3 articles
Follicular lymphoma (FL) is a slow-growing B-cell lymphoma with a generally favorable prognosis. Nevertheless, its clinical course is heterogeneous, with a significant subset of patients experiencing early progression or histological transformation into diffuse large B-cell lymphoma (DLBCL), both considered to be high-risk events associated with treatment resistance and markedly inferior outcomes. Importantly, clinical risk factors have limited value in predicting these complications. This review outlines the key biologic features of FL, discussing how the novel molecular biology approaches can explain the clinical heterogeneity and high-risk disease evolution of FL.
A focused literature review was conducted using the PubMed/MEDLINE database to identify studies on follicular lymphoma and its histological transformation to diffuse large B-cell lymphoma. Priority was given to original research or review articles investigating genetic, epigenetic, transcriptional, or microenvironmental determinants of FL.
Evidence from early cytogenetic and DNA sequencing studies established BCL2 deregulation as an initiating lesion in FL, with further genetic alterations in epigenetic regulators like KMT2D, EZH2, CREBBP/EP300 occurring early on and persisting throughout the disease course. Studies of transformed FL samples indicate that aggressive evolution is associated with acquisition of additional genetic lesions, such as those affecting the cell cycle regulators CDKN2A/2B and TP53. More recently, integrated genomic, transcriptomic and spatial resolved techniques have demonstrated substantial transcriptional heterogeneity within individual genetic subclones, suggesting that the genotype alone does not determine the phenotype of the malignant cells and supporting a pathogenetic model in which clinical trajectories reflect the combined effects of genomic evolution, transcriptional cell state, and tumor-microenvironment crosstalk. Important findings, including greater infiltration with LAG3+CD8+ T cells in cases of histological transformation to DLBCL and upregulation of transcriptional programs that promote stromal expansion and B-cell receptor signaling in cases of early FL relapse, indicate that integrated profiling represents a promising avenue for identifying the biomarkers and treatment targets that are specific to high-risk disease.
Continued research concentrated on multiomic profiling of both malignant and non-malignant tumor compartments is essential in order to reveal the mechanisms of FL heterogeneity and translate these data into practical biomarkers and therapeutic strategies.
Psoriasis is a chronic immune-mediated inflammatory condition and is considered a potential risk factor for the development of hematologic malignancies, particularly in the context of immunosuppressive therapy and T-cell dysfunction. B-cell non-Hodgkin lymphomas are neoplasms of the lymphatic system with variable clinical manifestations, most commonly presenting with peripheral lymphadenopathy. Primary localization in the soft tissues of the head, with bone invasion, is rare.
We report a rare case of cephalic aggressive NHL Not Otherwise Specified (NOS) in a 63-year-old patient with a history of psoriasis vulgaris and Clear cell carcinoma (T1N0M0, treated in 2021 at the Oncology Institute in Chișinău), who presented with a painless right temporo-parietal mass. MRI revealed a 48×19×50 mm lesion in the temporal soft tissues with extension into the frontal bone. Surgical biopsy and immunohistochemistry (CD20+, CD79a+, CD45+, BCL6-) confirmed the diagnosis of B-cell NHL NOS. In 2022, the patient received 8 induction cycles of immunochemotherapy followed by maintenance therapy with Rituximab. PET/CT evaluation showed a Deauville score of 3, indicating a partial favorable response. Associated comorbidities (psoriasis, type 2 diabetes mellitus, hypertension) required multidisciplinary monitoring.
This case illustrates an unusual cranial localization of aggressive B-cell lymphoma NOS and highlights the potential link between psoriasis and lymphoproliferative risk, as previously suggested in the medical literature.
Non-Hodgkin lymphoma is a heterogeneous group of malignant lymphoid tumors. Hemostasis disorders in non-Hodgkin lymphoma are often asymptomatic but can develop into severe complications. The risk of venous thromboembolism increases according to the totality of risk factors assessed directly in each individual patient, based on age, gender, comorbidities, performance status, and both congenital and acquired thrombophilia.
This study aims to evaluate the incidence of hemostasis disorders based on age, gender, NHL type, degree of dissemination, B symptoms, disease onset, tumor size, positivity of anticardiolipin, anti-β2-glycoprotein I, and lupus anticoagulant antibodies, fibrinogen level, lactate dehydrogenase, D-dimers, and Eastern Cooperative Oncology Group performance status.
A total of 161 patients diagnosed with NHL at the Oncology Institute of the Republic of Moldova were evaluated in a prospective cross-sectional descriptive study. Anticardiolipin and anti-β2-glycoprotein I antibodies were measured by enzyme-linked immunosorbent assay, and lupus anticoagulant was assessed by the turbidimetry method. Quantitative testing of D-dimers was performed using automatic latex-agglutination with photometric detection. Plasma fibrinogen levels were assessed by coagulometry. The data were statistically analyzed using Microsoft Excel, GraphPad Prism ver. 9.3.0, Epi Info 7.2, EpiMax Table, and IBM SPSS Statistics version 26.0.
The study included 161 de novo patients, with 48% women and 52% men, and a median age of 59 years. Among them, 56.5% had aggressive non-Hodgkin lymphoma (NHL), and 43.5% had indolent NHL, with a higher prevalence of advanced stages (65.8%). Hemostatic disorders were observed in 10.6% of cases, with venous thromboembolism occurring in 6.7%, more frequently in patients with aggressive non-Hodgkin lymphoma, tumor sizes ≥ 7 cm, a mean age of 50 years, in men (82%), mainly in the first 3-4 weeks, with higher levels of fibrinogen and D-dimer at diagnosis. Anticardiolipin, anti-β2-glycoprotein I, and lupus anticoagulant antibodies were recorded in 3.7% cases of venous thromboembolism cases. Statistical significance was not reached when analyzing thrombosis according to performance status.
The risk of venous thromboembolism in non-Hodgkin lymphoma is dependent on gender, type, tumor size, mediastinal onset, hyperfibrinogenemia, antibody synthesis, and high LDH level. The distribution of patients with non-Hodgkin lymphoma and venous thromboembolism according to disease stage, B symptoms, and performance status was statistically insignificant.