JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-P10

 

 

Signalment (JPC #1621137):  A dog

 

HISTORY:  None

 

HISTOPATHOGIC description:  Esophagus:  Focally expanding the tunica muscularis, compressing adjacent skeletal myocytes and overlying submucosal glands, and elevating the overlying submucosa and mucosa is a 14 x 8 mm inflammatory nodule centered on numerous transverse and longitudinal sections of adult spirurid nematodes surrounded by abundant plasma cells, macrophages (often hemosiderin-laden), fewer lymphocytes, and rare neutrophils and eosinophils. This inflammatory infiltrate extends into the submucosa, tunica muscularis, and serosa.  Nematodes and inflammatory cells are surrounded by numerous reactive fibroblasts and small caliber blood vessels (granulation tissue) progressing peripherally to more dense fibrous connective tissue (fibrosis).  Adult nematodes are 1 mm in diameter and have an 8 μm thick, smooth cuticle, coelomyarian-polymyarian musculature, prominent lateral cords, a pseudocoelom containing a moderate amount of brightly eosinophilic fluid, an intestine lined by uninucleate columnar epithelium with a prominent brush border, and female reproductive organs.  Multifocally, adjacent myocytes are compressed and shrunken (atrophy) and are often separated/replaced by fibrosis.

 

Morphologic diagnosis:  Esophagus:  Esophagitis, nodular, fibrosing, lymphoplasmacytic and histiocytic, chronic, marked, with adult spirurid nematodes, etiology consistent with Spi,rocerca lupi, breed unspecified, canine.

 

Etiologic diagnosis:  Esophageal spirocercosis

 

CAUSE:  Spirocerca lupi

 

General DISCUSSION:

• Spirurid nematode of canids (dog, red fox, wolf, coyote, jackal) and some wild felids (bobcat, lynx, snow leopard) and other carnivores
• Two species: lupi (tropics and the United States) and S. arctica (northern Russia)
• Lesions usually in the distal esophagus, cardia of stomach, and aorta; however, lesions may occur at other locations (urinary bladder, kidneys, subcutaneous tissue, thoracic vertebrae) because of aberrant larval migration
• Most domestic animals are infected by ingestion of insectivorous paratenic hosts (e.g. chicken, rodents, reptiles) 
• lupi is associated with esophageal fibrosarcoma and osteosarcoma

 

PATHOGENESIS:

• Canid (or other carnivore) ingests third stage Spirocerca larvae encysted in the intermediate host (dung beetle) or insectivorous paratenic host
• Larvae are liberated in gastric lumen and migrate through gastric mucosa, gastric arteries, and subintimal thoracic aortic wall to caudal esophagus, where they mature and promote formation of a fibroblastic nodule, often with fistula through which the tail of the female worm may protrude
• Esophageal fibroblastic nodule can undergo malignant transformation to sarcoma; the mechanism of neoplastic transformation is unknown, but recent studies indicate that  increased expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and IL-8 may have a role in transformation

 

LIFE CYCLE:

• The adult lupi is a large red nematode (female: 6-7 cm long, males: 3-4 cm long) which persists in a nodule within the wall of the final host’s (canid) esophagus
• The female lays small (35 x 15 μm) embryonated eggs, which are transferred through a tract in the nodule into the esophageal lumen
• The eggs pass through the gastrointestinal tract and are excreted in the feces or vomitus where they are ingested by coprophagous beetles (intermediate host), and mature to infectivity (L3) stage within two months; carnivores are directly infected by ingestion of an infected beetle containing L3 stages or by ingestion of the paratenic host (poultry, wild birds, lizards, and rodents that consumed the beetles)
• The infective larvae are freed in the stomach of the final host; they penetrate the gastric mucosa and migrate within the walls of the gastric arteries to the thoracic aorta
• The larvae migrate from the aorta to the esophagus at a point about midway between the diaphragm and the aortic arch; here, they undergo the final phase of maturation and incite nodule-like granulomas
• Approximately 3 months post-infection of the final host, the larvae complete their development and molt into immature adults that migrate to the esophagus and repeat the nematode’s life cycle

 

TYPICAL Clinical FINDINGS:

• Clinical disease is uncommon
• May see esophageal obstruction; dysphagia; vomiting or regurgitation; coughing
• May see sudden death from rupture of an aortic aneurysm or malignant neoplasm

 

TYPICAL GROSS FINDINGS:

• Esophagus: Cystic lesion in the esophagus or cardia
• Terminal thoracic and anterior abdominal aorta: Rough, granular, linear or oval plaques on endothelium; aneurysms, thrombi, mineralization, and nematodes
• Thoracic vertebra: Spondylosis deformans (aberrant larval migration)
• May see hypertrophic osteopathy with sarcoma (fibrosarcoma or

osteosarcoma)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Esophagus: Variably mature collagen capsule and lymphoplasmacytic inflammation; pre-neoplastic lesions have activated fibroblasts with varying degrees of atypia (multinucleation, polygonal shape) and frequent mitoses
• Spirocerca lupi: The intestine appears tri-layered because the nuclei are at the base of the microvilli; very small eggs are arranged like seeds in a pomegranate; it has a smooth cuticle, coelomyarian-polymyarian musculature, prominent lateral cords, a pseudocoelom containing a moderate amount of eosinophilic material, an intestine lined by uninucleate columnar epithelium with a prominent brush border and male or female reproductive organs

• Aorta: May include intimal and medial hemorrhage and necrosis;  intimal roughening with thrombosis; aneurysm with aortic rupture; intimal and medial mineralization and heterotopic bone deposition

 

ADDITIONAL TESTS:

• Optimal accuracy is gained by combining fecal floatation with a PCR-based assay that uses feces or mucus from the final host and targets the lupi cox1
• Plasma and serum VEGF concentrations can be used to differentiate nonneoplastic and neoplastic spirocercosis (higher in neoplastic spirocercosis)
• Decreased antithrombin (AT) activity may indicate a hypercoagulable state seemingly more severe with neoplastic transformation
• Serum alkaline phosphatase (ALP) activity is not a marker for neoplastic transformation of esophageal nodules in canine spirocercosis
• There is no association between concentrations of acute phase proteins, haptoglobin (Hp), C-reactive protein (CRP) measured on initial presentation (admission to hospital) and the number of esophageal nodules; furthermore CRP cannot be used to differentiate between benign and malignant spirocercosis

 

COMPARATIVE PATHOLOGY:

Esophageal parasites:

• Gongylonema: Spirurid nematode that affects ruminants, pigs, horses, primates, and rodents; thin, red, serpentine nematode; 10-15 cm in length; easily visible to the naked eye; reside in the esophageal mucosa; intermediate hosts are the cockroach and dung beetle
• Gasterophilus: Affects equids; fly larvae lay eggs on skin and licking activates them; burrow into the oral mucosa, molt, then migrate down the esophagus; attach to mucosa via oral hooks; lesions are present in the distal esophagus and stomach
• Hypoderma lineatum: Affects ruminants; larvae of the warble fly; migrate to the esophageal adventitia, then to the subcutaneous tissue of the back
• Sarcocystis gigantea: Affects sheep; white nodules on the serosal surface of the esophagus; spread by cats; cyst rupture possibly associated with eosinophilic myositis

 

Parasites associated with neoplasia (Mnemonic SOCS-T):

• Spirocerca lupi: Esophageal sarcomas in dogs
• Opisthorchis , Clonorchis (Opisthorchis) sinensis (liver flukes): Cholangiocarcinoma in cats and humans
• Cysticercus fasciolaris (larval stage of feline cestode Taenia taeniaeformis): Hepatic sarcoma in rats
• Schistosoma haematobium: Urinary bladder transitional cell carcinoma in humans
• Trichosomoides crassicauda: Papillomas of the urothelium in rats
• Heterakis isolonche: One case report of metastatic neurofibromatous mesenchymal neoplasia in a pheasant (Himmel, J Vet Diagn Invest. 2017)
• Heterobilharzia americanum: Linked with lymphoma in a dog (single case)

 

 

References:

1. Alexander AB, Poirotte C, Porton IJ, et. al. Gastrointestinal parasites of captive and free-living lemurs and domestic carnivores in eastern Madagascar. J Zoo Wildl Med. 2016; 47(1):141-149.
2. Blume GR, Reis Junior JL, Gardiner CH, et al. Spirocerca lupi granulomatous pneumonia in two free-ranging maned wolves (Chrysocyon brachyurus) from central Brazil. J Vet Diagn Invest. 2014;26(6):815-817.
3. Brenner OJ, Botero-Anug AM, Rojas A, Hahn S, Baneth G. Aberrant Mesenteric Migration of Spirocerca lupiLarvae Causing Necrotizing Eosinophilic Arteritis, Thrombosis, and Intestinal Infarction in Dogs. Vet Pathol. 2020;57(2):281-285.
4. Gardiner CH, Poynton SL. Spirurids. In: Gardiner CH, Poynton SL, eds. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 1999:30-34.
5. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:356-357.
6. Himmel L, Cianciolo R. Nodular typhlocolitis, heterakiasis, and mesenchymal neoplasia in a ring-necked pheasant (Phasianus colchicus) with immunohistochemical characterization of visceral metastases. J Vet Diag Invest. 2017; 29(4): 561-565.
7. Keel MK, Terio KA, McAloose D. Canidae, Ursidae and Ailuridae. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 236-7.
8. McAloose D, Stalis I. Prosimians. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 336.
9. Pazzi P, Goddard A, Kristensen AT, Dvir E. Evaluation of hemostatic abnormalities in canine spirocercosis and its association with systemic inflammation. J Vet Intern Med. 2014;28(1):21-29.
10. Phythian CJ, Stafford KD, Coles GC, Morgan ER. Taeniid and other parasite ova in the faeces of working sheepdogs in south-west England. Vet Rec. 2018; 182(21):603.
11. Ruggeri M, Rojas A, Chai O, et. al. Detection of Intraspinal Spirocerca lupi in Canine Cerebrospinal Fluid by Polymerase Chain Reaction. J Comp Pathol. 2019:170:105-112.
12. Shipov A, Kelmer G, Lavy E, Milgram J, Aroch I, Segev G. Long-term outcome of transendoscopic oesophageal mass ablation in dogs with Spirocerca lupi-associated oesophageal sarcoma. Vet Rec. 2015; 177(14):365.
13. 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; 2016:34-35.
14. van der Merwe LL, Kirberger RM, Clift SJ, Williams M, Keller N, Naidoo V. Spirocera lupi infection in the dog: a review. Vet J. 2008;176(3):294-309.

 

 

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