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Pathology in Practice
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Abdominal distention and lethargy in a 6-year-old spayed female ferret
History
A 6-year-old 630-g spayed female ferret was evalu- ated for a 7-day history of progressive lethargy, an- orexia, decreased water intake, and abdominal disten- tion. The animal had a known history of adrenal disease and was being managed with subcutaneous deslorelin acetate implants. The last implant had been placed 7 months prior to presentation.
Clinical and Gross Findings
At presentation, abdominal ultrasound revealed a large, mixed echogenic mass (measuring at least 6.2 X 3.6 cm) occupying the mid-abdomen. During the ultrasound examination, the patient developed respiratory arrest and died shortly after cardio- pulmonary resuscitation was discontinued per the owner’s request.
At necropsy, the abdomen was markedly dis- tended and pendulous. A large, encapsulated, mul- tinodular, dark red to light brown mass (measuring 8 X 6.5 X 5 cm and weighing 81 g [approximately 12.9% of the animal’s body weight]) was present in the caudodorsal abdomen. The mass displaced and compressed both kidneys. On cut section, it was multinodular, light yellow, and soft, with multiple cavitations (5 mm to 2 cm) containing dark red fri- able material (Figure 1). The left adrenal gland was not identified grossly. Additional findings included moderate splenomegaly and a 5 mm cyst in the cor- ticomedullary junction of the left kidney. No gross abnormalities were noted in the remaining organs.
Carolina Fontana, DVM, MS1; Luan Henker, DVM, PhD2; Arthur Cheng, DVM2; Rachel L. A. L. T. Neto, DVM, MS, DACVP2*
1Laboratory of Animal Pathology, Federal University of Paraná, Palotina, Paraná, Brazil
2Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL
*Corresponding author: Dr. Neto (rtn0004@auburn.edu)
Received July 2, 2025 Accepted August 15, 2025 Published online September 24, 2025 doi.org/10.2460/javma.25.07.0442 @AVMA
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Formulate differential diagnoses, then continue reading.
Histopathologic Findings
Histologically, the abdominal mass consisted of a densely cellular neoplasm composed of polygonal cells arranged in packets, trabeculae, and alveolar- like structures, often centered around cystic spaces containing amphophilic material (interpreted as pseudocysts; Figure 2). Neoplastic cells had mod-
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erate amounts of eosinophilic cytoplasm, round to oval nuclei with finely stippled chromatin, and indis- tinct nucleoli. Anisocytosis and anisokaryosis were moderate to marked. We assessed 10 different non- overlapping random regions with the least amount of necrosis or cystic distention within the neoplasm core, rendering an average of 3 mitotic figures per 2.37 mm2 (microscope, 40x objective, 10x ocular field number, 22 mm), with occasional bizarre ones.
In some regions, the pseudocysts contained ba- sophilic, wispy extracellular material consistent with mucin, highlighted in blue with alcian blue (Figure 2). No vascular or capsular invasion was observed in the primary mass. However, numerous pulmonary vessels were partially to completely occluded by ag- gregates of neoplastic cells, consistent with tumor emboli (Figure 3).
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: ad- renocortical carcinoma with myxoid differentiation, left adrenal gland (intra-abdominal mass), with pul- monary neoplastic emboli.
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Comments
Hyperadrenocorticism, secondary to adreno- cortical hyperplasia or neoplasia, is a common en- docrine disorder in domestic ferrets. Adrenocortical tumors are the second most frequently diagnosed neoplasm in this species, following insulinomas in prevalence.1 Unlike canine or feline adrenocortical disease, which typically involves glucocorticoid ex- cess, ferret adrenocortical disease is characterized by excessive production of sex steroids, particularly androgens, resulting in hyperandrogenism.2
Clinical manifestations of hyperandrogenism in ferrets include bilateral symmetrical truncal alo- pecia, vulvar enlargement in females, prostatic hy- perplasia in males (with risk of secondary urinary obstruction), mammary gland hyperplasia, and be- havioral changes such as mounting, urine marking, and aggression in sterilized animals. Bone marrow suppression may occur in severe cases.2 In this case, the ferret had a prior diagnosis of adrenal disease and had been managed with subcutaneous deslorelin acetate implants, a depot GnRH agonist. The timing of the last implant was 7 months prior to presentation, and no dermatologic lesions were noted on clinical examination.
In the United States, most ferrets are neutered before 6 weeks of age. Although early neutering has been historically associated with a higher incidence of adrenal disease, similar rates are observed in coun- tries like the Netherlands, where neutering typically occurs at 8 to 11 months of age, prior to the breed- ing season. Therefore, the link between early neuter- ing and disease prevalence remains uncertain.2
One proposed pathophysiologic mechanism involves disruption of hypothalamic negative feed- back following neutering. In the absence of gonadal steroid inhibition, persistent luteinizing hormone stimulation may drive differentiation of zona reticu- laris pluripotent cells into androgen-producing cells capable of secreting estradiol, androstenedione, and 17-hydroxyprogesterone.1-3
Indoor housing has also been suggested as a risk factor, potentially due to prolonged exposure
to artificial light. Gonadotropin secretion in fer- rets is influenced by photoperiod, and excessive light exposure (> 12 h/d) may chronically elevate luteinizing hormone concentrations, predisposing to hyperadrenocorticism.2
Adrenocortical proliferative lesions in ferrets in- clude cortical hyperplasia, adenomas, and carcino- mas. These can be unilateral or bilateral. Adrenocor- tical carcinoma with myxoid differentiation is a rare histologic variant reported in ferrets, cats, and cattle. It is characterized by extracellular mucinous material accumulation within neoplastic tissue.3,4
A previously published case series3 in ferrets demonstrated strong cytoplasmic immunoreactivity to vimentin and a-inhibin in the myxoid regions of such tumors, with variable weak labeling for synap- tophysin. In the current case, immunohistochemis- try was noncontributory. The mucinous matrix was highlighted with alcian blue, consistent with myxoid differentiation.3 While metastasis of adrenocortical carcinoma in ferrets is uncommon, reported sites in- clude the liver, regional lymph nodes, and, less fre- quently, the lungs. In this case, numerous neoplastic emboli were observed in pulmonary vasculature.
The differential diagnosis for intra-abdominal masses in ferrets includes lymphoma, lymphadenitis, and insulinoma. Among these, insulinoma is the most common, accounting for 20% to 25% of neoplasms in ferrets. Typically affecting middle-aged animals (2 to 8 years), insulinomas are not associated with sex predilection and have low metastatic potential in this species. Clinical signs, such as lethargy, ataxia, sei- zures, and syncope are secondary to episodic hypo- glycemia due to excessive insulin secretion.1,2
Lymphoma is the third most frequently diag- nosed neoplasm in ferrets and may present as ab- dominal masses involving mesenteric lymph nodes,
liver, spleen, and bone marrow. Clinical signs are often nonspecific and may include lethargy, inappe- tence, organomegaly, lymphadenomegaly, and body cavity effusions. While genetic factors contribute to lymphoma development in other species, such asso- ciations are not well established in ferrets.5
Keywords: ferret, adrenal, adrenocortical carcinoma, myxoid, hyperadrenocorticism
Acknowledgments
None reported.
Disclosures
ChatGPT (GPT-4) was used to help optimize the gram- mar and clarity of the originally drafted manuscript.
Funding
The authors have nothing to disclose.
References
1. Antinoff N, Williams BH. Neoplasia. In: Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. 3rd ed. Saunders; 2012:103-121. doi:10.1016/B978-1-4160-6621-7.00008-7
2. Rosenthal KL, Wyre NR. Endocrine disease. In: Quesenberry KE, Orcutt CJ, Mans C, Carpenter JW, eds. Ferrets, Rab- bits, and Rodents: Clinical Medicine and Surgery. 4th ed. Elsevier; 2020:77-91.
3. Peterson RA II, Kiupel M, Capen CC. Adrenal cortical carci- nomas with myxoid differentiation in the domestic ferret (Mustela putorius furo). Vet Pathol. 2003;40(2):136-142. doi:10.1354/vp.40-2-136
4. Attipa C, Beck S, Lipscomb V, et al. Aldosterone-pro- ducing adrenocortical carcinoma with myxoid differ- entiation in a cat. Vet Clin Pathol. 2018;47(4):660-664. doi:10.1111/vcp.12658
5. Schoemaker NJ. Ferret oncology. Vet Clin North Am Exot Anim Pract. 2017;20(1):183-208. doi:10.1016/j. cvex.2016.07.004