Liu N F, Gao M Z, Maltese P E, Bertelli M
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Peoples' Republic of China.
MAGI'S LAB S.R.L., Rovereto, Italy.
Lymphology. 2023;56(3):99-109.
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.
原发性淋巴水肿（PLE）是一种由淋巴管发育异常引起的慢性疾病，会发展为不可逆的组织水肿和肥大。迄今为止，对PLE的了解一直有限。本研究的目的是设计一种更新的PLE分类系统，纳入了1013例下肢PLE患者。记录了性别、发病年龄、部位、家族史和发病率。评估了磁共振淋巴造影（MRL）、吲哚菁绿淋巴造影（ICGL）和淋巴闪烁造影（LSG）的淋巴成像结果、皮肤组织免疫组化染色、全外显子测序以及基因型-表型的相关性。患者被分为先天性发病组和迟发性发病组。迟发性发病组根据发育年龄进一步细分。先天性发病与迟发性发病的PLE比例为1:4，最高发病率在青春期。先天性发病组和迟发性发病组的性别比分别为1.04:1和1.5:1。确定了三种主要的淋巴管异常，其中以淋巴管延迟显示或部分显示为特征的节段性淋巴管功能障碍最为常见，且与FLT4、GJC2、CELSR1和PTPN14突变相关。第二常见的类型是淋巴管增生，与FOXC2和GATA2变异相关，其次是初始淋巴管发育不全或功能障碍，在先天性PLE患者中更常见，且与FLT4突变相关。提出了一种淋巴管异常的功能和结构相结合的分类方法，包括节段性淋巴管功能障碍、淋巴管增生和初始淋巴管发育不全或功能障碍。
