Lymphoma & related disorders
Mature T/NK cell disorders
Pediatric NK/T cell disorders
Systemic EBV+ of childhood
Author: Dragos C. Luca, M.D.
Last author update: 1 January 2012
Last staff update: 18 August 2023
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Systemic EBV+ T cell lymphoproliferative disease of childhood
See also: Hydroa vacciniforme-like lymphoma (HVL)
Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Etiology | Postulated normal counterpart | Clinical features | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative staining | Molecular / cytogenetics description | Molecular / cytogenetics imagesCite this page: Luca D. Systemic EBV+ of childhood. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonbchild.html. Accessed September 26th, 2023.
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
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
Images hosted on other servers:
Bone marrow
Liver and lung
Liver with CD3 and CD20
Liver double staining with CD4 / EBER and CD8 / EBER
Spleen
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
Images hosted on other servers:
PCR for TCR gamma gene
