Iatrogenic changes in the urinary tract

Abstract

A handful of therapeutic procedures are used to treat malignancies of the urinary tract, most frequently intravesical immunotherapy or chemotherapy, but also neoadjuvant systemic chemotherapy. These treatment modalities produce morphological changes in the urothelium that can be mistaken for carcinoma; in particular, these therapies frequently mimic urothelial carcinoma in situ (CIS) urothelial dysplasia or true invasive neoplasia. Drugs such as mitomycin C used after transurethral resection of bladder tumour to reduce recurrences, bacillus Calmette-Guérin (BCG) intravesical immunotherapy to treat high-risk non-muscle-invasive bladder cancer and urothelial CIS and platin-based systemic chemotherapy to improve postcystectomy disease-specific survival are examples of therapy-related atypia seen in the urinary tract. To complicate the pathologist's life, a number of systemic drugs in use to treat other diseases, such cyclophosphamide, used to treat some autoimmune disorders or certain haematological malignancies or, in the case of anaesthetics, ketamine, used increasingly as an illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore need to be differentiated from intraepithelial neoplasia. Other less frequent procedures, such as photodynamic and laser therapy or the newer gene therapy to treat urothelial neoplasia, remain experimental. An immunohistochemical approach to reactive urothelium versus carcinoma in situ using p53, cytokeratin 20 and CD44 is also valid in the post-therapy setting. The pathologist should be aware of these novelties, as he or she plays a crucial role in evaluating treatment efficacy, but at the same time needs to avoid misdiagnosing secondary atypia as intraepithelial neoplasia.

Iatrogenic pathology of the urinary bladder

“…These limitations are relevant to daily practice of pathology. 60,61,99 There is limited data on utility of other markers in the setting…”

Atypical cytological changes mimicking SIL of the uterine cervix in allogenic hematopoietic stem cell transplantation recipients treated with busulfan

“…Although busulfan seems to be the agent most clearly involved with cytological atypia, other agents may cause or contribute to cytological atypical changes. Cyclophosphamide has also been associated with cytological alterations in the respiratory tract, breast, and urinary tract . However, no abnormalities in the uterine cervix have been described in association with cyclophosphamide in monotherapy or with cyclophosphamide in combination with other treatments different from busulfan.…”

Iatrogenic granulomatous changes in voided urine cytology

“…Different histological iatrogenic changes of the urinary tract have been described in patients undergoing treatment for bladder carcinoma 1 . Some of these changes are also evident in urine cytology.…”

“…Basically, two types of iatrogenic granulomatous reactions can be present in the bladder wall. First, those related to immunotherapy with bacillus of Calmette‐Guérin (BCG) and second, those present after transurethral surgical resections 1 . The presence of granulomas in voided urine samples is rare and reported cases have been related to bladder tuberculosis or BCG treatment 5‐7 .…”

“…Bladder pathologic changes induced by BCG treatment resemble those of tuberculosis. On histology, granulomatous reaction, denudation of the urothelium with associated reactive epithelial changes and acute inflammation are common findings 1 . Despite their high frequency on tissue biopsies, granulomas are rarely seen in urine cytology samples.…”