JPC Systemic Pathology

Histopathologic Description

Lung: Effacing and replacing approximately 40% of the pulmonary parenchyma are multifocal to coalescing inflammatory nodules composed of numerous macrophages and fewer lymphocytes, plasma cells, neutrophils, and eosinophils with abundant fibrous connective tissue and minimal hemorrhage, fibrin, and edema. Inflammatory nodules surround an adult trematode and many trematode eggs. The adult trematode are 2 mm x 3.3 mm, have a 45 µm thick spiny tegument, and spongy parenchyma that contains numerous subtegumental vitellaria with eosinophilic globular yolk material. Adjacent to the previously described adult trematode there is increased fibrovascular tissue oriented perpendicularly to small caliber blood vessels (granulation tissue). Trematode eggs are 80 µm x 100 µm, have a 1–3 µm thick, yellow, anisotropic shell, and contain metacercaria (larvae). In less affected areas, there are pigment laden macrophages, lymphoid aggregates, and hemorrhage, fibrin, and edema. Multifocally, bronchial and bronchiolar lumina are filled with sloughed epithelial cells, low numbers of macrophages, neutrophils, lymphocytes, and plasma cells. There is multifocal bronchiolar smooth muscle hypertrophy and hyperplasia of bronchial glands. Multifocally, the tunica media of small and medium blood vessels is thickened by smooth muscle hypertrophy (medial hypertrophy), and there is endothelial hypertrophy. The pleura is thickened 2-3 times normal by lymphocytes, plasma cells, macrophages, fibrous connective tissue, and hypertrophic (reactive) cuboidal to columnar mesothelial cells.

General Discussion

• Two important species: P. westermanii (Asia) and P. kellicotti (North America)
• Of the trematodes, Paragonimus is the only genus that has its final habitat in the lungs
• Usually found in fish-eating carnivores (e.g. mink); cats are the most affected domestic species; occasionally dogs and humans; rarely pigs

Pathogenesis

Indirect Life Cycle:

• 1st intermediate host (IH): Freshwater snails (gastropod); cercariae stage
• 2nd IH: Freshwater crabs or crayfish (crustacean); metacercariae stage
• Definitive host (DH): Fish eating carnivores
• Ingestion of 2nd IH containing metacercariae → liberation of the metacercariae into the intestines → migration across the peritoneal and pleural cavities into the lungs → mature to adult flukes and produce eggs → eggs are coughed up the tracheobronchial tree, swallowed, and passed in feces → ciliated miracidium released from eggs in fresh water > miracidium infects 1st IH → after asexual reproduction cercariae are released and penetrate 2nd IH → develops to metacercariae
• Alternate life cycle: Paratenic host eats infected 2nd IH, but metacercariae don’t mature in these hosts → metacercariae remain in tissues where they may be consumed by predator (or human) → infect new host and may complete life cycle (Izzati, et al, 2021 J Comp Pathol)

Typical Clinical Findings

• Generally asymptomatic
• Rarely chronic, deep, intermittent cough, weakness, and lethargy
• Rupture of pulmonary cysts may rarely cause pneumothorax leading to acute respiratory distress
• May cause peripheral eosinophilia

Typical Gross Findings

• Adult flukes are ovoid, red-brown, 7–16 mm long and 4–8 mm in diameter; present in pairs in cavitations (spherical, soft, dark red-brown, 1-3 cm in diameter) and occasionally in bronchi; cavitations most common in the caudal lobes especially the right lobe; this is similar to other verminous pneumonias
• Subpleural cysts up to 7 mm long with paired adults; ruptured cysts may result in pneumothorax and atelectasis; pleural hemorrhages and foci of eosinophilic and fibrinous pleuritis, which heal to form umbilicated scars
• Pleural adhesions; eosinophilic granulomas; focal areas of emphysema

Typical Light Microscopic Findings

• Cavitations composed of granulomatous and eosinophilic pneumonia or granulomas that surround adults and eggs; surrounded by fibrous capsule
• Mature cavitations establish connections with bronchioles and become partially lined by bronchiolar epithelium to form true cysts
• Adults have a spiny tegument, ventral oral sucker, loose parenchyma (lack a body cavity), paired ceca with dark pigment, vitellaria containing eosinophilic globular yolk material, gonads of both sexes
• Eggs are pigmented, gold-brown, operculated, 75-118 µm long by 42-67 µm wide; found in eosinophilic granulomas or in subpleural and mediastinal lymphatics leading to granulomatous pleuritis and lymphangitis; +/- free within pleural cavity with pigmented debris
• Eosinophilic bronchitis with hyperplasia of peribronchiolar glands and smooth muscle

Additional Diagnostic Tests

• Eggs (ova) can be found on fecal examination with flotation or Baermann apparatus
• Transtracheal and bronchoalveolar wash difficult to view ova:
  • Eosinophilic exudate +/- larvae and ova identified (at 10x)
• Possible to detect ova in aspirates of lung cysts; accompanied by eosinophils, neutrophils, lymphocytes, and necrotic debris
• Larva may be seen on brushings or biopsies of bronchi parasitic nodules

Differential Diagnosis (Parasitic Pneumonias)

• Aelurostrongylus abstrusus (P-P09) is the most common lung nematode of cats; eggs form nodular lesions within alveoli
• Angiostrongylus vasorum (P-P02): parasitizes the pulmonary arteries; lymphoeosinophilic interstitial pneumonia +/- multifocal to coalescing granulomas with giant cells
• Dirofilaria immitis (P-P02): parasite of the right ventricle that can produce pulmonary lesion; caudal vena cava syndrome, interstitial fibrosis, pulmonary arterial thrombosis, chronic arteritis
• Pneumocystis carinii sp. f. canis.: sporadic cause of chronic interstitial pneumonia in dogs with compromised system
• Toxoplasma gondii (P-P01): Interstitial pneumonia with protozoa

Comparative Pathology

• Paragonimus westermanii (oriental lung fluke)
  • Suid: Wild boar and domestic pigs are paratenic hosts and may serve as a reservoir for zoonotic infection; uncommonly infected; larvae may be found in skeletal muscle but not associated with clinical disease
  • Canid: definitive host; may be infected after eating paratenic hosts or 2nd IH
  • Humans: Triploid P. westermani most pathogenic in humans; infected through consumption of paratenic host (suid); cysts in lungs; diploid flukes cause pleural lesions, no lung lesions (Izzati, et al, 2021)
  • NHPs: Cynomolgus macaques infected by ingesting the parasite in raw crabs or crayfish
    • Adult flukes normally found in the lungs, but may be found in brain, liver, and other organs
    • Clinical signs include coughing, wheezing, bloody or red-tinged sputum, moist rales, and progressive weight loss; may be asymptomatic
    • Gross lesions: Focal areas of emphysema, 2-3cm red/brown cysts (containing 2 or more adult flukes) random pulmonary parenchyma distribution; cyst may be elevated above lung surface +/- pleural adhesions
    • Histo lesions: Leukocytic infiltration, mature fibrous capsule around parasites with hemorrhagic and purulent exudate and fluke eggs

References

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