Abstract
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome.
Similar content being viewed by others
References
Isaacson PG (1994) Gastrointestinal lymphoma. Hum Pathol 25:1020–1029
Aisenberg AC (1995) Coherent view of non-Hodgkin’s lymphoma. J Clin Oncol 13:2656–2675
Crump M, Gospodaroricz M, Shepherd FA (1999) Lymphoma of the gastrointestinal tract. Semin Oncol 26:324–337
Ang MK, Tao M, Quek R, Sng I, Tan L, Lim ST (2007) MALT lymphomas show different behaviour and clinical outcomes depending on their primary location. Poster Presentation for Lancet Asia Medical Forum 2007
Zucca E, Roggero E, Pileri S (1998) B-cell lymphoma of MALT type: a review with special emphasis on diagnostic and management problems of low grade gastric tumours. Br J Haematol 100:3–14
Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wundisch T, Ehninger G, Stolte M, Bayerdorffer E (1997) Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Nat Cancer Inst 89:1350–1355
Cogliatti S, Schmid U, Schumacher U, Eckert F, Hansmann ML, Hedderich J, Takahashi H, Lennert K (1991) Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients. Gastroenterology 101:1159–1170
Lim ST, Tao M, Cheung YB, Rajan S, Mann B (2005) Can patients with early-stage diffuse large B-cell lymphoma be treated without bone marrow biopsy? Ann Oncol 16:215–218
The International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994
Isaacson PG (1996) Recent development in our understanding of gastric lymphoma. Am J Surg Pathol 20:S1–S7
De Jong D, Boot J, Van Heerde P, Hart GAM, Taal BG (1997) Histological grading in gastric lymphoma: pretreatment criteria and clinical relevance. Gastroenterology 112:1466–1474
Hussell T, Isaacson PG, Crabtree JE, Spencer J (1993) The response of cells from low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet 342:571–574
Isaacson PG (1999) Gastric MALT lymphoma: from concept to cure. Ann Oncol 10:637–645
Zucca E, Bertoni F, Roggero E, Cavalli F (2000) The gastric marginal zone B-cell lymphoma of MALT type. Blood 96:410–419
Bayerdorffer E, Rudolph B, Neubauer A, Thiede C, Lehn N, Eidt S, Stolte M, MALT Lymphoma Study Group (1995) Regression of primary gastric lymphoma of mucosa associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet 345:1591–1594
Nakamura S, Akazawa K, Yao T, Tsuneyoshi M (1995) Primary gastric lymphoma. A clinicopathologic study of 233 cases with special reference to evaluation with the MIB-1 index. Cancer 76:1313–1324
Nakamura S, Matsumoto T, Suekane H, Nakamura S, Matsumoto H, Esaki M, Yao T, Iida M (2005) Long-term clinical outcome of Helicobacter pylori eradication for gastric mucosa-associated lymphoid tissue lymphoma with a reference to second-line treatment. Cancer 103:532–540
Morton JE, Leyland MJ, Vaughan Hudson G, Vaughan Hudson B, Anderson L, Bennet MH, MacLennan KA (1993) Primary gastrointestinal non-Hodgkin’s lymphoma: a review of 175 British National Lymphoma Investigation cases. Br J Cancer 67:776–782
Wotherspoon AC, Ortoz-Hidalgo C, Falzon MR, Isaacson PG (1991) Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 338:1175–1176
Roggero E, Zucca E, Pinotti G, Pascarella A, Capella C, Savio A, Pedrinis E, Paterlini A, Venco A, Cavalli F (1995) Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med 122:767–769
Montalban C, Santon A, Boixeda D, Redondo C, Alvarez I, Calleja JL, de Argila CM, Bellas C (2001) Treatment of low grade gastric mucosa-associated lymphoid tissue lymphoma in stage I with Helicobacter pylori eradication. Long term results after sequential histologic and molecular follow-up. Haematologica 86:609–617
Fischbach W, Goebeler-Kolve ME, Dragosics B, Greiner A, Stolte M (2004) Long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT) following exclusive Helicobacter pylori eradication therapy: experience from a large prospective series. Gut 53:34–37
De Jong D, Aleman BM, Taal BG, Boot H (1999) Controversies and consensus in the diagnosis, work-up and treatment of gastric lymphoma: an international survey. Ann Oncol 10:275–280
Chen L-T, Lin J-T, Tai JJ, Chen G-H, Yeh H-Z, Yang S-S, Wang H-P, Kuo S-H, Sheu B-S, Jan C-M, Wang W-M, Wang T-E, Wu C-W, Chen C-L, Su I-J, Whang-Peng J, Cheng A-L (2005) Long term results of anti-Helicobacter pylori therapy in early-stage gastric high-grade transformed MALT lymphoma. J Nat Cancer Inst 97:1345–1353
Morgner A, Miehlke S, Fischbach W, Schmitt W, Muller-Hermelink H, Greiner A, Thiede C, Schetelig J, Neubauer A, Stolte M, Ehninger G, Bayerdorffer E (2001) Complete remission of primary high-grade B-cell gastric lymphoma after cure of Helicobacter pylori infection. J Clin Oncol 19:2041–2048
Chen L-T, Lin J-T, Shyu R-Y, Jan C-M, Chen C-L, Chiang I-P, Liu S-M, Su I-J, Cheng A-L (2001) Prospective study of Helicobacter pylori eradication therapy in stage IE high-grade mucosa-associated lymphoid tissue lymphoma of the stomach. J Clin Oncol 19:4245–4251
Nakamura S, Matumoto T, Suekane H, Takeshita M, Hizawa K, Kawasaki M, Yao T, Tsunetoshi M, Iida M, Fujishima M (2001) Predictive value of endoscopic ultrasonography for regression of gastric low-grade and high-grade MALT lymphomas after eradication of Helicobacter pylori. Gut 48:454–460
Miki H, Hideo S, Harada H, Yamanoi Y, Uraoka T, Sotozono M, Ohmori M (2001) Early stage gastric MALT lymphoma with high-grade component cured by Helicobacter pylori eradication. J Gastroenterol 36:121–124
Montalban C, Santon A, Boixeda D, Bellas C (2001) Regression of gastric high-grade mucosa associated lymphoid tissue (MALT) lymphoma after Helicobacter pylori eradication. Gut 49:584–587
Jaffe ES, Harris NL, Sha VJ (eds) (2001) In: Tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. IARC Press, Lyon, pp 171–176
Chan JK, Ng CS, Isaacson PG (1990) Relationship between high-grade lymphoma and low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALToma) of the stomach. Am J Pathol 136:1153–1164
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting—Airlie House, Virginia, November 1997. J Clin Oncol 17:3835–3849
Musshoff K, Klinische Stadieneinteilung der nicht (1977) Hodgkin’s lymphoma. Strahlenthreapie Onkol 153:218–221
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez G, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an International Workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 17:1244–1253
Wotherspoon AC, Doglioni C, Diss TC, Pan L, Isaacson PG, Doglioni C, Moschini A, de Boni M (1993) Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–577
Castrillo JM, Montalban C, Obeso G, Piris MA, Rivas MC (1992) Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients. Gut 33:1307–1311
Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rube C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M for the German Multicenter Study Group (2001) Primary gastrointestinal non-Hodgkin’s lymphoma: II. combined surgical and conservative or conservative management only in localized gastric lymphoma- results of the prospective German Multicenter Study GIT NHL 01/92. J Clin Oncol 19:3874–3883
Taal BG, Boot H, van Heerde P, de Jong D, Hart AAM, Burgers JMV (1996) Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept. Gut 39:556–561
Hsu C, Chen C-L, Chen L-T, Liu H-T, Chen Y-C, Jan C-M, Liu C-S, Cheng A-L (2001) Comparison of MALT and non-MALT primary large cell lymphoma of the stomach. Cancer 19:49–56
Nakamura S, Matsumoto T, Takeshita M, Kurahara K, Yao T, Tsuneyoshi M, Iida M, Fujishima M (2000) A clinicopathologic study of primary small intestine lymphoma. Cancer 88:286–294
Villuendas R, Piris MA, Orradre JL, Mollejo M, Algara P, Sanchez L, Martinez JC, Martinez P (1992) Different bcl-2 protein expression in high-grade B-cell lymphomas derived from lymph node or mucosa associated lymphoid tissue. Am J Pathol 139:989–993
Hoeve MA, Gisbertz IAM, Schouten HC, Schuuring E, Bot FJ, Hermans J, Hopman A, Kluin PhM, Arends J-W, van Krieken JHJM (1999) Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy. Leukemia 13:799–807
Chan W-Y, Wong N, Chan AB, Chow JH, Lee JC (1998) Consistent copy number gain in chromosome 12 in primary diffuse large cell lymphomas of the stomach. Am J Pathol 152:11–16
Ott G, Kalla J, Steinhoff A, Rosenwald A, Katzenberger T, Roblick U, Ott MM, Muller-Hermelink HK (1998) Trisomy 3 is not a common feature in malignant lymphomas of mucosa-associated tissue type. Am J Pathol 152:689–694
Yoshino T, Omonishi K, Kobayashi K, Mannami T, Okada H, Mizuno M, Yamadori I, Kondo E, Akagi T (2000) Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features. J Clin Pathol 53:187–190
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ang, MK., Hee, S.W., Quek, R. et al. Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis. Ann Hematol 88, 417–424 (2009). https://doi.org/10.1007/s00277-008-0604-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-008-0604-7