- Case Report
- Open Access
Atypical burkitt's lymphoma transforming from follicular lymphoma
© Hwang et al; licensee BioMed Central Ltd. 2011
- Received: 28 March 2011
- Accepted: 8 July 2011
- Published: 8 July 2011
Amongst follicular lymphoma that transforms into a high-grade lymphoma, majority are diffuse large B cell lymphoma. Here we reported a rare atypical Burkitt's lymphoma transformation from an asymptomatic follicular lymphoma. Lymph node biopsy showed a composite lymphoma with infiltration of the inter-follicular areas by high grade small non-cleaved lymphoma cells amongst neoplastic follicles. Moreover, FISH and molecular genetic study confirmed concomitant MYC translocations and t(14;18) in the high-grade component, thereby suggesting the transformation of atypical Burkitt's lymphoma from an undiagnosed antecedent follicular lymphoma. The disease followed an aggressive clinical course, terminating in refractory disease 13 months after diagnosis. This is followed by a comprehensive review of the literature on lymphoma transformations from underlying follicular lymphoma after acquisition of MYC translocation, using Burkitt's lymphoma, follicular lymphoma, transformation and MYC translocations as keywords.
- Follicular Lymphoma
- Submandibular Lymph Node
- High Grade Transformation
- Composite Lymphoma
- High Grade Component
Follicular lymphoma (FL) is a low grade lymphoproliferative disease which frequently presents with generalized lymphadenopathy and frequent bone marrow involvement. The lymphoma arises from germinal centre lymphocytes with three histological grades based on the number of centroblasts in the neoplastic follicles. The pathogenesis of disease is due to the overexpression of the anti-apoptotic Bcl-2 associated with t(14;18), which juxtaposes BCL-2 gene on chromosome 18 to the enhancer of the immunoglobulin heavy chain gene (IgH) locus on chromosome 14. Moreover, as in their normal counterparts, the FL cells have on-going somatic hypermutations , which are implicated as a possible mechanism of high grade transformation .
Up to 30% of patients with FL had high grade transformation of their disease . In a study of 38 patients with histological progression from antecedent follicular lymphoma, the most common histology was diffuse large cell (68%), followed by diffuse mixed (21%), and small non-cleaved cell histology only constituted 5% of transformations from FL . On the other hand, in patients presenting with atypical Burkitt's lymphoma, about 25% were transformations from an antecedent FL .
MYC, located at chromosome 8q24, is a transcription factor involved in various translocations [t(8;14), t(8;22), t(2;8)], leading to its dysregulation and hence carcinogenesis. Acquisition of MYC translocation was reported in some high grade transformation of FL. Here we presented a patient with atypical Burkitt's lymphoma showing evidence of transformation from an undiagnosed antecedent FL. This is followed by a review of the literature on lymphoma transformations from underlying FL after acquisition of MYC translocation.
He received intravenous cyclophosphamide and vincristine together with oral prednisolone. After initial cytoreduction, he was induced with Stanford V regimen . He achieved only a partial response after a total of 5 cycles of Stanford regimen. Subsequent reassessment CT scan showed that while the other small intra-abdominal deposits reduced in size remarkably, there was only moderate shrinkage of the major central abdominal mass, which still measured seven cm in diameter (Figure 1B). The chemotherapy was therefore switched to ifosfamide, etoposide and high dose cytarabine (IVAC) . The disease remained refractory despite two cycles of IVAC with development of new hepatic lesions, progressive enlargement of central abdominal mass and serum LDH rising to more than 5000 U/L. This was further complicated by gastrointestinal bleeding but the bleeding source could not be localized despite upper endoscopy and colonoscopy. He was further salvaged with fludaradine, mitoxantrone and dexamethasone but he succumbed finally to refractory lymphoma.
- Kuppers R, Zhao M, Hansmann ML, Rajewsky K: Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 1993, 12: 4955-4967.PubMed CentralPubMedGoogle Scholar
- Rossi D, Berra E, Cerri M, Deambrogi C, Barbieri C, Franceschetti S, Lunghi M, Conconi A, Paulli M, Matolcsy A, Pasqualucci L, Capello D, Gaidano G: Aberrant somatic hypermutation in transformation of follicular lymphoma and chronic lymphocytic leukemia to diffuse large B-cell lymphoma. Haematologica. 2006, 91: 1405-1409.PubMedGoogle Scholar
- Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J, Vinnicombe S, Waters R, Rohatiner AZ, Lister TA: Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007, 25: 2426-2433. 10.1200/JCO.2006.09.3260.View ArticlePubMedGoogle Scholar
- Yano T, Jaffe ES, Longo DL, Raffeld M: MYC rearrangements in histologically progressed follicular lymphomas. Blood. 1992, 80: 758-767.PubMedGoogle Scholar
- Macpherson N, Lesack D, Klasa R, et al.: Small noncleaved, non-Burkitt's (Burkitt-like) lymphoma: cytogenetics predict outcome and reflect clinical presentation. J Clin Oncol. 1999, 17: 1558-1567.PubMedGoogle Scholar
- Bernstein JI, Coleman CN, Strickler JG, Dorfman RF, Rosenberg SA: Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt's and non-Burkitt's types). J Clin Oncol. 1986, 4: 847-858.PubMedGoogle Scholar
- Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID: Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996, 14: 925-934.PubMedGoogle Scholar
- Thangavelu M, Olopade O, Beckman E, Vardiman JW, Larson RA, McKeithan TW, Le Beau MM, Rowley JD: Clinical, morphologic, and cytogenetic characteristics of patients with lymphoid malignancies characterized by both t(14;18)(q32;q21) and t(8;14)(q24;q32) or t(8;22)(q24;q11). Genes Chromosomes Cancer. 1990, 2: 147-158. 10.1002/gcc.2870020211.View ArticlePubMedGoogle Scholar
- Knezevich S, Ludkovski O, Salski C, Lestou V, Chhanabhai M, Lam W, Klasa R, Connors JM, Dyer MJ, Gascoyne RD, Horsman DE: Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas. Leukemia. 2005, 19: 659-663.PubMedGoogle Scholar
- Bisiau H, Daudignon A, Le Baron F, Pollet JP, Preudhomme C, Duthilleul P, Bastard C: Transformation of follicular lymphoma with both t(14;18) and t(8;22). Nouv Rev Fr Hematol. 1995, 37: 241-244.PubMedGoogle Scholar
- Lee JT, Innes DJ, Williams ME: Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma. J Clin Invest. 1989, 84: 1454-1459. 10.1172/JCI114320.PubMed CentralView ArticlePubMedGoogle Scholar
- Takahashi T, Hara T, Yoshikawa T, Shimomura Y, Tsurumi H, Yamada T, Tomita E, Moriwaki H: Early transformation from follicular lymphoma to Burkitt lymphoma. Rinsho Ketsueki. 2005, 46: 1055-1059.PubMedGoogle Scholar
- Young KH, Xie Q, Zhou G, Eickhoff JC, Sanger WG, Aoun P, Chan WC: Transformation of follicular lymphoma to precursor B-cell lymphoblastic lymphoma with c-myc gene rearrangement as a critical event. Am J Clin Pathol. 2008, 129: 157-166. 10.1309/NKK3FEX2BE5L7EKB.View ArticlePubMedGoogle Scholar
- Voorhees PM, Carder KA, Smith SV, Ayscue LH, Rao KW, Dunphy CH: Follicular lymphoma with a burkitt translocation-predictor of an aggressive clinical course: a case report and review of the literature. Arch Pathol Lab Med. 2004, 128: 210-213.PubMedGoogle Scholar
- Li L, Gupta S, Bashir T, Koduru PR, Brody J, Allen SL: Serial cytogenetic alterations resulting in transformation of a low-grade follicular lymphoma to Burkitt lymphoma. Cancer Genet Cytogenet. 2006, 170: 140-6. 10.1016/j.cancergencyto.2006.05.015.View ArticlePubMedGoogle Scholar
- Gauwerky CE, Hoxie J, Nowell PC, Croce CM: Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma. Oncogene. 1988, 2: 431-435.PubMedGoogle Scholar
- Tomita N, Nakamura N, Kanamori H, Fujimaki K, Fujisawa S, Ishigatsubo Y, Nomura K: Atypical Burkitt lymphoma arising from follicular lymphoma: demonstration by polymerase chain reaction following laser capture microdissection and by fluorescence in situ hybridization on paraffin-embedded tissue sections. Am J Surg Pathol. 2005, 29: 121-124. 10.1097/01.pas.0000146027.76706.50.View ArticlePubMedGoogle Scholar
- Mukhopadhyay S, Readling J, Cotter PD, Shrimpton AE, Sidhu JS: Transformation of follicular lymphoma to Burkitt-like lymphoma within a single lymph node. Human Pathol. 2005, 36: 571-575. 10.1016/j.humpath.2005.01.004.View ArticleGoogle Scholar
- De Jong D, Voetdijk BM, Beverstock GC, van Ommen GJ, Willemze R, Kluin PM: Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma. N Engl J Med. 1988, 318: 1373-1378. 10.1056/NEJM198805263182106.View ArticlePubMedGoogle Scholar
- Parker SM, Olteanu H, Vantuinen P, Lawton CA, Schultz CJ, Christians KK, Fenske TS: Follicular lymphoma transformation to dual translocated Burkitt-like lymphoma: improved disease control associated with radiation therapy. Int J Hematol. 2009, 90: 616-622. 10.1007/s12185-009-0444-9.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.