Lymphatics, Volume 3, Issue 1 (March 2025) – 8 articles

The central conducting lymphatics (CCL) and mesenteric lymphatic systems are responsible for lipid absorption, fluid regulation, and protein delivery into the bloodstream. Disruptions in these systems can result in debilitating conditions such as chylothorax, plastic bronchitis, post-operative lymphocele, protein-losing enteropathy (PLE), and chylous ascites. Advances in imaging techniques, including magnetic resonance lymphangiography (MRL), computed tomography lymphangiography (CTL), and fluoroscopic lymphangiography, allow for detailed anatomic and functional evaluation of the lymphatic system, facilitating accurate diagnosis and intervention by interventional radiologists. This review explores the embryology, anatomy, and pathophysiology of the lymphatic system and discusses imaging modalities and interventional techniques employed to manage disorders of the conducting lymphatics in the chest and abdomen. Thoracic duct embolization (TDE), percutaneous transhepatic lymphatic embolization (PTLE), and sclerotherapy are highlighted as effective, minimally invasive approaches to treat lymphatic leaks and obstructions and have shown high success rates in reducing symptoms and improving patient outcomes, particularly when medical management fails. This review seeks to demonstrate how anatomical imaging can facilitate minimally invasive procedures to rectify disorders of lymphatic flow. Full article

The impaired repair of lymphatic vessels after tissue damage is an etiological hallmark of lymphedema. Previously, we demonstrated that lymphatic recanalization after the popliteal lymph node extirpation was delayed in Gata2 heterozygous mice. This impaired lymphatic vessel recanalization in Gata2 heterozygous mice was mitigated by administrating atelocollagen or crossing with heterozygous Gata3 deletion mice. To clarify the potential involvement of Gata3 heterozygosity in collagen gene expression within subdermal tissue, we conducted an RNAseq analysis and found 273 genes with up and 522 genes with down expression in Gata3 heterozygous mice, and these genes were categorized as collagen and extracellular matrix-related genes by GO analysis. We also found that Col6a1, a2, and a3, which compose type VI collagen, underwent a transient but significant upregulation during the lymphatic recanalization process. Histological analysis revealed that the collagen structure in the subdermal tissue exhibited thinner collagen fiber in Gata3 heterozygous deficient mice. These findings suggest that the altered collagen pattern in Gata3 heterozygous mice contributed to the enhanced lymphatic vessel recanalization in Gata2 heterozygous mice. The altered collagen expression pattern might play a role in shaping and maintaining the subcutaneous microenvironment. Full article

Background/Objectives: The prognosis of acute lymphoblastic leukemia has significantly improved with the incorporation of innovative therapies such as immunotherapy, tyrosine kinase inhibitors, and CAR-T cell-based treatments. Drug resistance, mediated by genes such as ABCB1, has been associated with reduced treatment efficacy in various clinical scenarios. Although measurable residual disease (MRD) is the most reliable tool for monitoring treatment response in acute lymphoblastic leukemia, the relationship between ABCB1 expression and MRD remains unclear. Aims: To evaluate the expression of the ABCB1 resistance gene and explore its potential relationship with measurable residual disease. Methods: Prospective cohort where 57 patients with de novo diagnosis of acute lymphoblastic leukemia were admitted to the Hospital General de México “Dr. Eduardo Liceaga” between 2022 and 2024. Results: A total of 57 patients undergoing chemotherapy-based treatment were included, with a majority being male (n = 30, 52.6%) and a mean age of 32 years (range 18–71 years). Analysis of ABCB1 gene expression revealed that 35.1% (n = 20) had low expression, 40.4% (n = 23) had overexpression, and 24.6% (n = 14) showed absent expression. No statistically significant association was identified between MRD positivity and the presence of the Philadelphia chromosome (p = 0.171, 95% CI) or the ABCB1 high-risk group (high or absent expression) (p = 0.538, 95% CI). Conclusions: Although ABCB1 expression remains a valuable tool for understanding drug resistance in acute lymphoblastic leukemia, this study did not identify a significant relationship with MRD. MRD continues to be the most reliable prognostic factor in chemotherapy-based treatments for acute lymphoblastic leukemia, underscoring its importance in personalized medicine. Full article

Post-transplant lymphoproliferative disorder (PTLD) is the most common malignancy in adults who receive solid organ transplantation (SOT), apart from skin cancer. It is a serious and potentially fatal complication of chronic immunosuppression (ISI) in SOT recipients. This report describes a 20-year (2001–2021) clinicopathological experience with 59 PTLD patients at an urban center. The median time from transplant to PTLD was 8.5 years and the most common types of transplants were kidney (41%) and liver (31%). Epstein–Barr encoding region (EBER) was positive in 51% tumors, and 50% patients had Epstein–Barr virus (EBV) viremia at diagnosis. Overall survival (OS) at 1 year and 5 years was 78% and 64%, respectively. OS was significantly (p < 0.05) shorter in males (hazard ratio [HR] 3.7), certain organ transplants (lung HR 10.4; liver HR 3.9 relative to kidney), PTLD diagnosed within 12 months of transplant (HR 4.1), multi-organ involvement at diagnosis (HR 7.1), vitamin D deficiency at diagnosis (HR 4.5), and low serum albumin level at diagnosis (HR 3.6). Our study highlights the prognostic factors of PTLD and corroborates improved PTLD outcomes in the past 20 years. Full article

Lymphatic malformations (LMs) are benign, congenital vascular anomalies caused by abnormal lymphangiogenesis during embryology, often presenting as fluid-filled cystic lesions. Though LMs can affect any part of the body except the brain, they primarily manifest in the head and neck or axilla regions of children. With a prevalence of approximately 1 in 4000 births, LMs are commonly diagnosed by age two, with symptoms varying based on lesion location and size. This paper reviews the classification of LMs and discusses the de Serres staging system, which aids in assessing prognosis based on lesion site. Mutations in the (PIK3CA) gene are implicated in most cases, and LMs are also associated with syndromic conditions like Turner and Noonan syndromes. They are diagnosed by ultrasound (USS) or magnetic resonance imaging (MRI), while a histologic analysis can confirm lymphatic origin. Treatment options range from conservative approaches, such as observation, to sclerotherapy, pharmacotherapy, and surgery. Sclerotherapy, particularly with agents like OK-432, bleomycin, and doxycycline, has shown significant efficacy in reducing LM size and symptoms with minimal side effects. Pharmacological therapies, such as sirolimus, that target the mTOR pathway are also increasingly being used, with a good effect on the burden of disease. While surgical excision remains a choice for symptomatic or large lesions, minimally invasive approaches are often preferred due to lower morbidity. Emerging techniques include gravity-dependent sclerotherapy, electrosclerotherapy, alpelisib, everolimus, and Wnt/β-catenin pathway stimulators (e.g., tankyrase inhibitors, porcupine inhibitors). Computational atomistic molecular dynamics (MD) and density functional tight binding (DFTB) techniques may offer an experimental approach to future therapeutic targets. This paper highlights a multidisciplinary approach to LM management, emphasising individualised treatment based on lesion characteristics and patient needs. Full article

Introduction: Studies on the association between immune-mediated disorders and lymphoid disorders have been very limited, especially in diverse populations. The objective of this study is to evaluate the relationship between a variety of immune diseases and lymphoid malignancies. Methods: The NIH “All of Us” database was utilized to perform a cross-sectional analysis between lymphoid disorders and various immune diseases. The adjusted multivariable logistic regression analysis was performed in R to examine the association between lymphoid disorders such as leukemia, lymphoma, and plasma cell neoplasms against a variety of autoimmune diseases. Results: In the study cohort of 316,044 patients, we found significant associations between lymphomas and the aforementioned immune-mediated diseases, with the exception of dermatomyositis and scleroderma. Lymphoid leukemias showed significant associations (p < 0.001) with several autoimmune conditions, including psoriasis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and hyperthyroidism. In plasma cell neoplasms, significant associations were found in all but dermatomyositis, scleroderma, vitiligo, and atopic dermatitis (p < 0.001). Conclusions: In this population-level analysis, the majority of immune-mediated diseases were found to be significantly correlated with an increased incidence of lymphoid malignancies. As such, patients diagnosed with immune-mediated diseases should undergo close surveillance and early screening with the goal of early identification and treatment of lymphoid malignancies. Full article

Multiple myeloma is an incurable hematologic malignancy arising from plasma cells. The uncontrolled growth of monoclonal plasma cells leads to an abnormal overproduction of immunoglobulins. The recommended course of treatment for MM is according to disease progression and responses to therapeutic intervention, highlighting the necessity for multiple treatment options that alleviate different parts of MM. This comprehensive review provides insights into the current treatments and how to take preventative and prognostic measures. In advanced MM, osteoporosis is a common symptom that originates from a lack of regulation in osteoclast activity and bone resorption. Bisphosphonates such as zoledronic acid and pamidronate along with monoclonal antibodies such as denosumab hinder osteoclast function and aid in reducing the risk of fractures in patients with advanced MM. For targeted therapy approaches, proteasome inhibitors impede protein degradation pathways that cause an accumulation of misfolded proteins promoting cancer cell proliferation in patients with MM. CAR-T is another targeted therapy that can utilize T cells to target and isolate MM cells. Overall, this review highlights the frontrunners of treatments for those diagnosed with MM. Full article

The soluble interleukin-2 receptor (sIL-2R) is a novel biomarker associated with a variety of immune-mediated diseases. It is produced through the proteolytic cleavage of the membrane-bound interleukin-2 receptor α-chain on activated T lymphocytes; hence, its increase reflects T-cell activation and immune dysregulation. Elevated sIL-2R levels are frequently documented in conditions such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, histiocytosis, hemophagocytic lymphohistiocytosis, lymphomas, and graft-versus-host disease, suggesting a potential role in monitoring disease activity and progression. However, sIL-2R levels may increase in the context of immune response to infections and malignancies, requiring careful interpretation. It is essential to determine whether elevated levels of this marker within specific ranges could suggest a specific entity, due to the implications this may have for the management of patients. This case-based review presents five patients with different immune-mediated diseases, highlighting how these different conditions can present with characteristic ranges of sIL-2R elevation. By integrating clinical findings with sIL-2R measurements, we emphasize the biomarker’s utility in guiding diagnosis, as well as monitoring disease activity and determining prognosis, which can enhance clinical decision-making and patient management in rheumatology and related fields. Full article