PMID- 29155023 OWN - NLM STAT- MEDLINE DCOM- 20171204 LR - 20190816 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 103 IP - 3 DP - 2017 Dec TI - Therapy-related myeloid neoplasm in an 18-year-old boy with B-lymphoblastic leukemia. PG - 263-266 LID - S0014-4800(17)30601-9 [pii] LID - 10.1016/j.yexmp.2017.11.007 [doi] AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Acute myeloid leukemia or myelodysplastic syndrome during the course of ALL is a rare entity. Some of these cases are therapy-related while the others occur due to lineage switch. The correct diagnosis relies on comparing the immunophenotypes and cytogenetic/molecular alterations of the myeloid neoplasm and the ALL. We present the clinical, pathologic and cytogenetic features of a case of an 18-year-old male with prior treatment for B-lymphoblastic leukemia (B-ALL) who developed therapy-related myeloid neoplasm (t-MN) 4-5years after his initial diagnosis of B-ALL. CASE PRESENTATION: A 13-year-old boy with no significant past medical history presented to Harbor-UCLA Medical Center (HUMC) in November 2012 with night sweats, fevers and chills, nausea, vomiting, diarrhea, fatigue, weakness, and weight loss. Peripheral blood flow cytometric analysis disclosed B-ALL. The blasts expressed CD10, CD19, CD22 (dim), CD34, CD38, HLA-DR, and TdT, and were negative for CD20, CD13, CD33, CD117, and cytoplasmic MPO. Chromosomal analysis and a supplemental fluorescence in situ hybridization (FISH) study performed on the bone marrow aspirate showed an abnormal karyotype (47,XY,+X,del(9)(p21p21)[4]/46,XY[16]). He achieved remission after induction chemotherapy and remained in remission until March 2016 when bilateral testicular masses were noted. Biopsy of the left testicular mass showed relapsed B-ALL. Cerebrospinal fluid (CSF) contained rare TdT-positive blasts, suggestive of minimal/early involvement by B-ALL. However, there was no evidence of acute leukemia in his bone marrow at this time. He was then treated with COG protocol AALL1331 randomized to blinatumomab arm and achieved second remission. In June 2017, the patient's peripheral blood smear showed 11% circulating monoblasts. By flow cytometry, the blasts expressed CD4, CD11b, CD13, CD15, CD33, CD38, CD56, and CD64. In addition, a few TdT-positive blasts were seen in his CSF cytospin smear. Bone marrow biopsy was subsequently performed which was consistent with evolving acute myeloid leukemia. A diagnosis of myeloid neoplasm, consistent with t-MN was made. Chromosomal analysis and FISH studies performed on his bone marrow aspirate showed normal karyotype (46,XY[20]), negative FISH result for deletion 9p21 locus, and positive KMT2A (MLL) rearrangement, respectively. Despite of chemotherapy, the patient died within one month after diagnosis. DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents and/or irradiation. In this case study, we diagnosed t-MN with KMT2A rearrangement in a patient with history of B-ALL with 9p deletion and gain of X chromosome. Unusual features associated with this case are discussed. CI - Published by Elsevier Inc. FAU - Qing, Xin AU - Qing X AD - Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. Electronic address: xqing@dhs.lacounty.gov. FAU - Panosyan, Eduard AU - Panosyan E AD - Department of Pediatrics, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. FAU - Yue, Changjun AU - Yue C AD - Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. FAU - Ji, Ping AU - Ji P AD - Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. FAU - Gotesman, Moran AU - Gotesman M AD - Department of Pediatrics, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. FAU - French, Samuel AU - French S AD - Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA. FAU - Cai, Junchao AU - Cai J AD - Foresight MedTech Research Center, Los Angeles, CA, United States. LA - eng PT - Case Reports PT - Journal Article DEP - 20171116 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (KMT2A protein, human) RN - 0 (Neoplasm Proteins) RN - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) SB - IM MH - Adolescent MH - Chromosomes, Human, Pair 9/genetics MH - Chromosomes, Human, X/genetics MH - Gene Expression Regulation, Leukemic MH - Histone-Lysine N-Methyltransferase/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Induction Chemotherapy/adverse effects MH - Leukemia, Myeloid, Acute/chemically induced/diagnosis/*genetics/pathology MH - Male MH - Myeloid-Lymphoid Leukemia Protein/*genetics MH - Neoplasm Proteins/genetics MH - Neoplasms, Second Primary/chemically induced/diagnosis/*genetics/pathology MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/diagnosis/*drug therapy/pathology OTO - NOTNLM OT - Acute leukemia OT - Lymphoblastic leukemia OT - Myeloid leukemia OT - Therapy-related myeloid neoplasms EDAT- 2017/11/21 06:00 MHDA- 2017/12/05 06:00 CRDT- 2017/11/21 06:00 PHST- 2017/11/15 00:00 [received] PHST- 2017/11/15 00:00 [accepted] PHST- 2017/11/21 06:00 [pubmed] PHST- 2017/12/05 06:00 [medline] PHST- 2017/11/21 06:00 [entrez] AID - S0014-4800(17)30601-9 [pii] AID - 10.1016/j.yexmp.2017.11.007 [doi] PST - ppublish SO - Exp Mol Pathol. 2017 Dec;103(3):263-266. doi: 10.1016/j.yexmp.2017.11.007. Epub 2017 Nov 16.