8.1.1. Viral filiform papilloma

Oral papilloma is a benign epithelial tumor, induced in dogs and cats by papillomaviruses. The tumor appears in particular in puppies, at a mean age of 1 year, while cutaneous papillomatosis occurs in adult and old dogs. Breed and sex do not seem to influence the tumor incidence. Viral papillomas are small formations, arranged in clusters, they are little aggressive, and may disappear spontaneously in 6–8 weeks.

In most cases, papilloma appears as a multiple tumor, being located in the oral mucosa, tongue, palate, pharynx and epiglottis. Lip papillomas develop much more slowly than papillomas located on the mouth [46].

Macroscopically, the tumor develops under the form of soft, flat, whitish nodules, several mm in diameter, which gradually become pedunculated or cauliflower-like formations. In general, the development of a papilloma is rapid, 2–3 months, but regression may also occur in a short time.

Microscopy shows either a development of spinous cells or a proliferation of basal cells, in both cases the tumor having benign characteristics. The microscopic structure is typically papillomatous, with a thickening of the squamous layer, aspect of epithelial hyperplasia. The spinous layer is hyperplastic, hydropic or with an acidophilic degeneration aspect with little obvious intercellular bridges. The general aspect is of hyperacanthosis of the spinous layer and excessive keratinization [13] (Fig. 8.1.).

Fig. 8.1

Squamous papilloma, lip.

Electron microscopy shows the tumefaction of mitochondria and disorganization of the endoplasmic reticulum. Intracellular chromatin condensation and a maximal production of DNA containing viruses occur. The virus stimulates cellular activity and proliferation, with the formation of papillomas, or it replicates and destroys the cell. The virus replication starts in the generating layer, subsequently the presence of viral particles is observed in the nuclei of the spinous layer cells. The virus rapidly spreads in the nuclei of the cells from the superficial layer of the keratogenic area. Viral particles are much easier to identify in the horny layer. Cells degenerate, they do not multiply, in contrast, they produce viruses [46]. The presence and multiplication of the virus in the superficial cells favor the diffusion and spreading of the disease. Basophilic intranuclear and basophilic intracytoplasmic inclusions can be identified in the spinous cells. The spontaneous transformation of oral papillomas into malignant forms is less frequent; in contrast, they may spontaneously disappear in 6–8 weeks.

In cattle, oral cavity papillomas are induced by type 4 bovine papillomavirus. Locations are morphologically similar to dog papillomas and are considered to be much more frequent than esophageal and reticuloruminal tumors.

In rabbits, oral papillomas are produced by the papovavirus, and they may have a high frequency, but they are less reported and studied by the literature. Papillomas are located on the ventral side of the tongue.

8.1.2. Tumorlike lesions (epulides)

The generic term epulis and the clinical term define masses similar to tumors, located in the gums. Inflammatory lesions are included, as well as hyperplastic growths, such as neoplastic epulides, numerous in dogs and sporadic in cats. A characteristic of hyperplasia and neoplastic epulides is that they can give way to confusions regarding the nature of epithelium and hard tissues originating in the stroma. According to DUBIELZIG et al. (1979), epulides originating from the periodontal ligament may be classified, based on histological criteria, into the following three types: fibromatous; ossifying; and acanthomatous. In the classification proposed by VERSTRAETE et al. (1992), of a number of 154 oral tumors, the authors identify the following forms of epulides in dogs: focal fibrous hyperplasia (43.5%); ameloblastoma (17.5%); odontogenic fibroma (16.9%); and pyogenic granuloma (1.95%). The conclusion is that the clinical description of epulis should be histologically determined, like in the case of humans. Based on the origin and structure of the hyperplastic tissue, BARKER et al. (1993) consider necessary the description of the following forms: pyogenic granuloma; giant cell epulis; gingival vascular hamartoma; fibrous hyperplasia; fibromatous epulis; and acanthomatous epulis.

Pyogenic granuloma in dogs appears as a well circumscribed, red or bluish, sometimes ulcerated formation, located in the gums. The microscopic structure is that of pyogenic granuloma, in chronic forms with abundant, well vascularized connective tissue.

In horses, granuloma has a periodontal origin, it is situated in the dental arch under the form of masses with tumoral aspect, having the structure of granulation tissue.

Gingival vascular hamartoma is a rare congenital abnormality, reported in the gums of young calves. The formation appears on an inflamed surface, being similar to granulation tissue, of pink to red color, under the form of a lobulated mass, frequently with a diameter of several centimeters, pedunculated. It can also be located in the tongue.

Microscopically, the tumor has an irregular vascular structure, with erythrocytes or protein material bordered by well differentiated endothelial cells. Vascular spaces are separated by fibrous stroma. Vascular hamartoma is a benign lesion and requires differential diagnosis with oral papillomatosis and granulomas.

Fibrous hyperplasia or fibrous epulis is the most frequent oral cavity tumor in the gums of the dog, but it has also been occasionally reported in cattle, sheep and felines. Under a multiple and generalized form, it has been described in Boxer dogs, sometimes with a family distribution. Fibrous epulis is frequently associated with periodontal lesions, which are chronic inflammatory reactions.

Histologically, a stromal component of poorly cellularized fibrous connective tissue is found, but epithelial cell nests may also be present. The inflammatory reaction is characterized by monocyte infiltration, with the predominance of plasmacytes, and adjacent epithelium is hyperplastic. At the ulcerated sites, neutrophilic granulocytes, hemorrhages and necroses are present.

Bone metaplasias are found in chronic evolutions.

Fibromatous epulis is a benign multicentric, peripheral odontogenic tumor, of mixed origin, being derived from periodontal epithelial squamous cells and odontogenic epithelium. The lesion is found in dogs and rarely in cats. Brachycephalic dogs have a higher tumor incidence, e.g. 30% of Boxer dogs aged over 5 years have fibrous epulis.

Macroscopically, it is similar to fibrous hyperplasia, from which it can only be differentiated by microscopic examination. Fibromatous epulides have a firm to hard consistency, pink-gray color, a mushroom appearance; they are frequently pedunculated, with a smooth and lobulated surface. In the depth, the lesion reaches the bone, without invading the bone tissue. Ulcerations and infections frequently occur, due to traumas.

Microscopically, fibromatous epulides have a stromal structure, with fibroblast cells and abundant vascularization. The gingival epithelium covers the fibrovascular proliferation and penetrates deeply, under the form of extensions and/or intensely ramified epithelial islands. The origin of these epithelial cells is difficult to establish, they may be derived either from odontogenic epithelium, dental laminar remnants, or they are digitiform expansions of the gingival epithelium from the surface to the depth of the tumor vascular connective tissue. Epithelial cells sporadically produce keratin. Bone metaplasias and calcareous deposits are frequently identified in the tumor stroma, under the form of osteoid or mature lamellar trabeculae. Bone tissue lies in a highly cellularized matrix, which frequently exhibits collagen and hyaline islands. This complex structure of stroma, bone tissue and epithelial cells suggests the origin in the odontogenic epithelium [46].

Fibromatous epulis is a benign tumor, after removal it does not recur and healing is obtained.

Acanthomatous epulis develops in the gums from epithelial cells, invading the dental alveolus, it has a papillary or sessile appearance, gray-pink color. Incidence in dogs is relatively high, up to 76% of all epulis forms being mentioned [66].

Microscopically, the tumor has an epithelial structure, under the form of layers, nodules and anastomosed bands, of cuboid or columnar cells, with round or oval nuclei and a moderate cytoplasm amount. Intercellular bridges are only found in some polyhedral cells from the tumor center. Sometimes epithelial cysts with eosinophilic material and cell remnats appear. The stroma is fine, among epithelial cell groups. Mitoses may be occasionally noted [1]. The authors underscore the difficulty of differential diagnosis with fibromatous epulis.

8.1.3. Squamous cell carcinoma

Squamous cell carcinoma has a high frequency, being located in cats on the ventral side of the tongue and in the gums, while in dogs, this neoplasm is second most frequent, after melanoma, with gingival and tonsillar location. The neoplasm has been diagnosed with a lower incidence in horses and cattle, exceptionally in sheep.

Squamous cell carcinoma in cats occurs in adult subjects, over 5 years old, the usual location being in the tonsils, gums and tongue [6, 22]. Macroscopically, the tumor is irregularly shaped, appearing as small, friable, red-gray nodules, it frequently presents ulcers on its surface, and it may be associated with inflammatory phenomena. The microscopic structure is characteristic of this neoplasm, with local invasive growth that can reach the bone, developing frequent metastases in regional lymph nodes and more rarely in the lungs.

Squamous cell carcinoma in dogs is an oral neoplasm with a high incidence, with tonsillar and gingival location. The tonsillar location is usually unilateral, with the aspect of a small granular plaque, on the mucosal surface. In advanced forms, the tonsil doubles its volume, it has a nodular appearance, it is firm, white and frequently ulcerated. Histologically, infiltrative growth is found, in the depth of tonsillar structures. Metastases occur in regional lymph nodes, but also at distance, especially in the lung. Gingival location is usually associated with chronic periodontitis. The tumor is located at the base of incisors and canines, with local invasion to the bone. Other locations may be in the labial, palatal and pharyngeal mucosa (Fig. 8.2, 8.3).

Fig. 8.2

Squamous carcinoma, tongue, cat.

Fig. 8.3

Squamous cell carcinoma, rumen.

Squamous cell carcinoma in horses is not too frequent, it has gingival and palatal locations, and is associated with chronic inflammations. The neoplasm is extensively ulcerated or crateriform, and infiltrative growth affects the bone or even extends to the nasal, orbital cavities and the cranial box.

The squamous cell carcinoma of the oral cavity in cattle is more rarely found, and it can be associated with oral papillomatosis. Other locations can be in the esophagus and forestomach. The neoplasm has been sporadically diagnosed in the lip mucosa of sheep [1, 33, 34].

In cattle and dogs, viral papillomas can undergo malignant transformation. In cats, FIV, FeLV and FSV may play a role. Chronic inflammation stimulates squamous metaplasia that may be promoted to squamous cell carcinoma by ingestion of a carcinogen. Immunosuppressive agents allow transformed cells to become an established neoplasm [71].

8.1.4. Verrucous (squamous) carcinoma (papillary squamous cell carcinoma)

A low-grade malignant tumor composed of well-differentiated papillary squamous epithelium overlying and continuous with a well-differentiated squamous cell carcinoma. This rare tumor has been described in the premolar gingiva of puppies under 6 months of age. The tumor is invasive on a broad front and causes osteolysis, but metastases and recurrence are unlikely [71].

8.1.5. Melanocytic tumors

Melanic tumors are the most frequent oral tumors in dogs and in their great majority have a malignant evolution [15, 29]. Locations are mainly in the lips, palate and gums, metastases occur extremely rapidly, and mortality is of 80% one year after treatment [45]. The more frequent locations are in the lips, gums, oral and palatal mucosa, extremely rarely in the tongue. Incidence seems to be higher in males, especially in breeds with pigmented oral mucosa and colored hair, so that the more affected breeds are: Terrier, Cocker, Shepherd and possibly Airedale dogs. In other species, cutaneous melanomas are frequent in horses and some pig breeds, but they are rare in the oral cavity. Likewise, these tumors are rare in cats [54].

Malignant melanoma

Tumors can be subdivided into 3 patterns on the basis of shape: 1) the cells of an epithelioid tumor are round to polygonal; 2) the cells in a spindle cell tumor resemble fibroblasts; and 3) mixed tumors show both cell types [71].

Macroscopically, melanomas grow rapidly, necroses and ulcerations are frequent, and in 70–90% of cases, they metastasize in the regional and more frequently in the submandibular lymph nodes.

Histologically, the neoplasm has the characteristics of melanoma, being either the highli melanotic type or the highly anaplastic amelanotic type. Of a total of 117 oral cavity tumors, DELVERDIER et al. (1991) diagnosed 29 melanomas, of which 8 were achromated. These peculiarities can make diagnosis difficult. Amelanotic malignant melanoma can be identified using Fontana-Masson silver stain, the DOPA reaction, immunohistochemistry or TEM to show the melanosomes [71]. Anaplastic melanocytes are large, with oval or elongated nuclei, with obvious nucleoli and abundant cytoplasm, with junctional activity, junctional infiltration between basal cells and in the submucosa.

Frequently, these are characterized by a mixed structure of epithelial-like cells and fusiform cells (Fig. 8.4), with a tendency to form cellular nests in the submucosa. Multinucleated cells have been noted. Normally, metastases are pigmented, but there are numerous cases in which primary tumors are pigmented and metastases are unpigmented, as well as the other way round.

Fig. 8.4

Malignant melanoma.

Oral cavity melanomas can be microscopically identified under the form of the following types: epithelioid type; spindle cell type; and mixed type, with epithelioid and fusiform cells [1, 33,34].

8.1.6. Fibroma and fibrosarcoma

Fibroma, with oral location, appears as a well circumscribed tumor, having the known microscopic characteristics of mature connective tissue, with numerous collagen fibers; the term fibroma mole is used when cells exceed collagen and fibroma durum when collagen fibers predominate. Incidence can be moderate in companion and production animals, except for swine [33, 34].

Fibrosarcoma is considered the third most frequent neoplasm in dogs, and the most common sarcoma of the oral cavity. The tumor is common in early life, being found in 25% of cases in dogs under 5 years of age. The more frequent locations are in the gums, around the upper molars, in the palate, in the upper mandibular third, in the oral mucosa, lips, tongue and palate.

The neoplasm frequently affects local bone tissue, by infiltrative growth. Growth is rapid and recurrences are common after excision. Metastases in the regional lymph nodes are around 35%, and pulmonary metastases are frequent.

In cats, this neoplasm is the second most frequent of all malignant oropharyngeal tumors. The most common locations are in the gums, on the ventral side of the tongue and the palate. Similarly to fibrosarcoma in dogs, bone invasion is also frequent in cats. Macroscopically, the tumor has a gray to red color, a large size, it is firm, with irregular shapes, generally nodular, with ulcerations and secondary infections.

Microscopically, the submucosa presents an extensive diffuse infiltration of pleomorphic fibroblasts, arranged in bands, separated by collagen. The tumor is more cellular with less collagen and reticulin fibers surrounding the cells, there is more cellular pleomorphism (fusiform, ovoid and stellate cells), both nuclei and nucleoli are larger, there are more mitoses and the nuclei are pleomorphic, multinucleate giant cells may be seen, and areas of hemorrhage and necrosis are more common; tumors are locally invasive but have few metastases [1, 71].

8.1.7. Leiomyoma and leiomyosarcoma

There are very rare reports of solitary nodules of leiomyoma in the mouths of dogs, cats and cattle; leiomyosarcomas of the canine tongue have been reported.

Leiomyoma, a benign tumor of strap-shaped smooth muscle cells with intracytoplasmic myofibrils. Macroscopically, it has a distinct border but no fibrous capsule. Histologically, it is composed of bundles of strap-shaped cells with ample eosinophilic cytoplasm. The bundles intersect at sharp angles. When cut longitudinally, the elongated nuclei have rounded blunt ends; when cut tangentially both cytoplasm and nucleus are spindloid; when cut transversely the nuclei are central. Mitoses are very rare. Van Gieson's or Masson's trichrome stains can be used to demonstrate the fibrous stroma [71].

Leiomyosarcoma, a malignant tumor with some areas of recognizable smooth muscle differentiation. The remarks concerning differentiation between fibroma and fibrosarcoma, and the behavior of malignant tumors, apply equally to smooth muscle tumor. When most of the tumor is poorly differentiated it might be confused with granular cell tumor or oncocytoma, but immunohistochemistry and electron microscopy can be used to establish a diagnosis [71].

8.1.8. Rhabdomyoma and rhabdomyosarcoma

Rhabdomyomatous tumors are rare in the upper alimentary tract of animals, but a few examples have been described in the tongue, cheek, jaw, pharynx and esophagus in the horse, cat, and most often in the dog.

Rhabdomyoma, a benign tumor composed of cells in which intracellular myofibrils with cross striations are fairly easily found. The cells are large, pleomorphic and polygonal with much cytoplasm that is rich in eosinophilic granules and vacuoles. The latter are periodic acid-Schiff (PAS)-positive and diastase-sensitive. There are 1 or 2 central round to oval nuclei but few mitoses [71].

8.1.9. Mastocytoma

Oral cavity mastocytoma is sporadically found in dogs and cats. The oral tumor can be the result of the extension of a cutaneous mastocytoma, especially from the lips, but it can initially develop in the oral epithelial tissue, frequently in the tongue, in dogs. Malignancy also manifests by metastases in regional lymph nodes.

In cats, differential diagnosis with eosinophilic granuloma, located in the lip, tongue and anterior foot will be considered. The histological examination of mastocytoma should be performed as soon as possible after death or biopsy sampling, since autolytic changes make evidencing granulations difficult [1, 33, 34].

8.1.10. Granular cell tumors

Granular cell tumors or myoblastomas have been diagnosed in dogs and cats, with locations in the tongue and gums, generally in old subjects. The origin of granular cells is considered to be interstitial fibroblasts, but also multipotential cells, such as Schwann cell precursors and granular cells. These tumors may have a benign evolution and manifestations, but they can have all the characteristics of malignancy. The possibility of a malignant evolution of a benign tumor is not excluded.

Macroscopically, the tumor bulges slightly, it is red, with granular or smooth surface, and in section it is white and firm. Microscopy shows the presence of large, round or polygonal epithelial cells, with numerous eosinophilic granules in the cytoplasm. Granulations are intensely PAS-positive. Nuclei are round or oval, central or eccentric, with one or two obvious nucleoli. In malignant forms, a more marked cellular pleomorphism and a higher mitotic index is found. Granular cells tend to form nests or cords, separated by fine reticulin fibers (Fig. 8.19).

Fig. 8.19

Granular cell tumor, tongue.

Myoblastoma does not recur after excision, nor does it produce metastases.

8.1.11. Other oral cavity tumors

The complex structure of the oral cavity allows the development of tumors in its components; the benign and malignant tumors of these structures have been extensively described in the chapters dealing with the neoplasms of the tissues concerned.

Hemangioma, a benign, circumscribed, but not encapsulated tumor of well-differentiated endothelial cells forming blood-filled vascular channels; the vessels may be as small as capillaries - capillary hemangioma, or large and cavernous -cavernous hemangioma [71].

Hemangiosarcoma or malignant hemangioendothelioma, a malignant tumor of pleomorphic endothelial cells; the vascular structures that are found contain blood and are often lined by more than one layer of cells. Hemangiosarcomas have been seen in the gingiva of the horse, the tongue and gum of old dogs, and the tongue, gum and palate of the cat [71].

Hemangiopericytoma, a malignant tumor, composed of round to spindloid cells forming whorls around vessels that are lined by a single layer of endothelium. Rare examples have been recorded in the tongue and gum of elderly dogs [71].

Hemangioendothelioma, a benign tumor formed mainly by uniform differentiated endothelial cells with only occasional capillary or cavernous vessels; very few mitoses are present. Rare examples have been recorded in the tongue and gum of old dogs and cats [71].

Systemic hemangiomatosis or disseminated cavernous hemangioma, a benign tumor characterized by multicentric hemangioma in several organs. Cases have been observed involving the tongue and gums as well as other organs in young calves [71].

Lymphangioma, a benign nonencapsulated tumor of lymphatic endothelium. Examples have been seen in the tongue of cats and pharynx of dogs [71].

Rare cases of other oral cavity tumors have been recorded in all species:

• bone and cartilaginous tissue tumors: osteoma; ossifying fibroma; myxoma; chondroma; osteosarcoma; chondrosarcoma; multilobular tumor of bone;
• peripheral nerve tumors: malignant schwannoma; neurofibrosarcoma;
• granular cell tumors: benign granular cell tumor; malignant granular cell tumor;
• neuroendocrine tumors: neuroendocrine carcinoma;
• tumorlike lesions: fibrous dysplasia; craniomandibular osteopathy; lymphoid hyperplasia; nasopharyngeal polyp; eosinophilic granuloma; calcinosis circumscripta.

8.2.1. Ameloblastoma

For the term ameloblastoma or adamantinoma, the recent literature suggests the designation acanthomatous epulis [1]. The term ameloblastoma is proposed to be used instead of the synonym adamantinoma or enameloblastoma. The tumor is benign and has been described in horses, dogs, cats, cattle, sheep and other species; however, incidence is low [20, 31, 29, 41, 61, 63, 65].

In veterinary medicine, according to NOLD et al. (1984), the notion ameloblastic odontoma is used, but human medicine differentiates two entities: ameloblastic fibroodontoma, which contains dentin and enamel; odontoameloblastoma, an ameloblastoma that also contains dentin and enamel formations. This subclassification cannot be applied to domestic animals, due to insufficient cases.

The tumor has been reported in adult animals, sporadically in young subjects, congenital ameloblastoma in calves [12], without any particular breed or sex influence. An ameloblastic odontoma has been diagnosed in a 2 month-old British Spaniel puppy [40] and a congenital form in a foal [42].

In both dogs and cattle, location is more frequent in the mandible than the maxilla, the tumor being more rarely reported in cats and horses. Macroscopically, ameloblastoma locally deforms the mandible or emerges at the gingival surface, it has a spherical, ovoid or multinodular shape, 2–5 cm in diameter, and is covered by mucosa, which is frequently ulcerated. The surface is rough, the tumor is dense, and in section it is cystic, sometimes containing bony or calcified granulations; color is white-gray or red.

Histologically, ameloblastoma is characterized by odontogenic epithelium, arranged in solid bundles and groups in a dense fibrous structure, with the total absence of enamel, dentin and cement. Epithelial cell islands or groups are delimited by a peripheral layer of characteristic tall columnar cells, with elongated nuclei. Sometimes, epithelial cells in the center of these islands have a squamous appearance, with the presence of keratin, which makes difficult differentiation from a squamous cell carcinoma. Some ameloblastoma forms are difficult to differentiate from epulides, in fact ameloblastoma represents an epithelial excrescence of an epulis [19, 25] (Fig. 8.13–8.15).

Fig. 8.13

Ameloblastoma.

Fig. 8.14

Ameloblastoma.

Fig. 8.15

Ameloblastoma.

Ameloblastoma has a local invasive growth, it frequently recurs following excision, and is similar to a low malignancy neoplasm. It invades the bone tissue, inducing osteolysis, with tooth loss.

8.2.2. Amyloid-producing odontogenic tumor or calcifying epithelial odontogenic tumor

Calcifying epithelial odontogenic tumors are rare benign forms, with unencapsulated gingival masses, found in dogs and cats. These tumors are characterized by a dental type epithelium, with the mineralization of the epithelium and stroma, with amyloid or amyloid-like deposits in the epithelium and stroma [41]. The epithelium is arranged in layers, nests or masses containing stellate reticulum spaces. Epithelial cells are large, polyhedral, with visible intercellular bridges lying in a fibrous stroma. Mineralization occurs under the form of small nodules, rings or amorphous masses. Amyloids may be nodular or amorphous, dispersed in the mineral mass. Osteoid/dentinoid trabeculae, similar to human calcifying epithelial odontogenic tumors, may appear in the tumor mass [67].

8.2.3. Canine acanthomatous ameloblastoma (acanthomatous epulis)

A distinctive aggressive tumor of the canine jaw that is characterized by the presence of interconnected sheets of odontogenic epithelium with palisaded outer epithelium and stellate reticulum-like acanthocytes away from the palisaded epithelium. Tumors are recognized as irregular verrucous masses adjacent to the tooth.

A characteristic feature of this tumor is the presence of interconnected sheets of odontogenic epithelium, characterized by easily distinguishable peripheral palisading of epithelial cells and abundant central acanthocytes with prominent intercellular bridges extending across the exaggerated extracellular space. Cyst formation is a common feature of the epithelium; keratinization or keratin pearl formation is rare; neoplastic epithelial cells show aggressive infiltration into surrounding bone. Acanthomatous ameloblastoma previously has been called acanthomatous epulis, peripheral ameloblastoma, basal cell carcinoma, and adamantinoma [71].

8.3.1. Ameloblastic fibroma

Ameloblastic fibroma or ameloblastoflbroma is a tumor whose structure includes both the epithelial and mesenchymal components, having a low incidence. It has been reported in cattle, with more abundant bone or connective tissue of the maxilla in young cows. Epithelial cords are similar to dental lamina, closely associated with pulp-like fusiform stromal cells, collagen is in a low amount [1, 33, 34].

Ameloblastic fibroma, also reported in young cats (under 1.5 years), is described as an epithelial odontogenic tumor with mesenchymal changes and is poorly differentiated. Odontogenic epithelium is arranged in cords and islands, some of which suggesting a cup-like structure, similar to dental enamel. The connective tissue is well cellularized with numerous fibroblasts suggesting dental papillae. The groups of epithelial cells are delimited by a basal membrane from the mesenchyme. Mesenchymal proliferation is well represented in the proximity of the epithelium and especially in cup-shaped invaginations [17,18, 69].

Ameloblastic fibroma behaves like a benign tumor, it does not recur following excision, and does not develop metastases.

8.3.2. Ameloblastic fibro-odontoma

Ameloblastic odontoma is similar to ameloblastic fibroma, but its structure contains dentin and enamel, and epithelium is more typical of enamel tissue. It has been diagnosed in horses, cattle and dogs, in young subjects. The tumor may be considered a complex or compound odontoma by ameloblastic tissue overlapping. Ameloblastic odontoma is formed by bundles of epithelial-like neoplastic tissue, by connective stroma with mixed enamel and dentin. Complex structures, similar to dental buds or supernumerary teeth, may also be found. Ameloblastic epithelial islands and irregular trabeculae with bony appearance are frequently found, which are distributed in the connective tissue stroma. Sometimes, odontoblasts are difficult to differentiate from ameloblasts, although both dentin and enamel are formed [44, 46] (Fig. 8.16, 8.17).

Fig. 8.16

Odonto - ameloblastoma.

Fig. 8.17

Odonto - ameloblastoma.

8.3.3. Feline inductive odontogenic tumor

A rare tumor of young cats that can occur in the central or peripheral tissue of the maxilla or mandible and is characterized by the presence of odontogenic epithelium and aggregated foci of collagen-poor primitive mesenchyme resembling dental pulp. Mesenchymal foci are characteristically situated adjacent to neoplastic epithelium, sometimes surrounded by epithelium in a pattern reminiscent of the cap stage of odontogenesis. These tumors are locally infiltrative and require complete excision; however, there is no known metastatic potential. Feline inductive odontogenic tumor is a tumor unique to cats with a distinct microscopic morphology [71].

8.3.4. Complex odontoma

A mass lesion with fully differentiated dental components that do not form tooth-like structures. Complex odontoma has been reported in young animals of different species, including horses, dogs, rodents, and primates. Histologically, the tumor is characterized by the presence of well-differentiated dentinal tissue, including dentin, enamel matrix, odontogenic epithelium resembling the enamel organ, and cementum in horse and rodents. Some authors consider this lesion to be a hamartoma rather than a neoplasm [71].

8.3.5. Compound odontoma

This odontoma is a malformation, more correctly designated as a hamartoma and not a neoplasm; all dental tissues are present, in a disorderly arrangement. Microscopically, layers of odontoma, enamel, dentin, cement and pulp are identified. Some tumors contain ameloblastic epithelium and separately, complex areas of compound odontoma, which is an odontomeloblastoma (Fig. 8.18). It is frequently located in the mandible or the maxilla and it is rare in cattle and horses, sporadic in other species. The tumor origin may be at the site of supernumerary teeth [33, 69, 71].

Fig. 8.18

Complex odontoma.

8.4.1. Cementoma

A benign mass of excess cementum around the tooth roots. Cementoma is seen as a local mass-like deposition of differentiated cemental matrix around the tooth root. Tumors are seen in dogs, cats, and herbivores, and can be associated with dental displacement, dental loss, and periodontal inflammation, a reactive hyperplasia; truly neoplastic lesions can also occur with proliferating cellular cementum [71].

8.4.2. Cementifying fibroma

A rare tumor analogous to ossifying fibroma; however, the matrix component has features suggestive of cemental differentiation, including complex basophilic lines in a mosaic pattern or, in some cases, a lamellar pattern typical of cementum; seen in horses and dogs. It is composed mainly of mesenchyme with a collagen matrix and intermittent foci of cemental differentiation. These tumors are locally aggressive with indistinct margins and require wide excision [71].

8.5.1. Fibromatous epulis of periodontal ligament origin

A gingival growth composed primarily of periodontal ligament-type stroma, characterized by the presence of regularly positioned stellate mesenchymal cells, smooth fibrillar collagen matrix, and regularly positioned dilated and usually empty blood vessels. Other features often present are cords of odontogenic epithelium and cell-poor collagen matrix resembling alveolar bone, cementum, or even dentin.

Fibromatous epulis of periodontal ligament origin is a common tumor, usually seen in dogs of any age, especially in Boxer dogs, sometimes with a family distribution, and in young cats. Surface ulceration and secondary inflammation can occur due to exposure. Histologically, the distinguishing feature is the presence of stroma that is similar to periodontal ligament and is characterized by regularly positioned stellate mesenchymal cells, abundant collagen matrix composed of small fibrillar collagen fibers which are distinctly different from the coarse fibers seen in normal gingival connective tissue, and regularly positioned dilated blood vessels which seldom contain blood cells. A distinct feature of bone-like matrix in fibromatous epulis is the presence of Sharpey's fibers deeply embedded in the matrix extending into the surrounding fibrillar collagen stroma. This is a characteristic feature of both cementum and alveolar bone. The epithelial cords are thought to arise from the cell rests of Malassez, but they can also connect with the surface gingival epithelium (see 8.1.2). The same peripheral odontogenic fibroma has been suggested because of the similarity to a human tumor with the same name [71].

8.6.1. Dentigerous cyst

An epithelium-lined cyst formed around tooth remnants; they are extremely rare in dogs and cats. Dentigerous cysts develop when the reduced enamel epithelium (odontogenic epithelium) is retained. The cyst cavity contains liquid secretion and the cysts are lined by a stratified squamous epithelium [71].

8.6.2. Radicular cyst

Squamous-lined epithelial cyst found adjacent to the tooth root. Radicular cysts are thought to be reactive hyperplastic lesions associated with inflammatory disease or trauma. The epithelial component of the radicular cyst is thought to be derived from the cell rests of Malassez adjacent to the tooth root within the periodontal ligament. These cysts have been seen in horses, cats, and rabbits [71].

8.6.3. Ovine odontogenic cyst

Radiolucent cystic lesion in the proximal mandible adjacent to the incisors of mature female sheep; characterized by stratified squamous epithelium overlying a thin layer of alveolar bone. The permanent incisors are often displaced and dental elements, including fully formed teeth and especially cementum, are often found in the cyst lumen. These lesions have been reported in New Zealand, Scotland, and England [71].

8.6.4. Temporal teratoma in horses

A congenital malformation found almost exclusively in young horses, which develops in the period of formation of permanent teeth. This malformation can appear in erratic locations, in the temporal area, at the ear base, but also in the dental arches. The lesion contains a tooth crown or root, in a cystic cavity. Sometimes the cyst may contain remnants of several tooth germs. Teeth can be macroscopically identified as molars, being well anchored, or they can be free. In time, the cyst may open and become infected. Microscopically, these teeth have the normal structure of a tooth, containing enamel, cement and dentin, in variable amounts. The cyst is lined by multistratified squamous epithelium [33, 34, 46].

8.7.1. Odontogenic dysplasia in aging rodents and lagomorphs

The disorganized development of the continuously erupting incisor teeth of rodents and lagomorphs. Inflammation, trauma, toxicosis, or age alone can lead to a disorganized development and tumorlike dysplasia at the base of the incisors. In some populations, as many as 25% of aged rodents are affected. Histologically, the decalcified section of the dysplastic segment reveals disorganized tissue proliferation an dysplastic differentiation of odontogenic elements, including odontogenic epithelium, enamel matrix or fully mineralized enamel, dentin, cementum, and dental pulp [71].

8.7.2. Inflammation of odontogenic structures and periodontal tissues

Inflammation affecting dental pulp, periodontal ligament, alveolar bone, or gingival soft tissue can lead to swelling and tumorlike masses [71].

8.7.3. Peripheral giant cell granuloma (giant cell epulis)

It is found in dogs, cats and cattle, with gingival location, red color, appearance of sessile, sometimes pedunculated granuloma. Microscopy shows hyperplasia of the gingival epithelium, ulcerations, an extremely well vascularized stroma. The presence of giant cells, with numerous central nuclei and abundant eosinophilic cytoplasm, situated in a dense stromal cell mass, is characteristic. Numerous uninucleate cells, with abundant cytoplasm, similar to giant cells, are also present [1, 33, 71] (Fig. 8.12).

Fig. 8.12

Giant cells epulis.

8.7.4. Gingival hyperplasia

Hyperplastic and proliferative inflammatory lesions of the gingiva are common. They are characterized by redundant amounts of nearly normal-looking gingival collagen and an intact epithelium. There may or may not be edema, vascular dilation, and/or perivascular lymphocytes; proliferative gingivitis is characterized by a profuse infiltrate of lymphocytes and plasma cells. The epithelium is often thrown into complex folds that extend both inward and outward (pseudoepitheliomatous hyperplasia) [71].

8.9.1. Pleomorphic adenoma (mixed tumor)

A benign primary salivary tumor formed by an intermingling of epithelium, myoepithelium and stroma, hence the term pleomorphic.

Pleomorphic adenoma (Fig. 8.6) is a mixed tumor that may be formed by: irregular canalicular structures; squamous cell bands or masses with intercellular bridges, which are sometimes keratinized; and polygonal or fusiform eosinophilic cell structures, supposed to be myoepithelial cells. Tumoral structures can involve mucoid, myxoid or chondroid nodules. Histologically, pleomorphic adenoma can be dominated by one of the three components, canalicular structures, squamous cells or eosinophilic cells; endochondral or membranous ossification may develop. This peculiarity requires the sampling and microscopic examination of different tumor areas, in order to establish a diagnosis of certainty.

Fig. 8.6

Pleomorphic adenoma, salivary gland.

The tumor has been reported as occurring in the horse, ox, dog and cat, but it is not the most common tumor of salivary glands in any of these species, unlike the situation in the human. Most examples have been seen in the parotid gland, but mandibular and even minor glands may be affected [71, 72].

8.9.2. Oncocytoma (oxyphil or oncocytic adenoma)

A tumor composed of large polyhedral cells that contain numerous mitochondria and are arranged in solid masses, trabeculae or tubules supported by a delicate stroma. Oncocytes are considered to be epithelial cells that have undergone metaplasia. Oncocytoma is rare, but has been recorded in the parotid gland of a cat.

Histologically, the cells have clear-cut borders and the cytoplasm is filled with eosinophilic granules when stained; nuclei are small, round to oval, hyperchromic and central. Scattered clear cells may be found, characterized by vacuolation of the cytoplasm that displaces the nucleus to the side of the cell, where it is surrounded by a little granular cytoplasm; there are few mitotic figures [71].

8.9.3. Canalicular adenoma

A benign salivary tumor composed of closely packed tubules in a delicate loose vascular stroma. The tumor is of ductal origin, bordered by cuboidal to columnar epithelium. The cell cytoplasm may have secretion vacuoles and nuclei tend to be basal. Sometimes the cyst is surrounded by connective tissue and even foreign body reaction, with lymphoid infiltrate and giant cells. This tumor type has been recorded occasionally in the dog and cat [71, 72].

8.9.4. Sebaceous adenoma

An encapsulated benign neoplasm composed of lobules of sebaceous glands. The peripheral cells have little cytoplasm and hyperchromic nuclei (reserve cells), while centrally the cells show progressive vacuolation. The tumor has been recorded in the alveolus of a cat [71].

8.9.5. Ductal papilloma

Benign proliferation of excretory ductal epithelium on a connective tissue core that projects into the duct lumen (intraductal papilloma) or extends into the periductular connective tissue (inverted papilloma). The cells are uniform and well differentiated, and there are few mitotic figures. There may be mucus-producing cells near the surface. There are reports of intraductal papilloma in the parotid ducts of dogs [71].

8.9.6. Cystadenoma

An encapsulated mass of cysts, often with papillary ingrowths (papillary cystadenoma). The lining is composed of a variable number of layers of cuboidal to columnar cells that are well differentiated and have few mitoses. If the majority of the cells are mucin producing and the cyst lumina are therefore filled with mucin, the term mutinous cystadenoma may be used. The tumor has been reported occasionally in the horse and the cat [71].

8.9.7. Acinic cell carcinoma

A low-grade malignant epithelial neoplasm with some areas composed of cells resembling the normal cells of salivary gland acini. Five cell types may be found in varying numbers in any one tumor.

Acinar cells are large round or polygonal cells having finely granular cytoplasm, and small dark eccentric nuclei. The cells are formed into small groups by a basement membrane and fine reticulum network.

Intercalated duct-like cells are smaller cuboidal cells grouped around small acini. They have small dark eccentric nuclei and basophilic cytoplasm.

Vacuolated cells resemble acinar cells, but have one or more vacuoles that may stain for mucopolysaccharide but not for fat or glycogen.

Clear cells resemble acinar cells or intercalated duct-like cells, but the cytoplasm does not stain with H&E or other stains.

Nonspecific glandular cells form a syncytium in which large vesicular nuclei are distributed, resembling pluripotential stem cells.

The 4 growth patterns are: solid with little stroma; microcystic; papillary cystic and follicular (resembling the thyroid).

Acinic cell tumors are low-grade malignancies, so there are few mitotic figures and little cellular atypia. They seldom have a distinct capsule and many show peripheral invasive growth. Distant metastases to lymph nodes and lung may be seen in advanced cases.

Some tumors previously classified as monomorphic and benign should be examined and reclassified in this group.

These are among the most common salivary gland tumors in the dog, but only a few cases have been recorded in the horse, ox, sheep and cat; these tumors tend to occur in older animals. The parotid gland is the most common site in all species, but any salivary gland may become neoplastic [71].

8.9.8. Mucoepidermoid carcinoma

A malignant tumor characterized by the presence of mucous cells, with the formation of cysts, bordered by occasionally keratinized squamous cells and intermediate cells; one of the structures is dominant.

Characteristic of malignancy is the grouping of mucoid cells into nests, numerous atypical mitoses, large polymorphic nuclei and infiltrative growth. In the case of the predominance of the epidermoid component, squamous cells are stratified, arranged in cords, with large vesicular nuclei and prominent nucleoli, and the presence of keratin is easy to detect (Fig. 8.7). PAS-positive mucopolysaccharide drops are evidenced in the cell cytoplasm; they have smaller cysts than low-grade tumors, the cysts may rupture, provoking a granulomatous reaction with giant cells and cholesterol clefts.

Fig. 8.7

Mucoepidermoid tumor, submaxillar salivary gland.

All these tumors may give rise both to local lymph node and distant metastases. Cases have been recorded in the dog and cat, mainly in the parotid gland and usually in older animals [71, 72].

8.9.9. Cystadenocarcinoma

A low-grade malignant tumor composed of a series of cysts lined by cuboidal to columnar epithelial cells, some or all of which may be mucus producing. The lining is often thrown up into papillae with thin fibrous cores, papillary cystadenocarcinoma. To differentiate this tumor from a cystadenoma, one should find numerous mitotic figures, nuclear pleomorphism and peripheral infiltrative growth. A possible case has been recorded in the zygomatic gland region of a dog.

8.9.10. Adenocarcinoma

Adenocarcinoma has been described in dogs, cats, and extremely sporadically in horses and cattle. The tumor has moderate malignancy characteristics.

The acinar aspect is structurally dominant, although papilliferous proliferations may also appear. Cells are round to polygonal, with basophilic cytoplasm and small oval nuclei. Clear cells have been identified in the tumors of small salivary glands from the dog tongue. In all species, it is most often seen in the parotid gland, but all major and minor glands can be affected. The degree of cellular atypia, mitotic activity and infiltrative growth vary widely, even within the same tumor, but especially from one case to another.

Adenocarcinoma has a local invasive growth, metastasis to the local lymph node is common (Fig. 8.8–8.11) [71, 72].

Fig. 8.8

Adenocarcinoma, parotid salivary gland.

Fig. 8.9

Adenocarcinoma, submandibular salivary gland.

Fig. 8.10

Adenocarcinoma, salivary gland.

Fig. 8.11

Adenocarcinoma, salivary gland.

8.9.11. Malignant myoepithelioma (myoepithelial carcinoma)

A tumor with pleomorphism, mitotic figures and peripheral infiltrative growth. Solid masses of spindle-shaped and polyhedral (plasmacytoid) cells which have the immunohistochemical characteristics of myoepithelium. A possible case has been recorded in the dog [71].

8.9.12. Carcinoma or sarcoma in pleomorphic adenoma (malignant mixed tumor)

Mixed tumors have the characteristics of a pleomorphic adenoma, and they can be considered as malignant forms with polymorphic structures. They are compared to mamary mixed tumors, carcinosarcomas. A tumor that has areas of benign epithelium, myoepithelium and mucoid, myxoid, cartilaginous or osseous ground substance, but also has regions that have developed malignant characteristics.

The malignant foci may involve the epithelium (undifferentiated carcinoma, squamous cell carcinoma, mucoepidermoid carcinoma, adenocarcinoma) or myoepithelium (malignant myoepithelioma) or mesenchyme (chondrosarcoma, osteosarcoma, undifferentiated sarcoma).

There are a few published examples of this category of tumor in old cattle, dogs and cats affecting the parotid, mandibular and pharyngeal glands. The tumors were locally invasive and spread to the drainage lymph nodes [71, 72].

8.9.13. Squamous cell carcinoma

A malignant tumor of squamous epithelium ranging in morphology from well differentiated with keratin whorls to poorly differentiated, which are recognized by cells with intercellular bridges. Salivary glands may be involved by contiguity from a squamous cell carcinoma in an adjacent organ, eg, feline lingual glands from a tumor in the tongue, canine pharyngeal glands from a tonsillar carcinoma, bovine parotid gland from "cancer eye". Once the acinar pattern of the extensive area of coagulative necrosis seen in salivary gland infarction has been recognized, it is unlikely that the metaplastic/hyperplastic ducts would be confused with viable squamous cell carcinomatous foci in a necrotic tumor. Despite these pitfalls, a few cases in the cat, dog, and cow have been established [71].

8.9.14. Undifferentiated carcinoma

A tumor of large round and spindle-shaped epithelial-type cells with vesicular nuclei, many mitoses and infiltrative growth, and no distinguishing features that would place it in a more specific category. Histologically, there are no features in the cell cytoplasm or in the cell patterns that place these tumors in one of the other categories of carcinoma, even when special staining methods are used. Examples have been recorded in young adult and older horses, cattle, sheep and dogs in both major and minor glands. Widespread metastases are often present by the time the tumors are first recognized [71].

Lymphoma (lymphosarcoma, malignant lymphoma)

Primary localized parotid lymphoma has been described in a horse. Secondary involvement by extension from adjacent lymph nodes may be seen in the dog. In the pig, salivary glands are infiltrated by not enlarged as part of inherited generalized lymphoma [71].

Mast cell tumor

A localized mast cell tumor in the mandibulary salivary gland has been recorded in a dog and cat that also had a cutaneous and visceral mast cell tumor [71,72].

Melanocytic tumors

Primary melanocytic tumors of salivary glands have been described in the dog and cat. In grey horses, the major salivary glands may be affected as part of a generalized melanotic tumor syndrome [71].

Sialadenosis

A bilateral enlargement of a major salivary gland (usually the parotid) due to degenerative change in the autonomic nervous system and atrophy of the myoepithelial cells. A case has been described in a sheep.

Hyperplastic masses

Foci of gland or duct hyperplasia or nodules of oncocytes.

Salivary gland infarction (necrotizing sialometaplasia)

Unilateral enlargement of a major salivary gland due to an area of coagulative necrosis separated from the surrounding normal gland by a zone of reactive connective tissue infiltrated by polymorphonuclear cells and macrophages [71].

Lipomatosis (fatty infiltration, lipomatous infiltration)

Lipomatosis can be distinguished from true fat tumors because although the lesion may be encapsulated, there are groups of normal salivary gland cells scattered throughout the lobules of well-differentiated fat cells. Unilateral enlargement of either parotid or mandibular glands by lipomatosis has been described in the dog [71].

Postinflammatory lipomatosis (parenchymatous atrophy)

Postinflammatory lipomatosis is differentiated from lipomatosis by remnants of damaged acini and cells of inflammation/repair scattered through the lobules of adipose tissue [71].

Salivary gland cysts

Extravasated pseudocyts (sialocoele, serocoele, mucocoele), lined by active reabsorptive connective tissue infiltrated by inflammatory cells. These pseudocysts are the result of rupture of the small ducts witin major or minor glands that do not have a distinct capsule. The secretion that escapes may migrate some distance from the point of release, eg, from the sublingual gland, to form a ranula alongside the tongue or down the neck, producing a cervical sialocoele. Such lesions are not uncommon in dogs, less common in cats, and have been seen in cattle [71].

True salivary cyst, a benign cyst lined entirely by salivary ductlike epithelium; monolayered when derived from minor ducts, but multilayered when derived from major ducts. A rare example of congenital retention cyst due to atresia of the opening of the parotid duct has been described in a young horse [71].

Branchial cyst, persistent sections of the pharyngeal pouches lined by nonkeratinizing stratified squamous epithelium that became cystic. Well-established cases in dogs and cattle have been recorded [71].

8.16.1. Gastric tumors

Gastric or/and intestinal tumors are more frequent in dogs [33, 34], and the main clinical manifestation is vomiting. Clinicomorphological studies have evidenced gastric neoplasms of adenocarcinoma type and adenomatous polyps [47]. Histological studies performed by biopsy [23] have diagnosed in 139 vomiting dogs a majority of malignant carcinomas and lymphomas, against an ulcerative gastritis background [56]. Among domestic animals, dogs most commonly develop spontaneous gastric tumors; gastric tumors are rare in dogs compared with their occurrence in humans. Carcinomas are reported to account for about 1% of all malignant neoplasms of dogs. They are extremely rare in cats. The average age for dogs with gastric carcinomas is 7–9 years, a predisposition has been found in males. Clinical signs of gastric carcinoma are nonspecific but related to progressive loss of gastric function: anorexia, vomiting, and emaciation. The alimentary form of malignant lymphoma is encountered in the stomach of the horse, dog and cat. The abomasum is a frequent site for the alimentary form of lymphoma in bovines [71].

Gastric Tumors (Head et al. 2003)

1. Epithelial Tumors
   • 1.1 Adenoma
     • 1.1.1 Tubular adenoma
     • 1.1.2 Papillary (villous) adenoma
     • 1.1.3 Tubulopapillary (tubulovillous) adenoma
   • 1.2 Adenocarcinoma
     • 1.2.1 Tubular adenocarcinoma
     • 1.2.2 Papillary adenocarcinoma
     • 1.2.3 Tubulopapillary adenocarcinoma
     • 1.2.4 Mucinous adenocarcinoma
     • 1.2.5 Signet-ring cell carcinoma
   • 1.3 Squamous cell carcinoma
   • 1.4 Undifferentiated carcinoma
2. Neuroendocrine Tumors
   • 2.1 Carcinoid (neuroendocrine carcinoma)
3. Mesenchymal Tumors
   • 3.1 Tumors of smooth muscle
     • 3.1.1 Leiomyoma
     • 3.1.2 Leiomyosarcoma
   • 3.2 Nervous tissue tumors
     • 3.2.1 Peripheral nerve sheath tumor (neurofibroma, schwannoma)
     • 3.2.2 Ganglioneuroma
   • 3.3 Tumors of fibrous tissue
   • 3.4 Gastrointestinal stromal tumor
   • 3.5 Tumors of vascular tissue
   • 3.6 Tumors of adipose tissue
4. Tumors of Hematopoietic and Related Tissues
   • 4.1 Lymphoma (lymphosarcoma, malignant lymphoma)
   • 4.2 Plasmacytoma
   • 4.3 Mast cell tumors
5. Mesothelioma
6. Secondary Tumors
7. Unclassified Tumors
8. Tumorlike Lesions
   • 8.1 Polyps
     • 8.1.1 Hyperplastic polyp (regenerative polyp)
     • 8.1.2 Inflammatory polyp (benign lymphoid polyp)
   • 8.2 Giant rugal hypertrophy (Ménétrier disease)
   • 8.3 Chronic idiopathic inflammatory gastritits
     • 8.3.1 Scirrhous eosinophilic gastritis
     • 8.3.2 Lymphoplasmocytic gastritis
   • 8.4 Pyloric stenosis

8.16.1.1. Gastric epithelial tumors

A. Gastric ADENOMAS are benign tumors that are macroscopically similar to non-tumoral hyperplastic forms. Histologically, adenoma presents cellular atypias and a higher number of mitoses, compared to the adjacent mucosa. Hyperplasias characteristic of preneoplastic structures appear.

Adenomas may develop as different types: papillary, tubular, and mixed tubulopapillary adenomas.

Gastric polyps have been reported in dogs, and intestinal polyps in cats, swine and cattle. In dogs, they occur as multiple gastric polyps, usually located in the proximity of the pylorus [47]. Clinical manifestations consist of vomiting, gas eructation and dilation with overloading. Rectal polyps in dogs may be associated with tenesmus and hemorrhage [14].

Macroscopically, gastric polyps appear as bulging sessile or pedunculated formations, with an arborescent surface or cluster aspect [14, 46]. Histologically, they are covered by a cubic or prismatic epithelium, on a connective vascular texture as a continuation of the submucosa. Gastric glands may have an irregular wall thickening, by cellular pluristratification, with large hyperchromatic nuclei. Differentiation from carcinoma is based on the microscopic character, in which malignancy images are reduced.

Papillary adenoma has a villous-like growth. Histologically, it appears digitiform, with a well differentiated epithelium at the surface, lying against a fine connective vascular texture. In most cases, it develops under the form of sessile, exceptionally pedunculated, tumors.

Tubular adenoma or adenomatous polyp appears as a pedunculated tumor, with ramifications and well differentiated epithelium.

Tubulopapillary or tubulovillous adenoma presents structures of both types, tubular and papillary patterns. Tubules differ from adjacent normal glands by irregular branching and budding. Dysplastic epithelial nuclei are irregularly enlarged and hyperchromatic, become rounded, lose their polarity, and become multilayered (stratified). The epithelium is usually of the superficial foveal type, but may be of the intestinal type with a brush border and goblet cells. The tubular pattern is seen most often and is frequently polypoid. Adenomatous polyps have been induced experimentally using a variety of chemicals in pigs and dogs [71].

Benign stomach tumors are characterized by either superficial epithelial proliferations or intestinal epithelial metaplasias.

Benign gastrointestinal glandular tumors are extremely rare in dogs, while in other species they have not been reported.

The diagnosis of gastrointestinal polyps will take into consideration the presence of hyperplastic mucosal forms that can mimic tumor growth. In humans, gastrointestinal polyps usually change into carcinomas, which has not been reported in animals.

B. Gastric ADENOCARCINOMA, a malignant glandular tumor, is found more rarely in domestic animals, being reported in dogs, and extremely sporadically in horses, cattle, sheep, cats and swine.

Like in man, gastric carcinoma in dogs is located in the antral area, along the small curvature of the stomach, with a higher frequency in the pyloric or caudal area. In the pyloric location, the tumor has an annular stenosing appearance, while the cardial location has an extensive diffuse aspect, significantly thickening the mucosa. Polyp proliferation forms, prominent in the lumen, as well as the circumscribed-ulcerated aspect are rarer in dogs. Gastric tumors in their majority are similar to ulcers, delimited by fibrosis [47].

By examining 20 dogs with gastric neoplasms, SAUTTER and HANLON (1976) found ulcerations in 11 subjects, of which 2 had perforated ulcers, complicated by peritonitis. The authors mentioned that, of 20 gastric tumors, 14 were carcinomas, 3 lymphosarcomas, 2 leiomyomas and 1 leiomyosarcoma. In another study, ROTH and KING (1990) found ulcers in all the 11 dogs with gastrointestinal adenocarcinomas.

In horses and mules, gastric neoplasms are located in the area of the esophageal type mucosa, and histologically, these are squamous cell carcinomas, not glandular carcinomas.

Gastric neoplasms, especially in dogs, manifest by vomiting, anemia and weight loss, possibly by hematemesis and/or melena. In the case of the presence of visceral metastases, hepatomegaly, ascites and jaundice are found.

The incidence of gastrointestinal neoplasms in dogs is not influenced by breed, the most affected age being around 9 years, and the male/female ratio varies according to different authors, who all agree that males are more affected. PATNAIK et al. (1978) mention some variations depending on the neoplasm type: the male/female ratio was 7/1 in intestinal carcinomas and 2/1 in diffuse carcinomas. In 20 gastric neoplasms in dogs, SAUTTER and HANLON (1976) found a 12/8 incidence ratio.

Radiological examination can offer additional data, without playing an absolute role in the making of diagnosis. Abnormal motility is mainly found, with deficient filling of the pylorus and small curvature of the stomach, delayed gastric evacuation and barium residues.

Papillary gastric adenocarcinoma is characterized by an epithelial proliferation with cuboid or prismatic cells against a connective vascular support. Neoplastic cells invade the mucosal muscular layer and meet in the blood and lymphatic capillaries.

Tubular gastric adenocarcinoma presents an epithelial proliferation with prismatic, cuboid or flat cells, arranged as ramified tubes, in a fibrous stroma, conferring a scirrhous character to the tumor (Fig. 8.24).

Fig. 8.24

Gastric adenocarcinoma.

Tubulopapillary adenocarcinoma, a malignant tumor showing both tubular and papillary features.

Mucinous gastric adenocarcinoma is characterized by excessive mucin in the glands, sometimes forming mucin pools, in which epithelial cell groups may be detected. At other times, macroscopically detectable mucous cysts may arise. In some cases, the tumor is formed by isolated cells, having mucin in the cytoplasm, and the nucleus is eccentric, which explains the term signet ring cells. Mucin can form intracytoplasmic vacuoles, having an acid reaction, or it can appear as neutral mucin granules.

Bone metaplasias may occur in the stromal mass, which is sometimes abundant.

• – carcinoma in situ, which is characterized by marked atypia of epithelial cells;
• – intramucosal carcinoma, with the presence of neoplastic cells in the lamina propria, with metastases in mucosal lymphatics (Fig. 8.2.);
• – dispersed superficial carcinoma, case in which the neoplastic cells have only penetrated the submucosa, with diffuse aspect, even at a great distance from the tumor focus [33, 34].

Signet-ring cell carcinoma, (Fig. 8.21–8.22) a malignant tumor in which more than half is composed of epithelial cells containing intracellular acid or neutral mucin displacing the nucleus to one side of the cell. There is a spectrum of behavior and morphology from low-grade tumors, where there are slightly more signs of dysplasia than in an adenoma, to high-grade tumors where there may be little evidence of a glandular pattern in the solid masses of cells or in the fields of isolated cells. The glands in a low-grade carcinoma are more closely packed than in an adenoma, with little intervening stroma. Branching glands are more obvious. The nuclei are larger, rounder, more hyperchromatic with prominent eosinophilic nucleoli, lie nearer the lumen, are more multilayered and show more mitoses. Metastasis is usually to the regional lymph nodes, with a low incidence of metastasis to the lungs [71].

Fig. 8.21

Gastric signet ring carcinoma.

Fig. 8.22

Gastric signet ring carcinoma.

Squamous cell carcinoma, a malignant tumor composed of cells with features of squamous epithelium. Although a spindle cell carcinoma pattern may be seen in some areas, well-differentiated cords of cells showing intercellular bridges form the bulk of the tumor in most cases. Some central cores of keratinized squamous cells may be seen. Degeneration of these cells results in cyst-like structures mimicking adenocarcinoma. Ulceration and infection of the luminal surface is common. Gastric squamous cell carcinoma is often associated with abundant abdominal fluid, which contains keratin that can be identified by abdominocentesis [71].

C. UNDIFFERENTIATED CARCINOMA. Depending on the histological structure and classification used for humans, the following types can be distinguished, at least in the case of dogs: intestinal type gastric carcinoma; diffuse type gastric carcinoma, and mixed type gastric carcinoma [52].

Intestinal type gastric carcinoma is characterized by a glandular structure, in both the primary tumor and metastases. Epithelium is well differentiated, with a glandular structure, having a brush border and basal nuclei. The groups of acini are well delimited by the connective stroma. Mucus is found in the acinar lumen and sometimes, due to acinar disorganization, the mucus mass can appear extracellularly. The mitotic index is low, with some variations from one case to another.

Depending on histological structure, three subtypes can be differentiated: the papillary, acinar and compact subtypes [52].

The papillary subtype is characterized by the proliferation of cubic and prismatic cells, with a stroma that confers a papillary structure. Epithelial cells have vesicular nuclei, abundant eosinophilic cytoplasm, containing mucin drops. Extracellular mucus occurs exceptionally. Lymph node and distant metastases are relatively frequent.

The acinar subtype is characterized by small acinar groups, being formed by 6–8 well differentiated cells with basal membrane, structures being similar to cardiac glands from the gastric mucosa. Some neoplastic cells of the primary tumor or metastases contain mucin, and others have eosinophilic cytoplasm. Metastases are relatively frequent.

The compact subtype or solid adenocarcinoma has been diagnosed in dogs. Structure is acinar and of papillary type. In the case of neoplastic cells, it has a high mitotic index, with marked anaplasia. Distant metastases are usually present.

Diffuse type gastric carcinoma has the highest incidence in dogs, being characterized by small round cell proliferation, with a poorly developed tubular structure and infiltrative growth. Some cells have a signet ring appearance.

Mixed or intermediate gastric carcinoma is characterized by either the presence of the two cell types mentioned for the previous types, or a compact carcinoma structure in association with acinar forms and well delimited tumor margins.

Gastric carcinomas in dogs. As it has been mentioned, in this species incidence is highest and shows structural similarities to human carcinomas. It is estimated that gastric carcinomas represent 1% of all malignant tumors in dogs. Gastric carcinomas have been reported in geographic areas with a high incidence in humans, as well as in areas with low frequency. Environmental factors, nutrition and other risk factors, almost identical for man and the dog, could not be incriminated in the incidence of gastric carcinomas in dogs.

Like other neoplasias, gastric carcinoma is more common in males, the male/female ratio being estimated at 12/8 [58] under 10 years of age, with location in the pyloric area. Tumors are predominant on the mucosal surface, under the form of plaques, with ulcerated surface, and in section, fibrous proliferation is noted, which confers a scirrhous aspect.

Microscopically, adenocarcinoma most frequently appears diffuse, with neoplastic cells infiltrated in the gastric wall structures, as crowdings, clusters or isolated cells. Cells are uniform, they frequently contain large mucus drops, but extracellular mucus masses can appear. Another histological type is formed by diffuse glandular structures.

Tubular or intestinal type adenocarcinomas are not so frequent in dogs. Characteristic is the tubular glandular structure, with a lumen, with well differentiated epithelium. Growth is diffuse infiltrative, with scirrhous connective proliferation. The tubular carcinoma may present epithelial foldings, under the form of papilliform growths, acinar structures and more rarely compact growths. Cells have an eosinophilic cytoplasm and they contain mucus [1].

In man, the intestinal metaplasia of the gastric mucosa is frequently associated with intestinal carcinoma. In dogs, PATNAIK et al. (1978) found intestinal metaplasia of the gastric mucosa, under experimental conditions as well as in 1/3 of subjects with spontaneous neoplasms.

Metastasizing is a common phenomenon for gastric carcinomas in dogs, frequently in regional and mesenteric lymph nodes. Metastases can also be found at distance, in the liver, lung, pancreas, adrenal gland, myocardium and spleen.

Positive diagnosis in gastric carcinomas in dogs is made by correlating clinical, radiological data and the microscopic examination of biopsy samples [4].

Gastric carcinomas in horses are predominantly of squamous type, glandular forms being extremely rarely diagnosed.

Squamous cell carcinoma is located on the esophageal type mucosa of the stomach, exceptionally in the glandular area [43].

Macroscopically, it appears as a cauliflower-like proliferation, frequently with erosions and ulcerations, 12–25 cm in diameter, sometimes larger, with a fungal extension appearance. Due to the involvement of the whole thickness of the gastric wall, exceeding the serosa, adherences to the liver and/or the diaphragm are found, sometimes with extensive peritoneal dissemination.

The neoplasm occurs in adult to old animals. Clinical manifestations consist of anorexia, sometimes dysphagia, with weight loss in a short time [35].

Between the gastric wall and the adjacent organs, necropsy reveals large, dense, connective masses, with deep ulcerations and hemorrhage. Tumor masses may develop in the pleurae, with distant metastases, in the liver and spleen. Dissemination on the peritoneal and pleural mucosae can be a reason to consider the neoplasm a mesothelioma. Occasionally, the carcinoma can extend to the distal esophageal area, causing obstruction [1, 50].

Microscopically, the tumor is formed by polyhedral cells, arranged in bands and nests, with numerous cysts and keratotic pearls. Neoplastic cells invade the submucosa, the muscular layer, exceeding the serosa, disseminating in the peritoneum, with metastases in the liver, spleen, adrenal gland, kidney, lung and mesenteric lymph nodes [43, 46].

Gastric carcinomas in cattle are rarely mentioned, in general being similar to those described in other species, having a marked scirrhous and invasive character.

The most frequently diagnosed neoplasms are abomasal lymphomas, in adult cattle. Neoplastic proliferation has a diffuse or nodular character in the mucosa and submucosa. Tumor formations can be ulcerated, with diffuse hemorrhage in the stomach thickness, white-gray nodules develop in the mucosa and submucosa, adjacent lymph nodes are unchanged. Lymphoblastic infiltration sometimes results in pyloric obstruction.

8.16.1.2. Gastric neuroendocrine tumors

Carcinoid or neuroendocrine carcinoma (see the sections on "Carcinoids of the alimentary tract"), a low-grade malignant tumor in which intracytoplasmic neurosecretory granules can be demonstrated by light microscopy using special stains. Rare canine gastric carcinoids have been recorded [71, 72] (Fig. 8.25).

Fig. 8.25

Gastric carcinoid tumor.

8.16.2. Tumors of the intestines

Intestinal tumors in domestic animals, as benign or malignant forms, are less common. Malignant neoplasms, in their majority of epithelial origin, are more frequent than benign forms. Rectal polyps in dogs, which may be adenomas or carcinomas, are an exception. Lymphomas are found in all species, with a higher frequency in cats. In swine, intestinal adenomatosis or proliferative ileitis is described on the background of proliferative-hemorrhagic enteropathy.

Histological Classification of Tumors of the Intestines (Head et al. 2003)

1. Epithelial Tumors
   • 1.1 Benign
     • 1.1.1 Adenoma
   • 1.2 Malignant
     • 1.2.1 Acinar adenocarcinoma
     • 1.2.2 Papillary adenocarcinoma
     • 1.2.3 Mucinous adenocarcinoma
     • 1.2.4 Signet-ring cell carcinoma
     • 1.2.5 Undifferentiated carcinoma
     • 1.2.6 Adenosquamous carcinoma
2. Neuroendocrine Tumors
   • 2.1 Carcinoid (neuroendocrine carcinoma)
   • 2.2 Adenocarcinoid
3. Tumors of Hematopoietic and Related Tissues
   • 3.1 Lymphoma (lymphosarcoma, malignant lymphoma)
     • 3.1.1 Extranodal marginal zone B-cell lymphoma of mucosa-associa-ted lymphoid tissue (MALT lymphoma)
     • 3.1.2 Large granular lymphoproliferative disorder (granular cell lymphoma, globular lymphocyte tumor, granulated round cell tumor)
     • 3.1.3 Intestinal T-cell lymphoma
   • 3.2 Plasmacytoma
   • 3.3 Mast cell tumor
4. Mesenchymal Tumors
   • 4.1 Benign
     • 4.1.1 Leiomyoma
     • 4.1.2 Benign peripheral nerve sheath tumor (neurofibroma, schwannoma)
     • 4.1.3 Ganglioneuroma
       • 4.1.3.1 Ganglioneuromatosis
     • 4.1.4 Hemangioma
     • 4.1.5 Lipoma
   • 4.2 Malignant
     • 4.2.1 Hemangiosarcoma
     • 4.2.2 Leiomyosarcoma
     • 4.2.3 Gastrointestinal stromal tumor
     • 4.2.4 Malignant peripheral nerve sheath tumors
     • 4.2.5 Osteosarcoma
     • 4.2.6 Chondrosarcoma
     • 4.2.7 Liposarcoma
5. Secondary Tumors
6. Unclassified Tumors
7. Tumorlike Lesions
   • 7.1 Polyps
     • 7.1.1 Adenomatous polyp
     • 7.1.2 Papillary (villous) polyp
     • 7.1.3 Hamartomatous polyp
     • 7.1.4 Inflammatory polyp
     • 7.1.5 Juvenile polyposis
   • 7.2 Porcine proliferative enteritis
   • 7.3 Malformations
     • 7.3.1 Diverticulum
       • 7.3.1.1 Meckel' s diverticulum
       • 7.3.2 Intestinal duplication
     • 7.4 Heterotopia
       • 7.4.1 Heterotopic gastric mucosa
       • 7.4.2 Heterotopic pancreas
     • 7.5 Inflammatory bowel disease
       • 7.5.1 Lymphoplasmocytic enteritis
       • 7.5.2 Scirrhous eosinophilic enteritis

8.16.2.1. Epithelial tumors

Adenoma, a benign neoplasm of epithelium arranged in acinar structures and papillary projections; often associated with adenocarcinoma. Polyps frequently appear in the anorectal junction area, in middle aged dogs, and especially in males. Clinical manifestations consist of tenesmus, prolapse, defecation with blood and diarrhea.

Macroscopically the tumor is sessile or with a short pedicle, of firm or friable consistency and hemorrhagic, frequently presenting ulcerations. Microscopically, the polyp structure may be predominantly tubular or papillary. The tubular type is characterized by ramifications bordered by well differentiated columnar to cuboid epithelial cells, lying on the lamina propria. The papillary type consists of villous-like projections, with connective support, on which columnar epithelial cells with a pseudostratified aspect are found. Nuclei have a basal arrangement, obvious nucleoli, and the mitotic index is variable. Tumor formations are well vascularized. Epithelial mucus is in variable amounts, sometimes being absent, at other times particularly abundant. Some polyps have histological malignancy aspects.

Solitary adenomas occur as polyps in the rectum of dogs and small intestine of cattle, and they have a premalignant significance. Surgical therapy is generally successful, recurrences being exceptional [71, 72].

Polypoid tumors in other species. Tumor masses with polyp appearance, 1 to several cm in diameter, may be found in various intestinal segments, especially in cattle. These formations are isolated, small, but can induce even partial obstructions. Tumors are flat or pedunculated, of brown color, prominent on the mucosa. Microscopically, structure is similar to that of benign tumors, such as rectal polyps in dogs (Fig. 8.26, 8.27).

Fig. 8.26

Polyp, duodenum.

Fig. 8.27

Polyp, high power of fig. 26.

A high incidence of intestinal adenomas developing into adenocarcinomas has been reported in Scotland and Northern England. These tumors coexist with papillomas and squamous cell carcinomas in the anterior digestive tract. In endemic areas, mentioned for cattle with adenomas, the following are distinguished: sessile plaques, adenomatous polyps and numerous adenomatous proliferations in the bile and pancreatic ducts before the duodenum.

Adenomatous polyps are frequently found in sheep with intestinal carcinomas, as well as in chronic forms of small intestinal coccidiosis in lambs and goats [1].

Malignant tumors

The incidence of intestinal adenocarcinomas in animals is lower, compared to humans. They are frequently found in dogs and sheep [52], but have also been reported in cattle, horses and cats [53].

Intestinal adenocarcinomas in dogs, approximately 0.5% of all malignant tumors, are found in the intestine, of which 40% are located in the colon and rectum.

The mean age of dogs with intestinal adenocarcinomas is 9 years. Breed does not seem to significantly influence the frequency of intestinal carcinomas, although PATNAIK et al. have found a higher incidence in the Boxer breed, and other authors in Collie, Poodle and German Shepherd dogs. According to the majority of authors, sex does not represent a risk factor, however, there are observations reporting a higher incidence in males. Duodenum and colorectum are the most common sites. In a study of 69 intestinal neoplasms, there were 31 adenocarcinomas and 4 carcinoids, and an incidence of 0.30% among the study population. There were more malignant than benign tumors (p < 0.005), and epithelial tumors were more common than nonepithelial tumors (p < 0.005). Most tumors were found in dogs < 10 years of age. The peak age was 9 to 10 and the median age was 9, significantly lower than that for nonepithelial tumors (p < 0.005). They were found more frequently in males, in contrast to nonepithelial tumors.

The gross appearance of these tumors was annular or intraluminal, the lumen was constricted because of the longitudinal infiltration of the tumor. Local infiltration and distant metastasis were associated with almost all intestinal adenocarcinomas in the study. Abdominal carcinomatosis (86%) and lymph node (74%) and liver metastasis (22%) were the most common forms. Carcinomatosis varied from 66% for papillary carcinoma to 100% in the case of carcinoids. Metastasis to lymph node varied from 64% for adenocarcinoma to 100% in the case of undifferentiated carcinoma and carcinoid. The liver was the most common site of metastasis in the case of carcinoids compared with other types of carcinoma [71].

The clinical picture is dominated by less specific enteral signs. The disease has a chronic evolution, with manifestations of constipation or diarrhea, vomiting, anorexia, emaciation and abdominal distension. In the case of colorectal locations, dogs manifest tenesmus and feces with blood or mucus. The majority of dogs are anemic.

Macroscopically, the tumor is white-gray and firm, arranged circularly, producing stenosis, thickening the whole intestinal wall. In most cases, the tumor is not ulcerated and does not project in to the lumen. Papillary or polypoid intestinal carcinoma causes intraluminal growths, involving large intestinal areas with horizontal extension. Thus, a dilation of the intestine occurs prior to tumor stenosis and obstruction, and at the same time, muscle hypertrophy proximal to the neoplasm may appear.

Four types of intestinal adenocarcinomas can be histologically differentiated in dogs [1]:

The acinar type is characterized by glandular structures, with the invasion of the mucosa and infiltration in the submucosa and muscular layer. Epithelial cells delimit the acini, cells are cuboid to columnar, with small hyperchromatic nuclei at the cell base. Amorphous eosinophilic material appears in the lumen of glandular structures. In rare cases, mucus appears. Frequent necroses delimited by inflammatory reaction and peripheral fibrosis are present. The hyperplasia of epithelial cells and crypts occurs adjacently to the tumor (Fig. 8.28–8.32.). In the colon, the tumor infiltrates the Peyer's patches at the primary site.

Fig. 8.28

Annular stenosing tubular adenocarcinoma, jejunum.

Fig. 8.29

Tubular adenocarcinoma, jejunum (fig. 21).

Fig. 8.30

Tubular adenocarcinoma, lower jejunum.

Fig. 8.31

Acinar, infiltrative, intestinal adenocarcinoma.

Fig. 8.32

Acinar, infiltrative, intestinal adenocarcinoma.

The undifferentiated solid type is characterized by the infiltration of the mucosa and intestinal wall with anaplastic epithelial cells arranged in nests and bands. There is a weak tendency of organization in acinar structures. Tumor cells have abundant amphophilic to basophilic cytoplasm and large vesicular nuclei with obvious nucleoli. Annular cells with scant mucus are sometimes noted. Metastasis to the lymph nodes, liver, and lungs may be seen.

The mutinous type is characterized by the proliferation of anaplastic epithelial cells, with pale eosinophilic cytoplasm. Large spaces of extracellular mucus appear in the stroma. This tumor, also referred to as colloid carcinoma or mucoid carcinoma, is characterized by acinar or irregular crypts. Peritoneal carcinomatosis and lymph node metastases are common [71].

The papillary type is characterized by papilliferous proliferations in the intestinal lumen, covered by intensely anaplastic columnar epithelial cells, with a high mitotic index. Hyperplastic crypts and villi contain cup-shaped cells. Tumor growth has a local invasion aspect. Grossly, these tumors involve larger segments of the intestines; they are mostly intraluminal, and are located mainly in the duodenum, rectum and colon.

Metastases are found in all types, less in the papillary type, and they occur in regional, mesenteric or/and abdominal lymph nodes, and at distance, in the liver, spleen and lung.

Intestinal adenocarcinomas in cats are relatively frequent, like lym-phomas, being less numerous compared to dogs. Frequency is higher in the Siamese breed and in females, and the mean age is 10–11 years, with variations between 4 and 14 years. Locations are in the ileum, then in the jejunum, especially in the proximity of the ileocecal junction, and at the same time in the large and/or small intestine. The incidence varies from 0.4% to 29%, incidence among alimentary tract neoplasms varies from 6.6% to 13%.

The clinical picture, as well as macroscopic aspects, is similar to those mentioned in dogs. Microscopic forms identify similar types to those described in dogs, but in cats osteochondroid metaplasias and scirrhous forms are frequently found.

Intestinal adenocarcinomas in sheep show the peculiarity of having an endemic character in certain geographic areas. Thus, in New Zealand, Iceland, Scotland, Norway and certain areas of Australia, the disease is present without the certain identification of the carcinogenic factors involved. Regarding the association of carcinogenic areas with the presence of ferns in the food of animals, this hypothesis is not supported at least for certain areas, since it is known that enzootic hematuria of cattle is not associated with the presence of intestinal adenocarcinomas in sheep fed under the same conditions.

Intestinal adenocarcinomas in sheep occur in subjects aged 5 years or more. Clinical symptoms gradually develop with abdominal distension, ascites, hydrothorax, prostration, weight loss and death. The prevalence varies in different countries, from 2% of all tumors in the least affected areas to 42% of all tumors.

Macroscopically, location is found in the middle or posterior area of the small intestine, more rarely in the colon. The tumor appears as a dense, firm, whitish mass, 0.5 to several cm in diameter, with the thickening of the intestinal wall, so that it can be noted even in the serosa. Polyps or plaques appear on the mucosal surface, which are dominant in the lumen, more rarely with ulcers. Due to the narrowing of the lumen, a dilation of the intestine occurs in the area anterior to the tumor. Metastases usually develop in mesenteric lymph nodes, and by implantation, dissemination occurs on the surface of abdominal serosae, under the form of white plaques or diffuse thickenings, obviously different from mesothelioma. Pulmonary and hepatic metastases are rare.

Microscopically, the tumor appears as a solid type proliferation or as nests, more rarely of acinar type. Well differentiated, highly aplastic epithelial cells are polyhedral, cuboid or columnar. Tumor cells can be disseminated or under the form of small aggregates, in a mass of reactive mesenchymal tissue. Mitotic forms are rare. Neoplastic cells infiltrate all structures of the intestinal wall, the submucosa and muscular layer, invading the lymphatics and blood vessels, nerve structures, the serosa and mesenteric lymph nodes. In all cases, the infiltration of neoplastic cells is accompanied by scirrhous reaction, where mineralization foci and/or bone metaplasia appear.

Positive diagnosis may be performed by the correlation of clinical data with histopathological examinations carried out on biopsy or necropsy samples.

Intestinal adenocarcinomas in other species, such as cattle, goats, horses and swine, are rare. In New Zealand, a higher incidence of these tumors is mentioned in cattle, as well as in humans and sheep. In this case, man, cattle, and sheep are exposed to the same carcinogenic nutrition factors with the activity of a certain gastrointestinal flora.

Macro- and microscopic morphology, the locations of intestinal neoplasms in these species are similar to those mentioned in sheep. Sometimes, neoplasms can extend by hematogenous route to the liver, lungs, kidneys, uterus and ovaries [72].

Unlike in cattle, lesions are solitary, usually mid-jejunal, with spread to the drainage lymph node, trasncoelomic peritoneum and rarely to the lung, but never to the liver.

In horses, intestinal lymphoma is more common than adenocarcinoma. The rare equine intestinal adenocarcinomas involve the cecum and large colon. The tumor is usually an acinar adenocarcinoma in the form of an ulcerated intraluminal plaque.

In pigs, intestinal adenocarcinoma is extremely rare, most commonly seen in the jejunum as annular, constrictive lesions, mostly acinar and often with goblet cells, desmoplasia and inflammatory cells [71].

Adenosquamous carcinoma, also referred to as adenoacanthoma and adenocarcinoma with squamous differentiation. Areas of transition from glandular epithelial cells to squamous cells are seen. This tumor is rarely found in the small intestine of dogs.

Carcinoids, neuroendocrine carcinomas, are tumors of endocrine enterochromaffin cells, disseminated in the epithelium of digestive, respiratory, urinary, genital mucosae, in the excretory ducts of the pancreas and breast.

Some facts should be emphasized regarding endocrine cells distributed in structures that are not specialized in endocrine secretion. These cells have a common embryonic origin, as well as common functional capacities. Thus, they produce polypeptide hormones and synthesize biogenic amines from the incorporated amine precursors, properties that have led to their inclusion in the "Amine Precursor Uptake and Decarboxylation" (APUD) system, and due to their dissemination in various structures from the organism, these endocrine cells are known as the "Diffuse Endocrine System" (DBS).

Carcinoids of the digestive tract have been reported and described in particular in humans, while in animals they are less known, being only sporadically reported. Thus, in domestic animals, gastrointestinal carcinomas have been reported in old dogs, and extremely sporadically in cats, cattle and horses (Fig. 8.20.).

Fig. 8.20

Ulcerated gastric carcinoma.

The data obtained from human pathology mention that gastrointestinal carcinoid neoplasms may be located in any segment of the digestive tract, in the anterior, middle and posterior intestine. The highest incidence of carcinoid locations is in the middle intestine, appendix and ileum, representing 60–80% of cases.

Carcinoids frequently have a multicentric growth, with slow development, in all cases they are potentially malignant, having an infiltrative invasive growth, with metastases in the regional lymph nodes and at distance. It has been found that carcinoid tumors with identical morphology and location can secrete different active regulating substances, which produce various clinical syndromes.

According to HEAD et al. (2003) [71], histologically, adenocarcinoids can be grouped into 3 categories:

1. Tubular adenocarcinoid: composed of tubular structures and trabeculae lined by cuboidal cells separated by stroma. The lumina contain various amounts of mucin. Neoplastic cells are poorly defined among the abundant stroma.
2. Goblet cell adenocarcinoid: characterized by sheets or groups of cells or rosettes with fibrovascular stroma mixed with signet-ring cells with intracytoplasmic mucin. Neuroendocrine cells are ovoid to spindle with vesiculated nuclei and 1 or 2 small nucleoli. Cells have pale eosinophilic cytoplasm with up to 2 mitotic figures per high-power field.
3. Mixed carcinoid and adenocarcinoma: an adenocarcinoma consisting of one or more patterns. One pattern is that of signet-ring cells, mucinous, and small cells occupying at least 50% of the tumor. The other pattern consists mostly of goblet cells mixed with scattered small cells, which should stain at least with a silver stain and peptide antibody, mostly serotonin.

Grossly, these neoplasms are annular, firm, and difficult to differentiate from carcinoid and adenocarcinoma. They are aggressive, like carcinoids, and frequently metastasize.

Intestinal carcinoids in dogs are located in the duodenum, colon and rectum, locations being reported in the ileocecal and anorectal junction [46]. Clinical manifestations are obstruction and anemia, secondary to hemorrhage from ulcers existing in the tumor.

Macroscopically, carcinoids are lobulated, firm, of red color and creamy consistency. The tumor develops in the submucosa or the subserosa under the form of nodules and ulcerations that traverse the mucosa.

Microscopically, the carcinoid is formed by round or oval to polyhedral endocrine type cells, with numerous eosinophilic granulations or vacuoles in the cytoplasm, vesicular nuclei with prominent nucleoli.

The presence of argentaffin granulations is constant. Cells are arranged in nests, large islands, cords, rosettes or are dispersed diffusely in the mucosa, submucosa and muscular layer. The vascular connective stroma penetrates the tumor, delimiting pseudolobules. Amyloid is present in pericellular or perivascular spaces. Multinucleated cells can be sometimes noted.

Intestinal carcinoids have been diagnosed in cattle, horses and cats. In cattle, location is in the jejunum, with multiple growths. Microscopically, tumor cells are compact or they form bundles, with different anaplasia grades. In cats, locations are in the ileum, cells being round or polygonal, with central round, ovoid or elongated nuclei, clear, vesicular cytoplasm, with eosinophilic granulations. Tumor cells are arranged in bundles [46].

The diagnosis of certainty is made by impregnations that reveal the argentaffin and argyrophilic properties of cells, as well as by electron microscopic examination (see Chapter "Tumors of the diffuse endocrine system").

8.16.2.3. Mesenchymal tumors

Leiomyoma in animals has been diagnosed in both the stomach and the intestine, being a tumor with a relatively high incidence. In dogs, it is frequently found in the small intestine and the cecum, causing obstructions.

Macroscopically, the tumor appears as an intestinal wall thickening, with limited aspect. Histologically, leiomyoma is characterized by bundles of fusiform, eosinophilic cells, with elongated nuclei and rare mitoses. The bundles have an interwoven structure, with the presence of nuclear palisades, similar to that of neurinomas.

Leiomyosarcoma has been diagnosed in dogs, cats and horses, with possible locations in all the segments of the digestive tract.

The tumor is clinically associated with weight loss, lethargy, anorexia, anemia due to intestinal hemorrhage, abdominal pain, diarrhea, vomiturition and dehydration. Leiomyosarcoma is frequent in old dogs, but can also be found in young animals; it has also been diagnosed in old horses, more rarely in other species. Males seem to be more predisposed than females.

Macroscopically, the tumor has a nodular or diffuse development, producing ulcers on the mucosal surface. Nodules may be well circumscribed, delimited by a fibrous capsule, of firm consistency, proliferating towards the serosa, or with a pedunculated aspect in the intestinal lumen.

Histologically, the tumor is formed by groups of oval or fusiform cells. Malignancy characteristics are evidenced by marked cellular pleomorphism and high mitotic index (Fig. 8.33).

Fig. 8.33

Well differentiated leiomyosarcoma, duodenum.

Cavernous hemangioma has been sporadically diagnosed in all species, while hemangioendothelioma, located in the digestive tract, has not been reported in animals.

Hemangiosarcoma, a malignant endothelial neoplasm forming irregular blood-filled vascular clefts and channels, is rarely reported in animals.

Lipoma and lipomatosis are exceptionally diagnosed in domestic animals, with location in the digestive tract. Lipomatous formations are frequently found in the mesentery and the retroperitoneal adipose tissue.

In horses, based on our personal cases, mesenteric lipomas can be pedunculated, producing small intestinal strangulation, infarction, colic and death.

In cattle, adipose deposits, under the form of nodules, are located in the peritoneum, mesentery and retroperitoneal area. The ileum and colon may present fibroadipose tissue, between the serous membrane and the muscular layer, sometimes with necroses and calcifications. Similar aspects can be found in other species, especially in obese individuals.

Gastrointestinal or peritoneal liposarcoma is a neoplasm that is rarely diagnosed in animals, being exceptionally reported in dogs.

Benign peripheral nerve sheath tumor (neurofibroma, schwannoma), characterized by spindle cells arranged in a storiform or whorling pattern. This extremely rare tumor has been reported as solitary multiple lesions in the small and large intestines of dogs, a cat, and a horse.

Ganglioneuroma, a benign neuroectodermal tumor of young animals that contains both mature ganglion cells and glial cells, is extremely rare. It has been reported in the cat, dog, cow and horse, both in the small and large intestine. Many animals are very young (6 weeks to 18 months), which indicates a congenital lesion.

Grossly, the neoplasm is seen as a thickening of the intestinal wall or an intraluminal mass with dilation of the lumen. Histologically, it is characterized by irregularly arranged bundles of nerve fibers associated with Schwann cells and connective tissue, together with individual or groups of ganglion cells. Nissl substance may be seen in some of the ganglion cells. Some of these neoplasms are functional and produce watery diarrhea [71].

Ganglioneuromatosis, segmentally extensive proliferation of nerve fibers, mature ganglion cells and supporting glia of peripheral ganglia. Ganglioneuromatosis of the intestine is extremely rare, only single cases have been reported, affecting both Meissner's and Auerbach's plexuses of dogs and cattle. The lesion consists of ganglion cells, Schwann cells, and associated satellite cells [71].

Leiomyosarcoma, a malignant smooth muscle tumor. Histologically: high mitotic index and an infiltrative border; even in clear-cut leiomyosarcoma, growth is usually slow and metastases develop late in the course of disease [71].

Gastrointestinal stromal tumor, a neoplasm presumed to originate from primitive mesenchymal cells capable of pluripotential differentiation; neoplastic cells have smooth muscle, neural, or dual differentiation. These nonepithelial, spindle and epithelioid cell tumors are to be distinguished from leiomyoma and schwannoma arising from the intestines.

HEAD et al. (2003) divided gastrointestinal stromal tumors into 4 basic morphologic patterns, which are seen in both humans and animals:

1. Storiform. These tumors are characterized by spindle cells forming a storiform pattern, with areas of whorling and palisading of the cells. In less malignant tumors, neoplastic cells are uniform, with spindle-shaped nuclei and prominent nucleoli. In highly anaplastic tumors, the storiform pattern is less obvious, and the neoplastic cells are pleomorphic, spindle to polygonal, with occasional multinucleated cells. Extensive necrosis is characteristic.
2. Myxoid. These neoplasms are characterized by the proliferation of scattered, noncohesive, spindle to polygonal cells with myxoid matrix. The cells contain vesicular nuclei and prominent nucleoli. Some have epithelioid cells with large vesicular nuclei and prominent nucleoli. Others have spindle or polygonal cells separated by large pools of myxoid material. Areas of storiform or fascicular patterns of neoplastic cells are also seen.
3. Fascicul. Spindle cells are organized into interlacing and criss-crossing bundles of varying cellularity and individual cellular morphology. Neoplastic cells have vesiculated nuclei and prominent nucleoli. Tumors are highly vascular with dilated vessels, extensive areas of hemorrhage, and necrosis.
4. Epithelioid. This pattern is characterized by nests or sheets of spindle, round to polygonal cells haphazardly arranged, separated by little stroma. The plump spindle cells have mostly round nuclei, prominent nucleoli, and eosinophilic cytoplasm. Hemorrhage and necrosis are common.

Multiple tumors have been described in old horses, dogs, and cats; metastases are rare [71].

Tumorlike lesions

Hyperplasia of perianal glands, diffuse and nodular proliferations of morphologically normal merocrine perianal glands. Diffuse hyperplasia is unlikely to be confused with an adenoma. Nodules of hyperplasia are differentiated from adenoma because they are usually smaller and, although the borders of the nodules are distinct, there is no compression capsule. Hyperplastic glands are larger than normal glands, but are similarly composed of many large round or polyhedral cells of constant size set in a delicate stroma (Fig. 4.28). The age, breed, sex, distribution and hormonal stimulus are similar to adenoma [71].

Hyperplasia of rectal-type glands (colorectal polyp), see section on intestinal tumors.

8.18.1. Exocrine epithelial tumors

Ductal (tubular) adenoma, a benign tumor with a pattern that resembles pancreatic ducts and tubules; these tumors are asymptomatic and therefore incidental findings at autopsy. There is a complete capsule with compression of the surrounding normal tissue. Tumors are composed of tubules lined by cuboidal cells or duct-like structures lined by columnar cells supported by a little delicate stroma. There is slight evidence of dysplasia (some anisocytosis, slight loss of basal position of the nuclei) and slight cellular pseudostratification [71].

Acinar adenoma, a benign tumor with a pattern that resembles pancreatic acini; they are usually solitary, small, and asymptomatic. They must be differentiated from the more common nodular hyperplasia by evidence of compression of the surrounding normal pancreas [71].

Ductal (tubular) adenocarcinoma, a malignant tumor composed of large duct-like structures and medium-sized tubules (Fig. 8.40). Adenocarcinoma may be solitary or multiple. Even large tumors seldom destroy enough islet tissue to produce diabetes mellitus. The tumor periphery shows invasive growth into tissue spaces and perineural lymphatics. This invasive growth is usually into the peripancreatic fat, but may invade the duodenum. Fat necrosis of the adjacent adipose tissue is common, especially in cattle.

Fig. 8.40

Pancreatic ductal adenocarcinoma.

Cases of adenocarcinoma are well-recorded in dogs and cats; they are less common in cattle, rarely seen in horses, and extremely rare in pigs [71].

Acinar cell carcinoma, a malignant tumor composed of recognizable pancreatic acinar cells; examples have been recorded in dogs, cats and cattle. The pattern in well-differentiated tumors is of small acini with basal nuclei and faintly granular cytoplasm that sometimes has PAS-positive diastase-resistant staining. The round nuclei are uniform in size and mitoses are frequent. Coarse stroma may divide the tumor into lobules, but the acini and cell masses are supported by a delicate stroma [71].

Undifferentiated (anaplastic) carcinoma, a malignant epithelial tumor with no evidence of squamous or glandular differentiation. Examples have been recorded in dogs and cats. Most of the tumor is formed by irregular masses of pleomorphic cells ranging from polyhedral to spindle-shaped and showing anisocytosis. Nuclei show anisokaryosis, some are hyperchromatic, the nucleoli are prominent, and there are many mitoses. Multinucleate giant cells may be found. Areas of necrosis and hemorrhage are common.

8.18.2. Endocrine tumors (neuroendocrine tumors)

Endocrine tumors have been recorded in older dogs, cats, and cattle. Adenocarcinomas are found more often than adenomas. Amyloid has been recorded in dog and cat tumors but it is not evident in these neoplasms in cattle. Adult ferrets have a disproportionately high incidence of islet cell tumors [71].

Islet cell adenoma, a benign tumor having the morphology and immunohistochemistry of functional pancreatic islet of Langerhans cells. Tumors are up to 2 cm in diameter, usually solitary but sometimes multiple. When multiple in cattle, they have been linked to unilateral adrenal pheochromocytoma as part of a multiple endocrine neoplasia syndrome. In dogs and cats, they can occur in a pancreas with nodular hyperplasia and exocrine adenocarcinoma [71].

Islet cell carcinoma, a malignant epithelial tumor with some areas having the morphology and immunohistochemistry of functioning islet cells. The cells are pleomorphic and show anisocytosis, anisokaryosis, nuclear hyperchromasia and numerous mitoses. Focal areas of necrosis and hemorrhage are usually an indication of rapid growth and malignancy. Blood-borne metastases occur in the liver, and lymphogenous spread is to the local drainage lymph nodes [71].

Nonepithelial tumors in the pancreas are rare. Fibrosarcoma, neurofibroma, and neurofibrosarcoma have been recorded in cattle. The pancreas may be involved in multicentric system disease such as hemangiosarcoma, malignant melanoma, and tumors of the hematopoietic system in dogs, cats and horses [71].

Secondary tumors. Blood-borne metastases from the thyroid and mammary gland to the pancreas have been recorded in dogs. Direct extension from contiguous organs has been seen from alimentary lymphoma, and from carcinoma of the stomach, duodenum or common bile duct [71].

Unclassified tumors, neoplasms that cannot be placed in any other category.

8.18.3. Tumorlike lesions

Nodular hyperplasia of acinar cells, a nonneoplastic focus of acinar-type cells sharply defined but without a capsule and showing no compression or infiltration of the surrounding normal pancreatic tissue (Fig. 8.39). These lesions are a common asymptomatic incidental finding at autopsy of old cats, dogs, and cattle [71].

Fig. 8.39

Nodular hypertrophy of exocrine pancreas.

Chronic pancreatitis, focal aggregation of ducts and endocrine cells set in fibrous tissue infiltrated by chronic inflammatory cells.

Heterotopic pancreas (ectopic pancreas), foci of pancreatic acini, ducts and islets located outside the boundaries of the normal pancreas. These asymptomatic microscopic groups of cells may be found in the stomach, duodenum, spleen, gallbladder and adjacent mesentery. They occur rarely in the dog and cat [71].

Pancreatic steatitis, an increase in the interstitial adipose tissue of the pancreas that often shows fat necrosis, steatitis, and calcification. The lesion is sometimes seen in cattle with peritoneal fibrolipomatosis [71].

Cysts. These fluid-filled sacs can be differentiated from cystic tumors because their lining cells are not neoplastic.

Congenital cysts, small multiple cysts set in collagenous fibrous tissue. Lesions have been found in lambs, often associated with similar lesions in the liver [71].

Acquired retention cyst, cystic dilation of the duct system associated with obstruction of the lumen at some point and subsequent retention of secretion. Pancreatolithiasis as a cause of the condition has been recorded in cattle more often than in horses and dogs [71].

Pseudocyst, a pseudocystic structure lined by granulation tissue and containing debris, rich in pancreatic enzymes.

Nesidioblastosis, a diffuse hyperplasia of islet cells in the pancreas [71].

Fig. 8.5

Hyperplasia, parotid salivary gland. ^*)

Fig. 8.23

Intramucosal adenocarcinoma. ^*)

Fig. 8.34

Adenocarcinoma of recto - anal jonction. ^*)

Fig. 8.38

Prolimphocytic malign limphoma, duodenum.