JPC SYSTEMIC PATHOLOGY

Respiratory System

September 2023

P-P14

 

SLIDE A: Signalment (JPC #1639870): Dogs, age and breed unspecified

 

HISTORY: Tissue taken from two dogs with chronic coughs

 

HISTOPATHOLOGIC DESCRIPTION: 

Lung: Diffusely, bronchial, bronchiolar, and alveolar lumina contain tangential and cross-sections of adult and rare larval nematodes. Adult nematodes are 100 µm in diameter and have a thin cuticle, coelomyarian-polymyarian musculature, and a pseudocoelom that contains a large intestine lined by a few multinucleated cells and that often contains golden-brown granules and reproductive tracts with developing larvae or sperm. Larvae are 20-30 µm in diameter with a thin eosinophilic cuticle containing many basophilic nuclei and a tapered end. Bronchial, bronchiolar, and alveolar lumina are filled with an exudate composed of plasma cells, lymphocytes, eosinophils, macrophages that are sometimes hemosiderin-laden, multinucleated giant cells (foreign body or Langhans type), and neutrophils admixed with small amounts of fibrin, hemorrhage, edema, and karyorrhectic and cellular debris (necrosis). Alveolar septa are mildly expanded by lymphocytes, macrophages, fibrin, and edema.   

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, pyogranulomatous and eosinophilic, diffuse, severe, with intraalveolar, intrabronchiolar, and intrabronchial adult and few larval metastrongyle nematodes, etiology consistent with Andersonstrongylus milksi, breed not specified, canine.

 

CAUSE: Andersonstrongylus milksi

 

SLIDE B: Signalment (JPC #1371567): A dog, age and breed unspecified

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: 

Trachea and peritracheal tissue: Diffusely infiltrating the tracheal submucosa, forming inflammatory nodules in the peritracheal adventitia, and extending into adjacent adipose tissue and skeletal muscle are eosinophils, lymphocytes, plasma cells, and fewer histiocytes and neutrophils admixed with fibrin, edema, and hemorrhage. Inflammatory nodules are multifocally centered on lymphatic vessels that contain intraluminal tangential and cross sections of adult nematodes. Adult nematodes are 80µm in diameter and have a 4µm thick cuticle, coelomyarian-polymyarian musculature, and a pseudocoelom that contains an intestinal tract lined by few multinucleated cells and a reproductive tract that either contains developing larvae or sperm. There is multifocal attenuation, erosion and ulceration of the tracheal epithelium.  

 

Tracheobronchial lymph node: The subcapsular and medullary sinuses contain few to moderate numbers of eosinophils and few neutrophils and histiocytes that occasionally contain intracytoplasmic erythrocytes (erythrophagocytosis) as well as fibrin, hemorrhage, and mild edema.

 

MORPHOLOGIC DIAGNOSIS: 1. Trachea: Tracheitis and peritracheitis, lymphoplasmacytic and eosinophilic, nodular, moderate, with submucosal and peritracheal intralymphatic adult nematodes, etiology consistent with Oslerus osleri, and tracheal ulceration, breed not specified, canine.

 

2. Lymph node, tracheobronchial: Sinus eosinophilia and draining hemorrhage, acute, diffuse.

 

CAUSE: Oslerus osleri

 

SLIDE C: Signalment (JPC #3103921): Adult female red panda

 

HISTORY: A captive-born panda presented for evaluation of dyspnea and thin body condition. She arrested while being anesthetized for radiographs.  

 

HISTOPATHOLOGIC DESCRIPTION:  

Lung: Multifocally bronchiolar and bronchial lumina contain cross and tangential sections of adult nematodes that are 350-400 µm diameter and have a thin cuticle, coelomyarian-polymyarian musculature, and a pseudocoelom that contains a prominent digestive tract lined by a few multinucleated cells and a reproductive tract containing larvae or clusters of eosinophilic sperm. Larvae are rarely noted within lumina of the bronchi, bronchioles, and alveoli; they are 10-15 µm in diameter with a thin eosinophilic cuticle and a basophilic granular interior. Multifocally, the lumina of bronchi and bronchioles are filled with a dense cellular exudate composed of viable and necrotic neutrophils, eosinophils, macrophages, and fewer plasma cells and lymphocytes admixed with necrotic karyorrhectic and cellular debris, eosinophilic fibrillar material (fibrin), edema, scattered foci of mineralization, few sloughed epithelial cells, and hemorrhage. The peri-bronchial and peri-bronchiolar connective tissue is moderately expanded by the previously described inflammatory cells, fibrin, and edema. There is multifocal stacking of respiratory epithelial cells (hyperplasia). Multifocally, alveolar lumina contain hemorrhage, fibrin, edema, and rare aggregates of pigment laden macrophages (hemosiderin and anthracosilicosis). There is multifocal type II pneumocyte hyperplasia. Alveolar septa are multifocally discontinuous (septal necrosis) with resultant confluent alveolar spaces (emphysema).There is increased perivascular clear space (edema). 

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchitis and bronchiolitis, eosinophilic and pyogranulomatous, chronic, multifocal, severe, with epithelial hyperplasia, emphysema, hemorrhage, and numerous intraluminal adult and rare larval nematodes, etiology consistent with Crenosoma spp.

 

CAUSE: Crenosoma vulpis

 

ETIOLOGIC DIAGNOSES: Metastrongylid pneumonia, tracheitis, and bronchitis

 

GENERAL DISCUSSION:

• Superfamily Metastrongyloidea:
  • Family Filaroididae:
    • Filaroides hirthi
    • Oslerus osleri (formerly Filaroides osleri)
  • Family Angiostrongylidea
    • Andersonstrongylus milksi (formerly Angiostrongylus milksi, Filaroides milksi)

• Family Crenosomatidae
  • Crenosoma vulpis 

• Filaroides/Oslerus/Andersonstrongylus: Respiratory parasites found in canidae (including wolves, foxes, dingos, and coyotes), mink, raccoons, badgers, wolverines, black bears, and monkeys
  1. Filaroides is occasionally seen in lab beagles used for pharmaceutical/toxicity studies where it can obscure/confound interpretation; endemic in some institutions
• Crenosoma: Respiratory parasite found in canidae, raccoons, Eurasian badgers, and red pandas; C. vulpis is the fox lungworm

 

LIFECYCLE:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          

• Similar for F. hirthi and O. osleri   (direct life cycle)
  • Adults in nodules in tracheal mucosa (O. osleri) or in bronchiolar/ alveolar lumina (F. hirthi) à produce thin-walled embryonated eggs à eggs coughed up and swallowed à passed in feces (most having ‘hatched’) à L1 swallowed à migrate via hepatic portal circulation and/or mesenteric lymphatic drainage to the trachea or lung > 4 molts > adult
  • Autoinfection (larvae infect before they exit the host) is possible; can cause superinfection
  • <1yr most affected; puppies often acquire infection from dam’s sputum, grooming, regurgitative feeding, or via fecal-oral transmission
• A. milksi lifecycle is unknown; molluscan intermediate host proposed
• Crenosoma sp. requires a snail/slug intermediate host
  • adults live in small bronchi/bronchioles à deposit larva à coughed up and swallowed à passed in feces à eaten by snail/slug à definitive host eats snail/slug 

 

TYPICAL CLINICAL FINDINGS:  

• Dogs (and other infected mammals) are asymptomatic or may have a chronic non-productive cough (‘retching’) which is exacerbated by exercise, excitement, or cold air
• Immunocompromised dogs may develop severe pneumonia that can be fatal

 

TYPICAL GROSS FINDINGS:

• F. hirthi/A. milksi (Lung): Gray-tan or black-green, 1-5 mm diameter nodules scattered widely in subpleural regions of the lung; may have clear cystic center or be white and firm
• O. osleri (Trachea): Single or multiple 1-10 mm diameter, firm, gray-pink, sessile submucosal nodules in trachea and bronchi, tracheal bifurcation; coiled worms are visible through the intact overlying mucosa
• C. vulpis (Lung): Grey consolidation of caudodorsal lung; adult worms live in bronchioles and small bronchi.

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Metastrongyles: Coelomyarian-polymyarian musculature, accessory hypodermal cords, intestine is large and lined by few multinucleated cells, larvae or embryonated eggs within uterus
• Greenish hue of Filaroides can be attributed to eosinophils recruited into lung and around nodules
• Live worms produce minimal reaction
• Dead worms result in severe granulomatous and eosinophilic inflammation 
• C. vulpis: Catarrhal, eosinophilic bronchitis and bronchiolitis
• Cannot distinguish eggs/larvae of Oslerus or Filaroides from each other; use location as a hint

 

ADDITIONAL DIAGNOSTIC TESTS:

• Fecal examination (Baermann and zinc sulfate flotation techniques)
• Tracheal wash/bronchoalveolar lavage 
• Bronchial brushing
• Radiography (visualize nodules); may resemble neoplasia 
• Endoscopy: Nodule sample and biopsy 
• Crush preparations of nodules (Oslerus)

 

DIFFERENTIAL DIAGNOSIS:

Pulmonary parasites of dogs:

• Crenosoma vulpis: Metastrongyle of foxes, dogs, wild carnivores, raccoons
• Eucoleus aerophilus (Capillaria aerophila): Aphasmid of the trachea and bronchi of foxes, dogs, and cats
• Angiostrongylus vasorum (Angiostrongylidae): Metastrongyle in pulmonary arteries and right ventricle of dogs/foxes 
• Dirofilaria immitis: Filarid nematode in pulmonary arteries with associated arteritis and thrombosis; other sequela include eosinophilic granuloma formation and eosinophilic pneumonitis 

Tracheal parasites of dogs:

 

COMPARATIVE PATHOLOGY:

Selected respiratory metazoan parasites (not comprehensive):

Species	Agent	Site of adult
Dog	Eucoleus aerophila, Spirocerca lupi	Trachea, bronchi
	Eucoleus (capillaria) boehmi	Nasal cavity - rare
	Angiostrongylus vasorum	Pulmonary arteries
	Oslerus osleri	Trachea, proximal bronchi
	Dirofilaria immitis (filarid)	Pulmonary artery
	Filaroides hirthi, Andersonstrongylus milksi	Bronchi, bronchioles, alveoli
	Linguatula serrata (pentastome)	Nasal passages
	Crenosoma vulpis	Bronchi and bronchioles
Cat	Eucoleus aerophila, Filaroides rostratus	Trachea, bronchi
	Aelurostrongylus abstrussus	Bronchioles, alveolar ducts
	Paragonamus kellicoti (fluke)	In inflammatory cavitations
	Troglostrongylus spp.	Sinuses, tracheaàbronchioles
Cattle	Dictyocaulus viviparous	Large bronchi
Sheep, Goat	Dictyocaulus filaria	Bronchi, bronchioles
	Protostrongylus rufescens	Bronchioles
	Muellerius capillaris	Alveoli
	Cystocaulus ocreatus	Alveoli & small bronchioles
	Oestrus ovis (bot)	Nasal cavity
Horse, Donkey	Dictyocaulus arnfieldi	Bronchi, bronchioles
Pig	Metastrongylus apri; M. salmi,	Bronchi, bronchioles
NHP	Filaroides and Filariopsis	Bronchioles à alveoli
Opossum	Didelphostrongylus hayesi	Bronchiàalveoli
Seal	Otostrongylus circumlitus	Bronchi, bronchioles
	Parafilaroides spp.	Bronchioles and alveoli
Dolphin	Skrjabinalius guevarai; Stenurus ovatus	Lungs and cranial sinuses
Avian	Syngamus trachea	Trachea
Mink / mustelids	Crenosoma spp.	Lower airway

 

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;173:83-91. 
2. Boes KM. Respiratory 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; 2023:225-228.
3. Bowman DD. Georgis Parasitology for Veterinarians. 11^th ed. St. Louis, MO; Elsevier; 2021:201-202; 204-206; 472-473.
4. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. St. Louis, MO; Elsevier; 2016:586-587. 
5. Cohn, LA. Diseases of the Pulmonary Parenchyma. In: Ettinger SJ, Feldman EC, Cote E, eds.  Textbook of Veterinary Internal Medicine. 8^th ed. St. Louis, MO; Elsevier; 1111-1112.
6. 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; 2014:263-264. 
7. Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 2006:27.
8. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:245-246. 
9. Lopez A, Martinson SA.  Respiratory System, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:632;637.
10. Lopez-Crespo RA, Lopez-Mayagoitia A, Ramirez-Romero R, Martinez-Burnes J, Prado-Rebolledo OF, Garcia-Marquez AJ. Pulmonary lesions caused by the lungworm (Didephostrongylus hayesi) in the opossum (Didelphis virginiana) in Colima, Mexico. J Zoo and Wildl Med. 2017; 48(2): 404-412.
11. Pool R, Chandradeva N, Gkafas G, Raga JA, Fernández M Aznar FJ. Transmission and predictors of burden of lungworms of the striped dolphin (Stenella coeruleoalba) in the western Mediterranean. J Wildl Dis. 2020; 56 (1): 186-191.
12. Strait K, Else J, Eberhard ML.  Parasitic disease of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman primates in biomedical research: Diseases. Waltham, MA: Academic Press, 2012: 222-229; 235-236

 

 

 

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