Oral Cavity, Salivary Glands, and Esophagus

GI Pathophysiology: Oral Cavity, Salivary Glands, and Esophagus

• The lecture material is credited to Dr. Joyce Knoll, Dr. Sam Jennings, and Dr. Kara Priest.
• Fabio Rosa, DVM, MS, PhD, DACVP, at [email protected].

Outline

Oral Cavity

• Developmental Disorders.
• Malocclusion & Improper Wear.
• Abnormal tooth coloration.
• Stomatitis.
• Viral and non-viral infections.
• Non-infectious oral cavity diseases.
• Neoplasia.

Salivary Glands

• Ranula/Sialocele.

Esophagus

• Esophagitis, choke/impaction/foreign bodies, neoplasia.

Learning Objectives

• Define pathology terms
• Recognize clinical signs of upper GI disease.
• Name the cause and outline the pathogenesis of major diseases, including epidemiologic features, contributing factors, and expected outcome.
• Recognize and categorize gross lesions and main histologic lesions of major diseases.
• Diagnose or prioritize differential diagnoses using signalment, historical information, clinical signs, clinical pathology results, diagnostic imaging results, gross lesions, and/or histologic lesions.
• Understand basic features of major GI, pathobiliary, and pancreatic diseases in domestic species.
• Key features include clinical signs, cause, pathogenesis, epidemiology, and gross lesions.
• Aim is to create a foundation for the third-year internal medicine course.
• This is not the last exposure to GI, hepatobiliary, and pancreatic diseases.

Oral Cavity - Big Picture

• Normal mucosa is the first line of defense, providing access to the rest of the GI tract.
• Normal mucosa is smooth, shiny, pink, and stratified squamous.
• Melanosis is an incidental variation in melanin that can be seen in the mouth, GI tract, lungs, liver, brain, etc.
• Large animals show a greater significance of infectious diseases and many reportable diseases.
• Small animals show neoplasia and autoimmune/idiopathic stomatitis, which are generally more important.
• Dentistry-related issues will be covered by Dr. Rosenblad.

Important Terminology

• Stomatitis: inflammation of the mouth.
• Gingivitis: inflammation of the gingiva.
• Glossitis: inflammation of the tongue (lingual).
• Cheilitis: inflammation of the lips (labial).
• Pharyngitis: inflammation of the pharynx.

Oral Cavity, Pharynx & Esophagus - Clinical Clues

• Reluctance to eat/chew properly can be due to pain or gagging.
• Weight loss and dropping food can be clinical signs.
• Unusual breath odors are clinical signs.
• Ptyalism is excessive salivation.
• Dysphagia is the inability/reluctance to swallow due to pain, obstruction, or neurological disease. Increased Saliva Production results from:
  • Nausea
  • Excitement
  • Certain drugs and toxins
• Regurgitation is a clinical sign associated with esophageal disease.
• Dysphagia is oropharyngeal disease, resulting in defective swallowing (often worse with liquids), usually immediate, and non-forceful expulsion.
• Regurgitation is esophageal disease, resulting in expulsion from the esophagus, passively initiated by gravity, with undigested food. Possible complication from these conditions:
  • Aspiration pneumonia

Developmental Disorders: Palatoschisis/Cheiloschisis

• Palatoschisis is a cleft palate.
  • Communication between the oral and nasal cavities
  • Can cause aspiration pneumonia
• Cheiloschisis is a cleft lip (harelip).
  • May cause growth retardation due to difficulty sucking/eating
• Palatocheiloschisis is both cleft palate and cleft lip.
• Causes include unknown factors, genetics (don't breed), and toxic plants.
• Toxic plants:
  • Veratrum californicum in small ruminants, causing cyclopia too
  • Hemlock
  • Tobacco
  • Lupines plants
• Cria with palatoschisis may develop aspiration pneumonia secondary to food material entering the airways.

Prognathism, Brachygnathism, Malocclusion

• Prognathia is a jaw that is too long.
• Brachygnathia is a jaw that is too short.
• Both prognathia and brachygnathia can cause malocclusion.

Malocclusion & Improper Wear

• Malocclusion/Abnormal chewing.
• Overgrowth.
• Insufficient roughage
• Malocclusion & Improper Wear is especially problematic with continually erupting teeth in horses, rabbits, and rodents.
• Sharp outer edges of the upper molars in horses can cause lacerations of the opposing buccal mucosa. The process is exacerbated by:
  • Insufficient roughage in diet Consequences are:
  • Ulcers
  • Malnutrition
  • Infections

Abnormal Tooth Coloration: Enamel Hypoplasia

• Canine distemper virus causes enamel hypoplasia in the teeth.
• Enamel hypoplasia:
  • Canine distemper virus;
  • Intrauterine BVDV and Fluorosis
  • Tetracycline in high doses: given to pregnant dams/young puppies
    • Discoloration of dentin occurs even at lower doses.
• Canine distemper virus causes a segmental hypoplasia of the enamel by direct infection of the cells of the enamel organ.
• Tetracycline binds to calcium ions in the teeth at the time of tooth mineralization or calcification. If tetracycline exposure happens before the teeth erupt through the gingiva (gums), it causes an initial fluorescent yellow discoloration.
• Very high doses of tetracyclines in healthy animals can induce enamel hypoplasia.
• Affects the ameloblasts

Stomatitis

• Stomatitis is inflammation of the oral cavity.
• Large Animals viral causes of stomatitis are mostly reportable.
• Bacterial causes of stomatitis in large animals are somewhat reportable.
• Uremia
• Small Animal stomatitis is immune-mediated/idiopathic
• Basically, all large animal viruses described are reportable in MA except Malignant Catarrhal Fever and bovine papular stomatitis.
• Actinomycosis in cattle and calicivirus in cats are also reportable in MA.

Viral Stomatitis - Major Lesion Types

• Papule/Plaque:
  • Proliferation of keratinocytes leads to a firm, raised lesion.
  • Plaques are broad and flat.
  • Warts are examples of papules/plaques.
• Vesicle:
  • Swelling of keratinocytes/rupture results in a thin-walled, fluid-filled, raised lesion.
  • Blisters are examples of vesicles.
• Erosion/Ulcer:
  • Loss of keratinocytes due to necrosis and damage results in a depression.
  • Viral and non-viral etiologies can cause all of these types of lesions.

Papule

• Mechanism: hyperplasia and hypertrophy/swelling of the cells.
• Pox & papillomaviruses.
• Bovine papular stomatitis (parapox), contagious echthyma (parapox), and papillomavirus in dogs are main examples in the oral cavity.

Vesicle

• Split is in layers of epithelium.
• Space is filled with serum, inflammatory cells, and debris.
• Mechanism:
  • Excessive cellular swelling/Disrupt intercellular junctions.
  • Lyse epithelial cells.
• Foot and Mouth Disease, Vesicular Stomatitis, Vesicular Exanthema, and Swine Vesicular Disease are main viral causes.
• Non-viral causes can include burns and friction.

Erosion/Ulcer

• Partial (erosion) or total loss of epithelium (ulcer).
• Mechanisms:
  • Epithelial injury: trauma, chemical, thermal, or progression of papule or vesicle.
  • Ischemia: vascular injury such as Bluetongue or Malignant Catarrhal Fever viruses.
  • Mixed mechanisms: BVD/MD, uremia, or NSAIDs.
• There is a crust made of inflammatory cells and dried serum. - Characteristic of mucosal disease or MCF - BVD = bovine viral diarrhea - MD = mucosal disease

Bovine Papular Stomatitis (parapoxvirus)

• Common, self-limiting.
• Leads to Papules/plaques leading to erosion/ulcer on the:
  • Lips
  • Mouth
  • Esophagus
  • +/- forestomach
  • +/- teats
• Zoonotic (minor skin lesions: erythema, occasional papules).
• Poxviruses cause ballooning degeneration and intracytoplasmic inclusions.
• Viral inclusion body can help you narrow down the cause.

Bovine viral diseases causing erosions/ulcers

• Bovine Viral Diarrhea/Mucosal Disease.
• Malignant Catarrhal Fever (MCF). Rinderpest - foreign animal dz is eradicated
• Morbidity/Mortality of all 3 have high mortality.
  • BVD/MD causes severe economic losses and is a reportable disease.
  • MD & MCF have low morbidity
• FMD contrast is high morbidity

Bovine Viral Diarrhea/Mucosal Disease

• There are generally no oral lesions with just BVDV infection (non-cytopathic strain).
• More often: early embryonic death, abortions, congenital defects, & immune suppression.
• Mucosal Disease (MD) is due to viral mutation of PI cattle or superinfected with cytopathic strain.
  • Persistent infection (PI carrier) only develops in utero; first 4 months of gestation.
  • Erosions/ulcers throughout GI tract (epithelial and vascular damage).
  • Fever, hemorrhagic diarrhea, death.
  • Immune suppression from lymphoid depletion; high mortality and low morbidity.
• Fetuses exposed to BVDV "in utero" in the first 4 months of gestation are tolerant to the virus and become persistently infected (PI) shedding extensively. If PI cattle become superinfected with a cytopathic strain (or as a mutation of the resident noncytopathic BVDV). Mucosal Disease develops → severe hemorrhagic diarrhea, with ulcerations (tongue, oral cavity, forestomach, stomach, intestine, colon). Lymphoid depletion due to BVDV helps distinguish MD from Malignant Catarrhal Fever.

Malignant Catarrhal Fever (usually from OHV-2)

• Frequently fatal disease of cattle, bison, deer Sheep, goats, wildebeest can be carriers; bison >1,000x more susceptible • Systemic infection
  • Erosions/ulcers in the Gl, respiratory and urinary tracts (vasculitis) -Widespread vasculitis (lymphocytic)
  • Enlarged lymph nodes (lymphocyte proliferation)
  • Corneal edema (blue eye)
• (MCF) is a frequently fatal disease syndrome primarily of certain ruminant species caused by one of several herpesviruses.
  • Occurs worldwide especially in the US and Canada;
  • Characterized by inflammation, ulceration, and exudation of the oral and upper respiratory mucous membranes, and sometimes eye lesions, nervous system disturbances, and dermatitis.
• Sheep infected with OvHV-2 are the principal source of MCF outbreaks in bison and cattle.
  • High levels of OvHV-2 viral DNA are consistently found in nasal secretions of sheep, suggesting that the nose is the important portal for OvHV-2 shedding.
  • The virus does not cause illness in sheep.
• MCF can be confused with Bovine viral diarrhea, salmonellosis, and pneumonia complex, among others.
  • Testing sick animals is the key to establishing an accurate diagnosis.
  • The diagnosis of MCF is based on epidemiology, clinical signs, pathology, and detection of viral DNA in tissues.
  • Serology is recommended for screening of subclinically infected carriers.
    • OHV-2 = ovine herpesvirus-2.

Foot-and-Mouth Disease (picornavirus)

• All cloven-hooved animals.
• Vesicles Ulcers: muzzle, mouth, coronary bands, teats Sheep (maintenance species): rarely get oral blisters; lesions on coronary band of hoof more likely Swine (amplification species): lameness main sign; vesicles on feet; can slough claws.
• Very high morbidity, low mortality.
• Survives weeks on fomites, travels easily (aerosolization), economic impact is high $$$
• FMDV can survive weeks on fomites; aerosols can travel miles on wind.
• Infected swine are exceptional disseminators of virus. - They can produce aerosols many times greater in virus concentration than those produced by cattle or sheep. - Sometimes referred to as "amplifier hosts". Sheep are maintenance hosts
• The 2001 Outbreak in the UK:
  • Took seven months - cost $16 billion - and >4 million cattle were slaughtered to control spread
• Last case in the US was in 1929

Vesicular Stomatitis (rhabdovirus)

• Cattle, small ruminants, swine, and horses. Zoonotic (Flu-like symptoms).
• Clinical picture nearly the same as FMD but not quite as high morbidity.
• Black flies and sand flies are vector; also direct contact.

Contagious Ecthyma (parapoxvirus) a.k.a. Orf

• Affects sheep and goats.
• Preexisting mucosal lesion → Virus infection: proliferation and necrosis of keratinocytes.
• Papules/plaques → Ulcers/Crust: muzzle, mouth, esophagus; +/- forestomach, feet, or skin.
• Analogous to Papular Stomatitis in cattle.
• Zoonotic (red, itchy, or painful lump) and reportable disease in MA.

Bluetongue (orbivirus)

• Infects endothelium → vascular injury → edema, effusions, hemorrhages, and necrosis. The Oral:
  • Muzzle erosions/ulcers, coronitis & lameness, abortion & birth defects (in utero infection or vaccination).
• Transmitted by biting insects, not directly contagious.
• Causes edema, hemorrhage, and cyanosis of the tongue.
• Reportable disease in MA.
• Differential diagnosis: FMD, Vesicular Stomatitis.

Swine - The vesicular diseases

• Vesicular Stomatitis (rhabdovirus) Foot-and-mouth Disease (picornavirus)
• Swine Vesicular Disease (enterovirus)
• Vesicular Exanthema of Swine (calicivirus) { Many species Pigs only
• Seneca Valley virus (SVV) is a small, non-enveloped picornavirus, unknown until 2002.
• SVV is linked to idiopathic vesicular disease and multiple cases of swine vesicular disease in the United States have been reported.
• SVV causes vesicular lesions in pigs that are clinically indistinguishable from foreign animal diseases such as FMD, SVD, vesicular stomatitis, and vesicular exanthema of swine virus. Lameness is commonly observed.
• All are identical grossly, requiring virus isolation and PCR for definitive diagnosis.

Comparison of Large animal Vesicular Diseases

• FMD = Foot and Mouth Disease
• VS = Vesicular Stomatitis
• MD = Mucosal disease
• MCF = Malignant catarrhal fever

Viral Stomatitis

Viral Stomatitis

• Canine Oral Papillomavirus
  • Has Papules, cauliflower-like (single or multiple)
    • Common in young dogs
    • Usually regress
    • Histo: Intranuclear inclusions (Pox causes intracytoplasmic)
• Bovine Papillomavirus

Viral Stomatitis - Cats: Feline Calicivirus

Causes:

• Ulcers
  • Orally/Lingually
  • plus oculonasal discharge (rhinitis/conjunctivitis)
• Very common
  • (high morbidity, low mortality) Most often affects kittens; most cats recover Occasional mutant strains may cause more severe systemic disease. DDx herpesvirus (- oral ulceration/ + keratitis).
• C albicans is a normal inhabitant of the nasopharynx, GI tract, and external genitalia of many species of animals and is opportunistic in causing disease.
• Factors associated with candidal infections are disruption of mucosal integrity, administration of antibiotics; and immunosuppressive drugs or diseases.
• Gross lesions of the skin and mucosae are generally single or multiple, raised, and circular, with white masses covered with scabs.

Bacterial and fungal oral infections

• Wooden Tongue causes penetrating injury (coarse feed) resulting in Actinobacillus lignieresii (bacteria) infection primarily in cattle. - Produces pyogranulomatous glossitis and fibrosis (lymphadenitis too)
• In Actinobacillosis, lignieresii is part of the normal bacterial flora of the upper digestive tract, and progressive inspiratory dyspnea and nasal discharge are found in patients having granulomas deeper in the nasal cavity, larynx, pharynx, or trachea.
• Difficulty swallowing occurs due to a stiff tongue.

Bacterial Oral Infections: Lumpy Jaw

• Primarily found in cattle. - Results from Penetrating injury (coarse feed)/ periodontitis → Actinomyces bovis - Produces Pyogranulomatous osteomyelitis and lymphadenitis
• A bovis is part of the normal oral flora of ruminants. gram-positive, nonacid fast pleomorphic rods to coccobacilli.
  • Bovis is the etiologic agent of lumpy jaw in cattle.
• Lumpy jaw has also been isolated from nodular abscesses in the lungs of cattle and infrequently from infections in sheep, pigs, dogs, and other mammals, including chronic fistulous withers and chronic poll evil in horses.
• Lumpy jaw is a localized, chronic, and progressive granulomatous abscess that most frequently involves the mandible, the maxillae, or other bony tissues in the head.
  • Alveoli around the roots of the cheek teeth are frequently involved.
  • The primary lesion appears as a slow-growing, firm mass that is attached to, or is part of, the mandible.
• Some cases:
  • Ulceration with or without fistulous tracts form
    • Drainage of purulent exudate
• Splendore-Hoeppli phenomenon (asteroid bodies) is characterized by microorganisms (fungi, bacteria and parasites) or biologically inert substances surrounded by radiating intensely eosinophilic material.
• "It's due to deposition of antigen-antibody complexes and debris from the host inflammatory cells, and appears as strongly eosinophilic amorphous material with radiating start-like or club-shaped configurations."

Fungal Oral Infections: Thrush/Candidiasis

• Candida albicans (yeast)
  • Is associated with immunosuppression or antibiotic/steroid use and most common in birds, foals and pigs
• C albicans is a normal inhabitant of the nasopharynx, GI tract, and external genitalia of many species of animals and is opportunistic in causing disease. Factors associated with candidal infections are disruption of mucosal integrity, administration of antibiotics; and immunosuppressive drugs or diseases. Gross lesions of the skin and mucosae are generally single or multiple, raised, circular, with white masses covered with scabs and Hyperkeratosis + yeast/ pseudohyphae grey-green pseudomembrane in the oral cavity and esophagus.

Non-Infectious Oral Cavity Diseases: Uremic Ulcers

• Are common in any species
• "Uremic toxins" → endothelial injury → thrombosis/ischemia → necrosis; increased blood and salivary urea → urease producing bacteria in oral cavity convert urea to ammonia → direct toxic epithelial injury (necrosis).

Eosinophilic Granuloma Complex

• Likely hypersensitivity reaction, primarily in cats and rarely in dogs.
• Several related entities in cats (young cats, especially <1 year of age).
• Has indolent ulcer on the upper lip (very distinctive, rarely biopsied). Causes include:
  • Ulcerations of the upper lip
  • Masses on the tongue, lip, palate
  • Eosinophilic plaque on haired skin on abdomen, and thigh.
• Creates eosinophilic granulomas: Masses on tongue, lip, palate.
• Creates eosinophilic plaque on haired skin on abdomen, and thigh.
• FNA or biopsy will show a mixture of inflammatory cells with increased numbers of eosinophils and mast cells, and multinucleated giant cells.
• On biopsy, you can see collagenolysis in the center of the eosinophilic granuloma.

Lymphoplasmacytic Stomatitis

• Highly possible immune-mediated condition in cats.
• Causes severe inflammation of the gum line (gingivitis) and tissues around teeth (periodontitis).
• Starts with a bacterial infection that dysregulates the immune system See Dr. Rosenblad's lecture
• Two manifestations: affects the gingiva close to the teeth, and/or ulcerations in the caudal oral cavity
• One treatment is tooth extraction to decrease inflammation

Gingival Hyperplasia

• Fleshy around Dogs (Boxer) typically get fleshy masses that DON'T deform teeth, which may appear worse if there is also inflammation. Main ddx is neoplasia if there is any mass

• Multifocal or diffuse, unlike tumors that are usually focal

• Possibly idiopathic, but can be drug-induced (cyclosporine)

• FFH = focal fibrous hyperplasia

Oral Cavity Neoplasia - General

• The main lesion is a Mass/Nodule, and some masses are non-invasive or minimally invasive such as:
  • Papillomas & Peripheral odontogenic fibroma Some are invasive (bone lysis on rads, and displace teeth)
• Acanthomatous ameloblastoma
  • Squamous cell carcinoma Melanoma & Fibrosarcoma NOTE: not including osteosarcoma or other bone tumors in this discussion although they can arise from the mandible
• Oral masses are usually a bad sign

Squamous Cell Carcinoma

• Is #1 malignant oral tumor in cats and #2 in dogs. The Same is true for horses but but is not a common overall and is locally invasive - (hard to excise)
• Most common site in cats: ventral surface of the tongue
• Bracken fern toxicity in cattle and high relatively low metastatic rate (except tonsillar SCC).
• Key feature of malignancy: cellular pleomorphism

Oral Melanoma

• Is malignant oral tumor in dogs that is rare in other species and locally invasive with a High risk of metastasis Commenly (but not always) pigmented
• "amelanotic melanoma" can be trickier to diagnose Amelanotic melanomas can be a diagnostic challenge and may resemble sarcomas, carcinomas, or round cell tumors.
• Perform Immunohisto-chemical staining for diagnosis: Express Melan-A, PNL-2, and tyrosine-related proteins-1 and -2
• Has a high rate of metastasis to local lymph nodes and lungs

Fibrosarcoma

• This is when there is no epithelium. This is the 2nd malignancy for feline mouths and 3rd malignancy for canine mouths.
• Low risk of metastasis

Odontogenic Neoplasia

• These typically do not metastasize
• They appear in 2 forms:
  1. Peripheral odontogenic fibroma (fibromatous epulis)
  2. Acanthomatous ameloblastoma (acanthomatous epulis) In the case of the two, POF is derived from periodontal ligaments. Its benign

AA is more invasive. can invade bones; both odontogenic epithelium and periodontal ligament

Peripheral odontogenic fibroma

• Primarily periodontal ligament stroma +/- some odontogenic epithelium
• Less invasive (usually don't recur)
• The Main gross ddx is gingival hyperplasia, earlier stages of malignant tumors

Acanthomatous ameloblastoma (acanthomatous epulis)

• Primarily odontogenic epithelium + periodontal ligament stroma Small biopsies may miss epithelium but it is: More invasive : harder to fully excise- Bone lysis The major gross ddx is malignant neoplasia

Oral Cavity Neoplasia- Summary

• Melanomas are the most common oral tumor to metastasize at high frequency but both SCC and FSA CAN metastasize but less commonly EXCEPT tonsillar SCC is (very aggressive and often mets) and generally, Odontogenic tumors don't metastasize

For malignant tumors, relative frequency: Dog: ~ Melanoma > SCC > FSA > others Cat: SCC >> FSA >> others

• Malignant tumors can loosen teeth

Ranula & Sialocele (Salivary Mucocele)

• Contains Both saliva-filled, fluctuant structures lined by granulation tissue without the presence of underlying gland However... This is under the tongue without the same "seal" leading to different presentation Sialocele is under the tongue with the former having a subcutaneous Most common in dogs: Usually involves compression- Obstruction of the duct → rupture Usually occurs as a result of trauma from inflammation however the location and palpating as well as cytology help ID
• Most common site: submandibular salivary glands
• Contains saliva, mucus, and inflammatory cells
• Treatment: surgical excision of mass and removal of the salivary gland, including ligation of duct

Esophagitis

Chemical injury from reflux in any species that lacks mucus bicarbonate barrier of stomach and usually as a result of taking Doxycycline tablets without food.

• It is recommended to give doxycycline with food and follow up with a water bolus Larger Animals often get :
  • Virus that causes stomitits & Bovine papillomarviruses
• Reflux esophagitis is the most common type
• Infectious esophagitis is uncommon, but vesicular diseases can cause it

Causes include: MU, MCF, "VESICULAR STOMATITS VIRUSES"

Choke/ Impaction/Foreign Bodies

It Occurs and creates horses>ruminants>dogs(FBs) especially in the case of improper chewing from teeth and if there is large amount of Dehydration & in the instance of foreign material and large food items. These conditions usually lead to Ptyalism, gagging, coughing, difficulty swallowing, and discomfort

• Check the teeth in large animals to rule out improper chewing Some major areas of narrowing are:
  • Thoracic Inlet & Heart Base leading to Diaphragm The aforementioned usually ends in Circumferential pressure and Necrosis

Choke/Impaction/Foreign Body Sequelae

• Aspiration pneumonia Pressure necrosis occurs and causes rupture in plueritits & lumen timpany causing ercutation

Stricture is caused from: 7 year old, MI, chihuahua presented for bloody drooling, regurgitation, and anorexia

• Can be due to sharp objects (chicken bones)

Megaesophagus

Occurs as result of eating as a dog, usually from solid food and result in regurgitation often followed by aspiration or pneumonia. It then further advances to Acquired Neuromuscular problems or diffuses issues which also occur via:

• Myasthenia Gravis
• Myopathies (polymositis) OR is congenital causing a segmental dilation usually from a physical blockage that comes about as result of A persistent Right Aortic Arch
• There is also Stricture(PRAA= Dilation cranial to the heart base
• Known association with:
  • Myasthenia gravis: autoimmune, affects acetylcholine receptors
  • Polymyositis: immune-mediated, affects multiple muscles including tongue
  • Congenital form: persistent right aortic arch, creating a vascular ring anomaly

Parasitic esophagitis: Spirocerca lupi

• This occurs in Nematode & Granulomatous and occurs as a result of Nodules that can develop from Neoplasia :
• can generate Fibrosarcomas or osteosarcomas
• Transmitted by ingestion of beetle (intermediate host) or paratenic hosts (chicken, rodents)
• Larvae migrate to the esophagus, forming granulomas
• Can progress to fibrosarcomas or osteosarcomas, with metastasis to the lung.

Esophageal Neoplasia

Occurs very rarely in all species(except cattle eating bracken fern) Epithelial- Papilloma (usually viral induced) then Squamous cell carcinoma Mesenchymal- Fibrosarcoma Smooth muscle (leiomyoma/sarcoma)