Clinical and pathologic features of an adenomatous polyp of the colon in a domestic ferret (Mustela putorius furo)

Abstract

A 6-year-old castrated male domestic ferret (Mustela putorius furo) with a 4-week history of intermittent diarrhea and straining during defecation had an intraluminal mass in the descending colon identified by abdominal ultrasound. The histopathological diagnosis of the resected mass was an adenomatous polyp of the colon. No post-operative complications were identified over a 32-month follow-up period.

Domestic ferrets (Mustela putorius furo) are common companion animal pets in North America and are frequently presented to veterinary clinics for medical attention. A relatively small number of clinical conditions is responsible for the majority of admissions to the Avian Exotic Service of the Ontario Veterinary College, University of Guelph, namely adrenal disease; lymphoid, pancreatic islet, and cutaneous neoplasia; and gastrointestinal problems including coronaviral enteritis and foreign body ingestion. The following describes a case of colonic neoplasia in a ferret that presented with evidence of intestinal disease.

Case description

A 6-year-old castrated male domestic ferret (Mustela putorius furo) was referred to the Ontario Veterinary College Veterinary Teaching Hospital (OVC-VTH) for investigation of an abdominal mass identified by abdominal ultrasound. The ferret had a 4-week history of intermittent diarrhea and straining during defecation and had been initially treated by the referring veterinarian with metronidazole (Apo-Metronidazole; Apotex, Toronto, Ontario), 12.5 mg/kg, PO, q12h, for 5 d. The diarrhea resolved but the straining persisted in spite of treatment. A caudal abdominal mass was palpated, and abdominal ultrasonography revealed a 1.7 cm × 1.3 cm, mixed echogenic, multi-cavitated mass in the caudal abdomen that, on color-Doppler evaluation, was vascularized and appeared to arise from the dorsal colonic wall. Based on these clinical and diagnostic findings, the ferret was referred to the OVC-VTH.

On presentation to OVC-VTH, the ferret was bright, alert, and responsive; all vital parameters were within normal limits. A complete blood (cell) count (CBC) and plasma biochemistry profile revealed a microcytic normochromic anemia (PCV 33%, reference range: 46% to 57%; MCV 40 fL, reference range: 42.6 to 51 fL), a mild neutrophilia (9.4 × 10⁹/L, reference range: 1.1 to 7.0 × 10⁹/L), and hypoglycemia (2.9 mmol/L, reference range: 4.1 to 7.4 mmol/L).

Abdominal palpation revealed an enlarged spleen and a firm, round mass approximately 2 cm in diameter in the caudal aspect of the abdominal cavity. Abdominal ultrasound re-confirmed the presence of an intraluminal mass in the descending colon and furthermore revealed an intussusception anterior to the mass. A mesenteric lymph node, closely associated with the colonic mass, had complex echogenicity, and a fine-needle aspirate of the node was performed. Cytology revealed a small number of non-degenerate neutrophils with no evidence of infectious organisms. Splenic enlargement was confirmed; however, the echogenicity was normal and uniform. No other abnormalities were detected on ultrasound examination. Surgical resection of the colonic mass was elected for diagnostic and potentially curative purposes.

The ferret was premedicated using acepromazine (Atravet; Wyeth Animal Health, Guelph, Ontario), 0.05 mg/kg, IM, and hydromorphone (hydromorphone injection USP; Sandoz Canada, Boucherville, Quebec), 0.05 mg/kg, IM. Propofol (Propofol injectable; Novopharm, Toronto, Ontario), 5 mg/kg, IV, was used for induction and a surgical state of anesthesia was maintained by using 1.5% isoflurane (AErrane; Baxter Corporation, Mississauga, Ontario) delivered through a 3-mm inner diameter uncuffed endotracheal tube. Morphine (morphine injection USP; Sandoz Canada), at a dose of 0.1 mg/kg was diluted to 0.2 mL in 0.9% saline and infused in the epidural space for additional analgesia. A balanced fluid solution containing 2.5% dextrose (Plasma-Lyte A; Baxter Corporation) was administered intravenously during anesthesia and recovery.

A routine ventral approach to the abdomen was performed, and an exploratory laparotomy revealed an intussusception of the descending colon and two 1- to 2-mm round, firm, raised masses on the distal 1/3 of the right pancreatic limb. The intussusception was reduced and was found to contain a firm 1.5 × 2 cm intramural mass. A routine resection and anastomosis was performed obtaining 2-cm margins orally and aborally. The pancreatic masses were resected using blunt dissection. The enlarged mesenteric lymph node observed during ultrasound examination was biopsied. No other abnormalities were detected within the abdominal cavity. The ferret recovered uneventfully from surgery; however, an intravenous catheter was maintained and ampicillin (ampicillin sodium for injection USP; Novopharm), 22 mg/kg, IV, q6h, was administered. Food was offered 2 h after surgery and normal defecation was noted within 24 h. Forty-eight hours after recovery the ferret’s intravenous catheter was removed and antibiotic treatment was changed to amoxicillin-clavulanic acid (Clavamox; Pfizer Animal Health, Pfizer Canada, Kirkland, Quebec), 15 mg/kg, PO, q8h, for 5 d. A mild intermittent rectal prolapse and mild irritation of the perianal region was noted at this time and was treated with topical anesthetic cream (EMLA cream, lidocaine 2.5%, prilocaine 2.5%; AstraZeneca Canada, Mississauga, Ontario), q12h for 3 d. The ferret was discharged from the hospital.

Tissue specimens (colonic mass, lymph node, and pancreatic biopsies), were fixed in 10% neutral-buffered formalin and submitted for histopathological examination. Macroscopically, the colonic mass was 1.7 × 1.3 cm, pedunculated, multinodular and firm. On the cut surface, multiple, variably sized (1–3 mm), cystic structures were observed (Figure 1). Tissue specimens were processed routinely and stained with hematoxylin and eosin. Additional sections of the colonic mass were stained with periodic acid-Schiff stain (PAS), and immunohistochemically for desmin, smooth muscle actin (SMA), and CD117.

Figure 1.

Adenomatous colonic polyp from a ferret. The pedunculated, multinodular colonic mass has multiple variably sized cystic structures on the cut surface (formalin-fixed tissue).

Microscopically, the colonic mass was polypoid, irregularly shaped, and glandular within an extensive stromal framework (Figure 2). The epithelial component was composed of irregularly shaped acinar and tubulo-acinar structures lined by tall columnar epithelial cells and large numbers of goblet cells (Figure 3). Epithelial cell nuclei were basal, oval to elongated, and hyperchromatic. Rare mitotic figures were observed. There were numerous dilated or cystic glands lined by a flattened to cuboidal epithelium that contained large amounts of mucinous material. Many also contained intact and degenerate neutrophils. The glands were embedded in a thick stroma in which multiple hyperplastic lymphoid follicles were observed. Stromal cells immediately surrounding and interdigitating among most of the glandular structures stained for desmin. In contrast, there was diffuse staining of stromal cells for SMA throughout the entire mass, again with increased intensity in the periglandular regions (Figure 4). No immunoreactivity for CD117 was evident among this population of cells. The mucosal surface of the mass was ulcerated, and multiple bacterial colonies and neutrophils were observed in the exposed lamina propria. There was no evidence of neoplastic infiltration in the adjacent unaffected colon. Based on both gross and microscopic appearance, the mass was diagnosed as an adenomatous polyp of the colon.

Figure 2.

Histological appearance of adenomatous colonic polyp from a ferret. Colonic mass illustrating multiple irregularly shaped acinar and tubulo-acinar structures, lined by tall columnar epithelial cells and large numbers of goblet cells, embedded in fibrovascular stroma. Hematoxylin & eosin × 100.

Figure 3.

Periodic acid-Schiff (PAS) stain of adenomatous colonic polyp from a ferret. Colonic mass illustrating mucin production by goblet cells in the glandular epithelium. PAS × 400.

Figure 4.

Immunohistochemical staining of stromal elements for smooth muscle actin in an adenomatous polyp from a ferret. × 200.

Histological examination of the mesenteric lymph node revealed marked cystic dilation of the subcapsular and medullary sinuses. These changes were presumed to be secondary to the obstruction of lymphatic drainage resulting from the colonic intussusception. There was no evidence of the inflammation noted on previous fine-needle aspirate. In the pancreas, a single 1-mm nodule formed by hyperplastic endocrine islet cells was present in 1 biopsy sample; the second was anatomically normal although a second nodule had been described at surgery. Based on these findings and the hypoglycemia noted clinically, the diagnosis of a pancreatic insulinoma was made. The ferret was followed for 3 mo and showed no evidence of clinical disease. Further communication with the owner revealed that there was no evidence of complications from or recurrence of an intestinal problem up to the time of the animal’s death, 32 mo after surgical intervention, at an age of 9 y.

Discussion

This case is the first report of the clinical and pathological features of an adenomatous polyp in the colon of a domestic ferret. The clinical signs in this animal suggested a colonic lesion and likely initially reflected the physical presence of the polyp, later complicated with the intussusception identified at ultrasound and surgery. The CBC results were consistent with blood loss and inflammation secondary to ulceration of the surface of the polyp. Although neutrophils were identified in the initial fine-needle aspirate of the associated lymph node, at biopsy there were no inflammatory cells present, no doubt reflecting the dynamic nature of neutrophil responses. The ferret’s hypoglycemia was attributed to the presence of 1 or more functional pancreatic insulinomas. Splenomegaly is a common finding in the ferret and can be associated with several disease conditions, including primary and metastatic neoplasia and extramedullary hematopoeisis (1). Based on the lack of associated clinical signs, and the normal, uniform echogenicity of the spleen, the cause of splenomegaly in this ferret was not pursued.

The most common neoplastic process involving the intestinal tract of the ferret is malignant lymphoma (2). A small number of other neoplasms have been reported: 2 unspecified “tumors” of the intestine, 1 in a 4- to 6-month-old ferret that showed clinical signs of lethargy, anorexia, and diarrhea; 5 intestinal adenocarcinomas; 1 rectal adenocarcinoma; 1 leiomyosarcoma of the cecum and 1 of the rectum; and 3 unspecified rectal tumors (2–4). Additional clinical or pathological details for these cases were not provided.

Tumors of the lower gastrointestinal tract are also relatively uncommon in domestic animals, although a wide variety of neoplasms and tumor-like lesions have been described (5). Among these are adenomatous polyps, also called papillary adenomas, papillotubular adenomas, colorectal polyps or adenomas, and polypoid carcinoma in situ. These neoplasms range from small, often pedunculated lesions, to large masses that are usually sessile and composed of tubular, villous, or tubulovillous epithelial proliferations within a fibrous stroma (5,6). Adenomatous polyps can occur in the stomach as well as in the small and large intestines (6). In dogs, the most common site for development is the distal rectum (5,7). In cats, benign adenomatous polyps have been reported in the stomach and the duodenum (5). Adenomatous polyps are differentiated from non-neoplastic lesions by the presence of epithelial dysplasia (6).

The extensive stromal/smooth muscle component of this tumor differs from the descriptions of colorectal polyps in dogs and benign adenomatous polyps of cats (5). The gross appearance of a luminal polypoid mass and the benign nature of the proliferative epithelial and stromal components were, however, considered sufficient for a diagnosis of adenomatous polyp. Despite immunohistochemical staining with SMA and desmin, the histologic appearance was not considered consistent with a diagnosis of leiomyoma, and the histologic appearance and lack of staining for CD117 make an intestinal stromal tumor unlikely (5). There have been insufficient publications of the histologic details of intestinal neoplasms in ferrets to place our case in context for the species.

Due to the low prevalence of intestinal epithelial tumors in domestic animal species, such as cats and dogs, there is scant information on the biological behavior of these tumors in animals. In humans, according to Hardy et al (8), more than 70% of colorectal cancers develop from sporadic adenomatous polyps. The malignant risk of these neoplasms is correlated with size, histological architecture, and severity of epithelial dysplasia (6). In dogs, polyps that are > 1-cm in diameter tend to have cells with a more anaplastic appearance, and recurrence is more probable (5,9). Although the polyp in this ferret was 2-cm in maximum dimension, its appearance and behavior were benign.

It has been suggested that colorectal adenomatous polyps in dogs may exhibit a different biological behavior than that observed with duodenal adenomatous polyps in cats (5). In cats, surgical excision appears to be curative; however, in dogs there is some controversy regarding the prognosis after surgical excision. Reoccurrence of clinical signs after surgical resection of colorectal neoplasia was reported in 41% of canine patients and malignant transformation of the tumor was documented in 18% (10). In humans, the success of polypectomy depends on complete removal of the adenoma (10). In ferrets, there is no specific information regarding the behavior of intestinal epithelial neoplasms.

Based on this case report, adenomatous colonic polyps should be considered in the differential diagnosis for ferrets that present with clinical signs of gastrointestinal disease including diarrhea and straining. Continued reporting of both the clinical and pathological features of neoplastic disease in the ferret is essential in order to determine the behavior of these tumors and the effectiveness of surgical resection.