Hydroa Vacciniforme Lymphoproliferative Disorder in a Young Spanish Woman: An Infrequent Case With Fatal Outcome.

ABSTRACT: Hydroa vacciniforme (HV) lymphoproliferative disorder is a rare NK/T-cell lymphoma mainly affecting children and with a clinical resemblance to HV, which is mostly reported in Latin American and some Asian countries. Overall, the mature T cell and NK-cell neoplasms are now grouped into 9 families based on diverse concepts: cell of origin/differentiation state, clinical scenario, disease localization, and cytomorphology. HV lymphoproliferative disorder is listed within the group of Ebstein Barr Virus-positive T-cell and NK-cell lymphoid proliferations and lymphomas of childhood according to the fifth edition of the World Health Organization Classification of mature lymphoid neoplasms. We report the extraordinary case of a 22-year-old white woman, native of Spain, first presented in 2016 when she started suffering from recurrent facial edema. Four years later, the disease progressed with lymph node spreading and a fatal outcome. Here, we describe the clinical and histological presentation of the lymphoma throughout its evolution. Cases like this can be difficult to classify posing a real challenge to clinicians and pathologists. So, it is vital to be aware of the rare presentation of this disease to be able to identify the clinical and histological picture to make a correct diagnosis and establish an early treatment.

Hydroa Vacciniforme.

This case report describes recurrent episodes of pruritic vesicular lesions and erosions on the face and photoexposed areas of the arms as well as multiple varioliform scars.

Diagnostic and disease severity determination criteria for hydroa vacciniforme lymphoproliferative disorders and severe mosquito bite allergy.

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) and severe mosquito bite allergy (SMBA) are both cutaneous forms of Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell LPDs and are closely related to chronic active EBV disease (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). HV-LPD is further divided into classic HV, a benign subtype mediated by EBV-positive γδT cells, and systemic HV, another life-threatening subtype mainly associated with EBV-positive αßT or γδT cells. The vast majority of patients with SMBA have increased numbers of EBV-infected NK cells in the blood. Clinical symptoms of HV-LPD and SMBA often overlap in the same patient and may progress to more serious disease conditions equivalent to the systemic form of CAEBV. To define the disease spectrum of HV-LPD and SMBA, we propose the diagnostic criteria and the determination criteria for disease severity. The proposed diagnostic criteria are consistent with those for CAEBV and EBV-HLH in the guidelines for the management for CAEBV and related disorders 2023.

Coexpression of natural killer cell antigens by T-cell large granular lymphocytes in hydroa vacciniforme lymphoproliferative disorder and the involvement of Vδ1 + epithelial-type γδT cells.

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a cutaneous variant of chronic active Epstein-Barr virus disease. We examined the coexpression of T- and natural killer (NK)-cell antigens in five patients with classic HV (cHV) and five with systemic HV (sHV). T-cell receptor (TCR) repertoire analysis was performed with high­throughput sequencing. All five cHV patients had increased γδT cells (> 5%), whereas five sHV patients showed γδT- and αßT-cell dominance in two patients each, and a mixture of abnormal γδT and αßT cells in one. Circulating CD3 + T cells expressed CD16/CD56 at 7.8-42.3% and 1.1-9.7% in sHV and cHV, respectively. The percentage of CD16/CD56 + T cells was higher in the large granular lymphocyte or atypical T-cell fractions in sHV, but no TCR Vα24 invariant chain characteristic of NKT cells was detected. Considerable numbers of CD3 + cells expressing CD56 were observed in sHV skin infiltrates. Of the circulating γδT cells tested, TCR Vδ1 + cells characteristic of the epithelial type of γδT cells were dominant in two sHV cases. Thus, atypical αßT and γδT cells in HV-LPD can express NK-cell antigens, such as CD16 and CD56, and Vδ1 + epithelial-type γδT cells are a major cell type in some HV-LPD cases.

Clinicoprognostic Study of Hydroa Vacciniforme-like Lymphoproliferative Diseases: A Systematic Review.

BACKGROUND: Limited clinicopathological and prognostic data are available on hydroa vacciniforme (HV)-like lymphoproliferative diseases (HVLPD). METHODS: This systematic review searched HVLPD reports in Medline via PubMed, Embase, Cochrane, and CINAHL databases in October 2020. RESULTS: A total of 393 patients (65 classic HV, 328 severe HV/HV-like T-cell lymphoma [HVLL]) were analyzed. Among severe HV/HVLL cases, 56.0% were Asians, whereas 3.1% were Caucasians. Facial edema, hypersensitivity to mosquito bites, the onset of skin lesion, and percentage of severe HV/HVLL differed significantly by race. Progression to systemic lymphoma was confirmed in 9.4% of HVLPD patients. Death occurred in 39.7% patients with severe HV/HVLL. Facial edema was the only risk factor associated with progression and overall survival. Mortality risk was higher in Latin Americans than in Asians and Caucasians. CD4/CD8 double-negativity was significantly associated with the worst prognosis and increased mortality. CONCLUSION: HVLPD is a heterogeneous entity with variable clinicopathological features associated with genetic predispositions.

[Delayed diagnosis of hydroa vacciniforme-like lymphoproliferative disorder in a patient with skin rashes].

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent EBV infection and can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma through the clonal expansion of EBV-infected T or natural killer (NK) cells. Hydroa vacciniforme lymphoproliferative disorder (HV) and hypersensitivity to mosquito bites (HMB) have been identified as skin diseases in EBV-associated T- or NK-cell lymphoproliferative diseases. We present the case of a 33-year-old man. The patient had frequent episodes of a facial rash for three years before he visited our hospital, he visited several dermatologists but did not receive a diagnosis of HV. He was referred to the hematology department of our hospital for assessment of atypical lymphocytes in peripheral blood. Based on routine blood and bone marrow test we were unable to diagnose HV. However, when the patient's liver function deteriorated six months later, we considered the possibility of HV after reevaluating the skin rash. After performing EBV-related tests, we were able to definitively diagnose CAEBV with HV. It is crucial to be able to connect clinical observations to EBV-related tests when diagnosing CAEBV. Hematologists must be knowledgeable of the EBV-associated skin conditions of HV and HMB.

Hydroa vacciniforme-like lymphoproliferative disorder in Ecuadorian children: A case series.

We report the clinical and histopathological features of hydroa vacciniforme-like lymphoproliferative disorder in five indigenous and Mestizo children. All the children resided at higher altitudes, experiencing maximal solar exposure. All cases presented with prurigo along with Epstein-Barr virus infection. Histopathologic examination showed an atypical, CD30 + lymphocytic infiltrate with angiocentricity in all, while three cases demonstrated panniculitis-like infiltrate.

An update on viral-induced cutaneous lymphoproliferative disorders. CME Part I.

Viral-induced cutaneous T-cell lymphomas are an uncommon group of lymphoproliferative disorders characterized by a viral infection of T and natural killer (NK) cells. This group of cutaneous T-cell lymphomas is more commonly encountered in Asians and Native Americans from Central and South America compared with Western populations. Viral-associated lymphoproliferative disorders include a spectrum of entities that range from nonneoplastic lesions, such as chronic active Epstein-Barr virus infection and infective dermatitis to malignant diseases, such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and adult T-cell leukemia/lymphoma. This review article will focus on hydroa vacciniforme-like lymphoproliferative disorder, extranodal NK/T-cell lymphoma, adult T-cell leukemia/lymphoma, lymphomatoid granulomatosis, and Epstein-Barr virus-positive mucocutaneous ulcers. We will review the pathogenesis of these conditions and the challenges of making a timely diagnosis in early-stage disease and discuss the common clinicopathologic manifestations, mutational landscape, and approaches to treat these highly aggressive and frequently lethal types of lymphoma.

Case report: Cellular therapy for hydroa vacciniforme-like lymphoproliferative disorder in pediatric common variable immunodeficiency with chronic active Epstein-Barr virus infection.

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein-Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.

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

The clinicopathological features of 32 patients (17 females and 15 males) with a median age of 8 years (range, 1.5-21 years) 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 22 months (range 3.6-71 months), and 15 patients died within a median follow-up of 6 months (range 0-60 months).

Ocular Involvement Preceded the Onset of Cutaneous Lesions in Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Case Report.

PURPOSE: To report a case of ocular involvement associated with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD). CASE REPORT: A 10-year-old HVLPD boy suffered conjunctivitis, interstitial keratitis, and anterior uveitis sequentially during the whole course. Interestingly, this case manifested initially only with ocular findings, which preceded 1 year earlier than the onset of cutaneous lesions. And his later ocular findings occurred simultaneously with cutaneous lesions. The patient was treated with oral prednisone, ganciclovir, and light protection. Topical corticosteroid drops used to control ocular inflammation. Since then, he has not had any flares of ocular inflammation, and the cutaneous lesions improved. Although corneal nebula had been formed, the vision was still good. CONCLUSION: Our case was supportive of ocular involvement in HVLPD. Ophthalmologists should be aware of ocular involvement in HVLPD could be preceded the onset of cutaneous lesions, and prudently perform a careful ophthalmic examination at regular intervals to limit long-term sequelae.

Hydroa vacciniforme-like lymphoproliferative disorder with eye involvement.

Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is characterized by vesiculopapular eruptions on sun-exposed and sometimes unexposed skin. Though ocular involvement in HVLPD is rare, it may present with conjunctivitis, corneal opacities, uveitis, and interstitial keratitis. We report a case of a 7-year-old boy with HVLPD, whose ophthalmic symptoms were neglected for over 2 years, who developed anterior uveitis and corneal nebulae without vision impairment. Awareness of eye involvement in patients with HVLPD may help to prevent severe complications.

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

BACKGROUND: 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. METHODS: 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. RESULTS: Eleven cases were included, with a male predominance and a mean age of 25.1 years. 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. CONCLUSIONS: 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 in an adult invades the liver and bone marrow with clear pathological evidence: a case report and literature review.

BACKGROUND: Hydroa 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 PRESENTATION: Here, 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. CONCLUSIONS: Our case confirms the liver damage was caused by HV-LPD and the effectiveness of antiviral treatment.