RESUMEN
Objective: To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement. Methods: From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed. Results: Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement (P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions: NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.
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Reordenamiento Génico , Secuenciación de Nucleótidos de Alto Rendimiento , Hibridación Fluorescente in Situ , Linfoma de Células B , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Linfoma de Células B/genética , Linfoma de Células B/diagnóstico , Hibridación Fluorescente in Situ/métodos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Ciclina D1/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Mutación , Proteínas Proto-Oncogénicas c-myc/genéticaRESUMEN
BACKGROUND: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale. METHODS: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10. RESULTS: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms. CONCLUSIONS: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL.
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Medición de Resultados Informados por el Paciente , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Reproducibilidad de los Resultados , Linfoma de Células B/diagnóstico , Calidad de Vida , Anciano de 80 o más Años , Fatiga/etiología , Linfoma no Hodgkin/diagnósticoRESUMEN
Primary pancreatic lymphomas (PPLs) are a subgroup of gastrointestinal (GI) lymphomas. They are an exceedingly rare entity, both in terms of pancreatic malignancies and also extranodal lymphomas. Epidemiological investigations have been challenging to do because of their rarity. This has resulted in a lack of clarity on the clinicopathological characteristics, differential diagnosis, best course of treatment, and prognosis of PPL. Because the clinical signs are frequently non-specific, it can lead to a diagnostic hazard for the unwary physician. Preoperatively, it is imperative to distinguish between adenocarcinoma and PPL, as they present similarly, but have vastly different treatment modalities and prognosis. We herein present a case of an elderly man who presented with obstructive jaundice and was found to have PPL.
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Neoplasias Pancreáticas , Humanos , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Ictericia Obstructiva/etiología , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Diagnóstico Diferencial , Anciano , Tomografía Computarizada por Rayos X , Páncreas/patologíaRESUMEN
A 72-year-old male was referred with a 2-week history of diplopia. Following magnetic resonance imaging, an area of abnormal signal intensity was observed along the lateral ventricle, without any unusual findings at other sites. Cerebrospinal fluid cytology revealed abnormal lymphocytes with atypia, which were positive for CD20 and light-chain restriction, as detected by surface marker analysis, leading to a diagnosis of primary meningeal B-cell lymphoma. The patient underwent chemoradiotherapy and achieved a remission. While meningeal lymphoma is a rare occurrence, pathological tissue biopsy is considered the gold-standard diagnostic method. However, obtaining a biopsy sample from the tumor site can be challenging. In this case report, cytology and flow cytometry played a vital role in the diagnosis of meningeal lymphoma.
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Citometría de Flujo , Neoplasias Meníngeas , Humanos , Masculino , Anciano , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico por imagen , Quimioradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Imagen por Resonancia Magnética , CitologíaRESUMEN
BACKGROUND: The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. AIMS: To identify clinical presentations associated with childhood and adolescent B-cell lymphomas and estimate symptom prevalence. METHODS: A systematic review of observational studies and meta-analysis of proportions was carried out. Medline and EMBASE were systematically searched, with no language restrictions, from inception to 1st August 2022. Observational studies with at least 10 participants, exploring clinical presentations of any childhood and adolescent lymphoma, were selected. Proportions from each study were inputted to determine the weighted average (pooled) proportion, through random-effects meta-analysis. RESULTS: Studies reported on symptoms, signs and presentation sites at diagnosis of 12,207 children and adolescents up to the age of 20. Hodgkin's lymphoma most frequently presented with adenopathy in the head-and-neck region (79% [95% CI 58%-91%]), whilst non-Hodgkin's lymphoma presented abdominally (55% [95% CI 43%-68%]). Symptoms associated with lymphoma included cervical lymphadenopathy (48% [95% CI 20%-77%]), peripheral lymphadenopathy (51% [95% CI 37%-66%]), B-symptoms (40% [95% CI 34%-44%]), fever (43% [95% CI 34%-54%]), abdominal mass (46% [95% CI 29%-64%]), weight loss (53% [95% CI 39%-66%]), head-and-neck mass (21% [95% CI 6%-47%]), organomegaly (29% [95% CI 23%-37%]), night sweats (19% [95% CI 10%-32%]), abdominal pain (28% [95% CI 15%-47%]), bone pain (17% [95% CI 10%-28%]) and abnormal neurology (11% [95% CI 3%-28%]). CONCLUSION: This systematic review and meta-analysis of proportions provides insight into the heterogeneous clinical presentations of B-cell lymphoma in childhood and adolescence and provides estimates of symptom prevalence. This information is likely to increase public and clinical awareness of lymphoma presentations and aid earlier diagnosis. This review further highlights the lack of studies exploring childhood and adolescent lymphoma presentations in primary care, where patients are likely to present at the earliest stages of their disease.
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Linfoma de Células B , Humanos , Adolescente , Niño , Linfoma de Células B/epidemiología , Linfoma de Células B/diagnóstico , Linfadenopatía/epidemiología , Estudios Observacionales como Asunto , Preescolar , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/diagnóstico , PrevalenciaRESUMEN
Despite excellent cure rates among children, adolescents, and young adults (CAYAs) with mature B-cell non-Hodgkin lymphomas (B-NHLs) treated with chemoimmunotherapy, CAYAs with relapsed/refractory B-NHL remain difficult to treat, with a dismal prognosis. Reinduction and subsequent therapeutic management are not standardized. The armamentarium of active agents against B-NHL, including antibody-drug conjugates, monoclonal antibodies, checkpoint inhibitors, T-cell engagers, CAR T cells, CAR-natural killer (CAR-NK) cells, and cell signaling inhibitors, continues to expand. This article reviews current management practices and novel therapies in this difficult to treat population.
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Linfoma de Células B , Humanos , Adolescente , Niño , Adulto Joven , Linfoma de Células B/terapia , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Recurrencia Local de Neoplasia/patología , Resistencia a Antineoplásicos , AdultoRESUMEN
Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.
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Ciclina D1 , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-bcl-6 , Humanos , Masculino , Proteínas Proto-Oncogénicas c-bcl-6/genética , Anciano , Ciclina D1/genética , Ciclina D1/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Reordenamiento Génico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/genética , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/uso terapéutico , Prednisona/uso terapéutico , Clasificación del Tumor , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Rituximab/uso terapéutico , Hibridación Fluorescente in Situ , Etopósido/uso terapéutico , Etopósido/administración & dosificaciónRESUMEN
Multiparameter flow cytometry data is visually inspected by expert personnel as part of standard clinical disease diagnosis practice. This is a demanding and costly process, and recent research has demonstrated that it is possible to utilize artificial intelligence (AI) algorithms to assist in the interpretive process. Here we report our examination of three previously published machine learning methods for classification of flow cytometry data and apply these to a B-cell neoplasm dataset to obtain predicted disease subtypes. Each of the examined methods classifies samples according to specific disease categories using ungated flow cytometry data. We compare and contrast the three algorithms with respect to their architectures, and we report the multiclass classification accuracies and relative required computation times. Despite different architectures, two of the methods, flowCat and EnsembleCNN, had similarly good accuracies with relatively fast computational times. We note a speed advantage for EnsembleCNN, particularly in the case of addition of training data and retraining of the classifier.
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Algoritmos , Citometría de Flujo , Aprendizaje Automático , Humanos , Citometría de Flujo/métodos , Linfoma de Células B/clasificación , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Linfocitos B/patología , Linfocitos B/clasificación , Linfocitos B/inmunología , Inmunofenotipificación/métodosAsunto(s)
Disnea , Fiebre , Linfoma de Células B Grandes Difuso , Humanos , Disnea/diagnóstico , Disnea/etiología , Fiebre/diagnóstico , Fiebre/etiología , Linfoma de Células B Grandes Difuso/diagnóstico , Interleucina-10/sangre , Masculino , Linfoma de Células B/diagnóstico , Diagnóstico DiferencialRESUMEN
Background: Canine lymphoma is the most common hematopoietic cancer in dogs. Numerous studies have evaluated the prognostic value of hematological abnormalities and ratios in both humans and dogs with lymphoma. Aim: To compare hematological parameters and complete blood count ratios between a population of dogs affected by lymphoma and healthy dogs to identify potential prognostic markers for lymphoma. Methods: This retrospective case-control study compares hematological parameters and complete blood count ratios between a population of 114 dogs affected by multicentric large B-cell lymphoma (LBCL) and 60 healthy dogs. Results: The study found several statistically significant differences between the hematological indices of LBCL dogs and healthy dogs, but no correlation between these parameters and the survival times of 78 dogs treated with chemotherapy Madison Wisconsin protocol. In addition, hematological alterations were evaluated such as anemia, leukocytosis, and thrombocytopenia. Conclusion: Hematological ratios have been suggested as potential prognostic markers for canine LBCL but their real prognostic value remains controversial and requires future investigation.
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Enfermedades de los Perros , Perros , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/diagnóstico , Estudios Retrospectivos , Estudios de Casos y Controles , Masculino , Femenino , Recuento de Células Sanguíneas/veterinaria , Linfoma de Células B Grandes Difuso/veterinaria , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B/veterinaria , Linfoma de Células B/sangre , Linfoma de Células B/diagnóstico , PronósticoRESUMEN
INTRODUCTION: Primary central nervous system lymphoma (PCNSL) presents a diagnostic enigma due to the inherent absence of lymphoid tissue in the central nervous system (CNS). The hypothesis posits that lymphocytes infiltrating the CNS during inflammatory responses could represent a cellular source for PCNSL, challenging traditional understandings of its etiology. PATIENT CONCERNS: In 2 illustrative cases, patients presented with neurological symptoms initially misdiagnosed as encephalitis and demyelinating disease, respectively. These diagnoses were established based on clinical assessments and initial biopsy findings. DIAGNOSIS: Subsequent biopsies, conducted months after the first signs of disease, confirmed the diagnosis of PCNSL in both patients. Identifying CD20-positive tumor cells was pivotal, indicating a B-cell lymphoma origin. INTERVENTIONS: Treatment strategies included high-dose methotrexate chemotherapy for both patients. In addition, the second patient underwent adjuvant whole-brain radiotherapy after the chemotherapy regimen. OUTCOMES: The therapeutic approach significantly reduced tumor size in both cases, with no evidence of recurrence observed during the follow-up period. This outcome underscores the potential efficacy of the chosen interventions. CONCLUSION: In response to inflammatory lesions, lymphocyte infiltration into the CNS may serve as a pivotal origin for tumor cells in PCNSL. These cases highlight the complexity of diagnosing CNS disorders and suggest that various forms of encephalitis in the early stages could influence the prognosis of lymphoma. This insight into the cellular origins and treatment responses of PCNSL contributes to a broader understanding of its pathophysiology and management.
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Neoplasias del Sistema Nervioso Central , Metotrexato , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Diagnóstico Diferencial , Encefalitis/patología , Encefalitis/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Imagen por Resonancia Magnética , Metotrexato/uso terapéuticoRESUMEN
B-cell lymphomas occur with an incidence of 20 new cases per 100 000 people per year in high-income countries. They can affect any organ and are characterised by heterogeneous clinical presentations and courses, varying from asymptomatic, to indolent, to very aggressive cases. Since the topic of B-cell non-Hodgkin lymphomas was last reviewed in The Lancet in 2017, a deeper understanding of the biological background of this heterogeneous group of malignancies, the availability of new diagnostic methods, and the development and implementation of new targeted and immunotherapeutic approaches have improved our ability to treat patients. This Seminar provides an overview of the pathobiology, classification, and prognostication of B-cell non-Hodgkin lymphomas and summarises the current knowledge and standard of care regarding biology and clinical management of the most common subtypes of mature B-cell non-Hodgkin lymphomas. It also highlights new findings in deciphering the molecular background of disease development and the implementation of new therapeutic approaches, particularly those targeting the immune system.
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Linfoma de Células B , Humanos , Linfoma de Células B/terapia , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , PronósticoRESUMEN
This MIB guide briefly summarizes the generation of patient-derived xenografts (PDXs) and highlights the importance of validating PDX models for the presence of B cell lymphoma of human origin before their use in radiotheranostic applications. The use of this protocol will allow researchers to learn different methods for screening PDX models for Epstein-Barr virus (EBV)-infected B cell lymphoma.
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Linfoma de Células B , Humanos , Animales , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/diagnóstico por imagen , Modelos Animales de Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto , Medicina de PrecisiónAsunto(s)
Neoplasias Pulmonares , Melanoma , Neoplasias de la Próstata , Programa de VERF , Neoplasias Cutáneas , Neoplasias de la Tiroides , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Programa de VERF/estadística & datos numéricos , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Incidencia , Melanoma/epidemiología , Melanoma/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/diagnóstico , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/diagnóstico , Estados Unidos/epidemiología , Femenino , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/diagnóstico , Persona de Mediana Edad , Neoplasias Renales/epidemiología , Neoplasias Renales/diagnóstico , Anciano , Linfoma de Células B/epidemiología , Linfoma de Células B/diagnóstico , Adulto , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/diagnósticoAsunto(s)
Médula Ósea , Citometría de Flujo , Inmunofenotipificación , Linfoma de Células B , Humanos , Citometría de Flujo/métodos , Médula Ósea/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/patología , Masculino , Persona de Mediana Edad , Anciano , Femenino , Sensibilidad y EspecificidadAsunto(s)
Neoplasias del Bazo , Proteína p53 Supresora de Tumor , Humanos , Neoplasias del Bazo/patología , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/genética , Proteína p53 Supresora de Tumor/genética , Linfoma de Células B/patología , Linfoma de Células B/genética , Linfoma de Células B/diagnóstico , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , FemeninoRESUMEN
In the 1980s, immunohistochemistry and clonality analyses became instrumental in the recognition and definition of new types of cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL) and the development of new classifications. By accepting loss of pan-T-cell antigens and clonal T-cell receptor gene rearrangements as important criteria to differentiate between benign and malignant T-cell proliferations, and monotypic immunoglobulin light-chain expression and clonal immunoglobulin gene rearrangements as crucial criteria to distinguish between benign and malignant B-cell proliferations, many cases, until then diagnosed as cutaneous lymphoid hyperplasia or pseudolymphoma, were reclassified as primary cutaneous CD4+ small/medium T-cell lymphoma (PCSM-TCL) or primary cutaneous marginal zone lymphoma (PCMZL), respectively. However, in recent years there is growing awareness that neither these immunohistochemical criteria nor demonstration of T-cell or B-cell clonality is specific for malignant lymphomas. In addition, many studies have reported that these low-grade malignant CTCL and CBCL have an indolent clinical behavior and an excellent prognosis with disease-specific survival rates of or close to 100%. As a result, recent classifications have downgraded several low-grade malignant cutaneous lymphomas to lymphoproliferative disorder (LPD). Both the 5th edition of the WHO classification (2022) and the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms reclassified PCSM-TCL as primary cutaneous CD4+ small/medium T-cell LPD and primary cutaneous acral CD8+ T-cell lymphoma as primary cutaneous acral CD8+ T cell LPD. While the 2022 ICC introduced the term "primary cutaneous marginal zone LPD," in the 5th edition of the WHO classification PCMZL is maintained. In this review we describe the background and rationale of the continually changing terminology of these conditions and discuss the clinical consequences of downgrading malignant lymphomas to LPDs.