Your search

BACKGROUND: lipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available. METHODS: in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema. RESULTS: Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema. CONCLUSIONS: the consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

Lipedema is a chronic disease characterized by the symmetrical accumulation of adipose tissue in the lower body, primarily affecting women. Despite being recognized for over 85 years, the pathophysiology, diagnosis, and treatment of lipedema remain complex and not fully understood. This review consolidates current knowledge, emphasizing histological, genetic, and hormonal factors, alongside diagnostic and therapeutic approaches. Histological studies highlight changes such as adipocyte hypertrophy, increased fibrosis, and vascular alterations like angiogenesis. Genetic studies suggest a strong familial component, with multiple loci potentially influencing disease onset, yet the condition remains polygenic and influenced by environmental factors. Hormonal influences, particularly estrogen, play a significant role in disease pathogenesis. Diagnostic imaging techniques like dual-energy X-ray absorptiometry (DXA), ultrasound (US), and magnetic resonance imaging (MRI) provide valuable insights but are not definitive. Therapeutic strategies, including diet, weight loss, and Complex Decongestive Therapy, offer symptom management but are not curative, with liposuction considered for severe cases where conservative methods fail. The condition's complexity stems from genetic, hormonal, and environmental influences, necessitating further research to improve diagnostic and treatment strategies. Integrating genetic and hormonal insights into clinical practice could enhance patient outcomes and quality of life, highlighting the need for continued exploration and understanding of lipedema.

Background: Emerging evidence suggests that lipedema may share hormonal, inflammatory, and genetic mechanisms with gynecologic diseases, particularly endometriosis. However, the extent and nature of these interrelationships remain poorly characterized, supporting the need for this scoping review. Objectives: To map and synthesize the available evidence on the clinical, pathophysiological, and epidemiological interrelationships between lipedema in women, endometriosis, and other gynecologic diseases. Methods: Searches were conducted in international and regional health databases, including MEDLINE (PubMed), CINAHL, Scopus, Embase, Web of Science, the Cochrane Library, LILACS/VHL, APA PsycInfo, SciELO, Epistemonikos, and La Referencia, as well as grey literature sources and relevant institutional websites. There were no language restrictions. The search period began in 1940, the year in which lipedema was first described by Allen and Hines. Study selection followed a two-stage process conducted independently by two reviewers, consisting of title and abstract screening followed by full-text review. Data extraction was performed using a pre-developed and peer-reviewed instrument covering participants, concept, context, study methods, and main findings. The review protocol was registered in the Open Science Framework. Results: Twenty-five studies from ten countries were included. Synthesized evidence supports the characterization of lipedema as a systemic condition with metabolic and hormonal dimensions. Key findings include symptom onset linked to reproductive milestones, a high frequency of gynecologic and endocrine comorbidities, and molecular features overlapping with steroid-dependent pathologies. These patterns reflect a recent shift from a predominantly lymphovascular paradigm toward a more integrated endocrinometabolic framework. Conclusions: The findings indicate that lipedema clusters with hormone-sensitive gynecologic and endocrine features across reproductive life stages.

Background. Lipedema is a chronic and progressive fat disorder that affects ~11% of the female population. It is characterized by bilateral, disproportionate accumulation of subcutaneous adipose tissue predominantly in the lower body. Symptoms include pain, bruising, swelling, and subcutaneous nodules that are resistant to traditional interventions such as diet and exercise. Aim. The objective of this review is to summarize recent evidence on the characteristics, pathophysiology, diagnosis and treatment of lipedema. Matherial and Methods. A literature search was conducted using the PubMed database. The inclusion criteria were “full free text” and English scientific articles, published between 2015 and 2025. A total of 74 records were found, of which    publications were ultimately included in the review. Results. Awareness of lipedema in the medical field is increasing, but its differential diagnosis still remains a challenge. Lipedema is often unrecognized or misdiagnosed as obesity or lymphedema. Conclusion. This narrative review provides a deeper understanding of lipedema as a serious condition, discusses its pathophysiology and treatment options. The data reveal advances in knowledge, particularly in conservative and surgical treatment with a focus on improving quality of life. However, there is a lack of scientific evidence confirming the safety and efficacy of various treatment methods. Further research is required to ensure the safety and increase the efficacy of treatment for this complex condition known as lipedema.

Background:  Lipedema is a progressive subcutaneous adipose tissue disorder predominantly affecting women. Characterized by painful nodules and inflammation, it impairs mobility and quality of life. Traditional nonsurgical treatments currently offer limited relief and necessitate additional interventions. This study aimed to evaluate the efficacy of SMiLE (Softening, Mobilization, Liposuction, Extraction), a lipedema reduction surgery (LRS) technique. This technique combines lymphatic-sparing liposuction with manual lipedema extraction to comprehensively remove lipedema nodules. Methods:  Sixty-two women who underwent LRS with the SMiLE technique by the primary author participated in the study and completed an online survey. Data were collected on prior medical history related to lipedema development and comorbidities and outcome measures such as pain, activities of daily living, and quality of life before and after surgery. Results:  The findings demonstrate significant improvements in patients’ daily lives following surgery. Pain levels decreased by an average of 73.9%, with the most notable reduction in the buttock shelf (81.3%). Mobility improved for 93% of participants who had faced challenges before LRS, and quality-of-life assessments indicated a 47.5% reduction in the negative impact of lipedema postsurgery. Conclusions:  The SMiLE technique offers an advancement in the surgical management of lipedema by enabling the effective removal of lipedema tissue. Alongside a reduction in pain and improvement in mobility, this method addresses physical and psychological burdens. This study suggested that the SMiLE technique could be considered an option as part of a comprehensive approach to treating patients with lipedema.

SUMMARY OBJECTIVE: The aim of this study was to characterize global scientific output on lipedema from 2000 to 2025 and identify emerging thematic trends, with emphasis on the emergence of immunological research. METHODS: Publications indexed in Google Scholar, PubMed, Crossref, OpenAlex, and Scopus were retrieved using the terms "lipedema" OR "lipoedema." Records were deduplicated by normalized title matching and DOI cross-referencing. Bibliometric indicators computed included publication volume, citation metrics, field h-index, exponential growth rate, geographic distribution, author metrics, specialty classification (journal-name keyword matching supplemented by OpenAlex concept tags), and immunological content (regular-expression pattern matching against a predefined term list). RESULTS: A total of 942 unique publications were identified, accumulating 13,688 citations (field h-index=60; mean 14.5 citations per article; median 2 citations per article). Annual output grew from below 12 per year through 2009 to 145 in 2025, with a doubling time of 3.6 years (R2=0.90; p<0.001). The United States, Germany, and Brazil were the most productive countries. Karen Lynn Herbst (USA) was the most influential researcher (46 papers; h-index=20; 1,586 citations). Lymphology and phlebology formed the dominant classifiable domain (17.1%), with 69.3% of publications spanning multiple disciplines. Publications with immunological content totaled 30 (3.2%), grew from essentially zero before 2019 to 4.8% of annual output in 2025, and received higher mean citations than non-immunological articles (16.6 vs. 14.5). CONCLUSION: Lipedema research is undergoing rapid exponential expansion driven by growing global recognition of a historically neglected condition. The accelerating immunological trend, with consistently higher citation impact, indicates an accelerating paradigm shift toward chronic adipose tissue inflammation as a unifying pathophysiological framework.

Background  The Questionário de avaliação sintomática do lipedema (QuASiL – Lipedema Symptom Assessment Questionnaire) assesses 13 distinct inflammatory symptoms of lipedema, but whether these symptoms resolve and recur simultaneously or follow a consistent order remains unknown. Objectives  To characterize the persistence hierarchy of the 13 QuASiL inflammatory symptoms in a retrospective lipedema cohort under heterogeneous conservative treatment, using 6 complementary rank-order analyses and testing the null hypothesis that symptoms resolve with equal magnitude. Methods  This retrospective longitudinal study included 1,300 patients who were clinically diagnosed with lipedema by a vascular surgeon and who completed the QuASiL on at least 2 occasions (minimum 14-day interval; median follow-up 181 days, IQR 92–380, maximum 1,787 days). A consensus ranking was computed across all analyses. A sensitivity analysis was conducted using the conventional T0 = first visit, T1 = last visit convention, and a Kaplan-Meier survival analysis estimated the time (in absolute days) to ≥ 50% reduction from baseline per symptom. Results  The symptoms did not resolve simultaneously (Friedman χ2 (12) = 168.08, p < 0.001). All 13 symptoms improved during follow-up, showing a consistent order across the 6 analyses. A slower-resolving core was identified: bruising (consensus rank 1.7), swelling (2.0), touch sensitivity (4.3), leg heaviness (4.7), and fatigue (4.7). A rapidly-responding group comprised skin irritation (66.4% proportional reduction), itching (62.0%), and walking difficulty (62.6%). Even the most resistant symptom (bruising) achieved a mean 39.1% proportional reduction, with half of patients reaching ≥ 50% improvement. During worsening, swelling and pressure/tension re-emerged first. The sensitivity analysis (T0 = first, T1 = last) produced an essentially identical ranking (Spearman ρ = 0.945, p < 10−5). The Kaplan-Meier analysis estimated a median of 546 days for bruising vs 207 days for itching to reach ≥ 50% reduction from baseline (log-rank χ2 = 44.6, p < 10−10); the fastest-resolving symptom was heat/burning at 203 days. Conclusions  In this retrospective cohort of patients under heterogeneous conservative treatment, the 13 QuASiL inflammatory symptoms improved following a consistent order across 6 independent analyses, with bruising and swelling as the most persistent symptoms. Keywords: lipedema; inflammatory symptoms; resolution order; bruising; patient-reported outcomes; longitudinal study

DiVA portal is a finding tool for research publications and student theses written at the following universities and research institutions.

Lipedema is a chronic adipose tissue disorder that predominantly affects women, although some rare cases do occur in men. We report the case of a 32-year-old man with symmetrical, lower-limb fat accumulation, foot sparing, pain, easy bruising, and a positive family history of lipedema. His first-degree female cousin exhibited the classic phenotype. Dual-energy X-ray absorptiometry demonstrated greater fat accumulation in the gynoid than in the android and visceral regions, reinforcing a predominantly gluteofemoral adiposity pattern. The patient underwent a 7-month personalized nutritional intervention consisting of a moderately hypocaloric, high-protein, low-glycemic diet with vitamin D supplementation and regular physical activity. This intervention was associated with reductions in anthropometric measurements and decreased pain scores on a Visual Analogue Scale. Laboratory tests revealed a preserved hypothalamic–pituitary–gonadal axis, except for mild idiopathic hyperprolactinemia that normalized during follow-up. This case highlights lipedema in men and the potential benefits of early lifestyle-based interventions.Keywords: lipedema; male patient; gluteofemoral adiposity; prolactin; case report

BACKGROUND: Lipedema is a chronic adipose tissue disorder with disproportionate fat accumulation in the extremities and is often misdiagnosed as obesity. Although women with lipedema appear to be metabolically distinct from body mass index (BMI)-matched controls, their fasting metabolism remains insufficiently characterized. We therefore aimed to define the metabolic signature of lipedema using serum NMR metabolomics and anthropometric profiling. METHODS: We conducted a study with 24 premenopausal women with lipedema and 21 BMI-matched controls. Fasting serum samples were analyzed using NMR spectroscopy and anthropometric data were collected. Regional body composition was additionally assessed in an exploratory matched DXA subset (n=12). To characterize coordinated metabolic differences beyond single analytes, we derived exploratory composite indices and applied multivariate analyses. RESULTS: Despite similar BMI, women with lipedema showed lower waist circumference, waist-to-hip ratio and lower fasting insulin than controls (age-adjusted p = 0.032). NMR profiling revealed lower alanine (p < 0.001), lactate (p = 0.004), pyruvate (p = 0.021), and elevated ketone bodies (3-hydroxybutyric acid: p = 0.009; acetoacetic acid: p = 0.035; acetone: p = 0.006). These alterations were reflected by significant group differences in composite indices for fat distribution (g = 1.26; p < 0.001), glycolysis (g = 0.74; p = 0.018), and ketone metabolism (g = 0.70; p = 0.018). Principal component analysis of the selected indices explained 78% of the total variance and showed partial group separation between lipedema and controls. CONCLUSION: Lipedema is associated with a distinct fasting metabolic profile characterized by reduced glycolytic intermediates, enhanced ketone body signals, and a more peripheral fat distribution despite comparable BMI. These findings support the concept of lipedema as a metabolically distinct phenotype and suggest that multivariate metabolic signatures may help refine future diagnostic and interventional approaches.

Lipedema is a chronic inflammatory disorder of adipose tissue that predominantly affects women and is characterized by disproportionate subcutaneous fat accumulation, pain, spontaneous bruising, and significantly impaired quality of life. Although hormonal influences on its pathophysiology have been increasingly recognized, evidence-based treatment options remain limited. Recently, gestrinone has been proposed as an off-label therapy based on hormonal mechanistic hypotheses. A critical narrative review of the literature was conducted using international databases to identify clinical or pharmacological evidence supporting its use in lipedema. No clinical trials, observational studies, case series, or case reports directly evaluating this therapy were identified. Existing proposals rely exclusively on theoretical extrapolations lacking clinical validation. Therefore, current evidence does not support the use of gestrinone in the treatment of lipedema, and its use should be considered experimental until adequately designed clinical studies are available.Keywords: lipedema; adipose tissue; hormone therapy; gestrinone; evidence-based medicine

Lipedema is a chronic disorder characterized by a disproportionate accumulation of subcutaneous adipose tissue in the extremities, typically sparing the hands and feet. It is commonly associated with pain, hypersensitivity, easy bruising, edema, and fibrotic nodules. Despite growing awareness, there is still no consensus on evidence-based therapeutic approaches. This integrative review aimed to identify physical therapy strategies described in the scientific literature for the assessment and conservative management of lipedema. Searches were conducted in the PubMed/MEDLINE, BVS, PEDro, Embase, and Cochrane databases, followed by critical appraisal and evidence synthesis, with applicable PRISMA-ScR checklist items used as a reporting guide for the study selection process. The findings indicate that physical therapy plays a key role in conservative treatment, particularly through complete decongestive therapy, compression therapy, exercise, manual therapy, and electrophysical agents. These interventions show potential benefits in reducing pain, improving functional capacity, controlling edema, and preventing disease progression. However, the available evidence remains limited, underscoring the need for more robust clinical trials to support evidence-based physical therapy practice in the treatment of lipedema.Keywords: lipedema; physical therapy modalities; conservative treatment

Lipedema is a chronic, female-predominant disorder of subcutaneous adipose tissue characterized by disproportionate fat expansion, pain, and fibrosis. Despite its high prevalence, the cellular mechanisms underlying lipedema remain poorly understood. While the clinical features have been extensively described, its biology of adipose tissue dysfunction and aberrant intercellular communication is still unclear. In comparison to obesity, lipedema is marked by local dysregulation of adipocyte-stromal and adipocyte-vascular interactions. In this hypothesis perspective, we discuss emerging mechanistic concepts from a cell biology perspective that are particularly relevant to lipedema, focusing on (i) organelle contact site dynamics in adipocytes and their role in lipid handling and stress adaptation; (ii) extracellular vesicle (EV)-mediated crosstalk between endothelial cells, adipocytes, and immune cells as a driver of localized inflammation and fibrosis; and (iii) estrogen-linked signaling pathways that may imprint EV cargo and cellular behavior in a sex-specific manner. By integrating these perspectives, we highlight open experimental settings and mechanistic parallels to other adipose tissue pathologies that help understanding lipedema as a distinct cellular and molecular entity. Investigating how organelle biology, extracellular vesicles communication and hormonal context intersect in adipose tissue may uncover novel biomarkers and therapeutic entry points for this long-neglected condition.

Adipose tissue derived stromal vascular fraction (SVF) has emerged as cell therapeutic applicable by point-of-care one-step procedures in autologous settings. Even a mechanical isolation, completed within minutes, is typically followed by multiple steps such as cell washing, filtration, erythrocyte lysis and cryopreservation, which may impact the cell isolate in terms of cell amounts and quality. Using the BioMicroMill, a straightforward device providing mechanically isolated SVF suited for multiple therapeutic doses, we aimed to evaluate the impact of relevant processing steps during isolation and cryopreservation on cell quantity and quality in terms of viability, the presence of regenerative cells, pro-regenerative secretome, vascular network formation. The mechanical isolation yielded in the mean 3.4 × 105 ± 1.42 × 105 SVF cells per ml of lipoaspirate with a mean viability of 38% ± 7.2%. It comprised a heterogeneous mixture of single cells, cell aggregates, extracellular matrix, and microvascular fragments enriched from adipose tissue, providing functionally relevant cell populations (CD31, CD34, CD90, CD105). Adipose-derived stromal cells (ASC) exhibited robust outgrowth, proliferation, and differentiation capacity in vitro. The SVF showed pronounced paracrine activity (IL-10, VEGF-A, HGF, IL-6, IL-8, MCP-1), including proangiogenic factors, and supported 3D vascular network formation, demonstrating strong proangiogenic potential. However, all additional SVF processing steps substantially influenced total cell yield, with cumulative cell losses (erylysis 68% ± 16%, filtration 67% ± 16%, washing 54% ± 9%) but no loss of viability or ASC attachment and proliferation in vitro was observed. In contrast to other processing steps, filtration substantially altered SVF composition towards single cells, which was also reflected in an altered paracrine activity (significant increase in IL-10 and reduction to minimal levels of HGF). Furthermore, despite further cell loss (mean 47% ± 16%), cryopreservation maintained functional cell populations including ASC, paracrine activity and support of 3D network formation in vitro. Taken together, our data demonstrate that processing steps can influence both cell yield and quality. Accordingly, protocol selection should be guided by the intended application and the required functional properties and therefore warrants careful consideration.

Review Article Background: Lipedema and advanced lymphedema are chronic disorders of adipose and lymphatic tissues that remain frequently underdiagnosed. Their coexistence poses therapeutic challenges, particularly when conservative management fails. Although international guidelines support surgical intervention in selected cases, real-world data from resourcelimited hospital settings remain scarce. Objective: To report the experience of a Moroccan tertiary university hospital in the surgical management of advanced lipedema and lymphedema and to compare clinical outcomes with current international recommendations. Methods: A retrospective descriptive case series was conducted between 2021 and 2024. Three patients underwent surgical treatment using tumescent liposuction or en bloc tissue resection with skin grafting. Postoperative outcomes were assessed clinically and through a structured quality-of-life questionnaire inspired by the SF-36, focusing on pain, mobility, and overall satisfaction. Results: All procedures were completed without intraoperative or postoperative complications. The volume of aspirated adipose tissue ranged from 2.1 to 4.0 L. One patient with advanced secondary lymphedema required surgical resection, with evacuation of 1.2 L of lymphorrhea. Postoperative satisfaction ranged from moderate to high, with reported quality-of-life scores between 5 and 8 out of 10. These findings are consistent with outcomes reported in recent international series. Conclusion: Surgical treatment of advanced lipedema and lymphedema is feasible, safe, and clinically beneficial, even in resource-limited settings. An individualized, guideline-based approach allows satisfactory functional and quality-of-life outcomes. Further prospective studies with standardized assessment tools are required.

Lipedema is a chronic adipose tissue disorder characterised by disproportionate accumulation of subcutaneous fat within specific anatomical depots, most commonly the lower extremities, with relative sparing of the trunk. Despite increasing clinical recognition, the mechanisms underlying the selective vulnerability of particular adipose depots and the progressive tissue remodelling observed in lipedema remain poorly understood. Emerging evidence suggests that lipedema is associated with complex alterations in adipocyte biology, adipose stem and progenitor cell (ASPC) function, immune signalling, vascular integrity, extracellular matrix remodelling, and lymphatic homeostasis, indicating that the disease extends beyond simple fat accumulation. Recent advances in adipose tissue biology have demonstrated that adipose depots are not functionally uniform structures, but rather anatomically distinct cellular ecosystems with unique developmental origins, transcriptional programs, stromal composition, immune niches, and metabolic properties. These depot-specific characteristics may provide an important framework for understanding the regional distribution and progression of lipedema. However, while substantial progress has been made in defining differences between visceral and subcutaneous adipose tissue, heterogeneity between individual subcutaneous depots remains comparatively underexplored despite its likely relevance to disorders of regional adipose expansion. The emergence of single-cell and spatial transcriptomic technologies has transformed the study of adipose tissue by enabling high-resolution mapping of adipocytes, stromal populations, vascular cells, and immune microenvironments within healthy and diseased tissue. These approaches offer an unprecedented opportunity to investigate depot-specific cellular states, intercellular signalling networks, and spatial tissue architecture in lipedema. In this review, we synthesise current evidence regarding tissue remodelling and adipose depot heterogeneity in lipedema and examine how single-cell and spatial omics approaches may advance mechanistic understanding of disease pathophysiology. We further discuss current technical and conceptual limitations within the field and highlight future directions for developing integrated adipose tissue atlases capable of identifying disease-driving cellular programs and therapeutic targets in lipedema.

Introduction  Lipedema is a chronic disease characterized by symmetrical and painful accumulation of subcutaneous fat, influenced by genetic and hormonal factors, and frequently misdiagnosed as obesity or lymphedema. Materials and Methods  In the present narrative review, we searched the PubMed and SciELO databases for articles published between 2015 and 2025, in Portuguese and English, addressing the diagnosis and the clinical or surgical management of lipedema. Results  In the PubMed search, we identified 299 studies, which were reduced to 106 after the removal of duplicates, with a progressive increase in publications since 2020; in the search on SciELO, we only retrieved 7 studies, all of which were also indexed in PubMed. The results reinforce that lipedema presents a complex pathophysiology, involving adipocyte hypertrophy and hyperplasia, chronic inflammation, microvascular dysfunction, and estrogen-related influence. International consensus indicates that diagnosis is essentially clinical, and that conservative treatment should be prioritized, including weight management, nutritional guidance, low-impact exercise, compression therapies, and psychosocial support. Surgical intervention, particularly tumescent or water-assisted liposuction techniques, is reserved for refractory cases and does not constitute a definitive cure. The growing alignment among consensus statements published over the past 5 years highlights the need for standardized diagnostic criteria and therapeutic protocols. Conclusion  The effective management of lipedema requires a multidisciplinary approach, continuous professional education, and strengthening of research that enable the establishment of evidence-based clinical guidelines. Keywordsdiagnosis; lipedema; literature review; surgery; treatment

Lipedema is a chronic and often debilitating adipose tissue disorder that primarily affects women. The disease is characterized by disproportionate and symmetrical accumulation of subcutaneous fat in the extremities. Despite the high prevalence of lipedema, which affects ∼10% of women, and its significant impact on patient quality of life, lipedema is understudied and often misdiagnosed as other disorders (obesity or lymphedema). In this review, we explore the current understanding of lipedema through clinical, tissue, and cellular lenses, and examine suspected pathological mechanisms, including hormonal influences (such as estrogen), adipocyte hypertrophy and hyperplasia, increased extracellular matrix (ECM) fibrosis, and specialized immune cell involvement, including M2 macrophage infiltration. Recent advancements in adipose tissue engineering, including organoids, fat-on-a-chip platforms, and the use of induced pluripotent stem cells (iPSCs) are explored as platforms to study lipedema pathogenesis.

Background/Objectives: Lipedema is a chronic, progressive adipo-fascial disorder characterized by connective tissue dysfunction, fibrosis, microangiopathy, and adipose tissue proliferation. Although lipedema has traditionally been described as a regionally confined disorder, emerging evidence suggests that it may reflect a broader stromal and connective tissue dysfunction. It is therefore plausible that anatomical regions not historically associated with lipedema may also exhibit alterations consistent with this dysfunctional stromal pattern. From this perspective, breast tissue-rich in fibro-glandular and stromal components-represents a compelling model in which to investigate whether such features are present. The breast, with its complex fibro-glandular and stromal architecture, represents a physiologically plausible site of involvement; however, its structural features in lipedema have never been systematically examined. The primary aim of this study was therefore to determine whether breast tissue-rich in fibro-glandular and stromal components-shows recurrent imaging or histopathological features suggestive of lipedema-related involvement. A secondary aim was to compare the frequency of these findings with patterns typically reported in healthy screening populations. Methods: This retrospective cross-sectional study analyzed 62 women (mean age: 44 ± 8 years), obtained between September and November 2025, with a clinical diagnosis of lipedema who voluntarily provided breast imaging reports (ultrasound, mammography, or magnetic resonance imaging, MRI). Results: The findings revealed a remarkably high prevalence of fibro-glandular parenchyma (45%), multiple diffuse cysts (42%), microcalcifications (21%), and fibroadenomas (43.5%), with frequencies substantially exceeding those documented in healthy screening populations. Additional features included significant breast asymmetry or tuberous morphology (6%), reactive or sclero-lipomatous lymph nodes (19%), and recurrent stromal hyperplasia on biopsy. Histological evaluations (n = 9) consistently showed fibroproliferative alterations, including stromal hypercellularity, adenosis, fibroepithelial lesions, apocrine metaplasia, and pseudoangiomatous stromal hyperplasia, suggesting a shared extracellular matrix-related dysplastic phenotype between lipedema-affected breast tissue and peripheral adipose tissue. Conclusions: These findings support the hypothesis that lipedema may express a characteristic breast phenotype driven by stromal and extracellular matrix dysregulation. If confirmed in larger controlled studies, these recurrent alterations could contribute to improved diagnostic frameworks and raise awareness of lipedema as a systemic connective tissue disorder with underrecognized breast manifestations.