Neoplasms of Subcutaneous Fat

Chapter 129
Neoplasms of
Subcutaneous Fat
NEVUS LIPOMATOSUS
SUPERFICIALIS
Thomas Brenn
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.5862
LIPOMATOSIS OF NERVE
(FIBROLIPOMATOUS
HAMARTOMA OF NERVE)
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
Epidemiology
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.
Histological Features
The histologic features show mature adipose
tissue in varying amounts within the superficial
dermis (eFig. 129-6.1).
PIEZOGENIC PEDAL PAPULES

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.6567 Piezogenic
pedal papules have also been reported on the wrist
and are present in about a third of patients with
EhlersDanlos syndrome.68,69 Etiologically, they are
thought to be due to herniation of subcutaneous
fat into dermis presumably due to connective tissue defects.
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
Copyright McGraw-Hill Companies, Inc. All rights reserved.
190 Chapter 129: Neoplasms of Subcutaneous Fat
PRECALCANEAL CONGENITAL
FIBROLIPOMATOUS
HAMARTOMA
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
Histologically, lobules of mature fat are surrounded and separated by hypocellular fibrous sheaths.
Prominent vessels are an additional finding.70,71
SPINDLE CELL AND

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.7987 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.7987
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.2,79,8890
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.7987 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
HIstological 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. 129-7.3129-7.5).
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.
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.
By immunohistochemical analysis, the spindle
cells express CD34 and rarely S100 protein.
Chapter 129:
Differential Diagnosis
The differential diagnosis for spindle cell and pleomorphic lipomas includes the following:
Atypical lipomatous tumor
Solitary fibrous tumor
Cellular angiofibroma

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

Ultrastructural analysis confirms adipocyte rather
than cartilaginous differentiation.97 Cytogenetically,
a balanced translocation involving chromosomes
11 and 16, t(11;16)(q13;p1213), 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 16p1213 locus.
Neoplasms of Subcutaneous Fat 191
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.97,100102 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.102104
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.
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 for chondroid lipoma includes the following:
Myxoid liposarcoma
Extraskeletal myxoid chondrosarcoma

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

Epidemiology

Treatment
Myolipoma of soft tissue is a benign neoplasm,
and recurrences have not been reported. Complete
excision is curative.
LIPOBLASTOMA/
LIPOBLASTOMATOSIS
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
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.118125 Infrequently, tumors may be congenital.126128 There is a male predominance, with a male
female ratio of approximately 2:1.118124
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.
The differential diagnosis for myolipoma of soft
tissue includes the following:
Liposarcoma
AngiomyolipomaAngiomyolipoma

Cytogenetic analysis has identified a recurrent translocation involving chromosome band
8q1113,129131 leading to rearrangements of the
transcription factor Plag1 (pleomorphic adenoma
gene).132135
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.118123 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).
Chapter 129:
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
tumors 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.
By immunohistochemistry, expression for S100
and CD34 is seen.124
Ultrastructurally, these tumors resemble maturing
adipose tissue rather than brown fat.119,136
The differential diagnosis of lipoblastoma/lipoblastomatosis includes the following:
Myxoid liposarcoma
Hibernoma
Lipofibromatosis

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
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.137139 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

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 56 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.
The differential diagnosis for hemosiderotic fibrohistiocytic lipomatous tumors includes the following:
Plexiform fibrohistiocytic tumor

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
Epidemiology
Lipofibromatosis is an uncommon pediatric
neoplasm that predominantly affects infants at a
median age of 1 year.141144 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. 1298.5 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).
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
The differential diagnosis for lipofibromatosis
includes the following:
Fibromatosis
Fibrous hamartoma of infancy

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.
DEDIFFERENTIATED
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.170172 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

The karyotypic findings are similar to those seen
in well-differentiated liposarcoma and involve
supernumerary ring and giant marker chromosomes.173
Chapter 129:
Cliinical Findings
Tumors present as large painless masses with a
predilection for the retroperitoneum followed by
the limbs and paratesticular area and spermatic
cord.170172 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.170172,175 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
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
The differential diagnosis of dedifferentiated liposarcoma includes the following:
Spindle cell liposarcoma
Pleomorphic liposarcoma
Other pleomorphic sarcomas

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.
PLEOMORPHIC LIPOSARCOMA
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, 5060 years). However, the age
range is wide.192194
Clinical Findings
Tumors present as enlarging firm masses, frequently with a short history. They are typically large,
deep-seated, and subfascial sarcomas measuring
810 cm in median. Presentation in subcutaneous
tissue is less frequent, and dermal location is unusual.192195 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.
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.
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.
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
The differential diagnosis of pleomorphic liposarcoma includes the following:
Dedifferentiated liposarcoma
Leiomyosarcoma
Pleomorphic rhabdomyosarcoma
Myxofibrosarcoma
Melanoma
Carcinoma

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Chapter 129

Nevus lipomatosus superficialis is a rare form of

Clinical Course, Prognosis, and

PIEZOGENIC PEDAL PAPULES

Copyright McGraw-Hill Companies, Inc. All rights reserved.

190 Chapter 129: Neoplasms of Subcutaneous Fat

SPINDLE CELL AND

Etiology and Pathogenesis

Copyright McGraw-Hill Companies, Inc. All rights reserved.

Clinical Course, Prognosis, and

Etiology and Pathogenesis