Bladder

Acute and chronic cystitis

 

• Common organisms are the same ones that cause pyelonephritis;
  • E.coli
  • Proteus
  • Klebsiella
  • Enterobacter
• Women are more likely to get cystitis due to our short urethras
• Candida albicans and Cryptococcus can cause cystitis particularly in the immunosuppressed and those on long term antibiotics
• Predisposing factors include;
  • Bladder caliculi
  • Urinary obstruction
  • Diabetes
  • Instrumentation
  • Immune deficiency
• Patients on cytotoxic antitumour drugs such as cyclophosphamide sometimes develop haemorrhagic cystitis
• Radiation of the bladder region can result in radiation cystitis (and may be haemorrhagic)
• Adenovirus can cause a haemorrhagic cystitis

 

Morphology

• Hyperaemia of the mucosa, possibly associated with exudates
• The type of inflammatory infiltrate depends upon whether it is acute or chronic
• Chronic infection gives rise to fribrous thickening of the muscularis propria and inelasticity of the bladder wall

 

• All forms of clinical cystitis are characterised by a triad of symptoms;
  • Frequency
  • Lower abdominal pain
  • Dysuria
• There may also be systemic signs of inflammation including temperature, chills and general malaise

 

Special forms of cystitis;

 

Interstitial cystitis (Hunner ulcer)

• Persistent painful form of cystitis which occurs more commonly in women and is associated with inflammation and fibrosis of all the layers of the bladder wall
• Characterised by intermittent, suprapubic pain, polyuria, urgency, haematuria and dysuria
• No evidence of bacterial infection
• Cytoscopically there may be fissures and punctuate haemorrhages
• In the late chronic phase some patients display mucosal ulcers – Hunner ulcers
• In the early phase submucosal haemorrhages are seen
• There is inflammation and granulation tissue in the muscosa, lamina propria and muscularis
• Mast cells play a prominent role
• Disease may be autoimmune in nature and is associated with SLE and other autoimmune disorders
• Requires to be distinguished from carcinoma in situ

 

Malacoplakia

• Pattern of vesical inflammation characterised by soft yellow, slightly raised mucosal plaques 3-4cm in diameter
• Histologically there is infiltration of large foamy macrophages and occasionally multinucleated giant cells with interspersed lymphocytes  
• Within the macrophages and other cells there are Michaelis-Gutmann bodies which are laminated mineralised concretions resulting from deposition of calcium in enlarged lysosomes
• It is related to chronic bacterial infection particularly by E.coli and proteus
• It occurs with increasing frequency in immunosuppressed transplant patients

 

Polypoid cystitis

• Inflammation resulting from irritation of the bladder muscosa
• Indwelling catheters are an important cause
• There is marked submuscosal oedema which results in the urothelium being thrown into broad, bulbous, polypoid projections

 

Neoplasms of the bladder

 

• Affect 1 in 5000 in the UK and account for 3% of all cancer deaths. The prevalence is increasing
• Uncommon before the age of 40
• M>F 4:1
• 95% of tumours are epithelial in origin and the rest are mesenchymal
• Of the epithelial tumours most are derived from urothelial cells (transitional) but there are also some squamous and glandular carcinomas which develop

 

Transitional cell Tumours

 

• Represent 90% of all bladder tumours and can vary from being small benign lesions which don’t recur to aggressive cancers which kill
• Can be multifocal at presentation
• Most commonly affect the bladder but the same type of tumour can be found at any site with urothelium – from the renal pelvis to the distal urethra
• There are two distinct precursor lesions to invasive urothelial carcinoma;
• Noninvasive Papillary tumours
  • Most common
  • The demonstrate a range of atypia and therefore there are a variety of classifications to reflect their behaviour
• Flat urothelial carcinoma
  • Simple referred to as carcinoma in situ
  • This is defined as high grade and therefore there is not a grading system assigned
• In about half of patients, by the time they present the tumour will already have invaded the bladder wall
• Although progression into the lamina propria worsen prognosis they major decrease in survival is seen once the tumour has invaded the muscularis propria or detrusor muscle. Once this occurs there is a 50% 5 year mortality rate

 

Morphology

 

Grading of Transitional Cell Tumours

• Urothelial papilloma
• Urothelial neoplasm of low malignant potential
• Papillary urothelial carcinoma                            Grade 1
• Papillary urothelial carcinoma                            Grade 2
• Papillary urothelial carcinoma                            Grade 3

 

• Most arise from the lateral or posterior walls at the bladder base
• Papillomas
  • Represent 1% of bladder tumours and are seen more commonly in young patients
  • Small, delicate tumours superficially attached to the mucosa by a stalk
• Papillary urothelial neoplasms of low malignant potential
  • Share many histological features with papillomas except that either the urothelium is thicker and there is nuclear enlargement.
  • These may recur with the same morphology, are not generally associated with invasion
• Low grade papillary urothelial carcinomas
  • Characterised by an orderly appearance both architecturally and cytologically. The cells are evenly spaced, maintain polarity and are cohesive.
  • There is some degree of nuclear atypia
  • Only rarely do these tumours invade although they can reoccur
  • Less than 10% invade
• High-grade papillary urothelial carcinomas
  • Cells are dyscohesive with large hyperchromatic nuclei. Some cells show frank aplasia
  • Mitotic figures are frequent and there is a loss of polarity
  • These tumours have a higher risk of invasion, progression and metastases
  • Around 80% invade
• Aggressive tumours not only extend into the bladder wall but can invade the adjacent prostate, seminal vesicals, ureters and retroperitoneim. They may also produce fistula connections with the vagina or rectum.
• About 40% metastasise to the regional lymph nodes
• Later on distant metastases to the liver, lungs and bone marrow can occur but is only associated with anaplastic tumours
• Carcinoma in situ
  • Defined by the presence of any cytologically malignant cell within a flat urothelium
  • Cells are non-cohesive so can be shed into the urine
  • Grossly carcinoma in situ usually appears as an area of mucosal thickening, reddening and granularity without an intraluminal mass
  • It is commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra
  • If untreated 50-70% of CIS progress to muscle-invasive cancer
• Invasive urothelial cancer;
  • Pathological tumour staging of bladder carcinoma
  • Noninvasive; papillary                           Ta
  • Carcinoma in situ; non invasive, flat                   Tis
  • Lamina propria invasion                                    T1
  • Muscularis propria invasion                               T2       
  • Microscopic extravesical invasion                      T3a
  • Grossly apparent extravesical invasion   T3b     
  • Invades adjacent structures                               T4

 

Other types of carcinoma;

 

• Squamous cell carcinoma
  • Represent about 5% of bladder cancers in the west but in countries endemic for shistosomiasis they occur more frequently
  • Nearly always associated with chronic bladder irritation and infection
• Mixed urothelial cell carcinomas with areas of squamous carcinoma
  • More frequent that pure squamous carcinoma
  • Most are invasive and can be ulcerative
  • True papillary patterns are almost never seen
• Adenocarcinomas
  • Rare and histologically identical to adenocarcinomas seen in the GI tract
  • Some arise from urachal reminants – these occur in the dome or anterior wall and arise within the wall rather than the mucosa. They extend out of the bladder toward the umbilicus

 

Epidemiology and Pathogenesis

 

• Epidemiology is similar to that of bronchial carcinoma;
  • More common in men
  • More common in industrialised countries
  • Associated with urban rather then rural dwelling
• 80% occur between 50 and 80 years
• Not generally familial

 

• A number of causative agents have been implicated;
  • Cigarette smoking – increases risk from 3 to 7 fold
  • Industrial exposure to arylamines – cancer appears 15 to 40 years after exposure
  • Shistosoma haematobium – 70% are squamous tumours the rest are urothelial in origin
  • Long term use of analgesics
  • Heavy long term exposure to cyclophosphamide
  • Prior bladder exposure to radiation

 

Genetic alterations

• Particularly common are;
  • Deletions of Chr 9 – present in superficial papillary tumours associated with loss of TSGs
  • Chr17p – related to p53 mutation and associated with invasion
  • Chr13q – involves the Rb gene and is also associated with invasion
  • Chr11p
  • Chr14q – seen in flat and invasive lesions, not papillary lesions. Associated with TSGs
• Based on these findings a two-way model of bladder carcinogenesis has been proposed;
  • The first pathway is initiated by deletions of TSGs on Chr9p and 9q leading to superficical papilloma tumours
  • A few may acquire p53 mutations and progress to invasion
  • A second pathway possibly initiated by p53 mutation leads to CIS and with loss of Chr9 proceeds to invasion

 

Clinical course

 

• Frequently present with painless haematuria
• May be accompanied by frequency, urgency and dysuria
• When the ureteral orifice is involved pyelonephritis and hydronephritis may follow
• Patients with uroepithelial tumours have a tendency to new tumours after excision which may exhibit a higher grade
• Papillomas, papillary urothelial neoplasms of low malignant potential and low grade papillary urothelial cancer have a 98% 10 year survival rate regardless of the number of recurrences
• Only about 40% of patients with high grade tumours survive 10 years
• Approximately 70% with squamous carcinoma are dead within 1 year
• The clinical challenge with these neoplasms in early detection and follow up. Neoplasms such as CIS and early small papillary lesions may produce only subtle muscosal changes and may be difficult to detect
• In some cases it may be possible to detect cancer using  cytological examinations and urine markers but these have relatively low specificity and false positives may occur if there is injured urothelium

 

Treatment

 

• Depends on grade, stage and whether the lesion is flat of papillary
• For small papillary low grade lesions  - resection plus follow up cytoscopies
• When the patient presents with multifocal lesions, topical chemotherapy is instilled into the bladder postoperatively which can reduce tumour recurrence
• After the biopsy site has healed patients with high risk of recurrence or progression receive topical immunotherapy consisting of intravesical installation of BCG
• Radical cystectomy is performed for;
  • Tumour invading into the muscularis propria
  • CIS or high grade papillary cancer refractory to BCG
  • CIS extending into the urethra and extending down the prostatic ducts beyond the reach of BCG
• Advanced bladder cancer is treated with chemotherapy

 

Bladder calculi

• Most commonly associated with urine stasis
• Infections increase the likelihood of developing calculi
• Bladder stones may be derived from further up the urinary tract
• Incidence is declining in the west, possibly due to infection control and improved diet
• When it does occur is more likely to in order me with bladder obstruction
• If a bladder stone is found in the western world you should do a full investigation to look for causes of urinary stasis. Causes include;
  • Benign prostatic hypertrophy
  • Urethral stricture
  • Neurogenic bladder
  • Bladder neck contracture
  • Bladder diverticula
• Patients may be asymptomatic but more commonly experience suprapubic pain, dysuria, haematuria, frequency and hesitancy
• Another symptom is termination of voiding with some degree of pain
• Pain is dull or sharp and is aggravated with movement