TY - JOUR
T1 - Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens
AU - Khurana, Sharad
AU - Melody, Megan E.
AU - Ketterling, Rhett P.
AU - Peterson, Jess F.
AU - Luoma, Ivy M.
AU - Vazmatzis, George
AU - Tun, Han W.
AU - Foran, James M.
AU - Jiang, Liuyan
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/1
Y1 - 2020/1
N2 - T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is usually diagnosed based on the presence of immature lymphoid marker terminal deoxynucleotidyl transferase (TdT), and T-cell specific markers, specifically CD3, by immunohistochemistry (IHC) staining on bone marrow and/or extramedullary tissue. We present a novel, TdT and CD3 negative, aggressive early T-cell precursor LBL (ETP-LBL) initially misdiagnosed as a high grade B-cell lymphoma due to expression of CD79a and the erroneous detection of BCL2/IGH fusion. The patient was eventually evaluated using molecular diagnostic techniques, including fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays that demonstrated PICALM-MLLT10 fusion and a NOTCH1 mutation in the absence of BCL2/IGH fusion. The use of NGS, specifically mate-pair sequencing (MPseq), subsequently confirmed an in-frame PICALM-MLLT10 fusion. Our retrospective analysis showed that PICALM-MLLT10 fusion has no association with CD3/TdT negativity, as 6/49 T-ALL/LBL cases from Mayo Clinic database (01/1998–09/2018), including this case, were noted to have PICALM-MLLT10 fusion; however, none of the other cases were associated with CD3/TdT negativity. We emphasize the importance of a comprehensive hematopathologic evaluation including multiple molecular studies for the appropriate interrogation and classification of a difficult acute leukemia diagnosis, and to prevent potential diagnostic errors of clinical significance.
AB - T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is usually diagnosed based on the presence of immature lymphoid marker terminal deoxynucleotidyl transferase (TdT), and T-cell specific markers, specifically CD3, by immunohistochemistry (IHC) staining on bone marrow and/or extramedullary tissue. We present a novel, TdT and CD3 negative, aggressive early T-cell precursor LBL (ETP-LBL) initially misdiagnosed as a high grade B-cell lymphoma due to expression of CD79a and the erroneous detection of BCL2/IGH fusion. The patient was eventually evaluated using molecular diagnostic techniques, including fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) assays that demonstrated PICALM-MLLT10 fusion and a NOTCH1 mutation in the absence of BCL2/IGH fusion. The use of NGS, specifically mate-pair sequencing (MPseq), subsequently confirmed an in-frame PICALM-MLLT10 fusion. Our retrospective analysis showed that PICALM-MLLT10 fusion has no association with CD3/TdT negativity, as 6/49 T-ALL/LBL cases from Mayo Clinic database (01/1998–09/2018), including this case, were noted to have PICALM-MLLT10 fusion; however, none of the other cases were associated with CD3/TdT negativity. We emphasize the importance of a comprehensive hematopathologic evaluation including multiple molecular studies for the appropriate interrogation and classification of a difficult acute leukemia diagnosis, and to prevent potential diagnostic errors of clinical significance.
KW - Early T-cell precursor LBL (ETP-LBL)
KW - Fluorescence in situ hybridization (FISH)
KW - Immunohistochemistry (IHC)
KW - Mate-pair sequencing (MPseq)
KW - Next generation sequencing (NGS)
KW - PICALM-MLLT10
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UR - http://www.scopus.com/inward/citedby.url?scp=85074950423&partnerID=8YFLogxK
U2 - 10.1016/j.cancergen.2019.11.002
DO - 10.1016/j.cancergen.2019.11.002
M3 - Article
C2 - 31739126
AN - SCOPUS:85074950423
SN - 2210-7762
VL - 240
SP - 40
EP - 44
JO - Cancer Genetics
JF - Cancer Genetics
ER -