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Journal of Clinical Oncology, Vol 26, No 9 (March 20), 2008: pp. 1555-1557 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.9856
Mantle-Cell Lymphoma (Multiple Lymphomatous Polyposis) of the Entire GI TractGastroenterology Unit, Alexandra Hospital, Athens, Greece
Department of Pathology, Metropolitan Hospital, Athens, Greece
Haematology Unit, Alexandra Hospital, Athens, Greece
Department of Clinical Therapeutics, Athens University, School of Medicine, Alexandra Hospital, Athens, Greece
Gastroenterology Unit, Alexandra Hospital, Athens, Greece
Department of Clinical Therapeutics, Athens University, School of Medicine, Alexandra Hospital, Athens, Greece A 65-year-old White man was admitted at to the emergency room with melena of moderate severity in May 2005. There was no particular history except an episode of upper GI (UGI) bleeding 25 years ago. He received daily 100 mg of aspirin, enalapril maleate, gliclazide, tamsulosine-hydrochloride, and latanoprost ophthalmic solution. Additionally, he received some nimesulid tablets for dental pain during the previous days. The patient was pale and tachycardic without orthostatic signs. Routine laboratory tests showed anemia with a decrease of hemoglobin level of 9.4 mg/dL. A same-day UGI endoscopy revealed blood in the stomach with many antral acute erosions and a bulbar duodenal ulcer with active oozing, necessitating a combination treatment with epinephrine injections (solution 1:10,000) and thermocoagulation with heater probe. He was transfused with 2 units of washed RBCs. A rapid urease-test for Helicobacter pylori (Hp; CLO-test; Ballard Medical Products, Draper, UT) was positive. The patient received omeprazole IV (8 mg/h for 3 days), a 10 days anti-Hp treatment with omeprazole, clarithromycin, and amoxicillin and iron supplementation for 3 months. Nine months after the episode of melena he presented with a persistent, well-tolerated iron deficiency anemia without other complaints. Hemoglobin was 10.5 mg/dL. A new UGI endoscopy revealed the same duodenal ulcer with no active bleeding (Fig 1C, arrow). In addition, a nodular pattern of the esophagus and the stomach (Figs 1A and 1B) was noted. A colonoscopy revealed many polyps ranging in size from 0.5 to 2 cm along the whole large bowel including the rectum and the terminal ileum, some of which were ulcerated. (Fig 1D, small arrows for ulcerations).
Antral and fundic biopsies as well as CLO-test were negative for Hp. Multiple biopsies of the whole GI tract showed diffuse or nodular infiltration of the mucosa by a mantle-cell lymphoma (MCL). Immunohistochemistry for the lymphoma cells (positive staining for CD20, CD79  , CD5, BCL2, cyclinD1, CD43 and negative staining for CD10, CD23, bcl-6) confirmed the diagnosis of multiple lymphomatous polyposis (Fig 2; 2A: esophagus; 2B: stomach; 2C: colon-CD5; 2D: cyclin D). Bone marrow biopsy showed infiltration by lymphoma cells. Multiple small lymph nodes were found by physical examination in the cervical, supraclavicular, axillar, and inguinal areas. There was no liver or spleen enlargement. Radiologic evaluation showed mesentery and paraortic lymphadenopathy, but no splenomegaly or hepatomegaly. Immunoglobulin values were within the normal limits, b2-microglobulin was 1.6 mg/dL (upper limit of normal < 1.8), C-reactive protein was 2.2 mg/dL (upper limit of normal < 0.5), and lactase dehydrogenase was normal. The patient had no B-symptoms and the International Prognostic Index score was 3.
He was treated with a combination of bortezomib on days 1, 4, 8, and 11, rituximab on day 8, and cyclophosphamide, doxorubicin, vincristine, and prednisone on day 8 every 21 days. The patient completed six cycles of chemotherapy with minimal toxicity. There was no lymphadenopathy in physical examination or computed tomographies, while a repeated bone marrow biopsy showed no infiltration by lymphoma cells. Endoscopy of the upper and lower GI tract and the corresponding multiple biopsies were normal. The patient has remained in complete remission since then. Mantle-cell lymphoma comprises 2.5% to 7% of all non-Hodgkin's lymphomas. The GI tract may be involved. Multiple lymphomatous polyposis (MLP) is uncommon and is regarded as the intestinal form of MCL.1 Although recognized two centuries ago, it was completely described and reviewed by Cornes in 1961. It accounts for 9% of primary GI lymphomas.2,3 The disease occurs more commonly in middle-age men. Revelatory GI symptoms may be abdominal pain, diarrhea, obstruction, hematochezia, or less frequently protein-losing enteropathy, intestinal malabsorption, chylous ascites, and acute abdomen due to perforation. Bone marrow is infiltrated in two thirds of patients at the time of diagnosis as well as liver, spleen, mesenteric, and peripheral nodes. The polyps usually appear in the ileocecal region and one third of cases are presented as a mass. The macroscopic appearance of polyps in MLP is not specific underlying the value of pathology and especially immunohistochemistry.4 Differential is necessary from a chronic lymphoid leukemia (CD5+, CD 23+), a follicular lymphoma of low degree of malignancy (CD10+, CD5–, CD 23–), and eventually mucosa-associated lymphoid tissue or a T-cell lymphoma. In a recent analysis of lymphomatous polyposis of the GI tract, only 12 out of 35 cases were MCL. The exact aetiopathogenesis of MCL is not known, but cytogenetic analysis shows rearrangement of the bcl-1 locus on chromosome 11 due to (t11:t14) (q13:q32) translocation, accompanied by cyclin D1 antigen overexpression.5 Involvement of the esophagus is unusual and complete GI involvement is extremely rare.4,6,7 In addition, while bleeding is frequently revealing MLP as hematochezia, it is exceptional that the source of the bleeding is a bulbar duodenal ulcer.8 To our knowledge, the association of the these extremely infrequent conditions has never been described and makes our case herein singular. Prognosis in MCL was considered poor. Treatment with cyclophosphamide-vincristine-prednisone achieved partial response in only three of 10 patients, while treatment with doxorubicin-teniposide-cyclophosmamide-prednisolone in 80%.3 In MCL, single-agent rituximab therapy produced response rates of approximately 30%, and when combined with an anthracycline-containing regimen, the response rate has increased to above 90%.9 However, relapses are common, and MCL has one of the poorest prognoses of all non-Hodkin's lymphoma subtypes with median failure-free survival of approximately 8 to 20 months there is no generally accepted therapeutic approach. NF-kB dysregulation is common in many lymphoproliferative disorders. Bortezomib, a selective proteasome inhibitor, downregulates NF-kB activity through modulation of the ubiquitin-proteasome activity. Bortezomib provides significant clinical activity in terms of durable and complete responses in patients with relapsed or refractory MCL and has been approved from the US Food and Drug Administration for this population.10,11 Due to poor prognostic features of the disease in our patient, an aggressive approach was recommended. However, he was a poor candidate for high-dose therapy12 reason, and the addition of a new agent with activity in MCL in combination with standard immunochemotherapy was offered to the patient on a compassionate basis.13 He is disease-free 20 months after treatment initiation. We describe a rare case of MCL involving the whole GI tract, revealed by upper GI bleeding. The patient received a regimen of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone combined with bortezomib without severe complications. The encouraging results 20 months after treatment initiation show that this combination is feasible and could be further evaluated as a treatment option for high-risk patients. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Harris NL, Jaffe ES, Stein H, et al: Perspective: A revised European-American classification of lymphoid neoplasm: A proposal from the International Lymphoma Study Group. Blood 84:1361-1392, 1994 2. Cornes JS: Multiple lymphomatous polyposis of the gastrointestinal tract. Cancer 14:249-257, 1961[CrossRef][Medline] 3. Ruskoné-Fourmestraux A, Delmer A, Lavergne A, et al: Multiple lymphomatous polyposis of the gastrointestinal tract: A prospective clinicopathologic study of 31 cases. Gastroenterology 112:7-16, 1997[CrossRef][Medline] 4. Kodama T, Ohshima K, Nomura K, et al: Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma. Histopathology 47:467-478, 2005[CrossRef][Medline] 5. Li JY, Gaillard F, Moreau A, et al: Detection of translocation t (11:14) (q13:q32) in mantle cell lymphoma by fluorescence in situ hybridazation. Am J Pathol 154:1449-1452, 1999 6. Tsuchiyama J, Yoshino T, Imajo K, et al: Lymphomatous polyp of mantle cell type in the duodenum complicated by gastric cancer: A case of trisomy 3 and t(11;14)(q13;q32). Ann Hematol 81:224-227, 2002[CrossRef][Medline] 7. Remes-Troche JM, De-Anda J, Ochoa V, et al: A rare case of multiple lymphomatous polyposis with widespread involvement of the gastrointestinal tract. Arch Pathol Lab Med 127:1028-1030, 2003[Medline] 8. Mundasad B, Hawe MJG: Lymphoma presenting as a bleeding duodenal ulcer: A case report. Internet Journal of Tropical Medicine. 3:7, 2006 9. Kauh J, Baidas SM, Ozdemirli M, et al: Mantle cell lymphoma: Clinicopathologic features and treatments. Oncology (Huntingt) 17:879-891, 2003[Medline] 10. Fisher RI, Bernstein SH, Kahl BS, et al: Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle-cell lymphoma. J Clin Oncol 24:4867-4874, 2006 11. Kane RC, Dagher R, Farrell A, et al: Bortezomib for the treatment of mantle cell lymphoma. Clin Cancer Res 13:5291-5294, 2007 12. Witzig T: Current treatment approaches for mantle-cell lymphoma. J Clin Oncol 23:6409-6414, 2005 13. O'Connor OA, Wright J, Moskowitz C, et al: Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-hodgkin's lymphoma and mantle-cell lymphoma. J Clin Oncol 23:676-684, 2005
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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