Different mutational profiles of subcutaneous panniculitis-like T-cell lymphoma and lupus panniculitis: an additional case series.

BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Real world effectiveness and safety of nivolumab in patients with relapsed or refractory classical hodgkin lymphoma. / Efectividad y seguridad en vida real de nivolumab en pacientes con linfoma de hodgkin clásico en recaída o refractario.

OBJECTIVE: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy. METHOD: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival and overall survival. Safety was measured as percentage of patients with adverse effects and severity. RESULTS: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2.0-4.5), including autologous hematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3.0-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%) and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95%CI: 0-49.1), median overall survival was not reached. At the study cutoff date, five patients had died (38.5%), four were in complete remission without active treatment (30.8%) and four were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, two suffered treatment delays (thrombocytopenia and hypertransaminemia) and one changed the regimen to monthly (pulmonary toxicity). CONCLUSIONS: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed in the study sample favorable effectiveness data, expressed as objective response rate of 46.2% and clinical benefit of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature.

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Single-Center Experience. Clinical Characterization, Mutational Landscape, and Clinical Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation Intensive Therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seems to have a more favorable prognosis.

Linfoma anaplásico de grandes células T associado ao uso de implantes (BIA-ALCL): relato de caso / Implant-associated anaplastic large T-cell lymphoma (BIA-ALCL): case report

Reconhecido pela Organização Mundial de Saúde em 2016, o linfoma anaplásico de grandes células associado ao implante mamário (BIA-ALCL) é um subtipo incomum de linfoma não Hodgkin de células T, que se desenvolve após a inserção de próteses mamárias. A doença é uma afecção rara que afeta cerca de uma a cada 30.000 pessoas com implante mamário texturizado. As principais manifestações clínicas são o seroma tardio, assimetria mamária, massa e contratura capsular, com frequência mais elevada do primeiro. O explante da prótese com capsulectomia total pode ser suficiente para tratar o ALCL, com ressecções estendidas a locais adjacentes, quando necessário. Entretanto, em alguns casos, é realizada a radioterapia e/ou quimioterapia adjuvante. Conclui-se que, para um diagnóstico precoce e um tratamento efetivo, mulheres com seroma de aparecimento súbito e tardio deverão realizar exames complementares para a exclusão dessa afecção, mesmo com tempo inferior à média de desenvolvimento, que é de cerca de 10,6 anos.

Recognized by the World Health Organization in 2016, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon subtype of T-cell non-Hodgkin lymphoma that develops after the insertion of breast implants. The disease is a rare condition that affects approximately one in every 30,000 people with textured breast implants. The main clinical manifestations are late seroma, breast asymmetry, mass, and capsular contracture, with a higher frequency of the former. Explantation of the prosthesis with total capsulectomy may be sufficient to treat ALCL, with resections extended to adjacent sites when necessary. However, in some cases, adjuvant radiotherapy and/or chemotherapy is performed. It is concluded that, for an early diagnosis and effective treatment, women with sudden and late-onset seroma should undergo additional tests to exclude this condition, even with a shorter development time than the average, which is around 10.6 years.

Thyroid abnormalities in patients with Hodgkin lymphoma: The importance of close surveillance.

INTRODUCTION: Survival in paediatric patients with Hodgkin lymphoma (HL) has increased over the last decades. However, these patients are at increased risk of developing late thyroid sequelae due to the treatment with irradiation and alkylating agents. METHODS: We conducted an observational and retrospective study in patients with a diagnosis of HL between 2007 and 2022, in a hospital that is a paediatric oncology reference centre, through the review of electronic health records. We collected data on demographic (age, sex), clinical, radiological and histopathological variables, the dosage of alkylating agents and radiotherapy (RT) and on thyroid disorders using Microsoft Excel. The data analysis was conducted with SPSS version 17, using the Fisher exact test for qualitative data, a nonparametric test for quantitative data and Kaplan-Meier curves. RESULTS: Sixty patients received a diagnosis of HL from 2007 to 2022. The median duration of follow-up was 78.5 months. There were 4 detected cases of hypothyroidism, 5 of thyroid nodules and 1 of subclinical hyperthyroidism. Treatment with RT was significantly associated with the development of hypothyroidism (P= .026), thyroid nodules (P= .01) and thyroid disease overall (P= .003). We estimated that the risk of thyroid disease increased 8-fold with each additional Grey received (hazard ratio, 1.081; 95% CI, 1.014-1.152; P= .017). CONCLUSION: Hodgkin lymphoma patients treated with RT are at increased risk of late thyroid disorders, mainly hypothyroidism and malignancy. This risk is greater the higher the RT dosage and the longer the follow-up. We did not find evidence of an association between the use of alkylating agents and an increase in the risk of thyroid disease.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [Artículo traducido] Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

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)

Linfoma extranodal de epiglotis en un paciente con recaída de leucemia linfoide aguda de células T. Presentación de un caso

Los linfomas localizados en la laringe representan un porcentaje muy bajo dentro de los comprendidos en los tumores de cabeza y cuello en la edad pediátrica. El linfoma no Hodgkin es el subtipo más comúnmente reportado en la literatura, el cual dependiendo de su etiología y extensión determinará el pronóstico del paciente. La certeza del diagnóstico, que suele ser muy difícil de alcanzar, se confirma generalmente mediante una biopsia de tejido. En la actualidad, no hay reportes de la literatura acerca de linfomas leucemoides diseminados a laringe. Se presenta el caso de un paciente masculino adolescente de 17 años con diagnóstico de una leucemia linfoide aguda con recaída extra-nodal en la laringe por falla en el esquema quimioterapéutico instaurado.

Lymphomas located at the level of the larynx represent a very low percentage of head and neck tumors in the pediatric age group. Non-Hodgkin's lymphoma is the most reported subtype in the literature, which depending on its etiology and extension will determine the patient's prognosis. Diagnostic certainty, which is often very difficult to achieve, is usually confirmed by tissue biopsy. At present, there are no reports in the literature about leukemoid lymphomas disseminated to the larynx. We present the case of a 17-year-old adolescent male patient diagnosed with acute lymphoid leukemia with extranodal relapse in the larynx due to failure of the chemotherapeutic regimen.

Linfoma de células B primario de mama en una paciente con sida. Presentación de un caso y revisión de la literatura / Primary B-cell lymphoma of the breast in an AIDS patient. Case report and literature review

Los LNH constituyen la segunda neoplasia más frecuente en pacientes con VIH. Estas neoplasias están ligadas a la inmunodeficiencia, suelen ser de período de latencia prolongado y más frecuentes en hombres. Más del 95% de estas neoplasias son de fenotipo B, de alto grado de malignidad, extranodales y representan la causa de muerte en un 12% al 16% de los casos. El linfoma no Hodgkin primitivo de mama (LPM) es una entidad infrecuente, que representa el 2,2% de todos los linfomas extranodales y el 0,5% de todas las neoplasias malignas de la mama. Se presenta una mujer con sida y linfoma primario de mama. (AU)

NHL is the second most common neoplasm in patients with HIV. It is linked to immunodeficiency, tends to have a long latency period and is more common in men. More than 95% of these neoplasms are of phenotype B, high-grade, extranodal and are the cause of death in 12% to 16% of cases. Primitive non-Hodgkin lymphoma of the breast is a rare entity, accounting for 2.2% of all extranodal lymphomas and 0.5% of all breast malignancies. A woman with AIDS and primary breast lymphoma is presented. (AU)

Enfermedad de Castleman: un enfoque integral a propósito de un reporte de caso / Castleman's Disease: A Comprehensive Approach Regarding a Case Report

Resumen Se presenta el caso clínico de una paciente del sexo femenino, de 30 años, con adenopatías supraclaviculares y axilares ipsilaterales, quien fue sometida a biopsia excisional con posterior estudio. El análisis histopatológico de la muestra de tejido resecado reveló una serie de características distintivas asociadas con la enfermedad de Castleman variante hialinovascular. La presentación de este caso no solo proporciona información detallada sobre la evolución clínica de la paciente, sino que también sirve como base para ilustrar los aspectos clave del diagnóstico histopatológico y las implicaciones inmunohistoquímicas en la enfermedad de Castleman. Además de hacer una revisión de tema respecto a esta patología poco común, en la cual los informes de casos son fundamentales para aumentar la comprensión de su variabilidad clínica y su abordaje diagnóstico, ilustrando los desafíos en el diagnóstico diferencial y como deben abordarse los mismos.

Abstract The clinical case of a 30-year-old female patient with supraclavicular and ipsilateral axillary lymphadenopathy who underwent excisional biopsy with subsequent study is presented. Histopathological analysis of the resected tissue sample revealed a series of distinctive features associated with hyalinevascular variant Castleman disease. The presentation of this case not only provides detailed information about the clinical evolution of the patient, but also serves as a basis to illustrate Key aspects of histopathological diagnosis and immunohistochemical implications in Castleman disease. In addition to making a review of the topic regarding this rare pathology in which case reports are essential to increase the understanding of its clinical variability and its diagnostic approach, illustrating the challenges in differential diagnosis and how they should be addressed.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Evolução da Captação Miocárdica de 18F-FDG em Paciente com Diagnóstico de Cardiotoxicidade / Progression of Myocardial 18F-FDG Uptake in a Patient with Cardiotoxicity

Resumo O objetivo deste relato é mostrar a evolução da cardiotoxicidade (CTX) por quimioterápicos em paciente com linfoma por exames de imagens, destacando a importância da captação miocárdica de flúor-18 fluordeoxiglicose (18F-FDG) pela tomografia por emissão de pósitrons, acoplada à tomografia computadorizada (PET/CT). Feminino, 43 anos, com linfoma uterino, submetida a histerectomia, três esquemas de quimioterapia (QT), sucessivamente, e radioterapia. Apresentou episódios de insuficiência cardíaca aguda dois anos após QT. Ecocardiograma mostrou redução da fração de ejeção do ventrículo esquerdo (FEVE). Análise retrospectiva do 18F-FDG PET/CT observou elevação da captação miocárdica em todos os exames durante o seguimento oncológico. Apesar da remissão oncológica, a paciente desenvolveu IC com FEVE reduzida. Durante a QT, ocorreu aumento difuso e significativo da captação miocárdica de 18F-FDG, que precedeu a queda do desempenho cardíaco, e pareceu refletir alterações metabólicas nos cardiomiócitos relacionadas à CTX. A análise da captação miocárdica de 18F-FDG modificaria o desfecho cardiológico da paciente? Esse questionamento é relevante, visto que outros pacientes podem se beneficiar desse método como marcador precoce de CTX. Os exames de imagem são imprescindíveis no acompanhamento de pacientes com risco de CTX. O ecocardiograma permanece como principal auxílio diagnóstico, porém o 18F-FDG PET/CT pode estar surgindo como uma poderosa ferramenta para um diagnóstico mais precoce dessa condição clínica.

Abstract The objective of this case report was to present the progression of chemotherapy-induced cardiotoxicity in a patient with lymphoma, highlighting the importance of myocardial fluor-18-fluorodeoxyglucose (18F-FDG) uptake by positron emission tomography coupled with computed tomography (PET/CT). 43-year-old female patient with uterine lymphoma, who underwent hysterectomy followed by three chemotherapy regimens and radiotherapy. The patient had episodes of acute heart failure two years after chemotherapy. Echocardiogram revealed a reduction in left ventricular ejection fraction (LVEF). A retrospective analysis of 18F-FDG PET/CT showed an increase in myocardial uptake in all tests performed during oncologic treatment. Despite disease remission, the patient developed heart failure with reduced LVEF. During chemotherapy, there was a diffuse, significant increase in myocardial 18F-FDG uptake, which preceded the decrease in myocardial performance and seemed to reflect metabolic changes in cardiomyocytes, related to cardiotoxicity. Would an analysis of myocardial 18F-FDG uptake yield a different cardiac outcome in this patient? This question is relevant, considering that other patients may benefit from the use of PET as an early marker of cardiotoxicity. Imaging tests are essential in the follow-up of patients at risk of cardiotoxicity. Although echocardiography remains the main imaging test in the diagnosis of cardiotoxicity, 18F-FDG PET/CT may be a powerful tool for the early diagnosis of this condition.

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.

Avaliação das manifestações clínicas e microscópicas dos linfomas em glândulas salivares maiores / Assessment of clinical and microscopic manifestations of lymphomas in major salivary glands

Os subtipos de linfomas não Hodgkin representam 2,8% de todos os novos casos de câncer no mundo, sendo o terceiro grupo mais comum de neoplasias malignas da região de cabeça e pescoço. As glândulas salivares maiores representam o terceiro sítio extranodal mais acometido pelo linfoma na região da cabeça e pescoço; entretanto, nas glândulas salivares maiores é muito raro, representando aproximadamente 1,7­3,1% de todas as neoplasias das glândulas salivares, acometendo a maioria dos casos as glândulas parótidas (79%), seguidas pelas glândulas submandibulares (18%) e sublinguais (1%). Os subtipos mais comuns são linfoma do tecido linfoide associado à mucosa (MALT), o linfoma folicular (FL) e o linfoma difuso de grandes células B (DLBCL), e a frequência destas neoplasias está associado com a ocorrência simultânea de condições sistêmicas que predispõem ao desenvolvimento de neoplasias linfoides como a Síndrome de Sjögren (SS). Entretanto, a literatura sobre linfomas em glândulas maiores permanece muito escassa e impede que conheçamos de forma apropriada as características destes pacientes. Assim, o objetivo deste estudo é avaliar as manifestações clínicas e microscópicas dos linfomas em glândulas salivares maiores. Para isto, foram recuperados de forma retrospectiva dos arquivos de patologia de algumas instituições todos os casos diagnosticados como linfomas acometendo estes sítios anatômicos. Foram coletados os dados clínicos referentes ao sexo, idade, localização, apresentação clínica, tempo de evolução, status, estadiamento e ocorrência da SS, e as informações histopalógicas foram coletadas de blocos de parafina e lâminas em hematoxilina e eosina e imuno-histoquímicas acessíveis. Os resultados obtidos foram avaliados de forma descritiva. As séries compreenderam de 7 casos de linfomas em glândula sublingual, 16 casos em glândula submandibular e 12 casos em glândula parótida. Clinicamente, os linfomas apresentam-se como aumento de volume assintomático, sendo os subtipos mais frequentes os de células B maduras de baixo grau (MALT, FL, MCL), mas subtipos de alto grau também foram observados (LDGCB, SOE). Dois pacientes, um de linfoma de células do manto (LCM) e outro de LDGCB,SOE em glândula sublingual apresentaram como doença disseminada, e apenas três casos de linfoma MALT em glândula parótida apresentam a SS. O tratamento dependeu do microscópico e estágio do tumor, variando de cirurgia, regimes quimioterápicos com R-CHOP e radioterapia. O prognóstico foi favorável principalmente para os casos de baixo grau (MALT,FL), e apenas dois pacientes de sublingual (LDGCB,SOE, MCL) e três de submandibular (LDGCB,SOE, linfoma plasmablastico e MALT) faleceram após o diagnóstico. Neste estudo concluímos que os linfomas em glândulas salivares maiores são afetados principalmente por neoplasias de células B maduras de baixo grau (MALT, FL, MCL) e esses pacientes devem passar por uma avaliação sistêmica criteriosa para determinar se a doença se trata de uma neoplasia primária ou disseminada.

Non-Hodgkin's lymphomas account for 2.8% of all new cancer cases worldwide and are the third most common group of malignant neoplasms in the head and neck region. The major salivary glands represent the third most common extranodal site affected by lymphoma in the head and neck region; however, in the major salivary glands it is very rare, representing approximately 1.7-3.1% of all salivary gland neoplasms, affecting most cases in the parotid glands (79%), followed by the submandibular glands (18%) and sublingual glands (1%). The most common subtypes are mucosa- associated lymphoid tissue lymphoma (MALT), follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), and the frequency of these neoplasms is associated with the simultaneous occurrence of systemic conditions that predispose to the development of lymphoid neoplasms such as Sjögren's Syndrome(SS). However, the literature on lymphomas in major glands remains very scarce and prevents us from properly understanding the characteristics of these patients. Therefore, the aim of this study was to evaluate the clinical and microscopic manifestations of lymphomas in the major salivary glands. To this end, all cases diagnosed as lymphomas affecting these anatomical sites were retrospectively retrieved from the pathology archives of a number of institutions. Clinical data was collected on gender, age, location, clinical presentation, time of evolution, status, staging and occurrence of SS, and histopathological information was collected from paraffin blocks and slides in hematoxylin and eosin and accessible immunohistochemistry. The results obtained were evaluated descriptively. The series comprised 7 cases of lymphomas in the sublingual gland, 16 cases in the submandibular gland and 12 cases in the parotid gland. Clinically, the lymphomas presented as asymptomatic enlargement, with the most frequent subtypes being low-grade mature B-cells (MALT, FL, MCL), but high- grade subtypes were also observed (LDGCB, SOE). Two patients, one with mantle cell lymphoma (MCL) and the other with LDGCB,SOE in the sublingual gland presented with disseminated disease, and only three cases of MALT lymphoma in the parotid gland presented with SS. Treatment depended on the microscopic subtype and stage of the tumor, ranging from surgery to chemotherapy regimens with R-CHOP and radiotherapy. Prognosis was mainly favorable for low-grade cases (MALT,FL), and only two sublingual patients (LDGCB,SOE, MCL) and three submandibular patients (LDGCB,SOE, plasmablastic lymphoma and MALT) died after diagnosis. In this study we conclude that lymphomas in the major salivary glands are mainly affected by low- grade mature B-cell neoplasms (MALT, FL, MCL) and these patients should undergo a careful systemic evaluation to determine whether the disease is a primary or disseminated neoplasm.

Linfoma vitreorretiniano: un reto diagnóstico / Vitreoretinal lymphoma: A diagnostic challenge

Se presenta el caso de un varón de 66años remitido por uveítis posterior con edema macular quístico recurrente en relación con posible enfermedad de Lyme previamente tratada. Debido a la recurrencia del edema macular pese al tratamiento corticoideo sistémico y local con dexametasona intravítrea, se instaura tratamiento biológico con adalimumab. Durante el seguimiento el paciente desarrolla lesiones subretinianas bilaterales compatibles con linfoma vitreorretiniano, por lo que se realiza vitrectomía, confirmando el diagnóstico de linfoma de célulaB grande.Se inicia tratamiento con quimioterapia sistémica con BRAM (carmustina, metotrexato, ara-C y rituximab), con buena respuesta. Dos años después, el paciente permanece sin recurrencias a nivel ocular ni sistémico.El linfoma vitreorretiniano es un tipo poco frecuente de linfoma primario del sistema nervioso central. El diagnóstico se ve frecuentemente retrasado debido a la inespecificidad de su sintomatología, que simula una uveítis posterior crónica; de ahí la importancia de la sospecha diagnóstica. (AU)

A 66-year-old man with posterior uveitis and recurrent cystic macular edema related to possible previously treated Lyme disease is presented. Due to the recurrence of macular edema despite systemic and local corticosteroid treatment with intravitreal dexamethasone, biological treatment with adalimumab was established. During follow-up, the patient developed bilateral subretinal lesions compatible with vitreoretinal lymphoma, so vitrectomy was performed, confirming the diagnosis of large B-cell lymphoma.Treatment with systemic chemotherapy with BRAM (carmustine, metotrexate, ara C, and rituximab) was started with a good answer. Two years later, the patient remains without ocular or systemic recurrences.Vitreoretinal lymphoma is a rare type of primary central nervous system lymphoma. The diagnosis is frequently delayed due to the nonspecific symptoms, which mimic chronic posterior uveitis, hence the importance with a diagnostic suspicion. (AU)

Linfoma difuso de célulasB grandes primario de cérvix. A propósito de un caso / Primary diffuse large Bcell lymphoma of the cervix: Clinical case

Introducción: La afectación primaria del tracto genital femenino por linfoma no Hodgkin es muy poco frecuente, por lo que no existe un consenso sobre el tratamiento, y por ello presentamos este caso clínico y el tratamiento realizado, así como el pronóstico de nuestra paciente. Hallazgos clínicos: La paciente presentada es una mujer de 72años que consulta por hemorragia vaginal. Diagnóstico Se diagnostica de linfoma no Hodgkin extranodal primario de cérvix de inmunofenotipoB de alto grado citológico y elevado índice proliferativo. Intervenciones terapéuticas y resultados: El tratamiento de elección fue únicamente quimioterápico. Esta paciente ha presentado una supervivencia libre de enfermedad de 5años. Actualmente se encuentra en seguimiento mediante la realización de controles analíticos anuales. Conclusión: Los síntomas de este tipo de tumor son altamente inespecíficos y la citología es frecuentemente negativa, por lo que es necesario recurrir a la biopsia. La inmunohistoquímica resulta fundamental tanto para el diagnóstico como para el pronóstico. Existen múltiples técnicas de imagen empleadas tanto para estudio de extensión como para seguimiento, destacando el papel del FDG-PET. Actualmente parece que el tratamiento más recomendable es la pauta quimioterápica R-CHOP seguida de radioterapia. El pronóstico en general es bueno, con hasta un 80% de supervivencia a los 5años.(AU)

Introduction: Primary involvement of the female genital tract by non-Hodgkin lymphoma is very rare, so there is no consensus on treatment, and for this reason we present this clinical case and the treatment performed, as well as the prognosis of our patient. Clinical findings: The patient presented is a 72-year-old woman who consulted for vaginal bleeding. Diagnosis: Primary extranodal non-Hodgkin lymphoma of the cervix with immunophenotypeB of high cytological grade and high proliferative index was diagnosed. Therapeutic interventions and results: The treatment of choice was chemotherapy only. This patient has presented a disease-free survival of 5years. It is currently being monitored by carrying out annual analytical controls. Conclusion: The symptoms of this type of tumor are highly non-specific, as well as cytology is frequently negative, which is why it is necessary to resort to biopsy. Immunohistochemistry is essential for both diagnosis and prognosis. There are multiple imaging techniques used for both extension study and follow-up, highlighting the role of FDG-PET. It currently seems that the most recommendable treatment is the R-CHOP chemotherapy regimen followed by radiotherapy.The prognosis is generally good, with up to 80% survival at 5years.(AU)

Linfadenopatías generalizadas como manifestación inicial de lupus eritematoso sistémico: a propósito de un caso clínico

La presencia de linfadenopatías generalizadas se ha asociado de forma usual con lupus eritematoso sistémico (LES), sin embargo, no es usual encontrar este hallazgo como manifestación inicial de la enfermedad. Existen múltiples diagnósticos diferenciales que incluyen la linfadenitis necrotizante histiocítica de Kikuchi, la enfermedad de Castleman, infecciones y el linfoma cuando se presenta este hallazgo como síntoma inicial de LES. Presentamos el caso de un hombre de 56 años que se presentó con 2 meses de linfadenopatía generalizada sin datos al examen o antecedentes que sugirieran diagnóstico de LES; se sospechó inicialmente linfoma o enfermedad infecciosa y se realizó un estudio exhaustivo incluido biopsia de ganglio cervical. La investigación de laboratorio finalmente reveló leucopenia, proteinuria significativa, ANA y anti-dsDNA positivos e hipocomplementemia, lo que confirma el diagnóstico de enfermedad autoinmune tipo LES. Este caso ilustra la importancia de reconocer esta forma de presentación inusual, dado que se trata de una enfermedad potencialmente fatal.

The presence of generalized lymphadenopathy has usually been associated with systemic lupus erythematosus (SLE), however, it is not usual to find this finding as an initial manifestation of the disease. There are multiple differential diagnoses that include Kikuchi histiocytic necrotizing lymphadenitis, Castleman disease, infections and lymphoma when this finding is presented as an initial symptom of SLE. We present the case of a 56-year-old man who presented with 2 months of generalized lymphadenopathy without examination findings or history suggesting a diagnosis of SLE; Lymphoma or infectious disease was initially suspected and an exhaustive study was performed, including cervical lymph node biopsy. Laboratory investigation finally revealed leukopenia, significant proteinuria, positive ANA, positive anti-dsDNA, and hypocomplementemia, confirming the diagnosis of SLE-type autoimmune disease. This case illustrates the importance of recognizing this unusual presentation, given that it is a potentially fatal disease.

Síndrome de dificultad respiratoria aguda por Mycobacterium tuberculosis de rápido crecimiento en una mujer con virus linfotrópico T humano tipo I-II / Acute respiratory distress syndrome due to rapidly growing Mycobacterium tuberculosis in a woman with human T-lymphotropic virus type I-II

La tuberculosis es una infección de distribución mundial con una alta morbimortalidad en países subdesarrollados. Presentamos el caso de una mujer de 55 años con cuadro de dos meses de adenomegalias cervicales, pérdida de peso y fiebre con posterior disnea de esfuerzo progresiva. Ingresó por urgencias en falla ventilatoria y hallazgos radiológicos compatibles con síndrome de dificultad respiratoria aguda (SDRA) requiriendo ventilación mecánica invasiva. Se demostró infección por M. tuberculosis por PCR en tiempo real GeneXpert MTB/RIF Ultra y en cultivo de medio líquido de esputo, con crecimiento en tiempo menor a tres días. La biopsia de las adenomegalias confirmó linfoma de células T periférico asociado a infección por virus linfotrópico T humano tipo I-II, presentando una evolución tórpida a pesar del esquema quimioterapéutico.

Tuberculosis is a globally distributed infection with high morbidity and mortality in underdeveloped countries. We present the case of a 55-year-old woman with a 2-month history of cervical lymph nodes, weight loss, and fever with subsequent progressive exertional dyspnea. She was admitted to the emergency department with ventilatory failure and radiological findings compatible with acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. M. tuberculosis infection was proved by a real-time PCR GeneXpert MTB/RIF Ultra and in culture of sputum liquid medium, with growth in less than 3 days. The biopsy of the lymph nodes revealed peripheral T-cell lymphoma associated with infection by human T-lymphotropic virus type I-II, presenting a torpid evolution despite the chemotherapy regimen.

Causa inusual de obstrucción traqueal: linfoma de células B no Hodgkin

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.