Article Author:
Logan Kolb
Article Editor:
Juan Rosario-Collazo
10/27/2018 12:31:41 PM
PubMed Link:


Lipomas are common, benign subcutaneous tumors of fat cells (adipocytes) that present as soft, painless nodules that are most commonly seen on the trunk. They are benign and have many histologic subtypes. The presence of multiple lipomas may be the presenting feature of a variety of syndromes.


The precise cause of lipomas is unknown. Genetics appear to play a role since 2% to 3% of affected patients have multiple lesions inherited in a familial pattern. There also are several genetic syndromes that feature lipomas as a clinical manifestation. The incidence of lipomas is increased in patients with obesity, hyperlipidemia, and diabetes mellitus.


Lipomas have a slightly higher incidence in males compared to females. Although they can occur at any age, they are often noted between the fourth to sixth decades of life. Despite being one of the most common neoplasms in humans, the incidence and prevalence of lipomas have not been reported in the literature.


The exact pathophysiology of lipomas is unclear. However, several cytogenetic abnormalities have been identified including the following: 

  • Mutations in chromosome 12q13-15, 65% of cases
  • Deletions of 13q (10% of cases), rearrangements of 6p21-33, 5% of cases
  • Unidentified mutations or normal karyotype, 15% to 20% of cases

Rearrangements of the 12q13-15 result in fusion of the high-mobility group AT-hook 2 (HMGA2) gene to a variety of transcription regulatory domains that promote tumorigenesis.


Histologic examination of lipomas reveals mature, normal-appearing adipocytes with a small eccentric nucleus. Adipocytes are intermixed among thin fibrous septa containing blood vessels. These features are indistinguishable from adipocytes in the subcutaneous tissue. Histologic subtypes of lipomas include angiolipomas, myelolipomas, angiomyolipomas, myelolipomas, fibrolipomas, ossifying lipoma, hibernomas, spindle cell lipomas, pleomorphic lipomas, chondroid lipomas, and neural fibrolipomas. Common lipomas and its variants must be distinguished from liposarcomas which are a malignant lipomatous neoplasm containing lipoblasts, which are characterized by coarse vacuoles and one or more scalloped, hyperchromatic nuclei.

History and Physical

Lipomas typically present as soft, solitary, painless, subcutaneous nodules that are mobile and not associated with epidermal change. They are typically slow-growing and grow to a final stable size of 2 to 3 centimeters. However, they are occasionally greater than 10 centimeters and referred to as "giant lipomas." Lipomas may appear anywhere on the body but tend to favor the fatty areas of the trunk, neck, forearms, and proximal extremities. They are rarely seen in acral areas. Lipomas may affect many cutaneous and noncutaneous sites, including dermal, subcutaneous, and subfascial tissues along with intermuscular, intramuscular, synovial, bone, nervous, or retroperitoneal sites.

Multiple lipomas are present in 5% to 10% of affected patients and are usually associated with familial lipomatosis or numerous other genetic disorders described in the differential diagnosis section. The use of protease inhibitors in HIV patients may induce lipomas and lipodystrophy; therefore, a thorough past medical and medication history should be obtained.


Common lipomas frequently are diagnosed clinically and sent for histologic examination after complete surgical excision. Radiologic imaging before surgery may be prudent in cases featuring the following: 

  • Giant size (greater than 10 centimeters),
  • Rapid growth
  • Pain
  • Fixation to underlying tissues
  • Location in deep tissues, the thigh, or retroperitoneal space

Treatment / Management

Lipomas do not involute spontaneously, although dramatic weight loss may make lesions more clinically prominent. Stable lesions often are observed clinically. The decision to treat depends on numerous factors including lesion size, anatomic location, symptoms such as pain, and patient comorbidities. If treatment is desired, surgical excision is commonly employed. Large lipomas have been removed via liposuction.

Differential Diagnosis

The differential diagnosis includes but is not limited to epidermoid cysts, hibernomas, angiolipomas, angiomyolipomas, and liposarcomas. Epidermoid cysts typically feature a punctum at its surface; however, lesions lacking this feature may be indistinguishable from lipomas. Hibernomas are rare, benign, slow-growing masses of brown fat that typically occur in the mediastinum or interscapular region of the back and present as a 3- to 12-centimeter, slow-growing mass in an adult. Angiolipomas are often painful, less than 2 centimeters in width, well circumscribed, and typically appearing on the forearm of teens or young adults. Angiomyolipomas often present on acral locations of adult males. Liposarcomas most commonly present as deep-seated tumors in the retroperitoneum or, classically, on the thighs.

Multiple lipomas can be a manifestation of the following syndromes:

  • Proteus syndrome due to activating mutations in AKT1 oncogene (or occasionally PTEN mutations). It consists of multiple lipomas, epidermal nevi, hemangiomas, palmoplantar cerebriform connective tissue nevi, hyperostoses of the epiphyses and skull, and scoliosis.
  • Dercum disease (adiposis dolorosa) consists of multiple painful lipomas on the trunk and extremities which often have overlying paresthesias of the skin. It often affects postmenopausal women who suffer from psychiatric disorders such as depression.
  • Familial multiple lipomatosis- patients typically present in the third decade with hundreds of discrete, encapsulated, noninfiltrating lipomas. It can be inherited in an autosomal dominant fashion.
  • Benign symmetric lipomatosis (Madelung disease) involves diffuse, infiltrative, symmetric painless lipomatous growths affecting the head, neck and shoulder region. Middle-aged alcoholic men are usually affected. Mutations in mitochondrial tRNA lysine gene have been identified in some affected patients.
  • Gardner syndrome is due to autosomal dominant mutations in the adenomatous polyposis coli (APC) gene. Nearly all patients develop adenocarcinomas of the GI tract. Cutaneous changes include multiple lipomas, epidermoid cysts, or fibromas. Other associated findings include congenital hypertrophy of retinal pigment epithelium (CHRPE), osteomas of the skull, mandible and maxilla, supernumerary teeth, and various malignancies including papillary thyroid carcinomas, adrenal adenomas, and hepatoblastomas.
  • Multiple endocrine neoplasia (MEN) type 1 is due to autosomal dominant mutations in MEN1. It consists of pituitary, parathyroid, and pancreatic tumors. Cutaneous changes include multiple lipomas (which may also occur in visceral sites), collagenomas, angiofibromas, and cafe au lait macules.
  • Cowden syndrome is due to mutations in PTEN and is associated with multiple lipomas, facial trichilemmomas, oral papillomas, punctate palmoplantar keratoses, and a variety of malignancies including breast adenocarcinoma, thyroid follicular carcinoma, endometrial carcinomas, and hamartomatous polyps of the gastrointestinal tract.
  • Bannayan-Riley-Ruvalcaba syndrome (BRRS) is also due to PTEN mutations and may represent a pediatric form of Cowden syndrome. Clinical findings include multiple lipomas, genital lentigines, intestinal hamartomas, macrocephaly, and mental retardation.


Lipomatous lesions arising in the midline sacrococcygeal region can be a manifestation of spinal dysraphism (along with skin tags, hair tufts, angiomas, and a variety of other cutaneous changes). For this reason, a neurosurgery consultation is indicated for lipomatous lesions in this region.


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