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Acquired non-neoplastic anomalies

Treatment effect

Reviewer: Monika Roychowdhury, M.D., University of Minnesota Medical Center - Fairview (see Reviewers page)
Revised: 14 June 2011, last major update June 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.


● Histologic changes associated with chemotherapy (systemic or topical), radiation therapy or surgery (J Clin Pathol 2002;55:641)


● See also granulomatis cystitis, radiation cystitis

Clinical features

● Cyclophosphamide causes hemorrhagic cystitis, and is associated with high grade bladder carcinoma and sarcoma

Case reports

● 71 year old man with bladder mass 6 years post-radiation therapy for prostate cancer (Arch Pathol Lab Med 2005;129:1067)

Gross description

● Chemotherapy may destroy tips of papillae in papillary tumors

Micro description

● General characteristics include pseudoinvasive urothelial nests wrapping around vessels associated with fibrin deposition; also hemorrhage, fibrin thrombi, fibrosis, acute and chronic inflammation; usually edema and vascular congestion; occasionally ulceration; no mitotic figures (Am J Surg Pathol 2004;28:909)
Radiation therapy: causes endothelial swelling and necrosis, mural thickening and hyalinization with late luminal narrowing; also pseudoinfiltrative epithelial cords and nests extending into lamina propria and wrapping around dilated blood vessels containing fibrin; radiation fibroblasts with cytoplasmic or nuclear vacuoles and prominent nucleoli, stromal edema, extravasated red blood cells, destruction of bladder tumor papillae (Hum Pathol 2000;31:678)
Surgery: associated with granulomatous reaction, postoperative spindle cell nodules, trapping of epithelial cells by inflammatory reaction resembling invasive disease, regenerative atypia resembling carcinoma in situ, reactive bone / osteoid
Systemic chemotherapy: nuclear atypia, hemorrhagic cystitis, polyoma virus related changes
Topical (intravesicular) Mitomycin C / ThioTEPA: may cause exfoliation of normal and abnormal urothelial cells, degeneration, multinucleation and bizarre reactive nuclear changes
Topical bCG (immunotherapy): causes focal epithelial denudation with granulomatous inflammation of lamina propria

Micro images

Various images

Chemotherapy-related changes: this is a characteristic but non pathognomonic reaction of superficial cells exposed to alkylating agents like TTP/MMC (AFIP fig 2-38)

bCG related changes: there is denudation of the urothelium and a chronic inflammation with poorly formed granulomas in the lamina propria (AFIP fig 2-41)

Radiation therapy-related changes: note the markedly narrow lumen (arrows) and thickened intima (AFIP fig 2-42)

Post-radiation therapy for prostate cancer
Fig 1: Bladder mucosa with dilated vascular spaces, hemorrhage, acute inflammation, fibrinous exudate and focal fibrosis in the lamina propria
Fig 2/3: Rounded and irregular tufts of bland urothelium, some in lamina propria suggestive of invasion but no mitotic activity
Fig 4: Focal urothelium surrounds dilated blood vessels containing fibrinous deposit

Post-radiation changes mimic dysplasia

Cytology images

Post-Mitomycin C therapy: the tumor cell (T) can be easily distinguished from the normal (N) and reactive superficial (R) cells (AFIP fig 2-39)

Differential diagnosis

Pseudocarcinomatous epithelial hyperplasia: similar changes may occur due to ischemia and chronic irritation, not treatment (Am J Surg Pathol 2008;32:92)
Urothelial carcinoma: usually no history of treatment; definite invasive changes, mitotic figures present

End of Bladder > Acquired non-neoplastic anomalies > Treatment effect

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