Lipomas, Lipomatosis, and Liposarcoma

Melvin A. Shiffman

BACKGROUND

Virchow¹ first stated that adipose tissue was merely a common connective tissue loaded with stored simple fats. This view was supported by Flemming²,³ but had been challenged by Toldt (1870),⁴ who held that adipose tissue was a specific organ and quite separate from connective tissue. Adipose tissue was derived from special primitive fat organs, which had a lobular structure and in which a distinct type of cell existed with a capacity for the storage or release of fat according to the metabolic requirements of the body.⁴

Lipomas are benign adipose tissue tumors that appear as masses and are only occasionally symptomatic. Lipomatosis consists of multiple lipomas associated with genetic disorders. Liposarcomas are malignant tumors that arise from adipocytes. They may recur locally and may metastasize, particularly when of the dedifferentiated subtype. Each of these disorders is discussed, including diagnosis, characteristics, classification, and treatment.

PRESENTATION

Patients complain of a lump or lumps that distort the smooth outline of the body. Patients usually question the diagnosis and decisions to be made about treatment. Many clinicians are unaware of the many different kinds of lipomatous and liposarcomatous lesions that may appear and their consequences.

DIAGNOSIS

Clinical Diagnosis

Lipomas

Lipomas are slowly growing, painless, mobile, soft, or rubbery nodules with smooth surfaces. They can be
dome- or egg-shaped and typically measure 2 to 10 cm in diameter. They most commonly appear on the shoulders, neck, trunk, and arms, although they may appear in any part of the body that possesses fatty tissue (Figure 6.4.1). Angiolipomas differ in that they may be painful or tender. Lipomas are usually superficial but may be deep but are not attached to underlying structures (Table 6.4.1). Lipomas may be intramuscular. When present inside an organ, such as muscle, the mass will be difficult to palpate and should be examined by computerized tomography (CT) and/or magnetic resonance imaging (MRI) (Figure 6.4.2). Lipomas have been

rarely found in many visceral, thoracic organs, as well as in the central and peripheral nervous systems and genitourinary organs (summarized in Table 6.4.2). A soft to firm nodule may represent the rare variant of fibrolipoma characteristic of Dercum disease (Figure 6.4.3A).

FIGURE 6.4.1 Clinical presentation of lipoma of the leg.

TABLE 6.4.1 Lipoma Subtypes

Diagnosis	Description
Lipoma	Benign, soft rubbery, encapsulated tumor of adipose tissue, usually composed of mature fat cells. Generally, occurs as a solitary lesion in the subcutaneous tissue of the trunk, nucha, or forearms but may occur in deeper soft tissues, such as intramuscular, intermuscular, intraarticular, intraspinal, intradural, or epidural. May be an annoyance to the patient owing to size and cosmetic appearance
Angiolipoma (hemangiolipoma, angiomyolipoma, vascular lipoma, lipoma cavernosum)	Consists of small, painful, fully encapsulated subcutaneous nodules. Usually located in the forearm, arm, and chest wall where the tumors are multiple, painful, yellow, firm, and circumscribed. May be infiltrating or noninfiltrating (sometimes invade skeletal muscle). Reported in various areas such as spinal epidural, parapharyngeal, thyroid gland, buccal mucosa, intracranial, breast, ileum, spine, colon, epidural, lumbosacral, intracranial, buccal mucosa, plantar, and neck
Chondrolipoma	Islets of hyaline cartilage in adipose tissue
Intermuscular lipoma	A slow-growing, infiltrating lesion composed of mature fat cells, occurring in the deeper soft tissues between muscle groups, predominantly thighs, shoulders, or arms of middle-aged to older adults
Intramuscular lipoma	Similar to intermuscular lipoma but occurring within muscle
Epidural lipoma	An intraspinal lipoma on or outside the thoracic or lumbar spinal dura mater, often causing spinal cord compression; Cushing disease and administration of steroids are common causes
Intradural lipoma	An intraspinal lipoma within or beneath the dura mater of the spine or sacrum
Intramedullary lipoma	An intraspinal lipoma within the spinal cord
Intraneural lipoma	Well encapsulated lipoma within a nerve; usually completely resectable
Intraspinal lipoma	A lipoma within the spinal canal; it may exist entirely within the canal or may protrude and form part of a lipomyelomeningocele
Intraosseous lipoma	A rare benign bone tumor arising from mature adipocytes
Lipoblastoma	Rare benign tumor of adipose tissue usually occurring in children. Limited excision is the therapy of choice
Lipofibroma (lipofibromatous hamartoma, lipoma fibrosum)	A benign tumor of fibrous connective tissue with a conspicuous number of adipocytes
Pedunculated lipofibroma (nevus lipomatosus, nevus lipomatosis cutaneous superficialis)	Slow-growing pedunculated tumors characterized by strands of fat cells embedded in the collagen bundles of the dermis. Pedunculated lipofibroma designated as the solitary form of nevus lipomatosus cutaneous superficialis. Sites of predilection are usually the pelvic girdle (buttocks sacrococcygeal area) and thighs, but they have been found in the axilla, knee, ear, hand, eyelid, neck, or scalp
Intraneural lipofibroma (lipofibromatous hamartoma, macrodystriophia lipomatosa)	Affects the peripheral nerves, most commonly in the upper extremity. There is infiltration of the epineurium by fibrofatty tissue that separates and compresses the nerve fascicles. Cannot be removed completely without permanent damage to the nerve. May be associated with enlargement of bone
Lipoma arborescens	An intraarticular tumor frequently occurring as a solitary lesion usually in the knee; it is characterized by numerous swollen treelike synovial villous projections of fatty tissue and may arise de novo or be associated with disorders such as degenerative joint disease, chronic rheumatoid arthritis, or previous traumatic injury
Lipoma capsulare	A fatty tumor due to increase of the fat in the capsule of an organ
Synovial lipomas	Can be both intra-articular (lipoma arborescens), commonly in the popliteal space, or extra-articular, occasionally seen around the hip and knee joints
Lipoma myxomatodes (myxolipoma, lipomyxoma)
Lipoma ossificans	An ossified lipoma
Lipomeningocele	Meningocele associated with an overlying lipoma, in spina bifida
Lipomyelomeningocele	Myelomeningocele with an overlying lipoma
Piezogenic pedal papules	Consists of asymptomatic (usually) papules along the sides of the plantar surface only when weight bearing. Occasionally painful and often seen in runners. Caused by herniation of subcutaneous fat into the dermis. Found in 10%-20% of the general population and more common in women
Hibernoma	A rare asymptomatic, benign tumor that arises mostly in adults from the remnants of fetal brown adipose tissue, and usually affects muscle and subcutaneous tissue. The brown fat is a specialized form of fat found in hibernating animals as well as in vestigial remnants in humans. Usually occurs between the ages of 20-50 y. The most common sites are the thigh, shoulder, back, neck, chest, arms, and abdominal cavity/retroperitoneum. The tumor is encapsulated, tan-brown in color, and lobulated. Infiltration of adjacent structures, especially striated muscle, may occur. The tumor tends to enlarge, sometimes causing compression of neighboring structures. Complete excision is usually necessary. Hibernoma is found in a variety of areas of the body. In rare instances it can occur in bone
Hibernoma: lobular type	Variable degrees of differentiation of uniform, round to oval cells with granular eosinophilic cells with prominent borders, alternating with coarsely multivacuolated fat cells (pale cells). There are usually small centrally placed nuclei without pleomorphism. The cells have large cytoplasmic lipid droplets interspersed throughout
Hibernoma: myxoid variant	Loose, basophilic matrix, with thick fibrous septa, and foamy histiocytes
Hibernoma lipoma type	Univacuolated lipocytes, with only isolated hibernoma cells
Hibernoma spindle cell variant	Spindle cell lipoma combined with hibernoma. Occurs in the neck or scalp and has features of spindle cell lipoma and hibernoma. Appears lipomalike and contains scattered hibernoma cells. The tumor is divided into lobules by thin septa, with large coarsely vacuolated cells, large finely vacuolated cells with eosinophilic granular cytoplasm, and mature univacuolated adipocytes
Posttraumatic lipomas	Thought to result from preadipocyte differentiation and proliferation mediated by cytokine release following soft tissue trauma and hematoma formation. Generally noted about 6 mo after injury. Posttraumatic pseudolipomas have been reported in various areas of the body. Trauma may cause tearing of the fibrous capsules and septae normally found in body fat resulting in the pseudolipoma
Lipopexia	The accumulation of fat in the tissues

FIGURE 6.4.2 Computed tomography (A) and surgical (B) images of intramuscular lipoma. White arrows highlight the borders of the lipoma within the muscle.

TABLE 6.4.2 Lipomas Arising in Organs

Location of Lipoma	Comments
Gastrointestinal system	May be associated with leiomyomas or multiple polyposis syndromes
Esophageal	Extremely rare
Stomach	More common in older individuals, may cause ulcerations, bleeding, pyloric obstruction, or intussusception
Small intestine	Rare, may cause bleeding or intussusception
Ileocecal intestine/colon	Rare but most common mesenchymal tumor of colon. More common in older individuals, may cause intussusception
Pancreas
Respiratory tract	Laryngeal, endobronchial, pulmonary lipomas are rare, often diagnosed postmortem
Heart	Rare, often diagnosed postmortem
Spleen	Extremely rare
Paratesticular, female genital tract	May occur at any site of female genital tract
Renal	Renal angiolipomas: associated with tuberous sclerosis
Central nervous system, peripheral nervous system	Corpus callosum, pia mater, intradural, intraspinal, peripheral nerves
Multiple lipomas	May be seen in neurofibromatosis type 1

A diagnostic challenge is the possible history of recent injury in the same area. The physician should be aware that traumatic hematomas will get smaller over time but lipomas and liposarcomas will remain the same or grow larger. Therefore, the patient should be seen at appropriate intervals of time for monitoring: 1 to 3 months for at least 1 year would be appropriate.

Lipomatosis

In familial lipomatosis, multiple rubbery nodules are present. See Table 6.4.2 and Subtypes below for clinical presentation.

Liposarcomas

Liposarcomas differ from lipomas in that they are deep-seated tumors, often growing on the thigh or groin or within the abdominal cavity. They sometimes enlarge more rapidly and may become painful. Any new mass present for more than 4 weeks should be considered possibly malignant. If there is involvement of deep tissues with suspicion of decreased mobility of the mass, or if the tumor is greater than 5 cm, then malignancy should be suspected.

Liposarcomas (Table 6.4.3) are most commonly found in the extremities, the retroperitoneum, and, less often, in the head and neck area. These tumors appear to arise from deep-seated, well-vascularized structures rather than from submucosal or subcutaneous fat. Liposarcomas of all subtypes can occur in the dermis and the subdermis; however, their primary occurrence in the skin is rare.⁵ All cases of liposarcomas in the skin tend to grow in an exophytic manner, presenting as either dome-shaped or polypoid lesions. These masses may resemble pleomorphic fibroma.⁶ Liposarcomas arise de novo, and the development of a liposarcoma from a preexisting benign lipoma is rare.

Initially, liposarcomas are asymptomatic and may not be detected until large enough to palpate (depending on depth of tumor) or if there is trauma to the

area that alerts the patient to a mass. When the tumor is larger and invades neighboring structures there may be tenderness, pain, numbness, fatigue, or functional disturbances. Liposarcomas in the retroperitoneal area are usually quite large before diagnosis is established.⁵

FIGURE 6.4.3 A, Fibrolipoma of the abdomen. B, Histologic micrograph of fibrolipoma.

TABLE 6.4.3 Lipomatosis Syndromes

Diagnosis	Description
Bannayan syndrome (Bannayan-Zonana syndrome, Riley-Smith syndrome, Ruvalcaba-Myhre-Smith syndrome, microcephaly-hamartomas syndrome)	Autosomal dominant familial syndrome characterized by symmetrical microcephaly, mild neurologic dysfunction, postnatal retardation, mesodermal hamartomas, discrete lipomas, penile pigmented macules, skin tags, and hemangiomas
Congenital diffuse lipomatosis (congenital infiltrating lipomatosis)	Malformation of the adipose tissues in which lipoblasts form discrete tumors and infiltrate the surrounding structures. In congenital lipomatosis of the extremities, lipomas are restricted to 1 or 2 extremities and associated with corresponding gigantism. In congenital lipomatosis of the trunk, the tumors are found in the lumbodorsal and scapular regions. Pelvic lipomatosis is an abundance of fatty tissue in the perirectal and perivescical spaces in the pelvis. There have been reports of facial congenital infiltrating lipomatosis
Congenital lipomatosis of the pancreas (Schwachman-Diamond syndrome)	An inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea), are slow to grow and gain weight (failure to thrive), and experience malnutrition
Dercum disease (Dercum syndrome, adiposis dolorosa, Anders syndrome, adiposalgia, adipositas, tuberosa simplex, fibrolipomatosis dolorosa, neurolipomatosis, lipoalgia, lipomatosis dolorosa)	Multiple nodules or more or less extensive accumulation of subcutaneous fat. Lumpy encapsulated masses are found on the thighs, abdomen, or axillary region. Intra-abdominally, the disease is encountered in the omentum with multiple tumors arranged like “beads” in a chain. Symptoms include asthenia, pain (ranging from tenderness to spontaneous severe attacks), and psychic disturbances. Usually seen in women and may cause death from pulmonary complications. The etiology is unknown but combined endocrine deficiency is a possibility. A hereditary relationship has been proposed. Different types can be identified according to the spread of pain. Type I or juxta-articular type: Has painful folds on the inside of the knees and/or hips and in rare cases evident in upper arm fat Type II or diffuse: Widespread pain is found, apart from that of type I, also often in the dorsal upper arm fat as well as the axilla, gluteal, stomach wall, dorsal fat folds, and on the soles of feet Type III or lipomatosis, nodular type: Intense pain in and around multiple “lipomas,” sometimes in the absence of general obesity. Lipomas are approximately 0.5-4 cm, soft, and attached to surrounding tissue. Histologically, these are not always encapsulated and some have been classified as angiolipomas
Diffuse lipomatosis (diffuse lipoma, congenital diffuse lipomatosis)	Abnormal increase of subcutaneous fat in parts of the pelvis, usually in males
Encephalocraniocutaneous lipomatosis (Fishman syndrome)	Sporadically occurring neurocutaneous syndrome. Intracranial lipomas, visceral lipomas, porencephalic cysts, unilateral eye lesions in the form of choristomas, skull hamartomas, bilateral lipodermoids, jaw tumors such as ossifying fibromas and compound odontomas, and mental retardation. First described by Haberland and Perou in 1970.
Familial lipomatosis	Has an autosomal dominant inheritance and shows histopathologically numerous, variably sized typical-appearing angiolipomas with 15%-50 percent vascular component (lipomas have less than 10% vascular component).
Familial multiple lipomatosis	Characterized by numerous, encapsulated lipomas on the trunk and extremities that generally affect consecutive generations within families, most likely autosomal dominant. Clinical features include oval to round subcutaneous, rubbery lipomas that first appear in the third through fifth decades. Liposuction and surgical excision are used for cosmetic purposes in patients with disfiguring and unusually large tumors. Genetically may be a translocation of the high-mobility group protein isoforms I-C on chromosome 12 and the lipoma preferred partner gene on chromosome 3
Lipomatosis atrophicans (lipodystrophia progressive)	Localized accumulations of fat occur in certain tissues, associated with emaciation of the rest of the body
Lipomatosis gigantica	A form in which adipose deposits form large masses
Madelung deformity	A distinct form of Madelung disease with a characteristic pattern of anterior-ulnar bowing of the radius and dorsal prominent ulnar head. Most subjects have dyschondrosteosis
Madelung disease (multiple symmetrical lipomatosis, benign symmetric lipomatosis, familial multiple symmetric lipomatosis, symmetric adenolipomatosis, Launois-Bensaude syndrome, Madelung-Launois-Bensaude syndrome, Buschke syndrome, Buschke II syndrome, Brodie II syndrome	This is a rare disease, with onset between 35 and 40 y of age. More prevalent in males of Mediterranean descent, with diffuse tumefaction in the posterior part of the neck. Characterized by enlarging, painless, symmetric, fatty deposits in specific areas of the body, especially the neck, submandibular region, shoulders, and proximal upper extremities, giving the patient a “horse collar” or “buffalo hump” appearance. Asthenia and apathy are usually present. Compression of peripheral nerves results in pain. Dyspnea, cough, cyanosis, and exophthalmus may develop. An association with the A8344G mutation of mitochondrial DNA has been reported
Madelung neck (Madelung deformity, annulare colli, lipoma annulare colli)	Described by Madelung in 1888 as “fat neck.” Consists of a haphazard accumulation of lipomas around the neck and is a variation of multiple symmetric lipomatosis
Nevus lipomatosis cutaneous (superficial lipomatous nevus, nevus superficialis, nevus lipomatodes cutaneous superficialis, Hoffman-Zurhelle)	A rare condition consisting of ectopic accumulation of nevus adipose tissue that occurs predominantly in the pelvic girdle area. Can be multiple or solitary. The appearance is of grouped, yellowish, soft papules or nodules, without tenderness that often coalesce into plaques. One form of the disease has been termed the Michelin tire baby syndrome with prominent crease and bands on the arms and legs with generalized nevus lipomatosis cutaneous superficialis or smooth muscle hamartomas
Nodular circumscribed lipomatosis	The formation of multiple circumscribed or encapsulated lipomas that may be distributed symmetrically (symmetrical lipomatosis), form a collar around the neck (Madelung neck), or appear haphazardly. At times they may be painful (lipoma or lipomatosis dolorosa)
Proteus syndrome	A sporadic disorder that causes postnatal overgrowth of multiple tissues that include skin, subcutaneous tissue, connective tissue (including bone), the central nervous system, and viscera. Progressive skeletal deformities occur with invasive lipomas and benign and malignant tumors. The disorder is caused by mosaic mutations in the AKT1 gene. The most notable case was that of Joseph Merrick, immortalized as the “Elephant Man”
Spinal epidural lipomatosis	Causes symptomatic compression of neural elements; reported frequently in association with chronic systemic corticosteroid injections
Relapsing febrile nodular nonsuppurative panniculitis (Weber-Christian disease)	Usually self-limiting and characterized by intermittent appearance of subcutaneous nodules and plaques caused by degeneration of fatty tissue, with subsequent inflammation. Characteristic are recurrent subcutaneous nodules in the lower extremities with the overlying skin usually erythematous. Clinically asymptomatic lesions resemble lipomas. Malaise and slight to moderate pyrexia often accompany the appearance of new nodules. Infrequently, the mesentery of obese patients may be involved and they may develop acute abdominal symptoms. Clinical distinction from acute appendicitis is often impossible because both diseases may have fever, leukocytosis, and abdominal tenderness. Steroids will curtail the period of acute manifestations in fulminating cases