Primary lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) in the urinary bladder mimicking recurrent urinary tract infection: a case report and literature review

Abstract

We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment.

Introduction

Primary lymphoma in the urinary bladder is rare, and its definitive diagnosis relies on histopathology and immunohistochemistry. We present the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder, mimicking urinary tract infection (UTI). The collaborative and multifaceted approach described in this study aims to provide the most appropriate and effective treatment for her rare condition.

Case presentation

A 79-year-old woman with a history of hypertension and diabetes mellitus presented to our urologic clinic with urinary frequency and urgency, as well as suprapubic pain. She had been experiencing the symptoms for 6 months and visited the emergency room multiple times over this period due to recurrent urinary tract infections (UTIs). No significant findings were observed during the physical examination. The initial urinalysis conducted at the time of the primary visit revealed a red blood cell count of 9 /µl and a white blood cell count over 500 /µl. The urine culture tests consistently revealed the presence of Escherichia coli. Upon her arrival at our outpatient department, she underwent a sonogram, reporting left renal cysts and a suspicious 3.2-cm bladder tumor. During cystoscopy, multiple bladder tumors were identified, predominantly in the anterior wall of the urinary bladder, near the neck. A biopsy was conducted, and the pathology results revealed atypical lymphoid infiltration. A high-contrast abdominal computed tomography (CT) scan revealed a 3.9-cm enhancement, identified as a polypoid lesion, on the anterior wall of the urinary bladder [Fig. 1a-b]. Lymph nodes were not enlarged. A transurethral resection of the bladder tumor (TURBT) was conducted, where the bladder tumors were resected using a thulium laser under an Fr. 27 transurethral endoscope [Fig. 1c-d]. On gross examination, the specimens were brownish and elastic tissue fragments. Microscopically, the urinary bladder revealed a widespread presence of various types of small B cells, such as marginal zone cells resembling centrocytes, monocytoid cells, small lymphocytes, immunoblasts, and centroblast-like cells. Additionally, a few nonneoplastic germinal centers are also observed. The tumor cells display uneven and angled nuclear shapes with indistinct nucleoli and pale cytoplasm [Fig. 2a]. The pathology report confirmed the diagnosis of extranodal marginal zone lymphoma of MALT. Immunohistochemical staining was positive for CD20 and BCL2 but negative for CD3, BCL6, CD10, MNDA, CD5, CD23, and cyclin D1 [Fig. 2b-d]. The patient’s ki-67 proliferation index was low [Fig. 2e]. We referred her to the Hemato-oncology Department for a bone marrow biopsy. The resulting pathology report disclosed no evidence of malignancy. The whole body positron emission tomography was prepared and conducted, revealing no definite abnormal fluorodeoxyglucose metabolic lesions of the head, neck, chest, abdomen, pelvis, or bones. The comprehensive staging work-up indicated that the patient was at clinical stage IEA of her disease according to the Lugano classification for lymphoma staging. However, follow-up imaging revealed some residual bladder tumors. To provide local control, adjuvant radiotherapy was initiated. She underwent 20 sessions of radiation therapy, receiving a total dose of 2400 cGy specifically targeting the urinary bladder. Chemotherapy was not administered. Her recovery after irradiation was smooth, with only a slight discomfort during urination. The urinalysis conducted after treatment showed a red blood cell count of 2 /µl and a white blood cell count of 5 /µl. No bacterial growth was detected in the post-therapy urine culture. She attains a complete response on imaging and cystoscopy during 9 months of follow-up. At present, she is attending follow-up appointments in our outpatient department.

Fig. 1

(a-b) The CT revealed a 3.9 cm mass on the anterior wall of the bladder. (c-d) During TURBT, the bladder tumors on the anterior wall near bladder neck were resected using a thulium laser under an Fr. 27 transurethral endoscope

Fig. 2

(a) Microscopically, the urinary bladder shows diffuse infiltrate of morphologically heterogeneous small B cells. The tumor cells have irregular angulated nuclear contours with inconspicuous nucleoli and pale cytoplasm. (b) Positive for CD20 (marker of low-grade lymphoma). (c) Negative for CD3 (marker of high-grade lymphoma). (d) Negative for BCL6. (e) Ki-67 proliferation index was low

Discussion

Primary lymphoma of the urinary bladder is a rare occurrence, accounting for approximately 1.0% and 0.2% of all bladder tumors and extranodal non-Hodgkin’s lymphomas [1]. It typically manifests with intermittent gross hematuria, urinary frequency and urgency, dysuria, nocturia, and suprapubic and abdominal pains [2]. Common risk factors include chronic inflammation, UTIs, and autoimmune diseases. Approximately 20% of cases have a history of chronic bladder inflammation [3], leading to the hypothesis that chronic cystitis is potentially associated with an increase in extranodal lymphoid tissue, ultimately progressing to lymphoma [2]. Regarding the association between Helicobacter pylori infection and gastric MALT lymphoma, the regression of bladder MALT lymphoma postantibiotic treatment of Escherichia coli-related UTIs has been documented by Oscier et al. [4]. This lymphoma type is frequently observed dome or lateral walls of the bladder. Typically, it does not invade the ureteral orifice or spread throughout the bladder, making hydronephrosis an uncommon clinical presentation [5].

Distinguishing the clinical symptoms and imaging findings of primary lymphoma of the urinary bladder from urothelial carcinoma (UC) can be challenging. Therefore, diagnosing these tumors often relies on histopathology and immunohistochemistry. Strong positive immunohistochemistry staining for the markers LCA and CD20 indicates B-cell-derived lymphoma, while negative staining for cytokeratin (CK), CK7, and CD45RO excludes various carcinomas. Lymphomas of the bladder are categorized into low- and high-grades. Low-grade lymphomas produce positive stains for the cell markers CD20, CD43, and CD21, while high-grade lymphomas for CD20, CD3, and CD30 [6]. The most common low-grade type is B-cell-derived non-Hodgkin’s lymphomas of MALT, which includes Burkitt’s and plasmacytoid lymphomas [1]; these tend to have long disease courses and insidious onset but favorable prognosis [2]. Furthermore, MALT lymphomas produce positive stains for CD19 and FMC7, and negative for CD5, CD10, and CD11c [5]. The most common high-grade type is diffuse large B-cell lymphoma (DLBCL) [1]; further imaging studies such as chest and abdominal CT scans, bone marrow aspiration evaluations, and bone biopsies are recommended to rule out systemic lymphoma.

Table 1 presents the epidemiology, clinical features, and therapies of the cases of primary lymphoma of the urinary bladder as studied from the literature. Previously documented cases exhibit a varied array of clinical features, therapies, and prognosis. The majority of patients were female, mostly over the age of 50, with hematuria being the most prevalent presenting symptom, followed by dysuria, urinary frequency, and recurrent UTIs. Treatments included chemotherapy, radiotherapy, and TURBT, with numerous cases demonstrating a positive outcome. In numerous instances, diverse chemotherapy protocols were utilized, and radiation therapy was frequently administered. TURBT served as a therapeutic alternative in certain instances, especially for localized illness. In one case, antibiotic therapy resulted in complete remission. The follow-up durations varied from several months to several years, with numerous patients being alive and disease-free at the time of assessment, suggesting a predominantly positive prognosis when treated adequately. Nonetheless, certain instances, especially those concerning DLBCL variations or associated problems, led to recurrence or mortality, highlighting the diversity in outcomes contingent upon lymphoma subtype and treatment approach.

Table 1 Epidemiology, clinical features, therapies and outcomes of the cases of primary lymphoma of the urinary bladder

Based on the current National Comprehensive Cancer Network (NCCN) guideline, the recommended first-line treatment for extranodal marginal zone lymphoma occurring outside of the stomach and skin is involved-site radiation therapy. TURBT may be used as a diagnostic and therapeutic procedure. Reportedly, the extent of surgical resection, whether it is total cystectomy, partial cystectomy, complete TURBT, or incomplete TURBT, does not significantly affect the overall prognosis. Moreover, the choice of surgical intervention may not be a major determinant of clinical outcomes. Rather, the primary goal of surgical intervention is to alleviate lower urinary tract symptoms [5]. In cases of local recurrence, it is advisable to contemplate the use of systemic chemotherapy, while radiation therapy can be a palliative approach to achieve local control. Patients experiencing systemic recurrence are treated similarly to those with nodal lymphomas, with systemic chemotherapy being the subsequent therapeutic choice. While there are no established guidelines on the most effective regimen for lymphoma of the bladder, CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) is commonly employed for four cycles. Incorporating rituximab into the treatment regimen is recommended, particularly for individuals who exhibit resistance to chemotherapy and have a BCL-2 gene translocation [7]. The mitochondrial pathway contributes to the development of non-Hodgkin’s lymphoma, and rituximab has been demonstrated to alleviate the chemotherapy resistance observed in individuals with BCL-2 overexpression. This is achieved by stimulating cell apoptosis through the BCL-2 regulated mitochondrial pathway [8]. Clinical observations of MALT lymphomas indicate that they typically manifest as indolent diseases with slow dissemination rates. The 10-year survival rate is approximately 90% [9]. To date, there are no formal guidelines on disease surveillance. Vempati et al. suggest annual cystoscopic monitoring for the first 2– 3 years with urine specimens obtained at each visit for cytology [10].

Conclusion

Among bladder tumors, primary lymphoma is a relatively rare and less malignant pathological subtype. Urologists should keep this less common diagnosis in mind before surgery. It is difficult to distinguish clinically and radiologically from UC, but treatment strategies differ significantly. An accurate diagnosis relies on histopathology and immunohistochemistry. More study is needed to determine the optimal treatment and prognosis.