JPC SYSTEMIC PATHOLOGY
Signalment (JPC #3134519): 12-year-old female mixed breed dog
HISTORY: The dog was kept in a kennel and died spontaneously overnight.
HISTOPATHOLOGIC DESCRIPTION: Lung: There are multifocal to coalescing granulomas that efface the pulmonary architecture. The granulomas are composed of a central core of eosinophilic necrotic debris admixed with myriad metastrongyle larvae and eggs surrounded by macrophages and multinucleated giant cells (foreign body type), which are further rimmed by fibroblasts, concentrically arranged mature collagen, lymphocytes and plasma cells. The larvae are elongated with a thin eosinophilic cuticle and a primitive intestinal tract. The thin-walled eggs are ovoid, 50-60 μm in diameter, and contain either a morula or larva. The bronchial lumina contain numerous eggs and larva intermixed with few histiocytes and multinucleated giant cells, sloughed epithelial cells and abundant mucus. Multifocally, pulmonary arteries are severely dilated and the tunica intima is thickened by moderate amounts of fibrous connective tissue and few lymphocytes and plasma cells (proliferative arteritis). Within the lumen there are few cross sections of two morphologically distinct nematode adults. The larger adult nematode cross section is 0.5-1 mm in diameter with a thin eosinophilic cuticle, internal cuticular ridges, tall coelomyarian/polymyarian musculature, and a small intestinal tract lined by cuboidal uninucleated cells (consistent with Dirofilaria immitis ). The cross section of the second smaller adult nematode is 100 to 250 μm in diameter with smooth 3-4 μm cuticle, thin coelomyarian/polymyarian musculature, and a large intestinal tract lined by few multinucleated cells, and a reproductive tract. Intravascular nematodes are surrounded by thrombi composed of lamellar bands of fibrillar eosinophilic fibrin, which multifocally are adhered to the vessel wall. Few vessels are occluded with organized fibrous connective tissue containing multiple small blood-filled channels (organized thrombus with recanalization). The tunica media of numerous pulmonary arteries is markedly thickened (smooth muscle hypertrophy).
MORPHOLOGIC DIAGNOSIS: 1. Lung, arteries: Endarteritis, proliferative, chronic, multifocal, marked, with organizing thrombosis, dilatation, and few intravascular adult metastrongylid and filarid nematodes, etiology consistent with Angiostrongylus vasorum and Dirofilaria immitis. 2. Lung: Pneumonia, granulomatous, multifocal to coalescing, marked, with hemorrhage, fibrosis, and many nematode larvae and eggs, consistent with Angiostrongylus vasorum.
ETIOLOGIC DIAGNOSIS: Pulmonary angiostrongyliasis and dirofilariasis
ETIOLOGY: Angiostrongylus vasorum and Dirofilaria immitis
- Dirofilaria immitis
- Filarid nematode in the order Spiruridae
- “American heartworm
- Angiostrongylus vasorum
- Metastrongylid nematode (superfamily Metastrongyloidae, family Angiostrongyloidae)
- “French heartworm” because it was first reported in France in the 1800’s
- Most pathogenic lungworm of dogs
- The bacterial organism Wolbachia harbored by D. immitis results in more severe vascular lesions
- Right heart failure: Inflammatory reaction to worms > myointimal proliferation mediated by platelet derived growth factor (PDGF) > fibromuscular vascular wall hyperplasia > pulmonary hypertension > right heart failure
- Vena caval syndrome: Large number of adult worms in right atrium and vena cava > venous obstruction > decreased venous return > shock
- Renal: Immune response to all forms of the parasite > immune complex formation > deposition in glomeruli > membranoproliferative glomerulonephritis
- Right heart failure and extensive pulmonary lesions are a consequence of egg embolization and pulmonary arterial thrombosis
- D. immitis
- L1, L2 and early L3 larvae are obligate parasites of Aedes, Culex, and Anopheles spp. > larvae enter definitive host when the mosquito feeds > larvae mature and reach the right ventricle in 3-4 months > adults reside in pulmonary vasculature and release microfilaria into the bloodstream
- A. vasorum
- Indirect life cycle: Intermediate host is a gastropod such as aquatic and terrestrial snails
- Adults shed eggs into pulmonary circulation > eggs deposited in pulmonary parenchyma where they develop and hatch > first stage larva penetrate the alveoli and are coughed up and swallowed > excretion in feces and ingestion by gastropod > maturation into L3 in gastropods > ingestion of gastropods by definitive host > L3 penetrate the GI tract > migration through mesenteric lymph nodes while development into immature adults > migration through the portal circulation and reach maturity in pulmonary arteries
TYPICAL CLINICAL FINDINGS:
- D. immitis
- Asymptomatic to severe systemic disease including vena caval syndrome
- Cough and exercise intolerance
- Vena caval syndrome (young dogs with large burden): Weakness, anorexia, bilirubinuria, hemoglobinuria, and anemia (microangiopathic anemia with schistocytes)
- A. vasorum
- Mild coughing and exercise intolerance to fatal cardiopulmonary disease
TYPICAL GROSS FINDINGS:
- D. immitis
- Adult heartworms in pulmonary arteries and right ventricle; less frequently in the left ventricle and vena cava in heavy infestations (> 50 worms)
- Caudal lobar pulmonary arteries most severely affected
- Hepatic chronic passive congestion
- A. vasorum
- Small 1-2 mm diameter, red, firm, multinodular to confluent areas of hemorrhage and edema at the lung periphery
- Chronic heart failure
- Adults have “barber pole” appearance due to helically arranged red digestive tract and white reproductive tract
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- D. immitis
- Pulmonary: Most commonly seen pulmonary parenchymal lesions are arterial thrombosis and periarterial and interstitial eosinophilic and granulomatous inflammation and fibrosis; diffuse pulmonary hemosiderosis
- Cardiovascular: Eosinophilic and proliferative endarteritis with infiltration of eosinophils and neutrophils
- Adult parasites are found in pulmonary artery and right heart and are characterized by evenly spaced lateral internal cuticular ridges, thick very well developed coelomyarian musculature, and a small (proportional to body size) intestine
- Renal: Membranoproliferative glomerulonephritis
- A. vasorum:
- Pyogranulomatous interstitial pneumonia
- Vascular lesions: Proliferative endarteritis, thrombosis, thickening of tunica intima by fibromuscular tissue, medial hypertrophy, infiltration of eosinophils, lymphocytes and plasma cells, chronic cases may have fibrosis and vascular recanalization of arterial thrombi
- Adults: Thin coelomyarian musculature, large strongylid intestine composed of few multinucleated cells, and uterus with eggs; found in pulmonary arteries and right heart
- All metastrongyles have coelomyarian musculature and L1 larvae have a distinctive kinked tail and small dorsal spine
- Aberrant migration of larva can cause granulomas, with or without association of larvae and eggs in multiple organs including: brain, kidney, tracheo-bronchial lymph nodes, adrenal gland, skin, liver, pancreas, pericardial sac, urinary bladder, femoral artery, intestinal tract, thyroid gland, pituitary gland, skeletal muscle, heart, and eye
ADDITIONAL DIAGNOSTIC TESTS:
- D. immitis: Antigen SNAP test
- A. vasorum: Identification of L1 via fecal examination using the Baermann technique or examination of bronchiolar lavage samples; serum enzyme-linked immunosorbent assay and Western blot analysis
Other pulmonary parasites
- Crenosema vulpis: Chronic coughing due to infection of bronchioles, bronchi, and trachea
- Eucoleus aerophilous (formerly Capillaria aerophila): Trichurid nematode; adult embeds in respiratory epithelium; causes inapparent to catarrhal inflammation; the distinguishing morphologic feature is eggs with bipolar plugs; features of adults include segmental thickenings of hypodermis (bacillary bands), a basophilic esophageal gland (stichosome), and embryonated eggs in the uterus
- Oslerus osleri (formerly Filaroides osleri): Single to multiple 1-10 mm, firm submucosal nodules in the trachea and bronchi which are most prominent at the tracheal bifurcation; granulomatous to pyogranulomatous inflammatory nodules containing adult parasites or fifth stage larvae
- Filaroides hirthi: Direct life cycle with most infections from the dam; adults live in alveoli and respiratory bronchioles; typically incidental findings at necropsy unless immunosuppressed; gray-tan to black-green nodules in subpleural regions of the lungs; nodules may be white or have cystic centers
- Andersonstrongylus milksi (formerly Filaroides milksi): Similar lesions as F. hirthi
- Parastrongylus cantonensis (formerly A. cantonensis - rat lungworm): Accidental hosts; infection results in ascending paralysis and lumbar hyperalgesia due to an obligate neural migration cycle
- D. immitis
- Cats: Usually infected with low numbers of adults (often one) and frequently male-only infections
- A. vasorum: Wild canids (foxes, coyotes, wolves, badgers); red foxes are the natural definitive host and an important reservoir for infection in domestic dogs
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