Mediastinal Lipoblastomatosis: Report of a
Case with Complex Karyotype and Review of
NASIR K. AMRA*AND SAMIR S. AMR
Pathology Services Division, Dhahran Health Center, Dhahran, Saudi Arabia
Received September 5, 2008; accepted February 3, 2009; published online February 4, 2009.
Lipoblastoma or lipoblastomatosis is an uncommon fatty
tumor seen in children up to the age of 5 years, with very
rare exceptions above that age. It usually occurs in the
extremities, but it can arise in other anatomical sites,
including the head and neck area, trunk, mediastinum,
mesentry, and retroperitoneum. We report a 9-month-old
boy with mediastinal lipoblastomatosis showing unusual-
ly complex chromosomal aberrations. Five years follow-
ing surgical excision that was incomplete as a result of the
tumor’s proximity to major blood vessels, the patient
developed a recurrence of the tumor in the mediastinum
with extension to the neck and spinal dura. We present a
review of the literature related to mediastinal lipoblas-
toma and lipoblastomatosis and the chromosomal abnor-
malities of these tumors.
Key words: fatty tumors, lipoblastoma, lipoblastomato-
sis, liposarcoma, mediastinal tumors, tumor cytogenetics
Since its 1st description in 1958 by Vellios and colleagues
, lipoblastomatosis has come to mean a benign
embryonal fatty tumor affecting children, with a predelic-
tion to the male gender. In 1973, Chung and Enzinger ,
in a review of 35 cases, suggested that the term
lipoblastoma be used for the circumscribed type and that
the term lipoblastomatosis be used for the diffuse
infiltrative or multicentric type. The tumor arises in many
different anatomic locations and can have morphologic
features that could be confused with liposarcoma ,
lipoma , fibrolipoma , lipofibromatosis , low-
grade fibromyxoid sarcoma , or even neurothekeoma
. Recently, a nonrandom distinct cytogenetic abnormal-
ity characterized by 8q11-q24 chromosomal aberration has
been demonstrated in lipoblastomas [8–11]. We report a
rare case of mediastinal lipoblastomatosis with complex
cytogenetic karyotype, and we review the medical
lipoblastoma and lipoblastomatosis unless we are discuss-
ing specifically the difference between the 2 entities.
A 9-month-old male infant presented with a 1-week history
of nonproductive cough and noisy exhalation with no
fever, vomiting, or diarrhea. The patient had a history of
intermittent lip cyanosis during crying. Anterior-posterior
and lateral chest X-rays demonstrated an upper mediastinal
mass that was pushing the trachea to the right, with a very
narrow airway entry. A chest computed tomographic scan
demonstrated a large septate fatty mass measuring 7 3 7 3
anterior mediastinum and into the middle mediastinum,
displacing major blood vessels, trachea, and thymus to the
right. The patient underwent thoracotomy, and a large
portion of the tumor was resected, as was the adjacent
thymus gland. A portion of the tumor was not resected
because of its proximity to major blood vessels. Postop-
eratively, the patient displayed left diaghragmatic paralysis
and had a residual tumor measuring 3.5 3 3 3 3 cm.
Over a follow-up period of 5 years, magentic
resonance imaging scans
demonstrated regrowth of the tumor, which grew to
measure 6.1 3 4.8 3 4.6 cm within the mediastinum,
with extension to the spinal dura but without spinal cord
invasion. The tumor also extended into the left sterno-
cleidomastoid and scalene muscles. Five years after the
operation, the patient does not have any persistant
physical discomfort or symptoms from this tumor.
and physical evaluations
*Corresponding author, e-mail: email@example.com
Pediatric and Developmental Pathology 12, 469–474, 2009
ª 2009 Society for Pediatric Pathology
An intraoperative consultation (frozen-section) diagnosis
of lipoblastoma was rendered on a small biopsy of the
tumor. The subsequently resected tumor weighed 68 g
and consisted of nodular, soft, tan tissue that was not
encapsulated (Fig. 1A).
Histological examination revealed mature adipocytes
with a lobulated architecture and peripheral spindle cell
proliferation (Fig. 1B). There were spindle cell areas with
associated myxoid stroma (Fig. 1C) and multivacuolated
lipoblasts (Fig. 1D). Focal dystrophic calcification with
fat necrosis was noted.
Chromosomal analysis of the tumor along with
fluorescent in situ hybridization (FISH) using multicol-
ored probes for all human chromosomes demonstrated a
Figure 1. (A) Partially resected lipoblastomatosis weighing
68 g. (B) Fatty tumor with peripheral spindle cell prolifera-
tion (hematoxylin and eosin, objective magnification 310).
(C) An area of abundant myxoid stroma (hematoxylin and
eosin, objective magnification 320). (D) An area of lipoblasts
(hematoxylin and eosin, objective magnification 340).
Figure 2. GTG-banding (A) and fluorescent in situ hybrid-
ization (FISH) (B) using multicolored probes for all human
chromosomes demonstrate a complex karyotype: 46,XY,
N.K. AMRA AND S.S. AMR
quite complex karyotype: 46,XY,der(2)inv(2)(q31q35)
der(14)t(2;5;14;10)ins(5;8)(q31;q13q24.1) (20 cells ana-
lyzed, 3 cells karyotyped). This karyotype includes the
characteristic rearrangement involving chromosome 8
that is seen with lipoblastoma, along with additional
complex chromosomal abnormalities (Fig. 2).
Lipoblastoma is typically circumscribed and located in
the superficial soft tissues, simulating a lipoma. The more
diffuse, infiltrative form is called lipoblastomatosis. This
is a slow-growing tumor with a male predilection that can
compress and displace adjacent structures, as it did in this
patient. It typically arises in the soft tissue of the
extremities and trunk, but rarely it can involve the
mediastinum and retroperitoneum. Aggregating published
large institutional reviews [2,12–15] of this entity
indicates that only 1% (1 of 102) of cases of this tumor
involve the mediastinum. This single case of mediastinal
lipoblastomatosis was reported in a series by Chung and
Enzinger  involving 35 total cases of lipoblastoma/
lipoblastomatosis. In addition, there are 20 individual
case reports of mediastinal lipoblastoma (14 cases) and
lipoblastomatosis (6 cases) [16–34] (Table 1). Cases
involving the chest wall, the lungs, or the pleural cavities
are not included in this review. The age range for cases of
mediastinal lipoblastoma is 4 months to 6 years (mean,
32.9 months). On the other hand, the age range for cases
of mediastinal lipoblastomatosis is 3 months to 20 months
(mean, 13 months). This mean age difference at initial
diagnosis between lipoblastoma and lipoblastomatosis
was observed in a large series  that comprised cases
from various anatomic sites. There was no preponderance
of males (10 cases) over females (10 cases) in these cases.
In most series [2,12] of lipoblastoma/lipoblastomatosis,
Table 1.Mediastinal lipoblastoma/lipoblastomatosis reported in the literature
Author(s)Age Sex Type Follow-upRemarks
Chung and Enzinger  2 yF Lipoblastomatosis 4.5 y NEDPresented with dyspnea and tumor extending
into the neck
500-g mass, filled right hemithorax
7.5 3 6.5 cm, displaced the heart to the right
Tabrisky and colleagues 
Dudgeon and Haller 
Marques Gubern and
Whyte and Powell 
Federici and colleagues 
Ko and colleagues 
18 m NED
2.5 y NED
11 y NED
20 mF Lipoblastomatosis 2 y NED
12 m NA LipoblastomatosisNA Diaphragmatic involvement
Chest wall involvement
Respiratory stridor and dyspnea on the supine
Intraspinal extension with formation of a
long segment of extradural mass
Left innominate vein and phrenic nerve were
sacrificed in total resection
10.5 3 5.5 3 2.5 cm, right paravertebral
Tumor is related to pleura and right lung is
displaced and collapsed
Lobulated homogeneous anterior mediastinal
mass (8 3 5 cm) in the right hemithorax
Suprascapular mass with spinal epidural
15 3 12 cm, filling left hemithorax
Dumbbell-shaped tumor involving both
Giant mass, 22 3 22 3 15 cm, 996 g
Irgau and McNicholas 6 yF LipoblastomaNA
Broeders and colleagues  6 yMLipoblastomaNA
Park and colleagues  4 mF LipoblastomaNA
Ng and colleagues 
Ching and colleagues 
12 m NED
Sharma and colleagues 2 yFLipoblastoma 4 m NED
Li and colleagues 
Rao and colleagues 
Binay and Shan 
Moholkar and colleagues 
Dogan and colleagues 
91 m NED
NAExtension to the neck and associated with
Tumor extended to spinal epidural space
from C7 to D9
Tumor recurred locally with extension to the
Guille ´n-Quesada and
Amra and Amir (current
27 mM Lipoblastoma NA
9 mMLipoblastomatosis 5 y
y indicates years; m, months; F, female; M, male; NA, not available; NED, no evidence of disease.
there had been a preponderance of males over females.
Several patients presented with symptoms related to
airway obstruction, including cough, tachypnea, and
circumoral cyanosis [2,16,21,25,29], and a few masses
attained large size [16,17,24,29,31]. In one case, the
tumor weighed 996 g . In another case, the tumor
weighed 500 g, and it filled the right hemithorax .
Our case involved a recurrence with extension to the
spinal canal. Several cases of mediastinal lipoblastoma
[22,28,34] or lipoblastomatosis  have been associated
with extension to the spinal canal, with associated
neurological manifestations, such as paresis. Other cases
of lipoblastoma arising in other anatomical locations,
such as the right side of the neck  or the back ,
have also been associated with intraspinal extension.
Histologically, lipoblastoma demonstrates a range of
adipocyte maturation encompassing spindle-shaped mes-
enchymal cells, unilocular lipoblasts, multivacuolar
lipoblasts, and mature adipocytes. Myxoid change and a
plexiform vascular network are other characteristic
features of this tumor .
The differential diagnosis of fat-containing tumors of
the mediastinum includes myxoid liposarcoma, teratoma
composed mostly of fat (when only a small biopsy is
taken), lipoma, fibrolipoma, thymolipoma, hibernoma, or,
rarely, low-grade fibromyxoid sarcoma (when normal fat
is incorporated within this fibrous tumor) . Thymo-
lipoma can be distinguished histologically from the other
tumors by the presence of thymic parenchyma with well-
developed Hassall corpuscles . The cytogenetic
findings help distinguish lipoblastoma (associated with
rearrangements of chromosome 8q11-13) from myxoid
liposarcoma (associated with chromosome t[12;16]),
lipomas, and fibrolipomas (associated with chromosomal
aberrations 12q13-15 and 6p21-23) as well as hibernoma
(associated with aberrations in chromosomal band 11q13)
[40,41]. The lack of cellular atypia in lipoblastoma and
the typical age incidence of myxoid liposarcoma (30–60
years) versus lipoblastoma (typically seen before the age
of 3 years) are additional helpful differentiating features.
Lipoblastoma is lobulated, a feature not often seen in
liposarcoma. Liposarcoma may contain microcystic areas,
which are not seen in lipoblastoma. Interestingly, low-
grade fibromyxoid sarcoma displays chromosomal aber-
ration of chromosome 16, as does liposarcoma. How-
ever, low-grade fibromyxoid sarcoma is associated with
fusion gene. Moreover, the lack of lipoblasts and the
histologic architecture of alternating areas of bland
spindle cells with collagen deposits and myxoid areas
distinguish this tumor from lipoblastoma or myxoid
Immunohistochemical stains have a limited role in
the above differential diagnosis of fatty tumors of the
mediastinum. However, a recent abstract  has
demonstrated in a small study that desmin immunohisto-
chemical stain can help differentiate lipoblastoma from
other fatty tumors. The spindled cells in lipoblastoma are
diffusely positive for desmin, in contrast to negative or
rare focal positivity in lipoma, lipofibroma, myxoid
liposarcoma, and well-differentiated liposarcoma .
Two case reports [45,46] illustrate the utility of
cytogenetics in helping differentiate lipoblastoma from
liposarcoma in atypical clinical presentations of fatty
tumors. One report involves a 14-year-old girl with a
lipomatous tumor of the right thigh that proved to be well-
differentiated liposarcoma by FISH studies . Another
case involves a 23-year-old male with lipoblastoma in the
right thigh, as proven by karyotyping and FISH studies
. More recently, 6 cases of lipoblastoma in patients
ranging from 14 to 24 years of age were reported ,
with results of FISH demonstrating rearrangements of the
PLAG1 region in 2 cases and polysomy for chromosome
8 in 3 other cases. None of the tumors had amplification
of MDM2 or CDK4. The authors  concluded that
lipoblastoma can rarely occur in young adults and should
enter into the differential diagnosis of ‘‘atypical’’ fatty
tumors in adults.
Complex cytogenetic abnormalities in lipoblastoma
have not been reported frequently. Similar complex
cytogenetic abnormalities have been seen in a case report
 of an intrascrotal lipoblastoma. While this case
demonstrates chromosomal aberrations (including addi-
tions and deletions) in 6 chromosomes, the intrascrotal
lipoblastoma involved 11 chromosomes. Only 3 chromo-
somal aberrations are shared between the 2 cases
(involving chromosomes 7, 8, and 10). It is unclear
whether these cases in this subset of lipoblastoma, with
their complex cytogentic findings, have a different
Cytogenetic karyotyping of lipoblastoma has shown
consistent chromosomal breakpoints involving 8q11-13.
The PLAG1 gene, located in 8q12, has been shown to be
involved in the chromosomal rearrangements that produce
the fusion genes HAS2/PLAG1 and COL1A2/PLAG1.
These fusion genes leads to transcriptional upregulation
of the fusion gene products through a promotor-swapping
mechanism. Polysomy of chromosome 8 is another
proposed [9,37,49] mechanism for increasing PLAG1
production in lipoblastoma.
PLAG1 is a zinc-finger transcription factor protein
that is usually expressed at very low levels postnatally. It
was first discovered as an oncogenic factor in pleomor-
phic adenoma (associated with t[3;8][p21;q12]) and has
been demonstrated to be elevated in hepatoblastoma, 20%
of acute myelogenous leukemia cases, uterine leiomyo-
ma, leiomyosarcomas, and smooth muscle tumors.
PLAG1 appears to mediate its oncogenic potential via
the insulin-like growth factor 2 signaling pathway; the
activation of which in turn increases mitogenesis via the
MAPK signaling pathway mediated by insulin-like
growth factor receptor (IGF-1R) . The recent
commercial availability of PLAG1 antibody raises the
possibility of detecting overexpression of PLAG1 by
immunohistochemical stain to aid in the diagnosis of
N.K. AMRA AND S.S. AMR
Surgical excision is the treatment of choice, which
offers an excellant prognosis. There is a reported
recurrance rate of 9% to 22% among all lipoblastomas
. Authors of one report  indicate that lipoblastoma
may spontaneously resolve with time and suggest that a
‘‘wait and see’’ approach can be pursued in cases in
which complete excision of the lesion cannot be
performed without mutilation or significant morbidity.
The authors acknowledge the use of Saudi Aramco
Medical Services Organization (SAMSO) facilities for the
research data utilized in this manuscript. They acknowl-
edge as well Robert Jenkins of the Mayo Medical
Laboratories for his assistance with cytogenetic analysis.
Opinions expressed in this article are those of the authors
and not necessarily of SAMSO.
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