Bladder Amyloidosis

Bladder amyloidosis is deposition of amyloid protein in the bladder wall. Most cases are primary localised amyloidosis of light chain (AL) type, which is a benign process confined to the bladder in which a local plasma cell clone produces the deposits.

Less often, bladder involvement is part of systemic AL amyloidosis, or secondary (AA) amyloidosis from chronic inflammation, such as familial Mediterranean fever, rheumatoid disease, bronchiectasis or tuberculosis.

It is rare, mostly in adults aged 50 to 70, and its main importance is that it mimics bladder cancer.

Pathophysiology. Misfolded proteins form insoluble beta pleated sheet fibrils that deposit in the lamina propria and around vessels, causing fragile vessels that bleed. Localised AL disease arises from a local clonal plasma cell population.

Systemic AL disease arises from bone marrow clones and may involve the heart, kidney, liver and nerves.

Painless gross haematuria is the commonest sign, followed by irritative symptoms and sometimes obstruction or a palpable mass. Systemic disease adds nephrotic syndrome, heart failure, neuropathy, macroglossia, periorbital purpura, hepatomegaly and fatigue.

• Cystoscopy: erythematous, flat, nodular or polypoid lesions that bleed easily and look like cancer.
• Biopsy with Congo red stain showing apple green birefringence under polarised light. Mass spectrometry or immunohistochemistry types the protein (AL versus AA). Biopsy of an abnormal area is safe, and bleeding is controlled by diathermy.
• Exclude systemic disease: serum and urine protein electrophoresis with immunofixation, serum free light chains, full blood count, creatinine, urine protein quantification, NT-proBNP and troponin, echocardiography, and a haematology opinion with bone marrow biopsy or fat pad biopsy when indicated.
• Ultrasound and CT for masses, hydronephrosis and other organ involvement.
• Urine cytology and exclusion of urothelial carcinoma, which can coexist.

Differential diagnosis.

• Urothelial carcinoma
• Cystitis glandularis
• Schistosomal or tuberculous cystitis
• Malakoplakia
• Encrusted cystitis
• Haemorrhagic cystitis of other cause

• Localised disease: transurethral resection or fulguration of lesions, which controls haematuria in most. Recurrence is possible, so repeat endoscopic treatment is used as needed.
• Intravesical dimethyl sulphoxide (50 mL of a 50% solution retained for 20 to 30 minutes) has been given weekly for 6 weeks in case series to control bleeding. Evidence is limited.
• Clot retention: three way catheter of 22 to 24 Fr with irrigation, then endoscopic clot evacuation and fulguration.
• Systemic AL amyloidosis: haematology led plasma cell directed treatment, for example daratumumab with cyclophosphamide, bortezomib and dexamethasone, selected by organ function.
• Secondary AA amyloidosis: treat the inflammatory cause. Familial Mediterranean fever: colchicine 1 to 2 mg orally once daily, with dose reduced in renal and hepatic impairment and when taken with strong CYP3A4 or P-glycoprotein inhibitors.
• Cystectomy is rare, for uncontrolled bleeding.

Monitoring. Cystoscopy every 3 to 6 months for the first year, then yearly. Serum free light chains and urine protein yearly, since progression to systemic disease from localised bladder disease is rare. Creatinine and haemoglobin when bleeding recurs.

Referral and escalation. Refer to urology, and to haematology for any evidence of systemic disease. Urgent referral for clot retention, uncontrolled bleeding or organ involvement.