Bladder leukoplakia is a metaplasia (degeneration) of the urothelium into a multilayered squamous epithelium, sometimes with keratinization. Symptoms may be absent, sometimes pathology is clinically manifested by frequent urination with discomfort, urgent urges, chronic pelvic pain syndrome. Diagnosis involves cystoscopy with biopsy, final verification is performed using morphological examination. Treatment can be conservative – antibiotics, drugs that improve blood circulation, vitamins, instillations or operative – aimed at eliminating pathological foci.
ICD 10
N32.8 Other specified bladder lesions
Meaning
Bladder leukoplakia (leukoceratosis, leukoplasia) occurs in 1:10,000 cases. The term itself implies the degeneration of a normal transitional epithelium into a pathological, atypical for mucous membranes — a multilayer keratinizing squamous cell. The condition was first described in 1862 by the Austrian pathologist K. Rokitansky, who drew attention to the excessive formation of cells with desquamation phenomena. This is the most dangerous type of leukoplakia, since keratinization either accompanies bladder carcinoma, or has a risk of malignancy. Non-keratinized type of bladder leukoplakia occurs in women and young children (rarely) and is not dangerous.
Causes
Pathogenesis and etiology are still debatable. Some practitioners consider bladder leukoplakia to be histological changes in tissue with long-term (more than 2 years) chronic cystitis with episodes of recurrence. Conditions that are considered as possible causes include:
- Chronic foci of infection in the body. Basically, these are pelvic inflammatory diseases that are initiated by specific (chlamydia, mycoplasma, herpes, HPV) and non-specific microflora (E. coli, streptococcus, proteus). Pathogens can enter the bladder not only ascending, but also hematogenically: from the uterus, intestines, kidneys, carious teeth or tonsils. Recurrent cystitis is considered as the main cause of leukoplakia.
- Endocrine disorders. Studies show that in patients with leukoplakia, menarche occurs later, in the future there are violations of menstrual function: menometrorrhagia, infertility, irregular anovulatory cycles. Taking some oral contraceptives contributes to the development of hypoestrogenism, against which the transitional epithelium of the bladder is replaced by a multilayer flat one.
- Traumatic factors. Installed artificial drains, their replacement, and urethral augmentation lead to permanent traumatization and provoke urothelial metaplasia. In the literature there are data on the development of bladder leukoplakia after surgical treatment, radiation exposure, with cystolithiasis.
- Dystrophic disorders. Violation of blood supply and innervation of the bladder wall prevents the normal trophic organ. Ischemia disrupts the composition of the mucin layer. The mucosa becomes looser, which predisposes to the introduction of bacteria and viruses. Constipation, sedentary lifestyle, varicose veins of the pelvis are factors contributing to congestion and insufficient tissue trophism.
Irrational use of certain drugs, smoking, chronic alcoholism and hypovitaminosis A with background immunosuppression are considered risk factors contributing to atypical cell differentiation. In tropical countries, metaplasia accompanies schistosomiasis, a parasitic disease in which helminth eggs can be found in small vessels of the bladder (genitourinary schistosomiasis).
Pathogenesis
Inflammation and other etiofactors cause a violation of the general and local reactions of the immune system, which is why infectious and conditionally pathogenic microflora persists on the mucous membrane. Persistent infection, alterations and repair processes lead to metaplasia and fibrosis. In the multilayer squamous epithelium, which is the result of a violation of cytodifferentiation, there is no glycogen formation, and in a number of observations, keratinization occurs.
Urine has an irritating effect on modified cells left without natural protection (the loss of the anti-adhesive factor allows microbes to linger), which supports inflammation and causes pain, even if adequate antibacterial therapy has been carried out. Through the destroyed layer, potassium ions also migrate from urine to the interstitium, which causes depolarization of nerve endings, spasm of smooth muscles, alteration of blood and lymph vessels. These mechanisms provide persistent dysuria.
Classification
Areas of leukoplakia may be isolated, but in severe cases, whitish plaques occupy a significant area of the bladder. There are 3 stages in the formation of leukoplakia: squamous cell modulation, squamous cell metaplasia and the addition of keratinization (keratinization). Depending on the histological features , consider:
- Non-keratinized subtype of leukoplakia. It occurs in the area of the urinary triangle (also called pseudomembranous trigonitis), a variant of the norm. Changes are registered mainly in women, there is no connection with chemical and physical stimuli, as well as the risk of malignancy. When symptoms appear, it is treated with estrogens.
- Keratinized subtype of leukoplakia. Pathology is more common in men, it is associated with mechanical action. With a number of observations, atypia is recorded, therefore the keratinizing subtype is a risk factor for squamous cell carcinoma.
Considering that bladder leukoplakia is a predominantly histological diagnosis, made on the basis of morphological examination, in practical urology, classification by stages is used – the tactics of patient management depends on it. There are three stages of the pathological process:
- Stage 1. It is characterized by metaplastic changes in the transitional epithelium, which are not visible during cystoscopy and are confirmed exclusively histologically. The number of cell layers has been increased by 2 times, typically a change in the shape of the upper layers (polygonal), bubble-like nuclei with multiple nucleoli. Histochemistry shows an excessive amount of glycogen and proceratin.
- Stage 2. There is a further modification of the epithelium, which can be observed during cystoscopy in the form of a whitish or yellowish plaque on the bladder mucosa. Single foci. The histological picture is represented by a metaplastic multilayered squamous epithelium with typical vertical differentiation. The lower layers are made up of small hyperchromic polygonal cells, the upper cells are larger in size, contain keratogyalin.
- Stage 3. The process is generalized, there is a spread of foci of leukoplakia involving almost the entire mucous membrane. Histological characteristics are identical. Inflammatory changes — thickening of the walls, swelling, dilation and fragility of blood vessels are expressed significantly.
Symptoms
At stage 1, there are no manifestations, as the disease progresses, there are complaints of difficulty urinating with cuts (53%), constant aching pains in the lower abdomen (80%), irresistible urge to urinate with urinary incontinence (14%). A pronounced pain syndrome indicates either a total lesion or leukoplakia of the neck of the bladder, especially rich in nerve endings.
With a common process, the symptoms can be so debilitating that the quality of life suffers significantly. The frequency of urge to urinate even at night can reach 5-6 times per hour. Pollakiuria is present in 83-95% of patients. In advanced cases, patients complain about the appearance of blood in the urine at the end of the act of urination (terminal hematuria), a change in its qualities – white flakes, leukocytes, bacteria often precipitate. The psychoemotional sphere suffers, irritability, insomnia, depressed mood join.
Complications
In 10-20% of patients, bladder leukoplakia with keratinization occurs with carcinoma. Almost always at stage 3, dyspareunia joins women – painful sensations during sexual contact, worsening of symptoms after sexual intimacy occurs in most patients. In men, bladder leukoplakia is accompanied by erectile dysfunction. Background recurrent urinary tract infection is detected in almost all patients.
A recurrent inflammatory process leads to the replacement of normal functional tissue with fibrous tissue, which disrupts normal urination (neurogenic dysfunction) and leads to the constant presence of residual urine. Inadequate emptying causes the formation of reflux and pyelonephritis in a third of patients, the addition of chronic renal failure in every fifth case and cystolithiasis in 22-35%. Another complication of leukoplakia is a decrease in the capacity of the bladder (microcysts) with frequent urination and muscle atrophy.
Diagnostics
There are no specific changes in the general urine analysis that would allow us to unequivocally confirm the diagnosis of bladder leukoplakia. Pathology is treated by a specialist urologist, when complications are added, a consultation of a nephrologist, an andrologist may be useful. The algorithm of research in leukoplakia can be as follows:
- Laboratory diagnostics. In the urine, the number of leukocytes, bacteria, erythrocytes is often increased, detached scales may be present. PCR diagnostics for STIs is informative. Additionally, a culture study is performed – urine culture on nutrient media in order to determine pathogens and sensitivity to drugs. In women, the hormonal profile (estradiol, progesterone, FSH) is examined.
- Instrumental diagnostics. The gold standard is cystoscopy, during which areas of leukoplakia are visible in the bladder. Tissue samples are taken from suspicious places for subsequent morphology, it is this that allows us to verify the diagnosis. Ultrasound of the kidneys and pelvic organs is prescribed to clarify the condition of nearby structures and assess possible complications.
Differential diagnosis is carried out with cystitis of fungal etiology, which is also characterized by whitish plaque on the mucous membrane of the organ. A similar cystoscopic pattern is observed in malacoplakia, a rare disease of unknown etiology with the appearance of yellowish or whitish plaques, sometimes with ulceration. With urogenital tuberculosis and amyloidosis, with the help of optics, you can see foci that resemble leukoplakia.
Treatment
In women with a non-keratinized subtype of leukoplakia, dynamic monitoring is carried out in the absence of complaints, when unfavorable symptoms appear, estrogens are prescribed. Treatment of leukoplakia with keratinization can be conservative at the initial stages (with mandatory supervision), then a surgical approach is recommended. In clinical practice , it is used:
- Medical treatment. Antibiotics are prescribed taking into account sensitivity, antiviral and anti-inflammatory drugs, immunomodulators. At the non-missed stages, a good therapeutic effect can be obtained after instillation of drugs based on glycosaminoglycans. With concomitant cystitis, antiseptic solutions, oils with anti-inflammatory and fortifying effects, painkillers are injected into the bladder.
- Physical therapy. As a physiotherapeutic effect, magnetotherapy, electrophoresis, laser and microwave therapy are used as part of complex therapy. During physiotherapy sessions, the severity of inflammation decreases, trophic improves (which is especially important for leukoplakia associated with dystrophic disorders), the concentration of the drug in the pathological area increases.
- Surgical treatment. Surgical treatment is performed at 2-3 stages. ILT (interstitial laser therapy) and bladder TUR (transurethral resection) are gentle operations for leukoplakia. With ILT, the probability of complications is less. Cystectomy is currently performed rarely and only with extensive lesions.
Prognosis and prevention
The prognosis depends on the stage of the disease and the subtype of leukoplakia, in the absence of keratinization, it is favorable. With leukoplakia with keratinization at stage 1-2, the prognosis is satisfactory with timely treatment, supportive treatment and regular monitoring in order to detect possible malignancy early. At an advanced stage, after successful surgical treatment, the outcome is relatively favorable. A common form of the disease with the development of complications leads to disability of the patient and social maladaptation.
Prevention implies timely referral to a urologist at the first symptoms of trouble on the part of the genitourinary organs, adequate treatment of inflammatory pathology, rejection of bad habits, rational medication. Considering that cystitis ‒ the main pathogenetic factor in the development of leukoplakia ‒ can be caused by STIs, it is advisable to adhere to monogamous relationships or use barrier means of protection in case of accidental sexual contact.