Leukoplakia of the bladder

    Last updated date: 11-Mar-2023

    Originally Written in English

    Leukoplakia of the bladder

    Leukoplakia of the bladder


    Bladder leukoplakia is a rare disorder. It is called Squamous metaplasia of the bladder because it is characterized by squamous metaplasia of the transitional epithelium and keratinization. The etiology and possible pathogenetic causes, such as recurring infections and hereditary factors.

    Because up to 42% develop cancer, early detection is critical. It is difficult to make a clinical diagnosis. The child may appear with vesical irritation symptoms, and the passage of flakes is pathognomonic.

    Cystoscopy and biopsies are used to make the diagnosis. The typical cystoscopic findings are discussed. A treatment plan and a follow-up plan are defined. For severe lesions, aggressive extirpation or cystectomy is recommended since conservative therapy is ineffective.


    How Does It Develop?

    urine excretory tract

    The urothelium covers the whole urine excretory tract. The urothelium has histologic characteristics that are halfway between squamous and glandular epithelium, therefore the name transitional epithelium. It has a strong ability to morphologically convert into squamous or glandular epithelium in response to damage, which is the basis for metaplasia.

    Metaplasia (Greek for "form change") is the transformation of one differentiated cell type into another, generally in response to a normal maturation process or an aberrant external stimulation. The shift in cell type is part of the cell's adaptation to a new environment.

    It is important to note that metaplasia may be reversed, as opposed to dysplasia, which is a change in cell morphology caused by genetic alterations in the cell as part of a neoplastic process. If the inciting stimulus is eliminated in metaplasia, the tissue may revert to a normal pattern of differentiation.

    In general, urothelial transformation or metaplasia occurs in response to a local stimulus, with a range of benign morphologic forms.


    Types of Squamous Metaplasia

    Squamous metaplasia

    Squamous metaplasia (Bladder leukoplakia) is a condition in which the urothelium is replaced by stratified squamous epithelium. It is classified into two types: non-keratinising squamous metaplasia ("vaginal metaplasia") and keratinising squamous metaplasia ("vaginal metaplasia"). Squamous metaplasia of the bladder affects around 40% of women and 5% of males and is frequently caused by infection, trauma, or surgery.

    • Non-keratinising squamous metaplasia

    It is frequent in pre-menopausal women's trigone and is considered a normal variety. It appears de novo with no signs of prior harm and is hormonally sensitive. There is no accompanying inflammation, and the squamous metaplasia in this situation is identical to the squamous mucosa of the vagina or cervix. Up until around twenty years ago, this condition was often and consistently misdiagnosed as diathermy.

    • Keratinising squamous metaplasia: 

    Males are more likely to develop it in a non-trigone area, such as a bladder diverticulum, and it can be localized or widespread. The squamous epithelium develops parakeratosis, hyperkeratosis, or a granular layer in keratinising squamous metaplasia, and can be visible as white or grey plaques upon cystoscopy ("leukoplakia"), typically with a background erythematous mucosa. When the plaques are removed, the mucosa bleeds easily. Males with haematuria, with or without irritative symptoms, account for 80 percent of cases.

    Keratinising squamous metaplasia develops as a result of prolonged irritation, most usually as a result of recurring infections. Between 50 and 100 percent of individuals have a urinary bacterial infection. Historically, TB and Schistosomiasis were the inciting organisms, but the most prevalent bacterial isolates are E. Coli, Proteus sp., and Streptococcus Faecalis. 

    Calculi, indwelling catheters, bladder exstrophy, bladder surgery, and vitamin A deficiency are further causes. Patients with spinal cord injuries are more vulnerable to developing this disease as a result of catheter damage and/or urinary tract infections, and they are at risk of developing cancer.


    Causes of Urinary Bladder Leucoplakia

    Causes of Urinary Bladder Leucoplakia

    There are numerous presumed aetiological factors, all of which result in chronic irritation of the bladder mucosa. 

    Urinary Tract Infections: Schistosomiasis is the most prevalent cause of squamous metaplasia worldwide. Urinary tract TB was usually linked with squamous metaplasia of the urinary tract prior to anti-tuberculous medication. This was also observed in the case of syphilis prior to the widespread use of penicillin. Currently, the three most common species found in patients with squamous metaplasia are Escherichia coli, Proteus, and Streptococcus faecalis. 

    Historically, the literature reports a percentage of confirmed infection in these individuals ranging from 49 to 100 percent. Urinary infections are thought to promote keratinizing squamous metaplasia in response to inflammatory damage. Furthermore, showed that abnormalities on the glycosaminoglycan layer of the bladder surface caused by non-keratinizing trigonal squamous metaplasia might contribute to infection.

    Urinary Tract Irritants. Indwelling catheters, urinary calculi, urinary outflow blockage, fistula, tumors, bladder extrophy, neurogenic bladder, prior bladder surgery, and vitamin A deficiency are all chronic irritants linked with squamous metaplasia. In a patient undergoing radiation therapy for transitional cell carcinoma, squamous cell metaplasia progressed to SCC.

    Genetic Factors: Mutations in the TP53 and KRAS genes may be linked to some occurrences of squamous metaplasia. Bladder cancer frequently has deletions of portions or the entire chromosome 9. Mutations in the RAS pathway and the fibroblast growth factor receptor 3 (FGFR3) gene have been found in low-grade cancer.

    Opium consumption: When compared to the general population, it raises the risk of bladder cancer by threefold, and concurrent use of opium and smoking increases the risk of bladder leukoplakia by fivefold.

    Environmental factors: Thirty percent of bladder cancers are most likely the consequence of occupational exposure to toxins. Benzidine (dyes manufacturing), 4-aminobiphenyl (rubber industry), 2-naphtylamine (azo dyes manufacturing, foundry fumes, rubber industry, cigarette smoke), phenacetin (analgesic), arsenic, and chlorinated aliphatic hydrocarbons in drinking water have all been linked to bladder metaplasia and cancer.

    Aristolochic acid, which is included in many Chinese herbal medicines, has been linked to urothelial cancer and renal failure. Aristolochic acid generates transversion mutations in the TP53 tumor suppressor gene by activating peroxidase in the urothelium.

    In addition to these significant risk factors, there are other additional modifiable variables, such as obesity, that are less strongly (i.e. 10–20 percent risk increase) related with bladder metaplasia. Although these are minimal impacts, risk reduction in the general population can still be achieved by lowering the incidence of a number of smaller risk factors at the same time.


    Symptoms of Bladder Leukoplakia & Cancer

    Symptoms of Bladder Leukoplakia

    Patients often appear with generalized irritative urine symptoms such as haematuria, dysuria, urgency, and frequency. There is a minor male-to-female ratio.

    Bladder metaplasia or cancer is characterized by the presence of blood in the urine, which may be visible or detectable only under a microscope. The most frequent sign is blood in the urine, which is painless along with irritative symptoms. Visible blood in the urine may only be present for a brief period of time, and a urine test may be necessary to establish the presence of non-visible blood. 

    Between 80 and 90 percent of children present with visible blood at first. Other disorders that might produce blood in the urine include bladder or ureteric stones, infection, kidney illness, kidney malignancies, or vascular malformations, however these conditions (excluding kidney cancers) are usually uncomfortable.

    Other potential symptoms include frequent urination, or the need to pee yet being unable to do so. These signs and symptoms are not unique to bladder cancer and can be caused by a variety of non-cancerous diseases such as prostate infections, overactive bladder, or cystitis. Some uncommon types of bladder cancer, such as urachal adenocarcinoma, create mucin, which is secreted in the urine and causes it to thicken.


    How Is It Diagnosed?

    Diagnosis of bladder leukoplakia

    Currently, cystoscopy is the best approach to diagnose bladder problems. This is a process in which a flexible or rigid tube (called a cystoscope) containing a camera and numerous equipment is put into the bladder through the urethra. The adaptable approach allows for a visual examination of the bladder, modest corrective treatment, and the collection of samples from worrisome areas for biopsy.

    A rigid cystoscope is utilized in the operating room under general anesthesia to enable corrective procedures, biopsies, and more comprehensive tumor excision. In contrast to papillary lesions, which extend into the bladder cavity and are easily seen, carcinoma in situ lesions are flat and hidden. Multiple samples from different locations of the internal bladder wall are required to detect carcinoma in situ lesions.

    Photodynamic detection (blue light cystoscopy) can help identify cancer in situ. A dye is injected into the bladder using a catheter in photodynamic detection. Cancer cells absorb the dye and become visible under blue light, offering visual cues on regions that need to be biopsied or removed.

    However, visual detection in any of the foregoing forms is insufficient for determining pathological categorization, cell type, or stage of the current tumor. A so-called cold cup biopsy performed during a standard cystoscopy (rigid or flexible) will also not enough for pathological staging. As a result, ocular identification must be followed by transurethral surgery. Transurethral resection of bladder tumor is the name of the operation (TURBT).

    Furthermore, before and after the TURBT, a rectal and vaginal bimanual examination should be performed to determine whether there is a palpable lump or if the tumor is fastened ("tethered") to the pelvic wall. The diagnostic categorization and staging information gained during the TURBT operation is critical for selecting the appropriate therapy and/or follow-up regimens.


    Can Bladder Metaplasia & Cancer Be Prevented?

    There is no foolproof strategy to avoid bladder cancer. Some risk variables, such as age, gender, ethnicity, and family history, are uncontrollable. However, there may be things you can take to reduce your risk.

    Do not smoke, and do not expose your children to smoke:

    Smoking is considered to be responsible for almost half of all bladder malignancies. (This covers all forms of smoking, such as cigarettes, cigars, and pipes.)


    Limit exposure to certain chemicals in the workplace:

    Workers in companies that utilize specific organic compounds are more likely to get bladder cancer. Rubber, leather, printing materials, textiles, and paint are just a few of the sectors where these compounds are regularly utilized. If you work in an environment where you may be exposed to hazardous substances, make sure to use proper work safety procedures.

    Some chemicals present in some hair dyes may also pose a risk, so it's critical for hairdressers and barbers who work with these products on a regular basis to utilize them responsibly. (Most studies have indicated that personal use of hair dyes does not raise the incidence of bladder cancer.)


    Drink plenty of liquids:

    There is evidence that consuming plenty of fluids, mostly water, may reduce a person's risk of bladder metaplasia.


    Eat a plenty fruits and vegetables:

    Some studies have shown that a diet rich in fruits and vegetables may help protect against bladder cancer, while others have not. Nonetheless, following a balanced diet has been found to offer several advantages, including decreasing the risk of some forms of cancer.


    Management of Bladder Leukoplakia

    Management of Bladder Leukoplakia

    Management of leukoplakia depends on the risk of developing bladder cancer:

    • Low-risk early bladder cancer:

    Transurethral excision of a bladder tumor(TURBT) is used to treat low-risk, non-muscle-invasive bladder cancer. When tissue samples are obtained for testing during your initial cystoscopy, this technique may be performed.

    TURBT is performed under general anaesthesia. The cystoscope is used by the surgeon to find visible tumors and cut them away from the bladder lining. A low electric current is used to seal the incisions, and you may be given a urinary catheter to empty any blood or debris from your bladder during the next several days.

    Following surgery, you should be given a single dosage of chemotherapy through a catheter straight into your bladder. The chemotherapeutic solution is held in your bladder for almost an hour before being evacuated.

    Most patients are able to leave the hospital less than 48 hours after undergoing TURBT and resume normal physical activity within two weeks.

    Follow-up visits with a cystoscopy should be provided to you at 3 and 9 months to monitor your bladder.

    If you’re the same condition reappears after 6 months and is minor, you may be offered a therapy known as fulguration. This method entails utilizing an electric current to eliminate abnormal cells.


    • Intermediate (moderate) risk early bladder cancer:

    People with intermediate-risk non-muscle-invasive bladder cancer should be administered at least 6 chemotherapy treatments. Using a catheter, the liquid is inserted straight into your bladder and held there for about an hour before being drained out.

    Follow-up appointments should be provided at 3, 9, and 18 months, and then once a year. A cystoscopy will be used to examine your bladder throughout these consultations. If your cancer returns within 5 years, you will be referred back to an urological expert team.

    Some chemotherapy medication may be remained in your urine after treatment, causing severe skin irritation.

    It helps if you sit down to urinate and avoid splashing yourself or the toilet seat. After shaving, always cleanse the skin surrounding your genitals with soap and water.


    • High-risk early bladder cancer:

    If you have high-risk non-muscle-invasive bladder cancer, you should be given a second TURBT procedure within 6 weeks after the first. A CT or MRI scan may also be required.

    Your urologist and clinical nurse specialist will go through your treatment choices with you, which will be one of the following:

    a procedure to remove your bladder a course of Bacillus Calmette-Guérin (BCG) therapy – using a variation of the BCG vaccination (cystectomy)

    The BCG vaccination is injected into your bladder via catheter and kept there for two hours before being emptied. The majority of patients require weekly treatments over a 6-week period.

    Follow-up appointments should be provided every 3 months for the first two years, then every 6 months for the next two years, and finally once a year. A cystoscopy will be used to examine your bladder throughout these consultations.

    If you choose to have a cystectomy, your surgeon will need to devise a new method for urine to exit your body (urinary diversion). Your clinical nurse specialist may go through your procedure alternatives with you, as well as how the urine diversion will be made.

    Following a cystectomy, you should be offered follow-up consultations, which should include a CT scan at 6 and 12 months, as well as blood testing once a year. For the next five years, males must have their urethra checked once a year.



    Leukoplakia of the bladder

    Metaplasia is frequent in the bladder urothelium, and it is often a normal finding or a reversible transformation in response to injury. The vast majority of metaplasias are reversible and not malignant. The exception is keratinizing squamous metaplasia, which has a substantial connection with the development of cancer and should be treated with total excision and ongoing surveillance. 

    The significance of intestinal metaplasia in the development of adenocarcinoma is unclear, and additional research is needed before any conclusions can be drawn. An intriguing recent discovery is that nephrogenic metaplasia, rather than urothelial metaplasia, may reflect implantation of renal tubular cells in the bladder.

    Keratinizing squamous metaplasia appears to be a reaction to prolonged bladder irritation. At this time, this process should not be called pre-malignant; that label is reserved for intra-epithelial neoplasia. However, these patients are at a greater risk of neoplasia, particularly those with severe lesions. A cystoscopy and biopsy are recommended along with regular follow-up. Transurethral resection should be used to treat lesions. Currently, cystectomy is not considered standard therapy.