JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-N08 (NP)

 

Signalment (JPC #2296428): An adult male European wild horse.

 

HISTORY: The horse became emaciated, depressed, and anorectic, developed liquid mucoid stools, and was refractory to treatment for gastroenteritis.

 

HISTOPATHOLOGICAL DESCRIPTION: Stomach, pars glandularis: Infiltrating and expanding the lamina propria, submucosa, and tunica muscularis, and elevating the overlying relatively normal glandular mucosa, is a multilobular, unencapsulated, poorly circumscribed, moderately cellular neoplasm composed of polygonal cells, often undergoing keratinization, arranged in islands, cords, and trabeculae supported by a moderate fibrovascular stroma and separated by anastomosing bands of desmoplastic fibrous connective tissue. Neoplastic cells often exhibit prominent intercellular bridging and have distinct cell borders, abundant eosinophilic granular cytoplasm, and one round to oval, vesiculate nucleus with finely stippled chromatin and one distinct, magenta nucleolus. Mitoses average 5 per 2.37mm² and there is marked anisokaryosis and anisocytosis. Multifocally, neoplastic cells undergo disorderly individual cell keratinization (dyskeratosis), surround variably sized accumulations of concentric, lamellated eosinophilic keratin (keratin pearls), and invade blood vessels. Multifocally within the stroma, there are areas of hemorrhage, fibrin, and edema with scattered lymphocytes, plasma cells, and fewer histiocytes and neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Stomach, pars glandularis: Squamous cell carcinoma, breed unspecified, equine.

 

GENERAL DISCUSSION:

• Rarely found on the gums and hard palate

 

PATHOGENESIS

• The underlying cause and pathogenesis has not been established
• Recently, a subset of equine gastric squamous cell carcinomas have been associated with equus caballus papillomavirus 2 infection (EcPV2) (Alloway, Vet Pathol. 2020)

 

TYPICAL CLINICAL FINDINGS: 

• Middle-aged to older horses (>10 years), with no breed or sex predilection
• Nonspecific clinical signs with gradual onset and chronic progression
• Inappetence is the most common presenting complaint
• +/- dysphagia, weight loss, emaciation, colic, hypersalivation, fever, tachypnea
• +/- mesenteric lymphadenopathy, which may be palpable per rectum
• Normocytic, normochromic anemia is the most common hematological abnormality
• Hypoalbuminemia is the most common serum biochemical abnormality
• +/- hypercalcemia (due to release of parathyroid hormone-related peptide, i.e. humoral hypercalcemia of malignancy [HHM]); hyperfibrinogenemia and hyperglobulinemia (due to secondary inflammation); increased liver enzymes (associated with hepatic metastases)

 

TYPICAL GROSS FINDINGS:

• Sharply-demarcated, cauliflower-like mass, 10-40 cm in diameter
• Thickened muscular wall with scirrhous, firm texture
• Superficial ulceration, deeper necrosis and hemorrhage
• May extend into and obstruct distal esophagus
• +/- proliferative or scirrhous tissue on gastric serosa
• +/- peritoneal implants on intestine, testicles, omentum, parietal peritoneum (i.e. carcinomatosis)
• +/- direct extension to adjacent liver, spleen, diaphragm, pleura
• +/- hematogenous metastasis to liver, lung, kidney, and/or adrenal gland
• +/- peritoneal effusion

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Islands, cords, and trabeculae of large, invasive epithelial cells with abundant eosinophilic cytoplasm and prominent intercellular bridging 
• Anisocytosis, anisokaryosis, +/- keratin pearls (well-differentiated SCC) or individual cell keratinization (poorly-differentiated SCC)
• Desmoplasia with plasma cells; neutrophilic inflammation in keratinized areas
• Tumor cells infiltrate lymphatics and blood vessels

 

ADDITIONAL DIAGNOSTIC TESTS:

• Neoplastic cells are commonly found in cytology of peritoneal lavage fluid
• Immunohistochemistry: Cytokeratin positive

 

DIFFERENTIAL DIAGNOSIS:

• Gross appearance in cases of carcinomatosis: Mesothelioma (distinguish by histopathology, co-expression of vimentin and cytokeratin)
• Other gastric neoplasms of horses: Adenocarcinoma, leiomyoma, lymphoma, leiomyosarcoma, gastrointestinal stromal tumor, papilloma, benign polyp

 

COMPARATIVE PATHOLOGY:

• Other common locations of SCC in the horse: genital mucosa (associated w/ EcPV2) 
• Rats: Have a stratified squamous gastric cardia; SSC may occur spontaneously or be induced in toxicologic studies
• Dogs: Up to 90% of malignant gastric tumors are adenocarcinomas

• Oral SCC is the second most common oral tumor behind melanoma; involves tonsil and oral mucosa

• Recent study found SCC is also the most common oral malignancy in captive nondomestic felids (Scott, Vet Pathol. 2020)

• Pigs: Gastric SCC of the esophageal region is not reported
• Cattle: SCC is associated with oral papillomatosis and bracken fern

• Other SCC locations: eyelid, conjunctiva (lateral limbus), third eyelid, esophagus, rumen

• Pet and aviary birds: SCC has been reported in the beak, oral mucosa, tongue, esophagus, and crop
• Primary gastric SCC has been reported in two Kenyan giant forest hogs, humans, llamas, dogs, Greenland collared lemmings (Dicrostonyx groenlandicus), a pademelon (Thylogale billardieri), and a lion
• Nonhuman primates: SCC is the most commonly diagnosed tumor of the oral cavity and esophagus
• Zoo, exotics, wildlife: 

• Smooth Green snakes: Oropharyngeal squamous cell carcinomas have been recently associated with Opheodrys herpesvirus 1
• California king snake: Diffuse-type gastric mucinous and signet ring cell adenocarcinoma has been identified
• Psittacines: Alimentary SCC cases have been reported in the oral cavity alone, crop alone, crop and esophagus, proventriculus alone, and crop, esophagus, and proventriculus (Gonzalez-Astudillo, J Vet Diagn Invest. 2021)
• Recent report of SCC of the tongue in two Brazilian anteaters (Renales, J Comp Pathol. 2020)
• Recent report of oral SCC associated with a novel herpesvirus in a Blanding’s turtle (Andersson, J Vet Diagn Invest. 2021)
• Cloacal SCC has been recently reported in captive bearded dragons (LaDouceur, J Comp Pathol. 2022)
• Relatively common in the snow leopard, where they are often associated with papillomavirus-induced hyperplasia in the oral cavity
• Oral papillomas in bottlenose dolphins can transform to carcinoma in situ and then to aggressive SCC
• SCC can occur in fish, but typically without the keratin pearl formation that is characteristic of mammalian SCC

 

 

REFERENCES:

1. Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012: 593-594.
2. Alloway E, Linder K, May S, et al. A subset of equine gastric squamous cell carcinomas is associated with Equus caballus papillomavirus-2 infection. Vet Pathol. 2020;57(3):427-31.
3. Andersson KE, Adamovicz L, Mumm LE, et al. Detection of a novel herpesvirus associated with squamous cell carcinoma in a free-ranging Blanding’s turtle. J Vet Diagn Invest. 2021;33(2):348-351.
4. Arenas A, Gardiner CH, Miranda FR, et. al. Pathology of free-ranging and captive Brazilian anteaters. J Comp Pathol. 2020;180:55-68.
5. Frasca SJ, Wolf JC, Kinsel MJ, Camus AC, Lombardini ED. Osteichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:951. 
6. Gonzalez-Astudillo V, Mete A, Navarro MA, et al. Alimentary squamous cell carcinoma in psittacines: 12 cases and review of the literature. J Vet Diagn Invest. 2021;33(5):906-912.
7. Jones AL, Suarez-Bonnet A, Mitchell JA, et al. Avian papilloma and squamous cell carcinoma: a histopathological, immunohistochemical and virological study. J Comp Pathol. 2020;175:13-23.
8. LaDouceur EEB, Argue A, Garner MM. Alimentary tract neoplasia in captive bearded dragons (Pagona spp). J Comp Pathol 2022;194:28-33.
9.  Munday JS, Lohr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th ed. Ames, IA: John Wiley & Sons; 2017:557-559.
10. Ossiboff RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:898. 
11. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015: 58, 63, 68.
12. Scott KL, Garner MM, Murphy BG, et al. Oral lesions in captive nondomestic felids with a focus on odontogenic lesions. Vet Pathol. 2020;57(6):880-884.
13. Spagnoli ST, Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:438-439.
14. St. Leger J, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:549. 
15. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 365, 598-600, 855, 864, CP16D.
16. Terio KA, McAloose D, Mitchell E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:269-272. 
17. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier Saunders; 2015:25-26,106-107.

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