Lymphatics, Volume 2, Issue 3 (September 2024) – 5 articles

Despite chronic fibrosis occurring in many pathological conditions, few in vitro studies examine how fibrosis impacts lymphatic endothelial cell (LEC) behavior. This study examined stiffening profiles of PhotoCol^®—commercially available methacrylated type I collagen—photo-crosslinked with the photoinitiators: Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), Irgacure 2959 (IRG), and Ruthenium/Sodium Persulfate (Ru/SPS) prior to evaluating PhotoCol^® permeability and LEC response to PhotoCol^® at stiffnesses representing normal and fibrotic tissues. Ru/SPS produced the highest stiffness (~6 kilopascal (kPa)) for photo-crosslinked PhotoCol^®, but stiffness did not change with burst light exposures (30 and 90 s). The collagen fibril area fraction increased, and dextran permeability (40 kilodalton (kDa)) decreased with photo-crosslinking, showing the impact of photo-crosslinking on microstructure and molecular transport. Human dermal LECs on softer, uncrosslinked PhotoCol^® (~0.5 kPa) appeared smaller with less prominent vascular endothelial (VE)-cadherin (cell–cell junction) expression compared to LECs on stiffer PhotoCol^® (~6 kPa), which had increased cell size, border irregularity, and VE-cadherin thickness (junction zippering) that is consistent with LEC morphology in fibrotic tissues. Our quantitative morphological analysis demonstrates our ability to produce LECs with a fibrotic phenotype, and the overall study shows that PhotoCol^® with Ru/SPS provides the necessary physical properties to systematically study LEC responses related to capillary growth and function under fibrotic conditions. Full article

Background: Some cases of classic Hodgkin lymphoma (CHL) display similarities to nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in terms of architecture, leading to potential challenges in diagnosis. However, these difficulties can be overcome by conducting a thorough set of immunohistochemical examinations. Objective: To examine cases of T-cell-rich CHL that closely resemble the diagnosis of NLPHL, specifically pattern D, which can pose challenges in accurately determining the diagnosis even after conducting a thorough immunophenotypic assessment. Materials and methods: Histopathology slides of three cases of T-cell-rich CHL were retrieved and thoroughly examined to assess their clinical, immunomorphologic, and molecular features. Results: We present three cases containing cells that resembled lymphocyte predominant and Hodgkin Reed–Sternberg cells, expressing some B-cell antigens and CHL markers but all were lacking Epstein–Barr virus-encoded small RNA. All three cases were found in a background rich in T-cells with focal remaining follicular dendritic cell meshwork in one case. Only one case had few eosinophils while the other two had no background of eosinophils and plasma cells. Two patients presented with stage IIA and B-symptoms presented in one of them. Two patients were treated with four and six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), respectively. One patient planned to be treated with four cycles of ABVD plus Rituximab therapy. Conclusions: Some cases of Reed–Sternberg cells can show expression of both B-cell and CHL markers. This overlapping characteristic, which has not been extensively discussed in the existing literature, presents a unique challenge for treatment. Further research into these neoplasms may reveal valuable diagnostic and therapeutic implications. Full article

Chronic lymphocytic leukemia (CLL) is the most common human leukemia. The disease is caused by abnormal proliferation and development of lymphocytes and their precursors in the blood and bone marrow (BM). Recent studies have shown that the CLL’s clinical course and outcome depend not only on genetic but also epigenetic factors. MicroRNAs (miRNAs) are involved in the development of hematological tumors, including CLL. The aim of this study is to identify the miRNA expression profile in CLL and determine the role of miRNAs in biological pathways associated with leukemogenesis in CLL. The following samples were used in this study: (1) samples obtained by sternal puncture and aspiration biopsy of BM (n = 115). They included samples from 21 CLL patients with anemia and indications for therapy and 45 CLL patients without anemia and with indications for therapy. The control group for the CLL BM samples consisted of patients with non-cancerous blood diseases (n = 35). (2) Lymph node (LN) samples (n = 20) were collected from CLL patients. The control group for the CLL LN samples consisted of patients with lymphadenopathy (n = 37). All cases were patients before treatment. We demonstrated a significant upregulation of miRNA-34a and miRNA-150 in CLL BM samples (p < 0.05) and downregulation of miRNA-451a in CLL LN samples (p < 0.05). We noted a dynamic increase in the levels of miRNA-150 and miRNA-34a in BM at various stages of tumor progression of CLL. We concluded that a dynamic picture of clinical manifestations of CLL closely correlates with changes in epigenetic characteristics of the tumor. Progression of the lymphoproliferative process and indications for cytoreductive therapy are associated with changes in the miRNA profile generated by cancer cells in different sites of clonal expansion. Full article

Lymphoedema is a potential adversity following axillary clearance, which is frequently performed in the setting of surgery for breast cancer or cutaneous malignancies of the upper limb. Often underestimated, lymphoedema can lead to debilitating symptoms which may decrease overall health-related quality of life. A retrospective cohort study was undertaken on 73 patients who underwent axillary clearance for breast and cutaneous malignancies from 2011 to 2021 at a tertiary centre in Melbourne, Australia. Bilateral upper limb circumference measurement was used to identify the prevalence of lymphoedema in this population. The lymphoedema quality of life (LYMQOL) questionnaire was used to assess the patient’s quality of life. Of 73 patients, 42 (58%) had lymphoedema; 33 (45%) were clinically detected as part of the study, and 9 were diagnosed with lymphoedema prior to our study. Patients with lymphoedema (n = 42) reported worse scores in all LYMQOL domains and the overall quality of life, but only the ‘appearance’ domain showed statistically significant differences in our cohort. These results demonstrate a substantial post-axillary clearance lymphoedema prevalence, without significant impacts on quality of life. Full article