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Baba AI, Câtoi C. Comparative Oncology. Bucharest (RO): The Publishing House of the Romanian Academy; 2007.

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Comparative Oncology.

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Chapter 5MESENCHYMAL TISSUE TUMORS

Mesenchymal tissue neoplasms are soft tissue tumors, also known as connective tissue tumors, which are relatively frequent in domestic animals and have a high incidence in some species. These tumors may be located in all organs, with a higher or lower incidence in some tissues, as it will be shown.

The incidence of connective tumors varies depending on the species, and in a certain species, some types may be more or less frequently found. Thus, in cats, connective tumors occupy the second position of all neoplasms diagnosed in this species, having an incidence of 17/10000, and in dogs, they are the third most frequent tumors, with an incidence of 35.8/100000, after skin tumors and melanomas [32].

In 1990, by examining 29649 benign and malignant tumors from dogs, MIALOT and LAGADIT diagnosed neoplasms of mesenchymal origin in 7.6% of cases, of which 960 benign tumors and 1283 malignant tumors. The authors noted a breed predisposition to mesenchymal tumors. Thus, incidence was higher in Shepherd breeds (German Shepherd, Colley, Belgian Shepherd, Briard, etc.). The predisposition of the Boxer breed to mesenchymal tumors is the result of sensitivity to mastocytoma, which is exclusively located subcutaneously. By examining 5609 tumors from cats, of which 764 benign and 4845 malignant, the same authors diagnosed 2006 mesenchymal tissue tumors, having the highest prevalence, 35.7%. Of all 2006 mesenchymal tumors, 126 were benign and 1880 malignant.

In horses, equine sarcoid is recognized as having a high incidence, with more frequent locations in the limbs and the head, with no age, breed or sex preference.

Soft connective tissue tumors have a high incidence, especially in companion animals, but an accurate classification and histological characterization are difficult. Malignant connective tumors, sarcomas, show an extremely high morphological heterogeneity. This is also due to the fact that the cellular origin of all soft sarcomas is a primitive mesenchymal cell, with an extremely high differentiation capacity, in various cell lines. The differentiation capacity of the primary connective cell does not allow to characterize the neoplastic cell from the point of view of its origin. This has required the introduction of the concept of sarcomas of intermediate malignancy [86].

The group of soft tissue tumors mainly includes the following: fibromatoses, fibrosarcomas, equine sarcoids, histiocytomas, neurofibrosarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcomas, angiosarcomas, synovial cell sarcomas, mesotheliomas and meningiomas. In addition to these tumors, there are others with a lower incidence or forms classified according to more detailed morphological and/or clinical systems. In spite of some differences, all classifications used in the literature are based on the histological structure and the predominance of a certain cell type. Such a classification, proposed by WEISS (1974), updated with more recent data, will be used in the description of connective tissue tumors:

  1. connective tissue tumors proper: hard, soft fibroma and myxoma; nodular fasciitis; fibrosarcoma; hemangiopericytoma; predominantly cellular sarcomas; fibrohistiocytoma; equine sarcoid; tumor-like lesions: cutaneous fibrous polyp, keloid and hyperplastic scars, calcinosis circumscripta;
  2. adipose tissue tumors: lipoma, liposarcoma;
  3. muscle tissue tumors: leiomyoma, leiomyosarcoma; rhabdomyoma; rhabdomyosarcoma;
  4. blood and lymphatic vessel tumors: hemangioma; malignant hemangioendothelioma or hemangiosarcoma; glomus tumors; lymphangioma; lymphangiosarcoma; synovial tumors; tumor-like lesions;
  5. mesenchymal tumors of peripheral nerves;
  6. mastocytoma;
  7. mesothelioma; histiocytic tumors;
  8. mixed tumors;
  9. unclassified tumors.

Histological Classification of Mesenchymal Tumors of Skin and Soft Tissues of Domestic Animals (Hendrick et al.1998)

  1. Tumors of Fibrous Tissue
    • 1.1 Benign
      • 1.1.1 Fibroma
      • 1.1.2 Collagenous hamartoma
      • 1.1.3 Nodular dermatofibrosis of the German shepherd dog
      • 1.1.4 Nodular fasciitis
      • 1.1.5 Myxoma
      • 1.1.6 Equine sarcoid
    • 1.2. Malignant
      • 1.2.1 Fibrosarcoma
        • 1.2.1.1 Feline postvaccinal
        • 1.2.1.2 Canine well-differentiated maxillary and mandibular
      • 1.2.2 Myxosarcoma
      • 1.2.3 Malignant fibrous histiocytoma
        • 1.2.1.1 Storiform-pleomorphic
        • 1.2.1.2 Inflammatory
        • 1.2.1.3 Giant cell
  2. Tumors of Adipose Tissue
    • 2.1 Benign
      • 2.1.1 Lipoma
      • 2.1.1.1 Infiltrative lipoma
      • 2.1.2 Angiolipoma
    • 2.2. Malignant
      • 2.2.1 Liposarcoma
        • 2.2.1.1 Well-differentiated
        • 2.2.1.2 Pleomorphic
        • 2.2.1.3 Myxoid
  3. Tumors of Smooth Muscle
    • 3.1 Benign
      • 3.1.1 Leiomyoma
    • 3.2. Malignant
      • 3.2.1. Leiomyosarcoma
  4. Tumors of Striated Muscle
  5. 4.1. Benign
    • 4.1.1 Rhabdomyoma
  6. 4.2 Malignant
    • 4.2.1 Rhabdomyosarcoma
      • 4.2.1.1 Embryonal rhabdomyosarcoma of the urinary bladder
  7. Tumors of the Vascular Tissue
    • 5.1 Benign
      • 5.1.1 Hemangioma
      • 5.1.2 Lymphangioma
      • 5.1.3 Scrotal vascular hamartoma
      • 5.1.4 Cutaneous bovine angiomatosis
    • 5.2 Intermediate
      • 5.2.1 Kaposi-like vascular tumor
    • 5.3 Malignant
      • 5.3.1 Hemangiosarcoma
      • 5.3.2 Lymphangiosarcoma
        • 5.3.2.1 Feline ventral abdominal angiosarcoma
  8. Tumors of Peripheral Nerves
    • 6.1 Benign
      • 6.1.1 Traumatic neuroma
      • 6.1.2 Granular cell tumor
      • 6.1.3 Benign peripheral nerve sheath tumor of the skin and subcutis [neurofibroma, schwannoma]
    • 6.2 Malignant
      • 6.2.1 Malignant peripheral nerve sheath tumor of the skin and subcutis [neurofibrosarcoma, malignant schwannoma]
  9. Tumors of Synovium
    • 7.1 Malignant
      • 7.1.1 Synovial cell sarcoma
  10. Tumors of Mesothelium
    • 8.1 Intermediate
      • 8.1.1 Mesothelioma
  11. Mast Cell Tumors
    • 9.1 Feline
      • 9.1.1 Feline, "histiocytic"
    • 9.2 Canine
      • 9.2.1 Canine, grade I
      • 9.2.2 Canine, grade II
      • 9.2.3 Canine, grade III
    • 9.3 Other species
  12. Histiocytic Tumors
    • 10.1 Benign
      • 10.1.1 Canine cutaneous histiocytoma
      • 10.1.2 Xanthoma
    • 10.2 Intermediate
      • 10.2.1 Cutaneous histiocytosis
      • 10.2.2 Systemic histiocytosis
    • 10.3 Malignant
      • 10.3.1 Malignant histiocytosis
  13. Miscellaneous Tumors
    • 11.1 Benign
      • 11.1.1 Calcinosis circumscripta
  14. Unclassified Tumors
    • 12.1 Malignant
      • 12.1.1 Canine hemangiopericytoma
      • 12.1.2 Malignant mesenchymoma

5.1. FIBROMA

Well circumscribed, encapsulated benign tumors, in which fibrocytes and collagen proliferate, are known under the generic designation of fibroma. The macroscopic aspect predisposes to confusions with fibrous scars or chronicized fibrosed inflammations.

Fibromas frequently appear in the dermis or subcutaneously, and they can be found at any site with connective tissue. Macroscopically, they appear as well delimited, ovoid or round, hard or soft formations; when they are subcutaneous, skin frequently presents erosions or even ulcers. In section, they have a gray color, being poorly vascularized.

Fibromas are found in all species, being more frequent in adult or old animals. Incidence does not seem to be associated with animal breed or sex.

Fibroma durum is a usually single, dense and well delimited benign tumor. Histologically, it is formed by mature fibrocytes and collagen fibers. Fibrocytes have elongated, fusiform or ovoid nuclei, they are hyperchromatic, and mitotic forms are absent or appear sporadically. Collagen fibers are oriented in different planes, resulting in vortex images, or they are parallel (Fig. 5.1).

Fig. 5.1. Fibroma composed of fibrocytes and abundant collagen.

Fig. 5.1

Fibroma composed of fibrocytes and abundant collagen.

Fibroma molle is well delimited, of white-gray color, elastic-soft consistency, wet and slightly sticky in section. Histologically, stellate cells are found, arranged in a fundamental mass, with the presence of adipocytes or even interstitial lipid deposits (Fig. 5.2).

Fig. 5.2. Fibroma molle, fine fiber reticular and fibrocits.

Fig. 5.2

Fibroma molle, fine fiber reticular and fibrocits.

Myxoma; myxosarcoma is macroscopically similar to fibroma molle, it can have a jelly-like appearance, with infiltrative aspect, and color varies from white-gray to citron-pink.

These neoplasms may be found in all species, but incidence is rare, being more frequent in adult and old animals, with no sex preference. In humans, LIE (1989) reports the presence of myxomatous nodules, some of which are calcified in the atrial musculature.

Microscopically, the benign form is difficult to differentiate from the malignant one, and the structure and cells are similar. Cells are in a mucinous, vacuolated, basophilic stromal mass, with rare collagen fibers. Cells may be grouped into nests, with a fusiform aspect, the cytoplasm has extensions, round or elongated nuclei, with multiple nucleoli. In the case of myxosarcoma, mitoses can be noted in a moderate number, the tumor is difficult to operate, being infiltrative, and metastases occur especially in the lung [124] (Fig. 5.3).

Fig. 5.3. Myxoma.

Fig. 5.3

Myxoma.

Rabbit myxomatosis is an infectious-contagious disease, produced by a virus from the Pox viridae family, Leporipoxvirm genus. The virus causes the formation of the tumor, the primary myxoma, and following viremia, secondary myxomas appear in the subcutaneous connective tissue. Myxomas develop in the head, mouth, eyelids and ears, then in the back, abdominal, perianal areas and in the genital organs.

Myxomas are soft, friable, and in section they have a yellowish or pink color, with a jelly-like aspect, being well vascularized [8].

Microscopically, a ballooning degeneration of the spinous layer of the skin epithelium is found, hyperacanthosis, and in the cytoplasm of epithelial cells, Splendore inclusions or bodies. In the dermis and hypodermis, the hyperplasia and tumefaction of capillary endothelium is noted, with the obliteration of the lumen, fibrinoid degeneration and capillary thrombosis. Concomitantly, the proliferation of pericytes occurs, which are arranged under the form of an onion bulb.

In the dermohypodermal foci, serous, hemorrhagic and eosinophilic exudate is noted, collagen fibers are fluidified, large cells with cytoplasmic extensions and voluminous nuclei with a tiger-striped aspect being present, myxomatous cells, in which Splendore bodies can be identified.

In lymph nodes, reticular cell hyperplasia with epithelial changes and polynuclear giant cells (polykaryocytosis) is found, as well as regressions of the lymphoid tissue (karyorhexis and atrophies), proliferation of immature hyperbasophilic cells, capillary endothelium hyperplasia, hemorrhage and necrotic purulent microfoci.

5.2. NODULAR FASCIITIS

The lesion is known as aggressive fibromatosis, pseudosarcomatous fibromatosis or nodular fasciitis, being closer to an inflammation, it has an aggressive character, suggesting a local invasive neoplasm that develops in the subcutaneous fascia. Nodular fasciitis has been diagnosed in dogs and cats, a higher incidence being supposed, but it has been confused with inflammatory lesions, granulation tissue or fibrosarcoma. The incidence of the lesion does not seem to be influenced by age, breed and sex. However, in 1985, LIUM and MOE described 43 cases of nodular fasciitis, all in the German Sheepherd breed, in association with multiple bilateral hereditary renal cystadenocarcinoma. SUTEER et al. (1983) reported generalized nodular fasciitis in 7 German Sheepherd dogs. In 1990, DEGORCE and PARODI described the lesion in a Saint-Bernard dog, with slow and benign evolution, associated with renal cancer.

According to STANNARD and PULLEY (1987), the lesion is located in the subcutaneous tissue, in fascias and the deep muscles of the head and face or on eyelids, the cornea and the sclera. Macroscopically, it appears as a dense mass, formed by poorly circumscribed nodules, with sizes varying between 0.2 and 5.0 cm, sometimes larger. In section, they are gray, with red or brown foci.

Histologically, nodules are formed by fusiform or large round fibroblasts, in a stromal network with variable amounts of collagen and reticulin fibers. Fibroblasts may be arranged in long or short fascicles, or as spirals around the capillaries. Structure is not homogeneous, in some areas fibroblasts are predominant, in others, collagen mass or reticulin fibers. Mitotic forms are rare. The presence of inflammatory type reaction is specific for this lesion, which is characterized by lymphocytic, plasmacytic and macrophagic infiltrations, sometimes with multinucleated cells at the periphery of the inflammatory foci. The lesion periphery is poorly delimited, the infiltration frequently extending to the adjacent connective and muscular tissues.

Although it has an infiltrative growth, nodular fasciitis cannot be diagnosed as malignant tumor growth. In fact, growth is slow, and after correct surgical removal, it does not recur. In some cases, locations in the eye and eyelid had an invasive character with multiple recurrences [124].

5.3. FIBROSARCOMA

Fibrosarcoma is a rare malignant tumor of fibroblasts, with the involvement of other mesenchymal cells and collagen.

Fibrosarcoma is frequently found in dogs and cats, as well as in other species, incidence being higher in adult and old animals. Breed and sex do not influence it. In young cats, under 4 years of age, fibrosarcoma can be caused by a retrovirus, the feline sarcoma virus (FeSV), which is a spontaneously recombined form of feline leukemia virus (FeLV) [31]. These are the most frequent skin tumors in cats, and the third most frequent tumors, between 20–30% of skin tumors and 13% of oral tumors [125].

5.3.1. Feline postvaccinal fibrosarcoma

ESPLIN et al. (1993) report the appearance of sarcomas, in cats, following vaccination. The authors mention 176 sarcomas, suspected of being postvaccinal. In cats, three types of fibrosarcomas are known: the multicentric form that appears until the age of 4 years, being caused by the feline sarcoma virus (FSV); the solitary form appears in young or old cats, without the intervention of FSV; fibrosarcomas that develop in the soft connective tissue, at the vaccination site. Vaccine induced sarcomas are extremely heterogeneous from a histological point of view, some of them being diagnosed as histiocytomas, others as liposarcomas, even osteosarcomas or chondrosarcomas. These tumors are easy to remove surgically, but the recurrence rate is extremely high, over 70%. Histological, the structure is characterized by nuclear hyperchromatism, multinucleate forms, and anaplasia. Lymphohistiocytic aggregates are often present around the periphery, containing variable amounts of intracytoplasmic grey-brown globular material shown to be vaccine product [155].

In dogs, fibrosarcomas are rare, being found in 8–10 year-old adult animals, but they have also been reported in pups under 12 months of age [97], without being correlated with sex and age; there are observations supporting the higher frequency of fibrosarcomas in the Cocker breed and females [91]. The splenic location is common, being found in 12% of non-vascular and non-lymphoid splenic sarcomas [147]. A rarer location was reported by GRIFFITH et al., 1987, in a dog, a synovial sarcoma of the jaw, with pulmonary metastasis.

Macroscopically, large variations are found, sizes ranging from several centimeters to impressive distorting formations. Usually, there are single, nodular, multinodular tumors, with dermal or subcutaneous location, adherent to subjacent tissues, sometimes ulcerated. In section, they appear poorly delimited, without a capsule, with firm or soft consistency, friable and bleeding, being lobulated and gray-white, with hemorrhagic and/or necrotic areas.

Fibrosarcoma may have extremely different locations in any body region, the limbs, the trunk and the interscapular area being more frequently affected. It frequently produces lymph node and pulmonary metastases.

Histological, a structure usually formed by fibroblasts, collagen and reticulin fibers is found. Tumor cells are fusiform, but they can also be stellate, separated by scarce collagen bundles. Mitoses are usually numerous, nuclei are anisomorphic, with prominent nucleoli, sometimes with the presence of multinucleated giant cells. The cell cytoplasm is poorly colored, varying in shape and size, cell margins are difficult to distinguish. Myxomatous microfoci, bone or cartilaginous metaplasias may be detected in the tumor mass. Fibrosarcomas are highly vascularized, capillaries have fine walls, which determines the presence of numerous hemorrhagic foci (Fig. 5.7.–5.8.).

Fig. 5.7

Fig. 5.7

Fibrosarcoma

Fig. 5.8

Fig. 5.8

Fibrosarcoma

Fibrosarcomas present a rapid infiltrative growth, they recur after surgical excision, but metastases are not very frequent; they are estimated at about 25%. In general, metastasizing occurs by blood route, appearing as secondary tumors especially in the lungs, but also in other organs. Regional lymph node metastases are rare.

The histological criterion of malignancy consists of the assessment of infiltrative growth, anaplastic forms, nuclear pleomorphism and the high mitotic index. The determination of the malignancy grade is difficult, since the subsequent evolution of the neoplasm may surprise by a rapid development with metastasizing, even in the case of poorly cellularized sarcomas, with abundant collagen and low mitotic index.

BOSTOCK and DYE (1979, 1989) established, in the case of fibrosarcomas in dogs and cats, a relation between the mitotic index and the possibility of recurrence or the frequency of metastases, allowing for assessment in two neoplastic grades. After removal, recurrence occurs in 63% of the cases, and the mean survival time is 16 weeks. The authors found a direct relation between the location of the tumor and its potential evolution; thus, fibrosarcomas of the flanks or ears are associated with a longer mean survival time (over 170 weeks), compared to those located in the back, limbs or head. In animals with these locations, euthanasia is required 9 months after surgery, due to recurrences.

The location of fibrosarcomas in the urinary bladder has a high malignancy grade with rapid metastasizing [96].

5.4. HEMANGIOPERICYTOMA

Hemangiopericytoma has been diagnosed in humans, while in animals, the proliferation of pericytes has been questioned. This explains the existence of different designations in the literature, such as: perithelioma, hemangiosarcoma, dermatofibrosarcoma, fibrosarcoma with perithelioma-like structure, etc. [143, 146].

The neoplasm was for the first time described in man in 1942, by STOUT and MURRAY [30], as a proliferation of contractile cells that surround the capillaries, having a vasomotor role.

Hemangiopericytoma was identified as a distinct neoplasm in the dog in 1949, by STOUT [124], subsequently by MULLIGAN, 1955, and by YOST and JONES, 1958. The first reports were considered to be hemangiopericytomas because a proliferation of pericytes could not be proved. Debates and doubts ended in 1986, when by electron microscopic examinations, XU demonstrated the existence of hemangiosarcoma in the dog, with the characteristics of the neoplasm described in man.

The incidence of hemangiopericytoma in dogs is estimated at 3–4% of skin tumors [16], while other authors [4] mention an incidence between 0.3 and 2%. The tumor has also been diagnosed in cats, being considered extremely rare in this species [99]. Some authors contest the existence of hemangiopericytoma in other species than the dog [124]. These authors state that hemangiopericytoma in dogs is rarer compared to mastocytomas, histiocytomas and lipomas, but more frequent than fibromas, fibrosarcomas and hemangiomas.

The tumor is more common in old dogs, between 6 and 14 years of age, with a mean age of 10 years, and a higher incidence is found in females [87, 88], while other authors find this lesion more frequently in males [154]. The breeds predisposed to this neoplasm are: Boxer, German Shepherd, Cocker Spaniel, Terrier, Colley, Beagle, Springer Spaniel [19, 30, 95, 124]. The tumor has been identified more rarely in horses and cattle.

The more frequent locations are cutaneous, on the lateral side of the anterior limbs and on calves; other areas with a lower incidence are: the chest, back, head, neck and tail [30,124]. Cardiac locations have also been diagnosed [4].

The tumor grows slowly, is adherent to tissues, has a firm to hard consistency, white-yellowish color, it is formed by multiple nodules, and in section, necrosed cystic formations or soft nodules may be found. Sometimes, skin is ulcerated at the level of the tumor. The tumor has variable sizes, from 0.5 to 25 cm in diameter [30, 124, 146], and sometimes it may be encapsulated. The tumor generally grows slowly, but progressively, having a local infiltrative character, with rare metastases, but postoperative recurrences.

Histologically, it is characterized by spiral proliferations around blood vessels, with a typical “fingerprint” arrangement of the cells disposed concentrically around the capillaries that are collapsed (Fig. 5.32.). Capillaries are frequently hyalinized. These images are not present in the whole tumor mass, but fascicular proliferations similar to connective tumors with fusiform cells can be noted. These cells are thickened in their middle portion, due to the central ovoid nucleus, with obvious nucleoli, and the cytoplasm, eosinophilic, is in a low amount. Multinucleated cells are exceptional. The cells, but especially the morphology of the nuclei, allow the differentiation from fibroblasts or other mesenchymal cells, which are in general more flattened and elongated [30, 124, 146]. Perivascular lymphocytic infiltrations have been found in 1/4 of the diagnosed hemangiopericytomas. The collagen stroma amount varies widely, sometimes being abundant; necrotic microfoci may be present.

Fig. 5.32. Canine hemangiopericytoma.

Fig. 5.32

Canine hemangiopericytoma.

Electron microscopy has shown cytoplasmic extensions arranged circularly around the capillaries and/or around the collagen bundles and the fibroblasts. No nerves have been found in the spiral proliferation centers. Basal membranes and tight junctions, which are usually present in human hemangiopericytoma and in normal pericytes, are absent in tumor cells in dogs. Cytoplasmic organelles are well developed, the Golgi apparatus is large and obvious, mitochondria are numerous and there is a moderate amount of granular endoplasmic reticulum. A particular aspect is that numerous tumor cells contain a various number of well defined filaments, 120 A in diameter [124].

The evolution of hemangiopericytoma consists of recurrence in 25–60% of cases, after 4 months to 4 years, with a mean of 13 months [46]. In dogs, metastases are rare, usually in the lymph nodes, lungs and liver, and survival is long [14,110].

5.5. OTHER SARCOMAS

These sarcomas are characterized by marked cellular pleomorphism, being formed by undifferentiated reticular cells, epithelial cells and giant cells with multiple nuclei. The mitotic index is high. Among cells, reticulin and collagen fibers are found in variable amounts, and large necrotic foci appear in the tumor mass. Tumor cell infiltrations may be noted in lymphoid nodes, in lymphatic and vascular vessels, forming metastases. It is possible that these tumors may be defined as pleomorphic sarcomas, with few fibers, having a fibroblastic origin [146].

Fibrohistiocytoma is a tumor considered to be of histiocytic origin [30], while other authors [145] suggest the possibility of differentiation from pluripotent primitive mesenchymal cells that can evolve towards fibroblastic and histiocytic cell forms.

According to ENZINGER and WEISS [30], in humans, fibrohistiocytomas are tumors of the deep soft tissues of the adult, located in the extremities, the abdominal cavity and the retroperitoneal area. In 1988, TANIMOTO et al. (1988) considered malignant histiocytoma in humans as rare. The authors described in a 7 year-old cat a histiocytic tumor, in which severe leukocytosis, neutrophilia and absolute lymphopenia were clinically found. Necropsy detected multiple neoplastic masses in the colon, with metastases in lymph nodes. Histologically, neoplastic cells were pleomorphic, with abundant eosinophilic granular cytoplasm and/or vacuoles. Nuclei were large, with prominent nucleoli. The ultramicroscopic, histoenzymological examination, with histiocytic markers, demonstrated the histiocytic origin of the tumor (Fig. 5.10).

Fig. 5.10. Malignant fibrous histiocytoma.

Fig. 5.10

Malignant fibrous histiocytoma. Inflammatory variant.

In animals, fibrohistiocytoma has been described in cats [27, 40, 68] and dogs [43, 136], more frequently in old subjects, with no preference for a certain breed or sex.

Macroscopically, the neoplasm appears as a single or multinodular tumor, of firm consistency, with poorly delimited margins, with variable shapes and sizes [30]. The more frequent locations in both dogs and cats are in the skin of the limbs or even fingers [21, 109], in the neck region [30], more rarely in deep tissues [116]. COCKERELL and MC COY, 1978, described histiocytoma as a benign tumor, present in young dogs, on the face, neck and ears, 0.5–1.5 cm in diameter. Histologically, these are pleomorphic tumors, with large, irregular cells and leukocyte infiltrate. Sometimes, they regress spontaneously; they do not recur postoperatively and do not produce metastases.

The histological structure of fibrohistiocytoma reveals an association in variable proportions of fibroblastic cells with histiocytes. Fibroblasts are fusiform, with eosinophilic cytoplasm, oval-elongated nuclei and obvious nucleoli. Histiocytes are round, with foamy eosinophilic cytoplasm, with occasionally vesicular nuclei. The two cell types are grouped in short, fine and undulated bundles, an aspect considered as characteristic. Multinucleated giant cells have also been noted, as well as inflammatory cells [21, 30, 40] (Fig. 5.9).

Fig. 5.9. Malignant fibrous histiocytoma.

Fig. 5.9

Malignant fibrous histiocytoma.

In humans, different types of histologically defined fibrohistiocytomas have been described: myxoid fibrohistiocytoma, with edematous structure; giant cell fibrohistiocytoma, sometimes similar to osteoclastoma; inflammatory fibrohistiocytoma wxanthosarcoma, with the presence of microvascular xanthomatous and inflammatory cells.

KONISH et al. (1984) proposed the study of histiocytoma in animals, as a model of investigations for man.

5.6. EQUINE SARCOID

This tumor was described by JACKSON in 1936 [124]; the term is used for fibroblastic skin proliferations, found in horses, donkeys and mules. The tumor should be differentiated from papillomas, fibromas and fibrosarcomas. It is a fibroblastic tumor, with local invasion, also having an epithelial component.

Sex, age, breed and skin color do not influence the incidence of the sarcoid. The most frequent location is on the skin of the limbs, trunk and head (eyelids, ears, lips). Tumor formations are usually multiple, more rarely solitary.

The sarcoid may have a sessile verroucous growth, with a dry, horny and cauliflower-like appearance. Sometimes multiple fibrous nodules appear, situated in the subepidermis. In some cases, proliferation is massive, the tumor reaching over 25 cm in diameter, with an ulcerated and bleeding surface.

Histologically, the sarcoid has a dermal and a subepidermal component. The epidermis presents a superficial hyperkeratotic layer and deep proliferations with spinous appearance, penetrating deep into the dermal connective tissue as tentacles. The dermal component is structured of fibroblasts, variable amounts of spirally arranged collagen. Cells are fusiform, nuclei are elongated, with numerous mitoses. The fibroblasts from the dermoepidermal junction are oriented perpendicular to the basal membrane. Ulcerated tumors present a poor development of the epidermis, while in sessile forms, the epidermal component is dominant (Fig. 5.4.5.6.).

Fig. 5.4. Equine sarcoid.

Fig. 5.4

Equine sarcoid. Epidermal and dermal proliferation.

Fig. 5.5. Equine sarcoid.

Fig. 5.5

Equine sarcoid.

Fig. 5.6. Equine sarcoid.

Fig. 5.6

Equine sarcoid.

According to KNOTTENBELT et al. (1995), the morphological classification of the sarcoid differentiates the following forms:

  • occult sarcoid, which is characterized by lesions limited to the surface of the epidermis, has a circular shape and is not covered with hair;
  • verrucous sarcoid, localized but poorly circumscribed, the epidermal component is well developed, it has a rough, uneven surface, with hyperkeratotic areas;
  • –nodular sarcoid, located completely subcutaneously, under the form of nodules of different sizes; the skin covering the neoplasms is thinned and under tension, it can ulcerate and evolve towards the fibroblastic type;
  • –fibroblastic sarcoid, a neoplasm that may be localized, pedunculated, uncircumscribed, sessile and invasive, frequently ulcerated, hemorrhagic and superinfected;
  • mixed sarcoid, which involves the concomitant presence of two or more types of sarcoid;
  • aggressive sarcoid, locally invasive, with the infiltration of regional lymph nodes and lymphatic vessels, without forming, however, real metastases, usually being the continuation of the fibroblastic type.

These forms or types of sarcoids may be considered as stages in the evolution of equine sarcoid.

The etiology of equine sarcoid seems to be elucidated by the researches performed by VOSS (1989) and RAGLAND et al. (1970), who successfully carried out the experimental transmission of the tumor by noncellular extract.

Older observations remarked the high incidence of sarcoids at the sites of contact with the harness, or of small repeated traumas. In 1901, CADEC [124] successfully transmitted the equine sarcoid by autograft. The same authors [124] cite OLSON and COOK who, in 1951, demonstrated that the supernatant from the bovine papilloma tissue inoculated in the horse skin induces fibromas, which suggests a common etiology of the two tumors. The absence of serum neutralization antibodies against the bovine papillomatosis virus is evidenced in horses with sarcoids, while horses with lesions induced by the bovine papillomatosis virus show antibodies.

The attempts of RAGLAND et al. (1970) to induce papillomas in calves, with equine sarcoid extracts, were unsuccessful. By using acellular tumor extract, VOSS (1989) managed to transmit the equine sarcoid after a mean incubation period of 94 days.

Viral-like intracytoplasmic particles, similar to oncoviruses, have been noted in cell lines from equine sarcoids or even natural tumors [124].

The findings of WATSON and LARSON (1974) regarding specific tumor antigens in an equine sarcoid cell line represent additional evidence of the viral etiology of the sarcoid. It may be supposed that the equine sarcoid virus is "masked" within tumor cells, similarly to the case of the bovine papilloma virus.

The genetic factor is incriminated and proved to be a risk factor in the appearance and development of the sarcoid. The predisposition of some subjects descending from a certain female, as well as the association with the major histocompatibility complex, demonstrates genetic control.

The growth of the sarcoid can be of verrucous or fibroblastic type. Verrucous growth is slow, with long stagnation periods, sometimes evolving into a more aggressive fibroblastic type. Sarcoids have a local invasive growth, they do not produce metastases, but frequently recur after surgical removal. Frequently, sarcoids regress spontaneously, over a year-long period [7].

5.7. RARE SKIN TUMORS AND TUMOR-LIKE LESIONS

5.7.1. Cutaneous fibrous polyp

This type of tumor growth is extremely rare. The cutaneous fibrous polyp appears on hairless skin, it has a pedunculated or fungal shape, its basic structure being formed by collagen fibers and few cells. The epidermis covers the tumor and exhibits superficial ulcerations. This lesion is extremely rare [146].

5.7.2. Keloid and hyperplastic scar

The keloid is the result of excessive scar tissue production, the consequence of a hyperreaction of the superficial cutaneous fibroblastic tissue, in response to irritations and traumas, especially burns. It has been found that no exuberant connective tissue is formed in the fibrous tissue covered by mucosae or in the connective tissue that is part of deep structures.

The keloid is structurally characterized by abundant collagen tissue, frequently having a "swollen", enlarged and hyalinized aspect, in which scarce compressed fibroblasts are found. This tissue, during the first stage of its formation, is cellularized and vascularized; later, collagen fibers become expanded and hyalinized, and the superficial fiber bundles tend to be parallel to the surface. As the keloid matures, blood vessels gradually disappear, so that the regenerating connective tissue stops growing.

The epidermis that covers the keloid may have a normal appearance, but usually it is thin, atrophic and sometimes hyperkeratinized; hair fibers, sweat glands and pilosebaceous follicles are generally absent. Although keloids are well-circumscribed nodules, they are not encapsulated, and their tissue intermingles discretely with the normal adjacent dermis.

Following extensive excision, healing may occur, although there is a risk of formation of a young keloid.

5.7.3. Calcinosis circumscripta

Lesions are characterized by a granulomatous aspect, more frequently in young dogs of large size breeds, with location in the skin of the limbs, especially in the subcutaneous pad tissue, above the bone prominences and extremely sporadically in the oral cavity, in the tongue. Structurally, central basophilic granule deposits of calcareous salts are found, surrounded by macrophages and giant cells [146] (Fig. 5.285.30.).

Fig. 5.28. Calcinosis circumscripta.

Fig. 5.28

Calcinosis circumscripta.

Fig. 5.29. Calcinosis circumscripta.

Fig. 5.29

Calcinosis circumscripta.

Fig. 5.30. Calcinosis circumscripta.

Fig. 5.30

Calcinosis circumscripta.

5.8. ADIPOSE TISSUE TUMORS

5.8.1. Lipoma

The tumor has the characteristics of a benign proliferation, formed by mature adipocytes. Lipomas, under the form of fat subcutaneous nodules, are more frequent in dogs, being more rarely found in horses and cattle, and exceptionally in cats, sheep and swine [30].

Incidence is higher in adult and old animals. The mean age in dogs is 8 years. Incidence does not seem to be influenced by breed, although the Cocker, Teckel and Braque breeds are more affected. In contrast, frequency is higher in females, especially in overweight ones, compared to males.

Lipomas may be single or multiple, in most cases being subcutaneous, similarly to human lipomas. The more frequent location, in dogs, is subcutaneous, in the thoracic area, the abdomen, limbs, between muscle bundles, etc. [135]. In horses, we have found it in the mesentery, where it is pedunculated, causing the strangulation of the intestine, colic and death. Similar aspects were described by MC LAUGHLIN and KUZMA, in 1991, in a dog. Pedunculated lipomas of the mesentery caused strangulation, the dilation and necrosis of the jejunum, with peritonitis and death. In cattle, multiple lipomas may appear in the abdominal cavity. Hepatic lipomas have been described in cats [124]. Vaginal and vestibular lipomas are uncommon [17].

In 1988, GILBERT and GRIFFIN [30] described in a 5-year-old castrated Teckel lipomatosis with multiple adipose nodular proliferations of the trunk. In humans, symmetric lipomatosis of the neck, trunk and limbs has been described. A lipoma with intracranial location was reported in a pig by TURNQUIST and MILLER (1993). The authors compared the case with human findings, this location being considered congenital in man.

Macroscopically, lipoma appears as a round, ovoid or flattened tumor, with a lobular structure. In most cases, it is well delimited by a connective capsule, having a soft-elastic consistency. In section, connective trabeculae that dissect the lipoma mass are found, the tumor is white and sticky. It does not adhere to adjacent tissues. Lipomas have a slow growth and do not recur after surgical removal.

Histologically, the tumor is formed by well-differentiated adipocytes, sometimes with necrotic microfoci or even calcareous deposits around which cellular reaction is found. Connective bundles are present in the lipoma mass, which separate the tumor into adipose lobules [30].

Diffuse lipomatosis is a rare form of this tumor and has been diagnosed in dogs, with neck and trunk skin folding aspects. Lipomas infiltrate and mix with the adipose tissue, making difficult the determination of the tumor margins.

Inter- and intramuscular infiltrative lipomas are rare in dogs and exceptional in cats. In dogs, they are found in particular in adult females, being located in the musculature of the trunk and limbs. They appear as soft nodules that are difficult to delimit, involving the subcutaneous adipose tissue, the adjacent musculature and the connective stroma. Infiltrative lipomas are considered to be intermediate malignancy sarcomas. Metastases are extremely rare.

Some lipomas may present abundant stromal connective tissue (fibrolipomas), cartilaginous stroma (chondrolipomas) or an abundant vascular component (angiolipomas). In spite of their benign nature, lipomas tend to increase in volume, and they are clinically difficult to differentiate from liposarcomas.

5.8.2. Liposarcoma

This malignant tumor of the adipose tissue is rare in domestic animals. No breed or sex predisposition has been reported in any species. However, in dogs, a higher incidence has been found in the Teckel and Cocker breeds. Regarding age, similarly to lipoma, liposarcoma appears in adult and old animals, and the most frequent location is also subcutaneous. There are observations [30] according to which the experimental inoculation of the feline leukemia virus (FeLV) in cats causes the appearance of liposarcomas.

TANIMOTO et al. (1987) bring some clarifications regarding liposarcoma in cats, finding by optical microscopy neoplastic cells with hyperchromatic, basophilic nuclei, some cells with a bizarre aspect, with finely granulated, eosinophilic, sometimes vacuolated and/or sudanophilic cytoplasm, pleomorphic liposarcoma. Ultramicroscopically, lipid inclusions appear, which does a membrane delimit, with the presence of few mitochondria and cells with digitiform cytoplasm extensions. Myofibroblasts with dense filaments and inclusions have been identified. Viral C type particles are present in neoplastic cells.

As it has been mentioned, location is more frequent in the subcutaneous connective tissue, but liposarcomas may also exist in the thoracic and abdominal cavity or in deep tissues [102].

The tumor has an infiltrative growth, being formed by round, ovoid, polygonal or fusiform cells. The nucleus of these cells is round, hyperchromatic, and the cytoplasm is more or less abundant, eosinophilic, with numerous small or extremely large lipid vacuoles; anaplastic forms show high aggressiveness, although the mitotic index is not too high (Fig. 5.13).

Fig. 5.13. Liposarcoma.

Fig. 5.13

Liposarcoma.

Like in humans, a great number of histological varieties of liposarcomas have been described, which has determined their classification into subtypes, with variable biological behavior.

Myxoid liposarcoma has been described in dogs [84], being the subtype with the highest incidence in man. In dogs, myxoid liposarcoma is histologically formed by mature or immature stellate or fusiform cells, arranged as loose bundles, in a myxoid mass, with ramified vessels whose endothelia are turgescent.

Sclerosing liposarcoma has been described in dogs, being formed by atypical immature adipocytes, arranged in lobules delimited by fibrous septa.

The evolution of liposarcomas is generally towards local infiltrative growth, and metastases are exceptional, rare or late, being located in the lung and regional lymph nodes. In 1973, BOZARTH and STRAFUSS found pulmonary metastases in one subject of 20 cases of liposarcomas in dogs.

Liposarcomas are characterized by metastases in the lung, spleen, liver and lymph nodes. The authors mention the possibility of the malignant transformation of lipomas, proposing the subdivision of liposarcomas into types with well-differentiated and poorly differentiated cells [112].

The prognosis of liposarcoma is reserved, depending on the characteristics of local growth, histological structure and the risk of postoperative recurrence.

5.9. SMOOTH MUSCLE TUMORS

In general, smooth muscle tumors are rare and they usually have a benign character. The attempts to classify and establish precise norms for the characterization of these tumors encounter difficulties, as there is a real and practical possibility for evolution to create stages in which one tumoral form may transform into another. There is a possibility of error when routine examination is performed by optical microscopy, thus, some neoplasms have been diagnosed as undifferentiated sarcomas, while electron microscopically and/or hystoenzymologically they may appear as muscle tumors [60].

5.9.1. Leiomyoma

The benign tumor of smooth muscle fibers is frequently located in the intestine and the female genital apparatus, especially in carnivores, being rarely mentioned in the skin structure. In 1987, NAKAMURA et al. communicated the presence of an auricular fibroleiomyoma in an 11-month-old pig, which impressed by the rapid evolution, in 10 weeks the tumor reaching 2.1 kg. Leiomyomas are more rarely mentioned but are not excluded in the male genital system. Thus, JOHNSON and STEINBERG (1989) described a leiomyoma in the left testicle of a 7-year-old stallion, and other authors report leiomyomas in the vaginal sheath of dogs. In large animals, leiomyomas represent 1/10–1/12 of all tumors of the female reproduction tract [60].

Leiomyoma appears as a solitary, dense, more or less delimited tumor. When they develop towards the cavities, leiomyomas may be pedunculated, like for example in the uterus, intestine, etc. Intramural development determines relatively well circumscribed nodules, without being encapsulated. In section, the tumor has a pink color and firm consistency. The microscopic structure is characterized by well-differentiated cells with scarce eosinophilic cytoplasm, nuclei centrally arranged; they are significantly elongated, with rounded ends, and collagen is in a low amount. Tumor cells are disposed in bundles, oriented in different planes.

Leiomyoma has a slow evolution, it does not produce metastases, and after removal, it does not recur.

5.9.2. Fibroleiomyoma

Fibroleiomyoma is a benign tumor that is preferentially located in the female genital tract, it is found in dogs and cats, more rarely in the vagina of cows, sheep and goats, almost exclusively in mature females, its growth usually being multicentric.

Fibroleiomyoma has a high incidence, representing 80% of uterine, vaginal and vulvar tumors in dogs, while incidence is much lower in cats [17]. The same authors mention that incidence increases with age, being more frequent around the age of 10 years, in subjects with several parturitions. The Boxer breed occupies by far the first place, compared to other breeds.

Macroscopically, some tumor formations, with vaginal location, may be noted towards the exterior or growth can be intramural, with multiple lenticular aspects. This latter aspect is more frequently found in the uterus and the cervix. The tumor is not well delimited; it has a lighter color than the basic tissue, and in section is similar to the wall of the uterine segment.

Microscopically, it has a structure in which one of the following components is predominant, depending on the different subjects - fibroblastic cells, collagen and smooth muscle fibers. Structure is very close to the normal aspect, only fibers may be arranged in different disoriented planes, and mitoses, although present, are not numerous and have a normal aspect.

Fibroleiomyoma may recur postoperatively, but more frequently excision associated with ovariectomy results in complete healing [60].

5.9.3. Leiomyosarcoma

This malignant tumor of smooth muscle fibers has a high incidence, especially in dogs, representing 20–30% of intestinal tumors in this species. In the spleen, the location of leiomyosarcoma is also extremely frequent [147]. Incidence is not correlated with the animal breed or sex.

An extensive study, performed by KAPATKIN et al. (1992) in 57 dogs with leiomyosarcomas, established 4 groups of primary tumors: in the spleen, in 16 dogs, with a mean age of 10.3 years; in the stomach/ small intestine, in 13 dogs, with a mean age of 10.3 years; in the caecum, in 10 dogs, with a mean age of 11.8 years, and in the liver, in 5 dogs, with a mean age of 9 years. Metastases were only found in dogs with primary leiomyosarcoma in the liver. In the other 3 groups with leiomyosarcoma, no metastases were found in 79% of cases. Survival was over 2 weeks in 64% of cases, the mean survival time in the 3 groups, except for the primary hepatic location, was 10 months; 48 dogs died of metastases, 32% of other causes, and 16% of unknown causes.

Leiomyosarcomas have also been diagnosed in the horse duodenum, with annular proliferation and partial obstruction [78].

Histologically, leiomyosarcoma is characterized by cell bundles, whose nuclei are hypochromatic, significantly elongated, with anaplastic cells, of which some are multinucleated, with a high mitotic index and necrotic microfoci. Due to infiltrative growth, the tumor is poorly delimited. Immunohisto chemical investigations have demonstrated that desmin is a useful marker for the diagnosis of leiomyomas and leiomyosarcomas [3] (Fig. 5.14.).

Fig. 5.14. Leiomyosarcoma.

Fig. 5.14

Leiomyosarcoma. Fascicles of spindloid cells with blunt-ended nuclei.

The evolution of leiomyosarcomas determines metastases in the regional lymph nodes, more rarely in the liver and the lung. Infiltrative growth causes recurrences after surgical removal, requiring a reserved or severe prognosis [30].

5.10. STRIATED MUSCLE TUMORS

Tumor proliferations of striated muscles have a low incidence in animals, although they are relatively easy to induce experimentally [60]. The same author mentions that striated muscle tumors seem to arise from embryonic rests under the form of myonic nodules, in different tissues, also due to the fact that their congenital nature could be proved. Striated muscle tumors may appear in tissues and organs in which there are no striated muscle structures (urinary bladder, kidneys and lungs) or as teratomatous neoplasms of the testicles and ovaries.

Benign forms maintain their characteristics all over the duration of their evolution, without tending to become malignant.

Malignant forms have a marked aggressive and destructive character, with metastasizing and generalization potential, by lymphatic or venous route. The malignant tumors of the striated muscles are characterized by multicentric development.

HULLAND (1987) distinguishes the following tumor forms of the striated muscle: congenital rhabdomyoma; rhabdomyoma; rhabdomyosarcoma; metaplastic rhabdomyosarcoma; rhabdomyosarcoma of the urinary bladder; granular cell myeloblastoma.

5.10.1. Congenital rhabdomyoma

Congenital rhabdomyoma has been reported in cattle, swine and sheep, with cardiac location. Most tumors have been detected neonatally, without a direct relation with the breed, although in pigs, the existence of a predisposition is suggested for certain breed lines [62].

Macroscopically, tumors appear as pedunculated or diffuse formations in the myocardium, frequently located in the interventricular septum, and second most frequently in the ventricles. Myocardial rhabdomyoma has a lighter yellowish or gray-pink color, and in section, the tumor is irregular, with a lobulated or slightly encapsulated aspect.

Microscopically, congenital rhabdomyoma has a variable structure, with the predominance of a population of large mononuclear cells, with abundant vacuolated and fine granular cytoplasm, myoblasts, numerous palisades under the form of cellular bands, other multinucleated cells or clear striations and myofibrils. Fibrosis may be extensive and impregnated with iron and calcium salts [62]. Mitotic forms are rare, which reflects the benign character.

5.10.2. Rhabdomyoma

This benign tumor of striated muscle fibers is extremely rarely found in animals. Histologically, it is formed by well-differentiated cells with hypochromatic vesicular nuclei, arranged in syncytial formations.

The evolution of rhabdomyoma is slow, and after surgical removal it does not recur [30,146].

5.10.3. Rhabdomyosarcoma

This neoplasm is rarely diagnosed in animals, being found in a proportion of up to 2% of splenic cancers, other than vascular and lymphoid [147]. Locations in the nose and sinuses have been described, as well as in the urinary bladder of the dog [96].

An extremely rare case in animals was reported by TEUNISSEN and MISDORP (1968) in a 1.5-year-old dog, a rhabdomyosarcoma located in the urinary bladder neck. In accordance with the literature, the authors suggested the existence of a congenital sensitivity/predisposition in the examined subject.

The necropsy of 7 old Holstein cows diagnosed undifferentiated alveolar rhabdomyosarcoma, with locations in the thoracic and abdominal cavities (lungs, liver, kidneys, adrenal gland and lymph nodes) [80].

Spontaneous rhabdomyosarcoma, in 4-week-old rats, was described by MINATO et al. (1983). The tumor was located subcutaneously, in the lower axillary area, and metastases appeared in the diaphragm. The authors mentioned the presence of numerous mitoses, and fusiform multinucleated cells were ultramicroscopically identified, which contained numerous bands with electron dense filaments and Z lines with a regular transversal arrangement.

Rhabdomyosarcoma has been reported in cows, sheep, horses, dogs and cats, with location in the musculature of the limbs, tongue, pharynx, esophagus, thorax, etc.

Macroscopically, the tumor has variable aspects, under the form of red-gray nodules, and larger formations contain necrotic and/or hemorrhagic foci. Metastases are present in the lymph nodes, lungs, heart, spleen, adrenal glands, kidneys and skeletal muscles.

Microscopically, rhabdomyosarcoma has a variable structure, consisting of embryonic cells, fibroblasts, with sarcoma appearance, or cells with a band-like or anarchic arrangement. Some cells show striations, others are multipolar or ramified. The histological characteristic is represented by the variability of cellular forms and nuclear sizes, with one or two nucleoli, and chromatin in variable amounts. The cytoplasm of these cells is abundant, being vacuolated or granular. Mitoses may be numerous, with irregular forms. The primary tumor, as well as the metastases, exhibit cells with a 2–3–4-fold higher number of chromosomes compared to the normal. Numerous rhabdomyosarcomas contain multinucleated cells, with 2 to 20 nucleoli, sometimes these giant cells being predominant [60] (Fig. 5.15.).

Fig. 5.15. Rhabdomyosarcoma.

Fig. 5.15

Rhabdomyosarcoma.

HORN and ENTERLINE [30] propose the following histological classification of rhabdomyosarcomas in humans:

  • – embryonal type: poorly differentiated, polymorphic cells, with little visible myofibrils; the tumor frequently has, at least locally, a myxoid aspect;
  • – botryoid type: poorly differentiated, dispersed cells; always associated with a mucosa, the tumor has an exophytic, polypous aspect;
  • – alveolar type: poorly differentiated cells, grouped into clusters in the center of which cells are loose, which confers an alveolar aspect; the cellular clusters are separated by fibrous bundles;
  • – polymorphic type: association of small and large, round and anaplastic cells.

There are still many unknown aspects in rhabdomyosarcoma, at least in animals, regarding the evolution and causes that might determine the appearance and development of the tumor.

5.10.4. Metaplastic rhabdomyosarcoma

Metaplastic rhabdomyosarcoma appears in tissues and organs that have no striated muscles, which supposes that this tumor is derived from a group of pluripotent cells that may also be at the origin of smooth muscles.

These tumor forms have been reported in the urinary bladder of young dogs and in the lungs of lambs [96,134]. Considering the young age, the authors suggest the possibility of the origin from pluripotent cells, similar to those covering the Wolffian duct in embryonic development.

Morphologically, some tumors are definitely botryoid. The obvious presence of striated fibers is mentioned, with a high differentiation degree. However, metastases have also been reported [60].

5.10.5. Urinary bladder rhabdomyosarcoma

Striated muscle tumors in the urinary bladder are rare; they appear in young dogs, which suggests the origin from erratic embryonic myoblasts. The cases reported have been found in young dogs, some of which under 18 months of age; large size breeds, Saint Bernard, Danish Dog, Doberman, etc. are the most affected, with a high incidence in females.

Macroscopically, the most frequent location has been found in the bladder neck, more rarely in the ureters. Proliferations are polypous, nodular or under the form of clusters, hard or flaccid, of white-gray to red color, and they frequently present superficial necroses [62].

Microscopically, the tumor is formed by fusiform and polygonal cells, scarce, granulated or eosinophilic fibrillar cytoplasm; cells are frequently multinucleated. Elongated cells are arranged in bands, with a characteristic aspect. The nuclei of the tumor cells are vesicular, with prominent nucleoli, mitoses being obvious.

Metastases are rare, and postoperative recurrences are frequent.

5.10.6. Granular cell myoblastoma

Granular cell myoblastoma or granular cell tumor has been reported in the right atrium of the dog [62], in the dog tongue and the horse larynx [42, 151]. In 1978, BERMAN et al. described a granular cell tumor in the rat, supporting the neurogenic origin of these cells. WILSON et al. (1989) reported the first case of granular cell tumor in a cat, with tonsillar location. The electron microscopic aspect characterized by polygonal cells, with round-oval nuclei, dispersed chromatin, and vesicular structures and electron dense amorphous granules in the cytoplasm justified the diagnosis of granular cell tumor established by these authors.

Regarding the origin of these granular cells, which may become cancerous, there is a debate whether these are myoblastic cells or of neurogenic origin. The studies performed by BERMAN et al. (1978) make these authors maintain, based on the electron microscopic examination of granular cells from rat schwannoma, the neurogenic origin of these tumor cells. The controversies regarding the histogenesis of granular cell tumors have been brought to an end by immunohistochemistry, these cells being neuron-specific enolase positive [148].

Macroscopically, tumors develop invasively, they do not induce metastases, they have a red-yellowish color and are clearly delimited by connective tissue, without being encapsulated.

Microscopically, cells are elongated, with the granular cytoplasm without striations, nuclei are homogeneous and dark, similarly to those of mesenchymal cells. The microscopic structure of the tumor is rich in collagen, muscle fibers, vessels and glands [30].

Granular cell myoblastoma has a low malignancy; consequently, surgical removal is successful.

5.11. BLOOD AND LYMPHATIC VESSEL TUMORS

5.11.1. Hemangioma

Hemangioma is frequent in dogs, especially after the age of 8–9 years, but it has also been diagnosed in young dogs. In Boxer, Airedale, and Scottish breeds and in males, the tumor is more frequent [140]. The tumor has been diagnosed with a lower incidence in other species: horses, cattle, sheep and cats [124]. LOMBARD and LEVESQUE (1964) report cutaneous hemangiomatosis in cattle, suggesting the congenital predisposition of this species to hemangioma. Cutaneous bovine angiomatosis, a benign vasoproliferative lesion seen in young adult cattle; it occurs as single or multiple poorly circumscribed dermal masses, most typically on the back [155].

Macroscopically, hemangioma appears as a single, more rarely multiple tumors, located in the skin of the limbs, flanks, neck, face, scrotum and perineum. In organs, it is more frequently located in the oral mucosa, spleen, liver, lung and heart. Scrotal hemangioma is reported in boars [93]. In horses, location is subcutaneous [49]. Tumors appear as round, well circumscribed, firm or fluctuating masses, of red, cherry or black color, with sizes between 0.5 and 3.0 in diameter. Cutaneous hemangiomas are smaller, with a sessile or pedunculated aspect, and they can be confused with cutaneous melanoma.

Lesions similar to hemangiomas have been described in cattle, dogs and boars. In cattle, cutaneous angiomatous formations are reported. Microscopically, they are found in the dermis, having venular or arteriolar structures, with inflammatory reaction and ulceration. Similar lesions, known as pyogenic granulomas, of staphylococcal etiology, are found in humans.

In dogs, location is in the skin of the scrotum, scrotal vascular hamartoma, more frequently in pigmented breeds. Lesions appear as melanic pigment excrescences. In boars, similar lesions have been noted in scrotal skin, and more rarely in females, in breast skin. Aspect and structure is wart-like.

Blood pools characterize microscopic structure, with vascular septa lined by well-differentiated endothelial cells. Histological, two aspects are distinguished, cavernous and capillary structures [30]. Vascular proliferation is accompanied by fibrosis. Microthrombi may be frequently identified, and connective septa are often hyalinized. The tumor is delimited but is not encapsulated (Fig. 5.16.).

Fig. 5.16. Cavernous hemangioma.

Fig. 5.16

Cavernous hemangioma.

Hemangiomas do not recur after surgical removal. In the case of tumors located in parenchymatous organs, death may occur by internal hemorrhage.

Kaposi-like vascular tumor, a focal or multifocal nodular proliferation of spindle cells forming angular slits in the dermis and submucosa of dogs, with areas identical to the histologic appearance of Kaposi sarcoma in humans. It is extremely rare, and of the few cases seen, all have been in middle-aged-to-old female dogs [155].

5.11.2. Hemangiosarcoma

This tumor is also known as angiosarcoma or hemangioendothelioma, being a neoplasm through the malignant proliferation of vascular endothelium. Incidence is extremely high in dogs and cats, being estimated at 0.3–2% of all tumors [4, 19, 95]. Congenital hemangioma refers to hamartoma and appears subcutaneously, in the spleen, heart, lung and liver [121].

Regarding the incidence of hemangiosarcoma, although some authors have not reported a breed predisposition [124], other researchers [4, 19, 71] have found a higher frequency in large size dogs, such as the German Shepherd, Boxer, English Setter, Pointer breeds, and especially after the age of 8 years. There is no sex predisposition in dogs or cats.

In felines, hemangiosarcoma is found after the age of 10 years, with a 1.5% prevalence of all non-hematopoietic tumors [99]. The literature reports the presence of hemangiosarcomas in other species, such as horses and cattle [142].

Hemangiosarcomas are located with a high frequency in internal organs: spleen, liver, heart, lungs, kidneys; as compared to hemangioma, locations in the subcutaneous connective tissue, muscles, the nasal and oral cavities are rarer [29]. In Beagles dogs, HARGIS et al. (1974) report hemangiomas and hemangiosarcomas in the unpigmented areas of the connective mucosa and in the cornea, suggesting the role of sunrays in the pathogenesis of the lesions.

Hemangiosarcomas appear as single or multiple tumors, with diameters varying from 1 to 10 cm, red-cherry color; they are poorly delimited, unencapsulated, sometimes lobulated, frequently adhering to the neighboring organs. Consistency is soft, fragile; the tumor can break, causing hemorrhage in the internal cavities or tissues, followed by severe anemia. In section, the tumor exhibits a spongy area, of red-gray to red-cherry color, which represents the neoplastic tissue. Hemorrhage, blood pools, sometimes blood clots may be noted. The invasive tumor produces metastases in the regional lymph nodes, as well as in the liver and lung, but also in other organs or tissues (kidneys, muscles, peritoneum, diaphragm and adrenal glands) [19].

In animals with hemangiosarcomas, blood coagulation disorders, inconsistent thrombocytopenia, leukocytosis and neutrophilia are found [19].

Microscopic examination (Fig. 5.175.20) reveals a gap-like vascular structure, with anastomoses, immature endothelial cells, arranged on the basal membrane. Endothelial cells are elongated, with extremely variable sizes and shapes, and marked pleomorphism. Nuclei are ovoid or round and hyperchromatic, with frequent mitoses. The connective stroma varies in amount and is difficult to differentiate from the neoplasm proper. Hemangiosarcoma should be differentiated from fibrosarcoma or anaplastic sarcoma. If necessary, the argentic impregnation of reticulin fibers will be performed, which allows the identification of vascular structures. The presence of cutaneous hemangioma requires the investigation of the organs with possible tumor locations.

Fig. 5.17. Hemangiosarcoma.

Fig. 5.17

Hemangiosarcoma.

Fig. 5.18. Hemangiosarcoma.

Fig. 5.18

Hemangiosarcoma.

Fig. 5.19. Hemangiosarcoma.

Fig. 5.19

Hemangiosarcoma.

Fig. 5.20. Hemangiosarcoma.

Fig. 5.20

Hemangiosarcoma.

The evolution of hemangiosarcoma is usually fatal, due to an extremely rapid growth, metastasizing in organs and tissues, as well as postoperative recurrences. Metastases appear relatively early, they are more frequent in the lung (65%) and the liver (52%), then, in decreasing order, in the heart, kidney, mesentery, intestine, adrenal gland and peritoneum [19]. PATNAIK and LIU, 1977, estimate that 67% of metastases in cats are located in the myocardium.

Radiological diagnosis for pulmonary forms is facilitated by the nodular form, almost all nodules having the same size and relatively small formations, distributed through the whole pulmonary parenchyma. When hemangiosarcomas are present in almost all parenchymatous organs and in tissues, it is very difficult to assess the origin of the primary tumor.

5.11.3. Glomus tumor

Glomus tumors are formed by cells similar to changed smooth muscle cells from the myoarterial glomus, being extremely rare in animals. In man, they are known as being formed by epithelioid angiomatous and neuromatous cells. Cells have a pink cytoplasm, large hypochromatic nuclei, hence the aspect similar to epithelial cells. The types similar to angioma or glomangioma have cells arranged on vascular structures with cavernous aspect, formed by endothelium alone, a resembling in incipient forms normal glomus structures. The neuron-like types are not certainly identified and recognized in dogs, and other glomus tumor forms are unlikely to have been identified in other animal species. Glomangiomyoma is dominated structurally by smooth muscle cells [146].

5.11.4. Lymphangioma

Lymphangiomas are benign tumors, rarely found in animals, being formed by lymphatic capillaries with a cavernous or cystic arrangement [108]. These tumors have been diagnosed in dogs under 1 year of age, but also at ages between 4 and 8 years [123, 138]. The cited authors report more frequent locations in the head, axillary area, posterior feet, retroperitoneal area and mediastinum.

Macroscopically, the tumor appears as a fluctuating mass, from which, in section, a serohemorrhagic fluid flows.

On microscopic examination, gap spaces are found, an extremely fine texture formed by flattened endothelial cells. Histological structure may lend the tumor aspects of capillary, cavernous, cystic lymphangioma, and hemangiolymphoma.

In 1978, STAMBAUCH et al. reported two recurrences, of four dogs with surgically treated lymphangiomas. In 1988, TURREL et al. used radiotherapy in a dog with lymphangioma, without any recurrence within the following 24 months.

5.11.5. Lymphangiosarcoma

This malignant tumor is extremely rare in animals. However, in carnivores, lymphangiosarcoma has been described in both cats and dogs, more frequently at adult age or at a more advanced age [39, 64, 99, 143]. Sporadic cases have been reported in horses, cattle, pigs and rats, with locations in different body areas.

In man, lymphangiosarcoma is extremely frequent (90%) in patients with postsurgical lymphedema after mastectomy in breast tumors, but also after traumatic, idiopathic, congenital or parasitic lymphedemas (filariasis) [30]. SAGARTZ et al. (1994) demonstrated the presence of lymphangiosarcoma in a young dog, which caused limb edema.

Macroscopically, subcutaneous locations appear as edematous, yellowish or whitish masses, with an invasive character, necrotic areas alternating with adipose tissue. Thoracic or abdominal neoplasms have the same edematous character, poorly delimited masses and the thickening of the mediastinum and the mesentery and/or other abdominal folds. In some cases, lymph nodes adjacent to the tumor have been caught in the tumor mass. Distant metastases have been found in the liver and the spleen, with the mention that metastases in lymphangiosarcomas are rare [54].

Histologically, lymphangiosarcoma is formed by an endothelial network separated by connective tissue. The tumor presents the characteristics of malignant vascular proliferation, having hyperplastic vascular regions with gap areas, delimited by malignant cells, and lumens are filled with a clear liquid, without red blood cells (fig. 5.21); the compact proliferation areas are formed by malignant cells, with hyperchromatic nuclei. Lymphangiomatosis, irregular spaces with sinusoidal aspect, are found at the tumor periphery [35]. Histological structure evidences three proliferation types: papilliferous; cavernous; and solid (compact). Papilliferous proliferations develop on a stroma of collagenous connective tissue; tumor cells are round or fusiform, with medium sized nuclei and numerous large nucleoli. In solid growths, cells are fusiform or polygonal, tightly intermingled, with large nuclei, one or more nucleoli and numerous mitoses. Lymphoplasmacytic nodules appear in the tumor structure. In metastatic lymph nodes, neoplastic cells are found in lymphatic sinuses [54].

Fig. 5.21. Lymphangiosarcoma.

Fig. 5.21

Lymphangiosarcoma.

Due to the difficulty in the differentiation of hemangiosarcoma from lymphangiosarcoma, WEISS and SOBIN propose the term angiosarcoma.

Metastasizing may occur early, with generalized dissemination, in the pleurae, lungs, spleen, kidneys and bone marrow [64].

The treatment of lymphangiosarcomas is based on radiotherapy and chemotherapy, as surgical removal is difficult to perform.

Feline ventral abdominal angiosarcoma, an infiltrative endothelial neoplasm, resulting in a diffuse "bruised" appearance to the caudoventral abdominal wall. Histologically, the subcutis in this area is diffusely edematous and hemorrhagic and infiltrated by neoplastic endothelial cells forming clefts and channels, it contains lymphocytes, plasma cells, and hemosiderophages. Angiosarcoma may be a more appropriate name for this uncommon entity [155].

5.12. SYNOVIAL TUMORS

Synovial tumors are rare in domestic animals, being only reported in dogs and cats, with periarticular locations. They usually develop in the articular capsule and/or tendons, but also in the abdominal cavity.

WEISS and SOBIN (1994) describe both benign and malignant forms.

Benign synovial tumors or synoviomas are formed by rounded mononuclear cells and giant osteoclast cells, frequently with the presence of xanthomatous cells, lymphocytes and hemosiderin. The authors describe localized forms, with tenosynovial cells, with growths of well-circumscribed nodules. These formations develop in the sheath of digital tendons.

Diffuse forms, extraarticular pigmented villonodular synovites, are structured as giant cell tumors, under the form of single, multiple or infiltrative masses. Tumors develop on the bursal capsule or in the proximity of the great joints, such as the knee. The above mentioned authors also propose terms such as "extraarticular pigmented villonodular synovitis" and "pigmented villonodular bursitis".

Histologically, DEGORCE and PARODI (1990) suggest the differentiation of 4 forms: a biphasic form, a fibrous type with monophasic forms, an epithelioid type, and a poorly differentiated or anaplastic form.

Malignant synovial tumors are formed by giant cells, being associated with microscopic sarcomatous images. The tumor is similar to malignant fibrous histiocytoma with giant cells (Fig. 6.24). In dogs, the most frequent sites include the stifle, elbow, shoulder, antebrachial-carpal, talocrural, and hip joints. Histologically, these tumors contain spindle-shaped cells and a synovioblastic component that tends to form more epithelioid-type cells, which can sometimes be found lining clefts and tubular cavities. The mitotic index is highly variable [156].

Regarding human synovial tumors, 28–70% produce local recurrences within 2 years and 50% metastasize especially in the lymph nodes, lungs and bone marrow [36].

Synovial tumors in animals require further studies along all scientific lines.

5.13. MASTOCYTOMA

Mastocytoma is a tumor of the subcutaneous connective tissue, but it can also be found in internal organs, in submucosae and the hematopoietic system. The term mastocytoma defines a neoplastic process, as it is known that there is a local reaction, with mast cell agglomerations (edema, allergic reactions, etc.), when the term mastocytosis is used. Mast cells are intensely pleomorphic, they can be fusiform, spherical or stellate, with a round or ovoid nucleus. Cytoplasmic granulations are metachromatic, with toluidine blue.

Mastocytoma in dogs. The highest incidence of mastocytoma is found in dogs; different authors find a frequency that varies between 6 and 8% of all tumors in this species and between 9 and 21% of all cutaneous neoplasms [77,137].

The mean age in dogs with mastocytomas is 8 years, with variations of 4 months to 18 years. Most authors agree that the Boxer breed is clearly predisposed to mastocytoma. Regarding the incidence of mastocytoma in various dog breeds, SIMOES et al. (1994) found that of 31 mastocytomas, 15 dogs (12.5%) were of common breeds, 13 (10.8%) were Boxer dogs, 13 (10.8%) Labrador dogs and 8 dogs (6.7%) of other breeds. Locations were in the thorax, back and abdomen. According to HOTTENDORF and NIELSEN (1967), 45.6% of the examined mastocytomas developed in Boxer dogs. The same authors remarked the general predisposition to tumors, especially to those of the hemolymphopoietic organs, of the Boxer breed, as well as of Boston Terrier and Bull Terrier breeds. Most authors agree that there is no sex dependent sensitivity to mastocytoma.

Mastocytoma has been diagnosed in other species: cats, cattle and horses [75].

Morphoclinically, mastocytoma in dogs presents two aspects:

  1. a solid tumor al form, represented by isolated or multiple cutaneous tumors and localized or isolated extracutaneous tumors;
  2. the diffuse tumoral form or mast cell leukemia is associated with one of the above mentioned solid tumoral forms, with blood generalization of the neoplastic process.

Solid tumoral forms, with cutaneous location may appear as single, isolated, large neoplasms or they can be multicentric neoplasms, with cutaneous generalization all over the body surface. HOTTENDORF and NIELSEN (1967, 1968) found multiple cutaneous mastocytomas in 7% and 14.3% of cases, respectively.

Cutaneous mastocytomas may be located in any body area, but the highest incidence, over 50% of cases, is found in the skin of posterior areas (lumbar area, posterior limbs, genital organs and groin areas). Regarding the location of cutaneous mastocytomas, there is a reverse relation between the number of mast cells located in the skin and the incidence of these neoplasms [137].

Macroscopically, in most of cases, mastocytomas appear as circumscribed, round or ovoid dermal nodules, which are rarely encapsulated. Malignant forms infiltrate subcutaneous tissues, or even deep musculature; sometimes the neoplasm may appear as a large edematous plaque, reaching up to 25 cm in diameter [57]. In section, mastocytoma has a homogeneous white-gray color or hemorrhagic and necrotic foci.

Microscopically, the tumor tissue is formed by cells arranged in cords or compact groups, separated by more or less dense collagen fibers. A massive diffuse infiltration with eosinophilic polynuclear cells, dense plasmocyte and lymphocyte accumulations frequently appears in the tumor mass. This infiltration was observed by HOTTENDORF and NIELSEN (1968) in over 11% of mastocytoma cases.

The majority of tumor mast cells have round or ovoid shapes, but sometimes they can be polygonal or elongated, 6–8 jam in diameter or even larger. The nucleus of mast cells has variable sizes and shapes, sometimes multinucleated giant cells and frequent mitoses may be noted in anaplastic tumors [56, 58,100].

Metachromatic granulations vary in number and size depending on the maturity of mast cells. These granulations are numerous, intensely metachromatic and large in mature cells, while in immature cells they appear pulverulent, poorly colored and with little obvious limits [56,101].

The microscopic image of neoplastic mast cells has allowed to group mastocytomas into three categories: mature, intermediate and anaplastic [124].

Mature forms are made up of round or ovoid mast cells, with uniform sizes, with a well-defined cytoplasmic membrane. Nuclei are uniform and spherical, and cytoplasmic granulations are large and intensely metachromatic. The connective stroma is well represented, sometimes markedly infiltrated with lymphocytes and polymorphonuclear cells (Fig. 5.23).

Fig. 5.23. Mast cell tumor; well-differentiated variant.

Fig. 5.23

Mast cell tumor; well-differentiated variant.

Intermediate forms are characterized by the immaturity of mast cells, large nuclei with mitotic forms (Fig. 5.24, 5.25).

Fig. 5.24. Mast cell tumor; moderately differentiated variant.

Fig. 5.24

Mast cell tumor; moderately differentiated variant.

Fig. 5.25. Mast cell tumor; moderately differentiated variant.

Fig. 5.25

Mast cell tumor; moderately differentiated variant.

Anaplastic mastocytoma presents high cellular polymorphism, with large vesicular nuclei and 1 -3 prominent nucleoli. The cytoplasm contains few immature and poorly colored granulations.

In the stroma of the canine mastocytoma, fibrinoid collagen necrosis and eosinophilic polymorphonuclear infiltration can be seen. Fibrinoid collagen necrosis appears under the form of eosinophilic foci, surrounded by eosinophilic polymorphonuclear cells, histiocytes, plasmocytes and lymphocytes. Eosinophilic polymorphonuclear cells are seen around intratumoral arterioles and venules, while the wall of these vessels undergoes fibrinoid degeneration or parietal sclerosis [56]. According to HOTTENDORF and NIELSEN (1967 and 1968), proteolytic enzymes contained in mast cells are at the origin of necrotic collagen lesions.

The single extracutaneous form has been described at the base of the third eyelid, in the oral and pharyngeal mucosa, lip, gum, palate and nasal septum [100, 137]. HARVEY and SYKES (1982) describe for the first time a mastocytoma located in the tracheal mucosa in a 8-year-old dog. Mastocytomas with other locations have been diagnosed, in the deep femoral muscles and lymph nodes.

The diffuse tumoral form or mast cell leukemia appears relatively rarely in dogs and much more frequently in cats. This form corresponds to a generalized tumor proliferation of malignant mast cells, especially in the lymph nodes, spleen, liver and bone marrow. The first case of mastocytic leukemia in a dog was described as early as 1963, by LOMBARD et al. [137], with the presence of multiple cutaneous mastocytomas, having 59100 leukocytes/mm3, of which 65% neutrophils and 23% tumor mast cells. Mastocytic leukemia was diagnosed in dogs that presented multiple cutaneous mastocytomas, by FOWLER et al. (1966) and ALLAN et al. (1974), in all cases metastases being present in organs and the bone marrow.

The classification of mastocytomas involves the making of diagnosis and prognosis, using extremely precise criteria, such as the diameters of the nuclei and the cytoplasm, the mitotic index, the cellular pleomorphic aspect, the cellularity of the neoplasm and the metachromasia of cytoplasmic granulations. Using these criteria, the authors established 3 grades of mast cell neoplasms: grade 1, poorly differentiated tumors; grade 2, tumors of intermediate or moderate differentiation, and grade 3, well differentiated tumors [56].

Malignant mastocytomas metastasize in the regional lymph nodes and in organs or tissues at distance. In a number of 91 dogs with cutaneous mastocytomas, 69 (76%) developed metastases in regional lymph nodes, 42 (46%) in the spleen, and 37 (41%) in the liver. Metastases were also found in the kidney of 8 dogs (9%), in the heart of 4 dogs (4%) and in the bones of 8 dogs (9%) [57].

Paraneoplastic syndromes. In canine mastocytomas, cutaneous manifestations have been observed, such as cutaneous erythema with pruritus, pruriginous and hemorrhagic wounds. Gastroduodenal ulcers have been reported, attributed to histamine discharges from neoplastic mast cells [22]. HOWARD et al. (1969) found gastrointestinal ulcers in 20 dogs of 24 subjects with cutaneous mastocytomas; more frequently in the stomach and fewer in the duodenum. In 3 subjects, the cause of death was multiple gastric tumors. This hypothesis may be contested by the fact that no mast cell accumulations are found in the ulcerated area, but it is known that epithelial gastric cells are able to produce and secrete histamine. Ulcers are located more frequently in the fundus, pyloric areas and in the first portion of the duodenum.

Coagulation disorders have been found in dogs with mastocytomas [55]. After the removal of cutaneous mastocytomas, the coagulation time has been restored to normal.

In more than 70% of the dogs with mastocytomas, focal glomerulonephritis has been detected, with plasmacytic infiltrate and amorphous material deposits, eosinophils on the basal membranes of the capillaries and the Bowman’s capsule [57]. Microscopic examination reveals pericapsular cellular infiltration, the accumulation of an amorphous, eosinophilic substance on the basal membranes of the glomerular capillaries, and the thickening of the Bowman’s capsule. An autoimmune mechanism may be incriminated in this process.

An increase in alpha-2-globulins and a diminution in the immune response have been noted in dogs with mastocytomas.

The etiology of canine mastocytoma remains uncertain, although LOMBARD, MALONEY and RICKARD [137] successfully transmitted the tumor by acellular infiltrate, suggesting the viral origin of the tumor. The same authors cite RICKARD and POST (1968), who found type C viral particles in the cells of the transmitted tumor. It may be concluded that viral etiology seems to be extremely valid, although the virus could not be identified, which pleads for caution.

The evolution of mastocytoma can be benign or malignant, unpredictable in the majority of cases. Single tumors may be considered benign, and multiple tumors, malignant, but all mastocytomas will be considered as potentially malignant.

For predictive purposes, in 1973, BOSTOCK proposed some criteria for the evaluation of mastocytoma malignancy:

  • – the ratio between the diameter of the nucleus and the total diameter of the cell;
  • – frequency of mitoses;
  • – degree of pleomorphism;
  • – arrangement of cells and tumor cellularization.

The same author proposed the standardization of malignancy, establishing three grades, depending on the histological structure of the neoplasm.

Assessment of mastocytoma malignancy, according to BOSTOCK, 1973

CriteriaGrade I malignantGrade II intermediateGrade III benign
Nucleus/cell diameter0.70.55–0.700.55
Cell peculiarities
  • – basophilic nucleus with irregular shapes
  • – little obvious cytoplasmic outline
  • – poorly basophilic, obvious nucleus
  • – indistinct cytoplasmic outline
  • – regular spherical nucleus
  • – extremely clear cytoplasmic outline
Frequency of mitosesoccasionally frequent mitosesrare mitosesextremely rare mitoses
Grade of pleomorphismmarked pleomorphismless marked pleomorphismmonomorphism
Cellularizationintensely cellularized tumorgrouped cellsdispersed cells

In 1984, PATNAIK et al. proposed another scale for the evaluation of mastocytoma malignancy. The authors considered the following criteria:

  1. tumor invasion degree;
  2. tumor cellularity and cellular morphology;
  3. mitotic index;
  4. nature and intensity of the stromal reaction.

MADEWELL and THEILEN (1987) particularly emphasized the importance of establishing a histological malignancy grade of mastocytoma, in the prediction of prognosis and treatment. This has led to researches and propositions of schemes to facilitate a prognosis close to the evolution of the neoplasm, as well as adequate treatment.

Evaluation of mastocytoma malignancy, according to PATNAIK et al., 1984

CriteriaGrade IGrade IIGrade III
0124
aInfiltration of the dermis and interfollicular spacesInfiltration of the deep dermis and subcutaneous tissue (neighboring muscles and tissues)Infiltration of subcutaneous tissue and deep tissues
b
  • – Cells arranged in short cords or small groups
  • – Well differentiated, round monomorphic cells
  • – Well delimited, abundant cytoplasm, with medium sized granules
  • – Round nucleus with dense chromatin
  • – Variable cellularity, grouped arrangement
  • – Reduced pleomorphism, round– ovoid shape, rare giant cells
  • – Well delimited cytoplasm, with fine granules or poorly delimited cytoplasm with large hyperchromatic granules
  • – Obvious, round nucleus, dispersed chromatin and single nucleolus
  • – Cells in seriate groups
  • – Pleomorphic cells, (round, ovoid, fusiform), numerous giant cells
  • – (Round, ovoid, fusiform) numerous giant cells
  • – Poorly delimited cytoplasm, indistinct fine granules
  • – Obvious nucleus, with vesicles and multiple large nucleoli
cNo mitosesRare mitoses (0–2/field)Frequent mitoses (3–6/field)
dReduced edema and necroses
  • – Diffuse edema and necrotic areas
  • – Fine fibro vascular, fibrocollagenous and hyalinized stroma
  • – Edema, multiple hemorrhages and necroses
  • – Stroma – see grade II

In the same direction, AYL et al. (1992) studied the correlation between DNA ploidy and histological grades, clinical aspects and survival in dogs with mastocytomas. The authors conclude that the correlation of the investigated data allows a prognosis closer to reality. Based on their own experience and by analyzing extensive literature data, the cited authors propose the use of the following therapeutic means: surgical excision, radiotherapy and chemotherapy. These therapies can be applied alone or in complex combinations.

Equine mastocytoma has a lower incidence. The tumor has been diagnosed with basic, ocular and generalized locations, in all cases with a nodular aspect [25, 75,124].

Macroscopically, tumors appear as isolated nodules or as lesional skin areas, subcutaneously and/or in the musculature, sometimes with ulcerations, with a diameter between 2 and 20 cm.

Histologically, the tumor is formed by well differentiated cells, with rare mitoses and necrotic hemorrhagic microfoci, sometimes with mineral deposits. The necrotic coagulation foci with eosinophilia and fibrosis are surrounded by mast cells, capillaries with hypertrophied endothelial cells, and small arterioles show medial fibrinoid degeneration.

The etiology of equine mastocytoma is unknown, and the implication of the Onchocerca sp. parasite could not be proved. The attempt to induce mastocytoma was unsuccessful [25], in contrast, the mentioned authors noted a spontaneous regression of generalized cutaneous mastocytomas, in a foal.

Feline mastocytoma is characterized by two distinct locations: cutaneous mastocytoma and visceral mastocytoma. Incidence in this species is lower than in dogs; it is estimated at between 1 and 9% of all tumors [92, 121] and 2–3% of all skin tumors [28].

Cutaneous mastocytoma appears as multiple lesions, with lymph node and/or visceral metastases. Cutaneous lesions have an aspect of dermal papules or subcutaneous nodules, with diameters varying from several mm to 2 cm. Cutaneous mastocytomas appear at a mean age of 10 years, males being at a higher risk, and they are frequently located in the head and neck. Histologically, cutaneous lesions are characterized by pleomorphic cells, a high nucleus/cytoplasm ratio, the presence of mitoses, nuclei with bizarre forms and the presence of multinucleated mast cells. These aspects may be confused with complex inflammatory eosinophilic granulomas found in this species.

Visceral mastocytoma is relatively frequent in cats, having splenic, hepatic, gastric and duodenal locations. The tumor is clinically associated with anemia, due to ulcerative lesions in the stomach and duodenum, frequently to splenic rupture.

Histological examination does not pose difficulties in making diagnosis. In all forms, mastocytoma is considered as a highly malignant neoplasm, metastasizing and postoperative recurrences being common phenomena.

Mastocytoma in other animal species has been described in cattle, swine and sheep [75,124].

Bovine mastocytoma may represent 3% of skin and subcutaneous tissue tumors. The tumor has been diagnosed in mature animals, without a sex predisposition. Location may be cutaneous or visceral. The cutaneous form has a generalized nodular aspect, a 1–10 cm diameter, nodules are frequently located subcutaneously, with metastases in the regional lymph nodes, liver, spleen, lungs, heart and kidneys.

Histological structure is similar to that of mastocytomas described in dogs and cats.

Swine mastocytoma has an exclusively cutaneous location, under a single or multiple nodular form, 0.5–2.5 cm in diameter. No visceral metastases have been diagnosed.

Ovine mastocytoma has been reported in two subjects, with hepatic location, without it being mentioned whether these were primary tumors or metastases.

5.14. HISTIOCYTOMA

Benign cutaneous histiocytoma is a tumor specific for young dogs, and in 70% of subjects the tumor appears under the age of 4 years. There is a debate whether histiocytoma should be considered a neoplasm or an inflammatory reaction, especially that lymphocytes can have a histiocytic appearance, which determines differentiation into benign and malignant forms.

Incidence seems to be higher in pure breeds, and among these, the Boxer and Teckel breeds are mentioned, without any sex differences.

Cutaneous histiocytoma of the dog appears as a solitary tumor, almost never multiple, being located in the head, neck, foot, frequently and specifically in the ear tips, as a compact, sometimes ulcerated formation, with a rounded shape, like a button, which is well delimited without being encapsulated, of whitish color. Spontaneous regression is frequently noted.

Histologically, the neoplasm is formed by uniform, round or polygonal cells with abundant acidophilic cytoplasm, infiltrated in the dermis or subcutaneously, in collagen fibers and adnexal skin structures. Cells are arranged in dense layers. Nuclei are round or oval, with a slightly eccentric arrangement; binucleate cells are frequently found, and mitotic forms are numerous.

The clarification brought by MAGNOL (1990) is extremely important; following electron microscopic examination and immunolabeling, the author could not prove the histiocytic nature of poorly differentiated cells, suggesting that the exact nature of this tumor remains to be demonstrated.

Systemic histiocytosis is a family disease of Bernese mountain dogs that present perivascular nodular infiltration; apparently, histiocytes are not neoplastic. Skin is frequently affected, as well as peripheral lymph nodes. Lesions are typical for young (2–5-year-old) male dogs.

Histologically, perivascular or vascular parietal nodules of massive or more reduced histiocyte accumulations are found, associated with lymphocytes and granulocytes, and subcutaneous lesions are more drastic, with fibrosis. Similar lesions are found in lymph nodes.

The diagnosis of cutaneous lesions by biopsy is difficult, due to the presence of similar histiocytic infiltrations, in various dermatoses.

Malignant histiocytosis is also a familial tumor form found in Bernese mountain dogs, exclusively in males, and also in their crossbreeds. Malignant histiocytosis affects old dogs (over 7 years of age), having a visceral location, especially in the lung, with pleomorphic and anaplastic histiocyte infiltration, in a fine vascular connective stroma. The presence of multinucleated cells, bizarre nuclei and mitoses is found, aspects completely different from canine histiocytomas and lymphoproliferations [62].

According to MAGNOL (1990), malignant fibrous histiocytoma is found in particular in cats and more rarely in dogs. The tumor appears as a subcutaneous or extremely deep infiltration, down to the muscle masses, with location in the thorax, interscapular area, limbs and pelvic area.

Histologically, the neoplasm originates from pluripotent mesenchymatous cells, which explains the presence of giant cells, cells with fibroblastic and histiocytic aspect (Fig. 5.95.12).

Fig. 5.11. Malignant histiocytoma.

Fig. 5.11

Malignant histiocytoma.

Fig. 5.12. Malignant histiocytoma.

Fig. 5.12

Malignant histiocytoma. Pleomorphic-storiform variant.

This tumor type is highly invasive, with local recurrences, without producing distant metastases.

5.15. TUMORS OF SEROSAL SURFACES (pleura, pericardium, peritoneum, and tunica vaginalis)

Primary tumors of serosal surfaces are rare in the veterinary literature; primary tumors exceptionally appear in the pleura, peritoneum and mediastinum; secondary tumors are also rare.

Histological Classification of Tumors of Serosal Surfaces (Head et al. 2003)

  1. Tumors of Mesothelium
    • 1.1 Benign mesothelioma
      • 1.1.1 Predominantly epithelioid benign mesothelioma
      • 1.1.2 Predominantly fibrous (spindle cell) benign mesothelioma
      • 1.1.3 Biphasic (mixed) benign mesothelioma
    • 1.2 Malignant mesothelioma
      • 1.2.1 Predominantly epithelioid malignant mesothelioma
      • 1.2.2 Predominantly fibrous (spindle cell) malignant mesothelioma
      • 1.2.3 Biphasic (mixed) malignant mesothelioma
  2. Other Primary Tumors
  3. Unclassified Tumors
  4. Secondary Tumors
  5. Tumorlike Lesions
    • 5.1 Tumorlike activated mesothelium

5.15.1. Tumors of mesothelium

Mesotheliomas are mentioned as having a low incidence, but over the last years, the literature has increasingly reported isolated cases or animal groups of various species, diagnosed with these neoplasms. These tumors are of mesodermal origin and are located on the surface of thoracic and/or abdominal serous membranes.

In most cases, mesothelioma is formed by two components, a cellular component, which structurally and functionally consists of epithelial and endothelial cells of mesodermal origin, cells that normally line the pleura, the pericardium and the peritoneum. The second component is connective vascular tissue, whose structure includes fusiform cells, collagen fibers and capillaries. Cells are flattened, but in the different animals, cells may be prismatic, ciliated or epithelial [90].

The incidence of mesothelioma is increasing, both in our cases and in those reported by the literature [149, 128]. A number of congenital mesothelioma cases have been described in calves, THOONEN et al., 1964 and BASKERVILL, 1967 [90] being among the first authors to report them. More recently, SCHAMER et al. (1982) and STÖBER et al. (1990b), WOLFE et al. (1991) histologically diagnosed in 8 meat cattle, over a period of 8 years, mesotheliomas located in 5 cases in the abdomen, in 2 cases in the pleura, and in 1 case in the vaginal sheath. The authors mention that of 737 neoplasms in adult cattle killed in slaughter houses, mesothelioma was diagnosed in 30 bovines. The authors cite SCHAMER et al. (1982), who found 7 mesotheliomas of a total of 592077 meat calves, while COTCHIN (1954) found no mesothelioma of 293 neoplasms diagnosed in old cattle.

Mesotheliomas have been diagnosed in other species as well: dogs, cats, horses and pigs.

In dogs, mesotheliomas have been described in relation or not with asbestosis [75]. LOUPAL (1987) reported 2 cases of sclerosing mesothelioma in German Shepherd dogs. In 1992, DONOUGH et al. mentioned a mesothelioma in a dog, with pericardial location.

Swine mesothelioma was reported in Germany by SEFFNER and FRITZSCH (1964) [90], who found 27 pleural mesotheliomas in 654 slaughtered pigs.

Mesothelioma has also been diagnosed in horses, with pleural or abdominal location [67].

In 1963, CHANDRA et al. communicated the presence of a natural mesothelioma located in the interventricular epicardium of 2 rats, of a total number of 2889 rats examined.

The etiology of mesotheliomas has been associated with asbestos pollution, especially after 1960, when these neoplasms have been described in asbestos workers from South Africa.

Over the past years, data have been collected that suggest the implication of asbestos fibers in the appearance of mesotheliomas in animals. Thus, JUBB, KENNEDY and PALMER (1993) found asbestos fibers in cattle with mesotheliomas, and incidence was high in cattle raised in the proximity of an asbestos mine site, with the mention that the drinking water contained asbestos. Investigations regarding epidemiology, environmental pollution, maintenance and histological classification proved that of 12 bovines with mesotheliomas, 8 were related to asbestos exposure [128, 129]. A similar situation was reported by SMITH, JONES and HUNT (1972), in dogs whose owners worked with asbestos.

The classification of mesothelial tumors takes into consideration the characteristics of the benign or malignant component, as well as histological structure [146].

Benign mesotheliomas:

  • localized fibrous mesothelioma;
  • – multicystic mesothelioma;
  • – adenomatoid mesothelioma or predominantly epithelioid benign mesothelioma;
  • – well differentiated papillary mesothelioma.

Malignant mesotheliomas:

  • localized malignant fibrous mesothelioma;
  • – diffuse mesotheliomas: epithelial, sarcomatoid and biphasic mesotheliomas.

Fibrous mesothelioma. Localized, it manifests as a benign tumor with pleural and/or peritoneal location. Histologically, fusiform fibroblasts are predominant, which are arranged similarly to a vascular pericytoma. Hyalinizations are frequently found in the tumor mass. The aspect and the microscopic structure justify the affirmation that this is a tumor of the submesothelial mesenchyma, which is also supported by the absence of cytokeratin.

Multicystic mesothelioma. It has a benign character and has been diagnosed in the pelvis of young females, as multiple cysts lined by mesothelium, incorporated in a myxoid stroma. This tumor type can be considered as multicystic peritoneal mesothelium.

Adenomatoid mesothelioma, a predominantly benign mesothelioma, is a benign circumscribed tumor, formed by mesothelial cells arranged in papillary cords, a tubular, acinar or solid pattern. In predominantly epithelioid mesotheliomas growing in a more nodular fashion, the epithelioid cells may extend into the underlying stroma in a tubular pattern, which when cut transversely gives a pseudoacinar appearance. Sometimes the epithelioid cells lying in the stroma form solid masses with slitlike spaces, trabeculae or cords; this is the solid pattern. [69]. The stroma in nodules may show foci of chondroplasia, osteoid, or even mineralized bone, reflecting the observation that in culture mesothelial cells are multipotent [157]. Frequent locations are: the spermatic cord, epididymis, uterus and ovary.

Well-differentiated papillary mesothelioma. It is usually multifocal, consisting of papillary formations lined by a layer of well-differentiated mesothelial cells.

Localized malignant fibrous mesothelioma. It is a tumor located in the pleura and the peritoneum, with pleomorphism, mitotic activity and necroses. The microscopic image reveals the characteristics of a malignant tumor.

Diffuse epithelial mesothelioma. It is formed by tubes, acini or layers of atypical mesothelial cells, with diffuse growth in the pleura or the peritoneum. The neoplasm is highly malignant and is found in the case of asbestos exposure.

Diffuse spindle cell sarcomatoid mesothelioma is formed by fusiform cells, which makes it resemble a fibrosarcoma, but it exhibits islands of epithelioid cells, and fusiform cells are immunoreactive to cytokeratin.

Diffuse biphasic mesothelioma. It has a low incidence, having a mixed structure, with both epithelioid and fusiform cells, without the intermingling of the two structures. The microscopic aspect is similar to biphasic synovial sarcoma.

In the study of the microscopic structures of the mesothelioma, STOBER et al. (1990) distinguished papilliferous and tubular structures developing in the stroma, cells being cuboid, tall prismatic and polymorphic. The same authors identified of 12 mesotheliomas in cattle, 8 cases of metastasized cells in regional lymph nodes.

Electron microscopy reveals the presence of intermediate filaments, microvilli, desmosomes, tight junctions and basal membrane in the characteristic structures. Neoplastic submesothelial cells are associated with collagen filaments and some mesothelial cells, structures being extremely well connected [51,128,129].

The histological and electron microscopic study leads to the conclusion that mesothelioma is a neoplasm of mesothelial cells and connective tissue, which proliferate together (Fig. 5.22).

Fig. 5.22. Malignant mesothelioma.

Fig. 5.22

Malignant mesothelioma.

Animal mesothelioma may represent a real "control tower" for the appearance of these neoplasms in humans.

Experimentally prolonged exposure of dogs to mineral dusts, such as asbestos, has produced pulmonary adenocarcinoma and widespread mesothelioma. In addition, pulmonary interstitial fibrosis and pleural fibrotic plaques were found in exposed dogs, without tumors. Asbestos fibers have been demonstrated in the lungs of mesothelioma cases in many species by electron microscopy on ashed or digested blocks of tissue, but ferruginous bodies were seldom found in light microscopic studies [157].

5.15.2. Other primary tumors

A teratoblastoma and several examples of mixed mesechymal neoplasms composed of fibrous tissue and cartilage have been found arising from the omentum and mesentery of calves.

Alveolar rhabdomyosarcoma has been described in the abdomen of an elderly cow and in a dog. In dogs, there are reports of a retroperitoneal lymphangioma and an omental leiomyoma. Examples of lipomas and liposarcomas have been described in several species in a few publications, but records of pedunculate lipomas causing strangulation of the intestines of horses are more common [157].

5.15.3. Secondary tumors

Transcoelomic metastases of adenocarcinoma can be confused with the tubular pattern of epithelioid mesothelioma.

Primary carcinomas of bovine ovary, uterus and intestine, ovine intestine, and canine prostate can be small compared to their extensive transcoelomic metastases [157].

5.15.4. Tumorlike lesions

Tumorlike activated mesothelium, a nonneoplastic proliferation and transformation of pavementtype mesothelial cells into cuboidal or columnar cells. Peritonitis can stimulate activation and can be confused with neoplasia where the causal organisms are few in number (e.g. tuberculosis in cattle) or where they have been mainly eliminated by therapy (e.g. nocardiosis in dogs). Lesions in other organs may point to the cause of mesothelial activation (e.g. feline infectious peritonitis, parasitism in herbivores, or traumatic reticulitis in cattle) [157].

Fig. 5.26. Well-differentiated mast cell tumor; toluidine blue.

Fig. 5.26

Well-differentiated mast cell tumor; toluidine blue..

Fig. 5.27. Mast cell tumor; cytology.

Fig. 5.27

Mast cell tumor; cytology.

Fig. 5.31. Canine hemangiopericytoma.

Fig. 5.31

Canine hemangiopericytoma. *)

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List of Figures 5.1-5.32

Footnotes

*)

Courtesy of W.H.O.

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Copyright © 2007, The Publishing House of the Romanian Academy.
Bookshelf ID: NBK9549

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