Central Nervous System Manifestations of Cutaneous LymphomasChakravarty
Curr Neurol Neurosci Rep (2025) 25 (1), 27
Abstract: Primary cutaneous lymphomas (PCL) are an uncommon malignancy of the lymphocytes, primarily presenting with dermatologic lesions. Central nervous system(CNS) metastatic manifestations, are even rarer. This review focus mainly on three aspects namely early suspicion of CNS involvement, selection of cases for CNS chemo-prophylaxis and lastly, the rare occurrence from skin straight to brain without other organ involvement.Primary extranodal large B-cell lymphomas are very heterogeneous. Recent molecular data have thrown some light on such divergent clinical behaviour. The peculiar, stage-independent risk of CNS spread in testicular, breast, uterine, and possibly Primary Cutaneous Diffuse Large B Cell Lymphoma Leg type (PCDBLCL-LT), may be related to prevalent MCD (MYD88/CD79B-mutated) genomic subtype in these lymphomas. It remains to be seen how this genotype might facilitate invasion of the CNS parenchyma, and whether therapies targeting the B-cell receptor or NF-κB signalling pathways could lower the risk. Some sites of extranodal involvement, almost always indicate disseminated disease with a high propensity to invade the bone marrow and leptomeningeal compartments, particularly in double-hit lymphoma. Conversely, unifocal bone, craniofacial, thyroid, or gastric DLBCL show a relatively favourable prognosis with standard immunochemotherapy. Their risk of CNS recurrence might be largely driven by potential local invasion due to anatomic proximity when epidural, orbital, or skull involvement is present, thus requiring a case-by-case approach to prophylaxis. Future studies can help clarify the relationship between extranodal DLBCLs and their indolent MALT counterparts, and whether the favorable behavior of some ABC-like lymphomas (Activated B-cell-like (ABC) diffuse large B-cell lymphomas (e.g. in the stomach or craniofacial sites) might be explained by less aggressive genotypes (e.g. BCL6/NOTCH2 subtype). MALT lymphoma is a type of non-Hodgkin lymphoma (NHL) that starts in the mucosa lining some body organs and cavities. It is a type of NHL called marginal zone lymphoma. PCL can be defined as non-Hodgkin lymphomas that initially present in the skin without any extra cutaneous manifestations at the time of diagnosis. The skin is the second most common site of occurrence of non-Hodgkin lymphomas, second only to the lymphatic system. PCL can be broadly divided into two types-T cell lymphomas and B cell lymphomas.Major subtypes of T cell lymphomas include mycosis fungoides (MF) and its variants, Sezary syndrome, CD30 + lymphoproliferative disorders, and other more rare entities like subcutaneous panniculitis- like T-cell lymphoma, extranodal NK/T cell lymphoma nasal type, primary cutaneous peripheral T-cell lymphoma not otherwise specified, and adult T-cell leukemia/lymphoma. Cutaneous B-cell lymphomas comprise approximately 25% of all cutaneous lymphomas. There are three main morphologic groups: primary cutaneous marginal zone lymphoma, cutaneous follicle-centre lymphoma, and diffuse large B-cell lymphoma, leg type(DLBCL). Other subtypes include - DLBCL other type (non-leg), and intravascular large B-cell lymphoma. Immunohistochemically cutaneous marginal zone lymphoma is classically bcl-2 positive and bcl-6 negative. This condition has an excellent prognosis, with five-year disease related survival noted to be > 95%. Primary cutaneous follicle-centre lymphoma is a lymphoma of cells of the follicle centre, usually including a combination of centrocytes and centroblasts. Immunohistochemically, the neoplastic follicle cells express bcl-6, and expression of bcl-2 is typically absent or faint. Prognosis is again excellent, with five-year disease related survival noted to be over 95%. Primary cutaneous diffuse large B-cell lymphoma, leg type is a neoplastic disorder of centroblasts and immunoblasts, which typically presents as a red to violaceous nodules or tumours on the lower extremities. Phenotypically, bcl-2 and bcl-6 are often expressed, as is MUM-1. Extracutaneous disease is common, with these tumours having a relatively high propensity to disseminate. Prognosis is variable with disease related 5-year survival being 40-50% in patients with multiple lesions at time of diagnosis, to 100% in those patients that present with a single lesion. Other, rare large B-cell lymphomas can also present in the skin. Intravascular large B-cell lymphoma is a subtype in which neoplastic B-cells have accumulated within blood vessels and often affect many organ systems (including brain), however rarely skin lesions only can occur. CNS involvement is uncommon in both types of cutaneous lymphomas and overall prognosis is not good. Brain masses and meningeal infiltration are the usual patterns though imaging may be negative with demonstration of lymphoma cells only in the CSF by flow cytometry. At times, no other organ involvement may be noted, albeit very rarely. Selection of patients who might benefit with CNS prophylactic agents is of utmost importance. On the whole, most cases of high grade cutaneous DLBCLs need to have CNS chemo-prophylaxis.© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseasesYoshikawa, Yanagita
Int Immunol (2025)
Abstract: Chronic kidney disease is a global health problem with high morbidity and mortality rates. Acute kidney injury substantially increases the risk of chronic kidney disease progression, particularly in the elderly, partly because of prolonged inflammation that exacerbates kidney fibrosis and dysfunction. Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates that develop in non-lymphoid organs during chronic inflammation, such as autoimmune diseases, cancers, and age-related inflammation. Age-dependent TLS formation is observed in various organs, such as the kidneys, bladders, lacrimal glands, and liver, potentially contributing to age-related disorders, including chronic kidney disease progression after acute kidney injury. TLSs contain heterogeneous cell populations, such as T cells, B cells, pro-inflammatory fibroblasts, and blood and lymphatic vessels, which orchestrate TLS development and expansion through intensive cell-cell interactions. Pro-inflammatory fibroblasts within TLSs drive TLS formation by producing various chemokines and cytokines that recruit and activate immune cells. Additionally, the CD153-CD30 signaling pathway between senescence-associated T cells and age-associated B cells, both of which increase with age, are essential for renal TLS maturation and expansion, which could be a promising therapeutic target in kidney injury in aged individuals. TLSs also develop in human kidney diseases, such as various glomerulopathies, transplanted kidneys, and renal cell carcinomas, thereby influencing patient outcomes. This review highlights the recent advances in our understanding of the cellular and molecular mechanisms underlying TLS development and pathogenicity, with a focus on age-dependent TLSs in the kidneys. Furthermore, the clinical relevance of TLSs in human kidney diseases is discussed.© The Author(s) 2025. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Characterization Of Beta Thalassaemia Mutations In Patients Having Borderline Haemoglobin A2 LevelsNoor, Bozdar, Malik
et alJ Ayub Med Coll Abbottabad (2024) 36 (4), 783-787
Abstract: The occurrence of a single beta thalassaemia allele is frequently related with microcytic hypochromic red blood cells and a rise in HbA2 levels. In some beta thalassaemia carriers, the outcome of this allele or its collaboration with other acquired or genetic defects may result in normal or borderline Haemoglobin bA2 levels. Objective was to establish the importance of molecular analysis in borderline HbA2 individuals and its significance in a population screening program.It was a cross-sectional study conducted over a period of six months, from July-December 2023. All 123 individuals with borderline HbA2 levels between (3‒3.9%) diagnosed by High-performance liquid chromatography (HPLC)/Capillary Zone Electrophoresis underwent molecular testing using multiplex amplification refractory mutation system-Polymerase Chain Reaction (ARMS-PCR) to detect common beta thalassaemia mutations: Fr8-9, IVS1-5, Fr41-42, Cd15, Cd5, IVS1-1, IVS1-1, Cd30, Cd30, Fr16, IVSII-1, Del619, and CAP+1 in the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi .Statistical tests were applied to compare Red Blood Cell indices and Haemoglobin A2 values among beta thalassaemia carriers and non-carriers.Among those tested, 47.1% (n=58) were found to carry Beta thalassaemia mutations. The most prevalent mutations were IVS1-5 (n=19,15.4%) and Fr8-9 (n=19,15.4%) followed by Fr41-42 (n=08,6.5%). Subjects with mutations exhibited significantly lower mean corpuscular volume and mean corpuscular haemoglobin compared to those without mutations (p-value= <0.001). Beta thalassaemia mutations were seen more frequently when HbA2 was in range of 3.5-3.9% (n=37,63.8%), as compared to HbA2 that was 3-3.4% (n=21,36.2%) and this difference was found to be significant (p-value= <0.001). The CAP+1 mutation was associated (n=02,1.6%) with normal mean MCV and MCH compared to other identified mutations.It is concluded that molecular study for the common beta thalassaemia mutations in Pakistani population plays a pivotal role in confirmation of borderline HbA2 thalassaemia carriers, specifically in areas with a high prevalence of the disease. Molecular testing for beta thalassaemia should be offered to all individuals with borderline HbA2 with values especially between 3.4‒3.9% and having microcytic hypochromic indices.
SOHO State of the Art Updates and Next Questions | Latest Advances in the Management of Primary Mediastinal B-Cell LymphomaLap, Dunleavy
Clin Lymphoma Myeloma Leuk (2025)
Abstract: Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct clinicopathologic entity that predominantly affects adolescents and young adults (AYA) and is more common in females. Although PMBCL was previously considered to be a subtype of diffuse large B-cell lymphoma, the clinical, histological, and biological characteristics overlap significantly with those of nodular-sclerosing Hodgkin lymphoma (NS-HL). Over recent years, the shared biology of these 2 entities has been highlighted in several studies, and mediastinal gray zone lymphoma, with features intermediate between PMBCL and NS-HL, has been recognized as a unique molecular entity. Although there is a lack of consensus about the optimal therapeutic strategy for patients with newly diagnosed PMCBL, highly curative treatment regimens that obviate the need for mediastinal radiation therapy (RT) are favored by most. Recently, the results from IELSG-37 were presented and demonstrated that patients with a negative PET/CT scan at the completion of treatment do not require consolidative RT. Progress in understanding the biology of PMBCL and its close relationship to NS-HL have helped pave the way for the investigation of novel strategies, including immune checkpoint inhibitors (ICI), CD30-targeting agents and adoptive T-cell approaches. Currently, a clinic trial is ongoing that is evaluating the role of nivolumab with chemo-immunotherapy for the frontline treatment of PMBCL, after ICI have shown robust responses in patients with relapsed and refractory (R/R) PMBCL. In the R/R setting, studies with anti-CD19 CAR-T-cell therapies and treatments with bispecific antibodies have shown good activity.Copyright © 2025. Published by Elsevier Inc.
膜杰作
Star Staining
