Transitional cell carcinoma

Transitional cell carcinoma
Histopathology of transitional carcinoma of the urinary bladder. Transurethral biopsy. H&E stain.
Classification and external resources
Specialty	Oncology
ICD-O	M8120/3-8130
eMedicine	med/2003 radio/711
MeSH	D002295

Transitional cell carcinoma (TCC) also urothelial carcinoma (UCC), is a type of cancer that typically occurs in the urinary system. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus. It is the second most common type of kidney cancer, but accounts for only five to 10 percent of all primary renal malignant tumors.

TCC arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs.^[1]

When the term "urothelial" is used, it specifically refers to a carcinoma of the urothelium, meaning a TCC of the urinary system.

Signs and symptoms

Signs and symptoms of TCC are entirely dependent on the location and extent of the cancer.

Causes

Urothelial carcinoma is a prototypical example of a malignancy arising from environmental carcinogenic influences. By far the most important cause is cigarette smoking, which contributes to approximately one-half of the disease burden. Chemical exposure, such as those sustained by workers in the petroleum industry, the manufacture of paints and pigments (e.g., aniline dyes), and agrochemicals are known to predispose one to urothelial cancer. Interestingly, risk is lowered by increased liquid consumption, presumably as a consequence of increased urine production and thus less "dwell time" on the urothelial surface. Conversely, risk is increased among long-haul truck drivers and others in whom long urine dwell-times are encountered. As with most epithelial cancers, physical irritation has been associated with increased risk of malignant transformation of the urothelium. Thus, urothelial carcinomas are more common in the context of chronic urinary stone disease, chronic catheterization (as in patients with paraplegia or multiple sclerosis), and chronic infections. Some particular examples are listed below:

1. Certain drugs, such as cyclophosphamide, via the metabolites acrolein and phenacetin, are known to predispose to TCC (the latter especially with respect to the upper urinary tract).^[2]
2. Radiation exposure
3. Somatic mutation, such as deletion of chromosome 9q, 9p, 11p, 17p,13q, 14q and overexpression of RAS (oncogene) and epidermal growth factor receptor (EGFR).

Pathology

TCCs are often multifocal, with 30–40% of patients having more than one tumor at diagnosis. The pattern of growth of TCCs can be papillary, sessile, or carcinoma-in-situ (CIS). The most common site of TCC metastasis outside the pelvis is bone(35%); of these bone metastases, 40 percent are in the spine.^[3]

Diagnosis

Bladder diverticula containing stones. Also note that the bladder wall is thickened due to possible transitional cell carcinoma.

Transitional refers to the histological subtype of the cancerous cells as seen under a microscope.

Classification

The 1973 WHO grading system for TCCs (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO^[4] grading (papillary neoplasm of low malignant potential [PNLMP], low grade, and high grade papillary carcinoma).

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  Histopathology of urothelial carcinoma of the urinary bladder, showing a nested pattern of invasion. Transurethral biopsy. Hematoxylin and eosin.
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  Histopathology of urothelial carcinoma of the urinary bladder.
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  Histopathology of urothelial carcinoma of the urinary bladder.
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  Micrograph of urethral urothelial cell carcinoma. H&E stain.

Treatment

Localized/early TCC of bladder

Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for localized stage TCC is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.

Localized/early TCC can also be treated with infusions of BCG into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to the BCG causing severe intolerance and a possible reduction in bladder volume due to scarring.

In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.

Advanced or metastatic TCC

First-line chemotherapy regimens for advanced or metastatic TCC consists of gemcitabine and cisplatin) (GC) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC).^[5] Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.

Prostate

TCC can also be associated with the prostate.^[6][7]

See also

• Transitional cell carcinoma of the ovary

References