JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-P09

 

Slide A: Signalment (JPC #1358025): Tissue from a cat

 

HISTORY: Incidental finding in a cat with small white spots adjacent to bronchioles

 

HISTOPATHOLOGIC DESCRIPTION: Lung, two sections: Diffusely filling 70% of alveolar lumina and to a lesser extent extending into terminal bronchiolar lumina are numerous nematode eggs, larvae, and fewer adults, admixed with an exudate composed of many alveolar macrophages, multinucleated giant cells, neutrophils, and eosinophils, scattered hemorrhage, fibrin, and eosinophilic proteinaceous fluid (edema). The nematode eggs are 40-60 µm, oval, thin walled, arranged in clusters, and are either morulated or embryonated. Larvae are approximately 25 µm in diameter, contain numerous nuclei, have lateral alae, and have one tapered end that forms an eccentric tip. Adult nematodes have a 5 µm cuticle, coelomyarian-polymyarian musculature, a pseudocoelom, an intestinal tract with birefringent yellow‑brown pigment, and a reproductive tract (ovaries). Multifocally, alveolar septa are lined by cuboidal epithelium (type II pneumocyte hyperplasia). Smooth muscle surrounding terminal bronchioles is thickened (hypertrophy). Bronchiolar epithelium is hyperplastic. Moderate numbers of lymphocytes and plasma cells surround larger blood vessels, bronchi, and bronchioles. Multifocally, the subpleural connective tissue contains few lymphocytes and plasma cells, and the overlying mesothelium is reactive.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, histiocytic, neutrophilic, and eosinophilic, diffuse, moderate, with type II pneumocyte hyperplasia, bronchiolar smooth muscle hypertrophy, and large numbers of metastrongyle eggs, larvae, and few adults, breed not specified, feline.

 

Slide B: Signalment (JPC #3135343): Five-month-old castrated male domestic-shorthaired cat.

 

HISTORY: This cat was found recumbent with shallow breathing and died shortly thereafter.

 

HISTOLOGIC DESCRIPTION: Lung: Multifocally and randomly filling and/or expanding alveolar lumina is an exudate composed of variable numbers of eosinophils, foamy alveolar macrophages, fewer lymphocytes and plasma cells, fibrin, edema, and multinucleated giant cells. Similar inflammatory cells multifocally expand alveolar septa up to 3-4x normal. Focally, the lung is consolidated and alveolar lumina are filled and/or expanded by multiple tangential and cross sections of previously described nematode larvae and eggs. Multifocally, alveolar septae and terminal bronchioles are thickened up to five times normal by hypertrophic smooth muscle. Diffusely, the tunica media of pulmonary arterioles is markedly thickened by hypertrophic smooth muscle (medial hypertrophy) which compresses the vessel lumina, and the tunica adventitia is mildly expanded by clear space (edema). Bronchi and bronchioles contain small amounts of previously described exudate, and there is moderate hyperplasia of goblet cells and bronchial submucosal glands. There is mild, diffuse subpleural edema.

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, eosinophilic and granulomatous, chronic, multifocal to coalescing, moderate, with diffuse marked alveolar septal smooth muscle metaplasia, terminal bronchiolar smooth muscle hypertrophy, pulmonary arteriolar medial hypertrophy, and few nematode eggs and larvae, domestic short-haired, feline. 

 

ETIOLOGY: Aelurostrongylus abstrusus

 

SYNONYMS: Feline lungworm

 

ETIOLOGIC DIAGNOSIS: Pulmonary aelurostrongyliasis

 

GENERAL DISSCUSION:  

• Aelurostrongylus abstrusus a common feline pulmonary nematode 
• Usually found in rural, hunting cats that eat snails and slugs (intermediate host), or in rodents, birds, frogs, and lizards (paratenic hosts)
• A. abstrusus is a metastrongyle and is a member of the superfamily Metastrongyloidea, family Angiostrongyloidae
• Normally subclinical and is considered an incidental finding, but may be associated with respiratory distress

 

PATHOGENESIS:

• The ova and larvae, not the adults, induce the inflammatory reaction
• Respiratory distress can be severe if there are secondary bacterial infections 

 

LIFE CYCLE:

• Adults reside in terminal and respiratory bronchioles > Oviparous female releases eggs, which form nodular deposits in alveoli, where they embryonate and hatch > First-stage larvae are coughed up and swallowed > Passed in feces > 
• Larvae enter intermediate host (snail/slug) > 2 molts > Paratenic host (AKA transport host) (rodents, birds, frogs, and lizards) ingests infected snail/slug > Third-stage larvae encyst in tissues of paratenic host > 
• Cat eats intermediate or paratenic host > Third-stage larvae migrate to lungs > Reach maturity 4-6 weeks later (larvae appear in cat feces)

 

TYPICAL CLINICAL FINDINGS:  

• Many cats are asymptomatic
• Moderate infections are manifested as coughing and anorexia
• Severe infections are manifested as dyspnea, coughing, polypnea, and death

 

TYPICAL GROSS FINDINGS:  

• Prepatent period: Multifocal to coalescing, white to hemorrhagic foci due to larval migration
• Patent period: Firm, slightly raised, white to pale yellow, 1-10 mm nodules throughout lungs containing viscous exudate, +/- consolidation in severe infections

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Alveolar or terminal bronchiole nodules containing masses of eggs and larvae and fewer adult worms; alveoli are dilated, and alveolar septa may be disrupted
• Eosinophils and neutrophils are present early, but most lesions are dominated by macrophages and multinucleated giant cells
• Airways (bronchioles and alveolar ducts) may also have smooth muscle hypertrophy and hyperplasia, submucosal/bronchial gland hyperplasia, and peribronchial/peribronchiolar lymphocytic nodules
  1. There may also be catarrhal and eosinophilic bronchiolitis +/- tracheitis

Pulmonary arteries and arterioles may have medial smooth muscle hypertrophy and perivascular lymphocytic nodules

• In older lesions (eggs and larvae disappeared), alveoli remain epithelialized and there may be granulomatous alveolitis, alveolar fibrosis, and fibromuscular hyperplasia
  1. Fibromuscular hyperplasia and bronchial gland hypertrophy can be seen in otherwise healthy cats, so the significance is unknown
• From Gardiner, An Atlas of Metazoan Parasites in Animal Tissue, 1999):
  1. Eggs: Oval, thin walled, 40-60 µm; often morulated (contain an early-stage embryo with 16 cells called blastomeres) or embryonated
  2. Larvae: 25 µm, nucleated, lateral alae, tail tip is eccentric to body
  3. Adults: 40-60 µm, coelomyarian musculature, intestine lined by multinucleate cells, accessory hypodermal cords; typically found in terminal and respiratory bronchioles

 

ADDITIONAL DIAGNOSTICS: 

• Cytology: Tracheal wash or bronchoalveolar lavage: 
  1. Eosinophils and neutrophils (more common in infection), larva and occasionally ova may be seen: Larvae are usually coiled on themselves and have a tail with a characteristic double bend/kinked tail and a dorsal spine
  2. There may be abundant free eosinophil granules (not to be confused with bacteria) that may coalesce into a large crystal known as a Charcot-Leyden crystal

 

DIFFERENTIAL DIAGNOSIS: 

Other parasitic pneumonias:

• Eucoleus aerophilis: A trichurid nematode that parasitizes the trachea and bronchi of wild canids, domestic dogs, and occasionally cats
• Eucoleus (Capillaria) boehmi: A trichurid nematode found in the nasal cavity and sinuses of canids
• Oslerus rostratus: A viviparous parasite of cats causing sinuous thickenings of the walls of large bronchi
• Troglostrongylus brevior and T. subcrenatus: Metastrongyloid nematode; trachea and bronchi
• Paragonimus kellicotti (P-P07): Lung trematode of mink, dogs, and cats; adults lack a body cavity, have paired ceca, oral suckers, and a spiny tegument with subjacent vitellaria; 80-100 µm yellow-brown operculate eggs
• Toxoplasma gondii (P-P01): Wide range of hosts and tissues; necrotizing pneumonia with intraepithelial and intrahistiocytic protozoal cysts
• Cytauxzoon felis (P-P05, H-P04): Domestic and wild felids; interstitial pneumonia with intravascular macrophages with shizont-laden macrophages

 

COMPARATIVE PATHOLOGY:  

Lungworms in other species

• Dog: Filaroides hirthi; Crenosoma vulpis; Eucoleus aerophilis (higher in respiratory tree than C. vulpus); Paragonimus kellicotti (fluke); Angiostrongylus vasorum, and Dirofilaria immitis (pulmonary arteries)
• Ox: Dictyocaulus viviparous
• Sheep and goats: Dictyocaulus filaria; Muellerius capillaris; Protostrongylus rufescens
• Horse: Dictyocaulus arnfieldi
• Pig: Metastrongylus apri; M. salmi; M. pudendotectus
• ZEW (Pathology of Wildlife and Zoo Animals, 2018)
  1. Cervidae (deer): Dictyocaulus viviparous, D. filaria. Other, less pathogenic species include Protostrongylus spp., Orthostrongylus macrotis (mule deer, moose) and Varestongylus spp.
  2. Canidae, Ursidae (bear), and Ailuridae (red panda):
     • Oslerus osleri (formerly Filaroides osleri): Dogs; infects trachea, tracheal bifurcation (most commonly affected site), and mainstem bronchi
     • Crenosoma vulpis (“fox lungworm”): Foxes, wolves, raccoons, dogs, badgers, wolverine, black bears; adults in trachea, bronchi, and bronchioles rather than pulmonary vasculature
  3. Felids: A. abstrusus has been identified in multiple species of large cats, including African lion, serval, caracal, leopard cat, ocelot
  4. Pinnipediae (seals, walrus): Parafilaroides species (small lungworm) including decorus, gymnus, hispida, normani, measuresae, hydrurgae, and gullandae; large lungworm, Otostrongylus circumlitus; infections more intestine in younger animals
     • Grey seals: Presented with segmental granulomatous and eosinophilic vasculitis with an intramural Splendore-Hoeppli reaction in medium to large pulmonary arteries secondary to Otostrongylus circumlitus (Barnett JEF, J Comp Pathol, 2019)
  5. Amphibia: Rhabdias spp.; histologic lesions associated with increased parasite burden
• Rat lungworm, Parastrongylus cantonensis (formerly Angiostrongylus cantonensis) (N-P10)
  1. Neurotropic metastrongylid lungworm of rats (lives in pulmonary arteries, rarely causes disease) that causes eosinophilic meningoencephalitis in aberrant hosts (dogs and humans) due to ingestion of ingest intermediate host (snails/slugs) or paratenic host
  2. Also seen in: Nonhuman primates (gibbons, orangutan, owl monkeys, callitrichids), horses, macropods, monotremes and marsupials (brushtail possums in Australia), Chiroptera (bat), and tawny frogmouths (avian)

 

REFERENCES:  

1. Barnett JEF, Bexton S, Fraija-Fernández N, Chooneea D, Wessels ME. Novel Pulmonary Vasculitis with Splendore-Hoeppli Reaction in Grey Seals (Halichoerus grypus) Associated with Otostrongylus circumlitus Infection. J Comp Pathol. 2019 Nov;173:83-91. 
2. Burkhard MJ. Respiratory Tract. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2016:224-225. 
3. Caswell JL, Williams KJ. Respiratory System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016: 509, 590-591.
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6. Farina LL, Lankton JS. Chiroptera. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:623-624. 
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12. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:399-400. 
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14. Pessier AP. Amphibia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:941. 
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