Madelung disease (MD) is also referred to as multiple symmetric lipomatosis, Launois–Bensaude syndrome, or benign symmetrical lipomatosis (Becerra-Bolaños et al., 2019). It is a rare disorder with diffuse and symmetrical adipose tissue deposition in the subcutaneous superficial fascia space and/or deep fascia space caused by adipose metabolic disorders (Chuang et al., 2004; Goetze et al., 2008; Tawara et al., 2022). In light of the characteristics of adipocyte distribution, MD is primarily divided into two types (Verna et al., 2008; Chen et al., 2018). Type I generally occurs in males. It is characterized by symmetrically distributed, superficial, fatty masses with a “pseudo athletic” appearance in the neck (“bull’s neck” sign), upper arm, and thigh, which are likely to cause compression symptoms. Type II is similar to widespread simple obesity and affects men and women. Fatty masses are mainly assembled in the upper back, deltoid area, hips, and thighs.

Epidemiology disclosed that the incidence of MD is approximately 1/25,000 (male/female about 15–30/1), primarily among Mediterranean adult males, of whom 60–90% consume chronically increased amounts of alcohol (Esposito et al., 2016; Chen et al., 2017; Pinto et al., 2017). The etiology and pathogenesis of MD are still not entirely elucidated (Chen et al., 2017). To date, it is assumed that mitochondrial dysfunction due to mutations of mitochondrial DNA and changes in the activity and number of β-adrenergic membrane receptors, resulting in the reduction of adrenergic-mediated lipolysis, are the leading causes of MD (Chen et al., 2018; Vassallo et al., 2019). Moreover, the enhancement of inflammatory reaction caused by alcohol consumption might serve as a predisposing or deteriorating element (Sebastian et al., 2011; Caponnetto et al., 2020).

The diagnosis of MD is mainly based on physical and histological examination, clinical features, and imaging. Imaging studies can determine tumor location, size, and the degree of adhesion and compression to adjacent tissue (Nisi and Sisti, 2016; Chen et al., 2018). Histologically, adipocytes in the cellulite of patients with MD are smaller, and the content of vascular and fibrous tissues is higher than those of healthy patients (Ramos et al., 2010; Caponnetto et al., 2020). Therefore, imaging and histological examination are also helpful with MD clinical differential diagnosis and preoperative assessment (Verhelle et al., 2003; González-García et al., 2004).

Currently, palliative surgery, such as lipectomy, liposuction, or lipectomy combined with liposuction, remains the most effective therapy for managing MD (Nisi and Sisti, 2016; Chen et al., 2018; Szewc et al., 2018; Caponnetto et al., 2020). However, palliative treatment is highly prone to relapses and metastasis after surgery (Chen et al., 2018; Yu et al., 2020). Therefore, as a benign tumor exhibiting the biological characteristics of a malignant tumor, the relationship between the tumor cells and immune cells of MD should be investigated further. In this study, we report a case of MD by using sc-RNA sequencing (seq) to decipher the effects of T-cell clusters on MD, expecting to provide a new understanding of the characteristics of MD.