December 2008

Case A

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A one-year-old Boer doe grazing tropical pasture developed lethargy, facial swelling and jaundice.

Example histopathological description

This is a triangular section (14x13x8 mm) of the liver margin with capsule on two sides. There is moderate to severe, random hepatocyte swelling, separation, vacuolar degeneration and scattered hypereosinophilia. There is moderate variation in nuclear size and rare cytosegrosomes are seen. Hepatic cords are disrupted and there is diffuse, mild to moderate single hepatocyte necrosis and apoptosis with low numbers of diffusely scattered neutrophils. Irregularity of the acinar pattern suggests significant previous hepatocyte loss. Kupffer cells are hypertrophic, hyperplastic and sometimes contain granular light brown pigment (presumptively bile). Portal areas exhibit moderate biliary hyperplasia and mild peribiliary fibrosis. Low numbers of mononuclear cells, predominantly lymphocytes with fewer macrophages, have infiltrated peribiliary areas. Multifocally, low numbers of acicular clefts, rarely containing blunt ended, narrow crystals are detected in bile ducts or intracellularly in biliary epithelial cells and nearby hepatocytes. There is cell debris and pink, finely granular material in some of the larger bile ducts.

Morphological Diagnosis

Cholangiohepatopathy, crystal-associated, subacute to chronic, diffuse, moderate, with hepatocellular necrosis and biliary hyperplasia.

Aetiological diagnosis

This is a case of crystal-associated cholangiophepatopathy


Given the history of grazing tropical pastures in Australia, it is probable that the pasture species Panicumor Brachiaria  are the cause of the hepatotoxicity. These plants may contain steroidal saponins. Glucuronide crystals from the saponins precipitate with calcium in bile. Bile duct obstruction, irritation and hyperplasia are the result. In addition, there is direct hepatocyte toxicity. Photosensitisation and jaundice are often evident clinically, as in this case. Needle-shaped (acicular) clefts are formed in bile ducts and nearby cells by the crystals, most of which are removed during routine histological processing.  P coloratrum, P dichotomiflorum and B decumbens (Signal grass) are particularly likely to have been involved. The summer weed Tribulus terrestris could also be a cause, but this is found in more temperate areas. A range of other plant species containing steroidal saponins have been linked with crystal-associated cholangiohepatopathy, including Agave lecheguilla, Nolena texana, Narthecium ossifragum, Yucca schidigera and Doranthes palmeri. However, these are unlikely to have been involved in this case due to their geographic distribution.

Case B

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Baboon with a history of weight loss, sudden collapse and death.

Example histopathological description

This is a 50 mm long, full thickness section of predominantly large intestine; presumptively caecum with some ileum. Along the mucosa and embedded in the intestinal glands are moderate numbers of metazoan parasites, up to 500 µm in diameter and up to 1500 µm in length, and lesser numbers of single eggs. Most of the mucosal epithelium is variably attenuated with focally extensive erosions associated with fibrin, cell debris, erythrocytes, mixed bacterial populations and large, sometimes ciliated, protozoa up 30-50 µm in diameter.

Other areas show cuboidal and squamous metaplasia of enterocytes and extensive zones of mucosal hyperplasia. There is scattered, mild crypt necrosis. The submucosa is expanded by moderate numbers of lymphocytes and plasma cells and lesser numbers of eosinophils, neutrophils and macrophages. Occasional submucosal lymphatics are dilated. The muscularis is normal, but the serosa shows multiple lymphatic dilations with presumptive mild fibrosis and one degenerate refractile body (presumptive helminth) surrounded by fibrous tissue. The helminths are cylindrical with a prominent cuticle, without lateral chords but with prominent hypodermal bands and areas of bacillary bands. Well defined reproductive organs contain ova and sperm at various stages of development consistent with hologenic germ cell development. The oesophagus is surrounded by a prominent stichosome. In the single uterus there are many eggs with bipolar plugs. Some eggs are embryonated. These features are consistent with aphasmid nematodes.

Morphological Diagnosis

Typhlocolitis, multifocally erosive, diffusely lymphoplasmacytic and eosinophilic, chronic, moderate, with intralesional nematodes, protozoa and bacteria.

Aetiological Diagnosis

Verminous (aphasmid) typhlocolitis caused by Trichuris trichura

Significance of findings

Infections with T trichura are common in wild and captive baboons and the parasite is a potential zoonotic agent.  Although often subclinical, infections can cause typhlocolitis and weight loss, but are not usually associated with sudden collapse and death. However, one report suggests a predisposition to intussusception (Hennessy A et al. Helminth infestation complicated by intussusception in baboons.Laboratory Animals 1994;28:270-273).

The ciliated protozoa are presumptively Balantidium coli, a common commensal of primates, pigs and rodents. They can occasionally contribute to intestinal inflammation. A silver stain will assist to determine if non-ciliated protozoa, such as Entomoeba histolytica, are also present. E histolytica is an opportunistic parasite of the large bowel of man, primates, and many other animals, and is sometimes associated with ulcerative typhlocolitis. Numerous bacteria are closely associated with mucosal injury and may also be playing a role. Species of concern include: Salmonella spp, Shigella spp and Campylobacter spp. Specific culture to rule out these pathogens is recommended.