Challenges and Opportunities in Lymphoma

Challenges and Opportunities in Lymphoma

Akshay Nigam, Anupama Sharma, Girish Chandra Sharma, and Sanjeev Kumar Singh


Lymphoma involves abnormal lymphoid cell growth, often originating in lymphatic tissue, but in this case series non-Hodking’s lymphoma is visible in the extra-nodal region. This research explores different lymphoma cases, focusing on diverse presentations and utilizing modern imaging for evaluation. Four cases are detailed, involving an 18-year-old woman with tonsillar lymphoma, a 69-year-old man with ocular lymphoma, a 38-year-old lady with abdominal lymphoma, and a 30-year-old man with gastric lymphoma. All cases received adjuvant chemotherapy (RCHOP), leading to significant symptom relief after four cycles.

The discussion highlights the debate surrounding the classification of primary extranodal non-Hodgkin’s lymphoma (NHL), challenging the existing Ann Arbor classification’s applicability.

A major challenge in managing primary extranodal lymphomas is the absence of specific treatment guidelines. Evaluation criteria, defining complete response as the disappearance of all evidence of the disease, guided the study. In conclusion, this case series underscores the importance of a multidisciplinary approach in diagnosing, staging, and managing non-Hodgkin’s lymphoma. Despite challenges in defining and treating primary extranodal non-Hodgkin’s lymphoma, the study demonstrates the effectiveness of adjuvant chemotherapy in providing relief, as all the cases revealed recovery after 4 continuous cycles of chemotherapy.

Mounia Bendari, Abderrahmane Elbouzidi, Mariam Ahnach, and Said Benchekroun


Background: Mantle cell lymphoma (MCL) is a distinct subtype of Non-Hodgkin Lymphoma (NHL), it affects 5 to 8% of NHL, it is a clinically heterogeneous disease occurring within a heterogeneous patient population. The median age at time of diagnosis is over 65 years old. The incidence increased with age, and also affects man more than women with ratio of 3 to 1. Overall survivor is different according to subtype of lymphoma. Most patients present at advanced stage, and 30% present in leukemic phase.

Case report: We report a case of 60-year-old women with relapsed mantle cell lymphoma. The patient had no medical past history. The diagnosis of mantle cell lymphoma was made in 2019 revealed by anemic syndrome, the morphological and histological study of lymph node and bone marrow biopsy confirmed the mantle cell lymphoma with expression of CD19+, CD20+, CD5+, CD23-, Cyclin D1+, and KI 67 at 60%.  The PET Scan showed FDG-avid disease, the laboratory studies remarques for high level of LDH, elevated B2 microglobulin. The patient underwent R-DHAP regimen (Rituximab, Aracytine, Cisplatin, prednisone) and achieved complete remission after 2 curses, the PET Scan was negative, and the bone marrow biopsy was normal, the collect of hematopoietic stem cell was performed, and the patients received 2 other courses of RDHAP regimen. She does not benefit from autologous hematopoietic stem cell transplant (HSCT) because of severe infection of COVID19. In reality, patient had a server pneumoniae with chronic fever, she was admitted for intravenous antibiotics, all biological exam showed a high level of C- reactive protein, and high level of d-dimers, but no sign of relapse was found. The patient still febrile during 6 months. Autologous hematopoietic stem cell transplant was not realized, but she received maintenance treatment with Rituximab. One year later, the patient developed a mass under the knee with deep deterioration of general condition, relapse was suspected, the surgical biopsy was performed and histological study confirmed the relapse of mantle cell lymphoma. The aim of this case report is to describe the difficulties to manage mantle cell lymphoma associated to covid 19 infection and report the consequences of therapeutic decision.

Conclusion: Not all mantle cell lymphoma is the same, it is crucial to identify patients appropriate for aggressive treatment, autologous hematopoietic stem cell transplant improves event free survival with unclear benefit in all patients, maintenance Rituximab improves overall survivor. Minimal residual disease may guide future therapeutic decisions and help physicians manage these patients. Our patient does not receive autologous hematopoietic stem cell transplant and suffers from chronic Covid19 infection.  This association is complicated for the physician and the difficulties of access to targeted therapy in our country limits the therapeutic proposals for patients in relapse.

Motoharu Shibusawa, MD and Erika Imamine, MD


Cardiovascular issues are important concerns in malignant lymphoma treatment. These issues can be broadly categorized into two groups: the invasion of malignant lymphoma into the heart and cardiovascular disease related to malignant lymphoma treatment. In terms of malignant lymphoma invasion of the heart, the presence of a heart lesion of malignant lymphoma often presents with heart-related symptoms and findings such as chest pain, heart failure, and arrhythmias. Notably, heart failure and arrhythmias can be fatal. The identification of heart lesions of malignant lymphoma will result in appropriate management and survival improvement. As for cardiovascular disease associated with malignant lymphoma treatment, the incidence and types of cardiovascular disease, management, and follow-up planning should be identified before starting treatment. This identification and plan will allow an understanding of the risk of developing cardiovascular disease and appropriate management and follow-up. In clinical practice, it is important to keep in mind that cardiac issues in patients with malignant lymphoma should be identified, assessed, and managed before initiating treatment.



Patients presented with soft tissue lesions without any β symptoms can be a case of Primary extranodal Non- non-Hodgkins lymphoma. According to the World Health Organization classification system, there are two types of Lymphoma with various sub-types of Hodgkins Lymphoma and Non-Hodgkin Lymphoma are classified to assess the disease burden Progression and metastasis Imaging modalities are helpful. Commonest site involvement in Non-Hodgkin Lymphoma in the gastrointestinal tract (44%) followed by Head and Neck and may Involve bone (8%) and Central Nervous System 5%. Diffuse large β-Cell Lymphoma is the most common subtype representing 30%-35% of all Non-Hodgkin Lymphoma Cases. Oral and Para oral sites were involved in 2.5% of the cases. A 27-year-old Male noticed a swelling in the flank which was progressively Increasing in size one year back later it was associated with pain which reduced mobility and pain was increased during walking. Due to the advancement of diagnostic techniques, it is easy to get the radiological picture and correlation with clinical presentation and pathological reports, but these facilities are not available at various centers. Usually, patients are present in very advanced stages because of a lack of awareness about the disease, and how to proceed for diagnosis and treatment resulting in poor outcomes for these patients. This presentation and clinical funding are rare in the case of Lymphoma. This case report allows us to think of another diagnosis rather than usual.

Muhamad Alhaj Moustafa


Follicular lymphoma (FL) is the most common type of indolent lymphoma in the Western world, accounting for approximately 30% of lymphoma cases. FL is known for its recurrent nature, necessitating diverse treatment options. The introduction of rituximab, an anti-CD20 antibody, has greatly improved FL outcomes and paved the way for targeted therapies. In this review, we thoroughly explore the structure, mechanism of action, clinical outcomes, and side effects of currently approved monoclonal antibodies (mAb) for FL. Furthermore, we provide insights into ongoing clinical trials and emerging monoclonal antibodies that hold promise for the future of FL treatment. A comprehensive literature search was conducted using various medical databases, including ASH and ASCO publications, as well as PubMed. The website was used to compile a list of investigational monoclonal antibodies from ongoing clinical trials. The future of antibody-based therapy for follicular lymphoma shows great promise, with a focus on enhancing antibody efficacy, prioritizing optimized combination therapies to address treatment resistance, and evaluating bispecific antibodies as first-line therapies, all while carefully balancing risks and benefits and sequencing treatments appropriately for better disease management. These directions have the potential to establish antibodies as a central component of follicular lymphoma treatment.

Aminder Singh


Background: Cutaneous lymphomas are a heterogeneous group of extra-nodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal lymphocytes. Less frequently, these lymphomas spread from the skin to the blood or a lymph node. The incidence of primary cutaneous lymphoma has been estimated to be 1:100,000 according to the World Health Organization. Usually, these lymphomas affect adults with a median age of 50 to 60 years. T-cell lymphomas predominate over primary B-cell lymphomas of the skin. The most important subtypes of cutaneous T cell lymphomas are Mycosis fungoides, Sezary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified. These subtypes present different clinical, histological, and molecular features, and can follow an indolent or a very aggressive course.

Aim: The aim of this study was to analyze cutaneous lymphomas to ascertain its clinical aspects including prevalence, histopathology and immune profile.

Material and methods: A retrospective analysis of skin biopsies over a 7-year period ranging from 2016 to 2022 was done, of which 11 cases were diagnosed as cutaneous lymphomas. These cases were analyzed in detail including immune profile.

Results & conclusions: The majority of the cases out of all cutaneous lymphomas were of T cell lymphoma and only one case was of B cell type. Definitive diagnosis of CTCL requires a multidisciplinary approach.

Christian Gisselbrecht, MD Pr. and Eric Van Den Neste, MD


Diffuse large B-cell lymphoma is a highly curable disease when complete remission after immunochemotherapy is achieved. Despite a high complete remission rate, which is a prerequisite for a cure, 20–40% of patients will relapse or fail first-line therapy. Salvage chemotherapy followed by intensification with autologous stem cell transplant (ASCT) has been established as a curative treatment for relapsed chemosensitive patients under 60 years of age. The results have been somewhat disappointing, with less than 50% of patients being eligible for transplant and relapse posttransplant ranging from 60–40%. Improvements have been made with new drugs in development, immunoconjugate bispecific monoclonal antibodies, and chimeric antigen receptor technology (CAR-T). A more precise evaluation of prognostic factors with PET scans and other biological factors during treatment will allow for the design of new treatment strategies. The exceptional response rate in phase 2 achieved with the three available CARTs has now been confirmed with a longer follow-up period. At 2 years, the overall survival (OS) expectancy is 50% with a plateau on the curves. Three randomized studies compared CARTs to the standard of care with ASCT and demonstrated the superiority of CARTs. Despite this superiority, the relapse rate remains 50%, which is significantly better than the standard of care. However, major improvements in OS have not yet been achieved. A clearer definition of eligible patients should also take into account their interim pet-scan, metabolic tumour volume, relation with Ct DNA with follow-up of minimal residual disease.

Joshua ML Casan, Mary Ann Anderson, and John F Seymour


Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma and remains a clinically challenging disease entity, particularly in the relapsed setting where outcomes are poor. However, recent innovations in targeted therapeutics have expanded treatment options and demonstrate significant efficacy even in relapsed disease. MCL frequently harbours aberrations of apoptosis pathways including over-expression of the anti-apoptotic protein BCL2. Such aberrancy promotes and sustains lymphomagenesis, thus rendering MCL an attractive target for venetoclax, the highly specific, orally bioavailable inhibitor of BCL2. Pre-clinical and early clinical data of venetoclax monotherapy demonstrated high response rates in relapsed/refractory MCL, though the durability of response in high-risk patients appears modest. More recently, clinical trials deploying combination strategies that pair venetoclax with other novel agents have been undertaken, with some promising early data reported. In this article, we review the biological rationale for deploying venetoclax in MCL, as well as the emerging data from clinical trials of venetoclax monotherapy and novel combinations.

Ruben Reinhard, Niklas Biermann, Britta Kuehlmann, and Lukas Prantl


Background: Breast implant–associated anaplastic large cell lymphoma (BIA ALCL) is a rare indolent yet lethal disease. Recently the WHO accepted it as an individual new entity. Since then national and international registries have attempted to collect epidemiological data, but incidence rates vary strongly. The aim of this article is to provide an update on the status of the national BIA-ALCL registries and identify pitfalls alongside the current collection and diagnostic algorhythm.

Methods: A systematic review of the literature was performed and epidemiological data from national registries were compared. Furthermore a case report of a false positive diagnosis was added and the pitfalls alongside the diagnostic algorhythm was worked out.

Results: The comparison of national registries revealed significant differences in the collected data. Mean start of the registries was 2014, median 2015. Reporting of BIA-ALCL cases is mandatory except in two countries. Capture rates vary between 0-100%. Incidence rates range from 0.0 up to 8.9 per million implant years. The number of deaths does not correlate with the number of implants or the total population. The very same strains of CD30 can be interpreted differently.

Conclusion: Comparing epidemiologic data revealed significant differences among national registries. In particular, non-published sales data of breast implants and non-mandatory recording of the disease lead to an overall underreporting of cases. Therefore, the incidence rates still cannot be compared uniformly. Furthermore the definition of CD30 straining intensity should be standardized and adjusted in the guidelines.

David Tucker and Cristina M. Thiebaud


The management of non-Hodgkin lymphoma (NHL), including refractory and relapsed high grade and low-grade NHL has been significantly improved in recent years with the development of cellular therapies which harness the powerful anti-cancer effects of the immune system. These include the ground-breaking and now established technology of chimeric antigen receptor cell therapy as well as the promising new range of bispecific monoclonal antibody therapies. This article will give a summary of the currently available cellular and bi-specific antibody therapies for the treatment of NHL in licenced use and clinical trials, including an overview of their proven efficacy and characteristic side-effect profiles which distinguish them from conventional immunochemotherapy.  The relative strengths and weaknesses of these comparable therapies will also be discussed together with consideration of where they may fit into the treatment sequence of NHL in the future.  The article will also address the challenges of delivering these innovative technologies in different healthcare settings and how they may alter the future of therapy for patients with this form of cancer.

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