History

An 8-year-old 3.95-kg (8.69-lb) neutered male domestic shorthair cat was presented to a referral practice for evaluation because of vomiting, lethargy, and anorexia of 2 to 3 days' duration. It was an outdoor cat and lived with another cat that had no clinical signs.

Clinical and Gross Findings

Clinical examination findings for the cat were generally unremarkable. Palpation of the cranial to midportion of the abdomen and palpation of the right iliopsoas muscle elicited signs of pain. A CBC and serum biochemical analysis revealed mild hypoalbuminemia; mild hypokalemia; marked leukocytosis characterized by neutrophilia, lymphopenia, and monocytosis; and high concentrations of urea and creatinine consistent with azotemia. Urea and creatinine concentrations normalized after the cat was administered IV fluids. Urinalysis indicated a urine specific gravity of 1.030; dipstick analysis revealed hematuria (2+) and proteinuria (1+). The latter was confirmed by a urinary protein-to-creatinine concentration ratio of 0.67 (reference interval, < 0.2). Urine sediment examination revealed mild leukocyturia and hematuria (many RBCs observed per hpf). Microbial culture of a urine sample yielded no growth. Abdominal ultrasonography and CT revealed moderate dilation of the right renal pelvis and right ureter and a distal ureteral mass. A large amount of fluid was present in the right retroperitoneal space, which was aspirated and examined cytologically, revealing suppurative inflammation consisting of numerous degenerated neutrophils with the presence of intracellular bacilliform bacteria. A fine-needle aspirate specimen of the ureteral mass was collected for cytologic examination, which revealed abnormal cells. The owner elected euthanasia (by IV injection of pentobarbital) of the cat and gave consent for a full necropsy.

On necropsy, the right ureter inserted into a blind-ending vas deferens, and severe right hydroureter was observed. The right ureter was bifurcated, with the presence of a solid mass (approx 2 × 1.5 × 1 cm) that occluded the ureteral lumen (Figure 1). Severe right hydronephrosis was present.

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Photograph of a focal, pale tan mass (M) occluding the right ureteral lumen from an 8-year-old neutered male cat. The cat had been evaluated because of vomiting, lethargy, and anorexia of 2 to 3 days' duration and was subsequently euthanized. The ureter inserts (asterisk) into the right blind-ending vas deferens (Vd), which is distended. The left and right kidneys (LK and RK, respectively), right ureter, urinary bladder (B), caudal portion of the vas deferens, and urethra are incised. BU = Bifid ureter (blind-ending). DC = Descending colon (cut cranially). Bar = I cm.

Citation: Journal of the American Veterinary Medical Association 258, 12; 10.2460/javma.258.12.1353

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Additional Necropsy Findings

The right, blind-ending vas deferens was markedly dilated (2 to 3 mm in diameter) and filled with purulent fluid; the fluid extended into the right ureteral lumen. There was no outflow of normally appearing urine from the right ureter. Along its entire length, the right ureter was severely distended with a diameter of 4 to 7 mm (hydroureter). At approximately 8 cm distal to the caudal pole of the right kidney, the right ureter was bifurcated with a blind-ending dilated branch, which pointed toward the right kidney, resulting in a Y shape of the ureter. At the bifurcation and involving both ureteral branches, there was a focal, poorly demarcated, raised, pale tan, multinodular, firm, solid mass that occluded the ureteral lumen (Figure 1). Cranial to the mass, each ureteral branch was distended with seropurulent and mildly fibrinous fluid and had a markedly thickened (1- to 2-mm) wall and diffusely rough white mucosa. Dorsal to the right ureter at the level of the mass, greenish pus was observed within the periureteral adipose tissue with severe pallor of overlying iliopsoas musculature, interpreted as muscle inflammation and necrosis. The right kidney had a severely dilated pelvis, which contained seropurulent and mildly fibrinous fluid, and severe compression atrophy of the medulla and cortex (hydronephrosis). The remaining renal parenchyma was multifocally pale tan and friable. The urinary bladder was empty and unremarkable. The left ureter and left kidney appeared normal.

Histopathologic Findings

Samples of the right kidney and right ureter were collected, fixed in neutral-buffered 10% formalin, and routinely processed for histologic examination. The ureteral mass consisted of a transmural, highly infiltrative, poorly demarcated, densely cellular, unencapsulated, and pleomorphic epithelial neoplasm, supported by a moderately dense fibrovascular stroma (Figure 2). The predominant growth pattern appeared solid. Multifocally, neoplastic cells formed tubules, which were lined by 1 or 2 layers of cuboidal to columnar cells (glandular differentiation).¹ Tumor cells varied in size (moderate anisocytosis), with maximal dimensions of up to 20 μm; the cells were polygonal, each with a distinct cell border and a moderate amount of pale eosinophilic cytoplasm. The nucleus was typically round to oval, of variable density, and often centrally located and contained a prominent single nucleolus to multiple nucleoli. Mitotic activity was moderate (1 to 5 mitotic figures/hpf [40×]). Squamous differentiation was present in < 5% of the sectioned and examined mass. Moderate, multifocal, intratumoral necrosis and a moderate lymphoplasmacytic inflammatory response were present. Adjacent periureteral fat was markedly expanded by severe suppurative inflammation, fibrinous exudation, and granulation tissue formation. Immunohistochemical analysis of sections of the neoplasm revealed that > 95% of neoplastic cells stained for cytokeratin,^a confirming their epithelial origin. Immunohistochemical analysis for uroplakin 3^b was attempted but failed to stain neoplastic tissue sections and positive control sections (unaffected left renal pelvic urothelium) obtained from the cat of the present report.

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Photomicrographs of sections of the cat's ureteral mass. The mass consists of a population of neoplastic epithelial cells, which deeply infiltrate the ureteral wall. Notice the predominantly solid growth pattern. H&E stain; bar = 100 μm. Inset—Neoplastic cells have diffuse cytoplasmic labeling for cytokeratin. Cytokeratin-specific immunohistochemical stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 258, 12; 10.2460/javma.258.12.1353

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: ureteral carcinoma in a unilateral right ectopic, blind-ending bifid ureter with unilateral right hydroureter, hydronephrosis, and suppurative ureteropyelonephritis.

Case summary: primary ureteral carcinoma in an ectopic and bifid ureter in a cat.

Comments

On the basis of gross findings for the cat of the present report, a nonneoplastic process, such as an abscess, was considered unlikely because of the location and extended involvement of multiple structures of the lower urogenital tract. However, a secondary infection of the dilated ureteral segments was considered possible. Given the histopathologic findings, a final diagnosis of concomitant primary ureteral carcinoma and unilateral right ectopic, blind-ending bifid ureter was made.

Congenital abnormalities of the ureter, including ectopy and duplication, are known to occur in people and animals and can affect one or both ureters. Ectopic ureters terminate outside of their normal insertion site, either within or outside of the urinary bladder. Most reported cases of ectopic ureters in animals have involved dogs, typically females, which often develop signs of urinary incontinence.² In the case described in the present report, the owner confirmed that the cat had always had mild urinary incontinence, but the problem was never investigated further. In animal species other than dogs, ectopic ureters appear to be rare.^3,4 During embryological development, duplication of the ureters occurs when 2 separated buds arise from a single Wolffian (mesonephric) duct. Ureteral ectopy may develop if the position of 1 or both ureteric buds is more proximal or distal than its normal point of origin within the mesonephric duct.⁵ Duplication of a ureter represents the most common urinary tract abnormality in people and is typically asymptomatic unless complications such as infections develop.⁶ In animals, ureteral duplication is poorly characterized; there are a few single case reports^{3,7,8,9,10,11} involving 2 dogs, a cat, an alpaca, a ram, and a pig. Ureteral duplication can be complete (ie, the supernumerary ureter enters the urinary bladder at a separate orifice) or incomplete (also referred to as bifid, wherein the ureters merge together before they enter the bladder via 1 orifice). Rarely, a duplicated ureter can terminate blindly on either the proximal or distal (or both) sides.¹² As observed in the cat of the present report, ureteral ectopy and duplication may coexist, although this is uncommonly identified in people and animals.^{3,10,11,13,14}

Urothelial carcinomas originate from the urothelium, most commonly in the urinary bladder and less commonly in the ureter or renal pelvis of people and animals.^1,15 Primary ureteral tumors are rare in men^16,17 and are sparsely described in the veterinary medical literature.^18,19,20 Most of these tumors are epithelial and malignant, consistent with primary ureteral carcinoma. Most primary ureteral carcinomas arise from the urothelium and are classified as upper urinary tract urothelial carcinomas, together with renal pelvis tumors.¹⁷ Despite a lack of uroplakin staining of sections of the neoplasm in the case described in the present report, the carcinoma was suspected to be of urothelial origin given its gross and histomorphologic features. The lack of uroplakin staining of normal and neoplastic urothelium in the present case was suspected to be attributable to the lack of antibody reactivity in feline tissue. Description of uroplakin staining of urothelium obtained from cats is rare.²¹ For the mass in the cat of the present report, the observed areas with glandular (as well as minimal squamous) growth were interpreted as representing divergent urothelial differentiation within a primary urothelial carcinoma,¹ possibly caused by metaplasia secondary to chronic inflammation.²² Alternatively, a primary ureteral adenocarcinoma, most likely arising from metaplastic glandular epithelium, could not be ruled out in this case. Evidence of gross or microscopic tumor metastasis was not observed in the cat of the present report. Given the tumor's transmural infiltrative growth and the lack of lymph node or distant metastasis, the tumor was classified as pT3N0M0 on the basis of the TNM classification system.²³ This determination was concordant with the single previous report¹⁹ of a primary ureteral tumor in a cat; for that cat, there was no evidence of tumor spread despite the tumor's locally highly infiltrative growth.

Primary ureteral tumors in ectopic^24,25 or duplicated^26,27 ureters have rarely been reported and have been reported only for people. Those tumors were urothelial carcinomas (transitional cell carcinomas) in all but 1 case²⁵ in which the tumor was diagnosed as a primary ureteral adenocarcinoma. With regard to primary ureteral tumors in ectopic or duplicated ureters in humans, no sex predisposition has been reported, but the very low number of known cases has hampered epidemiological investigations. Affected humans were between 34 and 81 years of age. Interestingly, all described tumors, including the tumor in the cat of the present report, were located in close proximity to the junction site (bifurcation) of the incompletely duplicated ureter or near the ureter orifice in cases of complete ureteral duplication.²⁶ Given that disturbance of normal urine flow would be expected to occur at the site of ureteral bifurcation, chronic irritation in this ureteral region would possibly make this area prone to tumor development.

In the case described in the present report, there was concurrent bacterial infection and inflammation of the peritumoral retroperitoneal adipose tissue and adjacent iliopsoas musculature. These lesions contributed to some of the clinical signs, such as signs of pain on palpation of the iliopsoas muscle. The cause of this local bacterial infection remained uncertain. Owing to the severe ureteral and renal pathological changes, abnormal urine flow may have resulted in an ascending bacterial infection. The ureter wall was severely affected by both neoplastic and inflammatory lesions, which may have extended into the periureteral tissue. An iatrogenic infection, possibly caused by a nonsterile injection during fine-needle aspiration of the neoplasm, was considered but interpreted as unlikely given the cat had clinical signs of iliopsoas muscle-associated pain before the fine-needle aspiration was performed. To the authors' knowledge, the present report represented the first description of a primary ureteral tumor in a malformed ureter in the veterinary medical literature.