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Systemic EBV+ T cell lymphoma of childhood



Last author update: 22 March 2024
Last staff update: 22 March 2024

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PubMed Search: Systemic EBV+ T cell lymphoma of childhood

See also: Hydroa vacciniforme-like lymphoma (HVL)

Michael Stone, D.O.
Carlos A. Murga-Zamalloa, M.D.
Page views in 2024 to date: 552
Cite this page: Stone M, Jeon YK, Murga-Zamalloa C. Systemic EBV+ T cell lymphoma of childhood. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonbchild.html. Accessed June 16th, 2024.
Definition / general
  • Often rapid and fulminant disease within the spectrum of childhood Epstein-Barr virus (EBV) positive T cell lymphomas
Essential features
  • Clinically characterized by systemic involvement, including the bone marrow, lymph nodes, spleen and lungs; most patients have a rapid, often fatal, clinical course
  • Neoplastic elements are EBV+ T cell lymphocytes identified in biopsies from end organ damage biopsy sites; EBV+ T cell lymphocytes predominantly have a cytotoxic immunophenotype
  • Neoplastic elements are mostly small lymphocytes without cytological atypia or effacement of the background tissue architecture
  • It occurs in pediatric and young adult immunocompetent patients and there is an overlap in symptoms, clinical outcomes, laboratory findings and histomorphological features with the other 2 EBV+ T / NK lymphoproliferative disorders of childhood: EBV+ hemophagocytic lymphohistiocytosis (EBV+ HLH) and T / NK systemic form chronic active EBV disease (T / NK sCAEBV)
    • These 3 entities represent different ends of a spectrum of end organ damage secondary to EBV infected hyperactivated T cell lymphocytes
Terminology
  • No longer recommended
    • Fulminant T cell lymphoproliferative disease
    • Sporadic fatal infectious mononucleosis
    • Fatal infectious mononucleosis
    • Fulminant EBV+ T cell lymphoproliferative disorder of childhood
    • Lethal hemophagocytic lymphohistiocytosis
    • Fulminant hemophagocytic syndrome in children
    • Severe chronic active EBV disease (CAEBV)
ICD coding
  • ICD-O: 9724/3 - systemic EBV positive T cell lymphoproliferative disease of childhood
  • ICD-10: C84.5 - other and unspecified T cell lymphomas
  • ICD-11: 2A90.4 - systemic Epstein-Barr virus positive T cell lymphoma of childhood
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
  • Symptoms include hepatosplenomegaly, fever, lymphadenopathy, malaise and upper respiratory tract symptoms
  • Often, there is rapid development of multiorgan failure, sepsis and death within a few days to a few months in immunocompetent patients
  • Proposed as a diagnosis of exclusion in EBV positive T / NK lymphoproliferative disorders of childhood that do not fulfill the criteria for T / NK sCAEBV or EBV positive HLH
  • References: Diagn Pathol 2021;16:48, Leuk Lymphoma 2017;58:53, Blood 2000;96:443
Diagnosis
  • Histologic, immunohistochemical, molecular and cytogenetic analysis of involved tissues and clinical correlation
Laboratory
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
  • More frequently, there is a mild expansion of small to medium sized T cell lymphocytes without cytological atypia or effacement of the background target tissue architecture
  • When involved, the spleen shows depletion of the white pulp, lymphocyte infiltration of the red pulp and prominent hemophagocytosis
  • When the liver is involved, findings include a sinusoidal and portal lymphocytic infiltrate; additional reported findings include cholestasis, steatosis and variable degrees of liver necrosis
  • Bone marrow shows a scattered to diffuse, medium / large atypical lymphocytic infiltrate and increased histiocytes and hemophagocytosis
  • Lymph nodes, when involved, usually show preserved architecture with open sinuses, expanded paracortical regions, sinus histiocytosis and hemophagocytosis (Pediatr Blood Cancer 2019;66:e27798, Blood 2000;96:443)
  • Few cases with diffuse sheets of atypical medium to large lymphocytes involving the liver, bone marrow, spleen, lung or lymph node have been reported
  • References: Diagn Pathol 2021;16:48, Leuk Lymphoma 2017;58:53, Blood 2000;96:443, Pediatr Blood Cancer 2019;66:e27798
Microscopic (histologic) images

Contributed by Yoon Kyung Jeon, M.D.
Lymphocytic infiltrates in the liver Lymphocytic infiltrates in the liver Lymphocytic infiltrates in the liver

Lymphocytic infiltrates in the liver

Lymph node, atypical infiltrates

Lymph node, atypical infiltrates


Lymph node, atypical infiltrates Lymph node, atypical infiltrates Lymph node, atypical infiltrates

Lymph node, atypical infiltrates

Lymphocytic infiltrates in the liver (CD3)

Lymphocytic infiltrates in the liver (CD3)

Positive stains
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:
PCR for TCR gamma gene

PCR for TCR gamma gene

Sample pathology report
  • Bone marrow core biopsy, touch imprints, aspirate and clot:
    • Hypercellular bone marrow with atypical EBV positive T cell lymphocytic infiltrates (see comment)
    • Comment: The T cell lymphocytic infiltrates feature aberrant loss of CD5 and concurrent T cell receptor rearrangement studies are consistent with a monoclonal T cell population. In the proper clinical context, these findings can be consistent with systemic EBV positive T cell lymphoma of childhood.
Differential diagnosis

Table 1: Comparison of the clinical and laboratory findings between the entities included in the differential diagnosis of systemic EBV+ T cell lymphoma of childhood (adapted from Am J Clin Pathol 2024 Feb 12 [Epub ahead of print])
Epstein-Barr virus associated hemolymphohistiocytosis (EBV HLH) Chronic active EBV disease of T / NK cell type systemic form (T / NK sCAEBV) Systemic EBV positive T cell lymphoproliferative disorder of childhood Nodal EBV positive T / NK cell lymphoma Aggressive NK cell leukemia
Morphological features Small T cell lymphocytes with no definitive cytological atypia The infiltrates are predominantly composed by lymphocytes and plasma cells with no effacement or distortion of the background tissue and without morphological atypia; HRS-like cells may be present Variable expansion of lymphocytic infiltrates composed by small to medium sized T cells with no morphological atypia Effacement of the nodal architecture by medium to large lymphocytes with marked cytological atypia Medium sized atypical lymphocytes, frequently with prominent nucleoli
Immunophenotype A subset of T cells are EBV and CD8 positive; loss of pan T cell markers may be observed The HRS-like cells are CD30 positive with variable expression of PAX5 and CD20; the EBV positive T cells are predominantly CD4 positive with loss of pan T cell markers (rare EBV+ CD8 T cells have been reported) Majority of cases are composed by CD8 positive neoplastic T cells (CD4+ cases are rare) A minimum of 30% EBV positive T cell lymphocytes is required; majority of the cases are composed by CD8 positive neoplastic cells Cytoplasmic CD3 expression and positive expression of CD2, CD56 and CD16; negative for CD57
Anatomical sites of presentation Bone marrow and liver Liver, bone marrow and spleen Bone marrow, liver, lymph nodes, spleen Lymph nodes Peripheral blood and bone marrow
Age at diagnosis Predominantly pediatric population Predominantly pediatric population Predominantly pediatric population Adult populations Peak incidence between 21 and 30 year old
Relevant clinical features Meets diagnostic criteria for HLH; good responses to etoposide based regimens Persistent mononucleosis-like symptoms and high EBV titers for at least 3 months; good responses to systemic chemotherapy and hematopoietic stem cell transplantation is curative in most of pediatric patients; dismal clinical course in adult populations Rapid development of multiorgan failure and end organ damage including liver failure, hepatosplenomegaly and pancytopenia, with high mortality rates Aggressive clinical course and poor responses to current chemotherapeutic agents Fulminant clinical course with a median overall survival of < 2 months
Relevant clinical features and prognosis Meets diagnostic criteria for HLH; overall good prognosis with good responses to etoposide based regimens Persistent mononucleosis-like symptoms and high EBV titers for at least 3 months; pediatric patients display good responses to systemic chemotherapy and hematopoietic stem cell transplantation is curative in most of pediatric patients; adult patients are characterized by dismal clinical course and poor prognosis Rapid development of multiorgan failure and end organ damage including liver failure, hepatosplenomegaly and pancytopenia, with high mortality rates and poor prognosis Aggressive clinical course, poor responses to current chemotherapeutic agents and bad prognosis Fulminant clinical course, median overall survival of < 2 months and dismal prognosis
Board review style question #1

Which of the following features supports a diagnosis of systemic EBV+ T cell lymphoma of childhood over EBV+ hemophagocytic lymphohistiocytosis (EBV+ HLH)?

  1. EBER positivity in CD8+ T cells
  2. Lack of cytologic atypia
  3. Onset of disease in childhood
  4. Presence of a clonal cytogenetic abnormality
Board review style answer #1
D. Presence of a clonal cytogenetic abnormality. Clonal cytogenetic abnormalities are found in systemic EBV+ T cell lymphoma of childhood but not EBV+ HLH. Answer A is incorrect because both systemic EBV+ T cell lymphoma of childhood and EBV+ HLH show EBER positivity in CD8+ T cells in most cases. Answer B is incorrect because systemic EBV+ T cell lymphoma of childhood and EBV+ HLH show no cytologic atypia; however, the presence of cytologic atypia would favor a diagnosis of systemic EBV+ T cell lymphoma of childhood. Answer C is incorrect because systemic EBV+ T cell lymphoma of childhood and EBV+ HLH most commonly occur in children and young adults (Int J Clin Exp Pathol 2014;7:5738).

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Reference: Systemic EBV+ T cell lymphoma of childhood
Board review style question #2

Which of the following is correct regarding EBV+ T cell lymphoproliferative neoplasms of childhood?

  1. An indolent clinical course characterizes EBV+ T cell lymphoproliferative neoplasms
  2. Diagnosis can be established only after documentation of T cell receptor clonality studies
  3. Distinction between systemic EBV+ T cell lymphoma and chronic active EBV disease of T / NK cell type, systemic form (T / NK sCAEBV) can be established solely on morphological analysis of the lymphocytic infiltrates
  4. These groups of diseases constitute a continuum with similar histological features and overlap in clinical and laboratory findings
Board review style answer #2
D. These groups of diseases constitute a continuum with similar histological features and overlap in clinical and laboratory findings. Systemic EBV+ T cell lymphoma, T / NK sCAEBV and HLH EBV overlap in clinical features, are indistinguishable in histological features and can precede one another. Answer A is incorrect because these entities usually have an aggressive clinical course. Answer B is incorrect because T cell receptor clonality studies are not positive in all cases and its presence is not required to establish the diagnosis. Answer C is incorrect because the histological features between systemic EBV+ T cell lymphoma and T / NK sCAEBV are similar (Leuk Lymphoma 2017;58:53, Am J Clin Pathol 2024 Feb 12 [Epub ahead of print]).

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Reference: Systemic EBV+ T cell lymphoma of childhood
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