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Radiation Cystitis with Pseudocarcinomatous Urothelial Hyperplasia
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Radiation Cystitis with Pseudocarcinomatous Urothelial Hyperplasia A 42-year-old woman who had undergone pelvic radiation therapy for endometrial cancer presented with hematuria. Transurethral resection of a bladder tumor was performed. Histological sections revealed dilated lamina propria blood vessels with hemorrhage and fibrin deposition (fig. 1). Small nests of urothelial cells in the lamina propia surrounded the vessels (fig. 2). These histological findings are indicative of pseudocarcinomatous urothelial hyperplasia of the bladder, a condition associated with radiation therapy and chemotherapy1,2 but also seen sporadically in the setting of bladder ischemia. Radiation therapy can generate a variety of pathological alterations in the bladder3e5 which can be categorized based on the time course of onset of clinical symptoms.3 The clinical symptoms and histopathological findings are time and radiation dose dependent.4,5 Clinically, acute symptoms can appear 4 to 6 weeks after radiotherapy.4 Stromal and epithelial (urothelial) histological changes are observed in the bladder after radiation therapy. Early stromal histological findings include lamina propria edema with acute inflammation, hemorrhage and vascular dilatation with fibrin thrombi, the latter of which was seen in this case
(fig. 1). Additional vascular abnormalities include endothelial cell swelling, and vessel wall thickening and necrosis. With severe mucosal edema, mucosal bullae can develop. Cytologically bizarre stromal cells can be seen in conjuction with the edema. Late pathological findings in the stroma and muscle wall, detected 6 months to a year after radiotherapy, can consist of chronic cystitis, ulcer beds with granulation tissue and fibrosis of the muscularis propria, resulting in contracture of the bladder. Arterioles may display hyalinized and thickened walls. So-called radiation fibroblasts with a stellate shape and nuclear atypia may be prominent in the stroma. Urothelial damage is at first focal with necrosis resulting in erosions that can progress with extensive denudation and mucosal ulceration. It is thought that the loss of mucosal impermeability results in the clinical symptoms of urinary frequency and dysuria, with reduction of bladder compliance.5 Radiation can induce significant nuclear atypia in urothelial cells, with cytomegaly, multinucleation and enlarged hyperchromatic nuclei. Such changes can mimic urothelial carcinoma in situ, although nuclear-to-cytoplasmic volume ratios are typically low.
Figure 1. Radiation effect with ectactic blood vessels in lamina propria of bladder.
Figure 2. Small nests of urothelial cells in lamina propria in pseudocarcinomatous hyperplasia.
0022-5347/13/1906-2251/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
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PATHOLOGY PAGE
Radiation can also cause urothelial hyperplasia, with nests and cords that extend into the lamina propria and around ectatic blood vessels, as in this case. This pseudoneoplastic condition, which can histologically mimic invasive urothelial carcinoma, is called pseudocarcinomatous urothelial hyperplasia. It is detected on average about 4.5 years after pelvic radiotherapy (range 9 months to 13 years) and is often associated with hematuria.6 Cystoscopically, erythema, papillary/polypoid lesions, broad based and elevated erythematous lesions, erythematous bullous edema and bleeding ulcers can be seen.6 Radiation cystitis with pseudocarcinomatous hyperplasia is not related to urothelial neoplasia.6 Its main significance resides in diagnostic recognition that it may be part of the spectrum of pathological aberrations seen in the bladder after radiation, so that it is not misdiagnosed as bladder cancer.
Peter A. Humphrey Department of Pathology and Immunology Washington University School of Medicine St. Louis, Missouri 1. Baker PM and Young RH: Radiation-induced pseudocarcinomatous proliferations of the urinary bladder: a report of 4 cases. Hum Pathol 2000; 31: 678. 2. Chan TY and Epstein JI: Radiation or chemotherapy cystitis with “pseudocarcinomatous” features. Am J Surg Pathol 2004; 28: 909. 3. Epstein JI, Reuter VE and Amin MB: Cystitis. In: Biopsy Interpretation of the Bladder, 2nd edition. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins 2010; chapt 10, pp. 243e247. 4. Cheng L, Lopez-Beltran A and Bostwick DG: Treatment effects. In: Bladder Pathology. Hoboken, New Jersey: Wiley-Blackwell 2012; chpt 24, pp. 515e519. 5. Fajardo LF, Berthrong M and Anderson RE: Urinary system. In: Radiation Pathology. New York: Oxford University Press 2001; chpt 18, pp. 281e288. 6. Kryvenko ON and Epstein JI: Pseudocarcinomatous urothelial hyperplasia of the bladder: clinical findings and followup of 70 patients. J Urol 2013; 189: 2083.
Radiation Cystitis with Pseudocarcinomatous Urothelial Hyperplasia A 42-year-old woman who had undergone pelvic radiation therapy for endometrial cancer presented with hematuria. Transurethral resection of a bladder tumor was performed. Histological sections revealed dilated lamina propria blood vessels with hemorrhage and fibrin deposition (fig. 1). Small nests of urothelial cells in the lamina propia surrounded the vessels (fig. 2). These histological findings are indicative of pseudocarcinomatous urothelial hyperplasia of the bladder, a condition associated with radiation therapy and chemotherapy1,2 but also seen sporadically in the setting of bladder ischemia. Radiation therapy can generate a variety of pathological alterations in the bladder3e5 which can be categorized based on the time course of onset of clinical symptoms.3 The clinical symptoms and histopathological findings are time and radiation dose dependent.4,5 Clinically, acute symptoms can appear 4 to 6 weeks after radiotherapy.4 Stromal and epithelial (urothelial) histological changes are observed in the bladder after radiation therapy. Early stromal histological findings include lamina propria edema with acute inflammation, hemorrhage and vascular dilatation with fibrin thrombi, the latter of which was seen in this case
(fig. 1). Additional vascular abnormalities include endothelial cell swelling, and vessel wall thickening and necrosis. With severe mucosal edema, mucosal bullae can develop. Cytologically bizarre stromal cells can be seen in conjuction with the edema. Late pathological findings in the stroma and muscle wall, detected 6 months to a year after radiotherapy, can consist of chronic cystitis, ulcer beds with granulation tissue and fibrosis of the muscularis propria, resulting in contracture of the bladder. Arterioles may display hyalinized and thickened walls. So-called radiation fibroblasts with a stellate shape and nuclear atypia may be prominent in the stroma. Urothelial damage is at first focal with necrosis resulting in erosions that can progress with extensive denudation and mucosal ulceration. It is thought that the loss of mucosal impermeability results in the clinical symptoms of urinary frequency and dysuria, with reduction of bladder compliance.5 Radiation can induce significant nuclear atypia in urothelial cells, with cytomegaly, multinucleation and enlarged hyperchromatic nuclei. Such changes can mimic urothelial carcinoma in situ, although nuclear-to-cytoplasmic volume ratios are typically low.
Figure 1. Radiation effect with ectactic blood vessels in lamina propria of bladder.
Figure 2. Small nests of urothelial cells in lamina propria in pseudocarcinomatous hyperplasia.
0022-5347/13/1906-2251/0 THE JOURNAL OF UROLOGY® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.09.019 Vol. 190, 2251-2252, December 2013 Printed in U.S.A.
www.jurology.com
j
2251
2252
PATHOLOGY PAGE
Radiation can also cause urothelial hyperplasia, with nests and cords that extend into the lamina propria and around ectatic blood vessels, as in this case. This pseudoneoplastic condition, which can histologically mimic invasive urothelial carcinoma, is called pseudocarcinomatous urothelial hyperplasia. It is detected on average about 4.5 years after pelvic radiotherapy (range 9 months to 13 years) and is often associated with hematuria.6 Cystoscopically, erythema, papillary/polypoid lesions, broad based and elevated erythematous lesions, erythematous bullous edema and bleeding ulcers can be seen.6 Radiation cystitis with pseudocarcinomatous hyperplasia is not related to urothelial neoplasia.6 Its main significance resides in diagnostic recognition that it may be part of the spectrum of pathological aberrations seen in the bladder after radiation, so that it is not misdiagnosed as bladder cancer.
Peter A. Humphrey Department of Pathology and Immunology Washington University School of Medicine St. Louis, Missouri 1. Baker PM and Young RH: Radiation-induced pseudocarcinomatous proliferations of the urinary bladder: a report of 4 cases. Hum Pathol 2000; 31: 678. 2. Chan TY and Epstein JI: Radiation or chemotherapy cystitis with “pseudocarcinomatous” features. Am J Surg Pathol 2004; 28: 909. 3. Epstein JI, Reuter VE and Amin MB: Cystitis. In: Biopsy Interpretation of the Bladder, 2nd edition. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins 2010; chapt 10, pp. 243e247. 4. Cheng L, Lopez-Beltran A and Bostwick DG: Treatment effects. In: Bladder Pathology. Hoboken, New Jersey: Wiley-Blackwell 2012; chpt 24, pp. 515e519. 5. Fajardo LF, Berthrong M and Anderson RE: Urinary system. In: Radiation Pathology. New York: Oxford University Press 2001; chpt 18, pp. 281e288. 6. Kryvenko ON and Epstein JI: Pseudocarcinomatous urothelial hyperplasia of the bladder: clinical findings and followup of 70 patients. J Urol 2013; 189: 2083.