{"title":"An Updated Classification of Primary Lymphedema Based on Age of Onset, Lymphatic Anomalies, and Genetics.","authors":"N F Liu, M Z Gao, P E Maltese, M Bertelli","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Primary lymphedema (PLE) is a chronic disease caused by lymphatic dysplasia and progresses to irreversible tissue edema and hypertrophy. Understanding of PLE has been hitherto limited. The aim of this study is to devise an updated classification system for PLE of 1013 patients with PLE of lower limb were enrolled. Sex, age of onset, location, family history and morbidity were documented. The lymphatic imaging findings of magnetic reso-nance lymphography (MRL), indocyanine green lymphography (ICGL) and lymphoscin-tigraphy (LSG), skin tissue immunohisto-chemical staining, whole exome sequencing and the correlation of genotype-phenotype were evaluated. Patients were divided into a congenital onset category and a late onset category. The late onset category was further divided according to developmental age. The ratio of congenital-onset to late-onset PLE was 1:4 and that the highest incidence was in adolescence. The sex ratio was 1.04:1 and 1.5:1 in congenital-onset and late-onset groups, respectively. Three major lymphatic anomalies were identified, in which segmental lymphatic dysfunction, characterized by delayed or partial demonstration of lymph vessels, is the most common and associated with FLT4, GJC2, CELSR1, and PTPN14 mutations. The next most common type is lymphatic hyperplasia, which is associated with FOXC2 and GATA2 variants, followed by initial lymphatic aplasia or dysfunction, which is more common in pa-tients with congenital PLE and associated with FLT4 mutation. A functional and structural combined classification of lymphatic anomalies is proposed, which includes segmental lymphatic dysfunction, lymphatic hyperplasia and initial lymphatic aplasia or dysfunction.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"56 3","pages":"99-109"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Fate of Implanted BioBridge<sup>tm</sup> Collagen Matrix - Findings in Histology, Scanning, and Transmission Electron Microscopy.","authors":"M Witt, A Ring, I Stricker, E Fruth","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The technique of lymphangioplasty or capillary thread drainage was historically performed with subcutaneously implanted surgical threads. It has recently been revived by introducing a thread-like aligned nanofibrillar collagen matrix (BioBridge<sup>tm</sup>). These collagen threads consitute subcutaneous neocollectors along which guided lymphangiogenesis is said to occur secondarily. We present for the first time a tissue examination of a 10-month implanted BioBridge<sup>tm</sup> sample with surrounding tissue from a human subject by histology, scanning and transmission electron microscopy.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"56 3","pages":"121-124"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modified Lymphoscintigraphy in Primary Lymphatic Insufficiency of the Lower Limb.","authors":"M Wald, J Svobodova, H Krizova","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Primary lymphedema of the foot and toes could be sometimes misdiagnosed by lymphoscintigraphy as a whole lower limb lymphatic insufficiency (LLLI). This is caused by using standard lymphoscintigraphic protocol based on one interstitial injection of radiotracer applied into the first interdigital space followed by image analysis of lower limb lymphatic vessels and lymph nodes. Here, we show that a modification of the lymphoscintigraphic protocol and introduction of a second dose of radiotracer right above the inner ankle to the clinically healthy tissue can more accurately describe morphological abnormalities of the superficial lymphatic system at the lower limb and thereby refine the diagnosis of the LLLI. Fourteen patients with swelling of the foot and toes (16 lower limbs) were examined using standard lymphoscintigraphic protocol. Subsequently, modified lymphoscintigraphy was performed. While standard lymphoscintigraphy showed severe lymphatic insufficiency of the superficial lymphatic system in all 14 patients (in 16 lower limbs), including significantly reduced number of inguinal nodes, modified lymphoscintigraphy revealed almost normal morphology of superficial lymphatic vessels in 11 patients (in 13 lower limbs) throughout the entire lower limb proximal to the application site. In conclusion, using the modified lymphoscintigraphy protocol in patients with foot and toes primary lymphedema can refine diagnosis and follow-up medical management.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"56 2","pages":"61-71"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Adondakis, H Ali, B P Salehi, R Friedman, W Sun, K Donohoe, G Kim, D Singhal, L L Tsai, J Weinstein
{"title":"Correlation of Inguinal Lymph Node Number and Volume with Lower Extremity Lymphedema Severity.","authors":"M Adondakis, H Ali, B P Salehi, R Friedman, W Sun, K Donohoe, G Kim, D Singhal, L L Tsai, J Weinstein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>There are very limited studies on the relationship of inguinal lymph node number and volume correlated with lower extremity lymphedema severity. In this IRB-approved retrospective study, patients who obtained an MRI for lower extremity lymphedema and who did not have lymph node resection or biopsy were identified. The MRI images were used to determine the number and volume of inguinal lymph nodes for each limb in addition to fat and fluid-based scoring using a validated grading system. Wilcoxon signed-rank tests were used to compare the greater-affected limbs with the lesser-affected limbs. The spear-man-rank correlation was performed on a 'per limb' basis for MRI-based scoring and clinical parameters with ipsilateral lymph node number and volume and for differences between the limbs. A total of 32 patients were included. The greater-affected limb had higher MRI fluid scores (median (interquartile range) = 3 (3 - 3) vs. 0 (0 - 1), (p < 0.01) relative to the contra-lateral limb and had a median fat asymmetry score of 2 (1 - 3). On the per-limb analysis, lymph node number and volume inversely correlated with total MRI scores (ρ = -0.47, p < 0.01 for node number and volume). The difference of lymph node number and volume correlated with MRI score difference (node number: ρ = -0.66, p < 0.01; node volume: ρ = -0.64, p < 0.01) and perometer difference (node number: ρ = -0.58, p < 0.01; node volume: ρ = -0.59, p < 0.01). Inguinal lymph node number and volume inversely correlate with lower extremity edema presence and severity.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"56 4","pages":"160-167"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oncolymphology: Immune Interactions and Cancer.","authors":"S P Leong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The proposed term \"oncolymphology\" encompasses the intimate relationship between cancer growth and the immune responses.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"56 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X Geng, L Chen, R S Srinivasan, R J Kylat, M H Witte, R J Erickson
{"title":"Lack of embryonic homozygous or adult heterozygous lymphatic phenotypes for a <i>Sos1</i> mutation and lack of lymphatic embryonic phenotypes for a homozygous <i>Cx47</i> mutation in mice.","authors":"X Geng, L Chen, R S Srinivasan, R J Kylat, M H Witte, R J Erickson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have studied the lymphatic phenotypes of 2 mutations, known to cause abnormalities of lymphatics in humans, in mice. The <i>Cx47</i> R260C mutation (variably penetrant in humans heterozygous for it and causing limb lymphedema) had an adult mouse phenotype of hyperplasia and increased lymph nodes only in homozygous condition but we did not find any anatomical phenotype in day 16.5 homozygous embryos. Mice harboring the <i>Sos1</i> mutation E846K (causing Noonan's in man which occasionally shows lymphatic dysplasia) had no adult heterozygous phenotype in lymphatic vessel appearance and drainage (homozygotes are early embryonic lethals) while day 16.5 heterozygous embryos also had no detectable anatomical phenotype.</p>","PeriodicalId":94343,"journal":{"name":"Lymphology","volume":"55 3","pages":"129-134"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583265/pdf/nihms-1937248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}