JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
October 2021
D-P28

SLIDE A: SIGNALMENT (JPC #2550908):  Adult female Barbary ape (Macaca sylvana)

HISTORY:  This animal was kept in a zoo.

HISTOPATHOLOGIC DESCRIPTION:  Liver: Expanding and replacing 50% of the hepatic parenchyma and compressing adjacent hepatocytes is a multilocular (alveolar) hydatid cyst composed of round to oval to irregular, intact and ruptured, 2-6 mm diameter parasitic cysts surrounded and separated by variably thick bands of fibrous connective tissue. Fibrous connective tissue extends into and replaces adjacent hepatic parenchyma and contains moderate numbers of lymphocytes, plasma cells, macrophages, and eosinophils, and many entrapped bile ductules.  Interior to the fibrous bands, cysts are lined by a 10-50 um thick eosinophilic hyaline outer laminated membrane and a 50-150um inner germinal epithelial layer containing basophilic nuclei, eosinophilic flocculant to granular material, and numerous 5-20 um basophilic calcareous corpuscles. Budding from the germinal epithelium or free within the cyst lumen are many thin-walled brood capsules containing multiple 100-150 um diameter protoscolices. Protoscolices have a 5 um thick tegument enclosing spongy parenchyma that contains calcareous corpuscles, a sucker, and a rostellum armed with birefringent hooks. Ruptured cysts are collapsed and contain variable amounts of eosinophilic necrotic debris admixed with degenerate neutrophils, eosinophils, lymphocytes, plasma cells, foamy macrophages, and multinucleated giant cells, which extend into the adjacent fibrous connective tissue. Multifocally throughout the adjacent hepatic parenchyma, hepatocytes are necrotic with shrunken hypereosinophilic cytoplasm and nuclear pyknosis, are individualized and surrounded by hemorrhage, are degenerate, with swollen, pale, vacuolated cytoplasm, or are lost and replaced by necrotic debris, hemorrhage, and/or fibrosis. Portal and fibrotic areas adjacent to the hydatid cyst have increased numbers of small bile duct profiles (ductular reaction).

MORPHOLOGIC DIAGNOSIS:  Liver: Hydatid cyst, multilocular, with multifocal fibrosis, hepatic necrosis, and ductular reaction, etiology consistent with Echinococcus multilocularis, Barbary ape (Macaca sylvana), primate.

ETIOLOGIC DIAGNOSIS:  Hepatic echinococcosis

CAUSE:  Echinococcus multilocularis

CONDITION:  Alveolar or multilocular hydatid disease

SLIDE B: SIGNALMENT (JPC #4098098):  Adult Irish draft horse (Equus caballus)

HISTORY:  Presented for acute onset of neurologic signs and ataxia after being imported from Ireland three days prior. CBC and chemistry were WNL. Cervical radiographs showed remodeling of articular facets at C5-C7. The horse became recumbent after 24 hours and was presented for autopsy.

HISTOPATHOLOGIC DESCRIPTION:  Liver: Expanding and replacing approximately 50% of the hepatic parenchyma and compressing adjacent hepatocytes is a 2.4cm, single, unilocular hydatid cyst surrounded by a thick band of fibrous connective tissue that extends into and replaces adjacent hepatic parenchyma. Fibrous connective tissue contains few lymphocytes, plasma cells, hemosiderin-laden macrophages, and eosinophils.  Interior to the fibrous band, the cyst is lined by a ~500µm thick eosinophilic hyaline outer laminated membrane and a 10-15µm inner germinal epithelial layer containing basophilic nuclei, eosinophilic flocculant to granular material, and few 5-20µm basophilic calcareous corpuscles. Budding from the germinal epithelium or free within the cyst lumen are occasional thin-walled brood capsules containing multiple 80-120µm diameter protoscolices. Protoscolices have a 5 um thick tegument enclosing spongy parenchyma which contains calcareous corpuscles, a sucker, and a rostellum armed with birefringent hooks. Multifocally throughout the adjacent hepatic parenchyma, hepatocytes are shrunken with hypereosinophilic cytoplasm and nuclear pyknosis (single cell death), are shrunken (atrophy), are swollen with pale, vacuolated cytoplasm (degeneration), or are lost and replaced by necrotic debris, hemorrhage and/or fibrosis.

MORPHOLOGIC DIAGNOSIS:  Liver: Hydatid cyst, unilocular, with multifocal fibrosis and hepatocellular degeneration and necrosis, etiology consistent with Echinococcus granulosus, Irish draft horse (Equus caballus), equine.

ETIOLOGIC DIAGNOSIS:  Hepatic echinococcosis

CAUSE:  Echinococcus granulosus

CONDITION:  Cystic echinococcus or unilocular hydatid disease

GENERAL DISCUSSION:

• The genus Echinococcus, a member of the Taeniidae family, includes multilocularis and E. granulosus
  • E. multilocularis: Intermediate hosts are rodents (voles, lemmings, deer mice) in temperate climates
  • E. granulosus: intermediate host is sheep; most commonly found in liver of ruminants, often incidental
• Sylvatic life cycle; red and artic foxes are the most important definitive hosts (i.e. adult taeniid tapeworm in intestine), other hosts (coyotes, raccoon-dogs, wolves) also are common
• Aberrent intermediate hosts include pigs, horses, nonhuman primates, humans, among others
• Human alveolar echinococcosis is a serious zoonosis
• Dogs can act as simultaneous intermediate and definite hosts
  • Dogs become aberrant intermediate hosts and develop alveolar echinococcosis via coprophagia or autoinfection from adult tapeworm intestinal infection

PATHOGENESIS:

• Cyst growth and exogenous budding compress and replace parenchyma, causing progressive hepatic loss and bile stasis
• Cysts spread by infiltration of germinal epithelium into surrounding tissue; germinal cells reaching vessels can become disseminated
• Host reaction: Lymphoplasmacytic to granulomatous inflammation with extensive fibrosis > progressive disease is fatal

LIFE CYCLE: 

• Definitive hosts (canids and other carnivores) with adults in their intestinal tract sheds eggs as gravid segments > ingested by intermediate host > oncosphere (L1) hatches and penetrates the gut wall > travels via portal circulation to the liver (or other aberrant location) > develops to L2 stage (hydatid cyst or metacestode) containing internal brood capsules and protoscolices (also called scolices)
• Intermediate host is ingested by the definitive host where protoscolices attach to GI epithelium and mature into adult tapeworms

TYPICAL CLINICAL FINDINGS:

• Definitive host: Asymptomatic
• Intermediate host:
• multilocularis: Signs depend on the organ involved; relentless proliferation of the parasite makes the condition invariably fatal;
• granulosus: often incidental

TYPICAL GROSS FINDINGS:

• Definitive host: Adult tapeworm is 5mm long with a scolex and approximately five segments
• Intermediate host:
  • Uni- or multi-loculated (depending on species of Echinococcus), encapsulated, white to grey, spongy, clear to flocculent fluid-filled hepatic cysts (brood capsules floating free in cyst fluid form “hydatid sand”)
  • E. multilocularis (multilocular echinococcosis) may be referred to as alveolar echinococcosis because multilocular budding cysts resemble alveoli
• Large cysts may have central areas of necrosis surrounded by a thin rim of viable proliferating parasites
• Hydatid cysts most commonly occur in the liver and lung, but may be found in the peritoneum, heart, bone, subcutis, brain, retrobulbar, and other areas throughout the body
• E. granulosus: Unilocular hydatid cyst; usually not invasive; confined to the connective tissue capsule; expansile growth

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Single or multiple variably sized cysts surrounded by fibrosis; +/- mineralization
• Cysts are lined by an inner germinal epithelium and prominent outer PAS-positive lamellar hyaline membrane; both are of parasitic origin
• Brood capsules budding from the inner germinal layer and free in the lumen contain variable numbers of invaginated protoscolices
• Protoscolices have birefringent, clear to golden-brown hooklets surrounded by parenchyma that occasionally contains calcareous corpuscles

DIFFERENTIAL DIAGNOSIS: 

• Taeniid larval (metacestode) forms:
  • Cysticercus – fluid-filled cyst with invaginated scolex of single larva
  • Strobilicercus – same as cysticercus but the larva begins to elongate like an adult while still in the intermediate host, and scolex evaginates
  • Coenurus – single or loculated fluid-filled cyst with numerous invaginated scolices
  • Hydatid cyst – uni- or mulitloculated with brood capsules that contain invaginated protoscolices

COMPARATIVE PATHOLOGY: 

• Other taeniid tapeworms and associated metacestodes (larval form):
  • Taenia taeniaformis – cats, wild felids; Cysticercus fasciolaris (D-P22)– liver of small rodents, may form fibrosarcoma
  • T. pisiformis – dogs, wild canids; C. pisiformis – liver of intermediate host
  • T. hydatigena – dog; C. tenuicollis – peritoneum of sheep, cattle, swine
  • T. ovis – dogs, wild canids; C. ovis – muscle of sheep (“sheep measles”)
  • T. saginata – dog; C. bovis – cattle (“measley beef”)
  • T. solium – dog; C. cellulosae (N-P12A) – swine
  • T. multiceps – dogs, wild canids; Coenurus cerebralis (N-P12B)– brain, spinal cord of sheep (“gid”), ungulates
• Echinococcus canadensis – gray wolves and cervids in Idaho, US
• Echinococcus equinus-Przewalski’s horses in a Canadian zoo
• Echinococcus granulosus – wild boars in central Italy
• Echinococcus multilocularis – old world monkeys (guenons, colobus monkeys, mangabeys, mandrills, rhesus monkeys); new world monkeys (marmosets); great apes (chimpanzee, gorilla, orangutan); prosimians (galagos, lemurs)

REFERENCES:

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3. Di Paolo A, Piseddu T, Sebastianelli M, et al. Detectin of Echinococcus granulosus G3 in a Wild Boar (Sus scrofa) in Central Italy using PCR and Sequencing. Wildl Dis. 2017 Apr;53(2):399-401.
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16. Zajac A, Fairman D, McGee E, et al. Alveolar echinococcosis in a dog in the eastern United States. J Vet Diagn Invest. 2020;32: 742-746.

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