Extensive inflammatory eosinophilic bladder tumors in children: experience with three cases.

ABSTRACT

Eosinopbilic cystitis, an uncommon lesion, is rare in children; <25 cases have been reported. The intense inflammatory changes in the bladder wall associated with this lesion may produce heaped-up excrescences, which resemble vesical rhabdomyosarcoma. Our experience with 3 patients shows that the initial diagnosis of eosinophilic cystitis may not be easily made, and that the lesions produced may mask other disease processes. We also report the fifth case of eosinophilic infiltration of the bladder occurring in association with chronic granulomatous disease.

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EOSINOPHILIC CYSTITIS, an uncommon lesion, is rare in children; <25 cases have been reported. (1-5) The intense inflammatory changes in the bladder wall associated with this lesion may produce extensive, heaped-up excrescences, which resemble vesical rhabdomyosarcoma and for which the term inflammatory eosinophilic tumor has been recommended. (6) Three boys <5 years of age presented to our hospital over an 18-month period and were subsequently found to have vesical excrescences, histologic examination of which was consistent with a diagnosis of eosinophilic cystitis. One patient ultimately was proven to have chrornic granulomatous disease, which is of note, since the association of chronic granulomatous disease and eosinophilic infiltralion of the bladder has only been reported 4 previous times. (7-9) This report shows that the initial diagnosis of eosinophilic cystitis may not be easily made and that the lesions produced may mask other disease process.

CASE REPORTS

Case 1. A 4-year-old boy presented with an episode of gross hematuria and dysuria, preceded by a 1-month history of frequency and enuresis. Initial laboratory tests showed no bacteria on urinalysis and a serum creatinine level of 0.4 mg/dL. An excretory urogram demonstrated bilateral ureteropyelocaliectasis to the level of the bladder, the most pronounced obstruction being noted on the left side, and an irregularity of the bladder wall. Two days later, his serum creatinine level had increased to 1.8 mg/dL (normal, 0.6-1.4 mg/dL), prompting the placement of a left-sided percutaneous nephrostomy. Magnetic resonance imaging of the bladder delineated a mass lesion on the posterior wall and floor of the bladder.

At cystoscopy, the trigone and posterior wall of the bladder were obscured by firm, pink, irregular excrescences that resembled rhabdomyosarcoma. Examination of frozen sections of the transurethral biopsies of the lesion did not yield a conclusive diagnosis; therefore, an implanted infusion port was placed. Permanent section evaluation showed a heavy infiltration of eosinophils, confirming a diagnosis of eosinophilic cystitis. It was elected not to initiate any other treatment, but to perform serial nephrostograms at follow-up visits. Eight days following the bladder biopsy, a nephrostograrn demonstrated prompt drainage, and ultrasonography showed greatly decreased ectasia of the collecting structures on the right side. One month following biopsy, ultrasound examination of the kidneys and bladder was normal, and the implanted infusion port was removed. The child has been asymptomatic for 3 years, and results of ultrasonography have been normal.

Case 2. A 7-month-old boy was admitted to our hospital with an 8-day history of increasing irritability and diarrhea. Serum creatinine level on admission was 2.7 mg/dL. Ultrasonography of the kidneys and bladder demonstrated a large bladder mass with marked bilateral ureteropyelocaliectasis and thin renal parenchyma on the left side. With catheter drainage of the bladder, the serum creatinine level decreased to 1 mg/dL in 48 hours. Large, heaped-up excrescences of the posterior wall of the bladder and trigone were noted on cystoscopy. The ureteral orifices could not be identified. Malignancy could not be conclusively ruled out on examination of the frozen sections of transurethral biopsy specimens of the bladder lesions, so an implanted infusion port was placed. On examination of permanent sections, however, marked infiltration of the submucosa and muscularis by eosinophils was seen, establishing a diagnosis of eosinophilic cystitis. To allow for upper tract drainage and to permit removal of the catheter from the bladder, a right percutaneous nephrostomy was placed. No other treatment was instituted, and within 1 month, the vesical lesions were no longer identifiable on ultrasonography. The upper tracts, however, were still greatly dilated, and it seemed apparent that the massive dilatation was not a result of the transient lesions of eosinophilic cystitis. A voiding cystourethrogram showed bilateral grade V vesicoureteral reflux and posterior urethral valves. Three years later, following fulguration of the posterior ureteral valves and bilateral ureteral reimplantation, he continues to do well.

Case 3. A 4 Y2-year-old boy was referred for evaluation of dysuria that had occurred every 2 to 3 months during the previous 2 years. There had been no episodes of urinary tract infection or gross hematuria, but he did have marked urgency and frequency. He occasionally had also been noted to have microscopic hematuria. He had been evaluated 1 week previously with voiding cystourethrography and renal and bladder ultrasonography. The bladder had been poorly filled on cystography, but the study had still suggested an irregularity of the posterior bladder wall, which was also noted on ultrasonography. For this reason, endoscopy of the bladder was performed. Surprisingly, the trigone was spared, but the posterior wall of the bladder was interspersed with blebs and excrescences suggestive of botyroid rhabdomyosarcoma. Examination of frozen sections of transurethral biopsies showed no evidence of malignancy, but there was evidence of cystitis. Permanent sections were examined and confirmed acute and chronic inflamma tion, and eosinophils were identified with Giemsa staining, resulting in a diagnosis of eosinophilic cystitis. No treatment was given. Bladder ultrasonography 3 weeks after the biopsy no longer showed any evidence of the irregularity of the bladder wall, and there was only minimal thickening. The child's irritative symptoms persisted, however, and were intermittently relieved with oxybutynin chloride treatment.

Fourteen months later, the patient presented with dysphagia. At that time, a partial obstruction of the esophagus was diagnosed as a manifestation of chronic granulomatous disease, confirmed by flow cytometry. Although ultrasound examinations of the bladder remain normal, he has intermittently developed pronounced episodes of dysuria and frequency that are quickly relieved with the administration of steroids.

DISCUSSION

The presentation and early clinical findings in children with eosinophilic cystitis have been well documented. (1-5) The most common initial complaints are hematuria, dysuria, and frequency. The etiology is unknown. (2) Imaging of the urinary tract with ultrasonography may demonstrate upper tract obstruction and extensive lesions of the bladder that mimic a tumor. The patients in cases 1 and 2 were exceptional, in that they were both noted to have rapidly rising serum creatinine levels and pronounced bilateral upper tract obstruction that necessitated a proximal diversion. Although the diagnosis is more straightforward if eosinophilic infiltration is noted in the vesical wall, it has been suggested that Qiemsa staining for eosinophils, or electron microscopy, if the eosinophils are deteriorating, be used to confirm the diagnosis. (2) In addition, inflammatory myofibroblastic tumors in children may, on occasion, contain extensive infiltration of eosinophils. (10) The initial pathologic diagnosis may be consist ent with malignancy, as noted by others, which will drive the early steps of management (as in our patients, who received implanted infusion ports) (6) As has been previously emphasized, eosinophilic cyscitis is self-limiting, and no specific therapy is needed. (1) Barring other contraindications, the use of steroid therapy has been recommended, due to the apparently more rapid resolution of symptoms and obstruction with this treatment. (2,11)

In retrospect, aspects of the management of the patients in cases 1 and 2 proved to be unnecessary. Eosinophilic cystitis does not lead the list of differential diagnoses, however, and our treatment course was primarily directed toward providing proximal drainage and preparing for management of a vesical malignancy. Because of the presence of brightly eosinophilic cells, as seen in rhabdomyosarcoma, the frozen section examinations in cases 1 and 2 did not rule out that a malignancy was not present. Biopsy of the bladder can rule out rhabdomyosarcoma and the clinician should observe that an apparent eosinophilic cystitis with or without tumefaction may be a manifestation of chronic granulomatous disease. Our experience also shows that the upper tract dilatation seen in conjunction with eosinophilic cystitis may have more than one cause.

References

(1.) Sutphin M, Middleton AW Jr: Eoisnophilic cystitis in children: a self-limited process. J Urol 1984; 132:11-119

(2.) Axelrod SL, Ring KS, Collins MH, et al: Eosinophilic cystitis in children. Urology 1991; 37:549-552

(3.) Sujka SK, Fisher JE, Greenfield SP: Eosinophilifc cystitis in children. Urology 1992; 40:262-264

(4.) Gerharz EW, Grueber M, Melekos MD, et al: Tumor-forming eosinophilic cystitis in children, case report and review of literature. Eur Urol 1994; 25:138-141

(5.) van den Ouden D: Diagnosis and management of eosinophilic cystitis. a pooled analysis of 135 cases. Eur Urol 2000; 37:386-394

(6.) Netto JMB, Perez LM, Kelly DR, et al: Pediatric inflammatory bladder tumors: myofibroblastic and eosinophilic subtypes. J Urol 1999; 162:1424-1429

(7.) Kontras SB, Bodenbender JG, McClane CR, et al: Interstitial cystitis in chronic granulomatous disease. J Urol 1971; 105:575-578

(8.) Cyr WL, Johnson H, Balfour J: Granulomatous cystitis as a manifestation of chronic granulomatous disease of childhood. J Urol 1973; 110:357-359

(9.) Bauer SB, Kogan SJ: Vesical manifestations of chronic granulomatous disease in children--its relation to eosinophilic cystitis. Urology 1991; 37:463-466

(10.) Albores-Saavedra J, Manivel JC, Essenfeld H, et al: Pseudo-sarcomatous myofibroblastic proliferations in the urinary bladder of children. Cancer 1990; 66:1234-1241

(11.) LaDocsi LT, Sullivan B, Hanna MK: Eosinophilic granulomatous cystitis in children. Urology 1995; 46:732-735

RELATED ARTICLE: KEY POINTS

* Eosinophilic cystitis is a rare lesion in children.

* The resultant inflammatory change produces heaped up excrescences, which resemble rhabdomyosarcoma.

* Chronic granulomatous disease may be associated with eosinophilic infiltration of the bladder.

* Eosinophilic cystitis is self-limiting and no specific therapy is needed.

* Steroid therapy may give a more rapid resolution of symptoms and obstruction.

From the Departments of Urology and Pathology, University of Arkansas College of Medicine and Arkansas Children's Hospital, Little Rock.

Reprint requests to John F. Redman, MD, Department of Urology, University of Arkansas College of Medicine, 4301 W Markham, Slot 540, Little Rock, AR 72205-7199.