A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood: A single tertiary care pediatric institution experience in North America

Amy M Coffey, Annisa Lewis, Andrea N. Marcogliese, M. Tarek Elghetany, Jyotinder N. Punia, Chung Che Chang, Carl E. Allen, Kenneth L. McClain, Amos S. Gaikwad, Nader Kim El-Mallawany, Choladda V. Curry

Research output: Contribution to journalArticle

Abstract

Background: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities. Design: Eight cases (six clinical and two autopsy) with S-EBV-T-LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T-cell receptor gene rearrangement studies were recorded. Results: Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV+ T-cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4+ or CD8+ T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH-94 or HLH-2004 protocols with or without bone marrow transplant. Conclusion: In this large pediatric clinicopathologic study of S-EBV-T-LPD of childhood in the United States, EBV-HLH, S-EBV-TCL, and S-CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH-directed therapies.

Original languageEnglish (US)
Article numbere27798
JournalPediatric Blood and Cancer
Volume66
Issue number8
DOIs
StatePublished - Aug 1 2019

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Lymphoproliferative Disorders
Tertiary Healthcare
North America
Human Herpesvirus 4
Pediatrics
T-Lymphocytes
Hemophagocytic Lymphohistiocytosis
Epstein-Barr Virus Infections
T-Cell Lymphoma
T-Lymphocyte Gene Rearrangement
T-Cell Receptor Genes
Gene Rearrangement
Serology
Viral Load
Hispanic Americans
Autopsy
Lymphoma
Flow Cytometry
Fever
Bone Marrow

Keywords

  • CAEBV
  • EBV
  • HLH
  • hemophagocytosis
  • lymphoma
  • lymphoproliferative disorder

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood : A single tertiary care pediatric institution experience in North America. / Coffey, Amy M; Lewis, Annisa; Marcogliese, Andrea N.; Elghetany, M. Tarek; Punia, Jyotinder N.; Chang, Chung Che; Allen, Carl E.; McClain, Kenneth L.; Gaikwad, Amos S.; El-Mallawany, Nader Kim; Curry, Choladda V.

In: Pediatric Blood and Cancer, Vol. 66, No. 8, e27798, 01.08.2019.

Research output: Contribution to journalArticle

Coffey, Amy M ; Lewis, Annisa ; Marcogliese, Andrea N. ; Elghetany, M. Tarek ; Punia, Jyotinder N. ; Chang, Chung Che ; Allen, Carl E. ; McClain, Kenneth L. ; Gaikwad, Amos S. ; El-Mallawany, Nader Kim ; Curry, Choladda V. / A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood : A single tertiary care pediatric institution experience in North America. In: Pediatric Blood and Cancer. 2019 ; Vol. 66, No. 8.
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abstract = "Background: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities. Design: Eight cases (six clinical and two autopsy) with S-EBV-T-LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T-cell receptor gene rearrangement studies were recorded. Results: Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV+ T-cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4+ or CD8+ T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH-94 or HLH-2004 protocols with or without bone marrow transplant. Conclusion: In this large pediatric clinicopathologic study of S-EBV-T-LPD of childhood in the United States, EBV-HLH, S-EBV-TCL, and S-CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH-directed therapies.",
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author = "Coffey, {Amy M} and Annisa Lewis and Marcogliese, {Andrea N.} and Elghetany, {M. Tarek} and Punia, {Jyotinder N.} and Chang, {Chung Che} and Allen, {Carl E.} and McClain, {Kenneth L.} and Gaikwad, {Amos S.} and El-Mallawany, {Nader Kim} and Curry, {Choladda V.}",
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T1 - A clinicopathologic study of the spectrum of systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood

T2 - A single tertiary care pediatric institution experience in North America

AU - Coffey, Amy M

AU - Lewis, Annisa

AU - Marcogliese, Andrea N.

AU - Elghetany, M. Tarek

AU - Punia, Jyotinder N.

AU - Chang, Chung Che

AU - Allen, Carl E.

AU - McClain, Kenneth L.

AU - Gaikwad, Amos S.

AU - El-Mallawany, Nader Kim

AU - Curry, Choladda V.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities. Design: Eight cases (six clinical and two autopsy) with S-EBV-T-LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T-cell receptor gene rearrangement studies were recorded. Results: Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV+ T-cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4+ or CD8+ T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH-94 or HLH-2004 protocols with or without bone marrow transplant. Conclusion: In this large pediatric clinicopathologic study of S-EBV-T-LPD of childhood in the United States, EBV-HLH, S-EBV-TCL, and S-CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH-directed therapies.

AB - Background: Systemic forms of EBV-associated T-cell lymphoproliferative disorders of childhood (S-EBV-T-LPD) comprise three major forms: EBV-positive hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV-positive T-cell lymphoma (S-EBV-TCL), and systemic chronic active EBV infection (S-CAEBV). These disorders occur rarely in children in Western countries. Here, we described eight children of such entities. Design: Eight cases (six clinical and two autopsy) with S-EBV-T-LPD of childhood were retrospectively identified from 1990 to 2015. Clinicopathologic parameters including histomorphology, immunophenotype, EBV studies, and T-cell receptor gene rearrangement studies were recorded. Results: Patients include five females and three males of Hispanic, Asian, and Caucasian origins with an age range of 14 months to 9 years. Fever, hepatosplenomegaly, cytopenias, abnormal EBV serologies, and very high EBV viral loads were common findings. Histologic findings showed EBV+ T-cell infiltrates with variable degrees of architectural distortion and cytologic atypia ranging from no to mild cytologic atypia to overt lymphoma and tissue hemophagocytosis. All showed aberrant CD4+ or CD8+ T cells with dim to absent CD5, CD7, and CD3, and bright CD2 and CD45 by flow cytometry or loss of CD5 by immunohistochemistry. TCR gene rearrangement studies showed monoclonal rearrangements in all clinical cases (6/6). Outcomes were poor with treatment consisting of chemotherapy per the HLH-94 or HLH-2004 protocols with or without bone marrow transplant. Conclusion: In this large pediatric clinicopathologic study of S-EBV-T-LPD of childhood in the United States, EBV-HLH, S-EBV-TCL, and S-CAEBV show many overlapping features. Diagnosis is challenging, and overall outcome is poor using current HLH-directed therapies.

KW - CAEBV

KW - EBV

KW - HLH

KW - hemophagocytosis

KW - lymphoma

KW - lymphoproliferative disorder

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