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.

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.

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).

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.

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: A study of clinicopathology and whole-exome sequencing in Chinese patients.

BACKGROUND: Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) encompasses a rare group of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases. OBJECTIVE: To define the clinical and pathologic characteristics of HVLPD and to identify mutant genes that may be related to the development of HVLPD. METHODS: Clinical 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. RESULTS: Thirteen 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. CONCLUSIONS: HVLPD 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.

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

BACKGROUND: Hydroa 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. METHODS: This retrospective study reviewed the clinical, morphologic, immunophenotypical features, and clinical treatment of 19 patients with HV-LPD. RESULTS: All 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. CONCLUSIONS: This 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.

Recent Advances in Cutaneous T-cell Lymphoma: Diagnostic and Prognostic Considerations.

This review describes the latest advances in the diagnosis of cutaneous T-cell lymphoma focusing on the most clinically useful features introduced since the publication of the World Health Organization revision in 2017. Clinical entities described include mycosis fungoides, Sézary syndrome, lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, primary cutaneous gamma delta T-cell lymphoma, primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, and hydroa-vacciniforme-like lymphoproliferative disorder. Distinguishing histologic clues to diagnosis are discussed, and important molecular advances are described. Key prognostic indicators that may assist clinicians with timely and appropriate management options are presented.

Hydroa vacciniforme-like lymphoproliferative disorder: Clinicopathologic study of 41 cases.

BACKGROUND: 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. OBJECTIVE: To report the characteristics of HVLLPD in Chinese patients. METHODS: Retrospective analysis of patients with HVLLPD from a single institute. RESULTS: 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. LIMITATIONS: This was a retrospective study. CONCLUSIONS: 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 DNA loads had an increased risk of their disease evolving into aggressive disease. Chemotherapy should not be considered as first-line treatment for most Chinese patients.

Hydroa vacciniforme-like lymphoproliferative disorder in an elderly Chinese patient and a literature review of adult cases.

Hydroa vaccinforme-like lymphoproliferative disorder (HVLPD) is a rare T-cell lymphoproliferative disorder driven by the Epstein-Barr Virus (EBV). It was initially designated under the 2008 WHO classification of tumors of hematopoietic and lymphoid tissues as a distinct entity but has been recently reclassified as a lymphoproliferative disorder under the 2016 revision of the 2008 WHO classification of lymphoid malignancies. HVLPD mainly affects Asian, Central, and South American children. It is rarely seen in adults. Although HVLPD may initially be limited to cutaneous involvement and run an indolent course, some patients may develop a rapidly aggressive course. We report a case of an elderly Chinese man with cutaneous-limited disease and a favorable course. A review of adult cases of HVLPD published in the English literature, with comparison to our case, is also presented in this paper.

Hydroa Vacciniforme-Like Lymphoma in Tibetan Children: 2 Cases and a Literature Review.

Hydroa vacciniforme-like lymphoma shows a marked predilection for the pediatric population, especially in Latin America and Asia. Here, we present 2 pediatric patients from Tibet of China, which is the first report from this area.

Hydroa Vacciniforme-Like T-Cell Lymphoma: A Further Brazilian Case.

Hydroa vacciniforme (HV)-like lymphoma is a rare, usually fatal Epstein-Barr virus-driven lymphoproliferative disease affecting children from Asia, Mexico, and South America. Cutaneous manifestations imitate HV, a benign photodermatosis in which systemic symptoms are not observed, and spontaneous regression occurs later in adolescence or young adulthood. We report a case of HV-like lymphoma in a 12-year-old girl, descendent from an ancient Amazon indigenous tribe that, as far as we know, represents the second Brazilian case ever reported in the medical literature.

Hydroa vacciniforme and hydroa vacciniforme-like T-cell lymphoma: an uncommon event for transformation.

BACKGROUND: Hydroa vacciniforme (HV) is associated with Epstein-Barr virus (EBV) infection and a risk of transformation to lymphoma. METHODS: We retrospectively analyzed six HV cases for EBV association and transformation to HV-like T-cell lymphoma. Clinicopathologic features were reviewed and cases were assessed for EBV-encoded RNA (EBER) by in situ hybridization, double staining with immunohistochemistry and EBER and for T-cell clonality. RESULTS: The male-to-female ratio was 5:1, with a median age at diagnosis of 18.5 years. All patients initially had recurrent vesicles, necrotic ulcers or scars on sun-exposed areas. Symptoms were present before diagnosis between 2 weeks to 10 years. The mean follow-up time was 106.3 months. Four patients (67%) were EBV-positive. All four EBV-positive and one EBV-negative patients had relapsing clinical course. Double staining proved EBV infection in T-cells. Moreover, one EBV-positive patient developed HV-like T-cell lymphoma with hemophagocytosis after 209 months of recurrent papulovesicular eruptions and eventually died. T-cell clonality was successfully performed in four HV patients and all showed polyclonal results; the transformed HV-like T-cell lymphoma was monoclonal. CONCLUSIONS: In EBV endemic areas, HV is frequently (67%) associated with EBV infection, but transformation to HV-like T-cell lymphoma seems to be uncommon (17%) and bear a dismal outcome.