What causes lipomas?

What Causes Lipomas?

The exact cause of lipomas remains unknown, though they are benign tumors composed of mature adipocytes that likely arise from a combination of genetic predisposition and, in some cases, environmental triggers such as blunt trauma. 1

Genetic Mechanisms

The most well-established causative factor involves genetic alterations:

• HMGA2 gene expression in adipose cells is a key molecular marker that enables differentiation of lipoma tissue from normal fat and liposarcoma 1
• Lipomas can run in families as familial multiple lipomatosis, indicating hereditary genetic susceptibility 1, 2
• They may occur as part of genetic syndromes including:
  • Multiple endocrine neoplasia type 1 1, 2
  • Neurofibromatosis type 1 1, 2
  • PTEN hamartoma tumor syndrome (Cowden syndrome) 1, 2
  • Proteus syndrome 1
  • PIK3CA-related disorders 2
  • Mitochondrial diseases (especially MERRF) 1, 2
  • Wilson's disease 1, 2

Trauma-Related Formation

A subset of lipomas appears linked to blunt soft tissue trauma, though this mechanism remains controversial:

• Post-traumatic lipomas develop at sites of prior blunt trauma, with an average latency of 2 years (range 0.5-5 years) after injury 3

• Approximately 80% of post-traumatic cases report extensive, slowly resolving hematomas at the site before lipoma formation 3

• Two proposed mechanisms exist 4, 3:

  1. Mechanical herniation: Fat tissue prolapses through fascia damaged by direct impact, creating "pseudolipomas" 4, 3
  2. Cytokine-mediated differentiation: Fat necrosis and hematoma formation trigger local inflammation, releasing cytokines that promote preadipocyte differentiation and proliferation into lipoma tissue 4, 3

• Only traumas causing fat necrosis appear capable of triggering lipoma formation 4

Clinical Context

• Most lipomas are sporadic and asymptomatic, arising without identifiable cause 1
• They consist of mature adipocytes that are relatively uniform in size without cytologic atypia 5
• Lipomas are slow-growing, benign lesions that can develop in any location containing adipose tissue 6
• The subcutaneous tissue of the trunk, neck, and limbs are most commonly affected 6

Important Caveats

• While trauma association exists in some cases, the majority of lipomas have no identifiable precipitating event 1
• Genetic testing is not routinely necessary for isolated, typical lipomas but becomes relevant when multiple lipomas occur or when associated with syndromic features 1
• The presence of lipomas does not necessarily indicate an underlying genetic syndrome unless other clinical features are present 1, 2