案例報告：原發性尿道瀰漫性大型B細胞淋巴癌

張哲睿¹、張德撝²

¹臺北市立聯合醫院忠孝院區外科部泌尿科; 臺北市立聯合醫院和平院區外科部泌尿科

Primary urethral diffuse large B-cell lymphoma: a case report

Che-Jui Chang¹, Te-Wei Chang²

¹Division of Urology, Department of Surgery, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan

²Division of Urology, Department of Surgery, Taipei City Hospital, Heping Fuyou Branch (Heping), Taipei, Taiwan

Introduction

Extranodal lymphomas account for 25–35% of all non-Hodgkin’s lymphoma (NHL), commonly affecting the gastrointestinal (GI) tract, head and neck, skin, central nervous system, bones, testicles, breast and thyroid. Primary urinary tract lymphomas (PUTLs) represent less than 5% of all extranodal NHL. Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL (30–40%). Common sites of extranodal DLBCL include craniofacial sites, thyroid, mediastinum, the GI tract, breast, kidney, testis, uterus and bone. The kidney is the site of the majority of DLBCL of the urinary tract (UT) (72.39%), followed by the urinary bladder (24.95%). The distinction between primary and secondary lymphoma involvement of extranodal locations may be difficult to establish. According to Krol et al.'s criteria, any lymphoma that initially presents at an extranodal site should be deemed extranodal. There are only few cases of primary DLBCL of the urethra have been reported. DLBCL is a highly aggressive disease that necessitates immediate treatment. If not properly treated, the patients have a few months to live. For early detection and treatment of this tumor, urologists and pathologists must be aware that it can occur anywhere in the urinary tract, including the urethra. Herein, we report a case of urethral DLBCL initially presenting with painless bulging mass of the urinary meatus.

Case report:

A 70-year-old Taiwanese woman presented to urology outpatient department (OPD) with painless bulging mass of the urinary meatus for 10 days. There was no history of fever, gross hematuria, dysuria, urgency, increased frequency of urine, flank pain, poor appetite, night sweats, body weight loss. She denied any systemic disease, except for operation for left ovarian cyst, uterine myoma, and arthroscopy of bilateral knee. She was a non-smoker and not worked in a place where chemicals or radiation exposed. She took hypnotic regularly. She had no known allergies. Her family history was negative for any oncological condition. Physical examination revealed an erythematous painless fixed and firm bulging mass, approximately 1.0*0.8 cm, without bleeding or purulent discharge over the prominent urethra (Fig. 1A). Mild urethral prolapse, atrophic vaginal mucosa and pitting edema 1+ over bilateral legs were also noted. There was absence of lymphadenopathy, and normal perineal skin coloration, without swelling or induration. Laboratory results showed that the complete blood counts, neutrophil counts, renal function tests, serum electrolytes were within normal limit, except for elevated lactate dehydrogenase 3559 (U/L), Aspartate aminotransferase (83 U/L). Serology for HBsAg, Anti-HBe, and Anti-HBc were positive, while HBV viral load, HBeAg, Anti-HBs, Anti-HCV were negative. Cystoscopy found nodular lesions over the bilateral trigone and the specimen was collected via trans-urethral resection of bladder tumor (TURBT) (Fig. 2). An excisional biopsy was also performed for the urethral mass (Fig. 1B). Histological examination of the bladder tumor and urethral mass revealed monotonous medium-sized lymphocytic cells infiltrating in the stroma, with occasional mitotic activity and apoptosis. Focal necrosis was also noted (Fig.3). Immunohistochemical study showed CK (-), CD3 (-), CD20 (+), CD10 (-), BCL2 (+), BCL6 (+, 20%), MUM-1 (+, 40%), Cyclin D1 (-), Ki67 (+, 90%) (Fig. 4). These features suggested the presence of a DLBCL, non-germinal center subtype. Computed Tomography (CT) scan for systemic survey was arranged and the results showed diffuse lymphadenopathy up to 25mm, especially para-external iliac vessels and bilateral inguinal regions (Fig. 5), which were consistent with the changes in lymphoma infiltration. Due to the highly invasive nature of the tumor, a bone marrow (BM) aspiration biopsy was arranged and revealed infiltration of abnormal medium to large sized lymphoid cells which have hand mirror or tadpole shape, consistent with DLBCL. Flow cytometry showed 67.1% aberrant clonal B cells with large size, CD19 (+), CD20 (+), CD5 (-), CD10 (-), partial CD11c (+), CD22 (+), CD23 (-), CD27 (+), CD31 (-), CD38 (-), CD39 (+), partial CD43 (+), CD49d (-), partial CD62L (+), CD81 (+), CD95 (-), CD103 (-), CD185 (+), partial CD200 (+), CD305 (-), and surface lambda restriction. The patient was diagnosed with stage IVA primary urethral DLBCL according to the Ann Arbor system for NHL staging and the International Prognostic Index score was 4 (High-risk group). The patient was referred to hematology OPD for R–CHOP regimen (Rituximab, Cyclophosphamide, Vincristine, Doxorubicin, Prednisolone) afterwards. Nevertheless, she had fever with dysuria before immunochemotherapy. Empirical antibiotic was prescribed, but her condition progressed into an increased oxygen demand. Elective intubation was done, whereas refractory lactic acidosis developed. After share decision making with her family, she underwent Rituximab therapy. Then, she expired 2 days after Rituximab regimen conducted.

Conclusion

Our case report intends to promote awareness of this rare disease, as primary urinary tract DLBCL is uncommon, especially urethra origin. Urologists and pathologists should be aware that DLBCL can develop in the urethra. The immunohistochemistry analysis is vital for the diagnosis because the disease's rarity and non-specific appearance make diagnosis difficult. Early detection of the disease allows for prompt and adequate treatment of an aggressive, but potentially curable, lymphoma. Chemotherapy with R‑CHOP is the main treatment option for primary urinary tract DLBCL.