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Fitzpatrick's Dermatology in General Medicine, 8e

Chapter 129. Neoplasms of Subcutaneous Fat

Thomas Brenn

Neoplasms of Subcutaneous Fat: Introduction

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Neoplasms of Subcutaneous Fat at a Glance

Adipocyte tumors are the most frequently encountered group of mesenchymal neoplasms. This is due to the high prevalence of lipoma and angiolipoma.
Tumors range from entirely benign neoplasms (e.g., lipomas) to those of intermediate malignant potential with risk for local recurrence (e.g., atypical lipomatous tumor) to high-grade pleomorphic sarcomas (e.g., pleomorphic liposarcoma).
Although liposarcoma is the single most frequently encountered sarcoma, the large majority of adipocyte tumors are benign.
The clinical presentation of adipocyte tumors is generally nonspecific.
Most adipocyte tumors show distinctive cytogenetic abnormalities that may be of diagnostic value.
Treatment is surgical excision. Adjuvant radiation therapy and/or chemotherapy may be of benefit for treatment of malignant tumors that are not amenable to complete excision or in cases of advanced disease.

Lipoma

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Lipoma at a Glance

Lipoma is the most common soft-tissue tumor.
It is benign and presents in adulthood as a small circumscribed mass. The anatomic distribution is wide with relative sparing of the head, hands, and feet.
Histologically, the tumors are circumscribed, encapsulated, and composed of mature white adipose tissue.

Epidemiology

Lipomas are the most common soft-tissue neoplasm. Although they affect individuals in a wide age range, they occur predominantly in adults between the ages of 40 and 60 years; presentation in childhood is rare. There is no gender predilection. Lipomas are multiple in approximately 5% of cases.1

Etiology and Pathogenesis

The majority of lipomas (approximately 75%) show karyotypic abnormalities. The cytogenetic findings are heterogeneous, but rearrangements of 12q13–15 are most common.2–4 Other affected loci are on chromosomes 6 and 13.2–4 Numerical abnormalities are scarce, and most tumors are diploid.

Clinical Findings

The most common presentation is as a painless, slowly enlarging mass involving the subcutaneous tissue of the trunk, neck, or proximal extremities. Involvement of the head, hands, and feet is uncommon. These superficial lipomas are typically small, measuring less than 5 cm.1 Lipomas may be multiple and familial and show a predilection for the arms and thighs in familial multiple lipomatosis (Fig. 129-1).5 The constellation of multiple lipomas, macrocephaly, lymphangiomas, and hemangiomas is known as Bannayan (Bannayan–Zonana) syndrome.6,7 This autosomal dominant disease shares features with other independently described entities and is currently also referred to as Bannayan–Riley–Ruvalcaba syndrome.8,9 Further clinical findings include intestinal polyposis, genital pigmented macules, and other hamartomas. The syndrome is caused by mutations in the PTEN gene and belongs to the larger family of PTEN hamartoma-tumor syndromes, including Cowden disease.10–15 Lipomas may also be seen as a manifestation of Gardner's syndrome. Gardner's syndrome is part of the spectrum of familial adenomatous polyposis and includes extracolonic manifestations such as desmoid fibromatosis, osteomas, cysts, and lipomas.

Figure 129-1

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Familial multiple lipomatosis: multiple lipomas of variable size show a symmetric distribution involving the forearms of this middle-aged man.

Less frequently, lipomas may be deep-seated and grow to sizes larger than 5 cm. They can affect a variety of anatomic locations, including the surface of bone (parosteal lipoma) and skeletal muscle (intramuscular and intermuscular lipoma). Intramuscular lipoma arises within skeletal muscle and may be circumscribed or infiltrative. It presents in adulthood and only rarely affects children. The range of anatomic sites is wide, but there appears to be a predilection for the trunk.16,17 In contrast, intermuscular lipoma develops between individual muscles and does not infiltrate skeletal muscle bundles. It is a rare lipomatous tumor with a predilection for the anterior abdominal wall.16,17 Lipomas of the forehead are frequently deep-seated, presenting in a submuscular or subgaleal location. They show a predilection for male adults.18,19 Lipoma arising in the orbit (orbital lipoma) is rare but may lead to exophthalmus and visual disturbances.20–22

Histologic Features

Conventional lipomas are circumscribed masses surrounded by a thin fibrous capsule. They are composed of lobules of mature white adipose tissue divided by delicate and inconspicuous fibrous septa containing thin-walled capillary-sized vessels (Fig. 129-2). The adipocytes are univacuolated and mature with eccentrically placed, compressed nuclei. There is only slight variation in adipocyte size, and nuclear atypia is not a feature. Morphologically, lipomas are indistinguishable from the surrounding adipose tissue and the identification of a distinct mass is necessary for the diagnosis. Lipomas may show changes of trauma with varying amounts of fat necrosis and inflammation. Extensive involvement of the dermis is known as dermal lipoma. These tumors are not encapsulated and are frequently less circumscribed than other forms of superficial lipoma (Fig. 129-3). Lipomas with increased fibrous tissue are referred to as fibrolipomas (Fig. 129-4). In contrast to atypical lipomatous tumors, cellularity is low within the fibrous strands, and no nuclear atypia is present. Myxolipomas are characterized by the presence of conspicuous myxoid stroma. Angiomyxolipoma or vascular myxolipoma is characterized by a myxoid stromal background in addition to a proliferation of vessels of variable sizes.23,24 A lipoma containing metaplastic bone or cartilage within the tumor is referred to as an osteolipoma or chondrolipoma, respectively. Cutaneous adenolipoma refers to the presence of intratumoral sweat ducts and sweat glands may be cystically dilated.25,26

Figure 129-2

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Lipoma: mature univacuolated adipocytes show only mild variation in size. Delicate intervening capillaries are present.

Figure 129-3

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Intradermal lipoma: mature adipocytes diffusely infiltrate preexisting dermal collagen bundles. Note the sparing of the papillary dermis.

Figure 129-4

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Fibrolipoma: this variant is characterized by the presence of increased fibrous tissue within a lipoma. The expanded fibrous bands contain bland appearing and uniform spindle cells. Cytological atypia is not a feature.

Intramuscular lipoma can either present as a circumscribed intramuscular mass or show an infiltrative growth of adipocytes in between skeletal muscle fibers (Fig. 129-5).

Figure 129-5

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Intramuscular lipoma: mature adipocytes show an infiltrative growth pattern within skeletal muscle splaying apart individual muscle fibers.

Clinical Course, Prognosis, and Treatment

Lipomas are entirely benign tumors and, with the exception of intramuscular lipomas, local recurrence is rare. The infiltrative variant of intramuscular lipoma is associated with an approximately 19% chance of local recurrence, but metastasis does not occur.16

Lipomatosis

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Lipomatosis at a Glance

Lipomatosis is characterized by diffuse overgrowth of adipose tissue infiltrating through preexisting structures.
Different clinical presentations are recognized.

Epidemiology and Clinical Findings

Diffuse lipomatosis 27,28 is characterized by overgrowth of adipose tissue involving subcutaneous tissue and skeletal muscle of the trunk and extremities. Osseous involvement may also be a feature. Young children are predominantly affected, but presentation may become apparent in adulthood. Tumors can grow to a large size, causing disfigurement and loss of function of the affected limb. Due to the diffuse growth of these tumors, complete excision may not be possible and recurrences are frequent.

Benign symmetric lipomatosis (Madelung's disease, multiple symmetric lipomatosis)29–36 is characterized by multiple symmetric masses composed of nonencapsulated adipose tissue with a predilection for the subcutaneous tissue and skeletal muscle of the neck, shoulder, and proximal upper limbs (Fig. 129-6). Presentation is in adulthood with a marked male predominance of 15:1. The estimated overall incidence is 1 in 25,000, with increased frequency in the Mediterranean region. The disease is associated with increased alcohol intake in the majority of cases. Two clinical variants are currently recognized. Type 1 disease is characterized by a symmetric distribution of adipose tissue, giving rise to a “pseudoathletic” appearance, whereas type 2 disease shows a more diffuse distribution, giving rise to a picture of more generalized obesity. An associated polyneuropathy affecting sensory, motor, and autonomic function is frequently present. The disease course is slowly progressive, and treatment is difficult due to infiltration of deep-seated structures and major nerves and vessels. There is significant disease-related mortality due to compression of vital structures as well as autonomic neuropathy with sudden cardiac death. Etiologically, the disease has been speculated to be a result of hypertrophy of brown fat due to a defect in adrenergic lipolysis.

Figure 129-6

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Symmetric lipomatosis: there is diffuse and symmetric overgrowth of adipose tissue affecting predominantly the upper trunk, neck, and proximal arms.

Pelvic lipomatosis37–40 is an unusual proliferation of adipose tissue involving the pelvis and retroperitoneal space. The disorder is most common among men in the third and fourth decades, and blacks account for about two-thirds of cases. Urinary symptoms are frequent presenting signs, and the disease is associated with cystitis in 75% of cases. Obstructive uropathy and renal failure may be complications of the disease.

Adiposis dolorosa (Dercum's disease)41–48 is rare and typically affects middle-aged women, although men may occasionally also be affected. The disease is typically sporadic, and familial cases are exceptional. There is an increased incidence with obesity. Patients present with multiple painful subcutaneous lipomatous lesions frequently associated with other symptoms such as weakness, depression, confusion, lethargy, or dementia. The disease predominantly involves the arms and trunk but may be progressive to involve large parts of the body. Treatment modalities include pain relief as well as surgical control with excision or liposuction. Weight reduction can be beneficial.

Human immunodeficiency virus lipodystrophy49–53 occurs in the setting of protease inhibitor treatment or other forms of antiretroviral therapy in patients with acquired immunodeficiency syndrome (see Chapter 198). There is a predilection for cervical fat pads, the breast, and visceral fat. Other associations include hyperlipidemia, insulin resistance, type 2 diabetes, and fat wasting affecting the face and limbs.

Histologic Features

The histologic features of all forms of lipomatosis are similar and show unencapsulated adipose tissue diffusely infiltrating preexisting structures such as skeletal muscle.

Lipomatosis of Nerve (Fibrolipomatous Hamartoma of Nerve)

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Lipomatosis of Nerve (Fibrolipomatous Hamartoma of Nerve) at a Glance

Lipomatosis of nerve is a rare tumor that affects infants and children and presents as a growing mass with a predilection for the hand.
Pathology shows a proliferation of adipose and fibrous tissue within the epineurium and perineurium. The median nerve is predominantly affected.

Epidemiology

Lipomatosis of nerve is rare and affects predominantly infants and young children. Presentation at birth is not uncommon.54 It is only rarely seen in young adults.

Clinical Findings

Clinical presentation is as a slowly growing mass that may be associated with pain and paresthesia due to compression of the affected nerve. There is a strong predilection for the hand, including the wrist, palm, and fingers, and, less frequently, the foot. The median nerve and its branches followed by the ulnar nerve are most commonly affected.54 Involvement of cranial nerves and the brachial plexus has been reported but is exceptional.55,56 In a subset of patients, there may be accompanying overgrowth of bone resulting in macrodactyly.

Histologic Features

The lesions are characterized by a proliferation of adipose and fibrous tissue within the epineurium infiltrating along and in between nerve bundles. There is marked concentric fibrosis affecting both epineurium and perineurium.54 Metaplastic bone formation may rarely occur.57

Clinical Course, Prognosis, and Treatment

The clinical behavior is entirely benign, but adequate treatment is difficult because of the anatomic location and involvement of major nerves.54

Nevus Lipomatosus Superficialis

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Nevus Lipomatosus Superficialis at a Glance

Nevus lipomatosus superficialis is a rare entity that affects children and young adults.
Papules and plaques show a predilection for the buttocks, lumbar back, and posterior thighs.
Bands of mature adipose tissue infiltrate dermal collagen.

Epidemiology

Nevus lipomatosus superficialis is a rare form of connective tissue-type nevus that affects children and young adults in the first two decades of life. There is an equal gender distribution.58–62

Clinical Findings

The classic presentation is as multiple papules and nodules that may coalesce to form larger plaques. There is a predilection for the buttocks, upper posterior thighs, and lumbar back. Occasionally, involvement may be extensive, and the lesions may form confluent linear plaques along the skinfolds. This phenomenon has been reported as the “Michelin tire man” appearance.63,64 Solitary lesions occur predominantly in adults and are more likely to represent a fibroepithelial polyp containing adipose tissue or an intradermal lipoma.

Histologic Features

The histologic features show mature adipose tissue in varying amounts within the superficial dermis (eFig. 129-6.1).

eFigure 129-6.1

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Nevus lipomatosus superficialis: infiltration of adipose tissue into the dermis with penetration of dermal collagen is a characteristic finding.

Piezogenic Pedal Papules

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Clinical Findings

Piezogenic pedal papules are relatively common. Patients present bilaterally with painful, small papules and nodules in the heel area of the foot. The lesions occur during periods of standing, but disappear when pressure is relieved.65–67 Piezogenic pedal papules have also been reported on the wrist and are present in about a third of patients with Ehlers–Danlos syndrome.68,69 Etiologically, they are thought to be due to herniation of subcutaneous fat into dermis presumably due to connective tissue defects.

Histological Features

Biopsy reveals a thickened dermis as well as loss of the normal compartmentalization of fat lobules in deep dermis and superficial subcutis. In addition, there is thinning or loss of subcutaneous fibrous septa.65

Precalcaneal Congenital Fibrolipomatous Hamartoma

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Epidemiology

Precalcaneal congenital fibrolipomatous hamartoma, also known as pedal papules in the newborn, is a poorly documented condition in the literature.70,71

Clinical Findings

Presentation is usually at birth or within the first few month of life as bilateral symmetrical papules on the medial plantar aspect of the foot in a precalcaneal location. The skin-colored nodules are painless, measure approximately 1 cm in diameter, and are slowly enlarging.70,71

Histologic Features

Histologically, lobules of mature fat are surrounded and separated by hypocellular fibrous sheaths. Prominent vessels are an additional finding.70,71

Angiolipoma

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Angiolipoma at a Glance

Angiolipoma is a relatively common lesion that presents as a small nodule with a predilection for the forearm.
Young adults are affected, and lesions are frequently multiple and painful.
Histologically, this circumscribed lesion shows an admixture of mature adipose tissue and a proliferation of capillary-sized vessels.

Epidemiology

Subcutaneous angiolipomas are relatively frequent and typically occur in young adults in their teens and 20s, with a strong male predilection.72–74 They are rare in children and in the elderly.

Etiology and Pathogenesis

Angiolipomas have traditionally been classified as adipocyte tumors. However, in contrast to most lipomas they appear to have a consistently normal karyotype, and it has been suggested that they may be reactive or hamartomatous rather than neoplastic.74 The fact that angiolipomas can occasionally be almost exclusively composed of blood vessels (cellular angiolipoma) has led to the speculation that they may in fact be hemangiomas rather than lipomas.74 There is an increased familial incidence, but no inheritance pattern has been elucidated as yet.75

Clinical Findings

A wide range of sites can be affected, but there is a predilection for the forearm followed by the trunk, upper arm, and legs.72–74 Angiolipomas are often multiple and present as subcutaneous nodules characteristically smaller than 2 cm. Tenderness and pain are frequently associated symptoms.

Histologic Features

Angiolipomas are circumscribed and encapsulated. They show an admixture of mature fat and capillary-sized small branching vessels in varying proportions (Fig. 129-7 and eFig. 129-7.1). The vascular density is often increased at the periphery in a subcapsular distribution. Fibrin thrombi are typically encountered. The term cellular angiolipoma is applied to those lesions that are almost exclusively composed of vascular elements (eFig. 129-7.2).76–78

Figure 129-7

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Angiolipoma: a proliferation of capillary-sized vessels is admixed with mature adipose tissue.

eFigure 129-7.1

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Angiolipoma: the adipocyte component can predominate.

eFigure 129-7.2

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Angiolipoma: lesions with a striking predominance of the vascular component are referred to as cellular angiolipoma.

Differential Diagnosis

The appearances of angiolipoma are quite characteristic. The differential diagnosis of cellular angiolipoma includes vascular tumors such as Kaposi sarcoma, spindle cell hemangioma, and angiosarcoma.

Clinical Course, Prognosis, and Treatment

The clinical behavior of angiolipomas is entirely benign. The tumors are frequently multiple as well as painful, however, and clinical management can be a challenge.

Spindle Cell and Pleomorphic Lipoma

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Spindle Cell and Pleomorphic Lipoma at a Glance

Spindle cell lipoma and pleomorphic lipoma are currently considered to represent a morphologic continuum.
They typically occur on the posterior neck, upper back, and shoulder of middle-aged men.
Morphologically characteristic is the admixture of mature fat with bland and uniform spindle cells in a myxoid stroma containing ropey collagen bundles and mast cells. Multinucleate (floret-type) giant cells are present in pleomorphic lipoma.

Epidemiology

Spindle cell lipoma and pleomorphic lipoma are believed to constitute a morphologic continuum. This view is based on the finding that there is significant clinical, histologic, and cytogenetic overlap and the fact that features of both can be present in a single lesion.79–87 These lipomas are rare; they represent only approximately 1.5% of all fatty tumors and are 60 times less frequent than conventional lipomas.80 They show a predilection for middle-aged to elderly adults (median age, 55 years) and a strong male predominance.79–87

Etiology and Pathogenesis

Spindle cell and pleomorphic lipomas show similar cytogenetic features. In comparison to conventional lipomas, their karyotype is more complex and frequently hypodiploid with frequent partial losses and few balanced rearrangements. Monosomy and partial losses involving chromosomes 13 and 16 are the most frequent findings.2,79,88–90

Clinical Findings

Spindle cell and pleomorphic lipoma present as circumscribed, mobile masses, often with a long-standing history. They are small, measuring around 5 cm, and almost exclusively present on the posterior neck, shoulder, and upper back.79–87 Other anatomic sites in the head and neck region, including the oral cavity, can occasionally be affected.91 Rarely, these tumors are multiple and familial.92,93

Histologic Features

Both tumors are circumscribed and are typically located within the subcutis. Spindle cell lipoma is characterized histologically by the presence of mature adipocytes admixed with bland-appearing and uniform, stubby spindle cells in a collagenous and myxoid stroma containing ropey collagen fibers and conspicuous mast cells (eFigs. 129-7.3, 129-7.4 and 129-7.5). Myxoid change can be prominent (eFig. 129-7.6), and occasionally slit-like spaces resembling vascular channels may be present (pseudoangiomatous variant).94 Mitotic activity is virtually absent. The characteristic feature of pleomorphic lipoma is the presence of bizarre multinucleate giant cells, termed floret cells. These cells show eosinophilic cytoplasm and multiple crowded and overlapping hyperchromatic nuclei arranged in a circle or semicircle resembling the petals of a flower (eFig. 129-7.7). As with spindle cell lipoma, there is a variably myxoid and collagenous matrix admixed with mature adipose tissue and containing spindled to rounded cells with hyperchromatic nuclei (eFig. 129-7.8). An inflammatory infiltrate may be present.

eFigure 129-7.3

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Spindle cell lipoma: mature adipocytes are admixed with short, loosely arranged spindle cells in a myxoid stroma. Mast cells are conspicuous.

eFigure 129-7.4

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Spindle cell lipoma: spindle cells predominate in this tumor. They are arranged in short fascicles.

eFigure 129-7.5

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Spindle cell lipoma: this field highlights the presence of spindle cells, ropey collagen fibers, as well as mast cells.

eFigure 129-7.6

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Myxoid spindle cell lipoma: extensive myxoid stromal change is seen in this tumor.

eFigure 129-7.7

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Pleomorphic lipoma: the characteristic floret-type giant cells contain overlapping hyperchromatic nuclei in a circular or semicircular arrangement.

eFigure 129-7.8

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Pleomorphic lipoma: floret-type giant cells are placed in a background of mature adipose tissue and myxoid stroma containing ropey collagen fibers.

Occasionally, spindle cell as well as pleomorphic lipomas arise within the dermis. These dermal tumors have features similar to those described earlier but are less circumscribed and show an infiltrative growth between dermal collagen bundles (eFigs. 129-7.9 and 129-7.10).95 In contrast to subcutaneous lesions, intradermal examples show a wide anatomic distribution.

eFigure 129-7.9

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Spindle cell lipoma: intradermal tumors are frequently less circumscribed and diffusely infiltrate preexisting dermal collagen bundles.

eFigure 129-7.10

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Spindle cell lipoma: this intradermal tumor shows an infiltrative growth through dermal collagen.

By immunohistochemical analysis, the spindle cells express CD34 and rarely S100 protein.

Differential Diagnosis

The differential diagnosis for spindle cell and pleomorphic lipomas includes the following:

Atypical lipomatous tumor
Solitary fibrous tumor
Cellular angiofibroma

Clinical Course, Prognosis, and Treatment

Spindle cell and pleomorphic lipomas are entirely benign adipocyte neoplasms and local recurrences are rare.

Chondroid Lipoma

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Chondroid lipoma is a rare and benign tumor that affects adults and shows a female predominance.
The anatomic distribution is wide, but there is a predilection for the proximal extremities and limb girdle.
The unique histologic features include the presence of mature adipose tissue, lipoblasts, and a chondroid matrix.

Epidemiology

Chondroid lipoma is a relatively recently recognized and exceedingly rare benign lipomatous tumor.96 It shows a predilection for adults and a wide age distribution with a median of 36 years. There appears to be a significant female predominance (estimated at 1:4).96

Etiology and Pathogenesis

Ultrastructural analysis confirms adipocyte rather than cartilaginous differentiation.97 Cytogenetically, a balanced translocation involving chromosomes 11 and 16, t(11;16)(q13;p12–13), has been shown in two separate tumors.98,99 The 11q13 locus has also been found to be involved in lipoma as well as hibernoma. However, rearrangements in these tumors are not associated with the 16p12–13 locus.

Clinical Findings

Chondroid lipoma is a relatively small tumor measuring approximately 5 cm. Larger examples of over 10 cm have also been reported. It presents as a painless circumscribed mass of variable duration and often comes to clinical attention because of a history of recent growth. The proximal extremities and limb girdles are the most frequently affected anatomic sites,96 but the trunk as well as the head and neck region, including intraoral sites, may also be affected.97,100–102 Tumors are typically deep-seated, involving deep subcutaneous tissue, fascia, and skeletal muscle.96 Imaging studies are rather nonspecific and show a multilobular and circumscribed mass containing fatty elements.102–104

Histologic Features

The characteristic feature of chondroid lipoma is the admixture of a mature adipocyte component and a chondroid matrix containing lipoblasts.96 This well-circumscribed tumor is frequently encapsulated and multilobulated. It is composed of univacuolated and multivacuolated cells, occasionally with eosinophilic cytoplasm, showing cytologic features reminiscent of those of lipoblasts or chondroblasts (eFig. 129-7.11).96 These cells contain small lipid droplets as well as periodic acid-Schiff-positive glycogen.96 They are arranged in cords, nests, and strands as well as more solid areas set in a background of a chondroid matrix typically containing chondroitin sulfates (eFig. 129-7.12).105 Intricately admixed are variable amounts of mature adipose tissue. Tumors can be highly vascularized and show areas of hemorrhage, fibrosis, and calcifications.

eFigure 129-7.11

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Chondroid lipoma: uni- and multivacuolated cells reminiscent of lipoblasts or chondroblasts are present adjacent to mature adipocytes. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

eFigure 129-7.12

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Chondroid lipoma: the cells are arranged in cords and nests in a myxohyaline, chondroid matrix. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

By immunohistochemical analysis, lipoblasts are positive for S100 protein. They are negative for epithelial membrane antigen and smooth muscle actin.105

Ultrastructural studies demonstrate intracytoplasmic lipid and glycogen as well as pinocytotic vesicles. These findings support adipocyte rather than cartilaginous differentiation.105

Differential Diagnosis

Differential diagnosis for chondroid lipoma includes the following:

Myxoid liposarcoma
Extraskeletal myxoid chondrosarcoma

Clinical Course, Prognosis, and Treatment

Chondroid lipoma is a benign lipomatous neoplasm, and neither recurrences nor metastases have been demonstrated so far. Excision is the treatment of choice.

Myolipoma of Soft Tissue

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Epidemiology

Myolipoma of soft tissue is also known as extrauterine lipoleiomyoma and is characterized by its admixture of mature adipocyte and smooth muscular components. It is an exceedingly rare tumor occurring in adulthood, with a female predominance of 2:1.106

Clinical Findings

Myolipomas can grow to a significant size and average 15 cm. They occur in deep soft tissue of the retroperitoneum, abdominal cavity, and inguinal area but can also arise within subcutaneous tissue of the trunk and extremities. Involvement of deep structures such as skeletal muscle and fascia is frequent. Myolipomas present as palpable masses but may be incidental findings when located at visceral sites.

Histologic Features

Myolipoma of soft tissue is a circumscribed and at least partially encapsulated neoplasm composed of mature adipose tissue with evenly distributed traversing fascicles of smooth muscle. It is important to note that there is no cytologic atypia or mitotic activity of either component, and thick-walled vessels as seen in angiomyolipoma are absent.

By immunohistochemical analysis, the smooth muscle component stains strongly and diffusely positive for smooth muscle actin and desmin.

Differential Diagnosis

The differential diagnosis for myolipoma of soft tissue includes the following:

Liposarcoma
Angiomyolipoma

Clinical Course, Prognosis, and Treatment

Myolipoma of soft tissue is a benign neoplasm, and recurrences have not been reported. Complete excision is curative.

Hibernoma

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Hibernoma at a Glance

Hibernoma is a benign neoplasm that resembles brown fat and typically presents in adulthood.
A wide range of anatomic locations may be affected.

Epidemiology

Hibernoma is a well recognized but rare benign adipocyte tumor that shows a wide age distribution. Young adults (mean age, 38 years) are predominantly affected, but presentation in the pediatric population as well as in the elderly is possible. Males appear to be affected only slightly more frequently than females.107

Etiology and Pathogenesis

The etiology of this rare tumor is unclear. Karyotypes can be slightly more complex than those observed in other benign lipomatous tumors, but structural rearrangements involving chromosome band 11q13 appear to be reproducible.108–111

Clinical Findings

Hibernoma is a painless, slowly enlarging tumor affecting a wide range of anatomic sites. There appears to be a predilection for areas in which brown fat can be found physiologically, and presentation on the trunk, especially the scapular area, the shoulder, and the head and neck is common. However, curiously the thigh appears to be the single most frequently affected site.107 Hibernomas are typically located in subcutaneous tissue or skeletal muscle but may occasionally affect the abdominal cavity, retroperitoneum, or intrathoracic location.112

Presentation as multiple separate lesions is exceptional.113 The average size is around 10 cm, but larger tumors up to 24 cm are not unusual.107 Imaging studies reveal a well-demarcated lobulated and septated mass showing contrast enhancement and tissue attenuation intermediate between those of fat and skeletal muscle.114–117

Histologic Features

Hibernoma is a well-demarcated and lobulated neoplasm. The hallmark feature is its morphologic resemblance to brown fat. The tumors are composed of variable numbers of multivacuolated adipocytes with small, centrally placed nuclei and pale to eosinophilic and granular cytoplasm (eFig. 129-7.13). On the basis of the appearance of these brown fat cells, the quality of intervening stroma, and the presence of a spindle cell component, six histologic variants are recognized.107

eFigure 129-7.13

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Hibernoma: the characteristic feature is the presence of multivacuolated adipocytes with centrally placed nuclei and clear to eosinophilic granular cytoplasm.

The typical variant is the most frequently encountered form and is characterized by large numbers of brown fat cells admixed with mature white fat (Fig. 129-8). Those tumors composed almost exclusively of brown fat cells with palely staining cytoplasm are further subclassified as the pale cell subtype. Tumors are labeled eosinophilic subtype when at least 50% of brown fat cells contain a deeply eosinophilic and granular cytoplasm. The mixed subtype is intermediate between the two and shows a roughly equal distribution of eosinophilic and pale-staining brown fat cells. Myxoid, lipoma-like, and spindle cell variants exist.

Figure 129-8

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Hibernoma: brown fat is admixed with mature adipose tissue.

Hibernomas showing acellular myxoid areas of the intervening stroma are recognized as the myxoid variant. This variant affects predominantly men and presents in the head and neck and shoulder area.

The lipoma-like variant shows large areas of white fat differentiation with only scattered hibernoma cells lying in between.

The least frequent is the spindle cell variant, showing overlapping features of spindle cell lipoma and hibernoma. Areas of brown fat are admixed with the short and bland spindle cells typical of spindle cell lipoma, and ropey collagen bundles, myxoid stroma, mast cells, and mature white fat are also present. As with spindle cell lipoma, this variant presents in the posterior neck and scalp.

By immunohistochemical analysis, hibernomas stain positively for S100. CD34 expression is seen in the spindle cells of the spindle cell variant of hibernoma.107

Differential Diagnosis

The differential diagnosis of hibernoma includes the following:

Granular cell tumor
Spindle cell lipoma
Atypical lipomatous tumor/well-differentiated liposarcoma

Clinical Course, Prognosis, and Treatment

The behavior of hibernoma is entirely benign without recurrence after local excision.

Lipoblastoma/Lipoblastomatosis

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Lipoblastoma/Lipoblastomatosis at a Glance

Morphologically, the benign adipocyte neoplasm lipoblastoma resembles fetal adipose tissue. It is most frequently found in individuals younger than 5 years of age.
Lipoblastoma has a multilobular and circumscribed appearance, whereas lipoblastomatosis shows an infiltrative growth.

Epidemiology

Lipoblastoma/lipoblastomatosis is an uncommon neoplasm affecting infants and young children. Its incidence decreases significantly in those older than 5 years of age, and presentation in adolescents is rare.118–125 Infrequently, tumors may be congenital.126–128 There is a male predominance, with a male–female ratio of approximately 2:1.118–124

Etiology and Pathogenesis

Cytogenetic analysis has identified a recurrent translocation involving chromosome band 8q11–13,129–131 leading to rearrangements of the transcription factor Plag1 (pleomorphic adenoma gene).132–135

Clinical Findings

Most tumors present as painless, slowly growing, solitary soft-tissue masses. Lipoblastomas are well circumscribed and located in subcutaneous tissue. In contrast, tumors with an infiltrative growth often extend into deeper structures such as skeletal muscle and are termed lipoblastomatosis.123 The extremities, trunk, and head and neck are predominantly affected sites.124 Visceral involvement of retroperitoneum, mediastinum, peritoneal cavity, or solid organs is rarely seen.118–123 Tumors are relatively small, measuring around 5 cm. However, larger tumors of more than 20 cm have been reported. In certain locations, tumors can become symptomatic due to compression of adjacent structures and organs.

Histologic Features

Lipoblastomas are well-circumscribed, lobulated tumors with fibrous septa (eFig. 129-8.1) composed of an admixture of mature and immature adipocytes in varying proportions (eFig. 129-8.2). Lipoblasts are present in different stages of development ranging from univacuolated forms with eccentrically placed and compressed nuclei to bivacuolated and multivacuolated forms (eFigs. 129-8.3 and 129-8.4). These lipoblasts show indented and scalloped nuclei, but cytologic atypia is not a feature (eFig. 129-8.3). Lipoblasts can be quite rare, and some tumors are predominantly composed of mature adipocytes. Varying amounts of a myxoid matrix containing uniform stellate spindle cells and a plexiform vascular pattern of capillary-sized vessels reminiscent of myxoid liposarcoma may be present (eFig. 129-8.4). Fibrous septa give rise to the tumor's lobulated appearance (eFig. 129-8.4). These septa may be quite cellular in areas. Lobulation is less pronounced in lipoblastomatosis, which has a more infiltrative growth pattern, and often preexisting structures such as skeletal muscle fibers are entrapped.

eFigure 129-8.1

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Lipoblastoma/lipoblatomatosis: lipoblastoma is a circumscribed tumor showing prominent multilobulation with dividing fibrous septa. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

eFigure 129-8.2

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Lipoblastoma/lipoblastomatosis: mature and immature adipocytes are admixed in varying proportions. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

eFigure 129-8.3

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Lipoblastoma/lipoblastomatosis: lipoblasts in different stages of development are present. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

eFigure 129-8.4

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Lipoblastoma/lipoblastomatosis: areas with a prominent myxoid stroma containing delicate branching capillaries, lipoblasts, and primitive stellate cells closely resemble myxoid liposarcoma. (Used with permission from Dr. S. Banerjee, Christie Hospital, Manchester, UK.)

By immunohistochemistry, expression for S100 and CD34 is seen.124

Ultrastructurally, these tumors resemble maturing adipose tissue rather than brown fat.119,136

Differential Diagnosis

The differential diagnosis of lipoblastoma/lipoblastomatosis includes the following:

Myxoid liposarcoma
Atypical lipomatous tumor
Hibernoma
Lipofibromatosis

Clinical Course, Prognosis, and Treatment

Lipoblastoma/lipoblastomatosis is a benign tumor with a tendency to recurrence if inadequately excised. Complete surgical excision is curative and is the treatment of choice.

Hemosiderotic Fibrohistiocytic Lipomatous Lesion/Tumor

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Epidemiology

The exceedingly rare hemosiderotic fibrohistiocytic lipomatous lesion or tumor was first described by Marshall-Taylor and Fanburg-Smith 137 in 2000. Only 25 cases have been reported in the literature so far.137–139 Although the age range of occurrence is wide, the lesion typically presents in adulthood (median age, 50 years) and affects women more frequently than men.137,138

Etiology and Pathogenesis

The finding of antecedent trauma in a significant number of cases in the original description of hemosiderotic fibrohistiocytic lipomatous lesion initially suggested that this may be a reactive condition.137 There has been further speculation about the role of venous stasis in the pathogenesis of the lesion.139 However, a subsequent study did not detect a history of trauma or other predisposing conditions in most patients.138 At the moment, it is unclear whether this is a truly neoplastic or reactive condition. The proposal that hemosiderotic fibrohistiocytic lipomatous lesion is related to or even represents a precursor of pleomorphic hyalinizing angiectatic tumor is so far largely speculative and unsubstantiated.140

Clinical Findings

The presenting sign is a slowly growing, relatively circumscribed subcutaneous mass ranging from 1 to 17 cm with a median size of 5–6 cm.137,138 There is a strong predilection for the distal extremities, especially the dorsal aspect of the ankle/foot as well as less frequently the hand.137,138 Involvement of other anatomic sites is unusual. A history of antecedent trauma is observed in a subset of patients.137,138

Histologic Features

Hemosiderotic fibrohistiocytic lipomatous tumors show a slightly infiltrating architecture microscopically. They are composed of three main constituents demonstrating an adipocyte as well as a spindle cell component and hemosiderin deposition.137,138 The proportions of the individual components may vary, but the adipocyte element usually predominates. The fatty element appears mature and lobulated and is divided by variably cellular fibrous septa. No adipocyte hyperchromasia or atypia is observed. The variably cellular spindle cell component is arranged in fascicles percolating through the fatty elements to create a “honeycomb” appearance.137,138 Spindle cells are short and uniform, occasionally showing mild atypia. Mitotic activity is not a feature. Rarely, the formation of small nodular areas may be observed in the spindle cell areas, and occasionally there may be myxoid features. Hemosiderin deposition can be highlighted with Perls’ iron stain and is present within macrophages and spindle cells. The presence of osteoclast-like giant cells is a frequent finding, and calcifications may be present.

By immunohistochemical analysis, expression of CD34 is seen in spindle cells.

Differential Diagnosis

The differential diagnosis for hemosiderotic fibrohistiocytic lipomatous tumors includes the following:

Atypical lipomatous tumor
Plexiform fibrohistiocytic tumor

Clinical Course, Prognosis, and Treatment

There is an approximately 30% risk of nondestructive local recurrence after incomplete excision. So far, no metastasis or adverse outcome has been reported.137,138

Lipofibromatosis

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Epidemiology

Lipofibromatosis is an uncommon pediatric neoplasm that predominantly affects infants at a median age of 1 year.141–144 It can be congenital, but children and adolescents may also be affected. There appears to be a significant male predominance.

Clinical Findings

The clinical presentation of an ill-defined, slowly growing, painless mass ranging from 1 to 7 cm is typical.144 Tumors are located most frequently on the hands and feet, followed by the limbs and trunk. Appearance on the head and neck is rare.

Histologic Features

Tumors are composed of mature adipose tissue in addition to a bland cellular spindle cell component arranged in short fascicles. The spindle cell element follows the septa of the adipose tissue without architectural distortion of its lobulation (eFigs. 129-8.5 and 129-8.6). Cytologic atypia is minimal, and mitotic figures are rare. An additional finding is the presence of small univacuolated cells at the interface of the spindle cell and adipocyte components (eFig. 129-8.6).

eFigure 129-8.5

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Lipofibromatosis: this tumor shows expanded fibrous septa with preservation of the lobular architecture.

eFigure 129-8.6

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Lipofibromatosis: the fibrous septa contain uniform spindle cells. Also note the presence of small univacuolated adipocytes adjacent to the fibrous strands.

Immunohistochemical analysis may show the spindle cells to be focally positive for CD34, S100 protein, smooth muscle actin, and epithelial membrane antigen, but results are negative for desmin.144

Differential Diagnosis

The differential diagnosis for lipofibromatosis includes the following:

Fibromatosis
Fibrous hamartoma of infancy

Clinical Course, Prognosis, and Treatment

There is a significant rate of local nondestructive recurrence especially in congenital lesions and after incomplete excision. Further risk factors may include male gender and increased mitotic activity in the spindle cell areas.144 No metastases have been reported.

Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma

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Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma at a Glance

Atypical lipomatous tumor/well-differentiated liposarcoma is a tumor of adulthood that presents as an enlarging mass with a predilection for the extremities, retroperitoneum, and paratesticular tissue.
Best prognostic predictor is anatomic location:
- Recurrence, risk of dedifferentiation, and mortality negligible if excised.
- Retroperitoneum and paratesticular region, where complete excision is difficult, characterized by high long-term mortality.
- When excision is curative, tumors are called atypical lipomatous tumors; when clear margins cannot be obtained should be regarded as well-differentiated liposarcoma.

Epidemiology

Atypical lipomatous tumor/well-differentiated liposarcoma is a neoplasm of adulthood with a peak incidence in the sixth decade.145–153 It represents the largest subgroup of liposarcomas. There is no gender predilection.

Etiology and Pathogenesis

Cytogenetically, atypical lipomatous tumors are characterized by supernumerary circular “ring” chromosomes as well as giant long marker chromosomes derived from the 12q13–15 region and resulting in consistent amplification of the MDM2 gene along with adjacent genes such as CDK4.154–160

Clinical Findings

Tumors typically present in deep soft tissue. The subcutaneous tissue may occasionally also be involved. The predominantly affected site is the musculature of extremities with a predilection for the thigh, followed by the retroperitoneum, groin, and paratesticular area as well as the mediastinum.145–153 A wide range of other anatomic sites including the larynx, orbit, oral cavity, and vulva may be affected.161–164 An enlarging painless mass is the typical presenting sign, and especially in a retroperitoneal location, tumors can grow to a very large size before becoming symptomatic.

Histologic Features

Atypical lipomatous tumors are large, multilobulated, and most often circumscribed. The most frequently observed adipocytic (lipoma-like) morphologic variant closely resembles a lipoma. It is composed of relatively mature-appearing adipocytes with marked variation in cell size (Fig. 129-9). Additional findings include focal adipocyte atypia (eFig. 129-9.1) and the presence of hyperchromatic and often multinucleate bizarre stromal cells in cellular fibrous septa (eFigs. 129-9.2 and 129-9.3). Floret-type giant cells may also be a feature (eFig. 129-9.4). Lipoblasts may be monovacuolated or multivacuolated and vary in number (eFig. 129-9.5). They may be entirely absent and are not a prerequisite for the diagnosis. Sclerosing, inflammatory, and spindle cell variants exist.

Figure 129-9

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Atypical lipomatous tumor/well-differentiated liposarcoma: note the marked variation in adipocyte size.

eFigure 129-9.1

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Atypical lipomatous tumor/well-differentiated liposarcoma: adipocyte atypia with nuclear enlargement and hyperchromasia is a focal finding.

eFigure 129-9.2

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Atypical lipomatous tumor/well-differentiated liposarcoma: the typical fibrous strands with increased cellularity are present in this field.

eFigure 129-9.3

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Atypical lipomatous tumor/well-differentiated liposarcoma: the cellular fibrous strands contain bizarre and often multinucleate hyperchromatic cells.

eFigure 129-9.4

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Atypical lipomatous tumor/well-differentiated liposarcoma: floret-type giant cells may also be a feature.

eFigure 129-9.5

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Atypical lipomatous tumor/well-differentiated liposarcoma: multivacuolated lipoblasts showing hyperchromatic and indented nuclei are a focal finding.

The sclerosing variant occurs most commonly in a retroperitoneal or paratesticular location and is the second most frequently encountered histologic pattern (eFig. 129-9.6). It is characterized by a paucicellular fibrillary collagenous matrix containing scattered hyperchromatic and bizarre-appearing stromal cells as well as rare multivacuolated lipoblasts (eFig. 129-9.7). The adipocytic component may be inconspicuous, and often extensive sampling is required for the diagnosis.

eFigure 129-9.6

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Atypical lipomatous tumor/well-differentiated liposarcoma: the presence of a paucicellular stroma with admixed adipocytes characterizes the sclerosing variant.

eFigure 129-9.7

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Atypical lipomatous tumor/well-differentiated liposarcoma: bizarre appearing stromal cells in a fibrillary matrix are highlighted in this field of the sclerosing variant.

Rarely, there is a marked chronic inflammatory infiltrate potentially obscuring the underlying adipocytic component. Such tumors have been designated as the inflammatory subtype. This variant occurs in the same distribution as the adipocytic subtype and is characterized by a heavy lymphoplasmacytic infiltrate arranged in a multinodular pattern and separated by variably cellular stroma. The lipogenic areas show features of the adipocytic variant. However, they comprise only a small fraction of the tumor.165

The spindle cell variant has only recently been recognized. It is rare and shows a predilection for the subcutaneous tissue of the shoulder girdle and upper limb. The characteristic finding is the presence of a proliferation of bland-appearing spindle cells arranged in fascicles and whorls and set in a myxoid matrix (eFig. 129-9.8). This is accompanied by an atypical adipocytic component showing classic lipoblasts.166

eFigure 129-9.8

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Atypical lipomatous tumor/well-differentiated liposarcoma: bland appearing spindle cells are arranged in fascicles in this example of the spindle cell variant. A background myxoid matrix is characteristic finding.

Immunohistochemistry for MDM2 and CDK4 aided by fluorescence in situ hybridization to detect MDM2-CDK4 amplification is a useful ancillary diagnostic tool to distinguish well-differentiated as well as dedifferentiated liposarcoma from benign adipocyte tumors as well as other nonlipogenic tumors.160,167

Differential Diagnosis

The differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma includes the following:

Lipoma
Spindle cell/pleomorphic lipoma
Dedifferentiated liposarcoma
Angiomyolipoma
Massive localized lymphedema

Clinical Course, Prognosis, and Treatment

The clinical behavior and prognosis are largely dependent on the anatomic site.168 Surgery is curative at anatomic locations where complete surgical excision with clear margins can be achieved (e.g., somatic soft tissue such as the limbs). The estimated rate of progressing to dedifferentiated liposarcoma is less than 2% with a mortality rate of virtually zero at these anatomic locations. In contrast, tumors arising at deep locations such as the retroperitoneum, mediastinum, or spermatic cord, where complete surgical clearance is not possible, are characterized by repeated local recurrence and ultimately may result in death from uncontrolled local disease or dedifferentiation with metastasis. The overall risk of development of dedifferentiated liposarcoma is estimated to be higher than 20% with an overall mortality rate of around 80% for tumors occurring in the retroperitoneum. The disease has a protracted course, and the median survival time ranges from 6 to 11 years.149,152,169 The primary approach to treatment is surgical excision. Adjunct chemotherapy and radiation treatment are reserved for advanced disease.

Dedifferentiated Liposarcoma

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Dedifferentiated Liposarcoma at a Glance

Tumors typically present as large masses in the retroperitoneum of adults.
The disease course is protracted, with a high rate of local recurrence and a significant risk for metastasis and associated mortality.
The morphologic characteristic is the presence of nonlipogenic areas adjacent to well-differentiated liposarcoma.

Epidemiology

The epidemiologic features of dedifferentiated liposarcoma are similar to those of well-differentiated liposarcoma, and it typically affects adults in the sixth decade.170–172 There is no gender predilection. De novo presentation is most commonly seen, occurring in approximately 90% of cases. Only around 10% of cases represent dedifferentiation of a previously well-differentiated liposarcoma.170,171

Etiology and Pathogenesis

The karyotypic findings are similar to those seen in well-differentiated liposarcoma and involve supernumerary ring and giant marker chromosomes.173

Clinical Findings

Tumors present as large painless masses with a predilection for the retroperitoneum followed by the limbs and paratesticular area and spermatic cord.170–172 Other sites, including the head, neck, and trunk, are rarely affected. Presentation in the subcutis is unusual.174

Histologic Features

The tumors are multilobulated and consist of yellow, fatty areas as well as discrete more solid areas representing dedifferentiation. The characteristic histologic finding is the presence of both atypical lipomatous tumor/well-differentiated liposarcoma and nonlipogenic sarcoma. The proportions may vary, and careful gross examination and adequate sampling may be necessary to identify the lipogenic areas. There is usually a very sharp demarcation between lipogenic and nonlipogenic areas (eFig. 129-9.9), but a more gradual transition or comingling may also be seen. The nonlipogenic component is most frequently morphologically high grade, showing a pleomorphic sarcoma-like (pleomorphic and storiform malignant fibrous histiocytoma-like) (eFigs. 129-9.10 and 129-9.11) or a myxofibrosarcoma-like appearance.170–172,175 Occasionally, the area of dedifferentiation may appear morphologically low grade and is then composed of bland-appearing spindle cells with a fascicular arrangement. Cellularity is significantly lower than in high-grade areas, cytologic atypia is mild, and mitotic figures are rare. A storiform growth reminiscent of dermatofibrosarcoma protuberans may be present.170,171

eFigure 129-9.9

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Dedifferentiated liposarcoma: frequently there is a sharp demarcation between dedifferentiated (right side) and well differentiated liposarcoma (left side).

eFigure 129-9.10

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Dedifferentiated liposarcoma: tumor cells are arranged in short fascicles and give rise to a storiform appearance.

eFigure 129-9.11

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Dedifferentiated liposarcoma: there is an admixture of spindle cells and large pleomorphic cells.

Heterologous elements are present in approximately 10% of cases and include predominantly osteosarcomatous or chondrosarcomatous as well as myogenic differentiation. A peculiar finding is the presence of meningothelial-like whorls often associated with metaplastic bone formation.176,177

Differential Diagnosis

The differential diagnosis of dedifferentiated liposarcoma includes the following:

Spindle cell liposarcoma
Pleomorphic liposarcoma
Other pleomorphic sarcomas

Clinical Course, Prognosis, and Treatment

Dedifferentiated liposarcoma is characterized by a protracted course with a high risk of local recurrence. Retroperitoneal tumors almost invariably recur if followed over a long period of time. The overall risk of distant spread is estimated at around 20%, with a disease-related mortality rate of approximately 30%.171 Although these rates are likely to be higher with long-term follow-up, the prognosis appears to be more favorable than that for other high-grade pleomorphic sarcomas, which are associated with a high mortality rate and shorter time to death. Anatomic location is the most important prognostic factor, and retroperitoneal tumors are associated with a poor prognosis. In contrast, neither the extent of dedifferentiation nor the morphologic features appear to be prognostically predictive. The mainstay of treatment is surgical removal with adjuvant chemotherapy and radiation in advanced disease.

Myxoid/Round Cell Liposarcoma

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Myxoid/Round Cell Liposarcoma at a Glance

Presentation is as a large mass involving the extremities and in particular the thigh of middle-aged adults.
There is a significant rate of local recurrence as well as metastasis.
Tumors are lobulated and circumscribed and are composed of a myxoid matrix containing primitive mesenchymal cells and lipoblasts in varying stages of differentiation. A prominent vascular pattern is a characteristic feature.
Round cell liposarcoma is currently regarded to represent the high-grade end of the morphologic spectrum.

Epidemiology

Myxoid liposarcomas represent approximately 10% of all soft-tissue sarcomas. They comprise more than one-third of all liposarcomas and are the second most frequent variant of liposarcoma.178 The tumor presents in young to middle-aged adults with a peak in the fourth to fifth decade and a slight male predominance.178–180

Etiology and Pathogenesis

Cytogenetically, myxoid liposarcoma is characterized by the translocation t(12;16)(q13;p11), present in approximately 95% of cases. The translocation involves the CHOP (DDIT3) gene on chromosome band 12q13 and the TLS (also known as FUS) gene located on 16p11 resulting in the generation of the TLS–CHOP hybrid gene.170,180–184 Rarely, the translocation t(12;22)(q13;q12), resulting in the EWS–CHOP hybrid gene, is observed.185–187 CHOP belongs to the family of leucine zipper transcription factors and is implicated in adipocyte differentiation and growth arrest, whereas TLS, similar to EWS, is a potent activator of transcription. In turn, the TLS–CHOP hybrid gene is speculated to interfere with normal adipocyte development and proliferation by aberrant transcriptional activation.

Clinical Findings

Presentation as a large, painless mass with a predilection for the extremities is characteristic. Tumors are located in deep soft tissue and involve the thigh in over two-thirds of cases.178–180 Presentation in subcutis or retroperitoneum is rare. Not infrequently, patients are found to have multifocal disease at initial presentation, which is generally regarded to represent metastases.185

Histologic Features

Tumors are large, well circumscribed, and multinodular with a gelatinous cut surface on gross examination. The appearance becomes fleshier in areas with increased cellularity, but large areas of tumor necrosis are not typically seen.

Microscopically, myxoid liposarcoma is a lobulated tumor composed of a mixture of bland-appearing oval mesenchymal cells without evidence of adipocyte differentiation and small univacuolated or bivacuolated lipoblasts, often with a signet-ring cell appearance (eFig. 129-9.12 and Fig. 129-10). The cellularity is low but increased toward the periphery of the tumor lobules (eFig. 129-9.12). The cells are placed in a myxoid matrix showing a characteristic pattern of delicate, branching capillary-sized vessels often referred to as chicken wire or crow's feet (eFig. 129-10.1). In the central areas, the extracellular mucin may become confluent to form mucin pools, giving rise to a pulmonary edema-like appearance (eFig. 129-10.2). In the well-differentiated areas, the tumors lack significant cytologic atypia, mitotic activity, or tumor necrosis. Poorly differentiated, high-grade tumors are characterized by increased cellularity with the formation of solid sheets of small-to-medium-sized round cells showing scant acidophilic cytoplasm (eFig. 129-10.3). Mitotic figures are more easily identified, but nuclear pleomorphism is not a feature.

eFigure 129-9.12

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Myxoid liposarcoma: these tumors are lobulated containing a myxoid matrix. Increased cellularity is frequently seen in the periphery of the tumor lobule.

Figure 129-10

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Myxoid liposarcoma: the presence of uni- to bivacuolated lipoblast and bland appearing oval shaped cells within a myxoid matrix is a characteristic feature.

eFigure 129-10.1

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Myxoid liposarcoma: delicate branching capillary sized resemble a chicken wire or crow's feet.

eFigure 129-10.2

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Myxoid liposarcoma: confluent areas of mucin pools give rise to a “pulmonary edema-like” appearance.

eFigure 129-10.3

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Myxoid liposarcoma/round cell liposarcoma: this high-grade tumor is characterized by increased cellularity. Pleomorphism is not a feature.

These cases have traditionally been classified as round cell liposarcoma and are associated with an adverse prognosis. However, the presence of classical myxoid and round cell areas within the same tumor with gradual transition from one to the other and the finding of identical cytogenetic alterations provide strong evidence that round cell liposarcoma represents the poorly differentiated, high-grade end of the spectrum of myxoid liposarcoma. Spindle cell differentiation may occasionally be seen in poorly differentiated tumors.

Differential Diagnosis

The differential diagnosis of myxoid liposarcoma includes the following:

Lipoblastoma
Myxofibrosarcoma
Low-grade fibromyxoid sarcoma
Chondroid lipoma
Myxoid melanoma

Clinical Course, Prognosis, and Treatment

The clinical course of myxoid liposarcoma is characterized by local recurrence with a rate of distant metastasis of 30%–40%.178–180 There is an unusually high incidence of soft-tissue and bone metastases in addition to metastases to the lung. Patients with multifocal disease at presentation have a poor prognosis, and adverse histologic features include the presence of round cell differentiation in more than 5% of the tumor, tumor necrosis, and p53 overexpression.179,180,188,189

Pleomorphic Liposarcoma

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Pleomorphic Liposarcoma at a Glance

Pleomorphic liposarcoma is an aggressive sarcoma that shows a predilection for the extremities of adults and is associated with a high rate of metastasis and mortality.
Histologic examination shows a pleomorphic high-grade sarcoma containing variable numbers of lipoblasts.

Epidemiology

Pleomorphic liposarcoma is a rare tumor representing only approximately 5% of all liposarcomas and up to 20% of pleomorphic sarcomas.190,191 It shows a slight male predominance and presents in adulthood (median age, 50–60 years). However, the age range is wide.192–194

Clinical Findings

Tumors present as enlarging firm masses, frequently with a short history. They are typically large, deep-seated, and subfascial sarcomas measuring 8–10 cm in median. Presentation in subcutaneous tissue is less frequent, and dermal location is unusual.192–195 The extremities are the most frequently affected sites, and there is a predilection for the lower limbs. The trunk, retroperitoneum, abdomen, mediastinum, head and neck, and pelvis may also be involved.

Histologic Features

Tumors can be well circumscribed but unencapsulated. However, more frequently they have infiltrative margins. In its classic appearance pleomorphic liposarcoma shows features of a high-grade pleomorphic (malignant fibrous histiocytoma-like) sarcoma containing pleomorphic spindle cells and multinucleate giant cells (eFig. 129-10.4). Admixed are lipoblasts in varying numbers. They may be scarce in areas or arranged in larger sheets (eFig. 129-10.5). Mitotic figures are frequent, including atypical forms, and areas of necrosis are often present. An additional finding is the presence of intracellular as well as extracellular eosinophilic hyaline droplets.

eFigure 129-10.4

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Pleomorphic liposarcoma: this tumor shows the classic appearances of a pleomorphic sarcoma.

eFigure 129-10.5

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Pleomorphic liposarcoma: admixed lipoblasts vary in number.

Two morphologic variants, a high-grade myxofibrosarcoma-like and an epithelioid variant, are recognized. One variant is characterized by the presence of areas resembling intermediate- to high-grade myxofibrosarcoma and containing large lipoblasts in varying amounts (eFig. 129-10.6). Another relatively recently recognized pattern is the epithelioid variant characterized by the presence of large, cohesive, and densely packed epithelioid cells containing abundant cytoplasm.196,197 The features are reminiscent of those of carcinomas, but scattered large lipoblasts can be identified.

eFigure 129-10.6

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Pleomorphic liposarcoma: lipoblasts can be identified in areas that are morphologically reminiscent of myxofibrosarcoma.

Immunohistochemically, tumor cells can focally express smooth muscle actin (approximately 50% of cases) and rarely desmin and cytokeratins (especially in the epithelioid variant). S100 highlights lipoblasts in about one-third of cases.

Cytogenetic analysis reveals complex karyotypes and high chromosome counts.198

Differential Diagnosis

The differential diagnosis of pleomorphic liposarcoma includes the following:

Dedifferentiated liposarcoma
Leiomyosarcoma
Pleomorphic rhabdomyosarcoma
Myxofibrosarcoma
Melanoma
Carcinoma

Clinical Course, Prognosis, and Treatment

Pleomorphic liposarcoma is characterized by a relatively aggressive clinical course with a more than 30% rate of local recurrence, a 30%–50% metastatic rate, and an estimated overall 5-year survival rate of 50%–60%. The lung is the preferred metastatic site. The treatment is surgical with adjuvant radiation and chemotherapy for advanced disease.

References

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1. Nielsen GP et al: Lipoma: World Health Organization Classification of Tumours. In: Pathology and Genetics of Tumours of Soft Tissue and Bone, edited by CDM Fletcher, KK Unni, F Mertens. Lyon, IARC Press, 2002

2. Sandberg AA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: Lipoma. Cancer Genet Cytogenet 150:93-115, 2004

3. Willen H et al: Comparison of chromosomal patterns with clinical features in 165 lipomas: A report of the CHAMP study group. Cancer Genet Cytogenet 102:46-49, 1998

4. Sreekantaiah C et al: Cytogenetic profile of 109 lipomas. Cancer Res 51:422-33, 1991

5. Leffell DJ, Braverman IM: Familial multiple lipomatosis. Report of a case and a review of the literature. J Am Acad Dermatol 15:275-279, 1986

6. Bannayan GA: Lipomatosis, angiomatosis, and macrencephalia. A previously undescribed congenital syndrome. Arch Pathol 92:1-5, 1971

7. Zonana J, Rimoin DL, Davis DC: Macrocephaly with multiple lipomas and hemangiomas. J Pediatr 89:600-603, 1976

8. Fargnoli MC et al: Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome. Arch Dermatol 132:1214-1218, 1996

9. Gorlin RJ et al: Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 44:307-314, 1992

10. Sansal I, Sellers WR: The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 22:2954-2963, 2004

11. Eng C: PTEN: One gene, many syndromes. Hum Mutat 22:183-198, 2003

12. Wanner M, Celebi JT, Peacocke M: Identification of a PTEN mutation in a family with Cowden syndrome and Bannayan-Zonana syndrome. J Am Acad Dermatol 44:183-187, 2001

13. Tok Celebi J et al: Identification of PTEN mutations in five families with Bannayan-Zonana syndrome. Exp Dermatol 8:134-139, 1999

14. Longy M et al: Mutations of PTEN in patients with Bannayan-Riley-Ruvalcaba phenotype. J Med Genet 35:886-889, 1998

15. Marsh DJ et al: Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333-334, 1997

16. Fletcher CD, Martin-Bates E: Intramuscular and intermuscular lipoma: Neglected diagnoses. Histopathology 12:275-287, 1988

17. Kindblom LG et al: Intermuscular and intramuscular lipomas and hibernomas. A clinical, roentgenologic, histologic, and prognostic study of 46 cases. Cancer 33:754-762, 1974

18. Worle B et al: Lipoma of the forehead. Hautarzt 51:661, 2000

19. Salasche SJ et al: Frontalis-associated lipoma of the forehead. J Am Acad Dermatol 20:462, 1989

20. Chi MJ et al: A case of orbital lipoma with exophthalmos and visual disturbance. Jpn J Ophthalmol 53:442-444, 2009

21. Shah NB et al: Orbital lipoma: 2 cases and review of literature. Ophthal Plast Reconstr Surg 23:202-205, 2007

22. Koganei Y et al: Orbital lipoma. Ann Plast Surg 20:173-182, 1988

23. Lee HW et al: Two cases of angiomyxolipoma (vascular myxolipoma) of subcutaneous tissue. J Cutan Pathol 32:379-382, 2005

24. Tardío JC, Martín-Fragueiro LM: Angiomyxolipoma (vascular myxolipoma) of subcutaneous tissue. Am J Dermatopathol 26:222-224, 2004

25. Hitchcock MG, Hurt MA, Santa Cruz DJ: Adenolipoma of the skin: A report of nine cases. J Am Acad Dermatol 29:82-85, 1993

26. Antúnez P et al: Cutaneous apocrine cystic adenolipoma. Am J Dermatopathol 27:240-242, 2005

27. Kindblom LG, Moller-Nielsen J: Diffuse lipomatosis in the leg after poliomyelitis. Acta Pathol Microbiol Scand [A] 83:339-344, 1975

28. Punia RS et al: Recurrent diffuse lipomatosis of the neck—A case report. Indian J Pathol Microbiol 47:41-42, 2004

29. Guilemany JM, Romero E, Blanch JL: An aesthetic deformity: Madelung's disease. Acta Otolaryngol 125:328-330, 2005

30. Fernandez-Vozmediano J, Armario-Hita J: Benign symmetric lipomatosis (Launois-Bensaude syndrome). Int J Dermatol 44:236-237, 2005

31. Gonzalez-Garcia R et al: Benign symmetric lipomatosis (Madelung's disease): Case reports and current management. Aesthetic Plast Surg 28:108-112, 2004

32. Busetto L, Strater D, Enzi G: Differential clinical expression of multiple symmetric lipomatosis in men and women. Int J Obes Relat Metab Disord 27:1419-1422, 2003

33. Lee HW et al: Multiple symmetric lipomatosis: Korean experience. Dermatol Surg 29:235-240, 2003

34. Nisoli E et al: Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells. J Pathol 198:378-387, 2002

35. Enzi G, Busetto L, Ceschin E: Multiple symmetric lipomatosis: Clinical aspects and outcome in a long-term longitudinal study. Int J Obes Relat Metab Disord 26:253-261, 2002

36. Ujpal M, Nemeth ZS, Reichwein A: Long-term results following surgical treatment of benign symmetric lipomatosis (BSL). Int J Oral Maxillofac Surg 30:479-483, 2001

37. Masumori N, Tsukamoto T: Pelvic lipomatosis associated with proliferative cystitis: Case report and review of the Japanese literature. Int J Urol 6:44-49, 1999

38. Heyns CF: Pelvic lipomatosis: A review of its diagnosis and management. J Urol 146:267-273, 1991

39. Klein FA, Smith MJ, Kasenetz I: Pelvic lipomatosis: 35-year experience. J Urol 139:998-1001, 1988

40. Grimmett GM, Hall MG Jr, Aird CC: Pelvic lipomatosis. Am J Surg 125:347-349, 1973

41. Campen R, Mankin H, Louis DN: Familial occurrence of adiposis dolorosa. J Am Acad Dermatol 44:132-136, 2001

42. Reece PH, Wyatt M, O'Flynn P: Dercum's disease (adiposis dolorosa). J Laryngol Otol 113:174-176, 1999

43. Devillers AC, Oranje AP: Treatment of pain in adiposis dolorosa (Dercum's disease) with intravenous lidocaine: A case report with a 10-year follow-up. Clin Exp Dermatol 24:240-241, 1999

44. Brodovsky S et al: Adiposis dolorosa (Dercum's disease): 10-year follow-up. Ann Plast Surg 33:664-668, 1994

45. DeFranzo AJ, Hall JH Jr, Herring SM: Adiposis dolorosa (Dercum's disease): Liposuction as an effective form of treatment. Plast Reconstr Surg 85:289-292, 1990

46. Held JL, Andrew JA, Kohn SR: Surgical amelioration of Dercum's disease: A report and review. J Dermatol Surg Oncol 15:1294-1296, 1989

47. Juhlin L: Long-standing pain relief of adiposis dolorosa (Dercum's disease) after intravenous infusion of lidocaine. J Am Acad Dermatol 15:383-385, 1986

48. Cantu JM et al: Autosomal dominant inheritance in adiposis dolorosa (Dercum's disease). Humangenetik 18:89-91, 1973

49. Carr A et al: HIV Lipodystrophy Case Definition Study Group. An objective case definition of lipodystrophy in HIV-infected adults: A case-control study. Lancet 361:726-735, 2003

50. Bornhovd E et al: Multiple circumscribed subcutaneous lipomas associated with use of human immunodeficiency virus protease inhibitors? Br J Dermatol 143:1113-1114, 2000

51. Behrens GM, Stoll M, Schmidt RE: Lipodystrophy syndrome in HIV infection: What is it, what causes it and how can it be managed? Drug Saf 23:57-76, 2000

52. Brinkman K et al: Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 354:1112-1115, 1999

53. Hengel RL, Watts NB, Lennox JL: Benign symmetric lipomatosis associated with protease inhibitors. Lancet 350:1596, 1997

54. Silverman TA, Enzinger FM: Fibrolipomatous hamartoma of nerve. A clinicopathologic analysis of 26 cases. Am J Surg Pathol 9:7-14, 1985

55. Price AJ, Compson JP, Calonje E: Fibrolipomatous hamartoma of nerve arising in the brachial plexus. J Hand Surg [Br] 20:16-18, 1995

56. Berti E, Roncaroli F: Fibrolipomatous hamartoma of a cranial nerve. Histopathology 24:391-392, 1994

57. Drut R: Ossifying fibrolipomatous hamartoma of the ulnar nerve. Pediatr Pathol 8:179-184, 1988

58. Dotz W, Prioleau PG: Nevus lipomatosus cutaneus superficialis. A light and electron microscopic study. Arch Dermatol 120:376-379, 1984

59. Hendricks WM, Limber GK: Nevus lipomatosus cutaneus superficialis. Cutis 29:183-185. 1982

60. Jones EW, Marks R, Pongsehirun D: Naevus superficialis lipomatosus. A clinicopathological report of twenty cases. Br J Dermatol 93:121-133, 1975

61. Mehregan AH, Tavafoghi V, Ghandchi A: Nevus lipomatosus cutaneus superficialis (Hoffmann-Zurhelle). J Cutan Pathol 2:307-313, 1975

62. Finley AG, Musso LA: Naevus lipomatosus cutaneus superficialis (Hoffman-Zurhelle). Br J Dermatol 87:557-564, 1972

63. Burgdorf WH, Doran CK, Worret WI: Folded skin with scarring: Michelin tire baby syndrome? J Am Acad Dermatol 7:90-93, 1982

64. Ross CM: Generalized folded skin with an underlying lipomatous nevus. “The Michelin Tire baby”. Arch Dermatol 100:320-323, 1969

65. Kohn SR, Blasi JM: Piezogenic pedal papules. Arch Dermatol 106:597-598, 1972

66. Schlappner OL et al: Painful and nonpainful piezogenic pedal papules. Arch Dermatol 106:729-733, 1972

67. Harman RR, Matthews CN: Painful piezogenic pedal papules. Br J Dermatol 90:573-574, 1974

68. Kahana M et al: Painful piezogenic pedal papules in patients with Ehlers-Danlos syndrome. J Am Acad Dermatol 17:205-209, 1987

69. Laing VB, Fleischer AB Jr: Piezogenic wrist papules: A common and asymptomatic finding. J Am Acad Dermatol 24:415-417, 1991

70. Ortega-Monzó C et al: Precalcaneal congenital fibrolipomatous hamartoma: A report of four cases. Pediatr Dermatol 17:429-431, 2000

71. Warren RB, Verbov JL, Ashworth M: Precalcaneal congenital fibrolipomatous hamartoma. Pediatr Dermatol 24:74-75, 2007

72. Howard WR, Helwig EB: Angiolipoma. Arch Dermatol 82:924-931, 1960

73. Dixon AY, McGregor DH, Lee SH: Angiolipomas: An ultrastructural and clinicopathological study. Hum Pathol 12:739-747, 1981

74. Sciot R et al: Cytogenetic analysis of subcutaneous angiolipoma: Further evidence supporting its difference from ordinary pure lipomas: A report of the CHAMP Study Group. Am J Surg Pathol 21:441-444, 1997

75. Kanter WR, Wolfort FG: Multiple familial angiolipomatosis: Treatment of liposuction. Ann Plast Surg 20:277-279, 1988

76. Kahng HC et al: Cellular angiolipoma of the breast: Immunohistochemical study and review of the literature. Breast J 8:47-49, 2002

77. Kanik AB, Oh CH, Bhawan J: Cellular angiolipoma. Am J Dermatopathol 17:312-315, 1995

78. Hunt SJ, Santa Cruz DJ, Barr RJ: Cellular angiolipoma. Am J Surg Pathol 14:75-81, 1990

79. Mandahl N et al: A new cytogenetic subgroup in lipomas: Loss of chromosome 16 material in spindle cell and pleomorphic lipomas. J Cancer Res Clin Oncol 120:707-711, 1994

80. Fletcher CDM, Martin-Bates E: Spindle cell lipoma: A clinicopathologic study with some original observations. Histopathology 11:803-817, 1987

81. Angervall L et al: Spindle cell lipoma. Acta Pathol Microbiol Scand 84:477-487, 1976

82. Azzopardi JG, Iocco J, Salm R: Pleomorphic lipoma: A tumor simulating liposarcoma. Histopathology 7:511-23, 1983

83. Beham A et al: Spindle cell and pleomorphic lipoma: An immunohistochemical study and histogenetic analysis. J Pathol 158:219-222, 1989

84. Bolen JW, Thorning D: Spindle cell lipoma: A clinical, light-, and electron-microscopical study. Am J Surg Pathol 5:435-441, 1981

85. Enzinger FM, Harvey DA: Spindle cell lipoma. Cancer 36:1852-1859, 1975

86. Pitt MA, Roberts ISD, Curry A: Spindle cell and pleomorphic lipoma: An ultrastructural study. Ultrastruct Pathol 19:475-480, 1995

87. Shmookler BM, Enzinger FM: Pleomorphic lipoma: A benign tumor simulating liposarcoma. A clinicopathlogic analysis of 48 cases. Cancer 47:126-133, 1981

88. Mandahl N et al: Cytogenetic aberrations in 188 benign and borderline adipose tissue tumors. Genes Chromosomes Cancer 9:207-215, 1994

89. Dal Cin P et al: Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas. Histopathology 31:222-225, 1997

90. Fletcher CDM et al: Correlation between clinicopathological features and karyotype in lipomatous tumors. Am J Pathol 148:623-630, 1996

91. Billings SD et al: Spindle cell lipoma of the oral cavity. Am J Dermatopathol 28:28-31, 2006

92. Mehregan DR et al: Spindle cell lipomas. A report of two cases: One with multiple lesions. Dermatol Surg 21:796-798, 1995

93. Fanburg-Smith JC et al: Multiple spindle cell lipomas: A report of 7 familial and 11 nonfamilial cases. Am J Surg Pathol 22:40-48, 1998

94. Hawley IC et al: Spindle cell lipoma-a pseudoangiomatous variant. Histopathology 24:565-569, 1994

95. French CA et al: Intradermal spindle cell/pleomorphic lipoma: A distinct subset. Am J Dermatopathol 22:496-502, 2000

96. Meis JM, Enzinger FM: Chondroid lipoma. A unique tumor simulating liposarcoma and myxoid chondrosarcoma. Am J Surg Pathol 17:1103-1112, 1993

97. Nielsen GP et al: Chondroid lipoma, a tumor of white fat cells. A brief report of two cases with ultrastructural analysis. Am J Surg Pathol 19:1272-1276, 1995

98. Thomson TA, Horsman D, Bainbridge TC: Cytogenetic and cytologic features of chondroid lipoma of soft tissue. Mod Pathol 12:88-91, 1999

99. Gisselsson D et al: Unique cytological features and chromosome aberrations in chondroid lipoma: A case report based on fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and molecular cytogenetics. Am J Surg Pathol 23:1300-1304, 1999

100. Darling MR, Daley TD: Intraoral chondroid lipoma: A case report and immunohistochemical investigation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:331-333, 2005

101. Furlong MA, Fanburg-Smith JC, Childers EL: Lipoma of the oral and maxillofacial region: Site and subclassification of 125 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98:441-450, 2004

102. Boets A et al: Chondroid lipoma of the trunk: MRI appearance and pathologic correlation. Skeletal Radiol 33:666-669, 2004

103. Green RA, Cannon SR, Flanagan AM: Chondroid lipoma: Correlation of imaging findings and histopathology of an unusual benign lesion. Skeletal Radiol 33:670-673, 2004

104. Logan PM et al: Chondroid lipoma: MRI appearances with clinical and histologic correlation. Skeletal Radiol 25:592-595, 1996

105. Kindblom LG, Meis-Kindblom JM: Chondroid lipoma: An ultrastructural and immunohistochemical analysis with further observations regarding its differentiation. Hum Pathol 26:706-715, 1995

106. Meis JM, Enzinger FM: Myolipoma of soft tissue. Am J Surg Pathol 15:121-125, 1991

107. Furlong MA, Fanburg-Smith JC, Miettinen M: The morphologic spectrum of hibernoma: A clinicopathologic study of 170 cases. Am J Surg Pathol 25:809-814, 2001

108. Maire G et al: 11q13 alterations in two cases of hibernoma: Large heterozygous deletions and rearrangement breakpoints near GARP in 11q13.5. Genes Chromosomes Cancer 37:389-395, 2003

109. Mertens F et al: Hibernomas are characterized by rearrangements of chromosome bands 11q13-21. Int J Cancer 58:503-505, 1994

110. Mrozek K, Karakousis CP, Bloomfield CD: Band 11q13 is nonrandomly rearranged in hibernomas. Genes Chromosomes Cancer 9:145-147, 1994

111. Dal Cin P et al: Chromosome changes in a case of hibernoma. Genes Chromosomes Cancer 5:178-180, 1992

112. Baldi A et al: Mediastinal hibernoma: A case report. J Clin Pathol 57:993-994, 2004

113. Baskurt E, Padgett DM, Matsumoto JA: Multiple hibernomas in a 1-month-old female infant. AJNR Am J Neuroradiol 25:1443-1445, 2004

114. Hardes J et al: Sonographic findings of hibernoma. A report of two cases. J Clin Ultrasound 33:298-301, 2005

115. Chatterton BE et al: Hibernoma: Intense uptake seen on Tc-99m tetrofosmin and FDG positron emission tomographic scanning. Clin Nucl Med 27:369-370, 2002

116. Anderson SE et al: Hibernoma: Imaging characteristics of a rare benign soft tissue tumor. Skeletal Radiol 30:590-595, 2001

117. Mugel T et al: MR and CT findings in a case of hibernoma of the thigh extending into the pelvis. Eur Radiol 8:476-478, 1998

118. Jung SM et al: Lipoblastoma/lipoblastomatosis: A clinicopathologic study of 16 cases in Taiwan. Pediatr Surg Int 21:809-812, 2005

119. Hicks J et al: Lipoblastoma and lipoblastomatosis in infancy and childhood: Histopathologic, ultrastructural, and cytogenetic features. Ultrastruct Pathol 25:321-333, 2001

120. Collins MH, Chatten J: Lipoblastoma/lipoblastomatosis: A clinicopathologic study of 25 tumors. Am J Surg Pathol 21:1131-1137, 1997

121. Mentzel T, Calonje E, Fletcher CD: Lipoblastoma and lipoblastomatosis: A clinicopathological study of 14 cases. Histopathology 23:527-533, 1993

122. Mahour GH, Bryan BJ, Isaacs H Jr: Lipoblastoma and lipoblastomatosis—A report of six cases. Surgery 104:577-579, 1988

123. Chung EB, Enzinger FM: Benign lipoblastomatosis. An analysis of 35 cases. Cancer 32:482-492, 1973

124. Coffin CM, Lowichik A, Putnam A: Lipoblastoma (LPB): A clinicopathologic and immunohistochemical analysis of 59 cases. Am J Surg Pathol 33:1705-1712, 2009

125. de Saint Aubain Somerhausen N et al: Lipoblastoma in adolescents and young adults: Report of six cases with FISH analysis. Histopathology 52:294-298, 2008

126. Harrer J et al: Lipoblastoma and lipoblastomatosis: A report of two cases and review of the literature. Eur J Pediatr Surg 11:342-349, 2001

127. Calobrisi SD et al: Congenital lipoblastomatosis of the lower extremity in a neonate. Pediatr Dermatol 15:210-213, 1998

128. Chang PF et al: Lipoblastomatosis in a newborn: Case report. Pediatr Surg Int 12:71-72, 1997

129. Chen Z et al: Evidence by spectral karyotyping that 8q11.2 is nonrandomly involved in lipoblastoma. J Mol Diagn 2:73-77, 2000

130. Dal Cin P et al: New discriminative chromosomal marker in adipose tissue tumors. The chromosome 8q11-q13 region in lipoblastoma. Cancer Genet Cytogenet 78:232-235, 1994

131. Fletcher JA et al: Cytogenetic findings in pediatric adipose tumors: Consistent rearrangement of chromosome 8 in lipoblastoma. Genes Chromosomes Cancer 6:24-29, 1993

132. Morerio C et al: PLAG1-HAS2 fusion in lipoblastoma with masked 8q intrachromosomal rearrangement. Cancer Genet Cytogenet 156:183-184, 2005

133. Gisselsson D et al: PLAG1 alterations in lipoblastoma: Involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms. Am J Pathol 159:955-962, 2001

134. Hibbard MK et al: PLAG1 fusion oncogenes in lipoblastoma. Cancer Res 60:4869-4872, 2000

135. Bartuma H et al: Cytogenetic and molecular cytogenetic findings in lipoblastoma. Cancer Genet Cytogenet 183:60-63, 2008

136. Alba Greco M, Garcia RL, Vuletin JC: Benign lipoblastomatosis: Ultrastructure and histogenesis. Cancer 45:511-515, 1980

137. Marshall-Taylor C, Fanburg-Smith JC: Hemosiderotic fibrohistiocytic lipomatous lesion: Ten cases of a previously undescribed fatty lesion of the foot/ankle. Mod Pathol 13:1192-1199, 2000

138. Browne T-J, Fletcher CDM: Haemosiderotic fibrolipomatous tumour (so-called haemosiderotic fibrohistiocytic lipomatous tumour): Analysis of 13 new cases in support of a distinct entity. Histopathology 48:453-461, 2006

139. Kazakov DV, Sima R, Michal M: Hemosiderotic fibrohistiocytic lipomatous lesion: Clinical correlation with venous stasis. Virchows Arch 447:103-106, 2005

140. Folpe AL, Weiss SW: Pleomorphic hyalinizing angiectatic tumor: Analysis of 41 cases supporting evolution from a distinctive precursor lesion. Am J Surg Pathol 28:1417-1425, 2004

141. Sasaki D et al: Lipofibromatosis arising in a pediatric forearm—A case report. Ups J Med Sci 110:259-266, 2005

142. Teo HE et al: Infantile lipofibromatosis of the upper limb. Skeletal Radiol 34:799-802, 2005

143. Herrmann BW, Dehner LP, Forsen JW Jr: Lipofibromatosis presenting as a pediatric neck mass. Int J Pediatr Otorhinolaryngol 68:1545-1549, 2004

144. Fetsch JF et al: A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis. Am J Surg Pathol 24:1491-500, 2000

145. Enterline HT et al: Liposarcoma. A clinical and pathological study of 53 cases. Cancer 13:932-950, 1960

146. Kindblom LG, Angervall L, Svendsen P: Liposarcoma a clinicopathologic, radiographic and prognostic study. Acta Pathol Microbiol Scand (253):1-71,1975

147. Enzinger FM, Winslow DJ: Liposarcoma. A study of 103 cases. Virchows Arch Pathol Anat Physiol Klin Med 335:367-388, 1962

148. Kindblom LG, Angervall L, Fassina AS: Atypical lipoma. Acta Pathol Microbiol Immunol Scand [A] 90:27-36, 1982

149. Lucas DR et al: Well-differentiated liposarcoma. The Mayo Clinic experience with 58 cases. Am J Clin Pathol 102:677-683, 1994

150. Evans HL: Liposarcoma: A study of 55 cases with a reassessment of its classification. Am J Surg Pathol 3:507-523, 1979

151. Evans HL, Soule EH, Winkelmann RK: Atypical lipoma, atypical intramuscular lipoma, and well differentiated retroperitoneal liposarcoma: A reappraisal of 30 cases formerly classified as well differentiated liposarcoma. Cancer 43:574-584, 1979

152. Weiss SW, Rao VK: Well-differentiated liposarcoma (atypical lipoma) of deep soft tissue of the extremities, retroperitoneum, and miscellaneous sites. A follow-up study of 92 cases with analysis of the incidence of “dedifferentiation”. Am J Surg Pathol 16:1051-1058, 1992

153. Rosai J et al: Combined morphologic and karyotypic study of 59 atypical lipomatous tumors. Evaluation of their relationship and differential diagnosis with other adipose tissue tumors (a report of the CHAMP Study Group). Am J Surg Pathol 20:1182-1189, 1996

154. Dei Tos AP et al: Coordinated expression and amplification of the MDM2, CDK4, and HMGI-C genes in atypical lipomatous tumours. J Pathol 190:531-536, 2000

155. Tallini G et al: Expression of HMGI-C and HMGI(Y) in ordinary lipoma and atypical lipomatous tumors: Immunohistochemical reactivity correlates with karyotypic alterations. Am J Pathol 151:37-43, 1997

156. Hostein I et al: Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: A potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas. J Pathol 202:95-102, 2004

157. Pilotti S et al: The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma. Br J Cancer 82:1271-1275, 2000

158. Pilotti S et al: Molecular abnormalities in liposarcoma: Role of MDM2 and CDK4-containing amplicons at 12q13-22. J Pathol 185:188-190, 1998

159. Pedeutour F et al: Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes Cancer 24:30-41, 1999

160. Binh MB et al: MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: A comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol 29:1340-1347, 2005

161. Nascimento AF, McMenamin ME, Fletcher CD: Liposarcomas/atypical lipomatous tumors of the oral cavity: A clinicopathologic study of 23 cases. Ann Diagn Pathol 6:83-93, 2002

162. Cai YC et al: Primary liposarcoma of the orbit: A clinicopathologic study of seven cases. Ann Diagn Pathol 5:255-266, 2001

163. Nucci MR, Fletcher CD: Liposarcoma (atypical lipomatous tumors) of the vulva: A clinicopathologic study of six cases. Int J Gynecol Pathol 17:17-23, 1998

164. Wenig BM, Weiss SW, Gnepp DR: Laryngeal and hypopharyngeal liposarcoma. A clinicopathologic study of 10 cases with a comparison to soft-tissue counterparts. Am J Surg Pathol 14:134-141, 1990

165. Kraus MD, Guillou L, Fletcher CD: Well-differentiated inflammatory liposarcoma: An uncommon and easily overlooked variant of a common sarcoma. Am J Surg Pathol 21:518-527, 1997

166. Dei Tos AP et al: Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases. Am J Surg Pathol 18:913-921, 1994

167. Sirvent N et al: Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: Utility in diagnosing adipocyte lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol 31:1476-1489, 2007

168. Evans HL: Atypical lipomatous tumor, its variants, and its combined forms: A study of 61 cases, with a minimum follow-up of 10 years. Am J Surg Pathol 31:1-14, 2007

169. Dei Tos AP et al: Atypical lipomatous tumour/well differentiated liposarcoma: Worls Health Organization Classification pf Tumours. In: Pathology and Genetics of Tumours of Soft Tissue and Bone, edited by CDM Fletcher, KK Unna, F Mertens. Lyon, IARC Press, 2002

170. Nascimento AG: Dedifferentiated liposarcoma. Semin Diagn Pathol 18:263-266, 2001

171. Henricks WH et al: Dedifferentiated liposarcoma: A clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation. Am J Surg Pathol 21:271-281, 1997

172. McCormick D et al: Dedifferentiated liposarcoma. Clinicopathologic analysis of 32 cases suggesting a better prognostic subgroup among pleomorphic sarcomas. Am J Surg Pathol 18:1213-1223, 1994

173. Sandberg AA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: Liposarcoma. Cancer Genet Cytogenet 155:1-24, 2004

174. Yoshikawa H et al: Dedifferentiated liposarcoma of the subcutis. Am J Surg Pathol 20:1525-1530, 1996

175. Hisaoka M et al: Retroperitoneal liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma-like myxoid areas. Am J Surg Pathol 23:1480-1492, 1999

176. Fanburg-Smith JC et al: Liposarcoma with meningothelial-like whorls: A study of 17 cases of a distinctive histological pattern associated with dedifferentiated liposarcoma. Histopathology 33:414-424, 1998

177. Nascimento AG et al: Dedifferentiated liposarcoma: A report of nine cases with a peculiar neurallike whorling pattern associated with metaplastic bone formation. Am J Surg Pathol 22:945-955, 1998

178. Tallini G et al: Combined morphologic and karyotypic study of 28 myxoid liposarcomas. Implications for a revised morphologic typing, (a report from the CHAMP Group). Am J Surg Pathol 20:1047-1055, 1996

179. Kilpatrick SE et al: The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases. Cancer 77:1450-1458, 1996

180. Antonescu CR et al: Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: A molecular and clinicopathologic study of 82 cases. Clin Cancer Res 7:3977-3987, 2001

181. Antonescu CR et al: Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma: Absence in predominantly myxoid well-differentiated liposarcomas. J Mol Diagn 2:132-138, 2000

182. Crozat A et al: Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363:640-644, 1993

183. Rabbitts TH et al: Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet 4:175-180, 1993

184. Knight JC et al: Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: Molecular and cytogenetic analysis. Cancer Res 55:24-27, 1995

185. Antonescu CR et al: Monoclonality of multifocal myxoid liposarcoma: Confirmation by analysis of TLS-CHOP or EWS-CHOP rearrangements. Clin Cancer Res 6:2788-2793, 2000

186. Panagopoulos I et al: Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia. Oncogene 15:1357-1362, 1997

187. Dal Cin P et al: Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: Clinicopathological features. J Pathol 182:437-441, 1997

188. Smith TA, Easley KA, Goldblum JR: Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma. Am J Surg Pathol 20:171-180, 1996

189. ten Heuvel SE et al: Clinicopathologic prognostic factors in myxoid liposarcoma: A retrospective study of 49 patients with long-term follow-up. Ann Surg Oncol 14:222-229, 2007

190. Azumi N et al: Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases. Am J Surg Pathol 11:161-183, 1987

191. Fletcher CD: Pleomorphic malignant fibrous histiocytoma: Fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma. Am J Surg Pathol 16:213-228, 1992

192. Hornick JL et al: Pleomorphic liposarcoma: Clinicopathologic analysis of 57 cases. Am J Surg Pathol 28:1257-1267, 2004

193. Gebhard S et al: Pleomorphic liposarcoma: Clinicopathologic, immunohistochemical, and follow-up analysis of 63 cases: A study from the French Federation of Cancer Centers Sarcoma Group. Am J Surg Pathol 26:601-616, 2002

194. Downes KA et al: Pleomorphic liposarcoma: A clinicopathologic analysis of 19 cases. Mod Pathol 14:179-184, 2001

195. Dei Tos AP, Mentzel T, Fletcher CD: Primary liposarcoma of the skin: A rare neoplasm with unusual high grade features. Am J Dermatopathol 20:332-338, 1998

196. Huang HY, Antonescu CR: Epithelioid variant of pleomorphic liposarcoma: A comparative immunohistochemical and ultrastructural analysis of six cases with emphasis on overlapping features with epithelial malignancies. Ultrastruct Pathol 26:299-308, 2002

197. Miettinen M, Enzinger FM: Epithelioid variant of pleomorphic liposarcoma: A study of 12 cases of a distinctive variant of high-grade liposarcoma. Mod Pathol 12:722-728, 1999

198. Mertens F et al: Cytogenetic analysis of 46 pleomorphic soft tissue sarcomas and correlation with morphologic and clinical features: A report of the CHAMP Study Group. Chromosomes and Morphology. Genes Chromosomes Cancer 22:16-25, 1998

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Etiology and Pathogenesis

Clinical Findings

Histologic Features

eFigure 129-7.11

eFigure 129-7.12

Differential Diagnosis

Clinical Course, Prognosis, and Treatment

Epidemiology

Clinical Findings

Histologic Features

Differential Diagnosis

Clinical Course, Prognosis, and Treatment

Epidemiology

Etiology and Pathogenesis

Clinical Findings

Histologic Features

eFigure 129-7.13

Figure 129-8

Differential Diagnosis

Clinical Course, Prognosis, and Treatment

Epidemiology

Etiology and Pathogenesis

Clinical Findings

Histologic Features

eFigure 129-8.1

eFigure 129-8.2

eFigure 129-8.3

eFigure 129-8.4