Clinicopathological findings of virus-associated hemophagocytic syndrome in bone marrow: Association with Epstein-Barr virus and apoptosis

Abstract Hemophagocytic syndrome (HPS) is characterized by an uncontrolled proliferation of macrophages displaying extensive phagocytosis of hematopoietic cells that can be associated with non Hodgkin lymphomas. However, Hodgkin lymphoma associated with hemophagocytic syndrome (HL-HPS) has rarely been published. We report here a large series of 34 patients presenting HL-HPS. Histological analysis and Epstein-Barr Virus (EBV) studies were performed. The 34 patients were enrolled from 1992 to 2006. HPS diagnosis was based on usual clinico-biological criteria. Bone marrow aspiration or biopsy were performed in all cases and confirmed HPS, showing hemophagocytic features in scattered macrophages. HL was documented on histological material in all 34 patients. The biopsies were performed on different localizations: lymph nodes (n=18), bone marrow (n=27), liver (n=2) and tonsil (n=1). All histological slides were reviewed and classified according to the World Health Organization (WHO) Lymphoma classification. The presence of EBV in the tumour cells was detected using EBER RNA in situ hybridization and the expression of viral proteins LMP-1, EBNA-2 by immunoperoxidase. Patients were 26 men and 8 women (sex ratio M/F = 3.3). The median age was 45 years (range 19–84). HIV status was negative in 26 patients and positive in 8 patients. All patients were in clinical stage IVB. HL subtypes (18 lymph nodes) were Mixed Cellularity (n=12, 67%), Nodular Sclerosis (n=2, 11%) and Lymphocyte Depleted (n=4, 22%). Extra nodal tissues were highly infiltrated by tumour cells in all cases. The presence of EBV in tumour cells was detected in 32 out of the 34 patients (94%). In all EBV positive cases, high levels of LMP-1 without EBNA2 expression were detected, defining a latency II. This study reports the largest series to date of HL-HPS. The features of HL-HPS are particular by the high proportion of mixed cellularity subtypes (67%) in contrast to the frequency of nodular sclerosis subtypes observed in the general population of non overt immunosuppressed patients, and by the striking high proportion of EBV associated HL (32 out of the 34 patients, 94%). Our findings suggest not only a pathogenic role of EBV, but also a defective immune system in the control of EBV infection in HL-HPS patients.The high predominance of male in our population of HPS-HL (sex ratio M/F = 4.3 after exclusion of HIV positive patients) and the strong association with EBV could suggest X-linked immune defect in these patients.

Download Full-text

Peripheral T-cell Lymphoma, NOS With Epstein-Barr Virus Positivity in an Elderly Patient With Myelodysplastic Syndrome: An Autopsy Case Report

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.178 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S81-S81

Author(s):

J Lanceta ◽

W Xue ◽

M Hurford ◽

H Wu

Keyword(s):

Bone Marrow ◽

T Cells ◽

Lymph Node ◽

T Cell ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Barr Virus ◽

Epstein Barr

Abstract Casestudy Epstein-Barr virus (EBV)-associated peripheral T-cell lymphomas are a group of aggressive neoplasms with a geographic predilection for South America and Asia, but are very rare in Western populations. Results We report a case of a 74-year-old Caucasian female who presented with pancytopenia and B symptoms with EBV-IgG detected on admission. Past medical history included: ITP, chronic urticaria, and recently diagnosed myelodysplastic syndrome (MDS) on bone marrow biopsy one month prior to admission. Excisional biopsies of an enlarged right neck lymph node (repeated within 6 months) and right axillary lymph node five years ago were negative for a lymphoproliferative disorder at the time. Repeated bone marrow biopsy, performed during the current admission, confirmed the diagnosis of MDS, with scattered T-cells without aberrant immunophenotype. Despite aggressive treatment from multiple specialties, the patient deteriorated and expired four weeks later from complications of MDS. At autopsy, there was diffuse lymphadenopathy involving the mediastinum, axilla, pelvis and peripancreatic fat. Lymph node sections demonstrated nodal architecture effacement by diffuse, vaguely nodular lymphoid infiltrates. Histologically, the infiltrates were composed of medium to large lymphocytes with round to slight irregular nuclei, rare Reed-Sternberg-like multinucleated cells, clumped chromatin, and indistinct nucleoli. Individual cell necrosis was abundant with mitotic figures readily identifiable. Immunohistochemistry revealed CD2+ CD3+ neoplastic T-cells that co-express MUM1 and a subset of CD30, while negative for CD4, CD5, CD8, CD56, ALK1, and TDT. EBV-encoded RNA in-situ hybridization was focally positive. The final postmortem diagnosis was peripheral T-cell lymphoma, not otherwise specified (NOS), with focal EBV positivity. Conclusion Co-existence of a de-novo MDS and non-Hodgkin lymphoma without any prior chemotherapeutic exposure is a highly unusual finding, although MDS-like presentations can occur with EBV-associated lymphomas. Peripheral T-cell lymphoma, NOS is an aggressive lymphoma and EBV positivity has been found correlated with a poor prognosis. This case demonstrates how postmortem examination remains an important tool in clinical- pathological correlation and highlights the potential pathogenetic role EBV plays in MDS and T-cell lymphoma.

Download Full-text

Cytomegalovirus-Associated Hemophagocytic Syndrome

PEDIATRICS ◽

10.1542/peds.75.2.280 ◽

1985 ◽

Vol 75 (2) ◽

pp. 280-283

Author(s):

ELIZABETH H. DANISH ◽

BEVERLY B. DAHMS ◽

MARY L. KUMAR

Keyword(s):

Viral Infection ◽

Epstein Barr Virus ◽

Hemophagocytic Syndrome ◽

Clinical Course ◽

Underlying Disease ◽

Barr Virus ◽

Pathologic Findings ◽

Immunosuppressed Patients ◽

Epstein Barr ◽

Herpes Group

Virus-associated hemophagocytic syndrome, first described by Risdall and co-workers in 1979,1 is a rare histiocytic proliferative syndrome characterzed by fever, hepatosplenomegaly, pancytopenia, and erythrophagocytosis by histiocytes that appear benign by histologic criteria. The clinical course and pathologic findings may be identical with another histiocytic disorder, familial erythrophagocytic lymphohistiocytosis, which occurs predominantly in infants. Diagnosis of virus-associated hemophagocytic syndrome depends entirely on evidence of concurrent viral infection, usually of the herpes group. Epstein-Barr virus has been associated with this syndrome in the few cases reported in children without underlying disease, whereas cytomegalovirus (CMV) has been implicated in immunosuppressed patients. We report a case of fatal CMV-associated hemophagocytic syndrome which occurred in a previously healthy infant.

Download Full-text

Transcription of latent and replicative Epstein-Barr-virus genes in bone-marrow and peripheral-blood mononuclear cells of healthy donors

International Journal of Cancer ◽

10.1002/(sici)1097-0215(19970304)70:5<524::aid-ijc6>3.0.co;2-# ◽

1997 ◽

Vol 70 (5) ◽

pp. 524-529 ◽

Cited By ~ 8

Author(s):

Roberta Gonnella ◽

Antonio Angeloni ◽

Antonella Calogero ◽

Antonella Farina ◽

Roberta Santarelli ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Epstein Barr Virus ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Barr Virus ◽

Healthy Donors ◽

Blood Mononuclear Cells ◽

Epstein Barr

Download Full-text

Clinical Warning of Hemophagocytic Syndrome Caused by Epstein-barr Virus

10.21203/rs.3.rs-47979/v1 ◽

2020 ◽

Author(s):

Jinjin Shi ◽

Chu Chu ◽

Min Yu ◽

Dandan Zhang ◽

Yuqin Li ◽

...

Keyword(s):

Laboratory Tests ◽

Epstein Barr Virus ◽

Hemophagocytic Syndrome ◽

Clinical Manifestations ◽

Prognostic Indicator ◽

Barr Virus ◽

Ebv Infection ◽

Ebv Dna ◽

Epstein Barr ◽

D Dimer

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

Download Full-text