UROLOGICAL SURVEY   ( Download pdf )

 

PATHOLOGY

Pseudocarcinomatous epithelial hyperplasia in the bladder unassociated with prior irradiation or chemotherapy
Lane Z, Epstein JI
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21231, USA
Am J Surg Pathol. 2008; 32: 92-7

  • Pseudocarcinomatous epithelial hyperplasia in the bladder is a little known phenomenon, recognized to be associated with prior irradiation and/or chemotherapy. Whether this process can occur outside of this setting has not been studied. We identified 8 of these cases mimicking invasive urothelial carcinoma from our consultation files from 07/04 to 07/06 with no prior history of radiation or chemotherapy. The mean age at diagnosis was 65 years (range, 42 to 81 y), with 5 of the 8 males. Seven patients had a potential etiology for these changes that could either have resulted in localized ischemia or injury to the urothelium. These included case 1: atrial fibrillation, hypertension, congestive heart failure, gastrointestinal bleeding, and coronary artery vascular disease; case 2: coronary angioplasty, atrial fibrillation, hyperlipidemia, and amputation of arm for ischemia; case 3: hypertension, uncontrolled diabetes, hyperlipidemia, and atrial fibrillation; case 4: underlying arteriovenous malformation of the bladder; cases 5 to 6: history of indwelling Foley catheter; and case 7: history of radical prostatectomy for prostate cancer but no radiation. One patient had no potential contributing factors. All 8 patients presented with gross hematuria. At cystoscopy, 7 patients had polypoid lesions with 1 appearing nonpolypoid. Histologically, all cases showed epithelial proliferation of urothelium with cells having prominent eosinophilic cytoplasm. This process that mimicked invasive cancer within the lamina propria was marked in 3 cases (38%). Moderate nuclear pleomorphism was seen in 6 cases (75%). Only 1 case revealed mitotic figures. Ulceration was seen in 1 case. All cases showed some degree of hemorrhage with hemosiderin deposition identified in 3 cases (38%). Fibrin deposition was present in 1 case within the stroma, 3 cases in the vessels, and 4 cases in both. Five cases show stromal fibrosis. Edema and vascular congestion were common features (90% and 100%, respectively). Six out of 8 cases were accompanied by moderate to marked acute and chronic inflammation. The original diagnosis included nested variant urothelial carcinoma (1 case), atypical suspicious for invasive carcinoma (5 cases), hemangioma (1 case), and eosinophilic cystitis (1 case). Patients were followed for a mean of 16.5 months (range, 10 to 34 mo), and none developed bladder cancer. As a rare response to ischemia and chronic irritation, pseudocarcinomatous epithelial proliferations in the bladder may be confused with invasive urothelial carcinoma. Pathologists must be aware of the histologic changes mimicking cancer, and recognize that it can occur outside of the setting of prior irradiation or chemotherapy.

  • Editorial Comment
    Irradiation and/or chemotherapy induce well known lesions in the urinary bladder. They include: acute cystitis with desquamation of the urothelial cells, hyperemia, edema in the lamina propria, atypical epithelial and/or stromal cells, hyalinization and thrombosis of the vessels, and prominent telangiectatic vessels that explain the hematuria that often occurs. Late complications of radiation injury include ulcers, marked contraction of the bladder because of fibrosis, and ureteral strictures that may lead to severe pyelonephritisd and death (1).
    A pitfall for the pathologist in radiation cystitis is pseudocarcinomatous proliferation of the urothelium simulating invasive urothelial carcinoma. In 2000, Baker and Young (2) reported 4 cases with this lesion. It is a reactive process and the authors point out some clues for the correct diagnosis: absence of mitotic figures, preservation or decrease of the nuclear-to-cytoplasmic ratio, prominent vacuolar change, and squamoid appearance of the epithelium.
    The report of Lane and Epstein’s is very important because it adds to pseudocarcinomatous epithelial hyperplasia in the bladder causes unassociated with prior irradiation or chemotherapy that must be known by the pathologist. One patient had no potential contributing factor, but 7 patients had ischemia and/or chronic irritation as possible causes for this reactive lesion mimicking invasive urothelial carcinoma. We had the opportunity to see in our Institution a biopsy of the urinary bladder of a 44-year-old male showing pseudocarcinomatous hyperplasia unassociated with prior irradiation or chemotherapy. This reactive lesion was associated to chronic cystitis due to a rectalvesical fistula secondary to diverticulitis.


References
1. Young RH: Non-neoplastic Epithelial Abnormalities and Tumorlike Lesions. In: Young RH (ed.), Pathology of the Urinary Bladder. New York, Churchill Livingstone, 1989; pp. 1-63.
2. Baker PM, Young RH: Radiation-induced pseudocarcinomatous proliferations of the urinary bladder: a report of 4 cases. Hum Pathol. 2000; 31: 678-83.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil