Masa paravertebral torácica como manifestación infrecuente del Linfoma de alto grado: Reporte de un caso

Paciente masculino de 44 años sin antecedentes patológicos previos, acude por cuadro de disnea y dolor pleurítico en hemitórax derecho. La radiografía de tórax tomada a su ingreso muestra importante derrame pleural derecho. Fue evaluado por el servicio de Neumología quienes realizan toracocentesis diagnóstica y evacuadora. Además, solicitaron tomografía contrastada de tórax, la cual reporta una gran masa mediastínica posterior (paravertebral), asociada a aparente infiltración de la médula ósea en múltiples cuerpos vertebrales, y adenopatías inguinales bilaterales. Posteriormente se realiza biopsia de la masa paravertebral, confirmando uno de los diagnósticos infrecuentes presentados como masas del mediastino posterior, Linfoma de células B grande. (provisto por Infomedic International)

A 44-year-old male patient with no previous medical history presented with dyspnea and pleuritic chest pain in the right hemithorax. The chest x-ray taken upon admission shows significant right pleural effusion. He was evaluated by the Pulmonology department who performed diagnostic and evacuative thoracentesis. In addition, they requested contrast-enhanced chest tomography, which reported a large posterior mediastinal (paravertebral) mass, associated with apparent bone marrow infiltration of multiple vertebral bodies, and bilateral inguinal lymphadenopathy. Subsequently, a biopsy of the paravertebral mass was performed, confirming one of the rare diagnoses presented as posterior mediastinal masses, large B-cell Lymphoma. (provided by Infomedic International)

Risco de recorrência em Sistema Nervoso Central de Linfoma Difuso de grandes células B e sua profilaxia em Serviço Público de Saúde em dois centros no Brasil / Risk of recurrence in the Central Nervous System of Diffuse Large B-Cell Lymphoma and its prophylaxis in a Public Health Service in two centers in Brazil

O linfoma difuso de grandes células B (LDGCB) é o subtipo mais comum de linfoma não Hodgkin. A recaída em sistema nervoso central (SNC) é um evento raro, variando de 5% a 10%, de acordo com fatores de risco previamente definidos através do Índice Prognóstico Internacional do SNC (CNS-IPI) e sítios extranodais específicos. Apresenta desfechos insatisfatórios, com sobrevida global mediana de dois a cinco meses. Ao longo dos anos, diversas estratégias para reduzir a recaída em SNC foram avaliadas, e são cada vez mais controversas. As profilaxias para evitar recaída em SNC frequentemente utilizadas diferem na forma de administração, baseados em metotrexato intratecal (IT-MTX) ou de forma sistêmica em altas doses (HD-MTX), associado ou não a outros agentes quimioterápicos. Os estudos até então disponíveis foram realizados em países de alta renda e é questionado se limitações encontradas em países de transição econômica, com maior dificuldade de acesso a métodos diagnósticos e terapêuticos, trariam impacto ou poderiam justificar profilaxia para recaída em SNC. Realizamos um estudo retrospectivo em dois centros de saúde pública em Belo Horizonte, Brasil, entre janeiro de 2018 e julho de 2022, para avaliar a incidência de recaída em SNC em pacientes acometidos por LDGCB. Estimamos sobrevida livre de progressão e sobrevida global. Um total de 120 pacientes, com idade média de 54,4 ± 15,4 anos e predomínio do sexo masculino (60,0%) foram avaliados no estudo. Destes, apenas sete (5,8%) receberam IT-MTX e quatro (3,3%) receberam HD-MTX. Não houve pacientes que receberam as duas vias de profilaxia. O escore prognóstico para risco inicial de recaída do SNC pelo CNS-IPI foi estimado como: baixo [0-1; 37 (30,8%)], moderado [2-3; 53 (44,2%)] ou alto [≥ 4; 27 (22,5%)]. A recaída em SNC foi confirmada em quatro (3,3%) pacientes. Apesar do estudo ter sido realizado em centros de referência oncohematológicas, o n disponível foi pequeno ao considerar a raridade do evento. Não conseguimos demonstrar se há benefício ou não de profilaxia específica para recaída em SNC. Considerando a morbimortalidade desta complicação, sugere-se realizar mais estudos e investigar acometimento oculto de SNC em LDGCB ao diagnóstico.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Central nervous system (CNS) relapse is a rare event, varying from 5% to 10%, according to risk factors previously defined through the CNS International Prognostic Index(CNS-IPI) and specific extranodal sites. It presents unsatisfactory outcomes, with a median overall survival of two to five months. Over the years, several strategies to reduce CNS relapse have been evaluated, and they are increasingly controversial. Prophylaxis to prevent CNS relapse frequently used differs in the form of administration, based on intrathecal methotrexate (IT-MTX) or high-dose systemic (HD-MTX), associated or not with other chemotherapeutic agents. The studies available so far were carried out in high-income countries and it is questioned whether limitations found in economic transition countries, with greater difficulty in accessing diagnostic and therapeutic methods, would have an impact or could justify prophylaxis for CNS relapse. We carried out a retrospective study in two public health centers in Belo Horizonte, Brazil, between January 2018 and July 2022, to evaluate the incidence of CNS relapse in patients affected by DLBCL. We estimated progression-free survival and overall survival. A total of 120 patients, with a mean age of 54.4 ± 15.4 years and a predominance of males (60.0%) were evaluated in the study. Of these, only seven (5.8%) received IT-MTX and four (3.3%) received HD-MTX. There were no patients who received both routes of prophylaxis. The prognostic score for initial risk of CNS relapse by CNS-IPI was estimated as: low [0-1; 37 (30.8%)], moderate [2-3; 53 (44.2%)] or high [≥ 4; 27 (22.5%)]. CNS relapse was confirmed in four (3.3%) patients. Although the study was carried out in oncohematological reference centers, the number available was small considering the rarity of the event. We were unable to demonstrate whether or not there is benefit from specific prophylaxis for CNS relapse. Considering the morbidity and mortality of this complication, it is suggested to carry out further studies and investigate occult CNS involvement in DLBCL at diagnosis.

Causa inusual de obstrucción traqueal: linfoma de células B no Hodgkin / Unusual cause of tracheal obstruction: B cell non-Hodgkin lymphoma

Las neoplasias de la tráquea son poco comunes, siendo más infrecuente aún el linfoma de células B no Hodgkin a este nivel. La presentación clínica de esta entidad es muy variable y sus síntomas son muy inespecíficos, simulando varias enfermedades, generando así un diagnóstico tardío. Actualmente se dispone de varias ayudas diagnósticas que permiten descartar otras patologías y confirmar la neoplasia traqueal, además la biopsia es fundamental para llegar al diagnóstico final y así instaurar el manejo en estadios tempranos, para impactar en la morbimortalidad. A continuación presentamos el caso de una paciente con linfoma de células B no Hodgkin como causa de obstrucción traqueal.

Tracheal neoplasms are uncommon, with non-Hodgkin B-cell lymphoma being even rarer at this level. The clinical presentation of this entity is highly variable and its symptoms are very non-specific, simulating several diseases, thus generating a late diagnosis. Currently, there are several diagnostic aids that allow us to rule out other pathologies and confirm tracheal neoplasia, in addition, biopsy is essential to reach the final diagnosis and thus establish management in early stages to impact morbidity and mortality. We present the case of a patient with non-Hodgkin's B-cell lymphoma as a cause of tracheal obstruction.

Características clínicas y patológicas de pacientes con linfoma B difuso de célula grande no especificado doble expresor diagnosticados en el Hospital de San José de Bogotá, Colombia / Clinical and pathological characteristics of patients with double expressor diffuse large B-cell lymphomas (DLBCLs) not otherwise specified (NOS), diagnosed at Hospital San José de Bogotá, Colombia

Resumen Introducción: el linfoma B difuso de célula grande (LBDCG) no especificado (NOS) con sobreexpresión de MYC y BCL2 por inmunohistoquímica constituye el grupo doble expresor, el cual se ha asociado con peores desenlaces comparado con el no doble expresor. Son escasos los estudios en la región sobre el comportamiento clínico del LBDCG NOS doble expresor. Objetivos: determinar las características clínicas, patológicas y tasas de respuesta de los pacientes con LBDCG NOS doble expresor diagnosticados en el Hospital de San José de Bogotá. Métodos: estudio observacional de tipo cohorte retrospectiva con pacientes con LBDCG NOS diagnosticados en el Hospital de San José entre 2016 y 2019. Se realizó una revisión central de patología para confirmar el diagnóstico, valorar la morfología celular y realizar evaluación de la expresión de MYC y BCL2. Resultados: se incluyeron 67 pacientes con LBDCG NOS. El 49,3 % de los casos fue de origen centro germinal. De total, 33 fueron clasificados como doble expresor (49,2 %). La tasa de respuesta global fue del 42,4 % en el grupo del LBDCG NOS doble expresor y 76,9 % en el total de los LBDCG NOS (76,9 %). Conclusión: el linfoma B difuso de célula grande doble expresor presentó tasas de respuesta global inferiores, posterior a inmunoquimioterapia estándar. El índice pronóstico internacional (IPI) de alto riesgo se asoció con menores tasas de respuesta completa

Abstract Introduction: diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS) with MYC and BCL2 overexpression by immunohistochemistry constitutes the double expressor group, which has been associated with worse outcomes compared to non-double expressor DLBCL. There is limited research on the clinical behavior of double expressor DLBCL NOS in the region. Objectives: to determine the clinical and pathological characteristics, as well as response rates, in patients diagnosed with double expressor DLBCL NOS at Hospital de San José in Bogotá. Methods: observational retrospective cohort study including patients with DLBCL NOS diagnosed at Hospital de San José between 2016 and 2019. Central pathology review was performed to confirm the diagnosis, assess cellular morphology, and evaluate MYC and BCL2 expression. Results: A total of 67 patients with DLBCL NOS were included. 49.3% of the cases originated from the germinal center and 33 cases were classified as double expressor (49.2%). The overall response rate was 42.4% in the double expressor DLBCL NOS group and 76.9% in the total DLBCL NOS population. Conclusion: Double expressor diffuse large B-cell lymphoma showed lower overall response rates following standard immunochemotherapy. High-risk International Prognostic Index (IPI) was associated with lower rates of complete response.

Linfoma no Hodgkin difuso de células B grande como linfoma primario de ovario. Presentación de caso / Diffuse large B-cell non-Hodgkin's lymphoma as primary ovarian lymphoma. Case presentation

Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1 % de estos se presenta en ovario y el 1.5 % de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuentes es el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia. Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario. Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario.

Background: Primary ovarian lymphomas are uncommon, 1% of these malignancies occur in the ovary, and 1.5% of all ovarian malignancies are lymphomas. The most common histologic types are diffuse large B-cell non-Hodgkin's lymphoma and BurKitt's lymphoma; treatment consists of surgery combined with chemotherapy. Objective: To report a case of primary ovarian diffuse large B-cell non-Hodgkin lymphoma. Case presentation: A 39-year-old female case is presented, with a personal pathological history; she went to the gynecology emergency service because she presented diffuse abdominal pain that was not relieved by analgesics. Physical examination revealed superficial and deep pain on palpation in the hypochondrium and right illiac fossa with a palpable tumor mass. Right adnexal ultrasound showed an image of low echogenicity and at the emergency laparoscopy, it was diagnosed as a tumor-like formation that appeared to correspond to the right ovary. She underwent a hysterectomy with double adnexectomy. The anatomopathologic diagnosis was primary ovarian non-Hodgkin's lymphoma. Conclusions: The patient in the presented case had an oligosymptomatic clinical presentation. Confirmation of the disease was obtained from a surgical sample, which means that B-cell non-Hodgkin's lymphoma is difficult to diagnose and although it is uncommon, it should always be considered in the differential diagnosis of unilateral ovarian tumors.

ASIA and BIA-ALCL as adverse reactions to silicone breast implants / ASIA e BIA-ALCL como reações adversas aos implantes mamários de silicone

Adjuvant-induced autoimmune/inflammatory syndrome leads to capsular contracture and fibrosis from the oxidation that takes place in silicone. Anaplastic large cell lymphoma occurs through the development of a seroma, with the formation of a periprosthetic effusion, or through the infiltration of the condition itself. To analyze these conditions, a review of the literature was carried out on the symptoms and pathophysiology of the autoimmune/inflammatory syndrome induced by adjuvants and anaplastic large cell lymphoma, searched using the terms "ASIA breast silicone," "Lymphoma," "Adjuvants" "Immunologic" " Breast Implants" on the PubMed platform. Analyzing the data obtained, it was noted that the symptoms of the autoimmune/inflammatory syndrome induced by adjuvants are nonspecific, such as fatigue, myalgia, arthralgia, morning stiffness, and night sweats, and therefore need attention. Anaplastic large cell lymphoma presents with breast pain, periprosthetic effusion, and palpable mass, among other characteristics. Because of these aspects, it is concluded that a good investigation should be carried out when nonspecific symptoms appear, regardless of the time the surgery was performed since these complications can occur years later.

A síndrome autoimune/inflamatória induzida por adjuvantes leva à contratura capsular e fibrose pela oxidação que acontece no silicone. O linfoma anaplásico de grandes células ocorre através do desenvolvimento de um seroma, com a formação de derrame periprotético ou por uma infiltração da própria afecção. Para análise destes acometimentos, foi realizada uma revisão da literatura acerca da sintomatologia e fisiopatologia da síndrome autoimune/inflamatória induzida por adjuvantes e linfoma anaplásico de grandes células, pesquisada através dos termos "ASIA breast silicone" "Lymphoma" "Adjuvants" "Immunologic" "Breast Implants" na plataforma PubMed. Analisando os dados obtidos, notou-se que os sintomas da síndrome autoimune/inflamatória induzida por adjuvantes são inespecíficos, como fadiga, mialgia, artralgia, rigidez matinal e suores noturnos, e, portanto, necessitam de atenção. Já o linfoma anaplásico de grandes células se apresenta com dor mamária, derrame periprotético, massa palpável, dentre outras características. Em vista destes aspectos, conclui-se que uma boa investigação deve ser realizada ao surgirem sintomas inespecíficos, independentemente do tempo que a cirurgia foi realizada, uma vez que estas complicações podem ocorrer anos após a cirurgia.

Leucemia aguda bilineal Monocítica/B BCR ABL positivo. Presentación de un caso / Bilinear Acute Monocytic Leukemia/B BCR ABL positive. presentation of a case

RESUMEN Introducción: Las leucemias de fenotipo ambigüo, se clasifican en leucemias indiferenciadas y de fenotipo mixto, éstas a su vez pueden dividirse en bilineales o bifenotípicas y suelen asociarse a mal pronóstico, sobre todo si se acompañan de translocaciones agresivas como la del cromosoma Filadelfia. Reporte de caso Presentamos el caso de una paciente adulta mayor que presentó una leucemia aguda bilineal con la presencia de una población de precursores de linaje monoblástico y otra linfoide B, evaluados por estudios de citometría de flujo, quien además presentó el transcrito BCR-ABL, detectado por estudios de PCR en tiempo real. La paciente cursó con mala evolución y falleció a los 11 días de su diagnóstico. Conclusión: Las leucemias de fenotipo mixto son de mal pronóstico y requieren un diagnóstico precoz por citometría de flujo y Biología molecular para brindar un tratamiento oportuno.

ABSTRACT Background: Leukemias with an ambiguous phenotype are classified as undifferentiated leukemias and mixed phenotypes, these in turn can be divided into bilinear or biphenotypic and are usually associated with a poor prognosis, especially if they are accompanied by aggressive translocations such as the Philadelphia chromosome. Case report: We present the case of an elderly adult patient who presented acute bilinear leukemia with the presence of a population of monoblastic lineage precursors and another, B lymphoid, evaluated by flow cytometry studies, who also presented the BCR-ABL transcript. , detected by real-time PCR studies. The patient had a poor evolution and died 11 days after her diagnosis. Conclusion: Mixed phenotype leukemias have a poor prognosis and require early diagnosis by flow cytometry and molecular biology to provide timely treatment.

Cost-Effectiveness Analysis of Rituximab for Chronic Lymphocytic Leukemia Using a Semi-Markovian Model Approach in R.

OBJECTIVES: This study aims to compare the strategies fludarabine, cyclophosphamide, and rituximab and fludarabine and cyclophosphamide for the treatment of chronic lymphocytic leukemia in Brazil. METHODS: A three-states clock-reset semi-Markovian model was constructed in R. The time horizon of the analysis was 15 years and monthly cycles were used. Transition probabilities were derived from the survival curves of the CLL-8 study. Other probabilities were also derived from the medical literature. Costs included in the model referred to the application of injectable drugs, prescription cost, cost of treating adverse events, and costs of supportive care. The model was evaluated by microsimulation. To determine the study result, multiple cost-effectiveness threshold values were used. RESULTS: In the main analysis, an incremental cost-effectiveness ratio of 19 029.38 PPP-US dollars (USD)/quality-adjusted life-year (QALY) (41 141.52 Brazilian real/QALY) was observed. In 1.8% of the iterations, fludarabine and cyclophosphamide was considered dominant over fludarabine, cyclophosphamide, and rituximab. It can be shown that at 1 gross domestic product (GDP) per capita/QALY, 36.1% of the iterations would consider the technology cost-effective. At 2 GDP per capita/QALY, this number rises to 82.1%. At 50 000 USD/QALY, 92.8% of the iterations would suggest the technology to be cost-effective. In terms of some threshold accepted or proposed around the world, the technology would be considered cost-effective at 50 000 USD/QALY, 3 GDP per capita/QALY, and 2 GDP per capita/QALY. It would not be cost-effective at 1 GDP per capita/QALY or the opportunity costs threshold. CONCLUSION: It can be considered that rituximab is cost-effective for the treatment of chronic lymphocytic leukemia in Brazil.

Desenvolvimento e avaliação de uma proteína quimérica recombinante para o diagnóstico e prognóstico das leishmanioses tegumentar e visceral / Development and evaluation of a recombinant chimeric protein for the diagnosis and prognosis of tegumentary and visceral leishmaniasis

As leishmanioses são doenças tropicais negligenciadas com alta endemicidade e que afetam milhares de pessoas no mundo. Sua infecção é causada por parasitos protozoários do gênero Leishmania. A diversidade biológica entre as espécies é quem permite determinar as manifestações clínicas, sendo elas na forma de leishmaniose visceral (LV) ou leishmaniose tegumentar (LT). Dentre estas manifestações, a LV é considerada a mais grave, devido sua alta letalidade e grande emergência em indivíduos com a infecção provocada pelo vírus da imunodeficiência humana (HIV). Atualmente, as medidas de controle e prevenção adotadas pela Organização Mundial da Saúde (OMS), baseiam-se em uma combinação de estratégias de intervenção contra a infecção, uma vez que o diagnóstico eficaz e precoce é indispensável para que se possa intervir com o tratamento adequado, diminuindo índices de mortalidade e a evolução de complicações clínicas. Entretanto, os testes sorológicos utilizados apresentam sensibilidade e especificidade prejudicadas em pacientes com leishmanioses e/ou coinfectados LV/HIV, devido a baixos ní-veis de anticorpos antileishmanial ou pela presença de doenças que causem reação cruzada, levando a resultados falso-positivos. A sensibilidade torna-se também variável em pacientes tratados, uma vez que a sorologia pode manter-se positiva por meses ou anos após o fim do tratamento e cura da doença. Buscando resolver tal problemática, a identificação de novos antígenos, por meio de análises de bioinformática associadas à imunoproteômica, tem permitido a detecção de novas proteínas com potencial aplicação diagnóstica. Em estudos anteriores, as proteínas hipotéticas LiHyT, LiHyD, LiHyV e LiHyP foram encontradas em espécies de Leishmania spp, e avaliadas em suas versões recombinantes por meio de ensaios de ELISA, obtendo resultados satisfatórios para a detecção da LV humana e canina. Com base nessas informações, o presente trabalho teve como objetivo desenvolver uma proteína quimera recombinante base-ada na predição de epítopos lineares específicos de células B das quatro proteínas antigênicas de L. infantum citadas e avaliar o potencial diagnóstico, assim como dos peptídeos individuais que a constituíram, frente à leishmaniose humana, bem como com a coinfecção com HIV, além de testar os antígenos como marcadores prognóstico após o tratamento da LV e LT. As sequências de aminoácidos das proteínas foram avaliadas e oito epítopos de células B foram preditos e utilizados na construção de uma nova proteína quimérica. A proteína foi expressa, purificada e avaliada como antígeno recombinante em ELISA para o diagnóstico de LV, LT, coinfecção LV/HIV e prognóstico em amostras de pacientes tratados de LV e LT. Os epítopos de células B usados na construção da quimera foram sintetizados e também testados em ELISA frente às mesmas amostras, assim como um extrato antigênico solúvel de Leishmania braziliensis (SLA). Os resultados mostraram que a proteína quimera apresentou sensibilidade e especificidade de 100% para diagnosticar a LV, LT e LV/HIV, enquanto os peptídeos sintéticos apresentaram sensibilidade variando entre eles de 9,1% a 90,9% para amostras de LT e 76,8% a 99,2% para amostras de LV e LV/HIV, já os valores de especificidade atingiram 98,3% a 99,1% para LT e 67,1% a 95,7% para LV e LV/HIV. O SLA apresentou sensibilidade e especificidade de 18,2% e 98,3% para LT, e 56,8% a 69,5% para amostras de LV e LV/HIV, respectivamente. Uma avaliação prognóstica preliminar mostrou ainda que os anticorpos anti-quimera diminuíram em níveis significativos, quando comparada a reatividade sorológica antes e seis meses após o tratamento, sugerindo um possível papel prognóstico da quimera para as leishmanioses. O presente estudo, mostrou-se eficaz na construção e avaliação de novos candidatos, que demonstram ter um bom desempenho na detecção diagnóstica e prognóstica para as leishmanioses e dos casos de coinfecção LV/HIV.

Leishmaniasis are neglected tropical diseases with high endemicity that affect thousands of people in the world. Infection is caused by protozoan parasites of the genus Leishmania. The biological diversity between species is what allows determining the clinical manifestations, either in the form of visceral leishmaniasis (VL) or tegumentary leishmaniasis (TL). Among these clinical manifestations, VL is considered the most serious, due to its high lethality and great emergence in individuals with infection caused by the human immunodeficiency virus (HIV). Currently, the control and prevention measures adopted by the World Health Organiza-tion (WHO) are based on a combination of intervention strategies against the infection, since an effective and early diagnosis is essential to intervene with the appropriate treatment, decrea-sing mortality rates and evolution of clinical complications. However, the serological tests used show impaired sensitivity and specificity in patients with leishmaniasis and/or coinfected with VL/HIV, due to low levels of anti-leishmanial antibodies or the presence of diseases that cause cross-reaction, leading to false-positive results. The sensitivity also becomes variable in treated patients, since the serology can remain positive for months or years after the end of the trea-tment and cure of the disease. Seeking to solve this problem, the identification of new antigens, through bioinformatic analysis associated with immunoproteomic, has allowed the detection of new proteins with potential diagnostic application. In previous studies, the hypothetical proteins LiHyT, LiHyD, LiHyV and LiHyP were found in species of Leishmania spp, and evaluated in their recombinant versions through ELISA assays, and satisfactory results were obtained for the detection of human and canine VL. Based on this information, the present work aimed to develop a recombinant chimera protein through on the prediction of specific linear epitopes of B cells derived from these four antigenic proteins of L. infantum and to evaluate its diagnostic potential, as well as the individual peptides that constitute it, against human leishmaniasis, as well as co-infection with HIV, in addition to testing them as possible prognostic markers of patients after VL and TL treatment. The amino acid sequences of the proteins were evaluated and eight B cell epitopes were predicted and used in the construction of a new chimeric protein. The protein was expressed, purified and evaluated as a recombinant antigen in ELISA for the diagnosis of VL, TL, VL/HIV co-infection and prognosis in samples from patients treated for VL and TL. The B cell epitopes used in the construction of the chimera were synthesized and also tested in ELISA against the same samples, as well as a soluble Leishmania braziliensis antigenic extract (SLA). The results showed that the chimera protein apresented sensitivity and specificity of 100% for diagnosing VL, TL and VL/HIV, while the synthetic peptides showed sensitivity ranging from 9.1% to 90.9% for TL samples and 76.8 % to 99.2% for VL and VL/HIV samples, while the specificity values reached from 98.3% to 99.1% for TL and 67.1% to 95.7% for VL and VL/HIV. The SLA showed sensitivity and specificity of 18.2% and 98.3% for TL, and 56.8% to 69.5% for VL and VL/HIV samples, respectively. A preliminary prog-nostic evaluation also showed that anti-chimera antibodies significantly decreased when com-pared to serological reactivity before and six months after treatment, suggesting a possible prognostic role of the antigen for leishmaniasis. The present study proved to be effective in the construction and evaluation of new candidates, who demonstrate good performance in diagnos-tic and prognostic detection for leishmaniasis and VL/HIV co-infection.

Biomarcadores genéticos de la leucemia linfoide aguda de linaje B / Genetic biomarkers of B - cell acute lymphoid leukemia

Introducción: La leucemia linfoide aguda es una proliferación y transformación maligna de las células progenitoras linfoides en la médula ósea, la sangre y los sitios extramedulares. Es la neoplasia más frecuente en la infancia. Constituye el 80 % de todas las leucemias agudas de la edad pediátrica y la más frecuente de las que se originan a partir del linaje de células B. Desde el punto de vista genético se presentan múltiples alteraciones moleculares y cromosómicas que son utilizadas para la estratificación pronóstica. Objetivo: Describir los biomarcadores genéticos de la leucemia linfoide aguda de linaje B y su implicación pronóstica. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se efectuaron un análisis y resumen de la bibliografía revisada. Conclusiones: En la leucemia linfoide aguda de linaje B se detectan múltiples alteraciones citogenéticas como las traslocaciones t(9;22) y la t(12;21), rearreglos en 11q23 que generan genes de fusión, así como otras aberraciones cromosómicas y mutaciones génicas. Este espectro genético involucra genes que participan en el desarrollo de las células linfoides y en la regulación del ciclo celular. El conocimiento de su biología, a partir del estudio de las alteraciones genéticas como biomarcadores predictivos, permite la estratificación de la leucemia linfoide aguda y la aplicación de tratamientos más personalizados para evitar recaídas.

Introduction: Acute lymphoid leukemia is a proliferation and malignant transformation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites. It is the most common neoplasm in childhood; it constitutes 80% of all acute leukemias in children; and the most frequent of those that originate from the B cell lineage. From the genetic point of view, there are multiple molecular and chromosomal alterations. Objective: To describe the genetic biomarkers of the disease and its prognostic implication. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine of Google Scholar, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Conclusions: In acute lymphoid leukemia, multiple cytogenetic alterations are detected, such as translocation t(9;22), t(12;21), rearrangements in 11q23 that generate fusions genes as well as other chromosomal aberrations and gene mutation. This genetic spectrum involves genes that participate in the development of lymphoid cells and in the regulation of the cell cycle. Knowledge of its biology, based on the study of genetic alterations as predictive biomarkers, allows the stratification of Acute lymphoid leukemia and the application of more personalized treatments to avoid relapses.

Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B / B-cell lymphocytosis in relatives of Colombian patients with chronic B-cell lymphoproliferative disorders

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados,lo que sugiere que no existe afectación degenes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µl is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

Autologous Anti-CD19 CAR T-Cells immunotherapy in relapsed/refractory acute lymphoblastic leukemia patients. A systematic review and meta-analysis / Imunoterapia de CAR T-Cells Anti-CD19 no tratamento de leucemia linfoblástica aguda refratária/recidivante. Revisão sistemática e metanálise

Introduction: Acute Lymphoblastic Leukemia (ALL) is the most prevalent malignancy in children; however, when the neoplasm becomes refractory/relapses (R/R) the cure possibilities are practically null. Objectives: To analyze the Anti-CD19 Chimeric Antigen Receptors (CAR) T-Cells immunotherapy efficacy in the treatment of R/R ALL, providing evidence about the efficacy and safety of the therapy for the analyzed group. Methods: The study consisted of a systematic review and meta-analysis based on the analysis of indexed articles. The searches were carried out with the terms: "acute lymphoblastic leukemia", "CAR T", and "CD19-specific chimeric antigen receptor". Results: Only 18 of the 94 articles obtained initially met the inclusion criteria and were selected for review, totaling 637 patients. Thus, it was observed in the responses that approximately 81% of the patients achieved a Complete Response; 7% did not respond; the neoplasm relapsed in 17% of the cases; and 6.1% of the patients died. The main side effects found were Cytokine Release Syndrome (CRS), Severe Cytokine Release Syndrome, and Neurotoxicity, present in 36.3%, 29%, and 24% of patients, respectively. Conclusion: Anti-CD19 CAR T-Cells immunotherapy is an effective therapy, capable of producing high rates of complete remission in R/R ALL treatment. [au]

Introdução: A Leucemia Linfoblástica Aguda (LLA) é a neoplasia maligna mais prevalente em crianças; entretanto, quando se torna refratária/recidivante (R/R) as possibilidades de cura são praticamente nulas. Objetivos: Analisar a eficácia da imunoterapia de Receptores de Antígenos Quiméricos anti-CD19 no tratamento da LLA R/R, fornecendo evidências sobre a efetividade e segurança da terapia para o grupo analisado. Métodos: O estudo consistiu em uma revisão sistemática e metanálise baseada em artigos indexados. As pesquisas foram realizadas com os termos: "acute lymphoblastic leukemia", "CAR T", and "CD19-specific chimeric antigen receptor". Resultados: Dos 94 artigos obtidos, apenas 18 atenderam inicialmente aos critérios de inclusão e foram selecionados para revisão, totalizando 637 pacientes. Assim, observou-se nas respostas que aproximadamente 81% dos pacientes obtiveram resposta completa; 7% não responderam; a neoplasia recidivou em 17% dos casos; e 6,1% dos pacientes morreram. Os principais efeitos colaterais encontrados foram síndrome de liberação de citocinas, síndrome de liberação grave de citocinas e neurotoxicidade, presentes em 36,3%, 29% e 24% dos pacientes, respectivamente. Conclusão: A imunoterapia com células CAR T anti-CD19 é uma terapia eficaz, sendo capaz de produzir altas taxas de remissão completa no tratamento de LLA R / R. [au]

Linfoma cutâneo primário difuso de grandes células B, tipo perna ­ rápida evolução e desfecho desfavorável: relato de caso / Diffused primary cutaneous lymphoma of large B cells, leg type - quick evolution and unfavorable outcome: case report

Linfomas cutâneos primários são a segunda forma mais comum de linfomas extranodais, sendo os linfomas de células B, (CBCLs) representantes de 20 a 30% dos casos. O linfoma cutâneo difuso de grandes células B, Tipo Perna (PCDLBCL-LT), representa o tipo mais agressivo de CBCLs. Na maioria dos casos, a apresentação clínica é caracterizada por placas ou tumores solitários, ora ulcerados, em uma ou ambas as pernas, de rápido crescimento. O diagnóstico é confirmado através do estudo histopatológico e imunohistoquímico. O tratamento é realizado por meio de quimioterapia e seu prognóstico é reservado com uma sobrevida de 50% a 60% em 05 anos. O objetivo deste trabalho é relatar um caso atendido de linfoma cutâneo primário difuso de grandes células B, tipo perna em um paciente de 75 anos, do sexo masculino com apresentação clínica clássica e desfecho desfavorável, realizar uma revisão bibliográfica do período de 2010 a 2020 na base de dados PUBMED sobre o assunto, dada sua raridade e agressividade ímpar. As informações foram obtidas através de revisão do prontuário, registro fotográfico e revisão da literatura. Por tudo isso, pode-se concluir a importância de estudos multidisciplinares, envolvendo dermatologistas, hematologistas, oncologistas e patologistas para que o diagnóstico e tratamento sejam instituídos o mais precoce possível, visto a raridade e agressividade do PCDLBCL-LT. [au]

Primary cutaneous lymphomas are the second most common form of extranodal lymphomas; with B cell lymphomas (CBCLs) representing 20 to 30% of cases. Diffuse cutaneous large B cell lymphoma, leg type (PCDLBCL-LT), represents the most aggressive type of CBCLs. In most cases, the clinical presentation is characterized by solitary plaques or tumors, sometimes ulcerated, on one or both legs, of rapid growth. The diagnosis is confirmed through histopathological and immunohistochemistry studies. Treatment is carried out through chemotherapy and its prognosis is reserved with a 50% to 60% survival in 5 years. The objective of this work is to report a case of diffuse primary B-cell cutaneous lymphoma, leg type in a 75-year-old male patient with a classic clinical presentation and unfavorable outcome, to perform a literary review from 2010 to 2020 in the PUBMED database on the subject, given its rarity and unique aggressiveness. The data was obtained by reviewing the medical record, photographic record and literature review. For all this, it is possible to conclude the importance of multidisciplinary studies, involving dermatologists, hematologists, oncologists and pathologists so that the diagnosis and treatment are instituted as early as possible, given the rarity and aggressiveness of the PCDLBCL-LT. [au]

Análise de custo do sequenciamento dos novos agentes para o tratamento de leucemia linfocítica crônica sob a perspectiva do sistema de saúde suplementar brasileiro / Cost analysis of sequencing new agents for the treatment of chronic lymphocytic leukemia from the perspective of the Brazilian supplementary health system

Objetivo: Estimar o custo do sequenciamento de tratamentos e por desfecho dos novos agentes disponíveis para o tratamento de pacientes com leucemia linfocítica crônica (LLC) em primeira linha (1L) e segunda linha (2L) em um horizonte temporal de 15 anos sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionada com quatro transições de estados de saúde (sem progressão em 1L, sem progressão em 2L, pós-progressão e morte), considerando os seguintes regimes: venetoclax + obinutuzumabe (VenO), venetoclax + rituximabe (VenR), ibrutinibe (Ibru) e acalabrutinibe (Acala). Foram consideradas na análise as posologias em bula e as curvas de sobrevida livre de progressão (SLP) dos respectivos estudos pivotais em cada uma das linhas terapêuticas. O custo total de cada sequência considerou a soma dos custos dos regimes utilizados em 1L e 2L, baseado no preço fábrica de cada medicamento. Resultados: As sequências de tratamento iniciadas com VenO apresentaram menores custos, especialmente o regime VenO>VenR (R$ 982.447), que apontou redução de aproximadamente R$ 3 milhões em 15 anos, quando comparada às sequências de Ibru>VenR ou Acala>VenR. Na análise de custo por desfecho, a sequência VenO>VenR apresentou o menor custo por ano de SLP (R$ 104.437), até 76% inferior em relação ao sequenciamento com maior custo por ano de SLP (Ibru>VenR). Conclusões: Os resultados desta análise demonstram o impacto significativo que a 1L de tratamento possui na jornada do paciente com LLC. Adicionalmente, o presente estudo aponta o menor custo de tratamento acumulado para o sequenciamento dos regimes VenO>VenR, sugerindo que os regimes de tratamento à base de venetoclax podem contribuir de maneira substancial em uma maior eficiência na alocação de recursos pelo gestor do sistema de saúde suplementar brasileiro.

Objective: To estimate the cost of treatment sequencing and per outcome of the new agents available for the treatment of patients with chronic lymphocytic leukemia (CLL) in 1st line (1L) and 2nd line (2L) in a 15-years time horizon from the perspective of the Brazilian supplementary health system. Methods: A partitioned survival model including four health state transitions (no progression in 1L, no progression in 2L, post-progression and death) was developed, considering the following regimens: venetoclax + obinutuzumab (VenO), venetoclax + rituximab (VenR), ibrutinib (Ibru) and acalabrutinib (Acala). The package insert dosages and progression-free survival (PFS) curves of the respective pivotal studies in each of the therapeutic lines were considered in the analysis. The total cost of each sequence considered the sum of the costs of the regimens used in 1L and 2L, based on the factory price of each drug. Results: Lower costs were observed when treatment sequences were initiated with VenO, especially the VenO>VenR regimen (R$ 982,447), which showed a reduction of approximately R$ 3 million in 15 years when compared to the Ibru>VenR or Acala>VenR sequences. In the cost per outcome analysis, the sequence VenO>VenR had the lowest cost per year of PFS (R$ 104,437), up to 76% lower than the sequencing with the highest cost per year of PFS (Ibru>VenR). Conclusions: Results show the significant impact that 1L treatment has on the CLL patient's journey. Additionally, the present study points to the lowest accumulated treatment cost for the sequencing of VenO>VenR regimens, suggesting that venetoclax-based treatment regimens can substantially contribute to greater efficiency in the allocation of resources by the manager of the Brazilian supplementary health system.

Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: A tertiary hospital.

BACKGROUND: Corticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. METHODS: Retrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a Spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. RESULTS: The study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD19, 0%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10,3 months (median; range 6,5-16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3,6 relapses/year in the previous year to the start of the treatment versus 0,1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83,3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87,5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96,5% decrease in the corticosteroids doses administered (28,5 mg/m2/day during the 3 months pre-treatment versus 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46,5 months, range 5-97 months). CONCLUSION: The favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Tratamento cirúrgico exclusivo de linfoma B primário cutâneo da zona marginal: relato de caso / Exclusive surgical treatment of a primary cutaneous marginal zone lymphoma: a case report

Os linfomas B primários cutâneos (LBPCs) são linfomas não Hodgkin, de acometimento exclusivamente cutâneo, e representam 25% dos linfomas primários cutâneos. São divididos, conforme comportamento clínico, em indolentes e intermediários. O tratamento das formas indolentes inclui a cirurgia, a radioterapia e, em casos extensos, o rituximabe. Relata-se o caso de mulher de 57 anos, com placa única no braço esquerdo, com diagnóstico de LBPC da zona marginal, tratado com excisão com margens de segurança de 5mm, sem recidiva após 36 meses de seguimento. A cirurgia é uma alternativa terapêutica com bom resultado clínico, sem impacto na sobrevida livre da doença.

Primary cutaneous B-cell lymphomas are non-Hodgkin lymphomas presenting only in the skin and represent 25% of all primary cutaneous lymphomas. Based on their clinical behavior, they are classified into indolent and intermediate forms. Treatment of indolent forms includes surgery, radiotherapy, and, in extensive disease, rituximab. We report a case of a 57-year-old woman with a single nodule in the left arm treated with surgical excision with 5-mm security margins, without relapse after 36 months. Surgery is a therapeutic option in these lymphomas without compromising disease-free survival.

Linfoma cutâneo difuso de grandes células B, tipo perna: sobre um caso típico / Cutaneous diffuse large B-cell lymphoma, leg type - a typical case

O linfoma cutâneo difuso de grandes células B, tipo perna, compreende uma neoplasia rara, agressiva e de mau prognóstico. Corresponde a 10-20% dos linfomas cutâneos de células B e afeta principalmente membros inferiores de mulheres idosas. Relatamos o caso de mulher de 81 anos, com nódulos e tumorações dolorosos, de crescimento rápido na perna esquerda. Os achados histopatológicos e a imuno-histoquímica, associados à ausência de comprometimento extracutâneo no estadiamento, concluíram o diagnóstico de linfoma cutâneo difuso de grandes células B, tipo perna. A raridade, a clínica e a epidemiologia típicas e a excelente resposta ao tratamento motivaram este relato

Cutaneous diffuse large B-cell lymphoma, leg type, is a rare, aggressive, and poorly prognostic neoplasm. It corresponds to 10-20% of cutaneous B-cell lymphomas and mainly affects the lower limbs of older women. We report the case of an 81-year-old woman with painful, fast-growing nodules and tumors in her left leg. Histopathological and immunohistochemical findings, associated with the absence of extra-cutaneous involvement during staging, concluded the diagnosis of cutaneous diffuse large B-cell lymphoma, leg type. The rarity of this limphoma, its typical clinic and epidemiology, and the excellent response to treatment motivated this report

Linfoma no Hodgkin primario de vagina o cuello uterino. Un diagnóstico en ocasiones incierto: a propósito de un caso / Primary non-Hodgkin´s lymphoma of vagina or cervix. A diagnosis sometimes uncertain: about a case

Resumen ANTECEDENTES: La afectación primaria del aparato genital femenino por un linfoma no Hodgkin es excepcional, se reporta en 0.2 a 1.1% de los casos. Los órganos afectados con más frecuencia son los ovarios, seguidos del cuello uterino; el endometrio y la vagina son los menos aquejados. Debido a su baja frecuencia aún no se llega a un consenso del tratamiento más adecuado de estos linfomas; hasta ahora, por lo general, se ha individualizado para cada caso en concreto. CASO CLÍNICO: Paciente de 29 años que consultó por sangrado genital anómalo e incapacidad para la inserción de tampones vaginales. En la exploración se encontró una masa pélvica, palpable a través de la vagina, que impresionaba al infiltrar toda la luz vaginal y la parte media e izquierda de la vulva. En los estudios de imagen se objetivó una gran masa pélvica de hasta 10 centímetros que parecía depender del cuello del útero y que se extendía e infiltraba el canal vaginal, la vulva y el tercio inferior de la vejiga. El reporte anatomopatológico de la biopsia fue: infiltración de pared vaginal por un linfoma no Hodgkin B difuso de células grandes. Se le indicaron seis ciclos de quimioterapia con ciclofosfamida, vincristina, adriamicina y prednisona con los que se consiguió la remisión metabólica completa. CONCLUSIÓN: El diagnóstico del linfoma genital primario puede resultar complejo por la posibilidad de simular una neoplasia ginecológica. En casos de enfermedad avanzada, la manifestación clínica más frecuente es el sangrado genital anómalo. El esquema de tratamiento más aceptado en la actualidad es con rituximab-ciclofosfamida, vincristina, adriamicina, prednisona seguido de radioterapia de consolidación.

Abstract BACKGROUND: Primary involvement of the female genital tract by non-Hodgkin's lymphoma is exceptional, reported in 0.2 to 1.1% of cases. The most frequently affected organs are the ovaries, followed by the cervix; the endometrium and vagina are the least affected. Due to their low frequency, there is still no consensus on the most appropriate treatment of these lymphomas; until now, it has generally been individualized for each specific case. CLINICAL CASE: A 29-year-old female patient consulted for abnormal genital bleeding and inability to insert vaginal tampons. On examination a pelvic mass was found, palpable through the vagina, which impressed by infiltrating the entire vaginal lumen and the middle and left side of the vulva. Imaging studies showed a large pelvic mass of up to 10 centimeters that appeared to be dependent on the cervix and that extended and infiltrated the vaginal canal, the vulva and the lower third of the bladder. The anatomopathological report of the biopsy was: infiltration of the vaginal wall by diffuse large cell non-Hodgkin's B lymphoma. She was prescribed six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisone with which complete metabolic remission was achieved. CONCLUSION: The diagnosis of primary genital lymphoma can be complex because of the possibility of simulating a gynecologic neoplasm. In cases of advanced disease, the most frequent clinical manifestation is abnormal genital bleeding. The most accepted treatment scheme at present is rituximab-cyclophosphamide, vincristine, adriamycin, prednisone followed by consolidation radiotherapy.

Linfoma no Hodgkin primario de ovario: reporte de caso y revisión de la bibliografía / Primary ovarian non-Hodgkin lymphoma: case report and review of literature

Resumen INTRODUCCIÓN: Los linfomas no Hodgkin son un grupo heterogéneo de neoplasias hematolinfoides, de manifestación principal ganglionar; un pequeño porcentaje tiene un origen extra-ganglionar. Se han descrito algunos casos de linfomas no Hodgkin primarios de ovario y, en general, del conducto genitourinario femenino. Debido a su poca frecuencia suponen un reto diagnóstico, clínico y patológico. Se informa el caso de una paciente con linfoma no Hodgkin primario de ovario, a quien se le practicó citorreducción quirúrgica primaria y tratamiento coadyuvante con quimioterapia sistémica. Se revisa la bibliografía en torno a los criterios diagnósticos y el pronóstico de la enfermedad. CASO CLÍNICO: Paciente de 65 años, que acudió a consulta debido a un síndrome constitucional y síntomas irritativos urinarios; al ingreso tuvo signos vitales dentro de los parámetros de referencia y en el examen físico se encontraron: edema grado 2, bilateral, en los miembros inferiores y marcada palidez mucocutánea. Los estudios complementarios evidenciaron anemia microcítica hipocrómica heterogénea y trombocitosis. La resonancia magnética reportó la existencia de una masa anexial derecha, compleja, por lo que se practicó la citorreducción quirúrgica primaria. El estudio anatomopatológico reveló que se trataba de un linfoma no Hodgkin B primario de ovario. El tratamiento consistió en quimioterapia, con esquema R-CHOP. Diez meses después se estableció la curación de la enfermedad mediante estudios de imagen y pruebas de laboratorio. CONCLUSIONES: El linfoma no Hodgkin primario de ovario es una causa poco frecuente de afectación extraganglionar y se trata de un diagnóstico de exclusión, que requiere confirmación histopatológica. El pronóstico sugiere que la enfermedad confinada al ovario muestra una tasa de supervivencia global de 79% a 10 años. Se requieren estudios adicionales, que caractericen el pronóstico y el procedimiento diagnóstico de esta enfermedad.

Abstract INTRODUCTION: Non-Hodgkin's lymphomas are a heterogeneous group of neoplasms hematolymphoid, with main lymph node manifestation; a small percentage have an extra-nodal origin. Some cases of non-Hodgkin's lymphomas have been described.Primaries of the ovary and, in general, of the female genitourinary duct. Because of his they infrequently pose a diagnostic, clinical and pathological challenge. We report the case of a patient with primary ovarian non-Hodgkin's lymphoma, who underwent primary surgical cytoreduction and adjuvant treatment with systemic chemotherapy. The bibliography around the criteria is reviewed diagnosis and prognosis of the disease. CLINICAL CASE: A 65-years-old patient who presented constitutional syndrome and urinary irritative symptoms, her vital signs at the admission were normal, at the physical examination bilateral grade 2 edema in lower limbs and mucocutaneous paleness was observed, heterogeneous hypochromic microcytic anemia, thrombocytosis and also a right complex ovarian mass were documented during the hospitalization, for this reason was treated with primary surgical reduction, the histopathological result was Ovarian Primary Non Hodgkin B-cell Lymphoma, for that reason systemic adjuvant chemotherapy with R-CHOP scheme was initiated, at the ten month follow-up radiological and nuclear examinations were performed confirming the remission of the disease. CONCLUSIONS: Primary ovarian non-Hodgkin lymphoma is an unusual extra-nodular hematolymphoid neoplasm that requires a histopathological confirmation. The prognosis according to the literature review for the disease limited to the ovary has an overall survival rate of 79% to 10 years after diagnosis. More studies are required to characterize the prognosis and diagnostic approach of this entity.