Transitional cell carcinoma, also called urothelial carcinoma, is a type of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
that typically occurs in the
urinary system
The 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 and bl ...
. It is the most common type of
bladder cancer
Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
and cancer of the
ureter
The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional epit ...
,
urethra
The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...
, and
urachus
The urachus is a fibrous remnant of the allantois, a canal that drains the urinary bladder of the fetus that joins and runs within the umbilical cord. The fibrous remnant lies in the space of Retzius, between the transverse fascia anteriorly and t ...
. It accounts for 95% of
bladder cancer
Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
cases.
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, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include spr ...
, but accounts for only five to 10 percent of all primary renal malignant tumors.
Transitional cell carcinomas arise from the
transitional epithelium
Transitional epithelium also known as urothelium 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 ...
, a tissue lining the inner surface of these hollow organs.
When the term "urothelial" is used, it specifically refers to a carcinoma of the
urothelium
Transitional epithelium also known as urothelium 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 ...
, meaning a transitional cell carcinomas of the urinary system.
Signs and symptoms
Signs and symptoms of transitional cell carcinomas depend on the location and extent of the cancer.
Causes
Urothelial carcinoma is a prototypical example of a
malignancy
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
arising from environmental
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
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 simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
, which contributes to approximately one-half of the
disease burden
Disease burden is the impact of a health problem as measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Both o ...
.
Chemical exposure, such as those sustained by workers in the
petroleum industry
The petroleum industry, also known as the oil industry or the oil patch, includes the global processes of exploration, extraction, refining, transportation (often by oil tankers and pipelines), and marketing of petroleum products. The larges ...
, the manufacture of paints and pigments (e.g.,
aniline
Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine
In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...
dyes), and
agrochemical
An agrochemical or agrichemical, a contraction of ''agricultural chemical'', is a chemical product used in industrial agriculture. Agrichemical refers to biocides ( pesticides including insecticides, herbicides, fungicides and nematicides) an ...
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
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, physical
irritation
Irritation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant. Irritants are typically thought of as chemical age ...
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
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
(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 neural ...
or
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
), and chronic
infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s. Some particular examples are listed below:
# Certain drugs, such as
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
, 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
Acrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colorless liquid with a piercing, acrid smell. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fa ...
and
phenacetin
Phenacetin (acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn ...
, 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 through a material medium. This includes:
* ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
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 mutatio ...
, such as deletion of
chromosome 9q,
9p,
11p,
17p 17P or 17.P or 17-P may refer to:
* 17P/Holmes, a comet
* SpaceShipOne flight 17P, a commercial spaceflight
* 17α-Hydroxyprogesterone, a steroid hormone and intermediate
* 17p, the short arm of the 17th human chromosome that has the p53 tumour s ...
,
13q,
14q and overexpression of
RAS
Ras or RAS may refer to:
Arts and media
* RAS Records Real Authentic Sound, a reggae record label
* Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service
* Rás 1, an Icelandic radio station
* Rás 2, an Icelandic radio stati ...
(
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 for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
(EGFR).
# Presence of an abnormal extra chromosome, classified as a
small supernumerary marker chromosome
A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each d ...
(sSMC), in this malignancy's tumor cells. The sSMC has an
isochromosome
An isochromosome is an unbalanced structural abnormality in which the arms of the chromosome are mirror images of each other. The chromosome consists of two copies of either the long (q) arm or the short (p) arm because isochromosome formation ...
-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
Sessility, or sessile, may refer to:
* Sessility (motility), organisms which are not able to move about
* Sessility (botany), flowers or leaves that grow directly from the stem or peduncle of a plant
* Sessility (medicine), tumors and polyps that ...
, or
carcinoma in situ
Carcinoma ''in situ'' (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, bre ...
. The most common site of transitional cell carcinoma
metastasis
Metastasis is a pathogenic agent's spread 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, then, ...
outside the
pelvis
The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also called bony pelvis, or pelvic skeleton).
The ...
is bone (35%); of these, 40 percent are in the
spine.
Diagnosis
![The Paris System for reporting urinary cytology 2](https://upload.wikimedia.org/wikipedia/commons/d/d7/The_Paris_System_for_reporting_urinary_cytology_2.0.png)
Transitional refers to the histological subtype of the cancerous cells as seen under a microscope.
Classification
Transitional cell carcinomas are mostly papillary (70%,
and 30% non-papillary).
The 1973
WHO
Who or WHO may refer to:
* Who (pronoun), an interrogative or relative pronoun
* Who?, one of the Five Ws in journalism
* World Health Organization
Arts and entertainment Fictional characters
* Who, a creature in the Dr. Seuss book '' Horton He ...
grading system for transitional cell carcinomas (
papilloma
A papilloma (plural papillomas or papillomata) ('' papillo-'' + '' -oma'') is a benign epithelial tumor growing exophytically (outwardly projecting) in nipple-like and often finger-like fronds. In this context, papilla refers to the projection cre ...
, 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).
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. Hematoxylin and eosin.
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. Hematoxylin and eosin 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 diagnos ...
.
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
The mitomycins are a family of aziridine-containing natural products isolated from ''Streptomyces caespitosus'' or ''Streptomyces lavendulae.'' They include mitomycin A, mitomycin B, and mitomycin C. When the name mitomycin occurs alone, it usually ...
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) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
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 to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
regimens for advanced or metastatic transitional cell carcinomas consists of
gemcitabine
Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by i ...
and
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
) or a combination of
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
,
vinblastine
Vinblastine (VBL), 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 ca ...
,
adriamycin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toget ...
, and
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
.
Taxanes or
vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy).
Immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
such as
pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast canc ...
is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.
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 endp ...
to
atezolizumab
Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular ...
for locally advanced or metastatic
urothelial carcinoma
Transitional epithelium also known as urothelium 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 ...
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
Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign tha ...
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
Sacituzumab govitecan, sold under the brand name Trodelvy, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.
The most co ...
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 both an Male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, ...
.
See also
* Bladder cancer in cats and dogs
* Transitional cell carcinoma of the ovary
References
External links
{{Male genital neoplasia
Urological neoplasia
Carcinoma