Lymphatics, Volume 3, Issue 4 (December 2025) – 8 articles

Introduction: Axillary reverse mapping (ARM) aims to reduce the risk of breast cancer-related lymphedema (BCRL) by preserving and limiting dissection of arm-draining lymphatics. The ideal type of dye and the location of injection, which maximize the sparing of lymphatics and improve outcomes of immediate lymphatic reconstruction (ILR), remain under-studied. The current literature reports inconsistent visualization of lymphatics using blue dye alone, whereas indocyanine green (ICG) near-infrared (NIR) lymphography has shown improved rates. However, optimized dual-dye workflows integrating breast–plastics co-surgery are lacking. Methods: A retrospective review of patients who underwent ILR following ALND for breast cancer between June 2021 and June 2023 was conducted. Patients who underwent ARM using our dual-dye technique were included, utilizing intradermal injections of indocyanine green (ICG) into the wrist and isosulfan blue (ISB) into the upper arm. Axillary reverse mapping channels were categorized by the type of dye used to visualize. Dye injection site, number of lymphatic channels visualized, channel diameter (mm), time-to-first channel, coordinates relative to fixed landmarks, ILR configuration, and pathologic findings were reviewed. Mann–Whitney U tests were used to compare channel visualization rates between types of dye. Results: Of 26 patients, 21 underwent dual-dye mapping and were included. A total of 115 ARM channels were identified: 99 (86%) via ICG and 29 (25%) via ISB. A total of 64 lymphaticovenous anastomoses were performed (mean: 2.46 per patient). Both dyes were identified in the axilla in only 11.7% of patients. At the end of the study, the lymphedema rate was 12%. Conclusions: We developed a reproducible dual-dye ARM technique for ALND with planned ILR, reducing lymphedema risk while maintaining oncologic safety. Dual-dye mapping reveals that proximal and distal lymphatics exhibit both overlapping and divergent drainage to axillary nodes. ICG’s higher axillary detection rate may reflect true anatomical differences or dye properties. These findings support the need for individualized lymphatic mapping during breast cancer surgery to guide preservation techniques and reduce the risk of BCRL. Full article

Lymphedema is a chronic, progressive, and debilitating disease of the lymphatic system with no current cure. Physiologic procedures, which address the underlying pathophysiology of lymphatic dysfunction, have gained traction in both treatment and prevention of lymphedema. This narrative review examines current physiologic lymphedema surgical techniques and emerging developments in this rapidly evolving field. While the two most common physiologic surgeries remain lymphovenous bypass (LVB) and vascularized lymph node transfer (VLNT), newer physiologic surgery techniques such as vascularized lymph vessel transfer (VLVT) and lymph node to vein anastomosis (LNVA) have been described in an effort to reduce donor site morbidity, with early promising clinical outcomes. The use of bioengineering with stem cells, pro-lymphangiogenic growth factors, and biomaterials such as Biobridge can be applied in conjunction with surgery to help promote lymphangiogenesis. Technological advances in robotic surgical systems and 3D exoscopes are helping to make supermicrosurgery more technically feasible and ergonomic, and increasing accessibility to lymphedema surgery. As our surgical armamentarium expands, treatment algorithms must be updated to determine how various surgical techniques can be combined and sequenced, how the indications for physiologic surgery can be expanded, and how surgical treatment can be tailored to the patient and disease process. Full article

This review analyzed approximately 115 peer-reviewed studies published between 2010 and 2025, focusing on molecular subtyping and circulating tumor DNA (ctDNA)-guided approaches in Diffuse Large B-Cell Lymphoma (DLBCL). Evidence was synthesized from retrospective cohorts, prospective clinical trials, and translational studies, highlighting how molecular heterogeneity, clonal evolution, and the tumor microenvironment complicate classification and treatment. While molecular subtypes such as MCD, BN2, EZB, A53, and ST2 have improved prognostication, their routine use in clinical practice remains limited due to cost, complexity, and restricted access to sequencing platforms. Tumor-informed ctDNA assays show promise for minimal residual disease (MRD) monitoring and adaptive therapy, yet their predictive power for CAR-T therapy, bispecific antibodies, and checkpoint inhibitors is still incompletely understood. Overall, the literature converges on the need for integrated strategies combining ctDNA, molecular subtyping, and immune microenvironment analysis to personalize frontline therapy. Full article

Acute lymphoblastic leukemia is the most common cause of cancer-related death in children and represents a poor prognosis for patients in high-risk groups. Current treatment protocols are based on intensive polychemotherapy, which is associated with a significant toxicity profile. Due to their higher specificity and lower toxicity, immunotherapies based on monoclonal antibodies, in particular antibody–drug conjugates (ADCs), are revolutionizing cancer therapy. However, reports on the potential efficacy of ADC-targeted therapy in ALL and its subgroups are limited. Gene expression data suggest that potentially new ADC antigens are highly abundant in ALL subgroups and represent promising targets for cancer therapy. In addition, the PI3K/AKT and RAS/MAPK signaling pathways are often persistently activated in ALL and recent data showed that active feedback loops following inhibition of these pathways can lead to redundancy of cell surface receptors that can potentially serve as antigens for ADC treatment. Therefore, we provide here an overview of the most interesting receptors of the various ALL subgroups and discuss the influence that feedback loops of the PI3K/AKT and RAS/MAPK signaling pathways may have on increasing protein expression of the aforementioned receptors, which could lead to targeted combination therapy approaches in the future. Full article

Gastrointestinal (GI) lymphomas are a diverse group of extranodal non-Hodgkin lymphomas primarily affecting the stomach, small intestine, and colon. They present with non-specific symptoms such as abdominal pain, weight loss, or GI bleeding, making early diagnosis challenging. Histologic subtypes vary, with mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) being the most common. Diagnosis involves endoscopic evaluation with biopsy, cross-sectional imaging, and often PET-CT. Management is subtype-dependent, including antibiotics for H. pylori-associated MALT lymphoma, chemotherapy, immunotherapy, and occasionally surgery. A multidisciplinary approach is essential for optimal outcomes. Core Tip: Gastrointestinal lymphomas are rare but clinically significant malignancies with variable presentations. Accurate diagnosis and tailored treatment based on the histologic subtype and site are critical, requiring close collaboration among gastroenterologists, pathologists, oncologists, and radiologists. Full article

Background: Castleman’s disease (CD), also known as angiofollicular lymph node hyperplasia, describes a rare group of diseases manifesting with enlarged lymph nodes and various inflammatory symptoms. The association between Castleman’s disease, paraneoplastic pemphigus and bronchiolitis obliterans has been described in the literature and is depicted thoroughly in this case. Case Presentation: We present a case of severe bronchiolitis obliterans developing in a 17-year-old female with paraneoplastic pemphigus and unicentric Castleman’s disease. Conclusion: Surgical resection of unicentric Castleman’s disease remains the treatment of choice due to its efficacy in preventing the recurrence of associated morbidity caused by bronchiolitis obliterans and paraneoplastic pemphigus. Full article

Free jejunum is used for reconstruction after resection of advanced head and neck cancer. Postoperative transplanted mesenteric lymph nodes swelling is often experienced, but its clinical significance is unclear. This study included patients who underwent free jejunal reconstruction at Gifu University Hospital between March 2017 and November 2023. Regarding the size change of postoperative mesenteric lymph node and risk factors, the correlation with metastasis and prognosis was investigated. This study included 51 patients, of whom 16 cases (31.4%) had postoperative mesenteric lymph node swelling and 2 cases (3.9%) had metastasis. Only two cases with metastasis showed an increase in size of 5 mm or more. Many cases without extracapsular extension and cases of salvage surgery had postoperative mesenteric lymph node swelling (p = 0.0429, p = 0.0269). No correlation was found between postoperative mesenteric lymph node swelling and prognosis. However, because all cases with metastasis were included in cases of postoperative mesenteric lymph node swelling, this could be one factor in determining whether or not metastasis occurred. The transplanted mesenteric lymph node swelling is one of the important postoperative evaluation items, and additional evaluation such as PET-CT may be recommended. Full article