JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2247995): Young adult female cynomolgus monkey (Macaca fascicularis).
HISTORY: This monkey was wild-caught in Southeast Asia or the Philippines, and was a control animal on a 14-week study. She was in apparently good health when euthanized.
HISTOPATHOLOGIC DESCRIPTION: Lymph node: Multifocally, within paracortical areas, medullary cords and sinuses are up to 1 mm diameter poorly organized coalescing eosinophilic granulomas composed of a central core of intrahistiocytic and/or extracellular trematode eggs surrounded by concentric layers of numerous multinucleated giant cell macrophages (Langhans and foreign body type) and epithelioid macrophages that are further surrounded by numerous eosinophils, fewer lymphocytes and plasma cells, and occasional layers of hypertrophied fibroblasts. Eggs are 40 x 50 um, with a yellow-brown, 2-3 um thick refractile shell, prominent lateral spines, and a central 30-40 um-wide, irregular eosinophilic miracidium with numerous 3 um-diameter basophilic nuclei. Remaining sinuses are diffusely filled with many macrophages, eosinophils, fewer neutrophils, lymphocytes, plasma cells, and are expanded by eosinophilic proteinaceous fluid or clear space (edema). Lymphoid follicles are diffusely increased in number and size and have prominent germinal centers (secondary follicles) and mantle zones, and there is expansion of paracortical areas (lymphoid hyperplasia), with increased numbers of tingible body macrophages.
Liver: Multifocally within portal and periportal areas, replacing hepatocytes and compressing surrounding cords and sinusoids, are coalescing, up to 1 mm eosinophilic granulomas, centered on schistosome eggs as previously described. Focally, the tunica media of one vessel wall, within a portal area is expanded and effaced by variable numbers of eosinophils, lymphocytes and fibrin which partially occlude the vessel lumen. Diffusely, portal areas are expanded by moderate amounts of fibrous connective tissue and moderate numbers of eosinophils, lymphocytes, plasma cells, and fewer macrophages. Biliary duct profiles are increased (ductular reaction). Sinusoids directly surrounding the granulomas contain low to moderate numbers of similar inflammatory cells, with small numbers of brown pigment-laden Kupffer cells.
- Lymph node: Lymphadenitis, granulomatous and eosinophilic, multifocal to coalescing, moderate, with numerous trematode eggs and moderate diffuse lymphoid hyperplasia, Cynomolgus monkey (Macaca fascicularis), nonhuman primate.
- Liver: Hepatitis, portal and periportal, granulomatous and eosinophilic, multifocal, with numerous trematode eggs.
ETIOLOGIC DIAGNOSIS: Lymph node and hepatic schistosomiasis
CAUSE: Flukes of the family Schistosomatidae
CONDITION: Schistosomiasis, bilharziasis
- Important venous trematode parasites in Africa, Asia, and other tropical and subtropical areas; also in the southern U.S.
- Usually subclinical but damage may occur as a result of localization of adult flukes and eggs in blood vessels of liver, lungs, alimentary, and urogenital tracts, and nasal cavity
- Family Schistosomatidae - blood flukes of birds and mammals
- Genera that parasitize mammals: Schistosoma, Heterobilharzia, and Orientobilharzia
- Characteristic of these trematodes that intermediate hosts are freshwater snails
- Unisexual and dimorphic (other trematodes are hermaphroditic): male is usually larger and has a ventral groove (gynecophoric canal) that carries the female (permanently coupled)
- Location of adult flukes depends on species; blood vessels of the liver, lungs, alimentary and urogenital tracts, +/- nasal cavity are most common
- Adults can live 20 –30 years
- Often an incidental finding in horses but more often associated with marked intestinal disease and hypercalcemia in dogs
- Most damage is caused by oviposition and extrusion of eggs through the tissues and mucous membranes with granulomatous inflammation and fibrosis being hallmark features
- Mated schistosomes move out into the smallest venous radicles, and eggs are deposited first in the lumen of the vessel; eggs adhere to and are eventually covered by the endothelium (hyperplasia)
- Eggs of some species have spines, which facilitate passive migration; the developing miracidium secretes compounds that diffuse through the shell and aid in active migration
- As eggs are deposited in deeper veins, the antigens released by miracidia induce a delayed hypersensitivity response and formation of small granulomas (“pseudotubercles”)
- Case report of T cell lymphoma associated with Heterobilharzia sp. infection in a dog; similar association previously made in humans
- Eggs laid in vessels inhabited by adults (usually mesenteric veins) > immature eggs contain miracidia > eggs migrate through tissues to and through mucous membranes of intestine or urinary bladder > expelled in feces or urine > eggs hatch in water, releasing miracidia > miracidia actively penetrate soft tissues of aquatic snails > emerge from snail as cercariae (infective stage) > cercariae enter the definitive host by burrowing through the skin > cercariae lose their tails and become schistosomula > enter venules in dermis and are conveyed passively in blood, through the lungs, and into systemic circulation > those that arrive at correct final habitat (portal vein for most species) develop further and those that arrive at other organs die > males and females together in vessels eventually resulting in deposition of eggs > granulomatous inflammation
- Entire cycle takes 8-12 weeks
TYPICAL CLINICAL FINDINGS:
- Nonhuman primates are often asymptomatic, and lesions are incidental at necropsy
- Acute phase: hemorrhagic diarrhea and weight loss (caused by rupture of congested mucosal vessels occurs at the time of patency and persists for a few weeks)
- Anemia, hypoalbuminemia, emaciation, pyrexia, hematuria, and ascites possible
- Dermatitis due to cercarial penetration of skin
- May be followed by spontaneous recovery in the absence of re-infection (immune response of host eliminates the parasites and suppresses the egg laying of survivors)
- Hypercalcemia with Heterobilharzia Americana in dogs
TYPICAL GROSS FINDINGS:
- Most frequently encountered lesion: thickened intestinal (typically large bowel) or urinary bladder wall and mesentery due to chronic inflammation (scar tissue, granulomas, lymphoid nodules) with polypoid and papillary projections
- Adult parasites (1-3 cm long) are in the mesenteric (S. manosoni and S. mattheei) and portal or pelvic (S. haematobium) veins; may incite endophlebitis and thrombosis
- Liver smaller or larger than normal with variable periportal, multifocal to diffuse hepatic fibrosis; eggs can be mineralized in multifocal hepatic granulomas with extensive fibrosis (“pipestem fibrosis”) that can lead to cirrhosis
- Granulomas may also be present in the lymph nodes, spleen, and lungs
- Proliferative granulomatous nasal lesions from S. nasale and in urinary bladder and ureters of cattle from S. mattheei
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Hallmark: granulomatous response to eggs entrapped in host tissues
- Fibrosis of liver particularly around portal vessels
- Liver, brain, spleen, gastrointestinal tract walls, and urinary bladder: granulomas, often with eggs in the center (some may mineralize); macrophages and multinucleated giant cells engulfing eggs; microabscesses with neutrophils and eosinophils
- Skin: acute dermatitis with edema may develop when cercariae penetrate the skin
- Adults: paired ceca, intestines, nonmuscular pharynx, suckers, vitellarian glands (female reproductive glands); those in veins elicit eosinophilic endophlebitis, often proliferative and may be in thrombi
- Eggs: yellow-brown, hyaline, elongate, oval, rounded at both ends and thin-shelled with a lateral or terminal spine, with no opercula; presence and location of spines is dependent on the species; Splendore-Hoeppli material can coat degenerate eggs
- Hematin pigments in various tissues: adult parasites ingest erythrocytes and regurgitate hematin pigments, which are phagocytosed by cells of the monocyte-macrophage system, especially in regional lymph nodes
- Granulomas may be widespread and in high numbers in severe infections, including the lungs in addition to the above mentioned tissues
ADDITIONAL DIAGNOSTIC TESTS:
- Demonstration of the ova in feces or urine
- PCR of fresh (unfixed) or frozen lung or liver
- Cytology: ovoid to round basophilic thin-walled eggshell fragments and ciliated miracidia
Eggs in nonhuman primate liver:
- Fasciola hepatica – operculum
- Athesmia foxi and A. heterolecithoides – flukes found in bile ducts of New World monkeys
- Capillaria hepatica – bipolar plugs
Important species that infect domestic animals:
- S. japonicum group
- S. japonicum- all domestic animals in Far East
- S. mekongi- dogs in Southeast Asia
- S. mansoni group
- S. rodhaini in dogs and carnivores in Central Africa
- S. hematobium group
- S. bovis in portal and mesenteric veins of ruminants, horses, camels, and pigs
- S. mattheei in portal and mesenteric veins, plus veins of urogenital tract and stomach of ruminants
- S. curassoni in ruminants
- S. margrebowiei & S. leiperi in wild artiodactyls
- S. indicum group
- S. spindale in mesenteric veins of ruminants, horses, and dogs
- S. nasale in nasal mucosal veins of cattle, goats, and horses
- S. indicum in portal and mesenteric veins of herbivores
- S. incognitum in pigs and dogs
Important species that infect nonhuman primates:
- S. mansoni – Chimpanzees, baboons, squirrel monkeys, mangabeys, guenons, pata monkeys, and African green monkeys in central Africa; in humans, a link between schistosomiasis and hepatocellular carcinoma; woodchuck animal model
- S. japonicum – Chimpanzees, rhesus monkeys, dogs, cats, rabbits, rats, and domestic farm animals in the Far East
- S. indicum – Horses, cattle and goats in India and southeast Asia
- S. hematobium – Chimpanzees, baboons, rhesus monkeys, guenons, and mangabey monkeys; in humans associated with bladder neoplasms
- S. mattheei - baboons
- Heterobilharzia americana – Dogs, raccoons (most important natural definitive host), bobcats, rabbits, horses, camelids, and nutria in the southern U.S.; IH is freshwater snail Bakerilymnaea cuensis or Pseudosuccinea columnella; causes hypercalcemia in >50% of cases
- Trichobilharzia sp., Austrobilharzia variglandis, Gigantobilharzia sp., and Microbilharzia sp. – Avian; report of obliterative endophlebitis in mute swans caused by Trichobilharzia sp.
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