Surgical removal of a mammary adenocarcinoma and a granulosa cell tumor in an African pygmy hedgehog

Abstract

A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred with a history of hematuria. Hyperglycemia and glucosuria were found at presentation. Mammary adenocarcinoma and a granulosa cell tumor were found and removed surgically. Glucosuria and hematuria resolved, and the hedgehog has done well for 10 mo postoperatively.

A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred to the Veterinary Teaching Hospital at the Ontario Veterinary College with a 1-month history of hematuria. It also had a previous history of dermatosis associated with mite infestation that had clinically resolved with SC administration of ivermectin 2 y previously. The hedgehog ate a diet of commercial hedgehog food, raisins, and apples. At the onset of the hematuria, the hedgehog was treated with chloramphenicol palmitate (62.5 mg, PO, q12h for 3 d); however, when the anorexia occurred, the treatment was changed to erythromycin (10 mg, PO, q12h for 10 d). When hematuria persisted, the hedgehog was referred.

On initial physical examination, the hedgehog was bright, alert, and responsive. It weighed 551 g and was judged to be overweight. It had mild seborrhea on the dorsum and dermatitis on the left hind leg. The pinnae were markedly notched and hyperkeratotic. The hedgehog was anesthetized by mask induction with isoflurane. On radiographs, there were multiple spinal abnormalities, with severe scoliosis at the thoracolumbar junction, mild kyphosis, and a 2nd lumbar (L2) block vertebra. Urine was collected by cystocentesis and analyzed with a urine strip (Chemstrip 9; Roche Diagnostics, Laval, Quebec); it showed a glucose of approximately 55 mmol/L, approximately 250 erythrocytes/μL, and trace protein. Urine was submitted for bacteriological culture. Blood was drawn from the jugular vein for a complete blood cell (CBC) count and a biochemical profile. The hedgehog was given 0.3 mg/kg of ivermectin, SC, for possible Caparinia spp. mite infestation, which is common in hedgehogs. Enrofloxacin (Baytril injectable, 50 mg/mL diluted to 20 mg/mL with strawberry syrup; Bayer, Toronto, Ontario) therapy, 5 mg/kg, PO, q12h for 10 d was initiated for possible bacterial urinary tract infection. The hedgehog was sent home pending laboratory results, with a suggested follow-up in 10 d. Abnormalities on the CBC count were a decreased white blood cell count (3.2 × 10⁹/L; normal 5.8 to 21 × 10⁹/L (1)) with toxic neutrophils, occasional Howell-Jolly bodies, and a thrombocytopenia (129 × 10⁹/L; normal 200 to 412 × 10⁹/L (1)). These changes were consistent with an infectious or inflammatory process. Abnormalities on the biochemical profile were hypophosphatemia (0.88 mmol/L; normal 1.5 to 2.1 mmol/L (1)), mildly elevated urea (12.8 mmol/L; normal 7.6 to 11.7 mmol/L (1)), mildly decreased creatinine (14.0 μmol/L; normal 17.7 to 35.4 μmol/L (1)), and hyperglycemia (14.0 mmol/L; normal 4.5 to 6.4 mmol/L (1)). Diabetes mellitus was a possible concern, although hyperglycemia due to stress or dietary sources was also considered. The owners were instructed to discontinue feeding fruit. Urine culture did not result in bacterial growth.

At the recheck appointment 21 d later, the owner reported that the hematuria had lessened but that there were still intermittent episodes of hematuria. On physical examination, the hedgehog was bright, alert, responsive, and weighed 551 g. Under isoflurane anesthesia, a 2.5-cm SC mass that had not been palpable at her previous examination was found in the right cranioventral part of the abdomen. Mild improvement in the seborrhea and dermatitis was seen. Ultrasonography showed an enlarged left ovary (1.42 × 0.63 cm) as compared with the right ovary (0.57 × 0.71 cm), and a large left adrenal gland, as well as the right SC cranioventral abdominal mass. An ultrasound-guided fine needle aspirate of the mass was taken and examined microscopically; clusters of cells with high nucleus: cytoplasm ratios, oval to oblong nuclei with finely stippled chromatin, and lightly basophilic streaming cytoplasm with poorly defined cell borders were observed. The diagnosis was carcinoma. Mastectomy and ovariohysterectomy were recommended, and the owner was provided with urinalysis strips to monitor urine glucose at home.

The hedgehog was presented for surgery 8 d later. On physical examination, it was bright, alert, responsive, and weighed 543 g. Anesthesia was induced with isoflurane and the hedgehog was intubated with a 2-0 uncuffed tube. It was given butorphanol (Torbugesic; Ayerst Laboratories, Montreal, Quebec), 0.75 mg/kg, IV, for pain control, and IV fluids (Plasmalyte-148, 7 mL/hour) via a catheter in the cephalic vein. A routine ovariohysterectomy was performed via a ventral midline incision. The linea alba was closed before a dissection was made laterally toward the mass. Blood vessels were identified and ligated, and the mass and surrounding fat were removed. The site was extensively lavaged with saline and sutures were placed to reduce dead space. The hedgehog recovered uneventfully. It was administered meloxicam (Metacam; Boehringer Ingelheim, Burlington, Ontario) 0.1 mg/kg, PO; enrofloxacin, 5 mg/kg, PO; and B-vitamin complex (Vetoquinol; Lavaltrie, Quebec), 0.25mL, PO, to aid with hepatic fat metabolism. The hedgehog was monitored overnight. The following day, the hedgehog was quiet, alert, and responsive. It was eating, urinating, and defecating. Normal self-anointing behavior was seen. The hedgehog was sent home with instructions to the owners to administer enrofloxacin, 5 mg/kg, PO, q12h for 14d, and meloxicam, 0.1 mg/kg, PO, q24h for 14 d.

On histopathologic examination, a mammary adenocarcinoma and a granulosa cell tumor were diagnosed. The mammary adenocarcinoma was composed of lobules of neoplastic tissue, separated and surrounded by dense connective tissue bands (Figure 1A). Within each lobule, cells formed irregular nests and ductules, and some lumina contained amorphous, faintly basophilic material. The neoplastic cells were columnar to polygonal with indistinct cell borders. Nuclei were round to ovoid with finely granular chromatin and contained 1 to 3 prominent nucleoli. There was 3-fold anisokaryosis and an average of 1 mitotic figure per high-powered field. Abundant single cell necrosis was present throughout the mass. Neoplastic cells were infiltrating the surrounding tissues.

Figure 1A. Mammary adenocarcinoma in an African pygmy hedgehog. Bar = 50 μm. Hematoxylin and eosin stain. 1B. Granulosa cell tumor in an African pygmy hedgehog. Bar = 20 μm. Hematoxylin and eosin stain.

The left ovary had a solid multinodular mass of polygonal cells with foamy eosinophilic cytoplasm. Occasional cells had giant nuclei. This was diagnosed as an early granulosa cell tumor (Figure 1B). There were also several large cystic structures in the left ovary, lined by 1 to 2 layers of flattened columnar epithelial cells and containing pale eosinophilic material. No abnormalities were found in the uterus.

Figure 1B. Continued.

At recheck 6 d postoperatively, the hedgehog was doing well. It had been eating, drinking, urinating, and defecating normally. On physical examination, it weighed 543 g. There was some bruising at the mastectomy site, but the incision was healing well. The owner was instructed to gradually restrict the hedgehog's food intake, with a target weight loss not greater than 15 g/mo. Tamoxifen (Gen-tamoxifen; Genpharm, Etobikoke, Ontario), 1 mg/kg, PO, q 24h, 2 mg/mL suspension, therapy was initiated, but the hedgehog resisted oral administration and therapy was discontinued after 2 wk.

Fourteen days postoperatively, the owner reported that there had been no glucosuria or hematuria seen on the urine strips.

At recheck 60 d postoperatively, the hedgehog continued to do well. It had been eating, drinking, urinating, and defecating normally. The owner reported that there had been no glucosuria or hematuria seen on the urine strips. On physical examination, the hedgehog weighed 496 g. The hedgehog was anesthetized with isoflurane. No seborrhea or dermatitis was observed. A 1 cm × 2 cm patch of dead skin was present over a granulation bed at the mastectomy site. Normal granulation tissue was present underneath the dead skin, which was removed. Abdominal ultrasonography was done, and no evidence of regrowth of the mammary adenocarcinoma was observed. On blood biochemical analysis, the only abnormality was hyperglycemia (9.4 mmol/L; normal 4.5 to 6.4 mmol/L (1)). Glucosuria was not present.

Ten months postoperatively, the owner reported that the hedgehog was doing well and that she had no concerns regarding its health.

Neoplasia is common in hedgehogs. However, to our knowledge, granulosa cell tumors have not previously been reported in hedgehogs. Retrospective studies of African pygmy hedgehog pathologic submissions have shown rates of neoplasia ranging from 29% (n = 14) (2) to 53% (n = 66) (3). The larger study reported that mammary gland neoplasms were the most commonly diagnosed tumor, and 7 of 8 of these were malignant (3). A previous report of mammary gland tumors submitted for pathologic examination described that after surgical excision of mammary gland tumors in 8 intact female hedgehogs, 3 died or were euthanized shortly after surgery, and 5 were lost to follow up (4). While earlier studies of mammary carcinoma in dogs did not show benefits of ovariohysterectomy, a recent study, which was controlled for age, histologic differentiation, and vascular invasion, found that ovariohysterectomy within 2 y prior to tumor surgery resulted in 45% longer survival times (5). Estrogen has been shown to promote the progression of human preneoplastic breast disease (6). However, as mammary tumors in dogs become larger and less well differentiated, the concentration of estrogen receptors is decreased (7). This suggests that ovariectomy may be of greater value earlier in the course of the disease. While tamoxifen or anastrozole represent medical alternatives for reducing the estrogen effect on mammary tissue, oral tamoxifen was poorly tolerated by this hedgehog, and it is not feasible to give oral medications to an unwilling hedgehog.

It is possible that the cause of the hematuria in this case was urinary tract infection, despite the fact that organisms were not cultured from urine. The hedgehog had a recent history of antibiotic therapy, which may have interfered with culture of bacteria, and it is also possible that a fastidious organism was present. Glucosuria predisposes animals to urinary tract infection. Neoplasia of the uterus has been reported to cause vaginal bleeding in hedgehogs (8). Although this is a more common cause of bleeding in the authors' experience, uterine or vaginal neoplasia was not present. The cause of the hyperglycemia and glucosuria in this hedgehog remains undetermined. Potential causes that were alleviated include production of a diabetogenic agent, such as progesterone, by the granulosa cell tumor, dietary issues, and obesity. Granulosa cell tumors have previously been associated with diabetes mellitus in a horse (9). While still hyperglycemic 60 d postoperatively, there was some improvement, and glucosuria was not seen after 1 wk postoperatively. The threshold for renal spillover of glucose in African pygmy hedgehogs is not known; it would appear to be between 9.4 and 14.0 mmol/L in this hedgehog.