JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

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 14x8 mm inflammatory nodule centered on numerous transverse and longitudinal sections of adult spirurid nematodes surrounded by abundant necrotic debris, 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, 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, breed unspecified, canine.

 

Etiologic diagnosis: Esophageal spirocercosis

 

CAUSE: Spirocerca lupi

 

GENEAL DISCUSSION:

 

LIFE CYCLE:

• Canid (or other carnivore) ingests third stage larvae encysted in intermediate host (dung beetle) or insectivorous vertebrate paratenic hosts (e.g. rodents, chickens, or reptiles)
• Third stage larvae (L3) penetrate host gastric mucosa -> Migrate along tunica adventitia of gastric arteries to the aorta -> In aorta, larvae migrate subintimally to the caudal thoracic area -> Form a granuloma within the aortic adventitia (lasts 2-4 months) and larvae develop into adulthood -> Adults migrate to adjacent esophagus, where they form large, thick-walled cystic granulomas within the submucosa with fistulae communicating with the lumen in which the tails of females protrude for release of ova into the GI tract

 

PATHOGENESIS:

• Aberrant larval migration (rather than from gastric arteries to aorta) may result in granulomas within the subcutis, urinary bladder, kidney, spinal cord, as well as stomach and intrathoracic locations
• Esophageal fibroblastic nodule can undergo malignant transformation to sarcoma; the mechanism of neoplastic transformation is unknown
• Vertebral body spondylitis occurs in >50% of cases; the pathogenesis is unclear but may be due to migrating worms or inflammatory mediators

  

TYPICAL CLINICAL FINDINGS:

• May see esophageal obstruction: Dysphagia; vomiting or regurgitation; coughing
• Aortic aneurysm rupture may lead to hemothorax and sudden death

 

TYPICAL GROSS FINDINGS:

• Esophagus (or stomach): 
  1. Cystic granuloma with luminal communication, most commonly in the distal esophagus or gastric cardia containing adult nematodes 
  2. Adult Spirocerca are large (female: 6-7 cm long, males: 3-4 cm long) and red
  3. With mesenchymal neoplasm, lesions may be firm, proliferative, and ulcerated
• Aorta
  1. Terminal thoracic and anterior abdominal aorta may be rough or granular with linear or oval plaques on endothelium; aneurysmal dilation; thrombi, mineralization 
  2. Aortoiliac thromboembolism has been reported
• Hypertrophic osteopathy: Periosteal new bone formation, usually confined to the limbs
• Vertebra (adjacent to aortic granuloma, esp. caudal thoracic vertebrae):  Spondylosis deformans or vertebral body spondylitis with exostoses or bony spurs arising from the ends of the vertebral bodies

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Esophagus (or stomach): 
  1. Adult nematodes within large, thick-walled cystic granulomas in the submucosa with variably mature collagen capsule and lymphoplasmacytic inflammation 
  2. Adults have smooth, thick cuticle, coelomyarian-polymyarian muscle, prominent lateral cords, a pseudocoelom with eosinophilic luminal fluid, and an intestine lined by uninucleate columnar epithelium
  3. Eggs are 35x15 µm embryonated
  4. Pre-neoplastic lesions have activated pleomorphic fibroblasts with varying degrees of atypia (multinucleation, polygonal shape) and frequent mitoses
• Aorta and other vessels: 
  1. Intimal to medial hemorrhage and necrosis; intimal roughening with thrombosis; aneurysm with aortic rupture; intimal and medial mineralization and heterotopic bone deposition
  2. Vasculitis and thrombosis may be present

        

ADDITIONAL TESTS:

• Fecal examination: Identify embryonated eggs
• 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 and histiocytic inflammation
  2. Ova were present within cerebrospinal fluid (CSF) in one case with aberrant spinal larvae

 

COMPARATIVE PATHOLOGY:

Esophageal parasites of other species:

• Gongylonema spp.: 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 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; 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 (larval stage of feline cestode Taenia taeniaeformis): Hepatic fibrosarcoma in rats
• Schistosoma haematobium: Urinary bladder transitional cell carcinoma in humans
• Trichosomoides crassicauda: Papillomas of the urothelium in rats

 

REFERENCES:

1. Boes KM. Chapter 6: Body Cavity Fluids. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:267.
2. Brenner OJ, Botero-Anug AM, Rojas A, Hahn S, Baneth G. Aberrant Mesenteric Migration of Spirocerca lupi Larvae Causing Necrotizing Eosinophilic Arteritis, Thrombosis, and Intestinal Infarction in Dogs. Vet Pathol. 2020;57(2):281-285.
3. Craig LE, Dittmer KE, Thompson KG. Bones and Joints. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:92-93, 115. 
4. De Lorenzi D, Pintore L. Chapter 15: Nervous System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:531.
5. Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:679, 696.
6. 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.
7. Grimes CN, Fry MM, LeBlanc CJ, Hecht S. The Lung and Intrathoracic Structures. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:284, 296. 
8. Hostetter SJ. Chapter 7: Oral Cavity, Gastrointestinal Tract, and Associated Structures. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:299.
9. 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: 247-249.
10. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:596.
11. McAloose D, Stalis IH. Prosimians. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:336. 
12.  Olson EJ, Dykstra JA, Armstrong AR, Carlson CS. Bones, Joints, Tendons, and Ligaments. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1080.
13. Robinson WF, Robinson NA. Cardiovascular System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:62, 83. 
14. 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.
15. 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; 2022:429. 
16. Strait K, Else JG, Eberhard ML. Parasitic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012: 226.
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; 2016:34-35, 44.

 

 

 

 

Click the slide to view.

---