A 71-Year-Old Man With a Bladder Mass

Archives of Pathology & Laboratory Medicine, Aug 2005 by Fine, Samson W, Chan, Theresa Y

A 71-year-old white man with a history of hypertension and prostatic adenocarcinoma in 1998 presented with gross hematuria and urinary retention in June 2004. The patient had been treated with external beam radiation therapy in 1998 and was stable, with a prostate specific antigen level of 0.62 ng/mL, until the presenting episode. Cystoscopy was performed, revealing a vascular, sessile lesion on the posterior wall of the bladder, for which the differential diagnosis considered was between carcinoma and angioma. The lesion was resected and sent for pathologic analysis, where gross examination showed a 0.5-cm pale, tan fragment of mucosal tissue.

A preliminary pathology report noted neither history of the patient's prior malignancy nor any therapeutic history. Microscopic examination revealed atypical mucosa and submucosa, with extensive vascular ectasia, thrombosis with fibrin deposition, and acute inflammation. It was noted that the lesion appeared to be a high-grade urothelial carcinoma, but no mitoses were present. Nevertheless, a provisional diagnosis of urothelial carcinoma with stromal invasion was rendered. This case was sent in consultation to our institution for a second opinion. Upon review of the slides, we observed a fragment of bladder mucosa with dilated vascular spaces, hemorrhage, acute inflammation, fibrinous exudate, and focal fibrosis in the lamina propria (Figure 1). Both rounded and irregular tufts of bland urothelium without mitotic activity were also present in the lamina propria, with foci conveying an invasive appearance (Figures 2 and 3). A peculiar feature noted was that some areas showed urothelium surrounding dilated blood vessels, which contained fibrinous deposits (Figure 4).

What is your diagnosis?

Pathologie Diagnosis: Radiation Cystitis With Pseudocarcinomatous Features

The term radiation cystitis, originally coined by Koss1 in 1975, denotes the marked edema and hyperemia associated with grossly thickened bladder mucosal folds, resulting from prior irradiation. Desquamation and surface ulceration may be subsequently observed. The urothelial atypia seen in these cases, consisting of enlarged, hyperchromatic nuclei, may mimic carcinoma in situ. However, the bizarre and occasionally multinucleated nature of these cells, along with their smudgy, degenerative-appearing nuclei, distinguishes them as radiation induced. In later stages, stromal scarring, arteriolar medial hyalinization, fibrinous exudates, and atypical mesenchymal cells predominate.1 Although these changes, especially the epithelial atypia, gradually disappear during a period of a few months, the alterations may persist, in the form of epithelial hyperplasia and focal atypia, for many years following completion of therapy.2

More recently, authors have recognized a distinct pattern of radiation- or chemotherapy-induced change, characterized by epithelial proliferations that architecturally mimic invasive carcinoma3; this pattern has been termed radiation cystitis with pseudocarcinomatous features (RCPCF).4 In the most recent series, these changes have been described in patients ranging in age from 40 to 85 years, with an 80% male predominance.4 Interestingly, the majority of patients present with hematuria, as opposed to the urgency, frequency, and dysuria seen with classic radiation cystitis. Patients with RCPCF have all undergone radiation or systemic chemotherapy for carcinomas of the prostate, endometrium, cervix, or colon, with a mean time from therapy to presentation of 27 months (range, 0-84 months).3,4 Cystoscopically, small papillary lesions or mucosal irregularity and erythema may be seen, but other lesions have shown no grossly detectable abnormalities.3

Microscopically, the characteristic feature of RCPCF is pseudoinfiltrative epithelial cords and nests extending into lamina propria and wrapping around dilated blood vessels containing fibrin. The fibrinous material may be observed in both blood vessels and lamina propria. Cytoplasmic or nuclear vacuolization and prominent nucleoli are common findings, along with stromal edema, vascular congestion, extravasated red blood cells, inflammation, and hemosiderin deposition. Mild cytologie atypia and mitoses may be present, but these are not common features.4 Finally, thickened blood vessels and fibrosis may be seen in RCPCF, similar to those seen in classic radiation cystitis.

Radiation cystitis with pseudocarcinomatous features may mimic a number of other epithelial proliferah'ons found in the lamina propria. The infiltrative appearance of RCPCF may be confused with true invasive urothelial carcinoma (UC), as in the preliminary diagnosis of the current case. However, the absence of the marked cytologie atypia and mitoses usually seen in UC, coupled with the finding of epithelial nests encircling fibrin-laden blood vessels, should aid in distinguishing RCPCF. Another malignant condition that may cause particular confusion in its distinction from RCPCF is the nested variant of UC. These lesions are typically small, closely packed irregular nests of epithelial cells infiltrating the lamina propria.4-6 Cytologically, the tumor may be very uniform, with only focal atypia, prominent nucleoli, and scant mitoses, further compounding the diagnostic dilemma. In this case, the constellation of reactive findings and urothelial cuffing of vessels with associated fibrin deposition usually seen in RCPCF are particularly useful, because they have not been reported in the nested variant of UC. Additionally, the nested variant of UC commonly exhibits muscle invasion, a feature absent in reported cases of RCPCE-1-4 Finally, prominent von Brunn nests are a benign cellular proliferation that may be mistaken for the larger epithelial tufts seen in RCPCF. However, von Brunn nests are typically rounded and regularly spaced and do not exhibit invasive features.7