Case Discussion <Chief Complaint>      Progressive left flank dull pain for two weeks <Brief History>      A 76-year-old man visited emergent department because of progressive left flank pain for two weeks. The pain was dull in character and was persistent. It was not associated with postural change and there were no radiation nor obvious aggravating and relieving factors. He experienced malaise, poor appetite, and body weight loss of 5Kg in one month. There were no hematuria and dysuria. He had history of urolithiasis and underwent extracorporeal shock wave lithotripsy (ESWL) two years ago. He denied history of psychiatric illness, smoking, drinking, or illicit drug use. The stool passage was normal. He was admitted to urology ward under the suspicion of urolithiasis. However, two episodes of hematemesis (about 150-200ml fresh blood in each episode) happened on the 4th day of hospitalization. Ketoprfen (intramuscular) was ever given three times for pain control during hospitalization. Gastroenterologists were consulted for further evaluation and management. <Physical Examination>      On consultation, physical examination revealed a thin but well-developed man with acute ill-looking. Heart rate was 114 bpm, temperature was 36.7 ℃, blood pressure was 106/70 mmHg. Conjunctiva was pale and a 1.5cm hard lymphadenopathy was noted at submandibular region. Auscultation of the abdomen showed hyperactive bowel sounds. There was no shifting dullness or hepatosplenomegaly. Knocking pain was noted at left flank area. <Laboratory and Image Study> 1. CBC/DC WBC RBC MCV MCHC Hb Hct PLT K/μL M/μL fL g/dL  g/dL % K/μL 6.2 3.83 80.6 31.2 8.1 31.6 141 Seg Mono Eos Baso  Lym % %  % % % 70.4 7 3 0 20  2. Biochemistry BUN Cr Na K AST ALT Glu CRP mg/dL mg/dL meq/L meq/L U/l U/l mg/dL  mg/dL 30 2.0 138 4.1 26 30 106 1.4  3. Urine analysis: Appearance Sp.gr PH Protein Glu Ketone Clear 1.006 6.0 -- -- -- OB Urobilinogen (EU/dL) WBC (/HPF) RBC (/HPF) Cast (/LPF) Crystal (/LPF) -- 0.1 50-60 3-5 -- --  Abdominal plain film: normal. Renal ultrasonography: enlargement of bilateral kidneys and mild hydronephrosis of left kidney. Ureteroscopic examination: narrowing of bilateral ureteral lumens without urolithiasis nor tumor.      Double J tube was inserted to the left ureter. <Course and Treatment>      Emergent upper endoscopy revealed multiple doughnut–like tumors at gastric body and antrum (Figure 1A , Figure1B). Giant gastric folds were also noted. As the bleeding was minimal (from gastric tumors) during endoscopy and there were no visible bleeding vessels in the stomach and duodenum, endoscopic hemostasis was not done. The bleeding stopped after NPO and intravenous omeprazole injection. Computed tomography (CT) of abdomen and pelvis showed perirenal mass enveloping bilateral kidneys and segmental bowel wall thickening at jejunum (Figure 2A ,  Figure2B). There was neither lymphadenopathy nor mass lesion compressing the ureters. Small bowel barium study showed segmental filling defects with thumb-printing appearance at jejunum and ileum (Figure 3 ).      However, acute renal failure progressed (serum urea and creatinine levels elevated to 59.4 mg/dL and 4.0 mg/dL, respectively). Histological evaluation of the gastric biopsy specimen revealed intermediate to large-size lymphoid cells crowding between glands in a classical starry-sky pattern. The cellular proliferation rate was extremely high, which was identified by nearly 100% Ki-67 positivity. Special stains for tumor cells showed CD20(+), CD21(-), and CD3(-). These findings were compatible with Burkitt’s lymphoma. Tumor cells were negative for Epstein-Barr virus (EBV) encoded RNAs. Serology test showed positive for EBV-VCA IgG and negative for human immunodeficiency virus (HIV). Both the urine cytology and cerebral spinal fluid (CSF) analysis disclosed lymphoblastic cells. Bone marrow aspiration and biopsy did not show marrow involvement of lymphoma.      Systemic chemotherapy with rituximab, BCNU, vincristine, methotrexate, etoposide, and methylprednisolone and intrathecal injection of methotrexate were administered after establishing the diagnosis of Burkitt's lymphoma. After two courses of systemic chemotherapy and intrathecal injection of methotrexate, his general condition improved remarkably and nearly complete remission was noted by follow-up panendoscopy, endoscopic ultrasonography, small bowel series, CT scan of abdomen, and cerebral spinal fluid cytoloty. Dramatic normalization of renal function was also noted soon after initiation of chemotherapy. Unfortunately, the patient died of pneumonia during the 3rd course of chemotherapy. <Analysis>         此病人的胃腫瘤的特色為多發性甜甜圈狀的腫瘤，同時可見持續性少量的滲血。這類型腫瘤的鑑別診斷包括Burkitt's 淋巴瘤，轉移至胃的腫瘤（常見的有黑色素瘤、肺癌、乳癌等），Gastrointestinal stromal tumor（GIST），或Kaposi's肉瘤等等。胃鏡下胃的distensibility還不錯，同時看到有巨大胃皺摺，電腦斷層及小腸攝影發現小腸亦有區段性增厚。頸部亦有淋巴結結腫大，加上LDH升高，而其他腫瘤指數正常，故臨床診斷為淋巴瘤，而病理檢查更進一步診斷為Burkitt's淋巴瘤。胃出血常見的原因包括消化性潰瘍、食道或胃之靜脈瘤或Mallorg-Weiss症候群。胃腫瘤引起的大量出血較不常見，胃淋巴瘤有15-30﹪會發生上消化道出血，但是僅有少數病例引發大量吐血。有些報告指出胃腫瘤引起之出血可利用內視鏡治療達到止血的效果。但在這個病人其胃腫瘤之出血是廣泛的、緩慢性的滲血，亦無看到明顯的血管，所以並未利用內視鏡進行止血治療。在支持性療法及化學治療之後，病人未再發生上消化道出血。       Burkitt's 淋巴瘤是Non-Hodgkin's lymphoma（NHL）的其中一種，占NHL的1-2﹪，最早是由Dennis Burkitt 在1958年時所發表，他發現烏干達的小孩易患有這類的淋巴瘤，它們腫瘤細胞生長得相當快速，而且，對化學治療的反應相當的好，但病人的預後較一般淋巴瘤差。後來在美洲也有發現Burkitt's 淋巴瘤的病例，但發生率較低，且好發在腸胃道及腹部淋巴結，與EB-virus的關聯性也較小。Burkitt's 淋巴瘤約有30-50﹪會侵犯到腎臟，常見的影像學包括單個或多個腎臟腫瘤，或瀰漫性腎臟浸潤，或從腎臟周圍包住腎臟（此病人的電腦斷層顯示為此類）。在治療方面，目前仍以化學治療為主，此病人使用之處方為R-BOMES（Rituximab BLNU ,Vincristine ,Methotrexate,Etoposide and methylprednisolone）治療後二個月，胃、小腸、頸部以及腎臟之病變幾乎完全消失。當發現多發現胃腫瘤時，應仔細找尋是否有淋巴結腫大或其他器官，如皮膚、肺部、乳房等等是否有腫瘤。腫瘤指數、胸部X光、腹部超音波掃描、電腦斷層掃描、上、下消化道及小腸攝影等檢查均可幫忙進一步診斷。     References: Collins J, et al.: Gastroenterology 1983; 85:425-429. Sharma et al.: Am J Hematol 2001; 67:48-50. Priebe WM: Gastrointest Endosc 1986; 32:352-354. Miyaguchi S, et al.: Endoscopy 1992; 24:603. Kadakia SC, et al.. Am J Gastroenterol 1992; 87:1418-1423.                             繼續教育考題 1. (B) Which of the following is right regarding the prevalence of Burkitt's lymphoma？ A It is an uncommon type of NHL and accounting for only 25-30% of all adult NHL cases B In the setting of HIV infection, Burkitt's lymphoma may account for about 35-40% of all NHL patients C In the pediatric non-HIV population, 1-2% of all NHL will be of Burkitt's variety D All of the above 2. (B) Which of the following characters is right about Burkitt's lymphoma？ A slow growing B rapid proliferation C poor response to chemotherapy D A+C E B+C 3. (D) In which of the following circumstances should emergent upper endoscopy be considered？ A massive hematemesis B fresh blood drained from NG tube C frequent and large amount loose tarry stool with unstable hemodynamic conditions D All of the above 4. (E) Which of the following is right about the clinical presentation of Burkitt's lymphoma？ A Endemic or African type usually involves the jaw, orbital, and retroperitoneal nodes B Sporadic or American type frequently presents with abdominal mass and GI involvement C it is most common in aged adults D A+B+C E A+B 5. (C) Which of the following gene abnormality is responsible for the occurrence of Burkitt's lymphoma? A t(8;21) B inv(16) C t (8;14) D t(9;22) E t(4;11) 6. (A) Which of the following is wrong about Burkitt's lymphoma? A Burkitt's lymphoma is a solid tumor of T- lymphocytes B In most (approximately 90%) of the cases of Burkitt's lymphoma is associated with c-myc gene translocation C The disease has a strong association with Epstein-Barr virus in Endemic or African type D All of the above 7. (D) Which of the following is (are) the possible cause(s) of acute renal failure in patients with Burkitt's lymphoma? A Renal involvement include renal infiltration of tumor B Bilateral urinary obstruction due to retroperitoneal fibrosis or tumor invasion of ureters and renal pelvis C Direct compression from retroperitoneal lymph nodes D All of the above 8. (B) What is the appropriate treatment for patients with Burkitt's lymphoma involving the GI tract in the absence of intractable GI bleeding？ A Surgical resection B Systemic chemotherapy C Endoscopic mucosal resection (EMR) D Surgical resection followed by systemic chemotherapy 9. (E) Which of the following is right about the prognosis of Burkitt's lymphoma？ A In patients with localized disease that respond well to chemotherapy, the survival rate is still poor. B For patients with extensive disease, a long-term survival rate of 70-80% now can be achieved with intensive chemotherapy regimens. C In AIDS patients with Burkitt lymphoma, death usually occurs shortly after diagnosis. D A+C E B+C 10. (A) Which is wrong about the treatment for Burkitt's lymphoma？ A Cyclophosphamide therapy alone is not effective for children from Africa with localized (early stage) disease. B Combination chemotherapy has markedly improved treatment results, particularly in patients with extensive disease. C Short-duration, intensive, alkylator-based multiagent regimens are necessary for patients with extranodal tumors and for all patients with the sporadic form of the disease. D The rapid administration of successive cycles to prevent tumor regrowth is important

答案解說 (B)  Burkitt's lymphoma constitutes 25-30% of all NHL in pediatric non-HIV infected patients, but is rare (1-2%) in adult, except for those infected with HIV (35-40%). (B)  The characters of rapid proliferation and dramatic response to chemotherapy of Burkitt's lymphoma put it in a distinctive class of NHL. (D)  Emergent upper endoscopy should be considered in the presence of massive hematemesis, fresh blood drained from NG tube, or unstable hemodynamic conditions attributed to massive upper GI bleeding. (E)  Although Burkitt's lymphoma can affect people of any age, it is most common in children and young adults, with a mean of 11 years of age. (C)  In most (approximately 90%) of the cases of Burkitt's lymphoma, a reciprocal translocation has moved the proto-oncogene c-myc from its normal position on chromosome 8 to a location close to the enhancers of the antibody heavy chain genes on chromosome 14. (A)  Burkitt's lymphoma is a solid tumor of B lymphocytes. The disease has a strong association with Epstein-Barr virus in Endemic or African type, but the association was not strong in Sporadic or American type (D)  The causes of renal failure due to renal involvement include renal infiltration of tumor, bilateral urinary obstruction due to retroperitoneal fibrosis or tumor invasion of ureters and renal pelvis, or direct compression from retroperitoneal lymph nodes (B)  Burkitt lymphoma is a very fast growing tumor. Systemic chemotherapy is the treatment of choice for this aggressive disease in all its stages. (E) 9. Patients with localized disease respond well to chemotherapy and have an excellent survival rate. (A) 10. Cyclophosphamide therapy alone has been curative for 80% of children from Africa with localized (early stage) disease.