Definitions of EBV+ T/NK-LPDs in this study
| Disease . | Eligibility criteria . | Exclusion criteria . | Lineages/clonality . | References . |
|---|---|---|---|---|
| Clinical category | ||||
| CAEBV of T/NK–cell type | (1) Illness ≥ 3 mo in duration (EBV-related illness or symptoms including fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, pancytopenia, uveitis, interstitial pneumonia, hydroa vacciniforme-like eruptions, and hypersensitivity to mosquito bites)* | (1) No evidence of previous immunological abnormalities or other recent infection that might explain the observed condition | T/NK cell | 12 |
| (2) Increased amounts of EBV detected by Southern blot hybridization or EBER+ cells in affected tissues or peripheral blood; ≥ 102.5 copies/μg of EBV DNA in PBMCs | (2) Congenital immunodeficiency including X-linked lymphoproliferative disorders | Polyclonal, oligoclonal, monoclonal | 16,29 | |
| HLH | (1) Clinical criteria (fever and splenomegaly) | (1) Hemophagocytic syndrome in accelerated phase of CAEBV of T/NK cell type | T/NK cell | 11 |
| (2) Laboratory criteria (cytopenia affecting 2 of 3 lineages in the peripheral blood, hypertriglyceridemia, and/or hypofibrinogenemia) | (2) Congenital immunodeficiency including familial HLH | Polyclonal, oligoclonal, monoclonal | ||
| (3) Histological criteria (hemophagocytosis in the BM, spleen, or lymph nodes) | ||||
| Severe mosquito bite allergy* | Hypersensitivity to mosquito bites characterized by high fever after bites, ulcers, necrosis, and scarring* | Any systemic symptoms in addition to the cutaneous lesions were categorized to CAEBV of T/NK cell type | T/NK cell, polyclonal, oligoclonal, monoclonal | 9,39 |
| Hydroa vacciniforme* | Recurrent vesiculopapules with central umbilication and crust formation mimicking herpetic vesicles usually occurring on sun-exposed areas | Any systemic symptoms in addition to cutaneous lesions categorized as CAEBV of T/NK cell type | T/NK cell, polyclonal, oligoclonal, monoclonal | 10,39 |
| Pathological classification | ||||
| Systemic EBV+ T-cell LPD | (1) Illness or symptoms including fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, hemophagocytosis, and interstitial pneumonia | Other overt leukemia and lymphoma such as extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, and peripheral T-cell lymphoma | T-cell, monoclonal | 7 |
| (2) Can occur shortly after primary EBV infection or in the setting of CAEBV | ||||
| (3) Monoclonal expansion of EBV-infected T cells with an activated cytotoxic phenotype in tissues or peripheral blood | ||||
| Hydroa vacciniforme-like lymphoma | (1) Recurrent vesiculopapules with central umbilication and crust formation usually occurring on sun-exposed areas with or without systemic symptoms including fever, wasting, lymphadenopathy, and hepatosplenomegaly | Other overt leukemia and lymphoma such as extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, and peripheral T-cell lymphoma | T/NK cell, monoclonal | 7 |
| (2) Monoclonality of EBV-infected cells | ||||
| Disease . | Eligibility criteria . | Exclusion criteria . | Lineages/clonality . | References . |
|---|---|---|---|---|
| Clinical category | ||||
| CAEBV of T/NK–cell type | (1) Illness ≥ 3 mo in duration (EBV-related illness or symptoms including fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, pancytopenia, uveitis, interstitial pneumonia, hydroa vacciniforme-like eruptions, and hypersensitivity to mosquito bites)* | (1) No evidence of previous immunological abnormalities or other recent infection that might explain the observed condition | T/NK cell | 12 |
| (2) Increased amounts of EBV detected by Southern blot hybridization or EBER+ cells in affected tissues or peripheral blood; ≥ 102.5 copies/μg of EBV DNA in PBMCs | (2) Congenital immunodeficiency including X-linked lymphoproliferative disorders | Polyclonal, oligoclonal, monoclonal | 16,29 | |
| HLH | (1) Clinical criteria (fever and splenomegaly) | (1) Hemophagocytic syndrome in accelerated phase of CAEBV of T/NK cell type | T/NK cell | 11 |
| (2) Laboratory criteria (cytopenia affecting 2 of 3 lineages in the peripheral blood, hypertriglyceridemia, and/or hypofibrinogenemia) | (2) Congenital immunodeficiency including familial HLH | Polyclonal, oligoclonal, monoclonal | ||
| (3) Histological criteria (hemophagocytosis in the BM, spleen, or lymph nodes) | ||||
| Severe mosquito bite allergy* | Hypersensitivity to mosquito bites characterized by high fever after bites, ulcers, necrosis, and scarring* | Any systemic symptoms in addition to the cutaneous lesions were categorized to CAEBV of T/NK cell type | T/NK cell, polyclonal, oligoclonal, monoclonal | 9,39 |
| Hydroa vacciniforme* | Recurrent vesiculopapules with central umbilication and crust formation mimicking herpetic vesicles usually occurring on sun-exposed areas | Any systemic symptoms in addition to cutaneous lesions categorized as CAEBV of T/NK cell type | T/NK cell, polyclonal, oligoclonal, monoclonal | 10,39 |
| Pathological classification | ||||
| Systemic EBV+ T-cell LPD | (1) Illness or symptoms including fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, hemophagocytosis, and interstitial pneumonia | Other overt leukemia and lymphoma such as extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, and peripheral T-cell lymphoma | T-cell, monoclonal | 7 |
| (2) Can occur shortly after primary EBV infection or in the setting of CAEBV | ||||
| (3) Monoclonal expansion of EBV-infected T cells with an activated cytotoxic phenotype in tissues or peripheral blood | ||||
| Hydroa vacciniforme-like lymphoma | (1) Recurrent vesiculopapules with central umbilication and crust formation usually occurring on sun-exposed areas with or without systemic symptoms including fever, wasting, lymphadenopathy, and hepatosplenomegaly | Other overt leukemia and lymphoma such as extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, and peripheral T-cell lymphoma | T/NK cell, monoclonal | 7 |
| (2) Monoclonality of EBV-infected cells | ||||
“Severe mosquito bite allergy” and “hydroa vacciniforme” were used as clinical categories, whereas “hypersensitivity to mosquito bites” and “hydroa vacciniforme-like eruptions” were used to designate symptoms.