B-cell non-Hodgkin lymphomas.

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.

Presentation of B-cell lymphoma in childhood and adolescence: a systematic review and meta-analysis.

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.

Identifying and addressing unmet clinical needs in primary cutaneous B-cell lymphoma: A consensus-based paper from an ad-hoc international panel.

Primary cutaneous B-cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence-based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple-step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners.

Flow-cytometry Assessment of DNA content and Immunophenotyping of Immune-cells in Lymph-node-specimens as a Potential Diagnostic Signature of Aggressiveness in B-Non-Hodgkin Lymphomas.

Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process. We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019-2022. Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8+ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45+ cells, total lymphocytes, CD4+ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs. These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.

Therapy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma in Children, Adolescents, and Young Adults.

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.

Synchronous occurrence of primary cutaneous B-cell lymphoma and cutaneous Rosai-Dorfman disease in distinct lesions: A unique association.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a rare subtype of reactive histiocytosis which is seldom associated with Hodgkin's and non-Hodgkin's lymphomas. To date, the coexistence in the same patient of extra nodal SHML and primary cutaneous B-cell lymphoma (PCBCL) has been reported in the literature, as metachronous diagnosis in the anatomical area of the original PCBCL or synchronous occurrence in the same lesions. However, no data have been published as for synchronous occurrence of the two pathological entities in distinct anatomical sites. Herein, we report the first ever described synchronous occurrence of PCBCL and SHML, detected in distinct lesions, affecting the same patient. The complete resolution of the patient's PCBCL after rituximab treatment and the concomitant regression of SHML suggest that this clinically benign reactive histiocytic proliferation, potentially triggered by the lymphoma microenvironment itself, may take place not only in the site of the PCBCL lesion, but also in other distant areas not directly affected by the primary cutaneous lymphoma.

Cutaneous lymphoproliferative disorders: Back to the future.

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.

How Many Tests Does It Take to Diagnose a Triple-Hit B-Lymphoblastic Lymphoma? (Hint, It's A Lot).

B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is a precursor B-cell neoplasm that often harbors specific cytogenetic/molecular abnormalities with distinctive clinical, phenotypic, and prognostic characteristics. Subcategorization of B-ALL/LBL therefore requires extensive cytogenetic and/or molecular testing to determine the appropriate classification and therapeutic interventions for these patients. Herein, we present a case of a 17-year-old young woman diagnosed with B-LBL harboring not only an IGH::MYC rearrangement but also BCL2 and BCL6 rearrangements (so-called "triple-hit") and somatic biallelic TP53 inactivation. MYC rearrangements are relatively rare in B-ALL/LBL, and the identification of a "triple-hit" elicited an initial diagnostic dilemma. However, a multimodal approach allowed for the classification of this complex case and helped guide selection of an appropriate therapeutic regimen.

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

Splenic cyst deroofing complicated with B lymphoma.

BACKGROUND: Splenic cysts are uncommon and very rarely malignant therefore their treatment isn't standardized. In case of symptomatic cysts different surgical approaches have been suggested. Primary malignant lymphoma of the spleen comprises less than 1% of non-Hodgkin's lymphomas. To our knowledge, only 203 cases of splenic large B-cell lymphoma (LBCL) have been reported to date and only 2 of them were fibrin-associated splenic cysts. CASE PRESENTATION: 27-year-old model with a 19 × 13 cm splenic cyst without data of malignancy in the preliminary study and therefore treated with laparoscopic deroofing. After histological diagnosis of LBCL with a fibrin/EBV-associated splenic pseudocyst, the patient received 4 cycles of Rituximab and a laparoscopic splenectomy was performed due to resurgence of the pseudocyst. No evidence of malignancy has been found during follow up (EBV viral load every 3 months during the first year, PET-CT every 6 months during the first year and annual afterwards) performed after the splenectomy. DISCUSSION AND CONCLUSIONS: The value of tumor markers and radiology for diagnosis of splenic cysts is put into question. Only 60 cases of Fibrin-associated LBCL (FA-LBCL) have been described in the literature therefore there are no treatment guidelines for them even though surgery together with systemic treatment has been the prevalent route with good results in most cases.

Could Cerebral Inflammatory Lesions be the Cellular Origin of Primary Central Nervous System Lymphoma?

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.

[Assessment of diagnostic utility of cerebrospinal fluid flow cytometry immunophenotyping and cytology in B cell non- Hodgkin lymphoma in a public chilean hospital]. / Evaluación de la utilidad diagnóstica de la citometría de flujo y la citología para el diagnóstico de compromiso de líquido cefalorraquídeo en linfomas no Hodgkin B en un hospital público chileno.

Cerebrospinal fluid (CSF) involvement in B cell non-Hodgkin lymphomas is a poor prognostic sign and diagnosis is made using techniques such as flow cytometry (FCM) and conventional cytology (CC). AIM: To evaluate the frequency of CSF involvement in B-NHL by both techniques in a public hospital. MATERIAL AND METHODS: 97 CSF samples were analyzed in tubes with cell preservative belonging to 70 patients, 71% male, median age 56 years (18-85 years), with a diagnosis of B-NHL and risk of infiltration according to medical criteria. Most were patients from new diagnosis (89%), diffuse large B cell lymphoma (60%), and Ann-Arbor stage III-IV (77%). In 67 samples (69%), CC and CMF were performed simultaneously. RESULTS: Of the samples analyzed by CMF, 99% were valuable, while by CC, only 67% (p<0,05). Globally, 25% of the samples showed infiltration by CMF, while 18% by CC (p<0,0001). Forty-four valuable samples were evaluable and analyzed by CC and CMF, finding a similar frequency of positive cases (27%), with two-thirds positive only by CC or CMF. Positive samples in diffuse large B cell lymphoma were 28% by CC and/or CMF. CONCLUSIONS: A higher proportion of infiltration cases were detected by CMF than by CC. In valuable cases, CC complements CMF.

Presumed solitary ocular lymphoma of large B-cell origin with Mott cell change in a dog.

A 4-year-old female Maltese dog was referred to our veterinary hospital with uveitis and conjunctivitis of the right eye. An ophthalmological evaluation revealed an intraocular mass that appeared to originate from the anterior uvea. Metastasis and regional invasion were not detected with CT examination. Enucleation of the right eye was recommended; however, the owner declined treatment. Six months later, the dog was re-presented with a right facial mass. At presentation, superficial lymph node enlargement was not appreciated, and no apparent alterations were noted on blood analysis or urinalysis. Computed tomography revealed an intraocular mass that invaded the surrounding tissues, including the frontal sinus. Presumed solitary ocular lymphoma with a large B-cell phenotype and Mott cell change was diagnosed via histopathological and immunohistochemical examination of a biopsy of the lesion. As the mass was too large for complete excision, neoadjuvant chemotherapy was administered. Complete remission was achieved using the L-COAP protocol and successful exenteration of the right eye. However, the dog was returned with enlargement of the right retropharyngeal lymph nodes. To the best of our knowledge, this is the first case report of presumed solitary ocular lymphoma with a large B-cell phenotype displaying Mott cell change in a dog. Key clinical message: This is the first reported case of a presumed solitary ocular lymphoma with a large B-cell phenotype and Mott cell change. Although systemic involvement was observed 6 mo after the initial visit, neoadjuvant chemotherapy and exenteration were effective.

Lymphome oculaire solitaire présumé d'origine à grandes cellules B avec modification des cellules de Mott chez un chienUne chienne maltaise de 4 ans a été envoyée à notre hôpital vétérinaire avec une uvéite et une conjonctivite de l'œil droit. Une évaluation ophtalmologique a révélé une masse intraoculaire qui semblait provenir de l'uvée antérieure. Aucune métastase ni invasion régionale n'ont été détectées par examen CT. Une énucléation de l'œil droit a été recommandée; cependant, le propriétaire a refusé le traitement. Six mois plus tard, le chien a été présenté à nouveau avec une masse faciale droite. À la présentation, l'augmentation de taille des ganglions lymphatiques superficiels n'a pas été réalisée, et aucune modification apparente n'a été notée sur l'analyse sanguine ou l'analyse d'urine. La tomodensitométrie a révélé une masse intraoculaire qui a envahi les tissus environnants, y compris le sinus frontal. Un lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B et une modification des cellules de Mott a été diagnostiqué via un examen histopathologique et immunohistochimique d'une biopsie de la lésion. Comme la masse était trop importante pour une exérèse complète, une chimiothérapie néoadjuvante a été administrée. Une rémission complète a été obtenue grâce au protocole L-COAP et à une exentération réussie de l'œil droit. Cependant, le chien a été vu de nouveau avec une hypertrophie des ganglions lymphatiques rétropharyngés droits. À notre connaissance, il s'agit du premier cas rapporté de lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B présentant une modification des cellules de Mott chez un chien.Message clinique clé :Il s'agit du premier cas rapporté de lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B et une modification des cellules de Mott. Bien qu'une atteinte systémique ait été observée 6 mois après la visite initiale, la chimiothérapie néoadjuvante et l'exentération ont été efficaces.(Traduit par Dr Serge Messier).

[Introduction on the update of the 5th edition WHO classifications of B-cell neoplasms].

The 5th edition WHO classification of B-cell tumors is a systematic update to the fourth revised version of the classification. The changes include updated names of entities, sharpened diagnostic criteria, and upgrades from provisional to definite entities. This review focuses on the changes in the content of each chapter of B-cell tumors, facilitating domestic colleagues engaged in the diagnosis and treatment of lymphohematopoietic tumors to understand the latest progress and guide daily work.

[Primary Meningeal Lymphoma Diagnosed Using Cytology and Flow Cytometry-A Case Report].

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.

Next generation sequencing in routine diagnostics of mature non-Hodgkin's B-cell lymphomas.

INTRODUCTION: Integration of molecular characterization of lymphomas in clinical diagnostics may improve subclassification and risk-stratification, and we implemented a next generation sequencing (NGS) analysis as part of routine diagnostic work-up of all mature B-cell non-Hodgkin's lymphoma (B-NHL). Here, we present data of mutational profiles with potential complementary diagnostic, prognostic, and predictive value detected in our consecutive non-selected cohort of B-NHL patients. METHODS: NGS results from 298 patients with both newly diagnosed and relapsed/refractory disease were included as a single center study. NGS was performed as routine analysis together with standard diagnostic work-up using a custom-made amplicon PCR-based multiplex NGS panel covering all coding exons and consensus splice sites in 59 genes. RESULTS: Mutations were detected in 94% of the 298 samples. Most lymphomas could be classified definitively, but 24 cases were classified as small B-cell lymphomas without defining characteristics. Of these, 50% (12/24 cases) could retrospectively be assigned a likely diagnostic subtype according to mutational findings. CONCLUSION: Implementation of a 59 gene exome sequencing panel added diagnostic value to 50% of unclassified cases and provided in 94% of the cases possible biomarkers for disease monitoring as well as potential diagnostic, prognostic, and predictive markers for future studies.

Mature B-cell lymphoma with acute myelitis as the first presentation: a case report and literature review.

BACKGROUND: Lymphomas are malignant tumors of the immune system that arise in lymphoid organs and can impact the central nervous system. However, lymphomas with acute myelitis as the first manifestation are exceedingly rare, and most of them are symptoms of spinal cord damage due to the lack of specificity in their clinical manifestations. The rate of early misdiagnosis is exceedingly high, and the prognosis is dire. Here, we report a case of mature B-cell lymphoma with acute myelitis as the first presentation and review the related literature. CASE PRESENTATION: In this study, We report a case of a 70-year-old male patient with bilateral lower extremity weakness, bowel and bladder dysfunction, and recurrent fever. A paraureteral mass was seen beneath the right kidney on imaging, and the final pathological biopsy revealed: CD20 ( +), mature B-cell tumor, The patient refused to undergo additional tests to ascertain the type of lymphoma and subsequent therapy and asked to be discharged. In mid-November 2020, the patient died. CONCLUSIONS: This case report shows that patients with lymphoma can present with acute myelitis as the first symptom, especially if they have recurrent fever, that conventional treatment for myelitis is ineffective, and that tumors are considered after other causes of myelitis have been ruled out. Furthermore, a focused search for tumor-related evidence, as well as early identification and therapy, may help patients live longer lives.

Non-Hodgkin's Lymphoma with Intraspinal Involvement Mimics Bilateral Thoracolumbar Plexopath.

PURPOSE: Non-Hodgkin lymphoma (NHL) is the most common type of lymphoma, and its extranodal manifestation is rare. Skeletal muscle involvement is noted in only 1.1% of patients with NHL. Here, we present a case of high-grade B-cell lymphoma (HGBL); it infiltrated the left neural foramina from the left psoas muscle before encroaching on the whole spinal canal and subsequently invading the contralateral neural foramina from T12 to L3. CASE REPORT: A 43-year-old man with HGBL who could function independently presented with numbness and weakness of the left thigh 2 months after a diagnosis of infiltrative lymphoma in the left psoas muscle. His symptoms were urine incontinence and unsteady gait. A neurological examination revealed weakness in the left psoas and quadriceps with hyporeflexia and hypesthesia. Lumbar spine magnetic resonance imaging (MRI) revealed intraspinal extradural invasion from T12 to L3 with multiple left-sided root compression despite the resolution of primary psoas lymphoma. At 6 weeks after symptom onset, his symptoms progressed to weakness, numbness, and hyporeflexia of the bilateral lower extremities with preserved anal sensation. Follow- up MRI revealed the progression of intraspinal invasion, which spread through the spinal canal and invaded the contralateral neural foramina from T12 to L3. The patient was finally bound to a wheelchair. CONCLUSION: Clinicians must check for possible intraspinal involvement in patients with HGBL, particularly patients with known paraspinal soft-tissue involvement. The resolved infiltration of the soft tissue does not preclude the possibility of further neurological involvement. Additionally, MRI may provide higher resolution findings for clarifying the structure of the neural foramina and thecal sac. Keyword: Non-Hodgkin's Lymphoma, high-grade B-cell lymphoma, plexopathy.

A case of spermatic cord B-cell lymphoma relapsing to the brain in a dog.

A 13-year-old, intact male mixed-breed dog was referred to our clinic for lethargy and asthenia following an episode of gastroenteritis. As an incidental finding during abdominal ultrasound, a mass on the right spermatic cord was seen. Cytology of the mass revealed a monomorphic population of large, round cells with a lymphoid appearance. A bilateral orchiectomy was conducted, and histopathology revealed the presence of a B-cell lymphoma in the right spermatic cord. Based on clinical staging, which showed no involvement of other sites, no additional treatment was administered. Recheck evaluations were scheduled for every 3 mo thereafter. Five months after surgery, the dog developed left central vestibular syndrome with a paradoxical right-sided head tilt. An MRI of the brain showed multifocal lesions and, due to a rapidly worsening clinical condition, the dog was humanely euthanized. The histopathology of the brain lesions was consistent with B-cell lymphoma. Key clinical message: This is the first report of a primary spermatic cord lymphoma relapsing to the brain in a dog. Although rare, spermatic cord tumors should be included among the differential diagnoses for masses arising from the spermatic cord. If lymphoma is diagnosed, location to other sites, especially to the central nervous system, should be considered.

Un cas de lymphome à cellules B du cordon spermatique récidivant au cerveau chez un chien. Un chien de race mixte mâle intact de 13 ans a été référé à notre clinique pour léthargie et asthénie à la suite d'un épisode de gastro-entérite. Comme découverte fortuite lors d'une échographie abdominale, une masse sur le cordon spermatique droit a été observée. La cytologie de la masse a révélé une population monomorphe de grosses cellules rondes d'aspect lymphoïde. Une orchidectomie bilatérale a été réalisée et l'histopathologie a révélé la présence d'un lymphome à cellules B dans le cordon spermatique droit. Sur la base du stade clinique, qui n'a montré aucune implication d'autres sites, aucun traitement supplémentaire n'a été administré. Des évaluations de contrôle étaient programmées tous les 3 mois par la suite. Cinq mois après la chirurgie, le chien a développé un syndrome vestibulaire central gauche avec une inclinaison paradoxale de la tête du côté droit. Une IRM du cerveau a montré des lésions multifocales et, en raison d'une détérioration rapide de l'état clinique, le chien a été euthanasié sans cruauté. L'histopathologie des lésions cérébrales correspondait à un lymphome à cellules B.Message clinique clé :Il s'agit du premier rapport d'un lymphome primaire du cordon spermatique récidivant au cerveau chez un chien. Bien que rares, les tumeurs du cordon spermatique doivent être incluses dans les diagnostics différentiels des masses provenant du cordon spermatique. Si un lymphome est diagnostiqué, la localisation vers d'autres sites, en particulier vers le système nerveux central, doit être envisagée.(Traduit par Dr Serge Messier).

Updates on CAR T-cell therapy in B-cell malignancies.

By increasing disease-free survival and offering the potential for long-term cure, chimeric antigen receptor (CAR) T-cell therapy has dramatically expanded therapeutic options among those with high-risk B-cell malignancies. As CAR T-cell utilization evolves however, novel challenges are generated. These include determining how to optimally integrate CAR T cells into standard of care and overcoming mechanisms of resistance to CAR T-cell therapy, such as evolutionary stress induced on cancer cells leading to immunophenotypic changes that allow leukemia to evade this targeted therapy. Compounding these challenges are the limited ability to determine differences between various CAR T-cell constructs, understanding the generalizability of trial outcomes from multiple sites utilizing unique CAR manufacturing strategies, and comparing distinct criteria for toxicity grading while defining optimal management. Additionally, as understanding of CAR behavior in humans has developed, strategies have appropriately evolved to proactively mitigate toxicities. These challenges offer complimentary insights and guide next steps to enhance the efficacy of this novel therapeutic modality. With a focus on B-cell malignancies as the paradigm for effective CAR T-cell therapy, this review describes advances in the field as well as current challenges and future directions.