Madelung Disease – Our Clinical Considerations and Management

Although Madelung Disease (MD) is a quite rare clinical entity, it may have some serious concerns regarding the patient’s quality of life. Such lesions are painless, however the exterior aspect may lead to social ostracism. The physio-pathological processes involved are not fully understood, however male sex and chronic alcohol consumption have been described as risk-factors. We hereby present our case of a middle-age man who came in our Hospital with the clinical complaint of a painless bulging masses on the posterior aspect of the neck, with extension into the occipital area. The mass grew in a period of almost 4 years and was considered trivial by the patient. The clinical examination and the imagistic studies confirmed the presence of symmetrical lipomatous deposits. We provided a surgical operation, consisting of a bilateral ablation of the two formations. The postoperative out-come was positive, with an optimal esthetical result achieved.


Introduction
Madelung disease, or Multiple Symmetric Lipomatosis (MSL) is a rare disturbance among the overgrowth syndromes and it is characterized by painless, symmetric and non-encapsulated fatty deposits in varies district of the body, including the cervical region, limbs, torso, neck, mammary and abdominal regions. The etiology of this disease is still not well elucidated and its risk factors are chronic alcoholic consumption and male sex. The chronical alcoholic consumption may play a role in adipocytes hyperplasia in genetically susceptible patients, however is not fully understood yet. Such kind of patients usually seek medical attention for esthetic reasons.

Case-Presentation
Here we report our case of a 37-year old male patient, without any relevant clinical history, which came in our hospital for this painless, bilateral and symmetric growing mass on the posterior aspect of the neck region, which grew in the last 4 years and speed up in the last year. At the beginning, the lesion was considered trivial by the patient. His main complaint was esthetical. At the physical examination, two well distinct lesions were described, as the left side was slightly bigger than the right side (10 cm; 8 cm as thier biggest diameter) and without any invasion of the skin layers.
We also provided the patient with a CT scan of the head and neck regions (Figure 1), which confirmed the adipocytic origin of the tumor, as well as its lacks of infiltration of other compartments.
There were no sign of airway obstruction or involvement of the superior aspect of mediastinum. The lesion was well delimitated and encapsulated.
Macroscopic aspect of the lesions.

B.
The patient is set in the Mayfield support. As other complaints, he presented with type I mild obesity. He denied a daily alcoholic intake, but he confirmed its sporadic use.
No other relevant disease or disturb was found through the clinical examination. The physical examination also revealed that the two masses were quite hard at touch, relatively firm in position and only in contact with the posterior aspect of the neck. No cervical vein engorgement was described ( Figure 2) A one-step surgical treatment was scheduled a few days later after the patient came in.
The surgical procedure consisted of a macroscopic ablation of the two formations through a bilateral vertical incisure and ablation was performed under general anesthesia and mechanic ventilation.
The operation lasted circa 3 hours. After the operation the patient was satisfied and was discharged a few days later. No complications were encountered. The esthetical result was satisfactory. Right side of the patient.  Tumor macroscopic aspect.

Materials and Methods
No dissection plan has been found during the operation and the 2 masses were firmly attached to bone and periosteal membrane.
The two masses have been sent to anatomo-pathological laboratory, which confirmed a great adypocytes proliferation. The masses were firmly attached to the occipito-nuchal region, hard in consistency and well encapsulated, slightly vascularized and with a macroscopical aspect compatible with adipos tissue overgrowth.
The lesions were hard at touch and homogenous, it could be gripped with ease and it was detached from the bone mostly by hand. No   Our case is classified as a type Ia Madelung disease, as it is shown in the pre-operative CT scans (Figure 1), with a bilateral mass over the posterior aspect of the nuchal region and the occipital bone.
The other most common locations are visible in the table above.
"The pathogenesis of this disease has not been completely defined, as such the abnormal proliferation of fat tissue is not related to an increase in caloric intake, but it looks like an active proliferation of the adipose tissue. The suggested-most mechanisms are defects in the respiratory chain or mutations/deletions in mitochondrial DNA" [4,5]. "Lipomatous fat deposits may originate from functionally defective brown adipous tissue and the tumoral fatty cells have an abnormal metabolic behaviour, which is characterized by a defect of the catecholamines acute lipolytic action. Some sort of alcoholic drinking disorder is present in more than 90%, however our case did not show any sign of chronic alcoholic intake. A decrease in the beta-adrenergic receptors and subsequent defects in mitochondrial DNA may be the explication of pathogenic alcohol action over the fat tissue" [6]. "Even though that the history, epidemiology and clinical features are the basis of MLS diagnosis [7] in some cases may be challenging, due to the common arise of obesity in the general population (1;4). Moreover, such patients usually presents with other significant commorbidities, such as type II diabetes mellitus, glucose intolerance or hyperuricemia. Diseases associated with chronic alcoholic consumption (macrocytic anemia, hepatopathy, periferal neuropaties) are very common is MSL" [7]. Our patient did not show any sign of liver suffering or chronic alcoholic consuption associated diseases. Although alcohol withdrawal and weight loss are recommended, these measures are not effective to reverse/ stop the progression of the tumors. Currently, surgical treatment is the only option available, and so the fat masses removal remains the only therapy of choice. However the overall recurrence rate is describe as up as 63% of cases [7].

Final Discussion
The Madelung disease is a rare clinical entity [8]. Despite the high chance of recurrence, its malignant potential is quite low. Its There is a suggested pathway of deletions and mutations over the mitochondrial DNA. Hence, it is not an energy intake related proliferation, but rather an uncontrolled metabolic behaviour. It is challenging to diagnose such a disease, with the rapidly increasing obesity frequency. As differential diagnostics, Cushing disease, Frölich syndrome and lymphoma must be considered. Usually these patients show signs of chronic alcoholic consumption (eg hepatopathy or macrocytic anemia) or metabolic disorders (DM type II, obesity) in up to 90% of cases [9].