Analysis of Madelung disease based on sc-RNA sequencing: A case report and literature review.

Madelung disease (MD) was first described by Brodie in 1846 as a rare multiple lipoma. It is a benign tumor characterized by symmetrical diffuse adipose tissue deposition in the proximal extremities and neck. Until now, the etiology and pathogenesis of the disease have not been fully explained, resulting in difficulties in diagnosis and treatment; moreover, palliative treatment, such as surgical resection of adipose tissue or liposuction, is still the mainstream treatment for MD. However, the effectiveness of palliative surgery is limited, and most patients still relapse or metastasize after treatment. Therefore, we analyzed the relationship between tumor cells and immune cells in MD using single-cell RNA sequencing for the first time and combined an analysis of our results with a review of previous literature reports. Our study provides a new perspective on the pathogenesis of MD and provides a vital clinical basis for targeted therapy. DATA AVAILABILITY: The authors declare that all the data supporting the findings of this study are available within the article and its Supplemental information files.

Prevertebral fat in Madelung disease mimicking cervical spine injury: A case report.

Madelung disease is defined by multiple symmetric fatty accumulations, usually involving the upper trunk, and may sometimes have excessive fat deposition in the prevertebral space. On magnetic resonance imaging (MRI), findings of fat that are hyperintense on T1w and T2w images, may simulate subacute hematoma and mimic cervical spine injury. This is the first reported case of Madelung disease with prevertebral fat deposition mimicking prevertebral hematoma found in cervical spine injury on MRI. Fat suppression techniques are helpful in order to differentiate between these two conditions, which should be taken into consideration during routine clinical practice.

Multiple symmetrical lipomatosis: A literature review and case report of a patient with Madelung's disease.

<b><br>Introduction:</b> Madelung's disease is a rare condition characterised by the symmetric growth of fatty tumours (lipomas) around the neck, shoulders, upper arms and trunk.</br> <b><br>Case report:</b> We present a description of a male patient with extensive adipose tissue overgrowth around the neck. Once the possibility of malignancy was excluded, the patient's history and clinical and radiological findings led to the diagnosis of Madelung's disease. A two-stage surgery was planned and the patient underwent lipectomy of the lipomas around the neck.</br> <b><br>Conclusions:</b> This article analyses the clinical data with Madelung's disease; discusses its aetiology, clinical manifestations, diagnosis and treatment methods; and provides help with clinical diagnosis and treatment.</br>.

[A case of Madelung's disease combined with laryngeal cancer].

Madelung's disease is a lipodystrophy of unknown etiology. This article reports a case of Madelung's disease complicated with laryngeal cancer. The clinical manifestations of the patient were progressive hoarseness and dyspnea, dysphagia, and diffuse symmetrical swelling of the neck, submental, and submandibular. Dynamic laryngoscopy revealed a giant cauliflower-like neoplasm in the throat, with the left vocal cord fixed. Laryngeal CT showed laryngeal carcinoma （transglottic type）, signs of lymph node metastasis in the left jugular chain region, and Madelung syndrome in the neck. Biochemical tests showed albumin 38.7 g/L, globulin 27.5 g/L, prealbumin 160 g/L, aspartate aminotransferase 14 IU/L, γ-transpeptidase 80 IU/L, alanine aminotransferase 7 IU/L, Creatinine 43 µmol/L. Preoperative pathology suggested squamous cell carcinoma. Admission diagnosis included laryngeal cancer （transglottic T4N1M0）, Ⅲ degree laryngeal obstruction, Madelung's disease and fatty liver. The patient recovered well after surgery.

Bilateral symmetric lipomatosis of the orbit in Madelung's disease.

Madelung's disease is a rare benign systemic lipomatosis, which often presents in the head, neck and upper trunk regions. The appearance of symmetrical, excessive adipose tissue in the subcutaneous layer is its clinical characteristic. Orbital involvement is unusual with only a few cases reported previously. In this study, we describe the clinical and radiological features of Madelung's disease in the orbits. A 42-year-old man with alcohol addiction presented with chronic bilateral masses of the lower eyelids and proptosis. Computed tomography (CT) scan showed excessive symmetrical non-encapsulated fat deposition in the orbital fat, lower eyelids, salivary glands, subcutaneous tissue along the neck and under the sternocleidomastoid muscles and supraclavicular areas bilaterally. Histopathological study of the orbital masses revealed mature adipose tissue interspersed with thin fibrous septae. He developed recurrent lipomatosis 1 year after surgical excision.

Multiple symmetric and multiple familial lipomatosis.

Lipomas are the most common soft tissue tumors and are malignant in only 1% of cases. Lipomatosis is defined as the presence of multiple benign lipomas on the body, without lipoatrophy. Their impact on quality of life is significant. Different entities have been described such as symmetrical multiple lipomatosis (MSL), also called Madelung's disease and familial multiple lipomatosis (FML). MSL occurs preferentially in men (but also women) who are alcohol abuser. There are different subtypes of the disease, the most classic of which affects the upper body and the nuchal region with a buffalo hump appearance. A metabolic component with obesity is frequent. In contrast to Dercum's disease, there is no pain. SAOS, complications of the metabolic syndrome and of alcohol abuse including cancers, may be associated and should be screened. FML has been little described in the literature since Brodie's first report in 1846. FML occurs preferentially in the third decade but equally in women and men. Its autosomal dominant component is classically accepted with variable penetrance within the same family. Association with naevi, angiomas, polyneuropathies and with gastrointestinal comorbidities has been reported. Interestingly, and in contrast with most lipodystrophy disorders, the patients show an insulin sensitivity profile. A better understanding of the underlying pathophysiological mechanisms would open up avenues on therapeutic research, since treatments are only symptomatic to date.

Madelung's disease in a non-alcoholic Ethiopian male patient mistaken for obesity: a case report.

BACKGROUND: Madelung's disease (MD) is a rare disorder of fat storage characterized by the presence of diffuse, symmetrical deposition of subcutaneous fat around the neck, shoulder, arm, trunk and thigh. Although its cause is not fully understood, this benign condition is commonly presented among adult males with Mediterranean origin and history of alcohol abuse. Patients often presents with compression of vital structures, cosmetic disfigurement and associated psychosocial problems and systemic comorbidities. It is often under-recognized by physicians, possibly due to obliviousness of the condition and often misdiagnosed as obesity. CASE PRESENTATION: We present a 65-year-old non-alcoholic black Ethiopian man, presented with a slowly growing body fat in his trunk and proximal limbs associated by multiple joint and back pain which got worse recently. He denied any history of chronic alcohol use. On examination, huge, bilateral, non-tender, soft, globular masses in his torso, shoulder, arm and thigh with bilateral breast enlargement. On investigation his biochemical profile was normal except hyperuricemia (10.6 mg/dl). Imaging of the cervical and lumbar vertebrae showed excess subcutaneous fat depositions with degenerative disc disease. Biopsy from the mass revealed non-encapsulated lipoma and he was diagnosed with type II MD. We treated his pain with supportive therapy and discharged in stable condition. The patient deferred surgical treatment. CONCLUSIONS: Madelung's disease is often reported among white adult males with chronic alcoholism. However, our case reported a black man without the typical risk factor which was misdiagnosed as obesity. Hence, clinicians should be aware of MD and need to consider it in their differential diagnosis when encountered with a patient having progressive centripetal fat deposition with or without a history of alcoholism and systemic comorbidities. As early detection of this disorder helps to avoid diagnostic delays and prevent complications through timely interventions which will in turn improves patient quality of life.

Madelung's disease. Two case reports with pseudoathletic appearance.

ABSTRACT: Madelung's disease is a rare syndrome characterized by the pre-sence of multiple masses of unencapsulated adipose tissue, symme-trically distributed throughout different regions. It predominantly affects middle-aged men of Mediterranean origin with a history of alcoholism. The pathogenesis is still unknown. Diagnosis is essentially established through clinical history and physical examination. We report two cases for their unusual presentation and to emphasize the importance of early diagnosis.

A case report of Multiple Symmetric Lipomatosis (MSL) in an East Asian Female.

BACKGROUND: Multiple Symmetric Lipomatosis (MSL) is a rare disorder related to fat metabolism and lipid storage. The condition results in characteristic depositions of fat, especially around the cephalic, cervical, and upper thoracic subcutaneous. It is much more common in adult males who live in the Mediterranean region and has only rarely been reported in Asian females. In this report, we present a case of an Asian female with MSL and also review the clinical features of the condition, including radiological and histological findings required for proper diagnosis and management. CASE PRESENTATION: A 59-year-old Korean female came in with a chief complaint of palpable mass present in shoulder and upper back regions. Images showed diffuse non-encapsulated adipose tissue in the subcutaneous layer of the suboccipital, posterior neck area. The patient wanted to remove the mass for cosmetic reasons and discomfort. Excisional biopsy was planned. Preoperative blood analyses showed deteriorated liver function, and the computed tomography findings were consistent with liver cirrhosis. Detailed history taking revealed that she consumed highly levels of alcohol. Lipectomy was performed and the histological findings demonstrated large dystrophic adipocyte morphology. The patient was recovered uneventfully. CONCLUSION: When patients have multiple symmetric lipomatous lesions, clinicians should suspect MSL and survey possible associated conditions, such as alcoholism, liver cirrhosis, dyspnea, and neuropathy in detail.

Multiple symmetric lipomatosis with secondary laryngeal obstruction: A case report.

INTRODUCTION: Multiple symmetric lipomatosis (MSL) is an uncommon medical condition characterized by symmetric fat accumulation mainly in the neck and other upper body regions. The involvement of the larynx is rare according to the literature, and we present a case of MSL with larynx involvement treated with a surgical approach. PATIENT CONCERNS: A 55-year-old male was admitted to our hospital due to progressively aggravated breathing difficulty, and tracheotomy was performed before transfer. When he tried to block the cannula, the breathing difficulty returned. The patient's neck had been thickening for the past 2 years. DIAGNOSIS: Pathological examination confirmed the diagnosis of MSL. INTERVENTIONS: The patient underwent lumpectomy and neck exploration. OUTCOMES: The lipoma was removed, the patient was free of any dyspnea symptoms and recovered well, and the tracheal cannula was removed at a local hospital. CONCLUSION: MSL can infiltrate the larynx and grow into the preepiglottic space and paraglottic spaces, resulting in breathing difficulties. Lipomas present in the spaces described above must be removed at the same time; otherwise, symptoms of dyspnea cannot be alleviated.

Multiple symmetric lipomatosis of the male breast: An unusual mimic of gynecomastia.

Multiple symmetric lipomatosis (MSL) is a very uncommon disease. Its etiopathogenesis is uncertain, although it has been linked to a variety of factors. Its main characteristic is the overgrowth of fat in form of an unencapsulated lesion. Most of the cases reported are in the head and neck region. We report a case that occurred in the breasts of a 62-year-old man. A clinical diagnosis of gynecomastia was initially made. Partial mastectomy was done and MSL was reported on histopathologic examination. Our literature search revealed no previous case of MSL in the breast reported from our environment.

Madelung's disease and pulmonary aspergillosis: a case report and literature review.

BACKGROUND: Madelung's disease (MD) is a rare disorder of fat metabolism, which is usually associated with diabetes, hyperuricemia, liver disease, nevertheless there is no report of a patient with MD and pulmonary aspergillosis (PA). This article aimed to enhance the awareness of this two diseases and discuss the possible mechanism of the combination of them preliminarily. CASE PRESENTATION: In this case, we described a 56-year-old male patient with cough, expectoration and dyspnea. His neck has a very peculiar appearance. Chest enhanced CT scan showed there were multiple nodules in both lungs, some of which had cavities and the mediastinal lymph nodes were swollen. Ultrasound scan of the neck showed diffuse hyperplasia of subcutaneous fat in neck and bilateral supraclavicular fossa. Fortunately, after performing pulmonary wedge resection aimed at pathological examination and giving relevant treatments, this patient was finally diagnosed as MD with PA, and his symptoms were significantly relieved. CONCLUSIONS: MD is rare, the phenomenon that MD combined with PA is rarer. Immune disorder may be the possible mechanism.

Rapidly progressive case of type I Madelung disease with bilateral parotid and minor salivary glands involvement.

Context: Madelung disease has been literally classified as a rare disease, more common in Mediterranean population. It is characterized by the presence of multiple symmetrical, non-capsulated storages of adipose tissue.Case description: We present a 56 year old woman with a sudden unexplained progression of swelling in the neck and upper thorax region associated with severe dyspnea. She was admitted with angioedema in the Allergology Department. Radiology images identified a bilateral adipose degeneration of the parotid and minor salivary glands.Conclusions: The diefinitive diagnosis concluded was Type 1 Madelung Disease. The decision was to keep the patient under periodic observation and if any deterioration takes place, surgical intervention will be taken under consideration. Despite non previous findings of Madelung disease in our population this case presented a challenge of emergency diagnosis.

Human Adipose-Derived Stem Cells in Madelung's Disease: Morphological and Functional Characterization.

Madelung Disease (MD) is a syndrome characterized by the accumulation of aberrant symmetric adipose tissue deposits. The etiology of this disease is yet to be elucidated, even though the presence of comorbidities, either genetic or environmental, has been reported. For this reason, establishing an in vitro model for MD is considered crucial to get insights into its physiopathology. We previously established a protocol for isolation and culture of stem cells from diseased tissues. Therefore, we isolated human adipose-derived stem cells (ASC) from MD patients and compared these cells with those isolated from healthy subjects in terms of surface phenotype, growth kinetic, adipogenic differentiation potential, and molecular alterations. Moreover, we evaluated the ability of the MD-ASC secretome to affect healthy ASC. The results reported a difference in the growth kinetic and surface markers of MD-ASC compared to healthy ASC but not in adipogenic differentiation. The most commonly described mitochondrial mutations were not observed. Still, MD-ASC secretome was able to shift the healthy ASC phenotype to an MD phenotype. This work provides evidence of the possibility of exploiting a patient-based in vitro model for better understanding MD pathophysiology, possibly favoring the development of novel target therapies.

Madelung's Disease Leading to Presenile Dementia in a Non-alcoholic Patient.

INTRODUCTION: Madelung's disease (MD) is a rare disorder of unknown etiology defined as the presence of multiple and symmetrical fatty accumulations most commonly involving the upper trunk, neck, and head. Excessive alcohol ingestion has been linked traditionally to the pathogenesis of the disease. The central and peripheral nervous system could both be affected. Presenile dementia, without alcohol abuse, has been rarely reported in the literature as a complication. AIM: The aim of this case report is to highlight that multiple symmetric lipomatosis can be complicated by presenile dementia even if the patient is non-alcoholic. CASE REPORT: This case report describes a middle age non-alcoholic woman who presented for increased forgetfulness. Brain CT scan showed cerebral and cerebellar atrophy inappropriate for her age. Despite being started on anticholinergic drug, her MMSE decreased 3 points in 1 year. CONCLUSION: Clinicians should consider early onset dementia as a potential complication of Madelung's disease even in patients with no preceding history of alcoholism. A brain MRI and MMSE can aid with identifying such a complication.

Calcyphosine-like (CAPSL) is regulated in Multiple Symmetric Lipomatosis and is involved in Adipogenesis.

Little is known on the causes and pathogenesis of the adipose tissue disorder (familial) Multiple Symmetric Lipomatosis (MSL). In a four-generation MSL-family, we performed whole exome sequencing (WES) in 3 affected individuals and 1 obligate carrier and identified Calcyphosine-like (CAPSL) as the most promising candidate gene for this family. Screening of 21 independent patients excluded CAPSL coding sequence variants as a common monogenic cause, but using immunohistochemistry we found that CAPSL was down-regulated in adipose tissue not only from the index patient but also in 10 independent sporadic MSL-patients. This suggests that CAPSL is regulated in sporadic MSL irrespective of the underlying genetic/multifactorial cause. Furthermore, we cultivated pre-adipocytes from MSL-patients and generated 3T3-L1-based Capsl knockout and overexpressing cell models showing altered autophagy, adipogenesis, lipogenesis and Sirtuin-1 (SIRT1) expression. CAPSL seems to be involved in adipocyte biology and perturbation of autophagy is a potential mechanism in the pathogenesis of MSL. Downregulation of CAPSL and upregulation of UCP1 were common features in MSL fat while the known MSL genes MFN2 and LIPE did not show consistent alterations. CAPSL immunostainings could serve as first diagnostic tools in MSL clinical care with a potential to improve time to diagnosis and healthcare options.

Síndrome de Madelung / Madelung's disease

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Madelung Disease: Analysis of Clinicopathological Experience in Taipei Veterans General Hospital.

BACKGROUND: The main feature of Madelung disease (MD), a rare condition, is the growth of adipose tissue without a capsule. Usually, this disease is known for its prominent features with fat deposition around the neck, shoulder, back, or chest wall. Clinically, the patient is likely to exhibit alcohol, neuropathy, and metabolic disorders; however, no clear cause has been confirmed. AIMS: The aim of this study was to analyze the morphological, pathophysiological, and various treatment methods of MD. We have presented and discussed 16 cases of treatment of this disease at our hospital and reviewed the literature on this subject. METHODS: We carried out a retrospective chart review of 16 consecutive patients with MD treated from 1989 through 2017. Patient demographic data, tumor size and location, and follow-up data were evaluated. Patients usually seek treatment because of the disfigured appearance, restricted range of the motion of the head and neck, inconvenience in daily activity such as eating or speaking, and worry about the mass effect. All patients underwent surgical resection and/or combined liposuction. RESULTS: Among the patients, 14 were men, aged 38 to 80 years, with a history of disease ranging from 6 months to 7 years. The mean duration from symptoms to diagnosis of MD was 4.4 years. The mean duration of follow-up was 82.8 months (range, 5-192 months). Three patients died of coronary artery disease at follow-up of 27, 78, and 141 months. The functional results were satisfactory in all patients. Severe complications were not observed. CONCLUSIONS: According to our experience, surgical resection is the main method of improving the appearance, ensuring eradication of the tumor, and reducing the possibility of recurrence. In addition, we have a case in which atypical changes were confirmed by histological examination in fractional surgery. A long follow-up period is recommended considering the high propensity and mean time to recurrence. Although malignant transformation of MD is rare occurrence, it occurred in 1 of the 16 patients.