Please cite this article in press as: J.C. Nguyen, et al., Successful treatment of both double minute of C-MYC and BCL-2 rearrangement containing large B-cell lymphoma with subsequent unfortunate development of therapy-related acute myeloid leukemia with t(3;3)(q26.2;q21), Pathol. – Res. Pract (2015), http://dx.doi.org/10.1016/j.prp.2015.07.004 ARTICLE IN PRESS G Model PRP-51422; No. of Pages 9 Pathology – Research and Practice xxx (2015) xxx–xxx Contents lists available at ScienceDirect Pathology – Research and Practice jou rn al hom epage: www.elsevier.com/locate/prp Teaching case Successful treatment of both double minute of C-MYC and BCL-2 rearrangement containing large B-cell lymphoma with subsequent unfortunate development of therapy-related acute myeloid leukemia with t(3;3)(q26.2;q21) John C. Nguyen a , Melanie J. Kubik a , H. Elizabeth Broome a , Peter T. Curtin b , Marie L. Dell’Aquila a , Huan-You Wang a,∗ a Department of Pathology, University of California San Diego Health System, La Jolla, CA 92093-0960, United States b Division of Hematology, Department of Medicine, University of California San Diego Health System, La Jolla, CA 92093-0960, United States a r t i c l e i n f o Article history: Received 25 May 2015 Received in revised form 25 June 2015 Accepted 13 July 2015 Keywords: Large B-cell lymphoma C-MYC Double minute Therapy-related acute myeloid leukemia t(3 ;3)(q26.2 ;q21) a b s t r a c t Double minute chromosomes (DMs), although relatively frequently encountered in solid tumors, are rare in hematologic neoplasms such as acute myeloid leukemia (AML), and even rarer in lymphoid neo- plasms. t(3;3)(q26.2;q21) is a very rare genetic alteration observed in myeloid neoplasm. Herein we report an interesting and unique case of concomitant C-MYC DMs and t(14;18)-containing large B-cell lymphoma, which was successfully treated with R-hyper-CVAD; unfortunately, the patient has developed a therapy-related AML (t-AML) 2 years since the start of his lymphoma treatment. His t-AML contains both t(3;3)(q26.2;q21) and monosomy 7, and the patient died of AML 10 months after the initial diagnosis of t-AML despite clinical remission. To the best of our knowledge, this is the first reported case of C-MYC DM-containing de novo large B-cell lymphoma, which was successfully treated with complete remission, but unfortunately died of t-AML harboring t(3;3)(q21;q26). © 2015 Elsevier GmbH. All rights reserved. Introduction Double minute chromosomes (DMs) are defined as extrachro- mosomal small circular chromatin particles/bodies that replicate and segregate in the absence of centromeres [1]. Together with homogenously staining regions (HSR), DMs are one of the genetic means employed mainly by tumor cells to amplify oncogenes and/or confer drug-resistance [2]. While DMs are frequently observed in solid tumors such as neuroblastoma and glioblastoma to name a few [2], they are rarely seen in myeloid neoplasms such as acute myeloid leukemia (AML) [3] or myelodysplastic syndrome (MDS) [4]. DMs identified in AML or MDS cases are mainly C-MYC and mixed lineage leukemia (MLL) gene [5]. DMs are an extremely rare genetic event in lymphoid neo- plasms, there has been so far only 2 reported cases of mature lymphomas containing DMs: one follicular lymphoma with REL- positive DMs [6] and one follicular lymphoma with large cell ∗ Corresponding author at: Department of Pathology, University of California San Diego Health System, 3855 Health Sciences Drive, La Jolla, CA 92093-0987, United States. E-mail address: huw003@ucsd.edu (H.-Y. Wang). transformation harboring C-MYC-containing DMs [7]. However, C- MYC DMs in de novo large B-cell lymphoma, to the best of our knowledge, has not yet been reported in the English literature so far. Therapy-related AML (t-AML) is thought to be a direct result of mutational events induced by cytotoxic therapy, such as chemotherapy, radiation, immunosuppressive therapy, or the com- bined effect of these modalities, as prescribed for a primary malignancy [8], although a direct mechanism of pathogenesis has not yet been proven. Cytogenetically, t-AMLs show a similar spec- trum of alterations as de novo AMLs; however, the frequency of unfavorable cytogenetic abnormalities, such as complex kary- otypes, deletions or loss of chromosomes 5 or 7, are significantly higher in t-AML [8]. Abnormalities of the long arm of chromosome 3 at bands q21 and q26, including inversions, namely inv(3)(q21q26), and translocations including t(3;3)(q21;q26) among others, are col- lectively referred as 3q21q26 syndrome [9]. While most forms of genetic abnormalities in 3q21q26 syndrome are rarely seen in MDS and dysplasia-related AML [10], among 9 reported AML with t(3;3)(q26.2;q21) by Secker-Walker et al. [10], none was t-AML. The genes involved in inv(3)(q21q26) and t(3;3)(q21;q26.2) are ecotropic viral integration site 1 (EVI1) on 3q26 and GATA2 on 3q21 http://dx.doi.org/10.1016/j.prp.2015.07.004 0344-0338/© 2015 Elsevier GmbH. All rights reserved.