Transitional cell carcinoma is a type of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

that arises from the

transitional epithelium Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and ...

, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the

urinary system The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, urinary bladder, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume ...

; in that case, it is also called urothelial carcinoma. It is the most common type of

bladder cancer Bladder cancer is the abnormal growth of cells in the bladder. These cells can grow to form a tumor, which eventually spreads, damaging the bladder and other organs. Most people with bladder cancer are diagnosed after noticing blood in thei ...

and cancer of the

ureter The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...

urethra The urethra (: urethras or urethrae) is the tube that connects the urinary bladder to the urinary meatus, through which Placentalia, placental mammals Urination, urinate and Ejaculation, ejaculate. The external urethral sphincter is a striated ...

, and

urachus The urachus forms from the distal end of the allantois in the embryo, and develops into a closed cord between the base of the bladder, and the navel. It drains the bladder of the fetus that joins and runs within the umbilical cord. The fibrous r ...

. Symptoms of urothelial carcinoma in the bladder include hematuria (blood in the urine). Diagnosis includes urine analysis and imaging of the urinary tract (

cystoscopy Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope. The urethra is the tube that carries urine from the bladder to the outside of the body. The cystoscope has lenses like a telescope or microscop ...

). It accounts for 95% of

cases and bladder cancer is in the top 10 most common malignancy disease in the world and is associated with approximately 200,000 deaths per year in the United States alone. It is the second most common type of

kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, a lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include ...

, but accounts for only five to 10 percent of all primary renal malignant tumors. Men and older people have a higher rate of urothelial carcinomas. Other risk factors include smoking and exposure to aromatic amines. Treatment approaches depend on the stage and spread of the tumour. Tumour removal (resection), chemotherapy and chemoradiation may be indicated. Immunotherapy with immune check point inhibitor medications may also be suggested.

Signs and symptoms

Signs and symptoms of transitional cell carcinomas depend on the location and extent of the cancer. Symptoms of bladder cancer is blood in the urine.

Causes

Urothelial carcinoma is a prototypical example of a

malignancy Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...

arising from environmental

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

ic influences. By far the most important cause is

cigarette smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

, which contributes to approximately one-half of the disease burden. Chemical exposure, such as those sustained by workers in the

petroleum industry The petroleum industry, also known as the oil industry, includes the global processes of hydrocarbon exploration, exploration, extraction of petroleum, extraction, oil refinery, refining, Petroleum transport, transportation (often by oil tankers ...

, the manufacture of paints and pigments (e.g.,

aniline Aniline (From , meaning ' indigo shrub', and ''-ine'' indicating a derived substance) is an organic compound with the formula . Consisting of a phenyl group () attached to an amino group (), aniline is the simplest aromatic amine. It is an in ...

dyes), and

agrochemical An agrochemical or agrichemical, a contraction of ''agricultural chemical'', is a chemical product used in industrial agriculture. Agrichemical typically refers to biocides (pesticides including insecticides, herbicides, fungicides and nematicide ...

s are known to predispose one to urothelial cancer. The 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 Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor. Causes There are ...

of the urothelium. Thus, urothelial carcinomas are more common in the context of chronic urinary stone disease, chronic catheterization (as in patients with

paraplegia Paraplegia, or paraparesis, is an impairment in motor or sensory function of the lower extremities. The word comes from Ionic Greek () "half-stricken". It is usually caused by spinal cord injury or a congenital condition that affects the neura ...

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

), and chronic

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s. Some particular examples are listed below: # Certain drugs, such as cyclophosphamide, via the

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s acrolein and phenacetin, may predispose to the development of transitional cell carcinomas (the latter especially with respect to the upper urinary tract). #

Radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...

exposure #

Somatic mutation A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline muta ...

, such as deletion of chromosome 9q, 9p, 11p, 17p, 13q, 14q and overexpression of RAS (

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

) and

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor (biochemistry), receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligand (biochemistry ...

(EGFR). # Presence of an abnormal extra chromosome, classified as a small supernumerary marker chromosome (sSMC), in this malignancy's tumor cells. The sSMC has an isochromosome-like structure consisting of two copies of the short (i.e. p) arm of chromosome 5. In consequence, the malignant cells bearing it have four copies of this p arm's genetic material, two from each of the normal chromosome 5's and two from the sSMC. "sSMC i(5)(p10)" is the single most common recurrent structural chromosomal abnormality in transitional cell carcinoma, being present in its malignant cells in most cases of the disease. Transitional cell bladder carcinomas associated with this sSMS are more aggressive and invasive than those not associated with it.

Growth and spread

Transitional cell carcinomas are often multifocal, with 30–40% of patients having more than one

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

at diagnosis. The pattern of growth of transitional cell carcinomas can be papillary, sessile, or carcinoma in situ. The most common site of transitional cell carcinoma

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

outside the

pelvis The pelvis (: pelves or pelvises) is the lower part of an Anatomy, anatomical Trunk (anatomy), trunk, between the human abdomen, abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also c ...

is bone (35%); of these, 40 percent are in the spine.

Diagnosis

The Paris System for reporting urinary cytology 2

Transitional refers to the histological subtype of the cancerous cells as seen under a microscope. Expression of p53 in urothelial neoplasms

Classification

Transitional cell carcinomas are mostly papillary (70%, and 30% non-papillary). The 1973 WHO grading system for transitional cell carcinomas ( papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO grading for papillary types (papillary

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

of low malignant potential NLMP low grade, and high grade papillary carcinoma). High-grade carcinoma typically displays more pleomorphism, multiple mitoses, euchromatin and relatively prominent nucleoli, and uneven distribution of nuclei. File:Low- and high-grade urothelial carcinoma.jpg, Transitional cell carcinoma, being low-grade to the left, and high-grade to the right.

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...

File:Papillary urothelial carcinoma (low-grade), intermed. mag.1.jpg, Papillary transitional cell carcinoma, low grade Image:Bladder urothelial carcinoma histopathology (1) at trigone.jpg, Histopathology of urothelial carcinoma of the urinary bladder, showing a nested pattern of invasion. Transurethral biopsy. H&E stain Image:Bladder urothelial carcinoma histopathology (2) at trigone.jpg, Histopathology of urothelial carcinoma of the urinary bladder. Image:Bladder urothelial carcinoma histopathology (3) at trigone.jpg, Histopathology of urothelial carcinoma of the urinary bladder. Image:urethral_urothelial_cell_carcinoma.jpg, Micrograph of urethral urothelial cell carcinoma. H&E stain

Treatment

Localized/early transitional cell carcinomas of bladder

Transitional cell carcinomas can be very difficult to treat. Treatment for localized stage transitional cell carcinomas 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 transitional cell carcinomas can also be treated with infusions of Bacille Calmette–Guérin 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 Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

or the patient becoming sensitized to 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 transitional cell carcinomas

First-line

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

regimens for advanced or metastatic transitional cell carcinomas consists of

gemcitabine Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...

and

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

) or a combination of

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

vinblastine Vinblastine, sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder canc ...

, adriamycin, and

(MVAC polychemotherapy). The side effects associated with some of these polychemotherapy treatment options are considered serious and mortality from MVAC treatment has been estimated at approximately 4%. Cisplatin and gemcitabine treatment may be associated with less severe side effects. Up to half of people with bladder cancer are not able to take these chemotherapy treatments due to their overall health. Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy). Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC, however this is based on low certainty evidence. In May 2016, the FDA granted

accelerated approval The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate end ...

to atezolizumab for locally advanced or metastatic

urothelial carcinoma Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears cuboidal when relaxed and ...

treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of

overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...

.Failed confirmatory trial raises questions about atezolizumab for advanced urothelial cancer. June 2017
/ref> In April 2021, the FDA granted accelerated approval to sacituzumab govitecan for people with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.

Prostate

Transitional cell carcinomas can also be associated with the

prostate The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

References

External links

{{Male genital neoplasia Urological neoplasia Carcinoma