January 2021 — Genitourinary

A 67-year-old female developed gross hematuria. Cystoscopy examination showed an abnormal appearing, irritated bladder mucosa. Her past medical history was significant for endometrial carcinoma and she was status-post hysterectomy and radiation therapy. She also had a history of radiation proctitis. Representative microscopic images from a urinary bladder transurethral resection specimen have been depicted.

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What is your diagnosis?

  • Metastatic endometrial carcinoma
  • Squamous cell carcinoma
  • Urothelial carcinoma with squamous differentiation
  • Pseudocarcinomatous urothelial hyperplasia

The correct answer is...

The correct answer is pseudocarcinomatous urothelial hyperplasia.

Histologic sections show superficial fragments with areas of normal appearing mucosa interspersed with areas that exhibit nests of squamoid appearing cells. These epithelioid nests have prominent cytoplasmic eosinophilia imparting "squamoid" appearance with irregular borders. Also noted are hyalinized vessels, fibrin thrombi, and nests of squamoid cells wrapping around these vessels. The background stroma exhibits edema, areas of hemorrhage, and atypical stromal fibroblasts. Although focally these cells exhibit mild-to-moderate atypia, overall, the histologic findings are most consistent with pseudocarcinomatous urothelial hyperplasia secondary to radiation therapy. This is a benign reactive condition that is often seen in the fifth to sixth decade (range: ages 33-85). Patients present with hematuria, and cystoscopy shows polypoid or erythematous lesions. Frequently, this entity is seen in the setting of radiation therapy/chemotherapy. The average time from radiation to the development of radiation cystitis is approximately 55 months; however, a wide time interval has been reported. In cases with no prior therapy, the pathogenesis often is related to chronic ischemia or chronic irritation of the urinary bladder.

The histologic changes may be misinterpreted as squamous cell carcinoma or urothelial carcinoma with squamous differentiation. However, these epithelial changes are usually limited to the submucosa with no deeply infiltrative cells extending to the muscularis propria. Absence of background radiation changes, stromal reaction, and no increase in mitosis also are helpful features to rule out carcinoma. Knowing the characteristic histologic features and clinical history often aids in the diagnosis of this entity.

1. Kryvenko ON, Epstein JI. Pseudocarcinomatous urothelial hyperplasia of the bladder: clinical findings and followup of 70 patients. J Urol. 2013;189(6):2083-2086.
2. Lane Z, Epstein JI. Pseudocarcinomatous epithelial hyperplasia in the bladder unassociated with prior irradiation or chemotherapy. Am J Surg Pathol. 2008;32(1):92-97.

Photo of Prasuna Muppa, M.B.B.S. Prasuna Muppa, M.B.B.S.
Fellow, Surgical Pathology
Mayo Clinic
Photo of Sounak Gupta, M.B.B.S., Ph.D Sounak Gupta, M.B.B.S., Ph.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Pathology
Mayo Clinic College of Medicine and Science

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