JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
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 2 per HPF (0.237mm²), and there is marked anisokaryosis and anisocytosis.  Multifocally, neoplastic cells undergo disorderly individual cell keratinization (dyskeratosis). Multifocally, neoplastic cells surround variably sized accumulations of concentric, lamellated eosinophilic keratin (keratin pearls). Multifocally, neoplastic cells 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:

• Squamous cell carcinoma (SCC) is the most common gastric tumor in horses
  • Rarely found on the gums and hard palate
• Arises from stratified squamous epithelium lining the pars esophagea (AKA pars nonglandularis), and may extend into esophagus (the slide in this case is of the pars glandularis but the overlying mucosa is relatively normal, suggesting the neoplasm arose in the adjacent pars nonglandularis rather than at the site of this section)

 

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 +
  • Canine oral SCC:
    • Cytokeratins (AE1/AE3, 34BE12), p63, and calretinin may be useful in discriminating between canine oral papillary squamous cell carcinoma, conventional squamous cell carcinoma, and canine acanthomatous ameloblastoma (Thaiwong, Vet Pathol. 2018)
    • Ki67 may be helpful in differentiation oral squamous cell carcinomas(higher) from canine acanthomatous ameloblastomas (lower) (Peralta, Vet Pathol. 2019)

 

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

• Cats: Oral SCC is the most common oral malignancy of cats, which is locally invasive
• 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

• 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
• Zoo, exotics, wildlife:
  • African pygmy hedgehogs:  Oral SCCs are common (Del Guila, J Vet Diagn Invest. 2019)
  • 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)

 

REFERENCES:

1. 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.
2. Del Guila G, Torres CG, Carvallo FR, et al. Oral masses in African pygmy hedgehogs. J Vet Diagn Invest. 2019;31(6):864-867.
3. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:366-367.
4. 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.
5. Hsueh CS, Li WT, Jeng CR, Pang VF, Chang HW. Diffuse-type Gastric Mucinous and Signet Ring Cell Adenocarcinoma in a Captive California King Snake (Lampropeltis getula californiae). J Comp Pathol. 2018;160:10-14.
6. Mikiewicz M, Pazdzior-Czapula K, Gesek M, et al. Canine and feline oral cavity tumours and tumour-like lesions: a retrospective study of 486 cases (2015-2017). J Comp Pathol. 2019;172:80-87.
7. Munday JS, Lohr CV, Kiupel M. Tumors of the alimentary tract. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th Ames, IA: John Wiley & Sons; 2017:557-559.
8. Peralta S, Grenier JK, McCleary-Wheeler AL, et al. Ki67 labelling index of neoplastic epithelial cells differentiates canine acanthomatous ameloblastoma from oral squamous cell carcinoma. J Comp Pathol. 2019;171:59-69.
9. 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.
10. Thaiwong T, Sledge DG, Collins-Webb A, Kiupel M. Immunohistochemical characterization of canine oral papillary squamous cell carcinoma. Vet Pathol. 2018;55(2):224-32.
11. 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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