Lipomas – Causes, Symptoms, Diagnosis, Treatment

Lipomas are benign subcutaneous tumors of fat cells (adipocytes) that present as soft, painless nodules that are most commonly seen on the trunk. Lipomas usually range from 1- >10 cm. They are mesenchymal tumors and are found anywhere in the body where normal fat cells are present and are enclosed in a fibrous capsule. They are benign and have many histologic subtypes. The presence of multiple lipomas may be the presenting feature of a variety of syndromes.[rx] Although lipomas are present in subcutaneous planes rarely, they may also involve fascia or deeper muscular planes. [rx][rx][rx]

Lipomas are common benign tumors usually located in the subcutaneous tissues. Resection of lipomas frequently requires incisions equal to the diameter of the tumor. The “squeeze technique” with a small incision is well-described, but is frequently not successful, particularly for lipomas in the shoulder region. We report a method for resection of subcutaneous lipomas that preserves retaining ligaments.

Lipomas can sometimes, though rare, be associated with certain disorders such as multiple hereditary lipomatosis, Gardner syndrome, adiposis dolorosa, and Madelung disease.[rx] [rx] Some unconventional forms of lipomas include the following: angiolipoma, chondroid lipoma, lipoblastoma, myelolipoma, pleomorphic lipoma/spindle cell lipoma, intramuscular and intermuscular lipoma, lipomatosis of nerve, lipoma of the tendon sheath and joint, lipoma arborescent, multiple symmetric lipomatosis, diffuse lipomatosis, adiposis dolorosa, and hibernoma.

Types of Lipomas

Lipomas are composed of adipose/fat tissue, are mobile, soft to the touch, typically painless, and present subcutaneously. These are surrounded by a thin, fibrous capsule that is not attached to the underlying muscle fascia. In their typical form, they rarely present a diagnostic challenge.[rx] These masses are typically less than 2 inches wide but maybe larger. They are commonly singular. However, some patients have more than one. They typically occur in the upper trunk, head, neck, shoulders, and back of patients. Histologic variants of lipoma are as follows:

Adenolipoma of Skin

• They are superficially located
• They may not be well encapsulated
• They contain entrapped eccrine glands[rx]
• The term adenolipoma is also used for a variety of lesions containing fat that occur in several organs
  • These are not considered to be related to lipomas

Angiolipoma

• Circumscribed subcutaneous mass
  • Frequently multiple
  • Rarely greater than 2 cm
  • Infiltrating intramuscular tumors are considered intramuscular hemangiomas
  • Spinal angiolipoma is regarded as a distinct entity
• These are composed of mature fat with numerous small blood vessels
• The vascular component may be patchy
  • Frequently accentuated in subcapsular area
  • Vessels are predominantly capillaries
  • Fibrin thrombi are almost always present
  • Fibrosis may be associated with a vascular component
• Cellular variant
  • • Defined as having 95% cellular, angiomatous tissue
    • Spindle cells are abundant in cellular areas
    • There is only mild pleomorphism
    • Mitotic figures are inconspicuous
  • These have been associated with usual angiolipomas in the same patient

Cartilaginous Metaplasia in a Lipoma

• Lipoma containing areas with true cartilage formation
• May coexist with osseous metaplasia
• Multiple cases reported in breast and pharynx

Chondroid Lipoma

• These are well-circumscribed and may be encapsulated
• Three components are seen in all cases
• Mature adipose tissue is interspersed or compartmentalized
• Myxoid or hyaline chondroid matrix prominent
• Alcian blue and colloidal iron positive
• Variable sensitivity to hyaluronidase
• Hemorrhage, sclerosis, and calcification may be seen
• Vacuolated cells
  • Usually in nests or cords
  • May be in lacunae
• Vacuoles of variable size [rx]
  • Cells with fine droplets resemble hibernoma cells
  • Cells with large droplets resemble lipoblasts
  • The cytoplasm may also be granular or fibrillar
  • Maybe glycogen positive
• The nuclei are usually oval and regular
  • They may be central or peripheral
  • The nucleoli are inconspicuous or small
  • The pleomorphic nuclei are reported in only 1/20 cases
• The mitotic figures are reported in only 1/20 cases

Fibrolipoma

• Lipoma with focally increased fibrous tissue
• These must not contain atypical cells
• This pattern may be seen in lipomas involving nerve
• Focal fibrous tissue in a lipoma is a fibrolipoma and whereas focal fat in a predominantly fibrous lesion is a sclerotic lipoma

Myelolipoma

• This is a circumscribed mass which is composed of mature fat and bone marrow elements
  • The fat component usually predominates
  • May have a prominent lymphoid component
• Most often occurs in adrenal
  • The most common extra-adrenal site is the pelvis
• Clinically relevant as it might create ambiguity in the differential diagnosis of adrenal tumors [rx]

Myolipoma

• This variant is composed of mature fat and bland, smooth muscle
• Muscle predominates in most cases
  • • Usually evenly interspersed
  • The muscle in short fascicles
• Both components lack any atypical features
  • No cytologic atypia or lipoblasts
  • No floret cells
  • No necrosis
• Stroma may be sclerotic or hyalinized
  • Occasionally myxoid
  • No prominent vascular component
• Occasional features (none affect behavior)
• Mitotic figures up to 1/10 HPF [rx]
  • No atypical mitoses
  • Focal hypercellularity of spindle cells
  • Degenerative atypia
  • Round cell morphology
  • Hemosiderin
  • Metaplastic cartilage and bone
  • Prominent eosinophils
• Sites of involvement
  • Females: pelvic, retroperitoneal, suprapubic, inguinal
  • Males: inguinal, abdominal wall, back
• Other sites include the eyelid, spinal cord, and pericardium

Myxolipoma

• Lipoma with prominent myxoid areas
• Must not contain lipoblasts
• If richly vascular, termed angiomyolipoma
  • Thin and thick-walled vessels
  • Maybe dilated

Ossifying Lipoma

• This variant contains mature metaplastic bone
• This variant may coexist with cartilaginous metaplasia in a lipoma.

Sclerotic Lipoma

• This is a circumscribed subcutaneous nodule
  • Occasional cases involve entrapped nerve, eccrine glands, or arrector pili muscle
• There are extensive sclerotic collagen bundles [rx]
• These range from highly sclerotic to myxo-collagenous
  • Generally haphazard but may be whorled or concentric
  • Vessels range from inconspicuous to prominent
• Spindled or stellate cells in sclerotic areas
  • Hypocellular
  • At most focal mild atypia
  • Mitotic figures rare
• Bi- or multinucleated cells may be present
  • Rare cases present with floret cells
• Admixed mature fat cells
• Usually, less than 10% of the lesion
  • Range 5-50%
  • Maybe more prominent at the periphery
• These are rare and mostly reported on fingers or scalp

Variants of lipoma defined by location include:

• Intermuscular lipoma
• Intramuscular lipoma
• Parosteal / periosteal lipoma
• Lipoma arborescens (synovial lipomatosis)

Biochemical and Genetic Pathology

Patients often complain of a soft, mobile mass of tissue they can feel under the skin. These are typically painless unless they encroach joints, nerves, or blood vessels. Patients often see these in the upper part of the body. Rarely, these lipomas can form in muscles or organs.

Lipomas are mostly harmless and are only treated or excised if they cause pain due to their location and/or impact an organ’s function. However, some patients choose to have these masses removed for cosmetic reasons, as they can often be seen through the skin as they lie subcutaneously. Small lipomas (less than 4 cm) can be removed through small incisions, and scarring is not usually a significant concern. Research conducted also concluded that open surgery is still a better option for removing giant lipomas (greater than 10 cm)compared with lipoma removal by suction-assisted lipectomy through small incisions as it allows better judgment, prevents recurrences, and avoids damage to the surrounding tissues.[rx]

A genetic link has been demonstrated that cites that about two-thirds of lipomas exhibit genetic abnormalities. In a subgroup of lipomas, the HMGA2 gene (located on 12q14.3) was involved in tumor pathogenesis.

The following structural rearrangements of chromosomes have been associated with lipoma occurrence:

• 12q13-15 region
• 13q portion loss
• 6p21-23 region
• Other loci anomalies or normal karyotype [rx

Colonic lipomas are usually discovered incidentally on colonoscopy. A biopsy specimen of the lipoma will most likely reveal mature adipocyte, which is called the “naked fat’ sign. As with other lipomas, colonic lipomas can also cause pain with obstruction and intussusception.

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.[rx][rx]

The techniques used for such include intralesional transcutaneous sodium deoxycholate (associated or not to phosphatidylcholine) injections, intralesional steroids combined with isoproterenol (a beta-2 adrenergic agonist) injections, liposuction of the tumor, or surgical excision. This latter is likely the most effective method to prevent them from reoccurring, though the encapsulation must also be removed for the most effective treatment and to decrease the risk of reoccurrence.[rx] If the decision is made to excise lipomas, then it should be done while the lesions are smaller rather than after they grow larger to reduce the risk of these encroaching on joints, nerves, and blood vessels, thus making the excision more difficult and invasive.

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 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 usually affects postmenopausal women who suffer from psychiatric disorders.
• Familial multiple lipomatosis– patients typically present in the ’30s with hundreds of encapsulated and noninfiltrating lipomas. It can be inherited in an autosomal dominant pattern.
• 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 present with this syndrome. Mutations in the mitochondrial tRNA lysine gene have been identified in a few of the affected patients.
• Gardner syndrome is due to autosomal dominant mutations in the adenomatous polyposis coli (APC) gene. Almost all patients develop adenocarcinomas of the gastrointestinal tract. Cutaneous changes include multiple lipomas or fibromas. Other associated findings include congenital hypertrophy of pigment epithelium of retina, osteomas of the skull, maxilla and mandible, 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 the MEN1 gene. It consists of the parathyroid, pituitary, and pancreatic tumors. Dermatologic 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 the PTEN gene. It is associated with multiple lipomas, oral papillomas, facial trichilemmomas, punctate palmoplantar keratoses, and malignancies, including breast adenocarcinoma, thyroid follicular carcinoma (TFC), endometrial carcinomas, and hamartomatous polyps of the gastrointestinal tract.
• Bannayan-Riley-Ruvalcaba syndrome (BRRS) is also due to PTEN gene mutations and may represent a pediatric form of Cowden syndrome. Clinical findings include multiple lipomas, intestinal hamartomas, genital lentigines, macrocephaly, and mental retardation.

References