Transitional cell carcinoma

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Transitional cell carcinoma, urine sediment, dog, Wright-Leishman stain. Bacteria and purulent inflammation are present in conjunction with neoplastic epithelial cells.
Transitional cell carcinoma, dog, Wright-Leishman stain. Neoplastic cells are scattered singly or arranged in variably-sized clusters.

Transitional cell carcinoma are a relatively rare, aggressive cancer of cats, frequently affecting the bladder but may also affect the ureters[1] and kidneys[2][3]. It is one of the more common neoplasia of the urinary tract[4].

Cats have much lower incidence of lower urinary neoplasia, primarily due to the low volume of renally-excreted tryptophan metabolites, ortho-aminophenol in particular, which can accumulate in the bladder of dogs and humans and act as a carcinogen[5].

The most common site of tumor development is the trigone area of the bladder. Less commonly, these neoplasms originate in the urethra and may involve the prostate gland of males or the vaginal vault of females. The pattern of neoplastic cell growth may be papillary, non-papillary, or invasive. Metastasis occurs approximately 50% of the time. The most common sites for metastasis include regional lymph nodes, surrounding soft tissues, bones of the hindquarters, and lung.

Cyclo-oxygenase-2 (COX-2) overexpression appears to be commonly associated with this disease, suggesting a role of chronic inflammatory/irritant triggers for onset of neoplastic changes[6].

Clinical signs

Transitional cell carcinomas are relatively slow growing and the mean age for development of clinical signs is approximately 9 years[7]. Early signs can be confused with FLUTD (feline lower urinary tract disease), but symptoms associated with urinary neoplasia usually progress over time, whereas those associated with FLUTD often wax and wan[8].

Common reported signs include dysuria, persistent hematuria, anorexia, lower abdominal pain and intermittent vomiting. Weight loss may also be apparent. Changes such as hematuria, pyuria, proteinuria, or bacteruria are common on urinalysis.

Diagnosis

Dysuria, hematuria, and pollakuria are very pertinent historical facts. Cytology may used to evaluate urine sediment or fine-needle aspirations of discrete masses or suspicious lesions. Fine-needle aspiration may be assisted by abdominal palpation or ultrasonographic location of the mass. A mass may also be palpable in the caudal abdomen. Urinary obstruction is not a consistnt sign. Other less common signs include weight loss, anorexia and intermittent vomiting[9].

Ultrasound and contrast cystography are useful imaging tools to define the presence and extent of a neoplasm or suspicious lesion.

Transitional cell carcinomas tends to be relatively aggressive tumours that have often invaded into the muscle layers of the bladder wall by the time of a diagnosis. Additionally, about 20 - 30% of cats present with metastasis at the time of diagnosis[10].

Differential diagnoses for transitional cell tumours include feline lower urinary tract disease (FLUTD), lymphoma and adenocarcinoma of the bladder.

Definitive diagnosis requires biopsy of neoplastic tissue, usually acquired via laparotomy. Anisokaryosis is a key cytologic feature; some affected nuclei may be extremely large (5-10 times normal)[11].

In dogs, the diagnosis of transitional cell carcinoma may be improved with the use of a commercially available bladder tumor antigen detection test. This test has not been recorded for use in cats[12].

Treatment

In cats, surgery is the recommended treatment in advanced cases or urinary TCC, involving partial cystectomy. Unlike humans, construction of an artificial bladder using ileal tissue and creation of a stoma is not normally performed.

In cases of ureteral or renal TCCs that are unilateral, nephrectomy and ureterectomy are advised. Metastases to the lung[13], large intestine, heart and lungs are not uncommon[3].

Median survival time is 6 - 8 months, but longer-term survival has also been reported in cats treated with meloxicam. In cats, there is a reverse relationship between survival and COX-2 status, with COX-2 negative cats surviving a mean of 375 days versus COX-2 positive cats (MST 123 days)[14].

Peroxicam may have had some effect against neoplastic cells in 3 of 10 dogs with TCC. This drug currently is being used as palliative treatment for transitional cell carcinoma in cats[15].

Intravesicular chemotherapy using intravescicular cisplatin and gemcitabine or immunotherapy using bacillus Calmette-Guérin (BCG), which are the standard method of car in human patients[16], may be warranted.

References

  1. Cohen L et al (2012) Bilateral ureteral obstruction in a cat due to a ureteral transitional cell carcinoma. Can Vet J 53(5):535-538
  2. Raffan E et al (2008) Transitional cell carcinoma forming a perirenal cyst in a cat. J Small Anim Pract 49(3):144-147
  3. 3.0 3.1 Hanzlicek AS et al (2012) Renal transitional-cell carcinoma in two cats with chronic kidney disease. J Feline Med Surg 14(4):280-284
  4. Brearly, MJ, Thatcher, C & Cooper, JE (1986) Three cases of transitional cell carcinoma in the cat and a review of the literature. Vet Rec 118:91
  5. Beatty, JA et al (1999) Haematuria in a geriatric cat. Aust Vet J 77:160
  6. Landolfli, JA & Terio, KA (2006) Transitional cell carcinoma in fishing cats (Prionailurus viverrinus): pathology and expression of cyclo-oxygenase-1, -2 and p53. Vet Pathol 43:674
  7. Knapp, DW (2007) Tumors of the urinary system. In Withrow S, Vail, D (Eds): Small animal oncology. 4th edition. Saunders, Philadelphia. pp:649
  8. Chun, R & Wilson, HW (2010) Urinary tract tumors: In August, JR (Ed): Consultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia
  9. Bennett, SL, Holland, JA & Meehan, MC (2003) Mural lymphoma associated with the urinary bladder of a cat. Aust Vet Pract 33:155
  10. Wilson, HM et al (2007) Clinical signs, treatments, and outcome in cats with transitional cell carcinoma of the urinary bladder" 20 cases(1990-2004). JAVMA 231:101
  11. Zinkl, J.G. (1999) Urinary sediment and cytology of the urinary tract. In Diagnostic Cytology of the Dog and Cat. R.D. Cowell, R.D. Tyler, and J.H. Meinkoth (eds). Mosby, St Louis
  12. Osborne, C.A. et al (1968) Neoplasms of the canine and feline urinary bladder: incidence, etiologic factors, occurrence and pathologic features. Am J Vet Res 29:2041-2053
  13. Wilson HM et al (2007) Clinical signs, treatments, and outcome in cats with transitional cell carcinoma of the urinary bladder: 20 cases (1990-2004). J Am Vet Med Assoc 231(1):101-106
  14. Bommer NX et al(2012) Clinical features, survival times and COX-1 and COX-2 expression in cats with transitional cell carcinoma of the urinary bladder treated with meloxicam. J Feline Med Surg Mar 9
  15. Norris, A.M.et al (1992). Canine bladder and urethral tumors: a retrospective study of 115 cases (1980-1985). J Vet Intern Med 6:145-153
  16. Griffiths TR et al (2013) Current perspectives in bladder cancer management. Int J Clin Pract 67(5):435-448