Transitional cell carcinoma overview

# Overview
Transitional cell carcinoma (also called urothelial cell carcinoma) is a type of cancer that typically occurs in the urinary system, the kidney, ureter, urinary bladder, and urethra. It is the most common type of bladder cancer and second most common type of kidney cancer. Transitional cell carcinoma arises from the transitional epithelium (also called urothelium), a tssue lining the inner surface of the urinary tract. Among transitional cell carcinomas,  upper urinary tract transitional cell carcinomas are rare cancers accounting for 5-7% of all transitional cell cancer cases transitional cell carcinoma commonly affects individuals older than 60 years of age with the average age of presentation being 65. Males are more commonly affected than females. The male to female ratio is approximately 2 to 1. Based on the growth pattern, transitional cell carcinoma may be classified into either papillary urothelial carcinoma or non-papillary urothelial carcinoma. Transitional cell carcinoma may be classified according to World Health Organization in a collaborative effort conjointly with the International Society of Urological Pathologists (ISUP) into two groups infiltrating urothelial carcinomas and non-invasive urothelial carcinomas. Based on the degree of cellular differentiation, transitional cell carcinoma may be classified into two grades: low grade and high grade. Genes involved in the pathogenesis of transitional cell carcinoma of bladder include HRAS, Rb1, PTEN/MMAC1, NAT2, and GSTM1. On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive transitional cell carcinomas; a large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds are characteristic findings of invasive transitional cell carcinomas. On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings of flat lesion; fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings of papillary lesion; invasion beyond the basement membrane is the characteristic finding of invasive transitional cell carcinomas. Transitional cell carcinoma of bladder must be differentiated from squamous cell carcinoma of the bladder, adenocarcinoma of the bladder, renal cell carcinoma, renal calculi, prostate cancer, and cystitis. Transitional cell carcinoma of renal pelvis must be differentiated from renal cell carcinoma, kidney metastasis, renal medullary carcinoma, renal lymphoma, renal abscess, renal tuberculosis, pyelitis cystica, and papillary necrosis. Common risk factors in the development of transitional cell carcinoma are smoking, occupational exposure to chemicals, chronic bladder irritation, chemotherapy, radiation therapy, arsenic, personal history of cancer in the urinary tract, congenital bladder anomalies, and aristolochic acids. Common complications of transitional cell carcinoma include metastasis, anemia, hydronephrosis, urethral stricture, and urinary incontinence. Depending on the stage and grade of the tumor at the time of diagnosis, the prognosis of transitional cell carcinoma may vary. However, the 5-year survival rate of patients with bladder transitional cell carcinoma is approximately 77.5% and of patients with upper urinary tract transitional cell carcinoma is approximately 75%. The staging of transitional cell carcinoma is based on the TNM staging system. The most common symptoms of transitional cell carcinoma of bladder include hematuria, urinary frequency,urinary urgency, and dysuria. The most common symptoms of transitional cell carcinoma of upper urinary tract include hematuria and pain in the flank or abdomen. Less common symptoms of transitional cell carcinoma include loss of appetite, weight loss, fatigue, and fever. Abdominal and pelvic CT scans may be helpful in the diagnosis and staging of transitional cell carcinoma. On CT scan, transitional cell carcinoma of bladder is characterized by either focal regions of thickening of the bladder wall, or as masses protruding into the bladder lumen, or in advanced cases, extending into adjacent tissues. On CT scan, transitional cell carcinoma of upper urinary tract is characterized by homogenously enhancing mass that centered on the renal pelvis and extend towards pelviureteric junction, preserved renal contour, and focal pelvicalyceal filling defect. On ultrasound, transitional cell carcinoma is characterized by solid, hypoechoic mass located within the renal pelvis or within a dilated calyx. CT urograohy may be diagnostic of transitional cell carcinoma. Findings on CT urography suggestive of upper urinary tract transitional cell carcinoma include filling defect within the renal collecting system, distortion, obliteration, or amputation of calices, and stipple sign. The predominant therapy for transitional cell carcinoma is surgical resection. MRI findings of transitional cell carcinoma of renal pelvis include isointense to renal parenchyma on T1 and T2, moderate enhancement on T1 contrast. MRI findings of transitional cell carcinoma of bladder and ureter include isotense to muscle on T1 signal, slightly hyperintense to muscle on T2 signal, and demonstrate enhancement on contrast MRI. Adjunctive chemotherapy, radiation therapy, and immunotherapy may be required. Patients with superficial tumors of bladder are treated with intravescical injection of BCG, whereas patients with local spread and distant metastasis are treated with systemic chemotherapy. External beam radiation therapy may be the treatment for people who cant have surgery. Surgery is the mainstay of treatment for transitional cell carcinoma. The feasibility of surgery depends on the stage of transitional cell carcinoma at diagnosis. Adjunctive chemotherapy, radiation therapy, and immunotherapy may be required. Primary prevention strategies of transitional cell carcinoma include cessation of smoking, avoid exposure to industrial chemicals, avoid aristolochic acids, taking lots of fruits and vegetables, and drinking plenty of liquids.

# Classification
Based on the growth pattern, transitional cell carcinoma may be classified into either papillary urothelial carcinoma or non-papillary urothelial carcinoma. Transitional cell carcinoma may be classified according to World Health Organization in a collaborative effort conjointly with the International Society of Urological Pathologists (ISUP) into two groups infiltrating urothelial carcinomas and non-invasive urothelial carcinomas. Based on the degree of cellular differentiation, transitional cell carcinoma may be classified into two grades: low grade and high grade.

# Pathophysiology
Genes involved in the pathogenesis of transitional cell carcinoma of bladder include HRAS, Rb1, PTEN/MMAC1, NAT2, and GSTM1. On gross pathology, flat lesions or papillary lesions are characteristic findings of non-invasive transitional cell carcinomas; a large infiltrative mass or a multifocal, flat to papillary lesion with delicate fronds are characteristic findings of invasive transitional cell carcinomas. On microscopic histopathological analysis, loss of cell polarity, nuclear crowding, and cytologic atypia are characteristic findings of flat lesion; fibrovascular stalks, umbrella cells, and eosinophilic cytoplasm are characteristic findings of papillary lesion; invasion beyond the basement membrane is the characteristic finding of invasive transitional cell carcinomas.

# Causes
There are no established causes for transitional cell carcinoma.

# Differentiating Transitional cell carcinoma from other Diseases
Transitional cell carcinoma of bladder must be differentiated from squamous cell carcinoma of the bladder, adenocarcinoma of the bladder, renal cancer, renal stones, prostate cancer, and cystitis. Transitional cell carcinoma of renal pelvis must be differentiated from renal cell carcinoma, kidney metastasis, renal medullary carcinoma, renal lymphoma, renal abscess, renal tuberculosis, pyelitis cystica, and papillary necrosis.

# Epidemiology and Demographics
Among transitional cell carcinomas, upper urinary tract transitional cell carcinomas are rare cancers accounting for 5-7% of all transitional cell cancer cases. The incidence of upper urinary tract transitional cell carcinoma was estimated to be 0.6-1.1 cases per 100,000 individuals in the United States. Transitional cell carcinoma commonly affects individuals older than 60 years of age with the average age of presentation being 65. Males are more commonly affected with transitional cell carcinoma than females. The male to female ratio is approximately 2 to 1.

# Risk Factors
Common risk factors in the development of transitional cell carcinoma are smoking, occupational exposure to chemicals, chronic bladder irritation, chemotherapy, radiation therapy, arsenic, personal history of cancer in the urinary tract, congenital bladder anomalies, and aristolochic acids.

# Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for transitional cell carcinoma.

# Natural History, Complications and Prognosis
Common complications of transitional cell carcinoma include metastasis, anemia, hydronephrosis, urethral stricture, and urinary incontinence. Depending on the stage and grade of the tumor at the time of diagnosis, the prognosis of transitional cell carcinoma may vary. However, the 5-year survival rate of patients with bladder transitional cell carcinoma is approximately 77.5% and of patients with upper urinary tract transitional cell carcinoma is approximately 75%.

# Diagnosis

## Staging
The staging of transitional cell carcinoma is based on the TNM staging system.

## History and Symptoms
The most common symptoms of transitional cell carcinoma of bladder include hematuria, urinary frequency, urinary urgency, and dysuria. The most common symptoms of transitional cell carcinoma of upper urinary tract include hematuria and pain in the flank or abdomen. Less common symptoms of transitional cell carcinoma include loss of appetite, weight loss, fatigue, and fever.

## Physical Examination
Common physical examination findings of transitional cell carcinoma of bladder include cachexia, pallor, and a pelvic mass may be palpated.

## Laboratory Findings
Laboratory findings consistent with the diagnosis of transitional cell carcinoma include blood in the urine, abnormal cells in the urine, and elevated tumor markers.

## CT
Abdominal and pelvic CT scans may be helpful in the diagnosis and staging of transitional cell carcinoma. On CT scan, transitional cell carcinoma of bladder is characterized by either focal regions of thickening of the bladder wall, or as masses protruding into the bladder lumen, or in advanced cases, extending into adjacent tissues. On CT scan, transitional cell carcinoma of upper urinary tract is characterized by homogenously enhancing mass that centered on the renal pelvis and extend towards pelviureteric junction, preserved renal contour, and focal pelvicalyceal filling defect.

## MRI
MRI findings of transitional cell carcinoma of renal pelvis include isointense to renal parenchyma on T1 and T2, moderate enhancement on T1 contrast. MRI findings of transitional cell carcinoma of bladder and ureter include isotense to muscle on T1 signal, slightly hyperintense to muscle on T2 signal, and demonstrate enhancement on contrast MRI.

## Ultrasound
On ultrasound, transitional cell carcinoma is characterized by solid, hypoechoic mass located within the renal pelvis or within a dilated calyx.

## Other Imaging Findings
CT urograohy may be diagnostic of transitional cell carcinoma. Findings on CT scan urography suggestive of upper urinary tract transitional cell carcinoma include filling defect within the renal collecting system, distortion, obliteration, or amputation of calices, and stipple sign.

# Treatment

## Medical Therapy
The predominant therapy for transitional cell carcinoma is surgical resection. Adjunctive chemotherapy, radiation therapy, and immunotherapy may be required. Patients with superficial tumors of bladder are treated with intravescical injection of BCG, whereas patients with local spread and distant metastasis are treated with systemic chemotherapy. External beam radiation therapy may be the treatment for people who cant have surgery.

## Surgery
Surgery is the mainstay of treatment for transitional cell carcinoma. The feasibility of surgery depends on the stage of transitional cell carcinoma at diagnosis. Adjunctive chemotherapy, radiation therapy, and immunotherapy may be required.

## Primary Prevention
Primary prevention strategies of transitional cell carcinoma include cessation of smoking, avoid exposure to industrial chemicals, avoid aristolochic acids, taking lots of fruits and vegetables, and drinking plenty of liquids.

## Secondary Prevention
There are no secondary preventive measures available for transitional cell carcinoma.