Clinicopathologic Features And Prognostic Analysis Of Patients With Hydroa Vacciniforme-like Lymphoproliferative Disorder

Background and objectiveHydroa vacciniforme-like lymphoproliferative disorder(HV-LPD)is a chronic disease related to Epstein-Barr virus(EBV)infection,which mainly damages the skin of the face,hands and lower limbs that exposed to the sun.Clinical manifestations is characterized by papulovesicles or clustered blisters,healed with pitted scars.Some patients may develop systemic symptoms including fever,lymphadenopathy,and hepatosplenomegaly.HV-LPD is a rare disease with an incidence of 0.34/100,000 approximately,normally occurred in children and young adolescents in East Asia and Latin America.This disease is of great heterogeneity,some patients would spontaneously recover in adolescent while some patients may progress to systemic malignant lymphoma with a poor prognosis.It is rarely analyzed with large numbers of samples and the domestic and foreign literatures are also reported in the form of case analysis.This study reviews the cases in our hospital and the reports at home and aboard,and analyzes the clinicopathological characteristics and prognostic factors of Chinese HV-LPD patients in order to provide more evidences for further study.MethodsAll the 21 patients with HV-LPD were diagnosed by pathology department admitted to our hospital from January 2012 to December 2019.They are follow-up during hospitalization or by telephone every 3 month,ended in December 2020.We also searched the literatures on "China Wan fang Medical Network" "China National Knowledge Infrastructure"and "PubMed" that reported by China medical institutions using“hydroa vacciniforme”、"hydroa vacciniforme-like lymphoma" or "hydroa vacciniforme-like lymphoproliferative disorder" as key words.A total of 42 patients with complete clinical data and follow-up records were enrolled in our study.SPSS 23.0(IBM,Armonk,NY,U.S.A.)was used to perform the statistical analysis.The Kaplan-Meier method was used for survival analysis and differences in OS were calculated by log-rank test.The predictive values of factors related to the mortality were assessed by Cox proportional hazards models.P<0.05 was considered statistically significant.Overall Survival(OS)was defined as the period from diagnosis to death or the last follow-up time.Results1.Clinical features:Among all patients,58 cases were children or adolescents and only 5 cases were adults,and the median age of disease onset was 6 years old(range from 2 to 50 years old),the ratio of male to female cases was 32:31.All cases presented typical papulovesicles or a cluster of blisters on sun-exposed areas of the body.Half of cases developed systemic symptoms and fever was the most common symptom.10 patients had hypersensitivity mosquito bite.2 patients complicated with hemophagocytic syndrome,which both occurred in children.2.Laboratory examination:31 cases showed EBV-DNA load in plasma≥1000 copies/ml.In addition,31 cases were found elevated level of lactate dehydrogenase in the plasma.3.Histological results:Most cases presented blister in the epidermis and variably dense lymphocytes infiltration throughout the dermis,mainly surrounding the skin appendages and blood vessels.The lymphocytes were small or medium,characterized with mild atypia and irregular nucleus.Subcutaneous fat layer was involved in 25 cases.4.Immunohistochemistry:CD3 and TIA-1 were positive in nearly all cases.15 cases expressed CD4,10 cases expressed CD8,and 9 cases showed both positive for CD4 and CD8.13 cases exhibited CD56(+)NK cells.20 cases were positive for CD30.40 cases indicated the Ki-67 proliferative index>20%.65 cases showed EBV-encoded RNA(EBER)positive.5.TCR gene rearrangement:45 cases performed TCR gene rearrangement test and 34 cases exhibited monoclonal rearrangement in the T-cell receptor genes.6.Treatment:26 cases received chemotherapy,of which CHOP regimen was widely used,and 3 cases accepted hematopoietic stem cell transplantation as salvage therapy after failure to chemotherapy,and they all live without disease at present.7.Survival outcome:59 cases with complete survival statistic and the median survival time is 24 months.Among them,38 cases survived,21 cases died,of which 11 patients died of systemic lymphoma,1 patients died of sepsis,and 9 patients died of rapid disease progression.The 1-year,3-year and 5-year OS rates were 84.9,74.1 and 54%,respectively.8.Prognosis analysis:Cox univariate analysis suggested that hepatosplenomegaly and subcutaneous tissue infiltration were both poor factor associated with mortality.However,In Cox multivariate analysis,subcutaneous tissue infiltration was an independent prognosis factors significantly.ConclusionHV-LPD in Chinese patients had more indolent and chronic course,although a few of cases progressed to EBV+ systemic T/NK lymphoma.There is no standard treatment,chemotherapy would improve the survival time in some relapse patients,but has no significant statistical difference in the overall survival rate.Hematopoietic stem cell transplantation may be a new choice for relapse and refractory patients.Our research demonstrated that subcutaneous tissue infiltration is an independent prognosis factors significantly.