Hydroa Vacciniforme-like Lymphoproliferative Disorder Research Articles

儿童种痘样水疱病样淋巴组织增生性疾病15例临床、病理及预后分析

Objective To analyze clinical features and prognosis of 15 children with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) . Methods Clinical features, histopathological findings, treatment outcomes in 15 patients, who were diagnosed with HVLPD in the Department of Dermatology, Children′s Hospital of Chongqing Medical University from 2014 to 2018, were retrospectively analyzed. Results Among the 15 patients, 7 were males and 8 were females. The age of onset ranged from 2 to 13 years, and the average age was 6.5 years. Main clinical manifestations included facial edema, and papules, blisters, ulcers and crusts repeatedly occurring on both the sun-exposed parts such as the face and limbs and non-sun-exposed parts such as the trunk. Of the 15 patients, 13 had intermittent fever, 13 had hepatosplenomegaly, and 15 had lymphadenectasis. Moreover, kidney failure occurred in 1 patient, hemophagocytic syndrome occurred in 2, and lymphoma occurred in 1. Laboratory examination showed that 15 patients were all positive for Epstein-Barr virus (EBV) -immunoglobulin G (IgG) antibody, and all negative for EBV-IgM antibody. Additionally, high replication of EBV DNA was detected. Histopathological study of skin lesions showed mild to dense perivascular and periadnexal infiltration of lymphocytes in the dermis and subcutaneous tissue. Immunohistochemistry study showed positive staining for CD4 and CD8 in 13 of 15 patients, for CD56 in 7 of 15 patients, and for CD3 in 12 of 13 patients. Moreover, 9 of 11 cases were detected positive for T-cell intracellular antigen-1, 8 cases were all detected positive for granzyme B, and the Ki-67 proliferation index ranged from 3% to 50% in 11 of 12 cases. The treatment protocols were similar among the 15 patients. After the treatment, 2 patients showed stable disease condition, and 10 experienced relapse. During the follow-up, 2 patients developed hemophagocytic syndrome, 1 developed lymphoma, and the 3 patients finally died of the worsening condition after chemotherapy. Conclusions HVLPD is closely associated with chronic active EBV infection. Its clinical symptoms can be relieved after immunomodulatory therapies such as glucocorticoids, gamma globulin and interferon, and the clinical manifestations, treatment outcomes and prognosis vary greatly among different patients. Key words: Lymphoproliferative disorders; Lymphoma, T-cell; Herpesvirus 4, human; Hydroa vacciniforme-like lymphoproliferative disorder

507 Hydroa vacciniforme-like lymphoproliferative disorder and systemic EBV+ T cell lymphoma of childhood and adulthood

507 Hydroa vacciniforme-like lymphoproliferative disorder and systemic EBV+ T cell lymphoma of childhood and adulthood

Clinicopathological categorization of hydroa vacciniforme-like lymphoproliferative disorder: an analysis of prognostic implications and treatment based on 19 cases

BackgroundHydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barr virus (EBV) infection, which occurs mainly in children in Latin America and Asia. It can progress to systemic lymphoma. However, prognostic factors and treatment remain unclear.MethodsThis retrospective study reviewed the clinical, morphologic, immunophenotypical features, and clinical treatment of 19 patients with HV-LPD.ResultsAll 19 patients had skin lesions in the face, extremities, or areas unexposed to the sun, including edema, blistering, ulceration, and scarring. The course was slowly progressive and relapsing. Histopathology showed an atypical lymphocytic infiltrate in the dermis and/or subcutaneous tissue. The lesions had a cytotoxic T/NK-cell immunophenotype. Among 19 patients, 7 (37%) exhibited CD4+ T cells, 5 (26%) exhibited CD8+ T cells, and 7 (37%) exhibited CD56+ cells. Of 12 cases with a T-cell phenotype, molecular analyses demonstrated that 7 had monoclonal rearrangements in the T-cell receptor genes. Three cases had an NK-cell phenotype and had polyclonal rearrangements in the TCR genes. All cases were associated with EBV infections. Among 19 patients, 9 (47.4%) received chemotherapy. Only one patient received allogeneic transplantation and EBV-specific cytotoxic T lymphocyte treatment after chemotherapy. That patient was the only one alive without disease at the latest follow up. Nine patients died of systemic lymphoma with disease progression, indicating irreversible process.ConclusionsThis study confirmed that HV-LPD is a broad-spectrum EBV+ lymphoproliferative disorder. It progressed to EBV+ systemic T/NK lymphoma, although some patients had a more indolent, chronic course. Cytopenia, elevated lactate dehydrogenase, destructive-multiorgan involvement, and older age were poor prognostic factors. Only allogeneic transplantation was curative.

Hydroa vacciniforme–like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites

AbstractPatients with classic hydroa vacciniforme–like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that whites were less likely to develop systemic EBV disease (1/10) than nonwhites (5/6). All (10/10) of the white patients were generally in good health at last follow-up, while two-thirds (4/6) of the nonwhite patients required hematopoietic stem cell transplantation. Nonwhite patients had later age of onset of HVLPD than white patients (median age, 8 vs 5 years) and higher levels of EBV DNA (median, 1 515 000 vs 250 000 copies/ml) and more often had low numbers of NK cells (83% vs 50% of patients) and T-cell clones in the blood (83% vs 30% of patients). RNA-sequencing analysis of an HVLPD skin lesion in a white patient compared with his normal skin showed increased expression of interferon-γ and chemokines that attract T cells and NK cells. Thus, white patients with HVLPD were less likely to have systemic disease with EBV and had a much better prognosis than nonwhite patients. This trial was registered at www.clinicaltrials.gov as #NCT00369421 and #NCT00032513.

Actinic Prurigo and Hydroa Vacciniforme

To summarize current knowledge pertaining to two photodermatoses, actinic prurigo (AP) and hydroa vacciniforme (HV), both of which routinely have onset in childhood. AP is an immune-mediated photodermatosis associated with human leukocyte antigen DR4 that commonly features cheilitis and conjunctivitis. It mostly affects American Indian/Latin American Mestizos and rarely white and Asian patients, who manifest different disease phenotypes. The diagnosis is clinical, but follicular cheilitis is a characteristic mucosal biopsy finding, and phototesting may be helpful. Hallmarks of treatment are photoprotection and thalidomide. HV is a photodermatosis related to Epstein-Barr virus infection that causes varioliform scarring. Classic HV is benign and self-limited and must be distinguished from hydroa vacciniforme-like lymphoproliferative disorder (HVLLPD), a systemic disease most common in Asia and Latin America with risk of progression to lymphoma. Limited treatments are available, but accumulating data suggest chemotherapy is associated with worse outcomes in HVLLPD. As understanding of these photodermatoses progresses, important knowledge gaps persist. AP’s pathogenesis remains incompletely elucidated, and therapeutic investigation has stagnated. Despite enhanced description of HV and HVLLPD, both lack standardized effective therapy.

Cutaneous Lymphoproliferative Disorders: What's New in the Revised 4th Edition of the World Health Organization (WHO) Classification of Lymphoid Neoplasms.

Cutaneous lymphoproliferative disorders remain a challenging aspect of dermatopathology, in part due to the rarity of the entities and extreme variability in clinical outcomes. Although many of the entities remain unchanged, the approach to some of them has changed in the new 2016 classification scheme of the World Health Organization. Chief among these are Epstein-Barr virus-associated lymphoproliferative disorders such as Epstein-Barr virus-associated mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and breast implant-associated anaplastic large cell lymphoma. In addition, translocations and gene rearrangements such as those involving the 6p25.3 locus have started to inform diagnosis and classification of anaplastic large cell lymphoma and lymphomatoid papulosis. In this review, we will examine what is new in the diagnostic toolbox of cutaneous lymphoproliferative disorders.

Hydroa vacciniforme–like lymphoproliferative disorder: Clinicopathologic study of 41 cases

Hydroa vacciniforme-like lymphoproliferative disorder (HVLLPD) is a rare Epstein-Barr virus (EBV)-related disease that is usually found in East Asians and Latin Americans. To report thecharacteristics of HVLLPD in Chinese patients. Retrospective analysis of patients with HVLLPD from a single institute. A total of 41 patients were enrolled. All patients presented with papulovesicular lesions, mainly distributed on sun-exposed areas, with 26 patients showing systemic symptoms. Follow-up data were available for 20 patients, 16 patients were alive, and 4 patients died. Of the 4 deceased patients, 3 had taken a serum EBV DNA test that showed high viral loads. These 3 patients also received chemotherapy. Histopathology was characterized by dense proliferation of lymphocytes in the dermis. Angiotropism or angiodestruction was found in the majority of patients, whereas prominent cellular polymorphism was noticed in only 4 patients. All patients were positive for CD3, TIA1 cytotoxic granule associated RNA binding protein, and EBV-encoded RNA in situ hybridization. This was a retrospective study. HVLLPD in Chinese patients showed indolent behavior in the majority of cases, which differed from the characteristics of HVLLPD in Latin Americans. Patients with high serum EBV DNAloads had an increased risk of their disease evolving into aggressive disease. Chemotherapy should not be considered as first-line treatment for most Chinese patients.

Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Diseases in Chinese Mainland.

Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders (EBV+ T/NK LPD) encompass a heterogeneous group of disorders, including chronic active Epstein–Barr virus infection (CAEBV), Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV+ T-cell lymphoma of childhood and hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) and so on, predominantly affecting children and young adults with high mortality. Patients with EBV+ T/NK LPD have overlapping clinical symptoms as well as histologic and immunophenotypic features. In this review, we summarized the clinical features of EBV+ T/NK LPD in Chinese patients from the published articles.

Clinicopathological analysis of the hydroa vacciniforme-like lymphoproliferative disorder with natural killer cell phenotype compared with cutaneous natural killer T-cell lymphoma.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is defined as a distinctive clinicopathological type of cutaneous lymphoma and a subset of patients with this disease exhibit the natural killer (NK)-cell phenotype. The HVLPD-NK cell phenotype may be difficult to distinguish from cutaneous natural killer T-cell lymphoma (CNKTL), as these two diseases share similar immunophenotypic markers. Therefore, the aim of the present study was to analyze the clinicopathological features of this rare disease and compare these features with those of CNKTL. The clinical, histopathological and molecular features of 5 patients with the HVLPD-NK cell phenotype and 11 patients with CNKTL were evaluated. As well as certain subtle histopathological differences, there marked differences the age, distribution of lesions and clinical course differed between patients with these two diseases. These results suggest that the HVLPD-NK cell phenotype should be classified as a separate disorder and treated accordingly.

Hydroa vacciniforme and hydroa vacciniforme-like lymphoproliferative disorder: Disease spectrum, responsible T-cell subsets and prognosis

Hydroa vacciniforme (HV) is a cutaneous subset of Epstein-Barr virus (EBV)-associated T/NK lymphoproliferative disorders (LPDs). Through our case series study of 31 patients with HV, HV-like LPDs and related diseases, we attempted to elucidate the disease spectrum, T-cell subsets responsible for each clinical subtype, and prognoses. Our results clarified a clinical spectrum of EBV-associated T/NK LPDs, which included HV, hypersensitivity to mosquito bites (HMB), chronic active EBV infection (CAEBV), and hemophagocytic lymphohistiocytosis (HLH). Patients with HV are divided into two groups: a benign subtype designated classic HV (cHV), and more serious systemic HV (sHV), also called HV-like LPD in the 2017 WHO classification. Patients with cHV usually have increased percentages of EBV-infected γδT cells, and patients with sHV without HMB are further classified into two groups: γδT-cell- and αβT-cell-dominant types. Patients with HMB, with or without HV-like eruptions, have increased numbers of EBV-infected NK cells in the blood. Patients with cHV and γδT-cell-dominant sHV show a favorable prognosis, but the other subtypes such as αβT-cell-dominant sHV and NK-cell-dominant HMB have a poor prognosis: mortality rates of 11.5 and 3.51 in 100 person-years, respectively. Based on the observations of our case series, we confirmed the poor prognostic indicators as follows: 1) the sHV and HMB clinical subtypes, 2) onset age over 9 years, 3) expression of the reactivation marker, BZLF1 mRNA, and 4) αβT-cell-dominant sHV and NK-cell-dominant HMB. No prognostic correlation was observed in anti-EBV antibody titers or EBV DNA load. From a therapeutic view point, we should exclude the benign subtypes such as patients with cHV and γδT-cell-dominant sHV from the other clinical subtypes.