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Journal of the American Animal Hospital Association 40:82-85 (2004)
© 2004 American Animal Hospital Association

Case Report

Ureteral Mast Cell Tumor in a Dog

Michele Steffey, DVM, Kenneth M. Rassnick, DVM, Diplomate ACVIM, Brian Porter, DVM and Bradley L. Njaa, DVM, MVSc, Diplomate ACVP

From the Departments of Clinical Sciences (Steffey, Rassnick) and Biomedical Sciences (Porter, Njaa), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853.


   Abstract
Top
 Abstract
Case Report
 Discussion
 Conclusion
 References
 
A 6-year-old, castrated male, mixed-breed dog was diagnosed with partial unilateral ureteral obstruction secondary to a ureteral mass. The ureteral mass was surgically resected, and an ureteroneocystostomy was performed. Histopathology of the ureteral mass was consistent with a poorly differentiated mast cell tumor (MCT). The patient recovered well but was euthanized 5 months postoperatively for central nervous system signs. A choroid plexus tumor was diagnosed during necropsy examination. There was no evidence of recurrence or dissemination of the ureteral MCT. Extracutaneous MCTs are rare in dogs, and primary MCT associated with the urinary tract has not previously been reported in the veterinary literature.


   Case Report
Top
 Abstract
 Case Report
Discussion
 Conclusion
 References
 
A 6-year-old, 36.8-kg, castrated male, mixed-breed dog was referred to the Cornell University Hospital for Animals with a presumptive diagnosis of ureteral obstruction. Two weeks prior to presentation, the patient presented to the referring veterinarian for a complaint of lethargy. The only abnormality noted at that time was a fever (temperature, 103.4°F [39.7°C]). Cephalexin (22 mg/kg body weight, per os [PO] q 8 hours) and metronidazole (15 mg/kg body weight, PO q 12 hours) were prescribed, and the dog’s attitude improved. One day prior to referral, the dog was anorectic, febrile, vomited twice, and exhibited abdominal pain. The referring veterinarian examined the dog and found it to be febrile again and experiencing abdominal pain. Ultrasonographic evaluation of the abdomen revealed retroperitoneal fluid, unilateral hydroureter, and unilateral hydronephrosis.

Physical examination findings at Cornell University revealed abdominal pain. The remainder of the physical examination was unremarkable. The dog was admitted to the hospital, and a complete blood count (CBC), serum biochemical profile, thoracic radiographs, and abdominal ultrasound were performed. Results of the CBC revealed a mild normocytic, normochromic anemia (hematocrit, 39%; reference range, 42% to 57%) and leukocytosis consisting of a mature neutrophilia (19.0 x 103 cells/µL; reference range, 3.4 to 9.7 x 103 cells/µL). The serum biochemical profile revealed mildly elevated aspartate transaminase (AST, 87 U/L; reference range, 16 to 50 U/L) and moderately elevated creatine kinase (CK) activity (668 U/L; reference range, 58 to 241 U/L). There were no other abnormal findings. Thoracic radiographs were unremarkable. Abdominal ultrasonography revealed a slightly enlarged left kidney with mild hydronephrosis, a torturous and moderately dilated left ureter, and retroperitoneal fluid. The remaining abdominal organs appeared normal. Fine-needle aspiration of the retroperitoneal effusion was performed using a 22-gauge, 3.8-cm, hypodermic needle. The level of potassium within the fluid was analyzed and compared to that within the patient’s serum. The fluid potassium level was extremely elevated (too high to measure), while the serum potassium was within the reference range. The fluid creatinine level was unavailable. This result was consistent with a diagnosis of uroretroperitoneum.

The dog was premedicated and placed under general anesthesia. An excretory urogram was performed using 50 mL of an intravenous contrast agent.a Excretory urogram demonstrated adequate opacification of both kidneys. The left kidney was slightly larger than the right, and the left renal pelvis and ureter were mildly dilated. At the caudal aspect of the left ureter, near the trigone of the urinary bladder, were focal dilatation and a soft-tissue opaque filling defect [see FigureGo]. The urinary bladder, right kidney, and right ureter were normal. No discrete site of urine leakage to the retroperitoneal space could be identified.



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  		Figure— Excretory urogram in a 6-year-old dog with a ureteral mass and hydroureter. Lateral abdominal radiograph demonstrates focal dilatation of the left ureter cranial to the bladder trigone.

 
A standard ventral midline surgical approach was made, and the abdomen was explored. Surgical exploration revealed a moderate amount of slightly yellow retroperitoneal fluid surrounding the left kidney and ureter. The left kidney was slightly enlarged, and the perirenal fat appeared irregular. At the level of entry of the left ureter into the bladder trigone, a 1-cm segment of the ureter was palpably thickened. The left ureter and the bladder wall surrounding the left ureteral papilla were resected. The left ureter was transected 3 cm cranial to the palpable thickening, and a left ureteroneocystostomy was performed according to previously described techniques.1 Both ureters were catheterized to the level of the renal pelvis; however, a macroscopic source for the leakage of urine was not found. The resected portion of the ureter and bladder were immediately fixed in 10% neutral buffered formalin. The patient made an uneventful recovery and was discharged from the hospital 3 days later.

Histopathological evaluation of the resected ureter revealed thickening of the ureteral wall by a transmural cellular infiltrate composed of a small number of round to polygonal neoplastic cells and a large number of eosinophils. The neoplastic cells were moderately pleomorphic, with a small to moderate amount of amphophilic, slightly granular cytoplasm. The nuclei were round to irregularly ovoid, had finely to coarsely stippled chromatin, and one to three nucleoli. There was a moderate amount of anisocytosis and anisokaryosis. Mitotic figures were rare. Rare cells contained intracytoplasmic metachromatic granules with Giemsa stain, Alcian blue stain at a pH of 0.4, and toluidine blue stain. The proximal and distal margins of the ureter had no evidence of neoplasia; however, neoplastic cells and accompanying eosinophils dissected through the tunica muscularis and serosa into adjacent adipose tissue. Histomorphological diagnosis was consistent with a poorly differentiated mast cell tumor (MCT). Immunohistochemical stains for leukocyte markers, including CD3, CD79-alpha, CD18, CD45 RA, BLA 36, Mac 387, and lysozyme were negative. Immunohistochemical staining for Ki-67 using the anti-Ki-67 antibody MIB-1 was performed, and a small number of neoplastic cells stained positively.

The dog was reexamined 2 weeks postoperatively. The dog had returned to normal attitude and activity, and a repeat abdominal ultrasound showed resolution of the hydronephrosis/hydroureter and retroperitoneal effusion. A CBC and serum biochemical profile were unremarkable. A buffy coat smear was performed, and cytopathological examination did not reveal any mast cells. Results of bone marrow aspiration cytopathology showed all hematopoietic cell lines to be normal in number and appearance, with no evidence of mast cells. No medications were prescribed, and only serial monitoring was recommended for the dog.

Abdominal ultrasound, thoracic radiographs, and cytopathological examination of buffy coat smears were performed at monthly intervals. On all occasions there were no abnormal findings. Five months after diagnosis of MCT of the ureter, the dog developed significant behavioral changes. The dog had a voracious appetite, was lethargic and unresponsive to interaction with the family, began circling to the left, and head-pressing. The owners elected to have the dog humanely euthanized, and a necropsy was performed.

At necropsy, there was a focal transmural thickening of the caudodorsal wall of the neck of the urinary bladder. The kidneys and ureters were normal in appearance. A small mass was present in the left thyroid gland, and there were multiple splenic nodules. Moderate dilatation of the lateral ventricles and a flattened appearance to the dorsal aspect of the right and left hemispheres of the cerebral cortex were present. Histopathological evaluation of tissues collected at necropsy yielded diagnoses of multiple neoplasms including a choroid plexus tumor, thyroid gland follicular cell adenocarcinoma, and pancreatic islet cell tumor (i.e., insulinoma). The focal thickening of the bladder wall at the site of the previous surgery consisted of bundles of histologically normal smooth muscle and collagen. The splenic nodules were consistent with extramedullary hematopoiesis. Histopathological examination of the bone marrow revealed no abnormal findings. There was no evidence of local or metastatic MCT found in any tissues examined.


   Discussion
Top
 Abstract
 Case Report
 Discussion
Conclusion
 References
 
To the authors’ knowledge, this is the first report of MCT associated with the ureter in the veterinary literature. The dog recovered without complication from the surgical intervention. Excision resulted in control of local disease, as there was no evidence of recurrence at necropsy 5 months later. The time to diagnosis of local or distant recurrence in dogs with MCT occurring in other locations may be as long as 50 months.2–4 Complete microscopic evaluation of all tissues obtained during necropsy failed to reveal residual or metastatic mast cells. Neoplastic cells may have been undetectable, however, and relapse may have occurred with time. Molecular techniques to detect minimal residual disease such as polymerase chain reaction (PCR) and flow cytometry are emerging in human oncology but are not yet available for veterinary patients.5

Ureteral neoplasia is very rarely described in the veterinary literature. Reported neoplasms of the ureter include transitional cell papilloma, transitional cell carcinoma, leiomyoma, leiomyosarcoma, and fibropapilloma.6–11 Diagnosis of ureteral neoplasia is difficult, as clinical signs may be minimal to absent until significant size is attained or clinical signs attributable to ureteral obstruction occur.12 In one report evaluating the diagnostic imaging findings in six dogs with ureteral neoplasia, all cases had obstructive hydronephrosis and hydroureter.6 Treatment options for primary tumors of the ureter include unilateral ureteronephrectomy or partial ureterectomy with ureteroneocystostomy. Surgical excision of ureteral tumors can be curative, as metastasis and recurrence have not been reported in any of the previously described cases.6–9

A pseudoneoplastic process known as eosinophilic cystitis has also been described in dogs.13,14 Extension of an eosinophilic cystitis lesion into the ureters was considered in the patient reported here, given the large number of eosinophils and small number of mast cells. However, there was a paucity of fibroblasts and fibrocytes, and the large cells scattered throughout the mass were negative for the immunohistochemical leukocyte markers but weakly positive for mast cells. Additionally, the urinary bladder mucosa was grossly normal and had no histopathological evidence of an underlying eosinophilic cystitis. Therefore, a diagnosis of ureteral MCT was made.

Mast cell tumors are frequently diagnosed tumors in dogs and occur most commonly in the skin. Mast cell tumors comprise 17% to 21% of all skin tumors in the dog and may arise in dermal or subcutaneous locations. The majority of malignant cutaneous MCT disseminate first to local lymph nodes, then to the spleen, liver, and bone marrow.15,16 Histopathological grade is strongly predictive of outcome for dogs with cutaneous MCT.4 Surgery is considered the initial treatment of choice for solitary cutaneous MCT, and with complete excision of grade I (i.e., well-differentiated) and grade II (i.e., moderately differentiated) tumors, most patients do not require additional local or systemic treatment.2–4 Despite surgery, histopathological grade III (i.e., poorly differentiated) MCT frequently recur and metastasize. Dogs with grade III cutaneous MCT typically die of their disease within 1 year.4,17 Adjuvant chemotherapy is recommended for these patients.18–20

Extracutaneous MCT in dogs are rare, and limited treatment information is available. Previously reported primary extracutaneous sites include the conjunctiva,21 oral cavity,22,23 nasal cavity,24 salivary gland,25 larynx,26,27 pharynx,23,28 trachea,29 mediastinum,30 intestine,22,31,32 mesenteric lymph nodes,23,33 spinal canal,34 and disseminated visceral disease of unknown origin.32,35,36 The biological behavior of MCT can be highly variable. Aside from MCT of the conjunctiva,21 extracutaneous MCT are reported to be more aggressive than the cutaneous form.22,32 However, most of these reports are solitary cases16,24–31,33–35 or case series of few patients.21,22,32 Furthermore, many patients with extracutaneous MCT have disseminated disease24,28,31,32,35,36 or were euthanized at the time of initial diagnosis.23,28,30,31,34 In one study of dogs with cutaneous MCT, if the tumor had been present for more than 7 months preoperatively, the patient had a better prognosis.37 Perhaps the lack of an easily observable superficial mass or specific clinical signs in dogs with some extracutaneous MCT delays diagnosis and contributes to a worse prognosis.

Several markers of cellular proliferation that describe associations between histopathological grade, biological behavior, and outcome in dogs with MCT have been reported.17,38,39 The nuclear protein, Ki-67, is expressed in cells during the active phases of the cell cycle. Abadie, et al., evaluated Ki-67 in dogs with cutaneous MCT, and the number of Ki-67 positive nuclei was associated with prognosis. Dogs with grade II MCT with <93 positive nuclei per 1,000 nuclei counted were less likely to die from their disease when compared to tumors with >93 positive nuclei. Also, very few dogs with MCT of any histopathological grade and <55 Ki-67 positive nuclei per 1,000 died during the 45-monthfollow-upperiodaftersurgery.17 Immunohistochemistry for Ki-67 was evaluated in the MCT of the dog reported herein, and a small number of positive nuclei were detected. This may have indicated a favorable outcome; however, follow-up time was relatively short since the dog was euthanized 5 months after diagnosis. There have been no previous reports of Ki-67 or other proliferation markers in any of the other dogs with extracutaneous MCT.


   Conclusion
Top
 Abstract
 Case Report
 Discussion
 Conclusion
References
 
Extracutaneous MCT are rarely diagnosed in dogs, and there has been no previous report of a primary MCT associated with the urinary tract. While the follow-up time in this patient was short, initial follow-up demonstrated a good outcome after surgical resection of the tumor.


   Footnotes
 
a Hypaque-76; Nycomed, Inc., Princeton, NJ Back


   References
Top
 Abstract
 Case Report
 Discussion
 Conclusion
 References
 

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