History

A 3-year-old 0.46-kg sexually intact male African pygmy hedgehog (Atelerix albiventris) was evaluated at the Veterinary Teaching Hospital at the Louisiana State University School of Veterinary Medicine because of a 4-day history of lethargy, anorexia, and decrease in water intake. The owners reported that the hedgehog was less active, they had not seen it defecate recently, and they thought it had possibly urinated on itself.

Clinical and Gross Findings

At the first clinical evaluation, the hedgehog was responsive, stable, and apparently clinically normal. The hedgehog was admitted to the hospital for a full diagnostic workup. During the second examination, only 2 hours later, the hedgehog appeared lethargic and SC fluid therapy was provided. Right after the beginning of the fluid therapy, the hedgehog began agonal breathing and was bradycardic (60 beats/min; reference range, 180 to 280 beats/min) and hypothermic (rectal temperature, 33.0 °C; reference range, 35.4 to 37 °C). Clinicians noticed a mass on abdominal palpation and suspected it to have been a splenic mass. Supportive care was started with external warming and administration of atropine (0.2 mg/kg, IM), but the animal had cardiac arrest and died.

On necropsy, the hedgehog was in good body condition and had pale-pink mucous membranes and a distended abdomen. The spleen was severely enlarged (approx 7 X 3.5 X 2 cm). The splenic parenchyma was diffusely pale pink and friable, with multifocal to coalescent dark-red areas (hemorrhage) and multifocal yellow to green areas (necrosis), which replaced approximately 70% of the parenchyma (Figure 1). The liver was also enlarged, comprised 5.65% (26/460 g) of the total body weight (reference range,¹ 4.58% to 5.16% of the total body weight), and had round borders, tan discoloration, and an accentuated lobular pattern throughout. Sections of the liver floated in neutral-buffered 10% formalin. The kidneys exhibited multifocal, well-delimited, white to yellow depressed areas (0.4 to 1.2 cm in diameter) in the cortex. In the distal colon, a 2-mm-diameter ulcer was in the mucosa, approximately 5 cm orad of the rectum. No other clinically meaningful lesions were observed.

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Postmortem photograph of the abdominal cavity of a 3-year-old 0.46-kg sexually intact male African pygmy hedgehog (Atelerix albiventris) that died 4 days after initial signs of lethargy, anorexia, and decrease in water intake. The splenic parenchyma is diffusely pale pink (asterisk) and has multifocal to coalescing areas of hemorrhage (arrow) and multifocal yellow to green areas of necrosis (arrowhead).

Citation: Journal of the American Veterinary Medical Association 260, 8; 10.2460/javma.20.09.0497

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Histopathologic Findings

Several samples of the main organs were collected and fixed in neutral-buffered 10% formalin. The tissues were processed for routine histologic evaluation, which revealed that the bone marrow had been nearly completely replaced by neoplastic round cells that had distinct cell borders and a moderate to marked amount of cytoplasm with abundant eosinophilic granules, consistent with eosinophils (Figure 2). These neoplastic cells had both immature and mature morphology. The immature cells had round to reniform nuclei, with coarsely stippled chromatin and prominent nucleoli. The mature cells had multilobulated and irregular nuclei, with dense chromatin and inconspicuous nucleoli. Anisocytosis and anisokaryosis were mild, with 1 to 2 mitotic figures/10 hpf. The numbers of megakaryocytes and erythroid blasts were markedly low.

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Photomicrograph of a tissue section of a kidney from the hedgehog described in Figure 1. The normal renal parenchyma is partially replaced by neoplastic round cells with distinct cell borders and a moderate to marked amount of cytoplasm with bright eosinophilic granules. H&E stain; bar = 200 µm.

Citation: Journal of the American Veterinary Medical Association 260, 8; 10.2460/javma.20.09.0497

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Approximately 70% of the splenic parenchyma was replaced by necrotic debris. The normal splenic architecture was replaced by dense sheets of neoplastic cells like those described in the bone marrow. In the hepatic parenchyma, hepatocytes were diffusely swollen with distinct clear cytoplasmic vacuoles (lipid-type vacuolar degeneration). The sinusoids were often expanded by similar neoplastic eosinophils as those described in the bone marrow. Perivascular areas predominantly in the periportal regions had aggregates of similar granulated immature and fewer mature eosinophils. In the lungs, similar neoplastic cells expanded the peribronchiolar and perivascular connective tissue and were observed in the blood vessels and alveolar capillaries. The renal interstitium (predominantly perivascular areas) was expanded by multifocal to coalescent sheets of immature eosinophils and fewer mature eosinophils similar to those described previously for other tissues in this animal. A few immature eosinophils were also entrapped in glomerular capillaries. The renal tubules had occasionally attenuated epithelium and intraluminal eosinophilic proteinaceous casts. Multifocal mineral deposits were present in the renal medullary tubules. An aggregate of immature and mature granulated cells was also present in the perirenal adipose tissue. In the colon, the lamina propria and submucosa were severely infiltrated by immature eosinophils and fewer mature eosinophils similar to those described previously. In the region of the grossly noted ulcer, the submucosa had a focus of variably sized and atypical proliferating spindle cells. Eyes and periocular tissues, nasal and oral cavities, salivary glands, pancreas, trachea, esophagus, stomach, small intestine, and cerebral choroid plexus were infiltrated by similar neoplastic cells. Luna staining² (Figure 3) highlighted the granules of both mature and immature eosinophilic granulocytes.

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Photomicrograph of a tissue section of the liver from the hedgehog described in Figure 1. The neoplastic eosinophils are highlighted by the strong, positive histochemical staining of the cytoplasmic granules. Luna stain; bar = 200 µm.

Citation: Journal of the American Veterinary Medical Association 260, 8; 10.2460/javma.20.09.0497

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Morphologic Diagnosis and Case Summary

Multiple tissues: eosinophilic leukemia.

Liver: hepatic lipidosis.

Case summary: eosinophilic leukemia in an African hedgehog.

Comments

Spontaneous neoplasia is common in adult African pygmy hedgehogs. No gender preference is observed. Increasing age is considered to be a risk factor; the median age of affected animals is 3.5 years, with the normal life span of pet hedgehogs being 3 to 6 years.³ In retrospective studies, the prevalence of neoplasia ranged from 29% (4/14)⁴ to 53% (35/66),³ and approximately 9% (3/35)³ of affected animals had > 1 neoplasm present. The most common sites of neoplasia development in hedgehogs are skin, mammary gland, lymphoid tissues, and the gastrointestinal, endocrine, and reproductive systems. Approximately 85% (34/40)³ of these tumors are malignant and tend to have a poor prognosis. Hematopoietic tumors can account for up to 20% (8/40) of tumors in hedgehogs.³ Lymphoma is the most common of these, with the multicentric and alimentary forms predominating, whereas leukemia in hedgehogs is considered to be uncommon or even rare.^3,5,6 Descriptions of leukemias in hedgehogs include eosinophilic leukemia and acute lymphocytic leukemia or lymphoma.^2,6,7

Eosinophilic leukemia is an infrequent variant of myeloid granulocytic leukemia, which has been described in cats,⁸ a Syrian hamster,⁹ humans,¹⁰ and African pygmy hedgehogs.^3,6,7 This type of neoplasm is considered to be chronic and has been designated as chronic eosinophilic leukemia in humans.¹⁰ The neoplastic cells can be observed in the peripheral blood and consist of mostly immature granulocytes with eosinophilic differentiation.⁶ High myeloid-to-erythroid ratio has been observed in the bone marrow of affected animals.⁷ Some authors suggest that hedgehogs may have a unique genetic susceptibility to this specific type of leukemia.⁶

Animals with myelogenous leukemia can be affected by concurrent cytopenias, like nonregenerative anemia and thrombocytopenia. Biochemical abnormalities depend on the organs affected by neoplastic cells; the literature describes a predominance of liver injury, leading to hypoalbuminemia.⁶ Histologically, it is common to see a neoplastic cell infiltrate in multiple organs including the bone marrow, liver, kidney, gastrointestinal tract, lungs, lymph nodes, heart, and spleen.^2,7 Even though eosinophils can be easily recognized on cytologic or histologic examination, immature cells can be a challenge to identify. Histochemistry and immunohistochemistry may help in the identification of the lineage of the neoplastic cells. In the case of eosinophilic leukemia, Luna stain is the most common method used for the histochemical identification of granules of immature and mature eosinophils.² Cytochemical staining, including myeloperoxidase, alkaline-phosphatase, and Sudan black, can be performed to demonstrate the eosinophil granules as well.⁶

Eosinophils can cause severe tissue damage because their granules contain toxic cationic proteins, which act as primary mediators of cellular damage when released into tissues. These toxins can cause an increase in vascular permeability, smooth muscle contraction, and secretion of mucus.^2,11 This can lead to tissue necrosis, which may have been the mechanism of the noted splenic necrosis in the African pygmy hedgehog of the present report. The focal ulceration in the colon could similarly have resulted from eosinophil-associated injury, with secondary fibroblast proliferation, as was also described in cats with hypereosinophilic syndrome.¹¹ However, in our case, it was not possible to differentiate between a fibroblastic lesion associated with the eosinophilic infiltrate and an incipient sarcoma. A previous unspecified injury could have also led to this type of fibroblastic proliferation.

Differential diagnoses for eosinophilic leukemia include idiopathic hypereosinophilic syndrome and paraneoplastic hypereosinophilia, both described as increases of solely mature eosinophils in blood and tissues.^2,7 The diagnosis of idiopathic hypereosinophilic syndrome is made by exclusion in the absence of an eosinophilic neoplasm (eg, leukemia) or of primary causes for reactive increase of eosinophils (eg, allergies, autoimmune disease, or parasitic infestation).⁷ Other neoplasms must be taken into account when considering severe splenomegaly, especially histiocytic sarcoma and lymphoma. Histopathology is sufficient for differentiating eosinophilic leukemia in these cases.¹²

Early detection of the neoplasm in hedgehogs allows for a more accurate prognosis.⁵ Eosinophilic leukemia has an aggressive behavior in hedgehogs, and no treatment has been established for this condition so far.⁶ Radiotherapy and chemotherapy can be considered, with protocols extrapolated from other mammals, but the efficacy of these modalities in hedgehogs is unknown.^5,7