JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-P07

Signalment (JPC #1642875): Cat

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Lung: Effacing and replacing approximately 30% of the pulmonary parenchyma are multifocal to coalescing nodular inflammatory aggregates composed of numerous macrophages and fewer lymphocytes, plasma cells, neutrophils, and eosinophils with abundant fibrous connective tissue and minimal hemorrhage, fibrin, and edema. These inflammatory nodules surround an adult trematode and trematode eggs. The adult trematode is 2x3 mm, has a 40µm thick spiny tegument, and spongy parenchyma that contains numerous subtegumental vitellaria with eosinophilic globular yolk material. The trematode is surrounded by increased amounts of fibrovascular tissue oriented perpendicularly to small caliber blood vessels (granulation tissue). Trematode eggs are 80 x 100µm and have a 1‑3µm thick, yellow, anisotropic shell. 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 and alveolar smooth muscle hypertrophy, as well as hyperplasia of peribronchial mucous glands. Multifocally the tunica media of small and medium blood vessels is thickened by smooth muscle hypertrophy (medial hypertrophy), and there is endothelial hypertrophy and vacuolation. The pleura is thickened 2-3 times normal by lymphocytes, plasma cells, macrophages, fibrous connective tissue, and hypertrophic (reactive) cuboidal mesothelial cells.

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, granulomatous, nodular, chronic, multifocal, moderate, with fibrosis, pleuritis, and adult trematodes and eggs, breed unspecified, feline.

ETIOLOGIC DIAGNOSIS: Pulmonary paragonimiasis

CAUSE: Paragonimus kellicotti

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 including mink, cats most commonly among domestic species; occasionally affects dogs and humans
Widely distributed in the U.S.; frequently found in the Great Lakes and Mississippi Valley regions

PATHOGENESIS:

Life Cycle:

1^st intermediate host: Small aquatic snails; cercariae stage
2^nd intermediate host: Freshwater crabs or crayfish; metacercariae stage
Definitive host: Ingestion of crayfish 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 snail species > after asexual reproduction within the snail, cercariae are released and penetrate the crayfish > develops to metacercariae in the crayfish
Alternate life cycle: Paratenic host eats infected 2^nd host, 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
Occasionally chronic, deep, intermittent cough, weakness, and lethargy
Rupture of pulmonary cysts may rarely cause pneumothorax -> acute respiratory distress

TYPICAL GROSS FINDINGS:

Adult flukes are oval, red-brown, 5‑10 mm long and 4‑7 mm in diameter; present in pairs in cavitations (raised, soft, dark brown, 1-3 cm in diameter) and occasionally in bronchi; lesions are most common in the caudal lobes especially the right lobe
Pleural adhesions, focal areas of emphysema
Migrating metacercariae produce pleural hemorrhages and foci of eosinophilic and fibrinous pleuritis, which heal as small umbilicated scars
Rupture of cysts may result in pneumothorax

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Granulomatous and eosinophilic pneumonia or granulomas that surround adults and eggs; hemosiderin laden macrophages
Adults have a spiny tegument, ventral sucker, loose parenchyma (lack a body cavity), paired ceca with dark pigment, vitellaria containing eosinophilic globular yolk material, gonads of both sexes
Cavitations are surrounded by a fibrous capsule; mature cavitations establish connections with bronchioles and become partially lined by bronchiolar epithelium to form true cysts
Eggs are gold-brown, operculate, 75-118 µm long by 42-67 µm wide; within eosinophilic granulomas or in subpleural and mediastinal lymphatics leading to pleuritis and lymphangitis
Catarrhal and 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
Difficult to find with transtracheal and bronchoalveolar wash:
1. Larvae and ova may be identified +/- eosinophilic exudate
Ova possible to see on aspirate of lung cysts (with eosinophils, neutrophils, lymphocytes, and necrotic debris)

DIFFERENTIAL DIAGNOSIS:

Aelurostrongylus abstrusus (P-P09) is the most common lung nematode of cats; eggs form nodular lesions within alveoli

COMPARATIVE PATHOLOGY:

Paragonimus westermanii (oriental lung fluke) is found in dogs, pigs and wild boar, goats, cattle, foxes, and small mammals, principally in Asia
1. Larvae may be found in skeletal muscle but not associate with clinical disease
2. Canid is definitive host
3. NHPs: Cynologus macaque affected, ingests parasite within crabs or crayfish
  - 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
  - Gross lesions: Focal areas of emphysema, 2-3cm red/brown cysts (containing 2 or more adult flukes) randomly located throughout pulmonary parenchyma
  - Histo lesions: Leukocytic infiltration, mature fibrous capsule around parasites with hemorrhagic/purulent exudate and fluke eggs
Syrian hamsters: Experimentally infected with P. kellicotti and may serve as small animal models of the disease

REFERENCES:

Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012.
Boes KM. Respiratory System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytolopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:189, 224-227.
Caswell JL, Williams KJ. Respiratory System. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 2, Philadelphia, PA: Elsevier; 2016:537, 591.
De Terlizzi R, English K, Cowell RL, Tyler RD, Meinkoth JH. Transtracheal and Bronchoalveolar Washes. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:257, 264.
Gardiner CH, Poyton SL. An Atlas of Metazoan Parasites in Animal Tissue. Washington, DC: Armed Forces Institute of Pathology; 1990:46-48.
Izzati UZ, Kaneko Y, Kaneko C, Yoshida A, Suwanruengsri M, Okabayashi T, Hirai T, Yamaguchi R. Distribution of Pseudorabies Virus Antigen in Hunting Dogs with Concurrent Paragonimus westermani Infection. J Comp Pathol. 2021;188:44-51.
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; 2022:595, 637.
Matz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:343-374.