Hydroa Vacciniforme-like Lymphoproliferative Disorder Research Articles

Epstein-Barr virus-related lymphoproliferative disorders of the skin

Epstein Barr Virus (EBV) is associated both solid (nasopharyngeal carcinoma, non-nasopharyngeal lymphoepithelioma- like carcinoma, gastric carcinoma, leiomyosarcoma) and hematolymphoid malignancies, some of the latter, however, spanning over a spectrum ranging from reactive and self-limiting to severe and life-threatening conditions. This review will focus on the disorder most commonly involving the skin, namely: EBVpositive mucocutaneous ulcer; lymphomatoid granulomatosis; EBV-positive diffuse large B cell lymphoma; plasmablastic lymphoma; post-transplant lymphoproliferative disorder; extranodal NK/T cell lymphoma, nasal type; angoimmunoblastic T cell lymphoma; severe mosquito bite allergy; hydroa vacciniformelike lymphoproliferative disorder. Given the uncommon occurrence of all these infiltrates in the skin, multidisciplinary approach, as well as referral to tertiary care centers are always advisable.

Clinical and Pathological Features of Hydroa Vacciniforme-Like Lymphoproliferative Disorder Along with Risk Factors Indicating Poor Prognosis.

To examine the clinical and pathological features, laboratory markers, therapeutic options and risk factors indicating poor prognosis of hydroa vacciniforme-like lymphoproliferative disorder (HVLPD). Seven patients with HVLPD had their clinical and pathological data collected. Immunohistochemical staining, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization experiments, T-cell receptor (TCR) gene rearrangement, RT-PCR tests and the Elisa assay were carried out. The main clinical manifestations were papulovesicular lesions and ulcers on the face, neck, or trunk. Five cases had systemic symptoms. Three of the deceased patients had significant facial edema, deep body necrosis, and ulceration. The pathological results demonstrated that lymphocytes infiltrated blood vessels and sweat glands in addition to the dermis and subcutaneous tissues. All patients tested positive for CD3 and EBER. Six cases tested positive for TCRβF1, but none tested positive for TCRδ. TCRγ monoclonal rearrangement, strongly positive expression of TIA-1 and a Ki67 proliferation index of 40% occurred in 3 fatal cases. When compared to the survival group, the plasma EBV DNA in the deceased group was considerably higher (P<0.05). IFN-γ and TNF-α cytokine levels in patients were higher than in the control group, particularly in the deceased group (P<0.05). The skin lesions on all patients recovered quickly underwent conservative care. Nonetheless, 3 patients passed away as the disease progressed in its latter stages. In our cases, the main infiltrating cells were T cells and the dominant lymphocyte subclass was αβT cells. A significant increase in lgE level, plasma EBV DNA, IFN-γ, and TNF-α cytokine levels, decreased hemoglobin level, strongly positive expression of TIA-1, high Ki67 proliferation index, and positive TCR gene rearrangement are all indicators of a poor prognosis.

ORAL MANIFESTATIONS OF HYDROA VACCINIFORME–LIKE LYMPHOPROLIFERATIVE DISORDER: CASE SERIES

Hydroa vacciniforme–like lymphoproliferative disorder (HVLPD) is a chronic Epstein-Barr virus (EBV)-positive lymphoproliferative disease that may either present as an indolent condition or progress to a systemic T-cell lymphoma. This study presents the clinicopathologic data, microscopic findings, and EBV status of 11 cases of HVLPD with oral involvement. A male predilection (7:4) was observed, with mean patient age of 25.1 years. The lips and buccal mucosa were the most affected sites. Lesions appeared as painful ulcers. The patients also showed facial edema and erythema. Microscopic findings included moderate to severe T-cell infiltrate with angiotropism, angiocentricity, and epidermotropism. Two cases affecting the skin on the lip exhibited a periappendageal lymphocytic infiltrate. Immunohistochemistry reactions confirmed the cytotoxic T-cell (CD8+) phenotype, and in situ hybridization showed the presence of EBV in all cases. The clinical course was aggressive, and all patients died. HVLPD is a rare and aggressive disease that may show oral involvement.

Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders.

Adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) often progress rapidly, and require allogeneic stem cell transplantation early in the course of treatment. Unrelated cord blood transplantation (UCBT) is a readily available option for patients without HLA-matched donors. We retrospectively analyzed the outcomes of 12 UCBT in adult patients with chronic active EBV infection (CAEBV, n = 8), EBV-positive hemophagocytic lymphohistiocytosis following primary EBV infection (n = 2), hydroa vacciniforme-like lymphoproliferative disorder (n = 1), and systemic EBV-positive T-cell lymphoma of childhood (STCLC, n = 1). The median age at transplantation was 31.5years (range 19-58). At the median follow-up time for survivors, which was 6.3years (range 0.3-11.3), 3-year overall survival (OS) rates in all patients and 8 CAEBV patients were 68.2% (95% CI 28.6-88.9) and 83.3% (95% CI 27.3-97.5), respectively. Graft failure occurred in 4 of 8 CAEBV patients, requiring a second UCBT to achieve neutrophil engraftment. The cumulative incidence of grade II-IV acute GVHD was 33.3% (95% CI 9.1-60.4%). The EBV-DNA load became undetectable or very low after UCBT in all cases. UCBT may be a promising treatment option for adult-onset EBV-T/NK-LPDs.

Hydroa vacciniforme-like lymphoproliferative disorder: Aretrospective study on clinicopathological characteristics of 32 cases.

The clinicopathological features of 32 patients (17 females and 15males) with a median age of 8years (range, 1.5-21years) from Southwestern China diagnosed with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) were reviewed. At presentation, 6 patients showed only skin lesions, while 26 patients showed both skin lesions and systemic symptoms, including fever, lymphadenopathy and hepatosplenomegaly. As the disease progressed, systemic symptoms occurred in all patients. Follow-up data of 29 patients showed that 14 patients were still alive with disease with a median follow-up time of 22months (range 3.6-71months), and 15 patients died within a median follow-up of 6months (range 0-60months).

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis-Experience of a Tertiary-Care Pediatric Institution and Review of the Literature.

Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. Data were retrospectively collected from the histopathologic database of the CHU Sainte-Justine, University of Montreal, Montreal, Canada. All patients up to 18 years of age with a diagnosis of a primary cutaneous lymphoma (including lymphomatoid papulosis), secondary cutaneous lymphoma or cutaneous manifestations of leukemia, followed from 1980 to 2019 at our center were reviewed. Thirty-six patients were included. Age at presentation ranged from birth to 18 years of age (mean 7.83 ± 5.16; median 7.0). Ten different hematologic disorders were identified according to the WHO-EORTC classifications: lymphomatoid papulosis (10 cases), mycosis fungoides (6 cases), anaplastic large cell lymphoma (4 cases), pre-B acute lymphoid leukemia (5 cases), primary cutaneous marginal zone B-cell lymphoma (4 cases), primary cutaneous CD4+medium T-cell lymphoproliferative disorder (1 case), extranodal NK/T-cell lymphoma (1 case), hydroa vacciniforme-like lymphoproliferative disorder (1 case), B-cell lymphoblastic lymphoma (1 case) and acute myeloid leukemia (3 cases). The most common subtype of cutaneous hematologic disease in our single institution study was lymphomatoid papulosis (type A and type C), followed by mycosis fungoides. Recognition of this large clinical and histological spectrum by dermatologists is important because diagnosis is often established by biopsy of skin lesions, even in secondary cutaneous cases. Moreover, the clinicopathological correlation is of utmost importance for the final diagnosis of those pathologies.

A Case of Hydroa Vacciniforme-Like Lymphoproliferative Disorder Presenting As Orogenital Ulcerations.

A Case of Hydroa Vacciniforme-Like Lymphoproliferative Disorder Presenting As Orogenital Ulcerations.

Varying Presentations of EBV-associated Clinical Entities with Emphasis on EBV-Associated T- and NK-cell Lymphoproliferative Disorders of Childhood

The Epstein-Barr Virus-associated T- and NK-cell lymphoproliferative disorders are a group of hematologic disturbances that occur in pediatric age groups. The literature describes extensive heterogeneity in the presentation of this disease, with a noncanonical reaction to Epstein-Barr virus infection underpinning the wide variety of clinical manifestations. In this review, we discuss chronic active Epstein-Barr virus infection, hypersensitivity to mosquito bites, Alice in Wonderland syndrome, Hydroa vacciniforme-like lymphoproliferative disorder, and the clinical and histologic findings of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and systemic Epstein-Barr-positive T-cell lymphoproliferative disorder of childhood.

Oral manifestations of Hydroa vacciniforme-like lymphoproliferative disorder: a clinicopathological study of a Peruvian population.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a chronic Epstein-Barr virus (EBV)-positive lymphoproliferative disease which may either present as an indolent condition or progress to a systemic T-cell lymphoma. All HVLPD diagnosed over a 10-year period were retrieved, and clinical data regarding sex, age, oral and systemic manifestations, and clinical follow-up were obtained. Immunohistochemistry was done in order to characterize the lymphoid cells, and in situ hybridization was used to demonstrate the presence of EBV. Eleven cases were included, with a male predominance and a mean age of 25.1years. Buccal mucosa and the lips were the most affected oral sites, appearing as painful ulcers. All patients exhibited facial oedema, usually affecting the lips, nose and periorbital region. The clinical course was gradual but progressive, with four patients having fever and 3 showing lymphadenopathies. All cases showed a moderate to severe lymphocytic infiltrate with angiotropism, angiocentricity and epidermotropism. Two cases affecting the lip skin exhibited a periappendageal lymphocytic infiltrate. Few large pleomorphic cells were found, surrounded by smaller and medium-sized lymphoid cells, as well as reactive plasma cells, macrophages, neutrophils and eosinophils. All lesions exhibited a cytotoxic T-cell (CD8+) phenotype with a variable proliferative index. All cases were associated with EBV, and all patients died due to complications of the disease. HVLPD is a rare disease that may show oral involvement with a cytotoxic T-cell phenotype, and is strongly associated with EBV. As shown in this series, HVLPD may show aggressive clinical behaviour.

Hydroa vacciniforme‐like lymphoproliferative disorder: A clinicopathological, immunohistochemical, and prognostic study of 24 cases in China

Hydroa vacciniforme‐like lymphoproliferative disorder (HV‐LPD) is a rare cutaneous disease associated with Epstein–Barr virus infection. We retrospectively analyzed the clinical presentation, histopathological characteristics, and prognostic study of HV‐LPD in 24 Chinese patients. All patients presented with recurrent papulovesicular and necrotic eruptions on the face, neck, and extremities, with 11 showing systemic symptoms. Twenty patients were diagnosed with HV‐LPD in childhood (age < 18 years) and four in adulthood (age ≥ 18 years). The median age at diagnosis was 8.5 years old (range, 2–50). Histopathology revealed variably dense lymphocyte infiltration throughout the dermis. All cases were strongly positive for CD3 and Epstein–Barr encoding region based on in situ hybridization. Of 18 cases with a T‐cell phenotype, 15 harbored monoclonal rearrangements in T‐cell receptor (TCR) genes. Four cases with a natural killer cell phenotype carried polyclonal rearrangements in TCR genes. Among 24 patients, eight (33.3%) received chemotherapy, two (8.3%) allogeneic hematopoietic stem cell transplantation, and both are currently alive without disease. The median follow‐up period was 24 months (range, 7–120) and 23 patients were available: 15 (62.5%) were alive, and eight (33.3%) had died. Fourteen cases had a relapse of disease and three developed lymphoma within 24 months of diagnosis. The mean survival time of childhood‐onset patients was longer than that of adult‐onset patients (36.4 vs. 20.8 months). In summary, the wide clinical course and representative presentation of cases in our center reflect the pedigree characteristics of HV‐LPD. Allogeneic hematopoietic stem cell transplantation should be a preferred choice for relapse and refractory patients due to the poor effect of chemotherapy. Adult‐onset and high serum EBV DNA loads may indicate an increased risk of aggressive disease in patients with HV‐LPD.

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is an Epstein-Barr virus (EBV) associated disease

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is an Epstein-Barr virus (EBV) associated disease

Hydroa Vacciniforme-like Lymphoproliferative disorder in an adult invades the liver and bone marrow with clear pathological evidence: a case report and literature review

BackgroundHydroa Vacciniforme-like Lymphoproliferative Disorder (HV-LPD) is the name given to a group of Epstein-Barr virus (EBV)-associated diseases. It resembles hydroa vacciniforme (HV), the rarest form of photosensitivity, and is a T-cell disorder associated with an Epstein-Barr virus infection. The majority of diagnosed cases occur in East Asia and South America. It is rare in the United States and Europe. Multiple studies have revealed the clinical manifestation of an enlarged liver, but no gold standard such as pathology has yet supported this as a clinical sign of HV-LPD.Case presentationHere, we report a case of a 34-year-old Asian female with definite liver invasion. The patient had complained of a recurring facial rash for many years. The patient was admitted to the hospital because of an enlarged liver. After hospitalization, she was given an EB virus nucleic acid test. The EB virus nucleic acid test was positive, and pathological examination suggested that HV-LPD had invaded the skin, bone marrow, and liver. After being given antiviral treatment, the patient’s symptoms were mitigated.ConclusionsOur case confirms the liver damage was caused by HV-LPD and the effectiveness of antiviral treatment.

Hydroa Vacciniforme-Like Lymphoproliferative Disorder in Korea: Prognostic Implication of Clinical Signs and Whole Blood Epstein-Barr Virus DNA.

BackgroundHydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is rare Epstein-Barr virus (EBV)-associated disease. The classic form of HVLPD is a self-resolving disease, whereas the systemic form can progress to malignant lymphoma, resulting in fatal outcomes. However, the prognostic factors remain unclear.ObjectiveThis study aimed to evaluate the clinical characteristics of HVLPD and the association between whole blood EBV DNA and clinical outcomes.MethodsWe retrospectively reviewed our 25-year experience involving 11 patients with HVLPD from a single tertiary center in South Korea and evaluated the clinical characteristics of HVLPD and the correlation between whole blood EBV DNA and clinical outcomes.ResultsOf the total 11 patients, 54.5% (6/11) manifested classic HVLPD that resolved with conservative treatment, while 45.5% (5/11) patients had systemic HVLPD, four of whom died of progressive disease or hemophagocytic syndrome. Five patients with systemic HVLPD manifested severe skin lesions such as prominent facial edema, deep ulcers and necrotic skin lesions involving sun-protected areas. Median EBV DNA levels at initial diagnosis were higher in three dead patients than in those alive (2,290 vs. 186.62 copies/µl).ConclusionWhen EBV DNA levels were high, patients showed severe skin lesions and when EBV DNA levels were low, skin lesions tended to improve. Thus, patients with high EBV DNA levels showed an increased risk of severe skin lesions and disease progression.

Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein-Barr Virus Infection.

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

17646 Hydroa vacciniforme-like lymphoproliferative disorder initially presenting as severe insect allergy in a 46-year-old woman

Background: Hydroa vacciniforme–like lymphoproliferative disorder (HV-LPD) is a chronic EBV-associated lymphoproliferative disorder most commonly seen in Asian and South American children. Initially thought to be a benign photodermatosis, HV-LPD is a disorder of monoclonal or rarely polyclonal T cells or NK cells.

Hydroa vacciniforme-like lymphoproliferative disorder in Korea

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is a rare Epstein–Barr virus (EBV)-associated lymphoproliferative disease. The disease course of HVLPD varies from an indolent course to progression to aggressive lymphoma. We investigated the characteristics of HVLPD in Korean patients. HVLPD patients at Seoul National University Hospital between 1988 and 2019 were retrospectively analyzed. This study included 26 HVLPD patients who all presented with recurrent papulovesicular and necrotic eruption on the face, neck, and extremities. EBV was detected from the skin tissues of all patients. HVLPD was diagnosed during childhood (age < 18 years) in seven patients (26.9%) and in adulthood (age ≥ 18 years) in 19 cases (73.1%). The median age at diagnosis was 24.0 years (range 7–70 years). HVLPD has various clinical courses, from an indolent course to progression to systemic lymphoma. Fourteen patients (53.8%) developed lymphoma: systemic EBV-positive T-cell lymphoma (n = 9, 34.6%); extranodal natural killer/T-cell lymphoma, nasal type (n = 3, 11.5%); aggressive natural killer/T-cell leukemia (n = 1, 3.8%); and EBV-positive Hodgkin lymphoma (n = 1, 3.8%). Mortality due to HVLPD occurred in five patients (26.3%) in the adult group, while it was one patient (14.3%) in the child group. As lymphoma progression and mortality occur not only in childhood but also in adulthood, adult-onset cases may need more careful monitoring.

Hydroa Vacciniforme-Like Lymphoproliferative Disorder in an Adult Patient With Chronic Lymphocytic Leukemia

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a rare Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder (LPD) which primarily affects children from Latin America and Asia. Typical features include vesicles and ulceration in sun-exposed areas which may be accompanied by systemic symptoms such as fever, lymphadenopathy and hepatosplenomegaly. We report a 73-year-old man diagnosed with HV-LPD in the context of zanubrutinib (oral Bruton tyrosine kinase (BTK)-inhibitor) treatment for chronic lymphocytic leukemia (CLL). The patient presented with slowly progressive peri-orbital edema and erythema non-responsive to topical therapies which eventually progressed to focal crusting and erosion. Prednisolone was subsequently introduced, which led to a good response in the patient’s symptoms. J Med Cases. 2020;11(11):366-369 doi: https://doi.org/10.14740/jmc3576

Hydroa vacciniforme-like lymphoproliferative disorder: A study of clinicopathology and whole-exome sequencing in Chinese patients

BackgroundHydroa vacciniforme-like lymphoproliferative disorder (HVLPD) encompasses a rare group of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases. ObjectiveTo define the clinical and pathologic characteristics of HVLPD and to identify mutant genes that may be related to the development of HVLPD. MethodsClinical data and archived formalin-fixed, paraffin-embedded tissue were obtained from 19 patients. Specimens were analyzed by immunohistochemistry and in situ hybridization to detect EBV-encoded RNA (EBER1/2) and for T cell receptor (TCR) gene rearrangements. Whole-exome sequencing (WES) analysis was also performed in this study. ResultsThirteen patients survived between 3–58 months (median, 21 months) during the follow-up. Six patients who were almost adults (>15 years old) and died of the disease presented with facial edema. Lactate dehydrogenase (LDH) levels were elevated, and the TCR gene rearrangement test was positive more frequently in the patients who died. Compared with Chinese patients in a similar previous report, our patients had significantly higher proliferation (in all cases, the Ki-67 index was greater than 10 %) and a more aggressive clinical course. Moreover, after WES and Sanger verification, STAT3, IKBKB, ELF3, CHD7, KMT2D, ELK1, RARB and HPGDS were screened out in our patients. ConclusionsHVLPD refers to a heterogeneous group of cutaneous lymphoproliferative diseases with different clinical and pathological features that affect patient outcomes. Gene mutations may be correlated with the development of HVLPD, and our study may provide new therapeutic targets for HVLPD.

Hydroa Vacciniforme-like Lymphoproliferative Disorder Treated with Intravenous Immunoglobulin: Long-term Remission Without Haematopoietic Stem Cell Transplantation or Chemotherapy

Hydroa Vacciniforme-like Lymphoproliferative Disorder Treated with Intravenous Immunoglobulin: Long-term Remission Without Haematopoietic Stem Cell Transplantation or Chemotherapy

1792. Viral DNA Loads in Various Blood Components of Patients with EBV-Positive T/NK Cell Lymphoproliferative Diseases

BackgroundEpstein–Barr virus (EBV) is associated with T- and NK-cell lymphoproliferative disorders (EBV T/NK-LPD). For diagnosis of EBV T/NK-LPD, quantification of EBV DNA loads in peripheral blood by real-time PCR has been widely used. However, optimal blood components and cut-off values for diagnosis were not fully evaluated.MethodsFifty-nine patients with EBV T/NK-LPD including chronic active EBV infection (CAEBV), severe mosquito bite allergy, hydroa vacciniforme-like lymphoproliferative disorder (HV), and EBV- hemophagocytic lymphohistiocytosis (EBV-HLH) were enrolled. EBV DNA loads were compared among disease categories in each blood component from the same whole blood sample. The association between EBV DNA loads and disease activity were evaluated in CAEBV patients. Furthermore, the diagnostic cut-off value for EBV DNA loads in whole blood from CAEBV patients as compared with infectious mononucleosis patients was determined.ResultsEBV DNA loads in whole blood and peripheral blood mononuclear cells (PBMCs) were not significantly different among disease categories, whereas EBV DNA loads in plasma were significantly higher in EBV- HLH patients than in HV patients. EBV DNA loads in whole blood and PBMCs showed strong correlation (Figure 1). EBV DNA loads in plasma were significantly higher in CAEBV patients with active disease than in those with inactive disease (median: 104.5 IU/mL vs. 100.8 IU/mL, P < 0.001) (Figure 2). Diagnostic cut-off values for whole blood EBV DNA loads of CAEBV patients as compared with those of infectious mononucleosis was 104.2 ( = 15,800) IU/mL (Figure 3).ConclusionMeasuring EBV DNA loads in whole blood can be considered as initial evaluation for diagnosis of EBV T/NK-LPD. EBV DNA loads in plasma are more closely related to disease activity of CAEBV than EBV DNA loads in whole blood and PBMCs. Disclosures All authors: No reported disclosures.