https://orcid.org/0009-0007-8547-1141
Abstract
Eosinophilic cystitis is a rare inflammatory disorder of the bladder that may closely mimic malignancy, creating a diagnostic challenge during bladder cancer surveillance. We report the case of a 68-year-old man previously treated for high-grade pT1 urothelial carcinoma with transurethral resection and intravesical Bacillus Calmette–Guérin therapy, who subsequently developed recurrent gross hematuria and bladder wall thickening suspicious for tumor recurrence. Histopathological examination revealed marked eosinophilic infiltration without evidence of malignancy, confirming eosinophilic cystitis. Bacillus Calmette–Guérin therapy was discontinued and conservative treatment led to complete clinical resolution, with no recurrence detected during follow-up. This case emphasizes the importance of histological confirmation before escalating oncological treatment in patients with suspected bladder cancer recurrence.
Introduction
Eosinophilic cystitis is a rare inflammatory disorder of the bladder that remains insufficiently documented, with limited awareness of its clinical presentation, histopathological features, and natural history [1]. Its main clinical significance lies in its ability to mimic bladder malignancy. It may coexist with superficial bladder cancer and simulate muscle-invasive disease, creating substantial diagnostic uncertainty during urothelial tumor surveillance [2]. Eosinophilic cystitis has also been reported after intravesical Bacillus Calmette–Guérin (BCG) therapy for non-muscle-invasive bladder cancer, further complicating the interpretation of suspicious findings during follow-up [3]. We report a case of eosinophilic cystitis diagnosed during surveillance after transurethral resection and intravesical BCG therapy, initially suspected to represent tumor recurrence.
Case report
A 68-year-old active smoker with an estimated 30 pack-year history had been followed for non-muscle-invasive bladder cancer for ~3 years. Initial transurethral resection of the bladder tumor revealed high-grade pT1 urothelial carcinoma with a focal 10% micropapillary component and concomitant carcinoma in situ.
He subsequently received intravesical BCG immunotherapy, completing 19 instillations over 18 months. The 20th instillation was withheld because of poor tolerance. He later developed recurrent episodes of gross hematuria with clots. In this oncological context, the main differential diagnoses were tumor recurrence, a post-BCG inflammatory reaction, and hemorrhagic cystitis.
Laboratory investigations showed no peripheral eosinophilia, systemic inflammatory syndrome, or coagulation abnormality. Urine culture was sterile. Because urogenital tuberculosis was also considered, repeated urinary mycobacterial investigations and imaging assessment were performed and were negative. The only relevant laboratory abnormality was normocytic normochromic anemia, which required blood transfusion.
CT urography demonstrated bladder wall thickening, prompting endoscopic reassessment and transurethral resection. Cystoscopy revealed diffuse inflammatory changes of the bladder mucosa, with erythema and congested, edematous thickening of the bladder wall, but no clearly identifiable papillary or solid lesion (Fig. 1). Although non-specific, this appearance raised concern for recurrent tumor because of the patient’s oncological history.
Cystoscopy showing regular thickening of the bladder wall on a background of erythematous and congested inflammatory mucosa (arrows), without any clearly identifiable papillary lesion.
Histopathological examination showed largely denuded urothelium without cytological atypia, preserved polarity, and an edematous lamina propria containing a dense eosinophil-rich inflammatory infiltrate with scattered lymphoplasmacytic cells (Fig. 2A and B). A granulomatous reaction with foreign body-type giant cells was also reported on histopathological examination. No histological evidence of malignancy was identified.
Histological findings suggestive of eosinophilic cystitis: (A) bladder mucosa lined by a globally preserved urothelium, without overt atypia visible in this field, resting on an edematous, congested, and inflamed lamina propria. (B) Markedly altered bladder lamina propria containing multiple microcystic spaces (yellow arrow) within an edematous and inflamed stroma with bladder mucosa rich in eosinophils (black arrow), suggestive of eosinophilic cystitis, and no histological evidence of malignancy.
These findings were consistent with eosinophilic cystitis. BCG therapy was discontinued, and conservative treatment was initiated with oral prednisone, started at 30 mg/day and progressively tapered over 6 weeks, together with cetirizine 10 mg/day, bladder irrigation, and symptomatic measures. The clinical course was favorable, with complete resolution of hematuria. Follow-up cystoscopies performed at 1, 3, 6, and 12 months showed no evidence of tumor recurrence.
Discussion
Eosinophilic cystitis is rarely encountered in routine clinical practice [1, 4, 5]. In uro-oncology, its main importance lies in its pseudotumoral appearance and its ability to mimic recurrence or progression during bladder cancer follow-up [4–7]. Hematuria, irritative lower urinary tract symptoms, focal or diffuse bladder wall thickening, and even radiological or metabolic findings suggestive of locally advanced malignancy have all been described [1, 2, 4–8]. In our patient, previous transurethral resection and intravesical BCG therapy made the newly detected bladder abnormality particularly suspicious [2, 3].
The pathophysiology of eosinophilic cystitis remains incompletely understood [1, 4, 5]. Proposed mechanisms include an immuno-allergic reaction, an exaggerated inflammatory response of the bladder wall, and eosinophil-mediated tissue injury [4, 5]. Reported predisposing factors are multiple and non-specific, including allergens, infection, urological instrumentation, parietal injury, local irritative treatments, and underlying neoplasia [1, 4, 5]. Repeated instrumentation may act as a contributing factor [1]. In patients with bladder cancer, interpretation is particularly difficult because the respective roles of the underlying urothelial disease, repeated endoscopic procedures, and intravesical treatments cannot always be separated [1, 2]. BCG exposure should therefore be regarded as a possible associated factor, although a causal relationship cannot be established [3]. In our patient, the inflammatory process was likely multifactorial.
The principal diagnostic challenge lies in the non-specific nature of clinical, cystoscopic, and imaging findings [1, 2, 4–6]. Eosinophilic cystitis may present as focal or diffuse bladder wall thickening, a pseudotumoral lesion, or an apparently locally advanced process [2, 4, 6, 7]. Symptoms such as hematuria and lower urinary tract symptoms are insufficient to distinguish it reliably from bladder cancer recurrence [5, 8]. The differential diagnosis includes recurrent urothelial carcinoma, carcinoma in situ, granulomatous cystitis, interstitial cystitis, bladder tuberculosis, and non-specific inflammatory cystitis [1, 2, 5].
Histopathology therefore remains the cornerstone of diagnosis [1, 2, 4, 5]. In our patient, the absence of cytological atypia or malignant tissue, combined with a dense eosinophil-rich infiltrate, established the diagnosis and prevented unnecessary escalation of oncological treatment. Similar published cases have required biopsy or endoscopic resection before malignancy could be excluded [1, 2, 4, 5]. However, this reassurance must be interpreted cautiously because eosinophilic cystitis may coexist with superficial bladder cancer, making continued cystoscopic surveillance essential [2].
Management is mainly conservative and is based on withdrawal of any potential triggering factor, together with symptomatic and anti-inflammatory therapy [1, 3, 5, 9]. Reported options include corticosteroids, antihistamines, nonsteroidal anti-inflammatory drugs, bladder irrigation, and supportive measures tailored to the clinical presentation [5, 9–11]. Therapeutic regimens described in the literature include prednisone combined with cetirizine or hydroxyzine, usually followed by gradual corticosteroid tapering [9–11]. Second-line treatments have been reported in refractory or relapsing disease, reflecting the absence of a standardized therapeutic strategy [10, 11].
In our patient, discontinuation of BCG and conservative treatment resulted in sustained clinical improvement, resolution of hematuria, and absence of recurrence on 12-month cystoscopic follow-up. This favorable outcome is consistent with reports supporting a non-radical approach once malignancy has been excluded [3, 9–11].
Conclusion
Eosinophilic cystitis should be considered when a suspicious bladder lesion develops during uro-oncological surveillance. Histological confirmation is essential before diagnosing recurrence or intensifying treatment, thereby avoiding overtreatment while maintaining appropriate oncological follow-up [1–3, 5]. Greater awareness of this rare entity may improve diagnostic accuracy and prevent inappropriate radical management.
Conflicts of interest
None declared.
Funding
None declared.
Consent
Informed consent was obtained from the patient for the publication of all images, clinical data and other data included in the main manuscript.
