Hydroa Vacciniforme-like Lymphoma Research Articles

Diagnosis and Management of Hydroa Vacciniforme

Hydroa vacciniforme (HV) is a rare photodermatoses with the most frequent onset in childhood. The exact pathogenesis of HV is still not known. This disease is a spectrum with almost similar clinical symptoms, but with a very different prognosis. Classic HV has the best prognosis, but affects the quality of life due to scar formation, while hydroa vacciniforme-like lymphoma (HVLL) is the variant with the worst prognosis. HV needs to be considered as a differential diagnosis, especially in childhood-onset photodermatoses. Classical HV must be distinguishes from hydroa vacciniforme-like lymphoproliferative disorders (HVLPD) because it is related to prognosis. There is still no consensus or guidelines on diagnosis and management for HV.

Hydroa vacciniforme–like lymphoma: Clinicopathologic description, treatment, and outcome

To the Editor: Hydroa vacciniforme-like lymphoma (HVLL) is associated with Epstein-Barr virus and usually occurs in childhood, with most reports coming from East Asia and South America. It manifests clinically with papules and vesicles, mainly on the face and upper extremity, which eventually ulcerate with scar formation. Patients with HVLL may present with systemic manifestations.1

Hydroa vacciniforme-like lymphoma

Hydroa vacciniforme-like lymphoma is a rare cutaneous T-cell lymphoma occurring in children associated with Epstein–Barr virus (EBV) infection. We reported a 15-year-old Chinese boy who presented with a 3-month history of recurrent special clinical manifestations including vesicles, erythematous papules, ulcer, crusting, and smallpox-like scar on his head, face, neck, limbs, and ankles. EBV-DNA level was positive. Immunohistochemistry showed CD2(+++), CD3(+++), CD4(+), CD5(++), CD7(+), CD8(±), CD56(+), ki67 (30%+), Gr-B(+++). The patient showed a significant improvement in clinical symptoms after being treated with interferon alpha and prednisone.

Epstein-Barr virus and skin

AbstractEpstein-Barr virus is a DNA virus infecting human beings and could affect 90% of human population. It is crucial to take in account that in Latin America, unlike what happens in developed countries, the exposure to the virus is very early and therefore people have a much longer interaction with the virus. The virus is related to many diseases, mainly the oncological ones, and when the onset is in cutaneous tissue, it can present many clinical variants, as well acute as chronic ones. Among the acute ones are infectious mononucleosis rash and Lipschutz ulcers; the chronic presentations are hypersensivity to mosquito bites, hydroa vacciniforme, hydroa vacciniforme-like lymphoma, its atypical variants and finally nasal and extra-nasal NK/T-cell lymphoma. Although they are not frequent conditions, it is crucial for the dermatologist to know them in order to achieve a correct diagnosis.

Primary cutaneous T-cell lymphoma: experience from the Peruvian National Cancer Institute.

BackgroundPrimary cutaneous T-cell lymphomas constitute a heterogeneous and rare group of diseases with regional particularities in Latin America.ObjectiveTo determine the clinicopathological features, relative frequency and survival among patients from a Peruvian institution.MethodsPrimary cutaneous T-cell lymphomas were defined based on the absence of extracutaneous disease at diagnosis. Classification was performed following the 2008 World Health Organization Classification of Neoplasms of the Hematopoietic and Lymphoid tissues. Risk groups were established according to the 2005 World Health Organization-EORTC classification for cutaneous lymphomas. Data of patients admitted between January 2008 and December 2012 were analyzed.Results74 patients were included. Mean age was 49.5 years. In order of frequency, diagnoses were: mycosis fungoides (40.5%), peripheral T-cell lymphoma not otherwise specified (22.95%), adult T-cell lymphoma/leukemia (18.9%), CD30+ lymphoproliferative disorders (6.8%), hydroa vacciniforme-like lymphoma (5.4%), extranodal NK/T-cell lymphoma (4.1%) and Sézary syndrome (1.4%). Predominant clinical patterns were observed across different entities. Mycosis fungoides appeared mainly as plaques (93%). Peripheral T-cell lymphoma not otherwise specified and adult T-cell lymphoma/leukemia presentation was polymorphic. All patients with hydroa vacciniforme-like lymphoma presented with facial edema. All cases of extranodal NK/T-cell lymphoma appeared as ulcerated nodules/tumors. Disseminated cutaneous involvement was found in 71.6% cases. Forty-six percent of patients were alive at 5 years. Five-year overall survival was 76.4% and 19.2%, for indolent and high-risk lymphomas, respectively (p<0.05). High risk group (HR: 4.6 [2.08-10.18]) and increased DHL level (HR: 3.2 [1.57-6.46]) emerged as prognostic factors for survival.Study limitationsSmall series.ConclusionPrimary cutaneous T-cell lymphomas other than mycosis fungoides or CD30+ lymphoproliferative disorders are aggressive entities with a poor prognosis.

Epstein-Barr virus and associated cutaneous lymphomas

Epstein-Barr virus (EBV) infection rate is very high in populations. It has been found that EBV is associated with many human diseases including an obviously heterogeneous group of cutaneous lymphomas, such as extranodal natural killer (NK) /T-cell lymphoma, hydroa vacciniforme-like lymphoma, Hodgkin′s lymphoma, Burkitt′s lymphoma, HIV-associated lymphoma and so on. EBV-associated cutaneous lymphomas have various clinical manifestations, a spectrum of histological changes with chronic or critical disease course and poor prognosis. Mechanisms of EBV-mediated oncogenesis are still unclear. By the interaction between functional molecules of EBV and the host, EBV can escape from cellular immunity in host, modulate multiple signaling pathways, promote tumor inflammation, induce blood vessel formation and gene mutations, and finally immortalize host cells. In clinic, high-risk population should be tracked and monitored, such as undernourished and immunocompromised persons, especially children, the elderly, organ transplant patients, and HIV-infected individuals, so as to early diagnose and interfere in EBV-associated cutaneous lymphomas. Key words: Herpesvirus 4, human; Skin; Lymphoma; Methods; Diagnosis

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

Hydroa vacciniforme (HV) is associated with Epstein-Barr virus (EBV) infection and a risk of transformation to lymphoma. 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. 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. 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.

Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts.

Mature T- and NK-cell non-Hodgkin lymphoma in children and young adolescents.

Mature T/Natural killer (NK)-cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein-Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas- nasal-type or extra nasal-type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV-positive lymphoproliferative disorders of childhood, hydroa vacciniforme-like lymphoma, hepatosplenic T-cell lymphoma and primary cutaneous gamma/delta T-cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline-based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future.

Clinical analysis of 14 cases of rare non-Hodgkin lymphoma in children

Objective To analyze the clinical characteristics and prognosis of 4 rare types of non-Hodgkin lymphoma(NHL) in children, and to discuss the progress in treatment. Methods Clinical data of 14 patients with rare types of NHL at Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine between January 2004 and December 2014 were retrospectively analyzed, and their clinical features, treatment and prognosis were discussed. Results Fourteen cases were reported including 6 subcutaneous panniculitis-like T-cell lymphoma(SPTCL), 3 hydroa vacciniforme-like cutaneous lymphoma(HVLL), 2 pediatric follicular lymphoma(PFL) and 3 extranodal NK/T-cell lymphoma, and nasal type(ENKTL). Ten patients (71.4%) primarily presented with skin lesions and underwent a long course of illness before they were finally diagnosed (the median was 10 months), 71.4%(10/14 cases) of them associated with fever and 50.0%(7/14 cases) with liver and spleen enlargement, and no evidence of central nervous system (CNS) and bone marrow (BM) involvement was observed, while 28.6% patients (4/14 cases) had more than two lines' abnormalities in peripheral blood examination.Since there were no standard treatment guidelines, most patients received CHOP (Cyclophosphamide+ Adriamycin+ Vincristine+ Prednisone) and/or mature B-cell NHL-like therapy, and 50.0%(7/14 cases) of them received interferon therapy in addition, while 1 patient received allogeneic hematopoietic stem cell transplantation after recurrence.The complete remission was achieved in 71.4%(10/14 cases) of all the patients.Two of them died, 3 lost follow-up, and 1 relapsed.The 3-year overall survi-val and event free survival rates were 0.84 and 0.57, respectively, after a median follow-up of 26 months (range 12-64 months). Conclusions Pediatric rare types of NHL show atypical clinical manifestation, low incidence of CNS/BM infiltration and long course.It is hard to make pathological diagnosis and differentiation.It is also inappropriate to apply the commonly used staging system to these rare types of NHL.No standard treatment has been found by now.SPTCL, HVLL and PFL have relatively good outcomes when treated with mature B-cell NHL-type therapy plus interferon therapy. Key words: Subcutaneous panniculitis-like T-cell lymphoma; Hydroa vacciniforme-like cutaneous lymphoma; Pediatric follicular lymphoma; Extranodal NK/T-cell lymphoma, nasal type; Child

Clinicopathologic Features of Hydroa Vacciniforme-Like Lymphoma: A Series of 9 Patients.

Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER-1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis.

Paediatric cutaneous lymphomas: a review and comparison with adult counterparts.

Primary cutaneous lymphomas (CL) in children is rare. Only a few studies focused specifically on paediatric CL and therefore little is known whether primary CL in children are similar to or different from their adult counterparts with respect to the clinicopathological presentation, behaviour and prognosis. An extensive literature search using PubMed/MEDLINE from January 1995 through July 2014 was undertaken for articles reporting cases of paediatric CL. In addition, we identified 31 children with CL in our institutions. Mycosis fungoides and lymphomatoid papulosis are the two most prevalent lymphoma forms in children. A few entities of cutaneous lymphomas such as cutaneous diffuse large B-cell lymphoma leg type, and Sézary syndrome have not been reported so far in children. Other lymphoma entities such as hydroa vacciniforme-like lymphoma are mostly seen in certain geographic areas (Asia, Central and South America). In the paediatric population, low-malignant indolent forms such as primary cutaneous marginal zone lymphoma and primary cutaneous follicle centre lymphoma are very rare, whereas the more aggressive forms of B-cell lymphomas, precursor lymphoblastic lymphomas, and blastic plasmacytoid dendritic cell neoplasm are the most common forms in children, mostly involving the skin secondarily. Most paediatric lymphomas have similar clinicopathological features and course as their adults counterparts, particularly in the group of cutaneous T-cell lymphomas. The spectrum of cutaneous B-cell lymphomas in children significantly differs from the one in adults. Diagnostic work-up and treatment of paediatric patients with lymphomas are best achieved in close collaboration with paediatric haematopathologists and oncologists.

Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Epstein–Barr virus‐associated T/natural killer‐cell lymphoproliferative disorders

Primary infection with Epstein-Barr virus (EBV) is usually asymptomatic and, in a normal host, EBV remains latent in B cells after primary infection for the remainder of life. Uncommonly, EBV can infect T or natural killer (NK) cells in a person with a defect in innate immunity, and EBV infection can cause unique systemic lymphoproliferative diseases (LPD) of childhood. Primary infection in young children can be complicated by hemophagocytic lymphohistiocytosis or fulminant systemic T-cell LPD of childhood. Uncommonly, patients can develop chronic active EBV (CAEBV) disease-type T/NK LPD, which includes CAEBV infection of the systemic form, hydroa vacciniforme-like T-cell LPD, and mosquito-bite hypersensitivity. The clinical course of CAEBV disease-type T/NK LPD can be smoldering, persistent or progressive, depending on the balance between viral factors and host immunity. Aggressive NK-cell leukemia, hydroa vacciniforme-like T-cell lymphoma, or uncommonly extranodal NK/T-cell lymphoma can develop in children and young adults with CAEBV disease-type T/NK-cell LPD. Extranodal T/NK-cell lymphoma is a disease of adults, and its incidence begins to increase in the third decade and comprises the major subtype of T/NK LPD throughout life. Aggressive NK-cell leukemia and nodal T/NK-cell lymphoma of the elderly are fulminant diseases, and immune senescence may be an important pathogenetic factor. This review describes the current progress in identifying different types of EBV-associated T/NK-cell LPD and includes a brief presentation of data from Korea.

Hydroa vacciniforme-like cutaneous T-cell lymphoma

A 14-year-old Chinese girl had a 6-year history of recurrent lesions on her head, face, and limbs. Epstein-Barr virus (EBV)-IgM was positive. Histopathological findings revealed focal lymphocyte invasion in subcutaneous panniculus adiposus, mainly surrounding the blood vessels. Immunohistochemistry showed CD3+, CD4+, CD5+, CD8+, TIA-1+, GrB+, CD56-, and L26-. In situ hybridization staining for EBV-encoded small nonpolyadenylated RNA (EBER)-1 was positive. The patient showed significant improvement in clinical symptoms after being treated with acyclovir and IFN-α in this patient.

Hydroa vacciniforme-like lymphoma: a chronic EBV+ lymphoproliferative disorder with risk to develop a systemic lymphoma

AbstractHydroa vacciniforme–like lymphoma (HVLL) is an Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorder of childhood that occurs mainly in Central and South America and Asia. We present the clinicopathological features of 20 Mexican children with HVLL with a median age of 8 years at diagnosis (range, 1-15). All patients presented with skin lesions involving sun-exposed areas, but not exclusively. Fever, lymphadenopathy, and hepatosplenomegaly were often observed. Most patients were treated with immunomodulators and/or immunosuppressive agents, resulting in temporary remission. For 13 patients follow-up was available for a median of 3 years (range, 1 month-13 years). Three patients with long follow-up (9-13 years) are alive with disease. Four patients died, 2 after developing systemic lymphoma. Histologically, the skin showed a predominantly angiocentric and periadnexal Epstein-Barr early RNA+ lymphoid infiltrate with variable atypia and subcutaneous involvement. Fifteen patients showed a T-cell phenotype (12, αβ; 2, γδ; 1, silent phenotype) and monoclonal T-cell receptor-γ rearrangements, whereas 6 exhibited a natural killer (NK)-cell phenotype. Four patients had hypersensitivity to mosquito bites. One patient showed both phenotypes. HVLL is an EBV-associated lymphoproliferative disorder of αβ-, γδ-, or NK-cell phenotype with a broad clinical spectrum, usually prolonged clinical course, and risk for progression to systemic disease.

Epstein-Barr virus-associated lymphoid malignancies: the expanding spectrum of hematopoietic neoplasms.

Ubiquitous Epstein-Barr virus (EBV) infects not only B cells but also T and NK cells, and is associated with various lymphoid malignancies. The spectrum of EBV-associated lymphoid malignancies is expanding from Burkitt lymphoma to the newly defined systemic EBV+ T cell lymphoproliferative disease of childhood and hydroa vacciniforme-like lymphoma. However, some EBV-associated malignancies are not defined well and overlap other diseases. Furthermore, the role of EBV in tumorigenesis of lymphoid malignancies is still not clear. Further studies are necessary to clarify the pathogenesis of EBV-associated lymphoid malignancies for a better classification of each disease and for the establishment of effective treatment.

Hydroa vacciniforme-like lymphoma: two cases report and literatures review

Two children with hydroa vacciniforme-like lymphoma (HVLL) were reported for a better understanding of this disease. The clinical manifestation, pathological characteristics, therapeutic outcomes of two children with HVLL were analyzed and presented by compared with what described in literatures. Two children were girls, who treated firstly in the hospital in May 2012, July 2012 and their duration were 1 years, more than 10 years respectively. Their clinical manifestations were both limbs and craniofacial polymorphous rashes. Pathological findings revealed that the dermis and subcutaneous tissue were profiled by atypical lymphocytic infiltration. Immunohistochemistry showed that the infiltration of cells from T/NK cell, and Epstein-Barr virus encoded small RNA (EBER)(+). Case 1 was treated with chemotherapy, but her condition continued to deteriorate. Case 2 just received symptomatic treatment, her skin lesions gradually reduced and rash disappeared completely 2 months later. HVLL is found with special clinical manifestation, its diagnosis mainly depend on skin biopsy and immunohistochemistry, there is no specific treatment method now, and its prognosis still needs further research.

Hydroa vacciniforme-like lymphoma of an adult: a case report with review of the literature

Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7644172219178472Hydroa vacciniforme-like lymphoma (HVL) is a rare type of Epstein-Barr virus (EBV)-positive lymphoma of cytotoxic T-cell or natural killer cell origin that mainly affect children, characterized by a vesicopapular skin eruption that clinically resemble hydroa vacciniforme (HV). In current study, we report an adult patient with the tumor. The patient presented similar morphologic, immunophenotypic and genotypic changes of the disease with that occurred in children, whereas clinically, he showed a prolonged clinical course without hepatosplenomegaly or generalized lymphadenopathy. Whether there are some differences in biologic behavior between children and adults still remains unknown and it is necessary to collect more data to observe and to investigate in the future.

Non–Mycosis Fungoides Cutaneous T-Cell Lymphomas

Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.