A 60-Year-Old Woman With Lymphoma and Postchemotherapy Thickening of the Urinary Bladder Wall

A 60-year-old woman with a history of hypertension and dyslipidemia presented with lower back and sacral pain of 1 month's duration associated with low-grade fever and weight loss. Imaging studies demonstrated a sacral soft tissue mass and a biopsy confirmed the diagnosis of diffuse large B-cell lymphoma. She was treated with 5 courses of Rituxan and CHOP (cyclophosphamide, hydroxydoxorubicin/adriamycin, oncovin/vincristine, prednisolone) chemotherapy. Routine follow-up imaging directed at the sacral mass showed hydronephrosis, hydroureter, and diffuse thickening of the urinary bladder wall, thought to represent involvement of the bladder by lymphoma. She had no hematuria or other irritative bladder symptoms. Cystoscopy revealed diffusely erythematous bladder mucosa with necrotic debris. No distinct mass lesion was seen. Random bladder biopsies showed acute inflammation of the bladder mucosa with submucosal vascular congestion (Figure 1) and no evidence of lymphoma. In addition, there were scattered markedly enlarged endothelial cells and leukocytes in the lamina propria with purple intranuclear inclusions and smaller basophilic cytoplasmic inclusions (Figure 2). Similar inclusions were also found in a few stromal cells (Figure 3). Immunohistochemistry was performed to confirm the nature of the inclusions (Figure 4).What is your diagnosis?This case is an unusual case of asymptomatic cytomegalovirus-induced cystitis in a 60-year-old patient with previously diagnosed diffuse large B-cell lymphoma in the sacral region. She was treated with 5 courses of chemotherapy and, on follow-up computed tomography scan examination, was found to have a thickened bladder wall. Histologic examination showed several typical inclusions of cytomegalovirus with mild cystitis. No evidence of lymphoma was seen.Viral cystitis is uncommon in immunocompetent individuals.1 Adenovirus is recognized as an important cause of viral hemorrhagic cystitis, especially in children, whether healthy or after bone marrow transplant. Other causes of viral cystitis include herpes simplex virus 2, herpes zoster, and human papilloma virus.1Cytomegalovirus (CMV) is a common cause of morbidity and mortality in immunocompromised patients. The virus can affect many organ systems; however, reports of hemorrhagic cystitis in this setting are very rare.2 The first case of CMV-induced hemorrhagic cystitis was reported in 1970 in a patient with uterine sarcoma treated with cyclophosphamide.3 Cytomegalovirus cystitis has also been described in patients with acquired immune deficiency syndrome (AIDS).4 Cytomegalovirus can also affect other parts of the urinary tract, causing ureteritis and interstitial nephritis. The response to antiviral agents seems to be excellent.Perhaps CMV should be considered in the differential diagnosis of hemorrhagic cystitis, especially in immune-suppressed patients, because effective therapy is available.2 Cystoscopy and biopsy should lead to a definitive diagnosis once the characteristic giant cells and intranuclear and/or perinuclear cytoplasmic inclusions are recognized. In our case, the diagnosis was confirmed by immunoreactivity for CMV. Our patient was asymptomatic and the CMV infection was an incidental finding on imaging performed as part of the routine follow-up of her treatment for sacral lymphoma. She was treated with ganciclovir. Cyclophosphamide-induced hemorrhagic cystitis has been documented to occur within hours of administration of cyclophosphamide. In this particular patient, there were no clinical symptoms of hemorrhagic cystitis; therefore, we think that the thickening and edema noted on imaging is secondary to CMV-induced cystitis, which occurred months after cyclophosphamide administration.

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