RESUMO
BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are lymphoid proliferations associated with post-transplant immunosuppression. Most originate from B cells and are associated with Epstein-Barr virus (EBV) infection. Although extranodal involvement is common, cutaneous presentation is rare. OBJECTIVE: To report and characterize cutaneous manifestations of PTLD from clinical, histopathologic, and immunohistochemistry standpoints. METHODS: Patients' information was obtained retrospectively by reviewing medical records. Skin biopsies were submitted to histological and immunohistochemistry analysis, and EBV detection was performed by in situ hybridization and polymerase chain reaction (PCR) analysis. Staging examinations were included. A literature review of reported cutaneous PTLD cases was performed. RESULTS: We describe two cases of primary cutaneous and 2 cases of systemic PTLD with secondary cutaneous manifestations. All had late onset disease, which presented at least 6 years after transplantation. Histopathologic findings were compatible with monomorphic PTLD in three cases and plasmacytic hyperplasia in one case. EBV was detected in two patients. Both patients with systemic disease had fatal outcome, and those with primary cutaneous involvement responded to treatment. LIMITATIONS: Due to the rare incidence of cutaneous manifestation of PTLD, the analysis of a large number of cases was not possible. CONCLUSION: Although rare, PTLD should be considered in the differential diagnosis of late onset cutaneous complications post-renal transplant.
Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Infecções por Vírus Epstein-Barr/etiologia , Herpesvirus Humano 4 , Humanos , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Estudos RetrospectivosAssuntos
Infecções por Vírus Epstein-Barr/etiologia , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Úlcera Cutânea/etiologia , Azatioprina/efeitos adversos , Tratamento Conservador , Desprescrições , Infecções por Vírus Epstein-Barr/imunologia , Dermatoses Faciais/etiologia , Dermatoses Faciais/imunologia , Feminino , Testa , Humanos , Transtornos Linfoproliferativos/imunologia , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Úlcera Cutânea/imunologiaRESUMO
BACKGROUND Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing regions. In high-income countries, hepatitis E is an emergent zoonotic disease of increasing concern. Clinically, the infection is usually acute and self-limited in immunocompetent individuals, although rare chronic cases in immunocompromised patients have been reported. Both acute and chronic infections have been recently associated with several extrahepatic manifestations, including neurological and hematological disorders. CASE REPORT A case of autochthonous chronic HEV infection in a liver-transplanted man from a non-endemic country is presented. Phylogenetic analysis revealed a swine origin of the HEV human infection. Chronic hepatitis E was treated with a 9-week course of ribavirin, after which viral clearance was achieved. Subsequently, the patient developed a post-transplant lymphoproliferative disorder (PTLD) in the form of Burkitt lymphoma. At the time of lymphoma diagnosis, the patient had shown a strong reactivation of Epstein-Barr virus (EBV) infection. After additional antiviral ganciclovir therapy and chemotherapy, the patient had a complete recovery with no sequelae. CONCLUSIONS The differential diagnosis of persistently elevated transaminases in transplanted and/or immunocompromised patients should include testing for HEV by appropriate nucleic acid techniques (NATs). Cases of HEV infection with an atypical clinical outcome, such as the one presented herein, highlights the need for increased awareness of chronic hepatitis E and its association with a wide range of extrahepatic manifestations.
Assuntos
Linfoma de Burkitt/etiologia , Infecções por Vírus Epstein-Barr/etiologia , Hepatite E/etiologia , Hepatite Crônica/etiologia , Hospedeiro Imunocomprometido , Transplante de Fígado/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Non-Hodgkin's lymphoma represents 6-10% of pediatric malignancies, and diffuse large B-cell lymphoma (DLBCL) is one of the three major subtypes. The 2008 WHO classification included a new entity, Epstein-Barr virus (EBV)-positive DLBCL of the elderly, affecting patients >50 years. It has been demonstrated that EBV may play a role in tumor microenvironment composition, disturbing antitumor immune response and disease progression. As most studies were performed in adults, our aim was to assess EBV presence and latency pattern, as well as T-cell microenvironment in a pediatric DLBCL series of Argentina. The study was conducted on formalin-fixed paraffin-embedded biopsies from 25 DLBCL patients. EBV-encoded small nuclear early regions (EBERs) expression was performed by in situ hybridization, whereas EBV gene expression was analyzed using real-time PCR. Epstein-Barr virus latent membrane proteins (LMP)1, LMP2A, CD3, CD4, CD8 and Foxp3 expression were assessed by immunohistochemistry (IHC). Forty percent of cases showed EBV expression, with a significantly higher incidence among patients <10 years (p = 0.018), and with immunosuppressed (p = 0.023). T-cell subsets were not altered by EBV presence. Full EBV latency antigen expression (latency type III) was the most frequently pattern observed, together with BZLF1 lytic gene expression. One patient showed II-like pattern (LMP1 without LMP2A expression). Based exclusively on IHC, some patients showed latency II/III (EBERs and LMP1 expression) or I (EBERs only). These findings suggest that EBV association in our series was higher than the previously demonstrated for elderly DLBCL and that EBV latency pattern could be more complex from those previously observed. Therefore, EBV could be an important cofactor in pediatric DLBCL lymphomagenesis.
Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Antígenos Nucleares do Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4/fisiologia , Linfoma Difuso de Grandes Células B/virologia , Microambiente Tumoral , Proteínas da Matriz Viral/metabolismo , Latência Viral , Adolescente , Argentina/epidemiologia , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/etiologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prevalência , Prognóstico , RNA Mensageiro/genética , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Carga Viral , Proteínas da Matriz Viral/genéticaRESUMO
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly was included as a provisional entity in the 2008 WHO lymphoma classification. Most reports of this disease come from Asia and little is known about it in other regions of the world, including Latin America. Therefore, in this study, 305 diffuse large B-cell lymphomas in patients above 50 years were analyzed, 136 from Mexico and 169 from Germany. EBV was detected by Epstein-Barr early RNA (EBER) in situ hybridization. Only cases with EBER+ in the majority of tumor cells were regarded as EBV+ diffuse large B-cell lymphoma. The prevalence of EBV+ diffuse large B-cell lymphoma in Mexican patients was found to be 7% (9 of 136), whereas only 2% (4 of 169) of the German cases were positive. The median age at diagnosis was 66 years in the Mexican cohort, as opposed to 77 years in the German group. The site of presentation was in both groups predominantly nodal in nine cases (70%) and extranodal in four cases (30%). Of the 13 EBV+ cases, 10 (77%) were classified as polymorphic and 3 (23%) as monomorphic type. The polymorphic cases showed a non-germinal center B-cell immunophenotype (CD10- MUM1+). Twelve cases (92%) were LMP1 positive and two (15%) expressed EBNA2. An interesting finding was the high frequency of EBV type B with the LMP1 30 bp deletion found in the Mexican cases (50%). Eight of the 11 evaluable cases were B-cell monoclonal by polymerase chain reaction. In summary, we found a similar prevalence of EBV+ diffuse large B-cell lymphoma of the elderly in a Mexican population compared with what has been reported in Asian countries, and in contrast to the low frequency in Western populations (1-3%). However, compared with the Asian series, the Mexican patients were younger at diagnosis, presented predominantly with nodal disease and rarely expressed EBNA2 protein.
Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/etiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/virologia , Idade de Início , Idoso , Infecções por Vírus Epstein-Barr/patologia , Antígenos Nucleares do Vírus Epstein-Barr/análise , Antígenos Nucleares do Vírus Epstein-Barr/biossíntese , Feminino , Alemanha/epidemiologia , Herpesvirus Humano 4/genética , Humanos , Hibridização In Situ , Linfoma Difuso de Grandes Células B/patologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Proteínas da Matriz Viral/análise , Proteínas da Matriz Viral/biossíntese , Proteínas Virais/análise , Proteínas Virais/biossínteseRESUMO
Se describe un paciente masculino de 10 años de edad con historia de mialgia, debilidad progresiva en miembros inferiores, fiebre y vómitos. Se postuló el diagnóstico clínico de Síndrome de Guillain-Barré el cual fue subsecuentemente demostrado con el resultado de líquido cefalorraquídeo (LCR) y electromiografía. A su admisión se describió una faringoamigdalitis exudativa y una sinusitis etmoidal, y posteriormente durante el curso de su enfermedad desarrolló una parálisis facial derecha. No habia historia de enfermedad diarreica aguada o enfermedad respiratoria previa al inicio de sus síntomas neurológicos. Los frotis y cultivos de heces fueron negativos por Campylobacter jejuni, al igual que la inmunofluorescencia para virus respiratorios y serología por CMV. Se documentó mediante una IgM positiva en suero la infección aguda por el virus Epstein-Barr. El paciente fue tratado exitosamente con un curso de cinco días de gammaglobulina endovenosa y un mes después, en la consulta externa, se documenta la ausencia de secuelas neurológicas