Abstract
API2-MALT1 fusion and aneuploidy are common chromosomal abnormalities in MALT lymphoma. In studying their incidence and relationship in primary pulmonary MALT lymphomas, a translocation involving MALT1 and IGH was also identified. In all, 28 primary pulmonary MALT lymphomas were studied by fluorescence in situ hybridization using an API2-MALT1 probe and multiple centromeric probes, as well as IGH-BCL2, IGH-MALT1, and MALT1 breakapart probes in selected cases. Seven (25%) had API2-MALT1 fusion; all seven lacked aneuploidy except for two with trisomy 3 in a small clone. Three (11%) had IGH-MALT1 fusion; two also showed trisomy 3 and 12. A total of 11 (39%) had aneuploidy only, with trisomy 3 and 18 being the most common. Ectopic nuclear bcl-10 expression, which has been previously associated with API2-MALT1, was seen by immunohistochemistry in 86% of API2-MALT1 fusion-positive cases, one IGH-MALT1 fusion-positive case, two aneuploidy-only cases, and two normal cases. In primary pulmonary MALT lymphomas, cytogenetic abnormalities are common (75%) and heterogeneous, encompassing API2-MALT1 and IGH-MALT1, which are mutually exclusive, as well as aneuploidy, which may be present in the latter but is rare in the former. Ectopic nuclear bcl-10 expression is associated with API2-MALT1 but may also be seen in IGH-MALT1 fusion-positive, aneuploidy-only, and normal cases.
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References
Rosenwald A, Ott G, Stilgenbauer S, Kalla J, Bredt M, Katzenberger T et al. Exclusive detection of the t(11;18)(q21;q21) in extranodal marginal zone B cell lymphomas (MZBL) of MALT type in contrast to other MZBL and extranodal large B cell lymphomas. Am J Pathol 1999; 155: 1817–1821.
Remstein ED, James C, Kurtin PJ . Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol 2000; 156: 1183–1188.
Maes B, Baens M, Marynen P, De Wolf-Peeters C . The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding in marginal zone cell lymphoma of extranodal MALT-type. Ann Oncol 2000; 5: 521–526.
Baens M, Maes B, Steyls A, Geboes K, Marynen P, De Wolf-Peeters C . The product of the t(11;18), an API2-MLT fusion, marks nearly half of gastric MALT type lymphomas without large cell proliferation. Am J Pathol 2000; 156: 1433–1439.
Dierlamm J, Baens M, Stefanova-Ouzounova M, Hinz K, Wlodarska I, Maes B et al. Detection of t(11;18)(q21;q21) by interphase fluorescence in situ hybridization using API2 and MLT specific probes. Blood 2000; 96: 2215–2218.
Liu H, Ye H, Dogan A, Ranaldi R, Hamoudi RA, Bearzi I et al. t(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood 2001; 98: 1182–1187.
Yonezumi M, Suzuki R, Suzuki H, Yoshino T, Oshima K, Hosokawa Y et al. Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription polymerase chain reaction (PCR) and genomic long and accurate PCR analyses. Br J Haematol 2001; 115: 588–594.
Inagaki H, Okabe M, Seto M, Nakamura S, Ueda R, Eimoto T . API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma: multiplex RT-PCR detection using formalin-fixed paraffin-embedded specimens. Am J Pathol 2001; 158: 699–706.
Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G et al. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood 2002; 99: 3–9.
Remstein ED, Kurtin PJ, James CD, Wang XY, Meyer RG, Dewald GW . Mucosa-associated lymphoid tissue lymphomas with t(11;18)(q21;q21) and mucosa-associated lymphoid tissue lymphomas with aneuploidy develop along different pathogenetic pathways. Am J Pathol 2002; 161: 63–71.
Chuang SS, Lee C, Hamoudi F, Liu H, Lee PS, Ye H et al. High frequency of t(11;18) in gastric mucosa-associated lymphoid tissue lymphomas in Taiwan, including one patient with high-grade transformation. Br J Haematol 2003; 120: 97–100.
Ye H, Liu H, Attygalle A, Wotherspoon AC, Nicholson AG, Charlotte F et al. Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H.pylori in gastric MALT lymphoma. Blood 2003; 102: 1012–1018.
Streubel B, Lamprecht A, Dierlamm J, Cerroni L, Stolte M, Ott G et al. t(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood 2003; 101: 2335–2339.
Sanchez-Izquierdo D, Buchonet G, Siebert R, Gascoyne RD, Climent J, Karran L et al. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. Blood 2003; 101: 4539–4546.
Kurtin PJ, Myers JL, Adlakha H, Strickler JG, Lohse C, Pankratz VS et al. Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type. Am J Surg Pathol 2001; 25: 997–1008.
Isaacson PG, Muller-Hermelink HK, Piris MA, Berger F, Nathwani BN, Swerdlow SH et al. Mature B-cell neoplasms. In: Jaffe ES, Harris N, Stein HJ, Vardiman J (eds). World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Haematopoiectic and Lymphoid Tissues. Lyon: IARC Press, 2001, pp 157–160.
Kurtin PJ, Hobday KS, Ziesmer S, Caron BL . Demonstration of distinct antigenic profiles of small B-cell lymphomas by paraffin section immunohistochemistry. Am J Clin Pathol 1999; 112: 319–329.
Paternoster SF, McClure RF, Remstein ED, Kurtin PJ, Dewald GW . A new method to extract nuclei from paraffin-embedded tissue to study lymphomas using interphase FISH. Am J Pathol 2002; 160: 1967–1972.
Okabe M, Inagaki H, Ohshima K, Yoshino T, Li C, Eimoto T et al. API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Am J Pathol 2003; 162: 1113–1122.
Maes B, Demunter A, Peeters B, De Wolf-Peeters C . BCL10 mutation does not represent an important pathogenic mechanism in gastric MALT-type lymphoma, and the presence of the API2-MLT fusion is associated with aberrant nuclear BCL10 expression. Blood 2002; 99: 1398–1404.
Ye H, Liu H, Raderer M, Chott A, Ruskone-Fourmestraux A, Wotherspoon A et al. High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT lymphoma. Blood 2003; 101: 2547–2550.
Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, Ye H, Molina T, Bouhnik Y et al. Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet 2001; 357: 39–40.
Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C et al. t(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology 2002; 122: 1286–1294.
Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF et al. BCL10 and MALT1, independent targets of chromosomal translocation in MALT lymphoma, cooperate in a novel NF-kappa B signaling pathway. J Biol Chem 2001; 276: 19012–19019.
Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV et al. Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 2000; 6: 961–970.
Griffin CA, Zehnbauer BA, Beschorner WE, Ambinder R, Mann R . t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic lymphoma. Genes Chromosomes Cancer 1992; 4: 153–157.
Hosaka S, Akamatsu T, Nakamura S, Kaneko T, Kitano K, Kiyosawa K et al. Mucosa-associated lymphoid tissue (MALT) lymphoma of the rectum with chromosomal translocation of the t(11;18)(q21;q21) and an additional aberration of trisomy 3. Am J Gastroenterol 1999; 94: 1951–1954.
Wotherspoon AC, Pan LX, Diss TC, Isaacson PG . Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue. Cancer Genet Cytogenet 1992; 58: 35–38.
Wotherspoon AC, Soosay GN, Diss TC, Isaacson PG . Low-grade primary B-cell lymphoma of the lung. An immunohistochemical, molecular, and cytogenetic study of a single case. Am J Clin Pathol 1990; 94: 655–660.
Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet 1999; 22: 63–68.
Achuthan R, Bell SM, Carr IM, Leek JP, Roberts P, Horgan K et al. Bcl10 in malignant lymphomas – an evaluation using fluorescence in situ hybridization. J Pathol 2002; 196: 59–66.
Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I et al. Bcl10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma. Am J Pathol 2000; 157: 1147–1154.
Abe K, Hori Y, Ohtsu SY, Koike Y . A case of non-Hodgkin's lymphoma with macroglobulinemia. Acta Otolaryngol Suppl 1996; 523: 259–262.
Acknowledgements
The authors thank Ms Stephanie Brockman for her technical assistance in the fluorescence in situ hybridization laboratory, and Ms Kristin Rieger for her expert secretarial assistance.
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This work was presented in part at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, USA, December 8, 2002
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Remstein, E., Kurtin, P., Einerson, R. et al. Primary pulmonary MALT lymphomas show frequent and heterogeneous cytogenetic abnormalities, including aneuploidy and translocations involving API2 and MALT1 and IGH and MALT1. Leukemia 18, 156–160 (2004). https://doi.org/10.1038/sj.leu.2403185
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DOI: https://doi.org/10.1038/sj.leu.2403185
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