JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-P20

Signalment: (JPC #1622313): Female Swiss Webster mouse.

 

HISTORY: This female Swiss Webster mouse was injected with 200 cercariae of Schistosoma mansoni three months before it was found dead in its cage.

HISTPATHOLOGIC DESCRIPTION: Liver: Multifocally and randomly replacing hepatocytes and compressing adjacent parenchyma, there are numerous coalescing up to 0.5 mm diameter eosinophilic granulomas, often centered on a schistosome egg. These eggs are 100 x 50 µm, irregularly oval, have a 2-3 µm thick yellow-brown shell with a prominent lateral spine, and contain a miracidium within which are multiple nuclei-like structures. Eggs are surrounded by concentric rings composed of moderate numbers of eosinophils and epithelioid macrophages with fewer lymphocytes and plasma cells and occasional multinucleated giant cells, and further surrounded by and admixed with fibroblasts and moderate amounts of collagen (reactive fibroplasia). Multifocally expanding and occluding large veins there are cross and tangential sections of adult schistosomes with a papillated tegument, underlying muscle and parenchymal cells, and an intestinal tract containing dark brown hematin pigment. Occasionally a larger male schistosome envelopes a smaller female, with the two separated by a narrow clear space (female schistosome within the gynecophoric canal of the male). Occasionally females contain multiple 1-2 µm brightly eosinophilic globules within the parenchyma (vitellaria). Multifocally, macrophages in sinusoids contain brown hematin pigment. Rarely, the vessel wall adjacent to the parasites is expanded by primarily eosinophils, with fewer macrophages and lymphocytes, as well as eosinophilic and karyorrhectic debris (vasculitis). There are multifocal, random areas of coagulative necrosis characterized by retention of hepatic cord architecture with hypereosinophilic hepatocytes exhibiting nuclear pyknosis, karyorrhexis, and karyolysis. 

MORPHOLOGIC DIAGNOSIS: Liver: Eosinophilic granulomas, multifocal, random, moderate, with coagulative necrosis, eosinophilic vasculitis, schistosome eggs and intravascular adult schistosomes, Swiss Webster mouse, rodent.

ETIOLOGIC DIAGNOSIS: Hepatic schistosomiasis

CAUSE: Schistosoma mansoni

CONDITION: Schistosomiasis, bilharzia, bilharziasis

GENERAL

• Schistosomes are important venous parasites; schistosomiasis is a snail-borne fluke infection; often a disease of long duration
• Schistosomiasis is caused by digenetic (i.e. sexual and asexual reproduction) trematodes that live in blood vessels and parasitize birds and mammals, especially humans
  1. Asexual reproduction occurs in the snail as an intermediate host whereas sexual reproductions occurs in vertebrates as the definitive host
• The genera Schistosoma, Heterobilharzia, and Orientobilharzia parasitize mammals
  • Adult Schistosoma mansoni trematodes are usually found in the mesenteric and portal vasculature > intimal proliferation and thrombosis; eggs are usually found in the walls of the intestine and in the liver
• Schistosomiasis is a foreign parasitic diseases; occurs in tropical areas (e.g., Africa, Asia, South America, Caribbean, southern U.S.)
• Does not usually occur as clinical disease; pathology and clinical disease usually result from localization of adult flukes and eggs in blood vessels of the liver, lungs, alimentary and urogenital tracts, and the nasal cavity
• Causes multifocal to diffuse granulomatous enterocolitis 

LIFE CYCLE

• Indirect; intermediate hosts are snails 
• Eggs hatch in water > release ciliated larvae (miracidia) > penetrate snail > cercariae (infective stage) develop in the snail (asexual reproduction) > released in water > ingested or penetrate skin to infect definitive host > in the definitive host, cercariae lose their tails (become schistosomula) > enter dermal venules > conveyed in blood through the lungs and systemic circulation
• Eggs will penetrate the serosal wall of the intestines inciting a large inflammatory response 

• Eggs also migrate to the liver and are carried by portal circulation to various other organs – commonly pancreas and kidneys

• Maturation occurs in the liver

• Mature adults migrate to mesenteric veins where sexual reproduction occurs

• Intravascular mated schistosomes (in permanent copula) deposit eggs that penetrate capillary walls and leave the body via feces or urine; spines on eggs facilitate passive tissue migration > eggs hatch in water

PATHOGENESIS

• Pathology is secondary to oviposition and extrusion of eggs through the tissues (egg-induced TH₂ response > small granuloma formation “pseudotubercles”), activation of macrophages; spines may facilitate migration into tissue

• Symptoms generally not caused by the worms themselves but what the host response is to the eggs within the tissue

• Adult parasites ingest erythrocytes and regurgitate iron-porphyrin pigment (hematin), which is engulfed by macrophages (especially in lymph nodes and liver)
• Cercariae will invade skin of many animals > allergic reaction/dermatitis
• Enzymes facilitate transport of the eggs into the intestines, and they are ultimately excreted in the feces
• S. nasale develops in nasal mucosa; all other species develop in veins of the abdominal cavity (especially the portal vein) until sexual maturity > migrate to mesenteric veins

 

TYPICAL CLINICAL FINDINGS

• Anemia, hypoalbuminemia, +/- diarrhea
• Hypercalcemia (~50% of cases)

• Thought to be related to unregulated calcitriol synthesis by macrophages in the granuloma lesions (egg migration)

• In birds- Emaciation, dehydration, and pectoral muscle atrophy
• Can produce intrahepatic portal hypertension due to occlusion and increase resistance in vessels 

 

TYPICAL GROSS FINDINGS

• Thickened intestinal wall; may contain small granulomas and lymphoid nodules
• Engorged, tortuous submucosal and subserosal veins
• Thickened mesentery; enlarged, firm mesenteric lymph nodes; +/- ascites
• Adult parasites (1-3 cm long) in mesenteric and portal vessels; characteristic
• Periportal hepatic fibrosis (“clay pipestem”); gray discoloration to liver

• Surface of the liver is bumpy and cut surfaces have granulomas with widespread fibrosis and portal enlargement
• Greyness is due to accumulation of black pigment that is found within these flukes that accumulates in the Kupffer cells (iron-porphyrin compound)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS

• Portal venous thrombi with adult schistosomes, hemosiderin, characteristic schistosome eggs +/- intimal proliferation, eosinophilic vasculitis, and necrosis
• Multifocal lymphoplasmacytic eosinophilic to granulomatous inflammation
• Inflammation with eggs, especially in lung, intestine, pancreas, spleen, lymph nodes, and urogenital tract; eggs may be covered with eosinophilic Splendore-Hoeppli material (due to antigen-antibody complexes)

• Splendore–Hoeppli (asteroid bodies)- Microorganisms (fungi, bacteria and parasites) surrounded by intensely eosinophilic club-like material
• Eggs may be present in the mucosa, submucosa and muscular layers

• Adults: Tegument is eosinophilic and may have spines, no body cavity, oral suckers; paired ceca; intestine; non-muscular pharynx; vitellarian glands (female yolk-forming glands); male larger with a ventral groove (gynecophoric canal) that carries the female (permanently coupled)
• Eggs: Yellow-brown; thin-shelled; elongated oval; rounded at both ends (no opercula); lateral spine
• Hematin pigment in various tissues 

ADDITIONAL DIAGNOSTIC TESTS

• Eggs in urine or feces
• PCR – ELISA test for antibody indicating infection at some point but cannot necessarily coordinate with clinical status

DIFFERENTIAL DIAGNOSIS

COMPARATIVE PATHOLOGY 

Schistosomes sp. are classed by the distribution, host specificity, egg morphology, intermediate snail hosts and are as follows:

granulomatous cystitis and ureteritis result from trapped eggs) and stomach, of ruminants in central and southern Africa; S. curassoni in ruminants in West Africa; S. margrebowiei and S. leiperi in wild artiodactyls in Central Africa; S. hematobium – humans (associated with urinary bladder transitional cell carcinoma), chimpanzees, baboons, rhesus monkeys, guenons, and mangabeys, gibbons (experimental)

• S. mansoni group: S. rodhaini in dogs and other carnivores in Central Africa; S. mansoni in humans, chimpanzees (liver fibrosis), gorillas, baboons, squirrel monkeys, and African green monkeys; in humans, link between schistosomiasis and hepatocellular carcinoma; woodchuck is an animal model of the human disease
• S. indicum group: India and Southeast Asia—S. spindale in mesenteric veins of ruminants and, occasionally, of horses and dogs; S. nasale in nasal mucosal veins of cattle and, occasionally, of goats and horses; S. indicum in portal and mesenteric veins of herbivores; S. incognitum in swine and dogs
• S. japonicum group: S. japonicum, human by preference, in all domestic animals (dogs, cats, rabbits, and domestic farm animals - cattle and sheep) in the Far East, and chimpanzees, rhesus monkeys, and rats; S. mekongi in dogs and humans in Southeast Asia
• Heterobilharzia americanum: Dogs, raccoons, bobcats, white-tailed deer, rabbits, and nutria in the southern US; swimmers itch in humans

• Heterobilharzia americanum: Complex life cycle (snail and mammalian hosts , i.e., raccoon and domestic canids); dogs infected while swimming 

• S. mansoni, S. haematobium, S. mattheei – NMW, OWM, baboons 
• S. hippopotami, S. edwardiense - Intermediate host: snails; definitive host: Free-ranging Hippopotamidae
• Adult schistosomes live in the circulatory and nasal sinuses of birds

• Eight genera of schistosome trematodes infect Anseriformes (waterfowls)
• Three genera infect Ciconiiforms (stork like birds)
• Three infect Charadriiforms (small to medium species birds)

Parasites associated with neoplasia (mnemonic SOCS-T):

• Spirocerca lupi: Esophageal sarcomas in dogs
• Opisthorchis spp., Clonorchis (Opisthorchis) sinensis (liver flukes): Cholangiocarcinoma in cats, NHPs, humans
• Cysticercus fasciolaris (Taenia taeniaeformis): Hepatic sarcoma in rats
• Schistosoma spp.: S. mansoni associated with hepatocellular carcinoma in humans; S. hematobium associated with urinary bladder transitional cell carcinoma in humans
• Trichosomoides crassicauda: Papillomas of the urothelium in rats

            

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