Transitional cell carcinoma

From Felipedia

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 rare cancer of cats, affecting the lower urinary tract, although one of the more common neoplasia of the urinary tract. These tumours represent only about 0.4% or less of all tumours of cats^[1]. 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^[2].

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^[3].

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^[4].

Clinical signs

Common reported signs include dysuria, persistent haematuria, anorexia, lower abdominal pain and intermittent vomiting. Weight loss is commonly associated with this disease.

In cats, bladder neoplasms account for less than 0.8% of all neoplasms. The mean age for development of transitional cell carcinoma is approximately 9 years^[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.

Transitional cell carcinoma appear to occur more frequently in purebred cats such as Siamese.

Diagnosis

Dysuria, hematuria, and pollakuria are very pertinent historical facts. Changes such as hematuria, pyuria, proteinuria, or bacteruria are common on urinalysis. 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^[6].

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^[7]. Differential diagnoses for transitional cell tumours include feline lower urinary tract disease (FLUTD), lymphoma and adenocarcinoma of the bladder.

Cytologic Features

Normal urine may contain a few transitional epithelial cells, crystals (including amorphous crystal), hyaline casts, and fat droplets (especially in cats). Other contaminants may be observed in voided urine specimens. These contaminants may include squamous epithelial cells from the distal urethra, vagina, or prepuce and bacteria. Transitional cell carcinomas usually exfoliate large numbers of neoplastic cells. The cells may be scattered individually or arranged in variably-sized aggregates. Frequently, the cells are markedly pleomorphic with pronounced anisocytosis, anisokaryosis, and variations in tinctorial characteristics (Fig. 3).3,6,7 The cytoplasm may be decreased to a thin rim in some cells or may be abundant in other cells. Overall, the cells are reported to have a high nuclear to cytoplasm ratio, but this cannot be appreciated in all cytology preparations. Also, the cytoplasm may contain small to large pale vacuoles which may compress the nucleus. Occasionally, the vacuoles may be filled with a granular, magenta material, presumably of mucoid or glycoprotein origin. Anisokaryosis is a key cytologic feature; some affected nuclei may be extremely large (5-10 times normal). Nuclear chromatin may be finely or coarsely reticulated. Some nuclei may be light colored and vacuolated or have condensed chromatin along the nuclear membrane. The nuclei may lack visible nucleoli or may contain subtle to prominent nucleoli. Mitotic figures may or may not be observed. Squamous metaplasia also may be apparent, especially in urine sediments. However, mild anisokaryosis and hyperchromatic nuclei may be observed in both neoplastic and hyperplastic transitional epithelial cells^[8].

Cytologic features alone may not distinguish transitional cell carcinoma from transitional cell hyperplasia in all fine-needle aspirates or urine sediments. In dogs, the diagnosis of transitional cell carcinoma may be improved with the use of a commercially available bladder tumor antigen detection test (V-BTA test, POLYMEDCO Inc., 510 Furnace Dock Rd., Cortlandt Manor, NY 10567). This test uses a latex agglutination system to detect a unique tumor-associated glycoprotein in urine. The sensitivity and specificity of this test is 90% and 78%, respectively.8 The test works reliably in most instances; however, false positive tests may be associated with marked glucosuria (4+), heavy proteinuria (4+), and pyuria or hematuria (>30-40 WBC or RBC per microscopic hpf of view). The ise of the bladder tumor antigen test has not been recorded in cats^[9].

Treatment

In cats, surgery is the only treatment that offers a potential cure, provided the neoplasm can be completely excised and metastasis has not occurred. Although little information is recorded on cats, in a study of 11 dogs, 10 of which had transitional cell carcinoma, the median survival time was 365 days following surgical excision in the absence of detectable nodal or distant metastasis. Six additional dogs with incomplete surgical excision of the transitional cell carcinoma and no evidence of metastasis at the time of surgery had a reduction in median survival time to 120 days. If the tumor was located in bladder or urethra, the median survival times following surgery were 290 days and 277 days, respectively. If the bladder and urethra were involved concurrently, the median survival time was reduced to 90 days. In studies evaluating the use of carboplatin and cisplatin in the treatment of transitional cell carcinoma, neither drug was found to be of great benefit. However, peroxicam (a nonsteroidal antiinflammatory drug) 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^[10].

References

1. ↑ 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
2. ↑ Beatty, JA et al (1999) Haematuria in a geriatric cat. Aust Vet J 77:160
3. ↑ Chun, R & Wilson, HW (2010) Urinary tract tumors: In August, JR (Ed): Consultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia
4. ↑ 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
5. ↑ Knapp, DW (2007) Tumors of the urinary system. In Withrow S, Vail, D (Eds): Small animal oncology. 4th edition. Saunders, Philadelphia. pp:649
6. ↑ Bennett, SL, Holland, JA & Meehan, MC (2003) Mural lymphoma associated with the urinary bladder of a cat. Aust Vet Pract 33:155
7. ↑ Wilson, HM et al (2007) Clinical signs, treatments, and outcome n cats with transitional cell carcinoma of the urinary bladder" 20 cases(1990-2004). JAVMA 231:101
8. ↑ 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
9. ↑ 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
10. ↑ 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