Lymphomatous Polyposis: Case Report and Literature Review / Poliposis linfomatosa: reporte de caso y revisión de la literatura

Abstract Lymphomatous polyposis (LP) is the endoscopic feature of primary gastrointestinal mantle cell lymphoma (MCL), a rare type of B-cell non-Hodgkin's lymphoma (NHL) and a typical but rare endoscopic pattern of gastrointestinal tract involvement (GIT) by nodal MCL. We present the case of a 62-year-old man with nodal MCL, with LP as a manifestation of GIT, and review the literature.

Resumen La poliposis linfomatosa (PL) es la característica endoscópica del linfoma de células del manto (LCM) gastrointestinal primario, un tipo infrecuente de linfoma no Hodgkin (LNH) de células B, así como un patrón endoscópico típico, pero infrecuente, del compromiso del tracto gastrointestinal (TGI) por LCM nodal. Presentamos el caso de un hombre de 62 años con LCM nodal, con PL como manifestación del compromiso gastrointestinal, y realizamos una revisión de la literatura.

Blastoid mantle cell lymphoma: cutaneous infiltration

Abstract Mantle cell lymphoma is an aggressive B-cell, non-Hodgkin's lymphoma, with lymph node or extranodal origin, and a mean survival of three to five years. Skin involvement is rare, secondary and indicates neoplasia dissemination. The authors report a case of a female patient, 69 years old, diagnosed previously, after lymph node and bone marrow biopsy. She was undergoing the second chemotherapy regimen when she showed infiltrated plaque-like lesions, nodules and tumors on the trunk and thigh root. Histopathology and immunohistochemistry demonstrated cutaneous infiltration of the blastoid lymphoma.

Mantle cell lymphoma presenting with lethal atraumatic splenic rupture

Mantle cell lymphoma is characterized by t(11;14) with CCND1-IGH fusion and manifests with a spectrum of disease ranging from relatively indolent to aggressive. Here, we present a case of pleomorphic mantle cell lymphoma with three fusion signals that presented with lethal atraumatic splenic rupture. We discuss on the implications of variant CCND1 signal patterns as well as the epidemiology and pathophysiology of atraumatic splenic rupture.

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

ABSTRACT: The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.

Angiogênese e prognóstico em linfoma de células do manto / Angiogenesis and prognosis in mantle cell lymphoma

INTRODUÇÃO: Fatores prognósticos em Linfoma de Células do Manto (LCM) foram definidos em época sem padronização de tratamento e menos conhecimento de patogenia. Entre estes conhecimentos a participação da angiogênese ainda tem sido pouco estudada. Assim, a identificação de novos fatores prognósticos e melhor definição do impacto da angiogênese no LCM podem auxiliar na terapêutica e caracterizar grupos com maior risco de óbito. OBJETIVO: Avaliar a microdensidade vascular (MDV) em pacientes com LCM tratados no A.C.Camargo Cancer Center e relacioná-la a fatores que impactem na sobrevida global(SG). MATERIAL E MÉTODOS: Estudo retrospectivo, unicêntrico, transversal em portadores de LCM não indolente em cujas amostras histológicas foi quantificada MDV através de CD34 e avaliada angiogênese através de HIF-∝ e VEGF. Também foram consideradas variáveis demográficas, clínicas, laboratoriais, índices prognósticos e dados de tratamento e resposta ao tratamento. Modelo de riscos proporcionais de Cox simples foi ajustado para descrever a relação entre variáveis independentes e tempo até o óbito. Seleção das variáveis para modelo de regressão de Cox múltiplo foi considerada a partir dos resultados do modelo de Cox simples. RESULTADOS: No período de 2006 a 2014 analisamos 63 pacientes. A maioria foi do sexo masculino (68.3%) com estádio IV (81%). A mediana de idade foi de 64 anos e mediana de MIPI e MIPI-b de 5,7 e 6,2 respectivamente. Citarabina em alta dose foi utilizada em 44,4% dos pacientes e 36,5 % dos pacientes realizaram TACTH. O tempo mediano de seguimento foi 72,34 meses e a mediana de sobrevida global (SG) foi de 93,91 meses. Dos 63 pacientes iniciais, 34 dispunham de amostras para análise de MDV. A média e mediana de MDV foi de 14,88 e 3,5 vasos/mm2 respectivamente e 64,71% dos pacientes apresentaram VEGF e HIF-∝ ≥10%. Em análise univariada nenhum parâmetro de angiogenese apresentou significância estatística. Idade, hemoglobina , albumina, número de leucócitos, linfócitos, plaquetas, valores de MIPI e Ki-67 apresentaram significância estatística para SG. Em análise multivariada idade, concentração de albumina e plaquetas apresentaram significância permitindo estabelecer que pacientes com idade superior a 70 anos possuíram risco 8 vezes maior (HR=8,025; valor p=0,0101) de ir à óbito em relação aqueles com idade menor ou igual a 70 anos. Para cada incremento de unidade de albumina houve redução de 79,9% (HR=0,201; valor p=0,005) no risco de óbito mantido a idade constante enquanto pacientes com contagem de plaquetas acima de 146x109/l tiveram redução de risco de óbito em 78% (HR=0,231; valor p=0,003). CONCLUSÃO: Os resultados do presente estudo permitem concluir que a angiogênese não demonstrou ser um valor preditivo de óbito e que parâmetros diferentes dos habitualmente utilizados associam-se a maior risco de óbito. Tais achados devem ser validados em uma coorte mais ampla de pacientes.

INTRODUCTION: Mantle Cell Lymphoma (MCL) prognostic factors were defined in a no standardized treatment and less well-known pathogenesis time. Among them, angiogenesis has been little studied. Therefore, angiogenesis impact better definition and new prognostic factors can define higher death-risk groups and help MCL patients' management. PURPOSE: To evaluate microvascular density (MDV) in MCL patients treated at the AC Camargo Cancer Center as well as identify demographic, clinical and laboratory factors that impact on overall survival (OS). MATERIAL AND METHODS: We conducted a retrospective, single-center and cross-sectional study. We included all non-indolent MCL patients who underwent immuno-chemotherapy. MDV was quantified by CD34 analysis and angiogenesis was determined by HIF-∝ and VEGF markers. We took into account demographic, clinical, laboratory, prognostic indexes, treatment and response to treatment variables. Cox's proportional hazards model was adjusted to data to describe variables and time until death relationship. Variables selection for multiple Cox regression analysis model was considered from simple Cox model results. RESULTS: From 2006 to 2014, we analyzed 63 patients. The majority were male (68.3%) and Ann Arbor stage IV (81%) and they were 64 years old median age with median MIPI= 5.7 and MIPI-b= 6.2. High dose cytarabine was used in 44.4% of patients and 36.5% underwent TACTH. Median follow-up was 72.34 months and median overall OS was 93.91 months. Of 63 patients, 34 had samples for MDV analysis. The mean and median MDV was 14.88 and 3.5 vessels / mm2, respectively and 64.71% of patients had VEGF and HIF-∝ ≥10%. In univariate analysis, no angiogenesis parameter showed statistical significance. Age, hemoglobin, albumin, leukocytes, lymphocytes, platelets, MIPI and Ki-67 values were statistically significant for overall survival. In multivariate analysis, age, albumin concentration and platelet count were statistically significant, allowing the establishment of a predictive model. Patients over 70 years old had more than 8 times increased death-risk (HR = 8.025; p = 0.0101) in relation to those with less than or equal to 70 years old. For each albumin unit increment a reduction of 79.9% (HR = 0.201; p-value = 0.005) is expected in death-risk while patients with platelet count above 146 x 109/l had a 78% reduction in death-risk in relation to those with platelet count equal to or less than this value (HR = 0.231; p-value = 0.003). CONCLUSION: Angiogenesis has not been shown to have death predictive value. Diferent parameters from those commonly used are associated with higher death-risk. Such findings should be validated in a broader cohort of patients.

Resultados de pacientes con linfoma del manto: impacto de terapias basadas en citarabina y trasplante hematopoyético / Cytarabine and hematopoietic cell transplantation for mantle cell lymphoma: analysis of 20 patients

Background: Mantle cell lymphoma (MCL) has high relapse and mortality rates. There is a survival benefit when treatment is intensified with cytarabine (AraC), hematopoietic cell transplantation (HCT) and maintenance with rituximab. Aim: To assess the outcomes of patients with MCL treated in a university hospital. Material and Methods: Review of an oncology center database and medical records identifying patients with MCL treated between 2006 and 2017. Death dates were obtained from the death certificate database of the National Identification Service. We analyzed the response rate, overall survival (OS) and progression-free survival (PFS). As a secondary objective, the survival impact of AraC, HCT and maintenance with rituximab, was also analyzed. Results: Information on 20 patients aged 62 ± 11 years, followed for a median of 45 months was retrieved. Eighty-five percent were diagnosed at an advanced stage. The most used first-line regime was R-CHOP in 11 patients, followed by R-HyperCVAD in five. Only 47% achieved complete response. 4-year PFS and OS were of 30 and 77% respectively. Mantle Cell Lymphoma International Prognostic Index (MIPI) significantly predicted PFS and OS. Maintenance with rituximab or HCT was associated with better PFS (48 vs 21 months, p < 0.01). The exposure to AraC or HCT, in refractory or relapsed disease, was associated with an increase in PFS from 9 to 28 months (p = 0,02) and 4-year OS from 40 to 100% (p = 0.05). OS increased even more, from 25 to 100% in those with high-risk MIPI (p = 0.04). Conclusions: The incorporation of AraC, HCT and maintenance with rituximab in the therapeutic backbone of MCL, especially for high-risk cases, was associated with improved survival.

Characteristics of follicular and mantle cell lymphoma in Brazil: prognostic impact of clinical parameters and treatment conditions in two hospitals

ABSTRACT Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. Conclusion: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.

Ki-67 expression in mature B-cell neoplasms: a flow cytometry study

SUMMARY OBJECTIVE: Ki-67 is a nuclear protein associated with cellular proliferation in normal or leukemic conditions that can help identify more aggressive diseases and is usually evaluated with immunohistochemistry. The aim of this was to assess Ki-67 expression on mature B-cell neoplasms samples with flow cytometry immunophenotyping. METHOD: After surface staining with CD19 and CD45, intracellular staining for Ki-67 was performed in leukemic mature B-cells. Ki-67 expression was evaluated with flow cytometry. RESULTS: Ki-67 expression was higher in mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cases. It was also associated with CD38 mean fluorescence intensity. CONCLUSIONS: Ki-67 expression evaluated by flow cytometry can be a useful tool in the diagnosis of mature B-cell neoplasms. More studies are needed to validate Ki-67 assessment with flow cytometry immunophenotyping.

RESUMO OBJETIVO: Ki-67 é uma proteína nuclear associada à proliferação celular em condições normais ou leucêmicas que pode ajudar a Identificar doenças mais agressivas. Este marcador é geralmente avaliado com imuno-histoquímica. O objetivo deste estudo foi avaliar a expressão de Ki-67 em amostras de neoplasias de células B maduras com imunofenotipagem por citometria de fluxo. MÉTODO: Após marcação de superfície com CD19 e CD45, foi realizada marcação intracelular para Ki-67 em células B maduras leucémicas. A expressão de Ki-67 foi avaliada por citometria de fluxo. RESULTADOS: A expressão de Ki-67 foi maior em células de linfomas de manto, linfoma de Burkitt e linfoma difuso de grandes células B. Também houve associação de Ki-67 à intensidade de fluorescência média de CD38. CONCLUSÃO: A expressão de Ki-67 avaliada por citometria de fluxo pode ser útil no diagnóstico de neoplasias de células B maduras. São necessários mais estudos para validar a avaliação de Ki-67 com Imunofenotipagem por citometria de fluxo.

Síndromes linfoproliferativos gastrointestinales / Gastrointestinal lymphoproliferative syndrome

The gastrointestinal lymphoid system plays a relevant role. The daily and continuous interaction between gastrointestinal lymphocytes with food and intestinal microbes requires precise functioning. The pathologic spectrum of lymphocyte malfunction results in lymphomas. MALT lymphoma is the most frequently diagnosed lymphoma, but there are other lymphoproliferative diseases such as diffuse large B cell lymphoma, mantle cell lymphoma and T associated lymphoma. The gastroenterologist and the endoscopist need to know these diseases in detail to achieve early diagnosis and treatment.

El sistema linfoide de defensa abdominal tiene un relevante rol en el buen funcionamiento sistémico. La interacción diaria y continua con patógenos alimentarios y microbios comensales intestinales precisa un estrecho funcionamiento. Las alteraciones linfoides clonales favorecen el desarrollo de linfomas de diversos tipos. Si bien, el linfoma asociado a tejido linfoide de mucosas (MALT) es el más conocido en contexto de su asociación con Helicobacter pylori, el tracto gastrointestinal se puede ver afectado por otros linfomas como el linfoma difuso de células grandes B y linfomas indolentes como el linfoma folicular, el linfoma del manto y el linfoma T asociado a enteropatía. El gastroenterólogo y endoscopista precisan conocer en detalle estas entidades para un oportuno diagnóstico y adecuado tratamiento.

Mantle cell lymphoma: involvement of nodal and extranodal sites in the head and neck, with multifocal oral lesions

Mantle cell lymphoma (MCL) is a malignant B-cell neoplasm, which comprises monomorphic and small- to medium-sized mantle zone-derived lymphoid cells. It is characterized by chromosomal translocation t(11;14)(q13;q32) and CCND1 truncation, resulting in cell cycle deregulation. It is an aggressive type of non-Hodgkin lymphoma with a propensity to present with extranodal involvement. This study shows the case of an 80-year-old Caucasian male who complained of a 2-month progressive swelling on the right side of his face. The magnetic resonance imaging exam showed multifocal involvement of the head and neck, including oral manifestations, bilateral parotid glands, palate, tongue, and floor of the mouth. An incisional biopsy of the tumor mass was performed. The morphological and immunophenotypic findings were consistent with the diagnosis of MCL. The patient died 4 months later, without any chance of undergoing a therapeutic approach. Although MCL is a rare condition, it should be subjected to a differential diagnosis when affecting the maxillofacial area. Imaging exams and both immunohistochemical and morphological analyses are needed to reach the correct diagnosis. Here, we present an unusual MCL with multifocal involvement of the head and neck.

Eficacia y seguridad de ibrutinib en el tratamiento de pacientes con diagnóstico de linfoma de células del manto, con al menos dos líenas de tratamiento previo / Efficacy and safety of ibrutinib in the treatment of patients diagnosed with mantle cell lymphoma, with at least two previous treatment regimens

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso de ibrutinib en el tratamiento de pacientes con diagnóstico de linfoma de células del manto. Aspectos Generales: El linfoma de células del manto (LCM) es un tipo muy agresivo de linforma no-Hodgkin que se origina por la malignización de los linfocitos B en el margen externo del folículo de un ganglio linfático o zona del manto y se caracteriza por la translocación cromosomal t)11,14) y la sobre-expresión de la ciclina D1(1). Su incidencia se estima en0.51 casos por cada 100,000 habitantes, representando el 2-10% de todos los linforma no-Hodgkin. Epidemiológicamente se caracteriza por ser más frecuente en varones entre los 60-68 años de edad. Tecnología Sanitaria de Interés: Ibrutinib, un inhibidor covalente de primera generación de la tirosina quinasa de Bruton (BTK, por sus siglas en inglés(, es una molécula pequeña que se une de manera irreversible al residuo 481 de cisteína en el dominio de la quinasa de la tirosina de Bruton de las células B. Adicionalmente, ibrutinib también se puede unir a otros dominios de quinasa que contienen un residuo de cisteína homólogo, tales como HER2, BLK y JAK3 entre otros. El linforma no-Hodgkin de células del manto es un tipo de neoplasia de células B. La quinasa de Bruton se encuentra por debajo de la cascada de señalización del receptor de las células B. La señal enviada por el receptor de dichas células, ya sea dependiente o independiente de antígenos, es considerada una de los principales mecanismos detrás de la progresión de este tipo de neoplasias, ya que juega un rol critico en la supervivencia y proliferación de las células B. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del uso de ibrutinib para el tratamiento de LCM en pacientes que han progresado a más de dos lineas de tratamiento previo. Esta búsqueda se realizó utilizando las bases de datos MEDLINES, EMBASE, SCOPUS, WEB OF SCIENCE, CINAHL, COCHRANE y TRIP DATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica hasta noviembre 2016 que sustente el uso de ibrutinib en el tratamiento de LCM para pacientes que han recibido dos o más líneas de tratamiento previo. CONCLUSIONES: En el presente dictamen se evaluó la evidencia científica publicada hasta noviembre 2016 en relación al uso de ibrutinib en pacientes con LCM que han recibido más de dos líenas de tratamiento. El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) no aprueba el uso de ibrutinib para el tratamiento de LCM en pacientes con al menos dos líneas de tratamiento.

Linfoma de células del manto con presentación radiológica atípica: Presentación de caso / Mantle Cell Lymphoma with Atypical Radiologic Presentation

El linfoma de células del manto hace parte del subgrupo de linfomas no Hodgkin (LNH). Este se manifiesta con adenopatías, esplenomegalia, síntomas B y compromiso cutáneo asociado a enfermedad diseminada. El compromiso esplénico se presenta como: Esplenomegalia sin lesión focal; lesiones sólidas únicas o múltiples e infiltración del bazo sin cambios morfológicos ni lesiones focales. La aparición de linfoma con lesiones quísticas es extremadamente rara, se encuentran solo unos cuantos casos en la literatura, ninguno de ellos en el bazo. Se expone el caso de una paciente de 59 años de edad, quien consultó por dolor abdominal intermitente. En los estudios diagnósticos se observó esplenomegalia con lesiones sólidas y quísticas. Se realizó esplenectomía con estudio histopatológico que confirmó compromiso por linfoma de células del manto.

Mantle cell lymphoma is a Non-Hodgkin Lymphoma (NHL). In cases of disseminated disease, lymphadenopathy, splenomegaly, B-symptoms and skin disease are present. Lymphoma affecting the spleen has several radiologic presentations, ranging from normal appearance, to splenomegaly or multiples focal solid lesions. Cystic presentation of lymphoma is rare and few cases have been reported, none of them involving the spleen. We report a case of a 59-year old female patient with cystic spleen lesions that after splenectomy were diagnosed as Mantle cell lymphoma.

Guía de Práctica Clínica para la detección, tratamiento y seguimiento de Linfomas Hodgkin y No Hodgkin en población mayor de 18 años / Clinical practice guideline for the detection, treatment and follow-up of Hodgkin and Non-Hodgkin lymphomas in a population over 18 years of age

Esta guía esta dirigida al personal de la salud involucrado directamente en la atención de pacientes adultos mayores de 18 años con sospecha o diagnóstico de linfoma no Hodgkin B difuso de célula grande (Linfoma B difuso de células grandes), linfoma folicular (LF), linfoma de células del manto (LCM) y linfoma Hodgkin (LH), y a las instancias administrativas, empresas aseguradoras y entes gubernamentales involucrados en la generación de políticas en salud. Esta GPC basada en la evidencia incluye los temas de diagnóstico y tratamiento del Linfoma B difuso de células grandes, LF, LM y LH, bajo la perspectiva del Sistema General de Seguridad Social en Salud colombiano. Objetivos: Determinar los métodos diagnósticos más apropiados en pacientes con LBDCG para garantizar un diagnóstico preciso que permita una adecuada selección del tratamiento; Establecer las líneas de tratamiento en pacientes con LF para disminuir la heterogeneidad en la atención y mejorar los resultados del tratamiento; Determinar los esquemas de tratamiento de primera línea para pacientes con LCM en diferentes grupos de edad para disminuir la heterogeneidad y mejorar los resultados del mismo; y Mejorar la supervivencia libre de enfermedad y la supervivencia global de los pacientes adultos con LH.

Resultados del tratamiento del linfoma de células del manto con varios regímenes de inmunoquimioterapia: estudio retrospectivo / Results of mantle cell lymphoma treated with various immunochemotherapy regimens: A retrospective stud

Objetivos: Describir las características clínicas y los resultados del tratamiento inicial de los pacientes con linfoma de células del manto atendidos en el Instituto Nacional de Cancerología (INC) entre los años 2007 y 2011. Métodos: Estudio descriptivo y retrospectivo, tipo serie de casos basado en fuentes secundarias institucionales. Resultados: Se incluyeron 41 pacientes con una edad promedio de 60,5 años (DE ±10,5) y que tenían en su mayoría un estado funcional adecuado. La mayor parte tenía enfermedad avanzada al momento de la presentación (85%). El compromiso de la médula ósea y la afectación extranodal fueron frecuentes, encontrándose en 73% y 39% respectivamente. El diagnóstico histopatológico de la malignidad se realizó en tejido ganglionar en la mayoría de los casos (56%). Los esquemas de quimioterapia de primera línea empleados con más frecuencia fueron R-CHOP y R-HyperCVAD, en 37% y 29% de los casos respectivamente. Tras la quimioterapia de primera línea se logró alcanzar una respuesta completa en 64% de los pacientes, la mediana de duración de la primera remisión fue 9 meses (RIQ0,9 - 15). La neutropenia febril fue una complicación común presentándose en 42% de los casos. Dieciocho individuos recibieron quimioterapia de segunda línea, los esquemas más frecuentemente empleados fueron R-DHAP y R-HyperCVAD. Conclusiones: Las características clínicas de los pacientes son similares a las descritas en series de referencia. Las tasas de respuesta completa y la duración de la primera remisión son inferiores a las publicadas por otros grupos con esquemas similares de tratamiento. © 2014 Instituto Nacional de Cancerología.

Objective: To describe the clinical features and the treatment results achieved with the initial therapy among patients with mantle cell lymphoma treated at the National Cancer Institute (INC) between 2007 and 2011. Methods: Descriptive study, based on secondary institutional sources. Results: A total of 41 patients were included, with a mean age of 60.5 years (Standard deviation SD ± 10.5) and a good functional status. Most of them had advanced disease at initial presentation (85%). Bone marrow involvement and extra-nodal disease were frequent, as they were seen in 73% and 39% of the patients, respectively. Histopathological diagnosis of the malignancy was mainly made on lymph node tissue (56%). First line chemotherapy regimens used with an increased frequency were R CHOP and R- HyperCVAD, in 37% and 29% of the cases, respectively. After first line therapy, a complete response was achieved in 64% of the patients, median duration of the first remission was 9 months (Interquartile range IQR 0.9 - 15). Febrile neutropenia was a frequent complication, seen in 42% of the cases. Eighteen individuals received a second line of chemotherapy, with R DHAP and R HyperCVAD being the regimens most commonly administered. Conclusions: The clinical features of the patients are similar to those described in larger series of patients with the disease described elsewhere. The rate of complete responses, as well as the duration of the first remission after chemotherapy, is inferior when compared with the results of other groups that used similar treatment regimens.

Expresión del factor de transcripción SOX11: Su implicancia en el linfoma de células del manto / Expression of SOX11 transcription factor: Its implication in mantle cell lymphoma

El gen SOX11, perteneciente a la familia de genes SOXC, es un factor de transcripción involucrado en la neurogénesis embrionaria y el remodelado tisular, participando asimismo en el control de la proliferación celular. Su rol en la linfomagénesis es desconocido. Estudios recientes han mostrado expresión proteica nuclear aberrante y sobreexpresión de los niveles de transcripto de SOX11 en pacientes con linfoma de células del manto (LCM). Si bien la mayoría de estos linfomas presentan un curso clínico agresivo, existe un subgrupo de pacientes con enfermedad indolente, sugiriendo una mayor heterogeneidad de esta patología. Actualmente, existen contradicciones respecto de la asociación entre la expresión del gen SOX11 y la evolución clínica del LCM; mientras algunos autores relacionan la ausencia de expresión de SOX11 con buen pronóstico, otros lo encuentran asociado a un curso clínico adverso. Esta diferencia en la expresión estaría relacionada a mecanismos epigenéticos, metilación del ADN y modificaciones a nivel de histonas, que permitirían la expresión aberrante de este gen en algunas neoplasias linfoides, incluyendo LCM. La profundización del conocimiento del gen SOX11 en LCM hará factible, sin duda, lograr una mayor comprensión de los mecanismos involucrados en la patogénesis y/o progresión de este linfoma, así como del rol de SOX11 en estos procesos.

SOX11, belonging to the family of genes SOXC, is a transcript factor involved in the embryonic neurogenesis and tissue remodeling, also participating in the control of cell proliferation. Its role in lymphomagenesis still remains unknown. Recent studies have shown aberrant SOX11 nuclear protein expression as well as mRNA levels in patients with mantle cell lymphoma (MCL). Although the majority of these lymphomas have an aggressive clinical course, there is a subgroup of patients with an indolent clinical evolution, suggesting a greater heterogeneity of this disease. Currently, there are contradictions regarding the association of SOX11 gene expression and outcome in MCL, while some authors have related the lack of SOX11 expression with good prognosis, others find it associated with an adverse clinical course. This difference in the gene expression could be associated to epigenetic mechanisms such as modifications at the histone level and DNA methylation that would allow the aberrant expression of this gene in some lymphoid neoplasias, including LCM. More knowledge of gene SOX11 in LCM will lead to a greater understanding of those mechanisms involved in the pathogenesis and progression of this lymphoma, also the involvement of SOX11 in these processes.