Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Amplifications of AURKA and AURKB in a Burkitt lymphoma immunodeficiency-associated type: a case report

ABSTRACT In equatorial Brazil, the association of Burkitt lymphoma and Epstein-Barr virus manifests at high rates. Here, we report, for the first time, amplifications of aurora kinase genes (AURKA/B) in a patient with a history of periodontal abscess and the presence of a remaining nodule, diagnosed with Burkitt lymphoma and Epstein-Barr virus, and /HIV positive. The patient was a 38-year-old man who presented with a 2-week-old severe jaw pain and a 3-day-old severe bilateral headache. He had a history of human papilloma virus. Interphase FISH analysis showed AURKA and AURKB amplification. The patient's condition worsened, progressing to death a month after the initial care. Changes in the MYCC and AURKA pathways are directly associated with genomic instability. Thus, MYCC rearrangements and higher expression of AURKA/B may be associated with therapy resistance, highlighting the importance of AURKA/B evaluation in Burkitt lymphoma.

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Primary hepatic lymphoma- A diagnostic dilemma

Primary non-Hodgkin lymphoma of liver is a very rare malignancy. Here we report the case of a 50 year old female who presented with dull ache in the right hypochondrium and decreased appetite since 1 month. CT scan of abdomen and pelvis showed an enlarged liver with an ill- defined soft tissue lesion arising from left lobe measuring 13 × 9 cm suggestive of primary hepatic neoplasm. CT scan of chest, abdomen, and pelvis and whole body positron emission tomography showed no involvement of bone marrow, lymph nodes, spleen, or any other organ. Her liver function tests, alpha fetoprotein and carcinoembryonic antigen levels were normal. Serology was negative for viruses. Pathological examination favored diagnosis of Burkitt's lymphoma. Cytogenetic studies for MYC translocation t (8;14) is suggested for confirming the diagnosis since Ki 67 index is > 70% and not nearly 100% which is characteristic of Burkitt's lymphoma.

Linfoma de Burkitt como diagnóstico diferencial de infecção odontogênica / Burkitt's Lymphoma as a differential diagnosis of dental infection / El Linfoma de Burkitt como diagnóstico diferencial de infección dental

Introdução: O linfoma de Burkitt é um linfoma altamente agressivo do tipo não-hodgkin originado a partir de mutação nos linfócitos B. Clinicamente demonstra características de malignidade como evolução rápida, destruição das corticais ósseas e mobilidade dentária, além de aumento de volume facial adjacente aos ossos maxilares. Esse tumor é de difícil diagnóstico devido às características clínicas inespecíficas, o que pode muitas vezes levar a um diagnóstico e tratamento tardio, piorando o prognóstico e a taxa de sobrevida do paciente. Relato de Caso: O caso clínico se trata de uma paciente, sexo feminino, 21 anos de idade, com história de aumento de volume em hemiface esquerda de evolução repentina, associada a dor, febre e relato de exodontia recente. A história clínica e os achados clínicos inespecíficos simularam uma infecção odontogênica, a qual atrasou o diagnóstico e o tratamento correto. Após exames imaginológicos específicos, exploração cirúrgica e exame histopatológico foi possível chegar a um diagnóstico definitivo de linfoma de Burkitt e manejo adequado dessa patologia. Conclusão: É de extrema importância o papel do cirurgião-dentista na detecção precoce dessa patologia com envolvimento dos maxilares, uma vez que a remissão e/ou a cura depende da extensão da doença, do seu comportamento biológico e do momento do diagnóstico... (AU)

Introduction: Burkitt's lymphoma is a highly aggressive non-Hodgkin type lymphoma originated from a mutation in B lymphocytes. It clinically demonstrates malignant characteristics such as rapid evolution, destruction of bone corticals and tooth mobility, in addition to increased facial volume adjacent to the maxillary bones. This tumor is difficult to diagnose due to its nonspecific clinical characteristics, which can often lead to a late diagnosis and treatment, worsening the patient's prognosis and survival rate. Case Report: The clinical case is a female patient, 21 years old, with a history of swelling in the left hemiface of sudden evolution, associated with pain, fever and a report of recent extraction. Clinical history and nonspecific clinical findings simulated an odontogenic infection, which delayed diagnosis and correct treatment. After specific imaging exams, surgical exploration and histopathological examination, it was possible to reach a definitive diagnosis of Burkitt's lymphoma and adequate management of this pathology. Conclusion: The role of dentists in the early detection of this pathology with involvement of the jaws is extremely important, since remission and/or cure depends on the extent of the disease, its biological behavior and the time of diagnosis... (AU)

Introducción: El linfoma de Burkitt es un linfoma de tipo no Hodgkin altamente agresivo originado por una mutación en los linfocitos B. Clínicamente demuestra características malignas como rápida evolución, destrucción de corticales óseas y movilidad dentaria, además de aumento de volumen facial adyacente a los huesos maxilares. Este tumor es de difícil diagnóstico debido a sus características clínicas inespecíficas, lo que muchas veces puede llevar a un diagnóstico y tratamiento tardíos, empeorando el pronóstico y la supervivencia del paciente. Caso Clínico: El caso clínico es una paciente femenina, de 21 años de edad, con antecedente de tumefacción en hemifacial izquierdo de evolución súbita, asociada a dolor, fiebre y reporte de extracción reciente. La historia clínica y los hallazgos clínicos inespecíficos simularon una infección odontogénica, lo que retrasó el diagnóstico y el tratamiento correcto. Luego de exámenes imagenológicos específicos, exploración quirúrgica y examen histopatológico, se logró llegar a un diagnóstico definitivo de linfoma de Burkitt y manejo adecuado de esta patología. Conclusión: El papel de los odontólogos en la detección temprana de esta patología con compromiso de los maxilares es de suma importancia, ya que la remisión y/o curación depende de la extensión de la enfermedad, su comportamiento biológico y el momento del diagnóstico... (AU)

Research advance in primary ovarian Burkitt lymphoma / 中国基层医药

Among all non-Hodgkin's lymphoma, primary ovarian Burkitt lymphoma (POBL) is a rare disease. Tumors can occur in one or both ovaries. The main symptoms of POBL are abdominal pain or a large abdominal mass. The differential diagnosis of POBL based on imaging characteristics and histopathological examination is the basis for further treatment of ovarian tumors from different sources. Although most patients with POBL have undergone surgical treatment after the discovery of ovarian masses, chemotherapy rather than surgery should be the main treatment method for them. Active chemotherapy combined with preventive central nervous system therapy leads to good prognosis. A variety of treatment schemes have been adopted, which greatly increase the survival rate of patients with POBL. In this review, we retrieved related literature and retrospectively reviewed the epidemiology, clinical manifestation, diagnosis and treatment of POBL. The purpose of this review is to draw clinicians' attention to the possibility of POBL when performing differential diagnosis of ovarian tumors.

Effect of Pulsatilla Saponin A on Proliferation and Apoptosis of Burkitt Lymphoma Cells Based on JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of pulsatilla saponin A （PSA） on proliferation and apoptosis of human Burkitt lymphoma （BL） cell line Raji cells and expression of related pathway proteins. MethodWith Raji cells as the research object， the cell proliferation was detected by cell counting kit-8 （CCK-8） method， and the half-maximal inhibitory concentration （IC50） values of 24 h， 48 h and 72 h were calculated to be 19.77， 18.31， 16.70 μmol·L-1， respectively. In subsequent related experiments， 0， 8， 16， 32 μmol·L-1 PSA were selected according to the IC50 value of Raji cells treated with PAS for 72 h. After 0， 8， 16， 32 μmol·L-1 PSA acted on Raji cells for 24， 48， 72 h， the optical density values of cell growth curve were detected by CCK-8 method. The zymogen activities of cysteine aspartate-specific protease （Caspase）-3， Caspase-8 and Caspase-9 in Raji cells treated with 0， 8， 16 and 32 μmol·L-1 PSA for 24 h were measured by Caspase-3， Caspase-8 and Caspase-9 colorimetric assay kit. The apoptosis rate and cell cycle of Raji cells treated with different concentrations of PSA after 24 h were detected by flow cytometry. The expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved poly（ADP-ribose） polymerase （cleaved PARP）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3） apoptosis related protein and Janus kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3）， phosphorylated-JAK2 （p-JAK2）， and phosphorylated- STAT3 （p-STAT3） pathway proteins in Raji cells after 24 h of treatment with 0， 8， 16 and 32 μmol·L-1 PSA were tested by Western blot. ResultCompared with control group， decreased cell survival rate， inhibited cell proliferation， activated zymogens of Caspase-3， Caspase-8 and Caspase-9 （P<0.01）， increased apoptosis （P<0.05， P<0.01）， and enhanced cell cycle arrest in Gap phase 2 （G2） were observed in 8， 16 and 32 μmol·L-1 PSA groups（P<0.05， P<0.01）. Compared with control group， cells treated with 8， 16 and 32 μmol·L-1 PSA had lower expression of Bcl-2， p-JAK2， p-STAT3 proteins （P<0.05， P<0.01）， and higher expression of Bax， cleaved PARP and cleaved Caspase-3 protein （P<0.01）， while no significant change was found in the expression of JAK2 and STAT3 proteins. ConclusionPSA could inhibit proliferation and induce apoptosis of Raji cells， and its potential mechanism might be related to the regulation of JAK2/STAT3 signaling pathway.

Clinical features and prognosis of children with Burkitt's lymphoma: an analysis of 62 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features and chemotherapy response of Burkitt's lymphoma (BL) in children and the influence of rituximab on the prognosis of children with BL.@*METHODS@#A retrospective analysis was performed for the medical data of 62 children with BL, including clinical features, therapeutic efficacy, and prognostic factors. The Cox regression model was used to identify the factors associated with poor prognosis in children with BL. According to whether rituximab was used, the children with advanced (stage III/IV) BL were divided into two groups: chemotherapy plus rituximab and chemotherapy alone. The prognosis was compared between the two groups.@*RESULTS@#For these 62 children, the median age of onset was 5 years (range 1-14 years), and there were 58 boys (94%) and 4 girls (6%). The primary site was abdominal cavity in 41 children (66%), and head and neck in 16 children (26%). There were 1 child with stage I BL (2%), 8 with stage II BL (13%), 33 with stage III BL (53%), and 20 with stage IV BL (32%). The median follow-up time was 29 months, with progression/recurrence observed in 15 children (24%), and the 3-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±5.2% and 77.3%±5.8%, respectively. For the children with stage III/IV BL, there was a significant difference in the 3-year the OS rate between the chemotherapy plus rituximab group (16 children) and the chemotherapy alone group (30 children) (93.3%±6.4% vs 65.6%±9.9%, P=0.042), while there was no significant difference in the 3-year EFS rate between the two groups (86.2%±9.1% vs 61.8%±10.1%, P>0.05). The Cox regression analysis showed that central nervous system involvement, lactate dehydrogenase >1 000 U/L, and early incomplete remission were the factors associated with poor prognosis (P<0.05).@*CONCLUSIONS@#Chemotherapy combined with rituximab can improve the prognosis of children with stage III/IV BL. Central nervous system involvement, elevated lactate dehydrogenase level, and early incomplete remission may indicate a poor prognosis in children with BL.

Linfoma de Burkitt como complicación de la agammaglobulinemia de Bruton / Burkitt's lymphoma as a complication of Bruton's Agammaglobulinemia

Introducción: La agammaglobulinemia de Bruton es una inmunodeficiencia primaria (IDP) originada por una mutación del gen que codifica la tirosina kinasa de Bruton (BTK). Se sospecha principalmente en varones con infecciones frecuentes de las vías respiratorias y tiene entre otras complicaciones, los tumores, fundamentalmente linfoproliferativos. Se reportan agammaglobulinemias autosómicas recesivas con similares características clínicas en ambos sexos. Objetivo: Presentar el primer caso pediátrico reportado en Cuba, con diagnóstico de linfoma de Burkitt asociado a esta inmunodeficiencia primaria y que además utilizó tratamiento combinado sustitutivo de inmunoglobulinas y antitumoral. Presentación del caso: Paciente masculino, que a los 2 años se le realizó diagnóstico de enfermedad de Bruton. Con el tratamiento de reemplazo con inmunoglobulina endovenosa (Intacglobín) se mantuvo tres años sin infecciones graves. A los 5 años de edad presentó linfoma de Burkitt, tratado con poliquimioterapia, según el esquema AEIOP al que se asoció rituximab. Aunque no se dispone de la detección por biología molecular de la mutación del gen BTK, la disminución por debajo del 2 por ciento de las células B CD19+ y los valores ausentes de IgG, IgA e IgM permitieron el diagnóstico. Conclusión: Coexistieron con resultados clínicos satisfactorios el tratamiento antitumoral y la terapia de reemplazo con inmunoglobulina endovenosa. El paciente se mantiene con buen estado general(AU)

Introduction: Bruton's Agammaglobulinemia is a primary immunodeficiency (PID) caused by a mutation in the gene that encodes Bruton's tyrosine kinase (BTK). It is suspected mainly in men with frequent respiratory tract infections and has, among other complications, tumors, mainly lymphoproliferative. Autosomal recessive agammaglobulinemias with similar clinical characteristics have been reported in both sexes. Objective: To present the first pediatric case reported in Cuba, with a diagnosis of Burkitt's lymphoma associated with PID and that also used combined immunoglobulin replacement and antitumor therapy. Case report: 2-year-old male diagnosed with Bruton's disease. With the replacement treatment with intravenous immunoglobulin (Intacglobin), he maintained three years without serious infections. At 5 years of age, he presented Burkitt's lymphoma, treated with polychemotherapy according to the AEIOP scheme, associating Rituximab. Although do not have molecular biology detection of the BTK gene mutation, the decrease of CD19 + B cells to below 2 percent and the absent values of IgG, IgA and IgM allowed the diagnosis. Conclusion: Antitumor treatment and intravenous immunoglobulin replacement therapy coexisted with satisfactory clinical results. The patient remains in good general condition(AU)

Abnormal Uterine Bleeding in Adolescence: When Menarche Reveals other Surprises / Hemorragia uterina anormal na adolescência: Quando a menarca revela outras surpresas

Abstract Introduction Abnormal uterine bleeding is more frequent in adolescence. Although, most commonly, it has a non-structural etiology, it may be due to any cause described. Clinical case A 12-year-old adolescent, with no relevant personal history, menarche 1 month before, was observed in the emergency department for severemenstrual bleeding with progressive worsening, and hemodynamic repercussion in need of transfusion support. Physiological ovulatory dysfunction associated with possible previously unknown coagulopathy was considered to be the most likely diagnosis and medical treatment was initiated. Without response, the patient was submitted to sedated observation and uterine aspiration, which ultimately led to the diagnosis of a Burkitt Lymphoma. Discussion Although structural causes, and particularly malignancy, whether gynecological or not, are a rare cause of abnormal uterine bleeding in this age group, they must be considered, thus enhancing the fastest and most appropriate treatment.

Resumo Introdução A hemorragia uterina anormal é mais frequente na adolescência. Apesar de maioritariamente de etiologia não estrutural, pode dever-se a qualquer causa descrita. Caso clínico Adolescente de 12 anos, sem antecedentes pessoais relevantes, com menarca há 1 mês, observada no serviço de urgência por hemorragia menstrual grave com agravamento progressivo e repercussão hemodinâmica com necessidade de suporte transfusional. Foi colocada a hipótese de disfunção ovulatória fisiológica associada a eventual coagulopatia desconhecida previamente e foi instituído tratamento médico. Por ausência de resposta a tratamento médico, foi submetida a observação sob sedação e aspiração uterina que evidenciou tratar-se de um Linfoma de Burkitt. Discussão Apesar de as causas estruturais, e particularmente as neoplasias, do foro ginecológico ou não, serem uma causa rara de hemorragia uterina anormal nesta faixa etária, elas devem ser levadas em consideração potenciando assim um tratamento mais célere e adequado.

Linfoma de Burkitt esporádico en cavidad bucal: caso clínico / Sporadic Burkitt´s lymphoma in the oral cavity: a clinical case report

Objetivo: Presentar un caso clínico de Linfoma de Burkitt esporádico en cavidad bucal como manifestación inicial en un paciente adulto joven, tratado en el Hospital Interzonal General de Agudos "General José de San Martín" de La Plata. Caso clínico: Un paciente masculino de 20 años de edad se presenta con una lesión tumoral localizada en sector posterior de reborde mandibular, pérdida espontánea de piezas dentarias y parestesia del nervio dentario inferior. Acompañado de un aumento de volumen testicular, compromiso intestinal y poliadenopatías. El cuadro morfológico y de inmuno-marcación confirma un Linfoma de Células B "agresivo". El paciente fue tratado con esquema intensivo de 6 bloques de quimioterapia y terapia intratecal. No se observaron señales de recurrencia durante el período de seguimiento de 12 meses. Las manifestaciones bucales iniciales del Linfoma de Burkitt deben considerarse en el diagnóstico diferencial de las enfermedades bucales benignas. Debido a su naturaleza agresiva, el reconocimiento temprano y rápido de este linfoma es esencial para la administración oportuna de la terapia adecuada y mejora el pronóstico del paciente (AU)

Aim: To present a case of sporadic Burkitt's lymphoma with oral initial manifestatios in a young adult patient, who received treatment at the Hospital Interzonal General de Agudos "General José de San Martín", La Plata. Clinical case: A 20-year-old male patient presents with a tumor lesion located in the posterior area of the mandibular ridge, spontaneous loss of teeth and paresthesia of the inferior dental nerve, increase in testicular volume, intestinal compromise and polyadenopathy. The morphological and immunostaining conditions confirm an "aggressive" B-Cell Lymphoma. The patient received an intensive scheme of 6 blocks of chemotherapy and intrathecal therapy. No signs of recurrence were observed during the 12-month follow-up period. Oral manifestations of Burkitt´s lymphoma in the initial stages should be considered in the differential diagnosis of benign oral diseases. Due to its aggressive nature, early and rapid recognition of these this lymphoma is essential for the timely administration of adequate therapy and for a patient's better prognosis (AU)

Linfoma de amígdala: reporte de un caso pediátrico / Palatine tonsil lymphoma: a pediatric case report

El linfoma es la neoplasia maligna de cabeza y cuello más común en la población pediátrica. Las anifestaciones clínicas de linfoma en amígdala palatina son generalmente asimetría amigdalina, alteración en la apariencia de la mucosa y adenopatías cervicales. Ante una hipertrofia amigdalina unilateral, se debe diferenciar de cuadros infecciosos, procesos crónicos, otros tumores o simplemente una hiperplasia amigdalina benigna. El seguimiento estricto de la asimetría amigdalina es un pilar importante a la hora del diagnóstico de los pacientes con linfoma amigdalino, debido a que un tratamiento temprano es fundamental para el pronóstico. Se presenta una niña de 14 años con hipertrofia amigdalina unilateral y odinofagia, de aproximadamente 21 días de evolución sin respuesta al tratamiento antibiótico, con diagnóstico de linfoma de Burkitt. Presenta remisión completa de la enfermedad al año del diagnóstico.

Lymphoma is the most common childhood malignancy in the head and neck. The most common clinical manifestations of lymphoma in palatine tonsil are the tonsils asymmetry, alteration in the appearance of the mucous and cervical lymphadenopathy. The unilateral tonsillar hypertrophy must be differentiated with infectious processes, with chronic processes, other tumors or benign tonsillar hyperplasia. The monitoring of tonsillar hypertrophy is strict, because early diagnosis and treatment are of great importance in the prognosis of tonsillar lymphoma patients. A 14 year-old girl presents unilateral tonsillar enlargement and odynophagia. After 21 days of antibiotic treatment, she has not clinical improvement. The diagnosis is Burkitt's lymphoma. One year after diagnosis, she presents complete remission of the disease.

Linfoma de Burkitt primario de mama durante el embarazo / Primary Burkitt's Lymphoma of the Breast During Pregnancy

El linfoma de Burkitt es una neoplasia altamente agresiva y es un tipo raro de linfoma no Hodgkin localizado. Aunque los niños son los más frecuentemente afectados, en adultos ocurren principalmente durante el embarazo o el puerperio. La mama rara vez constituye la localización primaria del linfoma no Hodgkin. Se presenta un caso de linfoma de Burkitt primario de mama durante el embarazo. Paciente de 37 años con embarazo de 24 semanas quien presentó aumento de volumen difuso de mama derecha. La mama estaba aumentada de tamaño, dolorosa y homogénea con tumoración elástica y firme. La ecografía demostró inflamación difusa con tumoración heterogénea e hipoecoica con contornos ligeramente irregulares, marcadores tumorales estaban normales las pruebas serológicas fueron negativas. La biopsia de la lesión mostró tejido mamario reemplazado por células linfoideas de tamaño mediano con citoplasma basófilo y múltiples vacuolas. Estudios inmunohistoquímicos fueron positivos para el antígeno leucocitario común, CD10, CD20, CD43, Bcl-6. El análisis cromosómico reveló que más del 90 % de las células neoplásicas exhibieron translocación t llevando al diagnóstico final de linfoma de Burkitt de mama. Luego de evaluar las posibilidades terapéuticas y del consentimiento de la paciente se inició tratamiento citostático sistémico. Los linfomas primarios de mama son extremadamente raros. El linfoma de Burkitt primario de la mama es mucho menos común que los otros linfomas. Los métodos de clasificación, detección y tratamiento de esta afección siguen siendo objeto de debates e investigaciones(AU)

The Burkitt's lymphoma is a highly aggressive neoplasm and is a rare type of localized non-Hodgkin lymphoma. Although children are the most frequently affected, in adults they occur mainly during the pregnancy or the puerperium. The breast rarely constitutes the primary location for non-Hodgkin lymphoma. The study of a case of primary Burkitt lymphoma of the breast during pregnancy is presented. This is a 37 year old patient with a 24 week pregnancy who presented a diffuse increase in the volume of the right breast. The breast was enlarged, painful and homogeneous with a firm, elastic mass. The ultrasonography showed diffuse inflammation with a heterogeneous and hypoechoic tumor with slightly irregular contours. The tumor marker values were normal and the serological tests were negative. The biopsy of the lesion showed breast tissue replaced by medium-sized lymphoid cells with basophilic cytoplasm and multiple vacuoles. Immunohistochemically studies were positive for the common leukocyte antigen, CD10, CD20, CD43, Bcl-6. The chromosomal analysis revealed that more than 90 % of neoplastic cells exhibited t translocation leading to the final diagnosis of Burkitt lymphoma of the breast. After evaluating the therapeutic possibilities and the patient's consent, systemic cytostatic treatment was started. Primary breast lymphomas are extremely rare. The primary Burkitt lymphoma of the breast is much less common than other lymphomas. The methods of classification, detection, and the treatment of this condition continue to be the subject of debate and research(AU)

Late recurrence of Burkitt's lymphoma in the jaw: numb chin syndrome as the only symptom

The Numb Chin Syndrome (NCS) is defined as facial and oral numbness restricted to the mental nerve's distribution involving the lower lip, skin of the chin, or gingiva of the lower anterior teeth. Hypoesthesia can occur unilaterally or bilaterally. Although this syndrome is rare, its importance is related to the fact that it represents the clinical manifestations of malignant diseases. Breast cancer and non-Hodgkin lymphoma are the most common cause of NCS. The patient, a 58-year-old woman, treated for a Burkitt Lymphoma (BL) nine years ago, described a two-week history of change in sensitivity and pain in the chin region, without relief with the use of analgesics. She had no headache, speech disturbance, dysphagia, visual disturbance, or other neurological symptoms. No surgical intervention has been performed recently. The intraoral examination revealed a healthy oral mucosa and a small area adjacent to the right mental nerve region that was uncomfortable to palpation. No changes were found in the bone trabeculae at cone-beam computed tomography. The contrasted magnetic resonance features made it possible to identify a change in the mandibular body extending to the entire right side, coinciding with the patient's complaint, indicating a probable mandibular medullary invasion. The patient was submitted to a biopsy to rule out a possible recurrence of BL. The microscopic findings were consistent with the diagnosis of BL. The present report described a very unusual presentation of late recurrent BL nine years after the first treatment, which manifested as an NCS.

Linfoma de Burkitt en paciente adulto inmunocompetente que se presenta como rotura esplénica espontánea / Burkitt's lymphoma in an immunocompetent adult patient presenting as spontaneous splenic rupture

RESUMEN El linfoma de Burkitt es un linfoma no Hodgkin de células B que ha sido denominado por la mayoría de los investigadores como el tumor humano de crecimiento más rápido, pues es capaz de lograr una tasa de duplicación celular entre 24 y 26 horas. Se presentó un paciente masculino de 48 años de edad, con diagnóstico de linfoma de Burkitt, inmunocompetente, con esplenomegalia gigante y rotura esplénica espontánea como complicación. El paciente tuvo una evolución desfavorable en un breve período de tiempo. El linfoma de Burkitt es una enfermedad altamente agresiva, donde la falta de sospecha clínica y diagnóstico no oportuno ensombrecen el pronóstico.

ABSTRACT Burkitt's lymphoma is a B-cell non-Hodgkin lymphoma that has been called by most researchers the fastest growing human tumor, as it is capable of achieving a cell doubling rate between 24 and 26 hours. We present a 48-year-old male patient with a diagnosis of Burkitt's lymphoma, immunocompetent, with giant splenomegaly and spontaneous splenic rupture as a complication. The patient had an unfavorable evolution in a short period of time. Burkitt's lymphoma is a highly aggressive disease, where lack of clinical suspicion and untimely diagnosis overshadow the prognosis.

Hepatoesplenomegalia relacionada a linfoma de Burkitt en paciente pediátrico / Hepatoesplenomegalia related to Burkitt´s lymphoma in a pediatric patient

RESUMEN El linfoma de Burkitt, se trata de un subtipo poco frecuente del linfoma no Hodgkin, con elevada frecuencia en aquellos pacientes con sida. La hepatoesplenomegalia es un signo clínico de gran importancia para el diagnóstico oportuno de algunas patologías; entre los mecanismos de formación de la hepatoesplenomegalia se encuentra la infiltración celular, ocasionada por la migración de células tumorales. Se presenta por inflamaciones debido a la presencia de infecciones por virus o bacterias las cuales son muy comunes en pacientes con sida. Se presentó un caso de un paciente masculino de 4 años, diagnosticado con VIH positivo, con la configuración correspondiente de criterios clínicos en clasificación C para sida. El cual desarrolló a nivel de cavidad oral un Burkitt primario, que se acompañó de hepatoesplenomegalia. Se pretendió describir la relación y el comportamiento de este tipo de linfoma con la hepatoesplenomegalia, así como la repercusión a nivel del sistema estomatognático, a nivel sistémico y el plan de tratamiento. Por el cuadro clínico e inmunológico del paciente estudiado, se planteó un pronóstico reservado por presentar un cuadro clínico infrecuente, en el que se observó Burkitt; tanto a nivel del sistema estomatognático como a nivel abdominal. Se hizo necesario realizar un diagnóstico oportuno y certero para iniciar el tratamiento a tiempo, se comenzó inmediatamente con tratamiento (AU).

ABSTRACT Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin lymphoma, with high frequency in those patients with AIDS. Hepatosplenomegaly is a clinical sign of great importance for the timely diagnosis of some pathologies; cellular infiltration is found among the mechanisms of hepatosplenomegaly formation; it is caused by the migration of tumor cells. It emerges by inflammations due to the presence of infections by virus or bacteria which are very common in patients with AIDS. The authors present the case of a male patient, aged 4 years, with a positive HIV diagnosis, and the correspondent configuration of clinical criteria in C classification for AIDS, who developed a primary Burkitt lymphoma at the level of oral cavity We present the case of a 4-year-old male patient diagnosed with HIV positive, with the corresponding configuration of clinical criteria in classification C for AIDS; who developed a primary LB at the oral cavity level that was accompanied by hepatosplenomegaly. The authors pretended to describe the relation and behavior of this kind of lymphoma with hepatosplenomegaly, and also the repercussion at the stomatognathic level, at the systemic level and the treatment plan. Due to the clinical and immunological characteristics of the studied patient a reserved prognosis was given because of presenting infrequent clinical characteristics in which a Burkitt was observed both, at the stomatognathic and at the abdominal level. It was necessary to make an opportune and accurate diagnosis to begin the treatment on time (AU).

A case series of unusual presentations of Burkitt's lymphoma

Context: Burkitt's lymphoma (BL) is one of the fastest growing malignancies. It is the most common subtype of Non-Hodgkin's lymphoma in childhood. It has three major subtypes – endemic, sporadic, and immunodeficiency-associated types. Aims: This study aims to study the clinicomorphologic features of this disease entity and to find optimal imaging technique for such cases. Setting and Design: A retrospective observational study in a tertiary care center of academic and research potential. Subjects and Methods: We are presenting three unusual cases of sporadic type of BL who presented initially as localized right iliac fossa mass mimicking as acute appendicitis. Initially, localized presentation progressed to diffuse abdominal mass lesions causing intestinal obstruction. Results: These cases had emphasized the importance of accurate diagnosis by the ultrasonography (USG) or computed tomography (CT) scan for early diagnosis so as to manage such cases simply by early appropriate medical treatment. Conclusion: In this article, we will discuss the clinical and imaging features of BL with the role of USG, CT scan and positron emission tomography/CT in the abdominopelvic imaging of pediatric patients

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

Objective@#To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance.@*Methods@#Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children′s Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis.@*Results@#A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ2=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ2=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ2=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ2=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ2=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL.@*Conclusion@#The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (0.759, 0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (0.011, 0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (0.006, 0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% . 94.7%, (2)=4.123, 0.042) and PFS (5-year estimate, 66.7% . 94.7%, (2)=5.822, 0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group ((2)=4.881, 0.027); however, there was no statistical significance in 5-year PFS rate (0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% . 95.7%, (2)=6.285, 0.012; PFS: 65.5% . 91.3%, (2)=5.405, 0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.