Transitional cell carcinoma
Encyclopedia
Transitional cell carcinoma (TCC, also urothelial cell carcinoma or UCC) is a type of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 that typically occurs in the urinary system: the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

, urinary bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...

, and accessory organs. It is the most common type of bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...

 and cancer of the ureter
Ureter
In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter....

, urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...

, and urachus
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...

. It is the second most common type of kidney cancer
Kidney cancer
Kidney cancer is a type of cancer that starts in the cells in the kidney.The two most common types of kidney cancer are renal cell carcinoma and urothelial cell carcinoma of the renal pelvis...

, but accounts for only 5% to 10% of all primary renal malignant tumors.

TCC arises from the transitional epithelium, 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
Urothelium
The urothelium is a form of transitional epithelial tissue layer that lines much of the urinary tract, including the renal pelvis, the ureters, the bladder, and parts of the urethra.-Structure and function:...

, meaning a TCC of the urinary system.

Signs and symptoms

Signs and symptoms depend on the location and extent of the cancer: see for example Bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...

.

Causes

  1. certain drugs such as cyclophosphamide
    Cyclophosphamide
    Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

     and phenacetin
    Phenacetin
    Phenacetin is an analgesic, once widely used; its use has declined because of its adverse effects.-History:Phenacetin was introduced in 1887, and was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market...

     are known to predispose to bladder TCC.
  2. long-term usage of analgesic
    Analgesic
    An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

    s
  3. radiation
    Radiation
    In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...

     exposure
  4. somatic mutation
    Mutation
    In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

     such as deletion of Chromosome 9p,9q,11p,17p,13q,14q and over expression of RAS (oncogene) and epidermal growth factor receptor
    Epidermal growth factor receptor
    The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

     (EGFR)
  5. cigarette smoke
  6. naphthylamines and aniline dyes

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 (flat) or carcinoma-in-situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...

 (CIS).

The most common site of TCC metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...

 outside the pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...

 is bone
(35%); of these bone metastases, 40% are in the spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...

.

Terminology

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

Classification

The 1973 WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

 grading system for TCCs (papilloma
Papilloma
Papilloma refers to a benign epithelial tumor growing exophytically in finger-like fronds. In this context papilla refers to the projection created by the tumor, not a tumor on an already existing papilla . When used without context, it frequently refers to infections caused by human...

, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO grading (papillary neoplasm of low malignant potential (PNLMP), low grade and high grade papillary carcinoma).

Treatment

Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for limited stage TCC is surgical resection of the tumor, but reoccurrence is common. Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 for TCC consists of the MVAC regimen (methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...

, vinblastine
Vinblastine
Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....

, adriamycin and cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...

).
TCC can also be treated with infusions of BCG
BCG as a treatment for bladder cancer
BCG , a live attenuated form of Mycobacterium bovis, is the most commonly used agent for intravesical therapy. A number of other intravesical agents have been compared to BCG, but none has proved consistently superior....

 into the bladder.

Associations

It is associated with phenacetin
Phenacetin
Phenacetin is an analgesic, once widely used; its use has declined because of its adverse effects.-History:Phenacetin was introduced in 1887, and was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market...

, aniline dyes, cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

, smoking, and those who drink excessive alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

. It is also associated with hereditary nonpolyposis colorectal cancer
Hereditary nonpolyposis colorectal cancer
Lynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...

.
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