Primary Extranodal Diffuse Large B-cell Lymphoma with Isolated Stomach and Urinary Bladder Involvement

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1 台灣癌症醫誌 (J. Cancer Res. Pract.) 27(3), , 2011 Case Report journal homepage: Primary Extranodal Diffuse Large B-cell Lymphoma with Isolated Stomach and Urinary Bladder Involvement Cheng-Han Wu 1, Sheng-Fung Lin 1,2, Wen-Chi Yang 1 * 1 Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract. Primary extranodal non-hodgkin s lymphoma (NHL) accounts for 25 35% of NHL. The gastrointestinal (GI) tract is the most commonly involved extranodal organ. NHL involving multiple isolated extranodal organs has only been seen in some case reports. We herein report an unusual case of primary extranodal diffuse large B-cell lymphoma (DLBCL) with stomach and bladder involvement in a 76-year-old female patient with an initial presentation of epigastralgia and urinary symptoms. Except for the stomach and bladder, no active lymphadenopathy was noted in a positron emission tomography (PET) scan. The patient received systemic chemotherapy R-CHOP (rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisolone), H. pylori eradication, and antibiotics therapy for chronic cystitis finally. 病例報告 Keywords : lymphoma, extranodal, PET 原發性侷限於胃和膀胱之結節外彌漫性大型 B 細胞淋巴瘤吳承翰 1 林勝豐 1,2 楊文祺 1 * 1 高雄醫學大學附設中和紀念醫院血液腫瘤內科 2 高雄醫學大學醫學院中文摘要原發性結節外之非何杰金氏淋巴瘤佔了所有非何杰金氏淋巴瘤 25-35% 左右, 而胃腸道是最常被侵犯的結節外器官只有少數的個案報告記載著多個器官同時具有局限性非何杰金氏淋巴瘤我們在此提出一個罕見的個案報告 - 一個診斷為胃及膀胱同時具有局限的原發性結節外彌漫性大型 B 細胞淋巴瘤之 76 歲女性, 而病人初始是以上腹痛和泌尿道症狀為表現在正子攝影中, 除了胃和膀胱的局限性病灶外, 並沒有任何淋巴結病變之顯影該病人最後接受 R-CHOP 之化學治療胃幽門螺旋桿菌之根除和泌尿道感染之抗生素治療關鍵字 : 淋巴瘤結節外正子攝影

2 118 C. H. Wu et al./jcrp 27(2011) INTRODUCTION Among all patients with non-hodgkin s lymphoma (NHL), approximately 50 percent of patients will develop secondary extranodal lesions, while onefourth to one-third percent of patients will have primary extranodal lesion at initial diagnosis [1]. Primary gastric and bladder NHL are uncommon and account for 6-11% and 0.2% of all cases of NHL, respectively [2]. In addition, NHL with multiple concomitant extranodal organ involvement without lymphadenopathy is very rare. We herein report an unusual case of primary extranodal diffuse large B-cell lymphoma (DLBCL) with isolated stomach and urinary bladder involvement. CASE REPORT A 76-year-old woman suffered from gastrointestinal (GI) and urinary tract symptoms lasting for several months. The GI symptoms were epigastralgia, hunger pain, poor appetite, abnormal taste, hiccups, and acid regurgitation; the urinary symptoms were frequency, urgency, dysuria, nocturia, hematuria, and incontinence. She denied any underlying disease. A gastroendoscopic examination revealed multiple nodal and ulcerative lesions from the gastric body to the antrum (Figure 1). The biopsy pathology showed diffuse infiltration of large lymphoid cells with oval to round nuclei and scant cytoplasm, and immunohistochemical study showed CD20 (+), CD3 (-), and a Ki-67 index of 80%, which demonstrated DLBCL (Figure 2). A positron emission tomography (PET) scan revealed diffuse and strong uptake of fluorodeoxyglucose (FDG) over both the gastric wall and urinary bladder without any lymph node involvement (Figure 3). A *Corresponding author: Wen-Chi Yang M.D. * 通訊作者 : 楊文祺醫師 Tel: ext.6109 Fax: wenchi @yahoo.com.tw cystoscopic examination revealed multiple nodal lesions over the irregular and erosive bladder surface (Figure 4). Biopsy was done, and the pathology revealed morphology and immunohistochemical staining similar to those of the gastric lesions, and also demonstrated DLBCL. Additionally, we performed bone marrow biopsy, and the pathology revealed negative for lymphoma involvement. The final diagnosis of the patient s malignancy was primary extranodal DLBCL with concomitant involvement of stomach and urinary bladder, Ann Arbor stage IVE. The presentation of Helicobacter pylori infection and Chlamydia-related chronic cystitis were thought to be risk factors of NHL in this patient, and it was proved by C 13 -urea breath test, urine strip analysis, and Chlamydia serum test. We performed chemotherapy with R-CHOP (rituximab, cyclophosphamide, daunorubicin, vincristine, and prednisolone) for the multiple isolated extranodal DLBCL. The patient also received H. pylori eradication therapy and the antibiotics therapy for chronic cystitis. DISCUSSION Extranodal NHL is less common than nodal NHL and accounts for one-fourth to one-third of all cases of NHL. Among the extranodal sites affected by NHL, the GI tract is the most commonly involved organ [2]; other organs include the skin, testis, bone, kidney, prostate, bladder, ovary, orbit, heart, breast, salivary glands, thyroid, and adrenal glands. Multiple isolated extranodal involvement of NHL is very rare and has only been described in a few case reports [3-5]. Primary gastric NHL constitutes about 6-11% of all cases of NHL, with DLBCL and mucosa-associated lymphoid tissue (MALT) lymphoma being the most common histological types [6,7]. H. pylori infection plays an important role in the pathogenesis of gastric MALT lymphoma, while its role in gastric DLBCL is still controversial. However, the eradication of H. pylori is still suggested [8].

C. H. Wu et al./jcrp 27(2011) 117-122 119 Figure 1. The gastroendoscopic examination revealed multiple nodal and ulcerative lesions between the lower (A) and upper body (B) A B C Figure 2.

and a Ki-67 index of 90% (C) NHL involving the bladder is very rare, representing 0.2% of primary lesion and 1.8% of secondary lesion of malignant lymphoma [9].

3 C. H. Wu et al./jcrp 27(2011) Figure 1. The gastroendoscopic examination revealed multiple nodal and ulcerative lesions between the lower (A) and upper body (B) A B C Figure 2. The photomicrography of the gastric tissue showed infiltration of large lymphoid cells with oval to round nuclei and scant cytoplasm (A), and immunohistochemical study showed positive for CD20 (B) and a Ki-67 index of 90% (C) NHL involving the bladder is very rare, representing 0.2% of primary lesion and 1.8% of secondary lesion of malignant lymphoma [9]. The mean age of patients with primary bladder lymphoma is 64 years, and prevalence in females is 6.5 times greater than in males. Hematuria is the most common symptom on presentation, and the findings of cystoscopy are often a solitary mass (70%), multiple masses (23%), and diffuse lesions (7%) [10,11]. MALT lymphoma is the most common histological type, and DLBCL accounted for less than 20% of all bladder lymphoma [12]. Chronic cystitis is frequently noted before the lymphoma diagnosis and is considered as one of the risk factors of bladder lymphoma [13,14]. Grem et al [15] reported the regression of bladder lymphoma after using doxycycline to control Chlamydia infection. Thus, our patient received H. pylori eradication and antibiotics therapy for the Chlamydia-related cystitis. The clinical application of PET scans in lymphoma staging may detect previously unnoticed lesions. The detection of lymphoma involvement by computed tomography and gallium scans is less sensitive compared with that by PET scans, especially for extranodal lesions [16,17]. In general, PET scans at diagnosis

120 C. H. Wu et al./jcrp 27(2011) 117-122 Figure 3. The PET scan for staging showed high uptake of FDG and hypertrophic change (green arrow) of gastric (A) and urinary bladder (B) walls.

4 120 C. H. Wu et al./jcrp 27(2011) Figure 3. The PET scan for staging showed high uptake of FDG and hypertrophic change (green arrow) of gastric (A) and urinary bladder (B) walls. No other nodal lesions were found during this exam result in upstaging of NHL in 10 40% of patients [18,19]. According to the PET scan findings of our patient, even though bladder lymphoma is rare [2] and her urinary symptoms were similar to those of urinary tract infection, we still arranged cystoscopy and obtained tissue proof of bladder lymphoma. Treatments for isolated gastric or bladder DLBCL are variable [10,11,20-22]. Owing to the lack of large clinical trials, the standard treatment remains controversial. In our patient, because of the concomitant lymphoma lesions in the stomach and bladder, we performed systemic chemotherapy with R-CHOP. After two courses of R-CHOP, partial remission of the gastric lymphoma was achieved according to findings of gastroendoscopic examination and CT scan. However, the patient expired owing to neutropenic fever and pneumonia. Even though the symptoms of irritable bladder were improved, we didn t perform cystoscopy and CT scan to follow the tumor size in the bladder.

C. H. Wu et al./jcrp 27(2011) 117-122 121 Figure 4.

5 C. H. Wu et al./jcrp 27(2011) Figure 4. The cystoscopic examination revealed multiple nodular and erosive lesions on the bladder mucosa In summary, we have reported an unusual case of primary extranodal DLBCL with isolated stomach and urinary bladder involvement. In addition to systemic chemotherapy, we prescribed the H. pylori eradication and antibiotics therapy for the Chlamydia-related cystitis to eliminate the risk factors. PET scan findings for bladder lymphoma serve as a reminder that PET scans are an essential tool for the clinical staging of lymphoma. REFERENCES 1. Anderson T, Chabner BA, Young RC, et al. Malignant lymphoma. 1. The histology and staging of 473 patients at the National Cancer Institute. Cancer 50: , Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 29: , Kim B, Oh SY, Lee S, et al. Unusual presentation of large B cell lymphoma- bone and stomachtreated with autologous transplantation. Cancer Res Treat 39: , Cheng G, Servaes S, Chamroonrat W, et al. Non-Hodgkin's lymphoma of the bone and the liver without lymphadenopathy revealed on FDG- PET/CT. Clin Imaging 34: , Krober SM, Aepinus C, Ruck P, et al. Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach. J Clin Pathol 55: , Koch P, del Valle F, Berdel WE, et al. Primary gastrointestinal non-hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 19: , Papaxoinis G, Papageorgiou S, Rontogianni D, et al. Primary gastrointestinal non-hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG). Leuk Lymphoma 47: , Psyrri A, Papageorgiou S, Economopoulos T. Primary extranodal lymphomas of stomach: clinical presentation, diagnostic pitfalls and management. Ann Oncol 19: , Kuhara H, Tamura Z, Suchi T, et al. Primary malignant lymphoma of the urinary bladder. A case report. Acta Pathol Jpn 40: , Hughes M, Morrison A, Jackson R. Primary bladder lymphoma: management and outcome of 12 patients with a review of the literature. Leuk Lymphoma 46: , Ohsawa M, Aozasa K, Horiuchi K, et al. Malignant lymphoma of bladder. Report of three cases and review of the literature. Cancer 72: , Coskun U, Gunel N, Eroglu A, et al. Primary high grade malignant lymphoma of bladder. Urol Oncol 7: , Maghfoor I, Koontz P, Weaver-Osterholtz D, et al. Primary extra-nodal lymphoma of the urinary bladder. South Med J 93: , Guthman DA, Malek RS, Chapman WR, et al.

6 122 C. H. Wu et al./jcrp 27(2011) Primary malignant lymphoma of the bladder. J Urol 144: , Grem JL, Hafez GR, Brandenburg JH, et al. Spontaneous remission in diffuse large cell lymphoma. Cancer 57: , Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging--do we need contrast-enhanced CT? Radiology 232: , Juweid ME, Cheson BD. Role of positron emission tomography in lymphoma. J Clin Oncol 23: , Michallet AS, Trotman J, Tychyj-Pinel C. Role of early PET in the management of diffuse large B-cell lymphoma. Curr Opin Oncol 22: , Ngeow JY, Quek RH, Ng DC, et al. High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma. Ann Oncol 20: , Raderer M, Chott A, Drach J, et al. Chemotherapy for management of localised high-grade gastric B-cell lymphoma: how much is necessary? Ann Oncol 13: , Ferreri AJ, Montalban C. Primary diffuse large B-cell lymphoma of the stomach. Crit Rev Oncol Hematol 63: 65-71, Koch P, Probst A, Berdel WE, et al. Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96). J Clin Oncol 23: , 2005.

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