RESUMO
Retrosternal goitre is not an uncommon entity owing to various reasons - ignorance, fear, lack of access to safe surgical technique, incomplete thyroid surgery. Retrosternal goitre could have varied presentations, especially in cases with prior thyroid surgery. Fifty-three-year-old female with history of thyroid surgery 20 years back presented with a large neglected anterior neck swelling. Computed tomography imaging revealed the rare entity of an isolated mediastinal goitre type 3 with no communication with the cervical thyroid gland. Careful evaluation of computed tomography and pathology indicated the need for extra - cervical approach. Patient underwent total thyroidectomy and mediastinal goitre excision via cervical and median sternotomy approach. Post operative histopathology revealed benign adenomatous goitre. CT imaging of retrosternal goitre is of primary importance along with appropriate CT grading. Mediastinal seeding of thyroid goitre could occur in cases with prior thyroid surgery. Extra cervical approaches for primary mediastinal goitre are recommended. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04663-2.
RESUMO
In this study, the health impacts of improving access to treatment with axicabtagene ciloleucel (axi-cel) was assessed in patients with relapsed/refractory diffuse large B-cell lymphoma after ≥2 lines of therapy in Spain. A partitioned survival mixture cure model was used to estimate the lifetime accumulated life years gained (LYG) and quality-adjusted life years (QALYs) per patient treated with axi-cel versus chemotherapy. Efficacy data were extracted from the ZUMA-1 trial for axi-cel and from the SCHOLAR-1 study for chemotherapy. In the base case, the incremental outcomes of axi-cel versus chemotherapy were evaluated in a cohort of 187 patients treated with CAR T-cell therapies, as reported by the "Spanish National Health System Plan for Advanced Therapies", and in the alternative scenario in the full eligible population based on epidemiological estimates (n = 490). Taking those currently treated with axi-cel, compared with chemotherapy, axi-cel provided an additional 1341 LYGs and 1053 QALYs. However, when all eligible patients (n = 490) were treated, axi-cel provided an additional 3515 LYs and 2759 QALYs. Therefore, if all eligible patients were treated with axi-cel rather than those currently treated as per the registry (n = 187), there would have been an additional 303 patients treated, resulting in an additional 2173 LYGs and 1706 QALYs in total. The lack of access in Spain has led to a loss of a substantial number of LYGs and QALYs, and efforts should be made to improve access for all eligible patients.
RESUMO
INTRODUCTION: Lymphoma tissue biopsies cannot fully capture genetic features due to accessibility and heterogeneity. We aimed to assess the applicability of circulating tumor DNA (ctDNA) for genomic profiling and disease surveillance in classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and diffuse large B-cell lymphoma (DLBCL). METHODS: Tumor tissue and/or liquid biopsies of 49 cHLs, 32 PMBCLs, and 74 DLBCLs were subject to next-generation sequencing targeting 475 genes. The concordance of genetic aberrations in ctDNA and paired tissues was investigated, followed by elevating ctDNA-based mutational landscapes and the correlation between ctDNA dynamics and radiological response/progression. RESULTS: ctDNA exhibited high concordance with tissue samples in cHL (78%), PMBCL (84%), and DLBCL (78%). In cHL, more unique mutations were detected in ctDNA than in tissue biopsies (P < 0.01), with higher variant allele frequencies (P < 0.01). Distinct genomic features in cHL, PMBCL, and DLBCL, including STAT6, SOCS1, BTG2, and PIM1 alterations, could be captured by ctDNA alone. Prevalent PD-L1/PD-L2 amplifications were associated with more concomitant alterations in PMBCL (P < 0.01). Moreover, ctDNA fluctuation could reflect treatment responses and indicate relapse before imaging diagnosis. CONCLUSIONS: Lymphoma genomic profiling by ctDNA was concordant with that by tumor tissues. ctDNA might also be applied in lymphoma surveillance.
RESUMO
Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.
Assuntos
Doença de Hodgkin , Linfoma Difuso de Grandes Células B , Neoplasias do Mediastino , Humanos , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/terapia , Estudos Retrospectivos , Doença de Hodgkin/patologia , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Adulto Jovem , Idoso , Estudos de Coortes , Resultado do Tratamento , Seguimentos , Prognóstico , Adolescente , Síndrome da Veia Cava Superior/etiologia , Intervalo Livre de Progressão , Taxa de SobrevidaRESUMO
Pancreatitis is an inflammatory pancreatic disease; common etiologies include infection, anatomic abnormalities, biliary, inborn errors of metabolism, trauma, and rarely malignancy. Primary mediastinal large B-cell lymphoma commonly presents in younger women with principally mediastinal involvement. We report the first documented case of a pediatric patient presenting with acute pancreatitis secondary to metastatic primary mediastinal large B-cell lymphoma. Since diagnosis, the patient underwent a combination of chemotherapy and immunotherapy treatments, and the tumor burden had decreased significantly. Malignancy is a rare documented presentation of acute pancreatitis in the pediatric population, and it should be included in a broad differential diagnosis.
RESUMO
The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Neoplasias do Mediastino , Rituximab , Humanos , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/terapia , Neoplasias do Mediastino/tratamento farmacológico , Adolescente , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/patologia , Masculino , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Vincristina/administração & dosagem , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Doxorrubicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapiaRESUMO
BACKGROUND: Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high-dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. METHODS: The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first-line cisplatin-based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression-free survival and overall survival were analyzed using the Kaplan-Meier method. Medians with 95% conï¬dence intervals were also calculated along with 2-year probabilities. RESULTS: The median age at HDCT was 30 years (range, 18-61 years). With a median follow-up of 4.7 years (range, 1-14 years), the 2-year progression-free survival rate was 31% (95% confidence interval, 16%-47%), and the 2-year overall survival rate was 35% (95% confidence interval, 19%-52%). At last follow-up, nine patients (28%) remained without evidence of disease, including two platinum-refractory patients and two patients who were receiving HDCT as third-line therapy. There were three treatment-related deaths. CONCLUSIONS: Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum-refractory and third-line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.
RESUMO
OBJECTIVES: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. MATERIAL AND METHODS: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). RESULTS: To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). CONCLUSION: This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans.
RESUMO
PURPOSE: An accurate diagnosis of thymic malignancies is important, but challenging due to the broad range of differential diagnoses. This study aims to evaluate the efficacy of PET/CT and tumor markers for diagnosing thymic malignancies. METHODS: Patients admitted to our department between January 2012 and December 2021 with primary anterior mediastinal tumors were retrospectively evaluated. We evaluated the relationship between the maximum standardized uptake value (SUVmax), tumor markers, and pathological diagnosis in four groups: thymic carcinoma, thymoma, lymphoma, and others. RESULTS: In total, 139 patients were included in this study. The SUVmax was significantly higher in lymphoma, thymic carcinoma, and thymoma, in that order. The cytokeratin 19 fragment (CYFRA 21-1) was significantly higher in thymic carcinoma than in the other groups. An ROC curve analysis indicated that the optimal cut-off values of SUVmax for thymic carcinoma plus lymphoma and CYFRA 21-1 for thymic carcinoma were 7.97 (AUC = 0.934) and 2.95 (AUC = 0.768), respectively. Using a combination of cut-off values (SUVmax = 8, CYFRA 21-1 = 3), the accuracy rate for diagnosing thymic carcinoma was 91.4%. CONCLUSIONS: The SUVmax and CYFRA 21-1 levels are significant indicators for the diagnosis of thymic carcinoma. Combining these indicators resulted in a more accurate diagnosis of thymic malignancies, which could facilitate the decision-making process for determining the optimal treatment strategies.
Assuntos
Biomarcadores Tumorais , Queratina-19 , Linfoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Timoma , Neoplasias do Timo , Humanos , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/diagnóstico , Diagnóstico Diferencial , Masculino , Timoma/diagnóstico por imagem , Timoma/diagnóstico , Feminino , Linfoma/diagnóstico por imagem , Linfoma/diagnóstico , Linfoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Adulto , Antígenos de Neoplasias , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
The safety and efficacy of CAR T-cell therapy are unknown in pediatric and adolescent patients with relapsed or refractory primary mediastinal large B-cell lymphoma (R/R PMBCL) which is associated with dismal prognosis. Here, we present a case report of a 16-year-old patient with R/R PMBCL treated with lisocabtagene maraleucel including correlative studies. Patient achieved complete response at 6 months without cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. She only experienced mild cytopenias, requiring filgrastim once. This report highlights the safety and efficacy of lisocabtagene maraleucel in this population, warranting prospective studies to improve clinical outcomes.
RESUMO
Undifferentiated carcinoma (or poorly differentiated carcinoma) of the mediastinum is a relatively rare pathological variant of anterior mediastinal tumors. Pathologists usually use the term to describe an epithelial tumor with no histological features that enable the identification of its site of origin. Invasion of adjacent vital cardiopulmonary structures is among the most problematic complications of anterior mediastinal masses. We report a case of a 60-year-old male presenting with easy fatiguability, significant weight loss, and chest pain. A CT scan of the chest revealed a large anterior mediastinal mass, compression of the main pulmonary artery, and a large pericardial effusion. The patient underwent pericardiocentesis, emergent radiotherapy, and platinum-based chemotherapy. His condition dramatically improved, and he was subsequently discharged home for further follow-up.
RESUMO
The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients.
RESUMO
BACKGROUND: Treatment with CHOP-based chemotherapy with consolidative radiotherapy (CRT) for primary mediastinal B cell lymphoma (PMBCL) has been the standard approach in the pre-rituximab era. Overtreatment with CRT for patients who may have already been cured by primary immunochemotherapy in the rituximab era is a significant concern due to the long-term toxicity associated with radiotherapy. Positron emission tomography (PET) may help to identify patients who may not benefit from further CRT. METHODS: We conducted a retrospective review of patients treated at the Royal Marsden Hospital between 2003 and 2020 for PMBCL to assess CRT use and survival outcomes. RESULTS: Forty-three patients were identified, with 95% of the patients receiving R-CHOP. CRT was given in 5 patients. Five-year event-free survival was 79% (95% confidence interval: 64%-89%) and 5-year overall survival was 88% (95% confidence interval: 73%-95%). Seven of 9 patients with DS4 did not receive CRT and instead monitored with serial PET scans. None of these 7 patients relapsed in the mediastinum. CONCLUSION: CRT may be omitted in patients with a negative end of treatment PET scans; however, careful observation may also obviate the need for CRT in PET positive patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Humanos , Rituximab/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Ciclofosfamida/uso terapêutico , Vincristina/efeitos adversos , Prednisona/efeitos adversos , Doxorrubicina/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológicoRESUMO
We report a fatal case of a 26-year-old nulliparous woman who presented with an anterior mediastinal mass in her late pregnancy. She had complained of a progressively increasing neck swelling and occasional dry cough in the early second trimester, which was associated with worsening dyspnoea, reduced effort tolerance and orthopnoea. Ultrasound of the neck showed an enlarged lymph node, and chest X-ray revealed mediastinal widening. At 35 weeks' gestation, the patient was referred to a tertiary centre for a computed tomography (CT) scan of the neck and thorax under elective intubation via awake fibreoptic nasal intubation as she was unable to lie flat. However, she developed sudden bradycardia, hypotension and desaturation soon after being positioned supine, which required resuscitation. She succumbed after 3 days in the intensive care unit. An autopsy revealed a large anterior mediastinal mass extending to the right supraclavicular region, displacing the heart and lungs, encircling the superior vena cava and right internal jugular vein with tumour thrombus extending into the right atrium. Histopathology examination of the mediastinal mass confirmed the diagnosis of a primary mediastinal large B-cell lymphoma. This report emphasizes the severe and fatal outcome resulting from the delay and misinterpretation of symptoms related to a mediastinal mass.
Assuntos
Doenças do Mediastino , Veia Cava Superior , Humanos , Feminino , Gravidez , Adulto , Tomografia Computadorizada por Raios X , RadiografiaRESUMO
A 39-year-old woman with myotonic dystrophy (DM) presented with syncope and was diagnosed with primary mediastinal large B-cell lymphoma, clinical stage IA. PET-CT revealed an upper mediastinal mass with high FDG uptake (SUVmax, 14.8). She had muscle weakness associated with DM, but her performance status was preserved. She was treated with 6 cycles of dose-adjusted EPOCH-R therapy and localized irradiation for the residual mass, without severe adverse events or recurrence of syncope. Patients with DM should be monitored for cardiac events and muscle weakness when undergoing lymphoma treatment.
Assuntos
Linfoma de Células B , Distrofia Miotônica , Humanos , Feminino , Adulto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Distrofia Miotônica/complicações , Debilidade Muscular , SíncopeRESUMO
A 28 -year-old man presented to our hospital with a rapidly growing nodule in the left cervical and bilateral axilla with a history of loss of weight. He has been experiencing a nodule in her right cervical since two years ago and had done FNAC and diagnosed extrapulmonary tuberculosis (EPTB), on Examination at left cervical colli; mass size 9cm x 7 cm, mobile, Lymphadenopathy at pre auricular size 3cm x 3cm, lymphadenopathy supraclavicular size 1cm x 0,5 cm. bilateral lymphadenopathy Axila size 4cmx 4cmx 2xcm mobile. The other physical exam was normal. Laboratory test Hb 10,4 d/dL, WBC 14.250/ mm3, LED 78 mm/hours, D-dimer 1,81 ug/mL, Fibrinogen 452 mg/dL. HIV test non-reactive. HbsAg and HCV test negative. CT-Scan Thorax: Enlarged Anterior mediastinal Lymph node with a diameter 0f 2.9 cm, right paratracheal with a diameter of 1,2cm and 1,1 cm, and right perihilar with a diameter of 1,3 cm. and the left perihilar diameter 0,9. And hypodense lesion of the spleen measuring 2,3cm x 1,6 cm. The patient underwent a biopsy with pathology biopsy and immunohistochemistry (IHC), CD 20+. CD 3-, CD 30+ CD79a +, MUM1 +, Ki67 80-90% +, CD15-, BCL6+ and BCL 2+. For this patient, we started an R-CHOP regimen (Rituximab 375 mg/m2 (d1), Cyclophopamid 750 mg/m2 (d1), Doxorubicin 50 mg/m2 (d1), Vincristine1,2 mg/m2 (d1) and 1 Prednisone 100 mg (d1-d5). We presented the patient with PMGZL has achieved a complete response, especially with chemotherapy R-CHOP regimens.
Assuntos
Linfadenopatia , Linfoma , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Linfonodos/patologia , Biópsia , Vincristina/uso terapêutico , Doxorrubicina/uso terapêutico , Rituximab/uso terapêutico , Linfoma/patologiaRESUMO
In recent years, lesbian, gay, bisexual, and transgender (LGBT) populations have been gaining acceptance in society. However, very few cases of malignancy in the LGBT population have been reported thus far. We herein report a transgender woman receiving estrogen supplementation who developed primary mediastinal large B-cell lymphoma (PMBCL) and was treated with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) therapy. The patient achieved complete remission after the sixth course of DA-EPOCH-R therapy. To help this LGBT patient continue receiving chemotherapy smoothly on admission, adjusting the hospital environment, such as the allocation of rooms, was essential.
RESUMO
Introduction: Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Materials and methods: Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit. Results: Higher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score. Conclusion: Total RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.
RESUMO
Primary mediastinal seminomas are exceedingly rare tumors, often localized to the anterior mediastinum. They may present with numerous complications, including superior vena cava syndrome, chylothorax, and pericardial effusions. Less commonly, they may present with paraneoplastic encephalitis. In this report we describe a case of a 19-year-old male with no significant past medical history who presented with bilateral hearing loss, progressive neuropathy, and ataxia. Subsequently the patient was found to have mediastinal mass with a high-titer anti-Hu antibody. To our knowledge, only one other case of mediastinal seminoma presenting with anti-Hu antibodies has been described in the literature. In this report, we describe a rare case of mediastinal seminoma, describe treatment options, and discuss additional known cases presenting with paraneoplastic encephalitis.
RESUMO
Since the description of primary mediastinal large B-cell lymphoma (PMBL) as a distinct entity from diffuse large B-cell lymphomas (DLBCL), numerous studies have made it possible to improve their definition. Despite this, this differential diagnosis can be challenging in daily practice. However, in some centers, PMBL may be treated according to a particular regimen, distinct from those used in DLBCL, emphasizing the importance of accurate identification at diagnosis. This study aimed to describe the histological and molecular characteristics of PMBL to improve the accuracy of their diagnosis. Forty-nine cases of PMBL were retrospectively retrieved. The mean age at diagnosis was 39 years (21-83), with a sex ratio of 0.88. All cases presented a fibrous background with diffuse growth of intermediate to large cells with an eosinophil (26/49, 53%) or retracted cytoplasm (23/49, 47%). "Hodgkin-like" cells were observed in 65% of cases (32/49, 65%). The phenotype was: BCL6+ (47/49, 96%), MUM1+ (40/49, 82%), CD30+ (43/49, 88%), and CD23+ (37/49, 75%). Genomic DNAs were tested by next generation sequencing of 33 cases using a custom design panel. Pathogenic variants were found in all cases. The most frequent mutations were: SOCS1 (30/33, 91%), TNFAIP3 (18/33, 54.5%), ITPKB (17/33, 51.5%), GNA13 (16/33, 48.5%), CD58 (12/33, 36.4%), B2M (12/33; 36.4%), STAT6 (11/33, 33.3%) as well as ARID1A (10/33, 30.3%), XPO1 (9/33, 27.3%), CIITA (8/33, 24%), and NFKBIE (8/33, 24%). The present study describes a PMBL cohort on morphological, immunohistochemical, and molecular levels to provide pathologists with daily routine tools. These data also reinforce interest in an integrated histomolecular diagnosis to allow a precision diagnosis as early as possible.