Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens

Sharad Khurana, Megan E. Melody, Rhett P. Ketterling, Jess F. Peterson, Ivy M. Luoma, George Vazmatzis, Han W. Tun, James M. Foran, Liuyan Jiang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)40-44
Number of pages5
JournalCancer Genetics
Volume240
DOIs
StatePublished - Jan 2020

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
DNA Nucleotidylexotransferase
B-Lymphocytes
Antigens
Diagnostic Errors
Molecular Diagnostic Techniques
T-Lymphoid Precursor Cells
T-Lymphocytes
B-Cell Lymphoma
Fluorescence In Situ Hybridization
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Non-Hodgkin's Lymphoma
Leukemia
Bone Marrow
Immunohistochemistry
Databases
Staining and Labeling
Mutation

Keywords

  • Early T-cell precursor LBL (ETP-LBL)
  • Fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Mate-pair sequencing (MPseq)
  • Next generation sequencing (NGS)
  • PICALM-MLLT10

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens. / Khurana, Sharad; Melody, Megan E.; Ketterling, Rhett P.; Peterson, Jess F.; Luoma, Ivy M.; Vazmatzis, George; Tun, Han W.; Foran, James M.; Jiang, Liuyan.

In: Cancer Genetics, Vol. 240, 01.2020, p. 40-44.

Research output: Contribution to journalArticle

Khurana, Sharad ; Melody, Megan E. ; Ketterling, Rhett P. ; Peterson, Jess F. ; Luoma, Ivy M. ; Vazmatzis, George ; Tun, Han W. ; Foran, James M. ; Jiang, Liuyan. / Molecular and phenotypic characterization of an early T-cell precursor acute lymphoblastic lymphoma harboring PICALM-MLLT10 fusion with aberrant expression of B-cell antigens. In: Cancer Genetics. 2020 ; Vol. 240. pp. 40-44.
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abstract = "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.",
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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

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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.

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