papillary cysts are found in women; in bitches they appear in most cases under the form of multiple cysts, in one or more mammary glands, and differentiation from duct dilation is arbitrary.

Papillary cysts are most frequently found in the bitch, under a complex form. Differentiation from intracystic, intraductal papillomas and from papillomatosis is arbitrary. The oncocytic transformation of epithelial cells towards papillary growth is accompanied by cytonuclear pleomorphism.

Adenosis is rarely found in dogs and cats, formations are little obvious, being clinically detected as irregular lesions. Microscopy identifies confluent, multilobular or multiductal foci of adenotic type, forming complex adenoma: intralobular adenosis and complex lobular hyperplasia are not distinct and can be confused in some cases with duct papillomatosis (Fig. 11.29). Usually, adenosis resembles other proliferation types.

Fig. 11.29

Lobular hyperplasia, adenosis, simple type.

Typical epithelial proliferation in ducts or lobules. This hyperplasia type is also known as epitheliosis and appears as an epithelial or hyperplastic proliferation in preexisting structures, not as a growth in cysts or dilated ducts, adenosis, etc. (Fig. 11.28, 11.31). The proliferation contains a single cellular type, but the presence of fusiform cells is suggestive of a mixture of myoepithelial cells. Proliferated epithelial cells have the shape of duct cells, being columnar, with hyperchromatic nuclei. This has led to the term “mural epitheliosis”.

Fig. 11.28

Ductal hyperplasia.

Fig. 11.31

Lobular hyperplasia, adenosis, epitheliosis, cat.

Normal epithelial proliferation is found in bitches, predominantly in ductolobular areas, more rarely organized as nodules. Epitheliosis in the bitch has a uniform growth, with unchanged cells, which makes difficult the subdivision into types.

Duct ectasia is frequent in female dogs and cats, which determines a spongy change of the mammary parenchyma. Ectasia affects terminal, intralobular tubules and some acini. Lobular hyperplasia includes the inflammatory type that is complicated by ectasia. Tubules are dilated, containing protein fluid with cell remnants. Ectatic formations are lined by columnar cells, and occasional papilliferous proliferations may appear. Spontaneous regressions or regressions following ovariectomy as well as progesterone administration may occur [51].

Fibrosclerosis is frequent in bitches, being associated with the persistence of the ovarian corpus albicans. The lesion appears under the form of small nodules, in which irregular collagenous bands are identified, with regressive changes or smooth scars.

Gynecomastia has been diagnosed in male dogs with active testicular tumors.

Non-inflammatory lobular hyperplasia is found in bitches and cats and appears as foci or nodules that can be sometimes large, in which secretory or myoepithelial epithelium is dominant. It is characterized by an extremely varied lesional picture, acinar and duct ectasia, sclerosis and secretion, with the presence of inflammatory or metaplastic cells. In order to be correctly interpreted, these lesions should be correlated with the physiological condition of the bitch, since they may lend to confusion with the lactating condition. In bitches that are not gestating or lactating, hyperplastic foci are histologically identified around the age of 3 years. The most frequent location is in the last two mammary gland pairs. Lobular hyperplasia could be considered as a preneoplastic condition [51].

Feline fibroepithelial hyperplasia is more rarely reported, almost all cases appearing in females under 2 years, even 1 year of age, exceptionally in old cats. Usually, all mammary glands are affected concomitantly, although some nodules can be larger. Formations appear as hard, non-painful masses, 2–5 cm in diameter, sometimes even larger. In section, they have a multilobular structure of white to slightly red color.

Microscopically, the lesion is clearly circumscribed, without being encapsulated, with a multilobular aspect, and an extremely marked proliferation of the intralobular duct system should be mentioned. Interlobular proliferation is less obvious. The proliferation of the intralobular duct system is structurally identical to physiological hyperplasia from the early gestational stage. Ramified canals have an envelope of epithelial cells, sometimes arranged in 3–4 layers. These cells are hyperchromatic, with the presence of mitotic figures. Intralobular connective tissue is intensely proliferated, edematous, and cells present mitoses. Hormonal factors are etiologically incriminated [37] (Fig. 11.19).

Inflammatory lobular hyperplasia. In dogs and cats, foci or inflammatory type nodules appear, which are frequently the result of (mucinous, squamous or oncocytic) metaplasia, with pigment accumulation in macrophages, lymphoplasmacytic infiltration of the stroma and granulocytes in the duct lumen (Fig. 11.21 and 11.22).

Fig. 11.21

Simple adenoma.

Fig. 11.22

Simple myoepithelial adenoma.

11.6. MAMMARY TUMORS IN OTHER SPECIES

Mammary tumors, which are rare or even very rare in other species, have been reported extremely sporadically in ruminants, horses and swine.

In mares, the few mammary tumors reported have been solid scirrhous carcinomas, with local invasive growth, and in all cases metastases have been identified [48].

In cows, fibropapillomas have been described in the galactophorous duct or in the large ducts, in all cases fibroma, squamous cell carcinoma and osteoma-fibrosarcoma being found [51]. Acinar and duct carcinoma was diagnosed in an 8-year-old Simental cow, under the form of multiple nodules and metastases in the mesenchymal serosae, liver, spleen, diaphragm, thoracic cavity, reproduction and gastrointestinal systems. Microscopically, neoplastic acinar and duct cells formed aberrant acini [43]. A multicentric papillary cystadenoma was diagnosed in a 9-year-old ovariectomized Holstein cow [45].

The experimental neoplasms of the mammary glands allow to understand carcinogenesis and implicitly, to prevent and/or fight mammary carcinoma. The mouse mammary tumor model has been used in order to study the characteristics of paraneoplastic lesions. The possibility of transplanting tissue and neoplastic cells from mouse mammary tumors has opened the way to studies whose results can be extrapolated to other neoplasms and even generalized for tumor disease. There is a possibility to elucidate oncogenic and cloning activities during tumor genesis, with the development of transgenic mice technology, opening the perspective of in vivo carcinogenesis studies. Transgenic mice and transgenic mammary glands provide a controlled system capable of answering the numerous questions of cancer disease. Experimental studies in mice have proved the existence of protoneoplastic lesions and increased malignant potential [9].

The problem of the implication of some viruses in the carcinogenesis of mammary neoplasms has also been studied in mice. The mouse mammary tumor virus is transmitted by milk and by sexual cells. It has been demonstrated that in order to be active, the mouse mammary tumor virus needs a certain hormonal context. The virus is of RNA type, it integrates into chromosomes, a reverse-transcriptase being needed to copy the retrovirus in the DNA, which in its turn integrates in chromosomal DNA. Mouse mammary cell cultures treated with corticosteroids stimulate viral RNA synthesis [12]. Viral particles have also been identified in spontaneous neoplasms, in carcinosarcomas in bitches [39].

Chemical substances, such as medroxyprogesterone acetate, capable of inducing mammary adenocarcinoma in female mice, have been experimented. Following the subcutaneous administration of 40 mg medroxyprogesterone acetate, mammary carcinomas have developed in both non-pubertal and gestating females, some subjects also developing metastases [24]. Medroxyprogesterone acetate is also used as contraceptive treatment in precocious puberty.

The in vitro study of mammary tumors in bitches has proved that 17-β-estradiol and, to a lower extent, progesterone induce the replication of mammary tumor cells, results being similar to those obtained in mammary cancer cells. Cells present specific hormone receptors. It can be supposed that the mitogenic effects of estradiol and progesterone on mammary cancer might be the result of an indirect stimulating mechanism, such as the production of autocrine or paracrine growth factors. Estrogen stimulation of tumor proliferation determines a shortening of the S phase of the cell cyle DNA [26].

Fig. 11.23

Complex adenoma.

Fig. 11.26

Basaloid adenoma, mammary gland, dog.

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List of Figures 11.1-11.32

• Fig. 11.1 Tubular adenocarcinoma, simple type.
• Fig. 11.2 Tubular adenocarcinoma, scirrhous type.
• Fig. 11.3 Papillary adenocarcinoma, simple type.
• Fig. 11.4 Tubular adenocarcinoma, simple type.
• Fig. 11.5 Tubular adenocarcinoma, simple type.
• Fig. 11.6 Tubular adenocarcinoma, simple type.
• Fig. 11.7 Tubular adenocarcinoma, complex type.
• Fig. 11.8 Tubular adenocarcinoma, complex type.
• Fig. 11.9 Papillary adenocarcinoma, simple type.
• Fig. 11.10 Papillary adenocarcinoma, simple type, pulmonary metastasis.
• Fig. 11.11 Cystic papillary adenocarcinoma, simple type.
• Fig. 11.12 Papillary adenocarcinoma and chondroma.
• Fig. 11.13 Solid carcinoma, simple type.
• Fig. 11.14 Solid carcinoma, complex type.
• Fig. 11.15 Mucinous carcinoma.
• Fig. 11.16 Mucinous carcinoma.
• Fig. 11.17 Anaplastic carcinoma.
• Fig. 11.18 Squamous carcinoma.
• Fig. 11.19 Osteoblastic osteosarcoma.
• Fig. 11.20 Chondroblastic osteosarcoma.
• Fig. 11.21 Simple adenoma.
• Fig. 11.22 Simple myoepithelial adenoma. ^*)
• Fig. 11.23 Complex adenoma.
• Fig. 11.24 Fibroadenoma.
• Fig. 11.25 Benign mixed tumor. ^*)
• Fig. 11.26 Basaloid adenoma, mammary gland, dog.
• Fig. 11.27 Duct papilloma, dog.
• Fig. 11.28 Ductal hyperplasia.
• Fig. 11.29 Lobular hyperplasia, adenosis, simple type.
• Fig. 11.30 Tubular adenocarcinoma, cat.
• Fig. 11.31 Lobular hyperplasia, adenosis, epitheliosis, cat.
• Fig. 11.32 Fibroadenomatous change, cat.