Lymphoma and plasma cell neoplasms
T / NK cell disorders
Systemic EBV+ T cell Lymphoproliferative Disease of Childhood (S-EBV-TLPD)

Author: Dragos Luca, M.D. (see Authors page)

Revised: 14 March 2017, last major update January 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Systemic EBV+ T cell Lymphoproliferative Disease of Childhood

See also: Hydroa Vacciniforme-like Lymphoma (HVL)
Cite this page: Systemic EBV+ T cell Lymphoproliferative Disease of Childhood (S-EBV-TLPD). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonBchild.html. Accessed August 20th, 2017.
Definition / general
  • Life threatening illness of children and young adults characterized by a clonal proliferation of EBV infected T cells with an activated cytotoxic phenotype (WHO 2008)
  • Increased frequency in Asians and Native Americans from Central and South America, and Mexico
Terminology
  • Overlapping clinicopathologic features with aggressive NK cell leukemia
  • Historical terms: fulminant EBV+ T cell lymphoproliferative disorder of childhood, sporadic fatal infectious mononucleosis, fulminant hemophagocytic syndrome in children (Taiwan, Am J Pathol 1994;144:1219), fatal EBV associated hemophagocytic syndrome (Japan), severe chronic active EBV infection
  • Severe chronic active EBV infection: infectious mononucleosis-like syndrome persisting for at least 6 months and associated with high titers of VCA IgG and EA IgG but no association with malignancy, autoimmune disease or immunodeficiency
Epidemiology
  • Most prevalent in Asia, primarily Japan and Taiwan; also reported in Mexico and rarely in West
  • Children and young adults, no sex predilection
  • Western version of chronic active EBV infection - progression to EBV-TLPD uncommon
  • Japanese version of chronic active EBV infection - more severe with high fever, hepatosplenomegaly, extensive lymphadenopathy, pancytopenia, higher viral copy numbers in peripheral blood T cells or NK cells, monoclonal proliferation, usually progresses to malignancy (Blood 2001;98:280)
Sites
  • Systemic: liver, spleen, lymph nodes, bone marrow, skin, lung
Etiology
  • Develops shortly after primary EBV infection or in the setting of chronic active EBV infection
  • Etiology unknown, but association with EBV and racial predisposition strongly suggest genetic immune defect
Diagrams / tables

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Progression free survival

Postulated normal counterpart
  • Cytotoxic CD8+ T lymphocytes or activated CD4+ T cells
Clinical features
  • Previously healthy, then acute onset with fever and general malaise suggestive of viral syndrome, hepatosplenomegaly and liver failure and variable lymphadenopathy
  • Aphthous stomatitis, ulcerative gingivitis, vesiculopapular and papulonecrotic mucocutaneous eruptions
  • Very fulminant clinical course
  • Rapid progression with multiple organ failure, sepsis and death, usually occuring in days to weeks
  • Lab: pancytopenia, abnormal liver function tests, abnormal EBV serology with low or absent anti-VCA IgM antibodies
  • Imaging: interstitial pneumonia, basal ganglia calcifications, coronary aneurysms
  • Complications: hemophagocytic syndrome (Leuk Lymphoma 1995;19:401), coagulopathy, GI ulcers, coronary aneurysms, CNS involvement, multiorgan failure and sepsis
Treatment
  • No standard treatment
  • Usually resistant to conventional chemotherapy; hematopoietic stem cell transplant has been introduced
  • Fulminant course in most cases with death within days or weeks
  • Subacute course of several months to a year also possible
Microscopic (histologic) description
  • Infiltrating, usually small T cells with no significant atypia; may have pleomorphic medium to large lymphoid cells, irregular nuclei and frequent mitoses
  • Marked sinusoidal infiltration and hemophagocytosis in liver and spleen, splenic white pulp depletion, hepatic portal and sinusoidal infiltration, cholestasis, steatosis and necrosis
  • Lymph nodes: preserved architecture, open sinuses, variable sinus histiocytosis with erythrophagocytosis
  • Bone marrow: lymphohistiocytic hyperplasia with prominent erythrophagocytosis
  • Lung: necrosis and peribronchial infiltration, sometimes angiocentricity and angioinvasion
  • Skin: extension from epidermis to subcutis, necrosis, angiocentricity, angioinvasion, periappendageal infiltration, epidermal ulceration
Microscopic (histologic) images

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Bone marrow

Liver and lung

Liver with CD3 and CD20

Liver double staining with CD4 / EBER and CD8 / EBER


Lymph nodes and skin

Spleen

Various images

Left: bone marrow-EBER1; Right: liver-CD45 RO

Positive stains
Negative staining
Molecular / cytogenetics description
  • Clonal TCR gene rearrangements
  • Clonal episomal form of EBV type A (wild type or the 30bp deleted product of LMP1) in all cases
  • No consistent chromosomal abnormalities, but often 6q deletion
Molecular / cytogenetics images

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PCR for TCR gamma gene