{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:47:54Z","timestamp":1792190874325,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lipedema Foundation","award":["27A"],"award-info":[{"award-number":["27A"]}]},{"name":"Lipedema Foundation","award":["19\/15"],"award-info":[{"award-number":["19\/15"]}]},{"name":"Lipedema Foundation","award":["21\/13"],"award-info":[{"award-number":["21\/13"]}]},{"name":"Sassella Foundation","award":["27A"],"award-info":[{"award-number":["27A"]}]},{"name":"Sassella Foundation","award":["19\/15"],"award-info":[{"award-number":["19\/15"]}]},{"name":"Sassella Foundation","award":["21\/13"],"award-info":[{"award-number":["21\/13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.<\/jats:p>","DOI":"10.3390\/ijms24087591","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T03:01:48Z","timestamp":1682046108000},"page":"7591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema"],"prefix":"10.3390","volume":"24","author":[{"given":"Julia","family":"von Atzigen","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisanne","family":"Gr\u00fcnherz","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Barbon","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunther","family":"Felmerer","sequence":"additional","affiliation":[{"name":"Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center G\u00f6ttingen, Georg-August-University, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Giovanoli","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-1004","authenticated-orcid":false,"given":"Nicole","family":"Lindenblatt","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Epameinondas","family":"Gousopoulos","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Lipedema","volume":"19","author":"Herpertz","year":"1995","journal-title":"Z. 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