JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
September 2021
D-P04
SIGNALMENT (JPC #2317402): African green monkey (Cercopithecus aethiops)
HISTORY: Incidental finding at necropsy
HISTOPATHOLOGIC DESCRIPTION: Liver: Multifocally and randomly affecting approximately 15% of the hepatic parenchyma are scattered, variably sized, up to 4mm, granulomas characterized by a central area of eosinophilic cellular and karyorrhectic debris (lytic necrosis) admixed with abundant degenerate eosinophils and neutrophils and a variable amount of basophilic material (mineral), surrounded by moderate numbers of epithelioid macrophages, eosinophils and few multinucleated giant cells, further surrounded by plasma cells, lymphocytes, few fibroblasts, and minimal fibrous connective tissue. Adjacent hepatocytes are frequently pale with swollen cytoplasm (degenerate), or, less commonly, shrunken with hypereosinophilic cytoplasm and pyknosis (necrotic). Multifocally associated with granulomas or randomly scattered within the parenchyma are round to oval apicomplexan merocysts ranging from 300-1800 um in diameter lined by a thin, eosinophilic, hyaline capsule and filled with multiple 25X50um, oval to elongate to irregular schizonts that are each lined by a 2um eosinophilic capsule that imparts an internally septate appearance to the merocyts, and are filled with abundant 2-3 um basophilic merozoites. Larger, more mature merocysts that are undergoing various stages of degeneration or rupture have a large, central cavitation that contains fibrillary, eosinophilic material and scattered, often peripheralized basophilic merozoites. There are low numbers of portal and periportal lymphocytes and plasma cells. Scattered Kupffer cells and hepatocytes contain brown granular pigment (hemosiderin).
MORPHOLOGIC DIAGNOSIS: Liver: Granulomas, eosinophilic, multiple, random, with protozoal merocysts, etiology consistent with Hepatocystis kochi, African green monkey (Cercopithecus aethiops), nonhuman primate.
ETIOLOGIC DIAGNOSIS: Hepatic hepatocystosis
CAUSE: Hepatocystis kochi
GENERAL DISCUSSION:
- Apicomplexan hemoprotozoan which is the most common malaria-like parasite of African primates; does not infect humans
- Distribution: India to the East Indies; Africa – south of the Sahara Desert
- Family Plasmodiidae; also includes the genera Plasmodium (malaria)
- Synonyms: H. kochi, joyeuxi, H. bouillezi, H. cerocopitheci, H. simiae, Plasmodium kochi, and Hepatocystis sp
- Reported in 40 – 75% of imported non-human primates; hosts include Old World monkeys (African green monkeys, guenons, mangabeys, baboons, patas monkeys, colobus monkeys, Formosa rock macaques, other Macaca and left monkeys), apes (gibbons), and orangutan
- Typically incidental; primary effect is interference with research data
PATHOGENESIS:
- Little or no inflammatory response to immature merocysts
- Suppurative response to the maturing merocyst upon release of merozoites, followed by progressive increase in histiocytes, formation of granulomas, and eventual resolution as a fibrous scar
LIFE CYCLE:
- kochi’s life cycle:
- Resembles Plasmodium, except asexual schizogony does not take place in erythrocytes of the host but in the liver where they form characteristic cysts known as merocysts, which are visible grossly
- Indirect; midges (Culicoides, ) are the biological vector for the gamont stage
- Sporozoite inoculated into circulation during feeding by vector Culicoides spp à sporozoite enters hepatocyte à develops into meronts (merocysts) filled with merozoites à merocyst ruptures after 1-2 months, releasing merozoites à merozoites invade erythrocytes and form ring-like trophozoite à microgamonts and macrogametes develop in the erythrocytes à infected blood ingested by Culicoides spp, where microgametes form and fertilization and sporogony occur, forming the infective sporozoites
TYPICAL CLINICAL FINDINGS:
- Typically asymptomatic; no cyclic fever or waves of parasites in the blood like with malaria due to schizogony occurring in the liver
- Occasionally mild microcytic anemia
TYPICAL GROSS FINDINGS:
- Random, multifocal 2-6 mm, grayish-white, somewhat translucent foci on the surface of the liver (mature merocysts) and/or white fibrotic scars (healed area where cyst ruptured)
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Multifocal merocysts in variable stages of maturation; may reach 4 mm in diameter
- Mature merocysts contain a large central vacuole filled with colloid surrounded by peripherialized merozoites; neutrophilic exudate surrounds the merocyst
- Chronic eosinophilic granulomatous inflammatory reaction with infiltration of lymphocytes and macrophages after cyst ruptures
- Healing results in fibrosis in and around the area of the cyst
ADDITIONAL DIAGNOSTIC TESTS:
- Cytology: Identification of parasite in thick or thin blood smears using Giemsa stain; trophozoites, microgamonts, and macrogamonts within erythrocytes
- Microgamonts have an unusual nucleus with large, oval, pink nucleoplasm that occupies one third or more of the parasite and red chromatin granules/threads
DIFFERENTIAL DIAGNOSIS:
- Plasmodium – do not form mature merocysts
- Tuberculosis - granulomas without merocysts
COMPARATIVE PATHOLOGY:
- Species infected by different Hepatocystis: Multiple nonhuman primate, fruit bats, oriental squirrels, deer mice, hippopotami
REFERENCES:
- Gardiner C, Fayer R, Dubey J. An Atlas of Protozoan Parasites in Animal Tissues. Washington, DC: American Registry of Pathology; 1998:67-8.
- Strait K, Else JG, Eberhard ML. Parasitic diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. San Diego, CA: Academic Press; 2012:211, 216-218.
