Primary amyloidosis of the bladder mimicking probable malignancy: A case report

Abstract

Primary amyloidosis of the bladder is a rare clinical occurrence, with only a limited number of cases documented in literature thus far. Herein, is the presentation of a case involving a 75 year old male who presented with painless gross hematuria. Subsequent laboratory results and imaging completed were misleading, creating a high suspicion for bladder malignancy. Further workup revealed bladder biopsies to have positive apple-green birefringence with Congo-red immunostaining, diagnostic of amyloidosis.

Introduction

Amyloidosis is a disease process characterized by extracellular deposition of amyloid protein within tissues, which can eventually cause symptomatic organ dysfunction. It can occur in a systemic or localized fashion, and is further classified as either primary or secondary amyloidosis depending on the underlying disease process. The symptoms commonly reported with bladder amyloidosis are painless gross or microscopic hematuria, dysuria, and irritative voiding symptoms.¹ The definitive diagnosis of amyloidosis is made by histopathology, which reveals the presence of amyloid fibrils on Congo-red immunostaining and apple-green birefringence upon polarization. Treatment of this condition is typically conservative with transurethral resection.² Follow up cystoscopy procedures can also be done to evaluate for reoccurrence.

Case presentation

A 75 year old male with a past medical history of urge incontinence and hypertension, presented with a one week history of painless gross hematuria, urinary urgency, and urinary frequency. He denied fevers, chills, or flank plain. The results of a urinalysis were positive for occult blood. Cytology analysis using fluorescence in situ hybridization (FISH) of cells recovered from a urine sample indicated a positive result for chromosomal abnormalities associated with bladder cancer. A computerized tomography urogram showed bladder wall thickening and irregular polypoid contours, however it could not differentiate between an inflammatory process or mucosal changes associated with transitional cell carcinoma. With probable concern for malignancy, it was recommended the patient undergo cystoscopy with transurethral resection. Cystoscopy findings included a bullous, erythematous, and edematous mucosa, extending into the vicinity of the ureteral orifices. Bilateral retrograde pyelograms were negative for any ureteral obstruction or filling defects. Deep resection biopsies were collected from three different parts of the bladder wall for histopathology evaluation (Fig. 1). Congo-red stain was positive for amyloid deposition in the lamina propria, a sub-epithelial connective tissue (Fig. 2), with associated acute hemorrhagic and eosinophilic cystitis. The specimens revealed an apple-green birefringence upon polarization, consistent with the diagnosis of amyloidosis (Fig. 3). Furthermore, there was no evidence of malignancy.

Fig. 1.

Bladder biopsy specimen under H&E stain.

Fig. 2.

Bladder biopsy specimen under Congo red stain, indicating the presence of amyloid.

Fig. 3.

Bladder biopsy specimen showing apple-green birefringence upon polarized light with Congo-red immunostaining.

Discussion

Amyloidosis refers to a group of conditions manifested by the abnormal deposition of amyloid protein in tissues and organs. Primary amyloidosis can occur in those with disordered immune cell function such as multiple myeloma, while secondary amyloidosis can occur as a complication of a chronic inflammatory or tissue destructive disease.² Deposition of amyloid within the urinary tract can occur in many different locations, however the kidney is almost always involved secondary amyloidosis and in about 50% of the cases of primary amyloidosis.² This highlights the paucity of primary and localized bladder amyloidosis as a urological disease. According to Tolofari et al. study, there have only been approximately 160 cases of primary and localized amyloidosis of the urinary tract documented in literature thus far.³

The presentation of bladder amyloidosis is very similar to that of bladder malignancy in regards to its symptomatology. Painless gross hematuria and irritative lower urinary tract symptoms are symptoms that are commonly implicated in malignancies such as transitional cell carcinoma.³ This often makes the diagnosis of bladder amyloidosis elusive. More than 50% of bladder amyloidosis cases are initially diagnosed as bladder tumors, as CT findings show bladder wall thickening, mass lesion, or filling defects, making it hard to differentiate from an invasive bladder tumor.³ Furthermore, it can be difficult to diagnose this condition as its radiological appearance may mimic an inflammatory or neoplastic lesion, and its appearance on cystoscopy may show nodular to polypoidal masses.²

Histologic diagnosis of this condition is essential. Bladder biopsies by transurethral resection can offer a definitive way to rule out malignancy. The presence of amyloid is confirmed by the appearance of apple-green birefringence upon polarized light with Congo-red immunostaining. Transurethral resection is typically the treatment of choice for primary bladder amyloidosis, with the post-resection recurrence rates estimating around 50%.⁴ A study by Kobayashi et al., reports a case of primary bladder amyloidosis recurring at the initial site, nine months after undergoing primary resection.⁵ Although there is no consensus for follow-up surveillance post-resection, cystoscopies can often be utilized to monitor for reoccurrence.^3,4

Conclusion

Primary amyloidosis of the bladder is a rare clinical occurrence, and its presentation can often mimic that of bladder malignancy. It is imperative to include bladder amyloidosis as a differential diagnosis when considering painless gross hematuria and irritative urinary symptoms to be signs of bladder cancer. Often times, results of laboratory and imaging modalities can be misleading, warranting a high degree of clinical suspicion. Its definitive diagnosis is dependent on biopsy and immunostaining with Congo-red, which reveals the presence of amyloid protein.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of interest

None.

Declarations of interest

None.