JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1621137): A dog
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 12 x 8 mm inflammatory nodule centered on numerous transverse and longitudinal sections of adult spiurid nematodes surrounded by high numbers of plasma cells, macrophages (often hemosiderin-laden), fewer lymphocytes, and rare neutrophils and eosinophils, which extend 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 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 eosinophilic material, an intestine lined by uninucleate columnar epithelium with a prominent brush border and male or 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 nematodes, etiology consistent with Spirocerca lupi, breed unspecified, canine.
Etiologic diagnosis: Esophageal spirocercosis
CAUSE: Spirocerca lupi
- 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. artica (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 (chicken, rodents, reptiles)
- lupi is associated with esophageal fibrosarcoma and osteosarcoma; 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
- 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 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 who 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
- 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
- Gongylonema: 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: 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 (Taenia 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)
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