To our knowledge, this is the second case reported in the literature of liposarcomatous transformation occurring in a patient affected by Madelung’s disease. The first description dates back to 1983, when Tizian et al.  reported on a 57-year-old woman with a 7-year history of progressive, symmetric thickening of the neck due to histologically confirmed benign lipomatosis. Changes of clinical appearance of the left side of neck lipomatosis, which had become smaller, harder and fixed to the skin, as well as the occurrence of dyspnoea and limited mobility of the cervical spine had accelerated the execution of radiographic studies which confirmed infiltration of soft tissues, but failed to document any tumor mass displacing the trachea. After surgical resection of lipomatous masses, histopathology had revealed the presence of areas of myxoid liposarcoma in the context of larger parts of embrional lipoblasts, and the patient had been triaged to adjuvant chemotherapy .
In our MSL case, the diagnosis of liposarcomatous progression was documented in the left axillary lipomas removed because of a coincidental diagnosis of breast cancer: indeed, at clinical examination, no suspicion of axillary tumor involvement had emerged; moreover, staging work up with US, mammography, and PET/CT scan also failed to document any abnormalities. CT and MRI have been reported to play a relevant role in assessing the extension and distribution of lipomatous masses , however, the difficulties to differentiate benign lipomas versus liposarcoma solely on radiological basis are also acknowledged . Therefore, any modification of lipomatous masses, especially if asymmetric, and the appearance of signs/symptoms of compression/infiltration of aerodigestive tract should be taken into account for planning surgery which still remains the mainstay of treatment. A prompt removal of lipomatous masses confirms histology, increases the chances of a radical excision, and could also help to diagnose malignant airway tumors whose symptoms could go underestimated because attributed to a long standing Madelung’s disease .
On the other hand, in cases refusing surgery or still considered as not requiring surgical removal of asymptomatic masses, a biopsy could be performed even though the diagnostic limits inherent in this procedure should be recognized.
No clear guidelines for the overall management of Madelung’s disease are available given the rarity of disease: removal of lipomatous masses by lipectomy, or US-assisted liposuction in selected cases  is strongly recommended. Recently, also intralesional injections of phosphatidylcholine (mesotherapy) has been reported as a potentially effective therapy for MSL .
Moreover, regular follow up visits could be advocated for early diagnosis of aerodigestive tract malignancies or liposarcomatous transformation. In fact, malignant transformation of lipomas documented by us and Tizian et al.  correspond to 0.6-0.7% of cases with Madelung’s disease reported in the literature (2 out of approximately 300 cases). A more in-depth analysis of molecular pathways associated with MSL would open novel perspectives in terms of disease management and understanding of pathogenesis: indeed, MSL adipocytes have been proposed to originate from the brown adipose tissue precursors given the similarity of morphological appearance and expression of specific molecular markers, such as the mitochondrial inner protein UCP-1 . Moreover, MSL adipocytes exhibit an increased, so-called tumor-like, proliferation rate, and have been described as showing intermediate morphological features between lipoma and liposarcoma . Whether the mutations of mitochondrial DNA described in MSL adipocytes are directly responsible of the increased growth rate  or are just an epiphenomenon of disturbances of other metabolic pathways remains to be established.