C-P01 (NP)

Signalment (JPC #740341): Dog; age, breed and gender unspecified

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Aorta: Multifocally, the tunica intima, tunica media, and tunica adventitia are expanded by nodular accumulations of lymphocytes, plasma cells, and macrophages which often surround cross sections of larval spirurid nematodes and extend into adjacent collagen, elastin, and smooth muscle fibers. In the tunica intima, the endothelium is often discontinuous or lost and the subjacent intima is expanded and replaced by abundant fibrin and edema with minimal hemorrhage, reactive fibroblasts, and scattered eosinophilic cellular and karyorrhectic debris (necrosis) which bulges into the lumen. The tunica media and adventitia are disrupted by multifocal to coalescing tracts composed of central necrotic debris admixed with abundant hemorrhage and fibrin and numerous macrophages with variable numbers of plasma cells, neutrophils, lymphocytes, and few hemosiderin-laden macrophages (larval migration tracts) surrounded by and admixed with foci of reactive fibroblasts embedded in loose eosinophilic collagen (fibrosis), separating elastic fibers. Larval spirurid nematodes within the vessel wall are up to 300 µm in diameter, with a smooth cuticle; coelomyarian-polymyarian musculature; prominent, stalked lateral chords; brightly eosinophilic material in the pseudocoelom; and a large intestine lined by many uninucleate, cuboidal epithelial cells with a prominent, tall brush border. Focally, there is osseous metaplasia within the tunica media. Smaller arteries and veins within the tunica adventitia (vasa vasorum) are lined by hypertrophic endothelium with increased mural clear space (edema), small amounts of fibrin, and transmigration of leukocytes (vasculitis).

MORPHOLOGIC DIAGNOSIS: Aorta: Arteritis, necrotizing, subacute, diffuse, severe, with larval spiurid nematodes and focal osseous metaplasia, breed unspecified, canine.

ETIOLOGIC DIAGNOSIS: Aortic spirocercosis

CAUSE: Spirocerca lupi (see also D-P10)

GENERAL DISCUSSION:

Spirurid nematode with a worldwide distribution that parasitizes the esophageal wall of canids (dog, red fox, wolf, coyote, and jackal) and some other carnivores (bobcat, lynx, and snow leopard)
Two species: S. lupi (tropics and the United States) and S. arctica (Russia)
Lesions typically present in the distal esophagus, stomach, and aorta; however, lesions may occur at other locations (urinary bladder, kidneys, subcutaneous tissue, thoracic vertebrae, and mesentery) because of aberrant larval migration
1. Persistent lesions within the aorta in the dog is evidence of prior infection with S. lupi, even in the absence of esophageal granuloma formation
Most domestic animals are infected by ingestion of insectivorous paratenic hosts (e.g. chicken, rodents, reptiles)
S. lupi is associated with esophageal fibrosarcomas and osteosarcomas

PATHOGENESIS:

Canids (or other carnivores) ingest third stage Spirocerca larvae encysted in the intermediate host (dung beetle) or insectivorous paratenic host
Larvae ultimately migrate to and mature within the submucosa of the distal esophagus and promote formation of a fibroblastic nodule, often with a fistula through which the tail of the female worm may protrude
The esophageal fibroblastic nodule may then undergo malignant transformation to sarcoma (typically fibrosarcoma or osteosarcoma); the mechanism of neoplastic transformation is unknown
These neoplasms are locally invasive and often metastasize to the lungs; hypertrophic osteopathy (M-N05) is also occasionally found concurrently in animals with Spirocerca-associated sarcomas

LIFECYCLE:

Adults within canid (definitive host) reside in esophageal nodules -> Females lay embryonated eggs into esophageal lumen -> Eggs pass through the gastrointestinal tract, excreted in the feces or vomitus -> Ingested by coprophagous beetles (intermediate host) -> +/- paratenic host (poultry, wild birds, lizards, and rodents that consumed the beetles) Larvae mature into infective (L3) stage larvae within two months -> +/- paratenic host
Carnivore ingests L3 larvae (beetle (intermediate host) or paratenic host) -> L3 liberated within canid stomach and penetrate the gastric mucosa -> Migrate via gastric arteries to aorta -> Continue migration through the subintimal tissue to the caudal thoracic area -> Advance to adventitia -> Develop for 2-4 months within a granuloma within the aortic adventitia -> Migrate to the submucosa of the distal esophagus or gastric cardia to develop into adults within cystic fibroblastic nodules

TYPICAL CLINICAL FINDINGS:

Clinical disease uncommon
Esophageal obstruction from large nodules can lead to persistent regurgitation/vomiting
Rarely, sudden death from rupture of an aortic aneurysm

TYPICAL GROSS FINDINGS:

Esophagus (or stomach): Cystic, fibrous nodule on the luminal surface near the gastric cardia covered by epithelium enclosing a cavity containing large, red nematodes (females 6-7 cm long; males 3-4 cm long) and purulent exudate
Caudal thoracic / cranial abdominal aorta:
1. Tumor-like nodules in aortic wall; scarring, necrosis, and aneurysm +/- rupture
2. Rough, granular, linear or oval plaques on endothelium
Thoracic vertebra:
1. Spondylosis deformans: Due to either proximity of vertebral body to aortic granuloma or aberrant larval migration
2. Spondylitis: Occurs in >50% of cases; characterized by exostoses arising from the vertebral bodies; suspected to be caused by migrating worms or inflammatory mediators
Spirocerca-associated neoplasia:
1. Esophageal mesenchymal neoplasms (fibrosarcoma or osteosarcoma); +/- hypertrophic osteopathy
Aberrant larval migration:
1. Recent report of intestinal infarctions in 32 dogs associated with aberrant migration of S. lupi larvae (Brenner, Vet Pathol. 2020)

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Nematode: Thick cuticle, prominent lateral chords, coelomyarian-polymyarian musculature, large intestine lined by uninucleate cells (appears tri-layered due to nuclei aligned at the base of the microvilli), prominent brush border, and eosinophilic material in the pseudocoelom
1. Distinctive (typical spirurid) small (35x15um), thick shelled, ovoid, and intensely-stained embryonated eggs may be present in tissues with adult females
Esophagus (or stomach):
1. Adult nematodes embedded within a mature cystic collagenous capsule and surrounded by a variably intense lymphoplasmacytic to granulomatous inflammatory response
2. Highly reactive fibroblasts with varying degrees of atypia (multinucleation, polygonal shape) and frequent mitoses can be found within the collagenous tissue of the nodules, suggesting a pre-neoplastic change
Aortic lesions:
1. Larval nematodes within the tunica adventitia and media
2. Intimal roughening with thrombosis
3. Vasculitis may be present; intimal and medial hemorrhage and necrosis with eosinophilic inflammation
4. Aneurysm +/- rupture
5. Intimal and medial mineralization and heterotopic ossification

ADDITIONAL DIAGNOSTIC TESTS:

Fecal flotation to identify small, thick-walled, embryonated eggs
Plasma or serum VEGF concentrations may be used to differentiate neoplastic from non-neoplastic spirocercosis
Esophageal endoscopy, radiography, and computed tomography: Identify mass within distal esophagus
PCR
Cytology (e.g., endoscopy/bronchoscopy + aspiration, thoracic fluid if perforation)
1. Identify embryonated eggs +/- neutrophilic, histiocytic inflammation
2. Ova present within cerebrospinal fluid (CSF) in one case with aberrant spinal larvae

DIFFERENTIAL DIAGNOSIS:

Gross:

Gongylonema spp.: Spirurid with broad host range; favors stratified squamous epithelium of the upper alimentary tract, particularly the esophagus, but also the stomach, rumen, and tongue; small thread-like worms that form serpiginous tracts within the mucosa and do not form nodules
Dirofilaria immitis: Adults are filarid nematodes found within the heart or vascular lumina

COMPARATIVE PATHOLOGY:

Spirocerca lupi is generally found in canids and other carnivores, but it is also reported to be a significant cause of mortality in captive Malagasy lemurs and reported in the aorta of other non-human primates

Other esophageal parasites:

Gongylonema spp.: Affects ruminants, pigs, horses, primates and rodents; thin, red and 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 spp.: 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; grossly visible 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 spp., Clonorchis (Opisthorchis) sinensis (liver flukes): Cholangiocarcinoma in cats and humans
Cysticercus fasciolaris (metacestode/larval form of adultTaenia taeniaeformis): Hepatic sarcoma in rats
Schistosoma haematobium: Urinary bladder transitional cell carcinoma in humans
Trichosomoides crassicauda: Papillomas of the urothelium in rats
Heterobilharzia americanum: Linked with lymphoma in a dog (single case)

REFERENCES:

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Brenner OJ, Botero-Anug AM, Rojas A. Aberrant mesenteric migration of Spirocerca lupi larvae causing necrotizing eosinophilic arteritis, thrombosis, and intestinal infarction in dogs. Vet Pathol. 2020;57(2):281-285.
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