RESUMO
Burkitt lymphoma is a non-Hodgkin B-cell lymphoma with a high prevalence in the pediatric population. Abdominal manifestations are well known in sporadic Burkitt lymphoma and vary from nonspecific symptoms to intestinal obstruction due to intussusception; however, mass-like splenic involvement has been scarcely described. OBJECTIVE: To present a case of a patient with a splenic mass whose histopathological analysis revealed Burkitt lymphoma. CLINICAL CASE: A 13-year-old female patient presented with abdominal pain, progressive weight loss, and fever. Imaging studies showed a splenic mass, intestinal thickening, and ileal intussusception. Histopathological analysis of spleen biopsy revealed Burkitt lymphoma. After the first cycle of chemotherapy (BFM95-NHL protocol), abdominal symptoms resolved; no other signs suggestive of intussusception were observed, as well as a significant reduction of the splenic mass was observed. CONCLUSIONS: Burkitt lymphoma in pediatric patients can present as a well-defined splenic tumor, causing no splenomegaly. In addition, its management does not require surgery since it can be resolved with chemotherapy.
Assuntos
Linfoma de Burkitt , Neoplasias Esplênicas , Humanos , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patologia , Linfoma de Burkitt/complicações , Linfoma de Burkitt/tratamento farmacológico , Feminino , Adolescente , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intussuscepção/diagnóstico , Intussuscepção/etiologia , Dor Abdominal/etiologiaAssuntos
Linfoma/patologia , Neoplasias Esplênicas/patologia , Esplenomegalia/etiologia , Humanos , Imuno-Histoquímica , Linfoma/imunologia , Linfoma/cirurgia , Masculino , Pessoa de Meia-Idade , Esplenectomia , Neoplasias Esplênicas/imunologia , Neoplasias Esplênicas/cirurgia , Resultado do TratamentoAssuntos
Humanos , Masculino , Neoplasias Esplênicas/patologia , Esplenomegalia/etiologia , Linfoma/patologia , Esplenectomia , Neoplasias Esplênicas/cirurgia , Neoplasias Esplênicas/imunologia , Imuno-Histoquímica , Resultado do Tratamento , Linfoma/cirurgia , Linfoma/imunologia , Pessoa de Meia-IdadeRESUMO
Background: Patients with human immunodeficiency virus (HIV) are more likely to develop cancer. Malignant lymphomas are the main cancer group seen in these patients. Diffuse large B-cell lymphoma including central nervous system lymphoma and Burkitt's lymphoma account for 90% of HIV-related non-Hodgkin's lymphomas. Clinical case: A 22-year-old man with fever up to 39 ° C, malaise, excessive tiredness and night sweats, loss of 8 kg of weight, abdominal pain in the right hypochondrium, all 5 months before hospitalization. Hemoglobin: 9.5 g/dL, leukocytes 5.13 x 103/mm3, platelets 124 000 cel/mm3; albumin 2.9 g/dL, alanine aminotransferase 28 IU/L, aspartate aminotransferase 105 IU/L; HIV reactive, beta 2 microglobulin: 20 000 ng/mL. Viral load for HIV 100 034 cp/mL, CD4: 76 cel/mcL (5%). It was performed abdominal ultrasound and denoted cysts in the liver and spleen. Abdominal-pelvic computed tomography with hepatosplenomegaly, retroperitoneal and inguinal adenopathies and free fluid in abdominal cavity. Splenectomy was performed and Burkitt's lymphoma was reported in the histopathological study. Conclusion: HIV predisposes patients to any type of cancer. Intra-abdominal findings should be a warning of lymphoma suspicious and may occur from infiltration of the small intestine, solid organ and soft tissues.
Introducción: los pacientes con virus de inmunodeficiencia humana (VIH) son más propensos a desarrollar cáncer. Los linfomas malignos son el principal grupo de cáncer que se observa en estos pacientes. El linfoma difuso de células grandes B, incluido el del sistema nervioso central y el linfoma de Burkitt, constituyen 90% de los linfomas no Hodgkin relacionados con VIH. Caso clínico: hombre de 22 años de edad, con fiebre de hasta 39 °C, malestar general, cansancio excesivo y sudoración nocturna, pérdida de 8 kg de peso y dolor abdominal en hipocondrio derecho, 5 meses previos a su hospitalización. Se reportó hemoglobina de 9.5 g/dL, leucocitos 5.13 x 103/mm3, plaquetas 124 000 cel/mm3; albúmina 2.9 g/dL; alanino aminotransferasa 28 UI/L, aspartato aminotransferasa 105 UI/L; VIH reactivo, beta 2 microglobulina 20 000 ng/mL. Carga viral para VIH 100 034 cp/mL, CD4 76 cel/mcL (5%). El ultrasonido abdominal mostró quistes en hígado y bazo. La tomografía abdominopélvica reportó hepatoesplenomegalia, adenopatías retroperitoneales e inguinal y líquido libre en cavidad abdominal. Se realizó esplenectomía y en el estudio histopatológico se reportó Linfoma de Burkitt. Conclusión: El VIH predispone a los pacientes a cualquier tipo de cáncer. Los hallazgos intraabdominales deben hacer sospechar de linfoma y se puede presentar desde infiltración del intestino delgado, órgano sólido y tejidos blandos.
Assuntos
Linfoma de Burkitt/etiologia , Neoplasias Hepáticas/etiologia , Linfoma Relacionado a AIDS/etiologia , Neoplasias Esplênicas/etiologia , Linfoma de Burkitt/diagnóstico por imagem , Linfoma de Burkitt/patologia , Infecções por HIV , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Linfoma Relacionado a AIDS/diagnóstico por imagem , Linfoma Relacionado a AIDS/patologia , Masculino , Neoplasias Esplênicas/diagnóstico por imagem , Neoplasias Esplênicas/patologia , Adulto JovemRESUMO
CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.
Assuntos
Vírus da Hepatite B , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/virologia , Adulto , Doença Crônica , Evolução Fatal , Feminino , Humanos , Linfoma de Células B/terapia , Pessoa de Meia-Idade , Neoplasias Esplênicas/terapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
ABSTRACT CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.
RESUMO CONTEXTO: Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, é uma doença rara, representando menos do que 1% de todos os linfomas não Hodgkin. Essa entidade é caracterizada por envolvimento de sinusoides da medula óssea e sangue periférico. A maioria dos casos está em estádio avançado ao diagnóstico. Sua patogênese ainda é pouco compreendida. RELATOS DE CASOS: Reportamos dois pacientes com vírus da hepatite B (HBV) crônica não replicante que desenvolveram linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos. Ambos estavam em estádio IV ao diagnóstico e evoluíram com doença agressiva. Ambos alcançaram resposta completa com a quimioterapia, porém um deles evoluiu a óbito por intercorrências infecciosas durante o transplante de medula óssea e o outro optou por não realizar o transplante e encontra-se sem evidência de doença até os dias atuais (três anos após tratamento). Alguns estudos demonstraram a possível associação entre linfomas não Hodgkin B e HBV. Entretanto, o mecanismo pelo qual esse vírus oncogênico interage com linfoma não Hodgkin B ainda é pouco compreendido. HBV é linfotrópico e pode se inserir no genoma do receptor, causando superexpressão de oncogenes e downregulation de genes supressores tumorais. Portanto, o estímulo crônico pelo HBV pode aumentar a proliferação de células B, promovendo expansão monoclonal dessas células, resultando em malignidade. CONCLUSÃO: HBV pode estar implicado na patogênese desse linfoma, entretanto, uma associação direta entre essas duas entidades não pôde ser provada no presente estudo e investigações adicionais são necessárias.
Assuntos
Humanos , Feminino , Adulto , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/virologia , Vírus da Hepatite B , Linfoma de Células B/patologia , Linfoma de Células B/virologia , Neoplasias Esplênicas/terapia , Tomografia Computadorizada por Raios X , Doença Crônica , Linfoma de Células B/terapia , Resultado do Tratamento , Evolução FatalRESUMO
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
Assuntos
Adenocarcinoma/patologia , Antígeno B7-H1/análise , Proliferação de Células , Neoplasias Pulmonares/patologia , Linfócitos T/patologia , Células A549 , Animais , Anticorpos Antineoplásicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Células Cultivadas , Citometria de Fluxo , Humanos , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais , Neoplasias Esplênicas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and potentially TCL1 as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.
Assuntos
Biomarcadores Tumorais/genética , Linfoma de Células B/genética , MAP Quinase Quinase 1/genética , Mutação , Receptor Notch1/genética , Neoplasias Esplênicas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia , Chile , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Deleção de Genes , Dosagem de Genes , Rearranjo Gênico , Genes de Cadeia Pesada de Imunoglobulina , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Linfoma de Células B/química , Linfoma de Células B/patologia , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Fenótipo , Valor Preditivo dos Testes , Fatores de Risco , Neoplasias Esplênicas/química , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Fatores de TempoRESUMO
B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.