Skeletal Radiology

https://doi.org/10.1007/s00256-021-03837-1

REVIEW ARTICLE

Update of pediatric soft tissue tumors with review of conventional

MRI appearance—part 2: vascular lesions, fibrohistiocytic tumors,
muscle tumors, peripheral nerve sheath tumors, tumors of uncertain
differentiation, and undifferentiated small round cell sarcomas
Ezekiel Maloney1 · Khalid Al‑Dasuqi2 · Lina Irshaid3 · Annie Wang2 · Kimia Kani4 · Andrew Haims2 · Jack Porrino2

Received: 17 December 2020 / Revised: 22 May 2021 / Accepted: 2 June 2021

© ISS 2021

Abstract
There are numerous soft tissue tumors and tumor-like conditions in the pediatric population. Magnetic resonance imaging is
the most useful modality for imaging these lesions. Although certain soft tissue lesions exhibit magnetic resonance features
characteristic of a specific diagnosis, most lesions are indeterminate, and a biopsy is necessary for diagnosis. We provide
a detailed update of soft tissue tumors and tumor-like conditions that occur in the pediatric population, emphasizing each
lesion’s conventional magnetic resonance imaging appearance, using the recently released ­5th edition of the World Health
Organization Classification of Soft Tissue and Bone Tumors as a guide. In part one of this review, pediatric tumor-like lesions,
adipocytic tumors, fibroblastic and myofibroblastic tumors, and perivascular tumors are discussed. In part two, vascular
lesions, fibrohistiocytic tumors, muscle tumors, peripheral nerve sheath tumors, tumors of uncertain differentiation, and
undifferentiated small round cell sarcomas are reviewed. Per the convention of the WHO, these lesions involve the connective,
subcutaneous, and other non-parenchymatous organ soft tissues, as well as the peripheral and autonomic nervous system.

Keywords  Pediatric · Soft tissue mass · Tumor · Sarcoma · Vascular malformation

Introduction adjacent anatomic structures such as nerves, arteries, fascia,

There are numerous soft tissue tumors and tumor-like condi-
tions that may present in the pediatric population. Magnetic
resonance imaging (MRI) is the most useful modality for
imaging these soft tissue lesions as a result of its detailed
anatomic portrayal of the mass, including its relation to
and periosteum [1, 2].
We provide an update of the soft tissue tumors and tumor-
like conditions that occur in the pediatric population, with a
review of each lesion’s conventional MRI appearance, utiliz-
ing the newly released World Health Organization (WHO)
nomenclature and classification, summarized in Table 1. We
have elected to address vascular lesions with deference to

* Jack Porrino Andrew Haims

jack.porrino@yale.edu andrew.haims@yale.edu
Ezekiel Maloney 1
Department of Radiology, University of Washington, Seattle
eze@uw.edu
Children’s Hospital, 4800 Sand Point Way NE, Seattle,
Khalid Al‑Dasuqi WA 98105, USA
khalid.aldasuqi@yale.edu 2
Yale Radiology and Biomedical Imaging, 330 Cedar Street,
Lina Irshaid New Haven, CT 06520, USA
lina.irshaid@yale.edu 3
Department of Pathology, Yale School of Medicine, 333
Annie Wang Cedar Street, New Haven, CT 06520, USA
annie.wang@yale.edu 4
Department of Radiology, University of Maryland Medical
Kimia Kani Center, 22 S Greene St, Baltimore, MD 21201, USA
kimia.kani@umm.edu

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Table 1  Overview of WHO classes of pediatric soft tissue tumors, excluding vascular lesions subsection
Adipocytic tumors Fibroblastic and myofibroblastic Muscle tumors Tumors of uncertain differentiation
tumors

Lipoma (Part 1, Fig. 2) Nodular fasciitis (Part 1, Fig. 6
and 7)
Lipomatosis (Part 1, Fig. 3) Proliferative fasciitis and myositis Fetal rhabdomyoma
Lipoblastoma and lipoblastomato- Myositis ossificans (Part 1, Fig. 8) Embryonal rhabdomyosarcoma
sis (Part 1, Fig. 4)
Myxoid and myxoid-pleomorphic Fibrous hamartoma of infancy
liposarcoma (Part 1, Fig. 5) (Part 1, Fig. 9)
Fibromatosis colli
Fibrohistiocytic tumors Juvenile hyaline fibromatosis
Plexiform fibrohistiocytic tumor Inclusion body fibromatosis
Calcifying aponeurotic fibroma
(Part 1, Fig. 10)
Perivascular tumors Gardner fibroma
Myopericytoma, including infan- Desmoid fibromatosis (Part 1,
tile myofibroma (Part 1, Fig. 17) Fig. 11)
Lipofibromatosis (Part 1, Fig. 12)
Giant cell fibroblastoma (Part 1,
Fig. 13)
Dermatofibrosarcoma protruber-
ans (Part 1, Fig. 13)
Inflammatory myofibroblastic
tumor (Part 1, Fig. 14)
Infantile fibrosarcoma (Part 1,
Fig. 15)
Low-grade fibromyxoid sarcoma
(Part 1, Fig. 16)
EBV-associated smooth muscle NTRK-rearranged spindle cell
tumor neoplasm
Synovial sarcoma (Part 2, Fig. 9)
Epithelioid sarcoma (Part 2,
Fig. 10)
Alveolar rhabdomyosarcoma (Part Alveolar soft part sarcoma (Part 2,
2, Fig. 5) Fig. 11)
Spindle cell/ sclerosing rhabdo- Desmoplastic small round cell
myosarcoma tumor
Ectomesenchymoma Extrarenal rhabdoid tumor
Peripheral nerve sheath tumors Undifferentiated small round cell
sarcomas
Schwannoma Round cell sarcoma with EWSR1-
non-ETS fusions
Neurofibroma (Part 2, Fig. 6 and CIC-rearranged sarcoma
7)
Benign triton tumor/neuromuscu- Extraskeletal Ewing sarcoma
lar choristoma
Malignant peripheral nerve sheath Sarcoma with BCOR alterations
tumor (Part 2, Fig. 8) (Part 2, Fig. 12)

the International Society for the Study of Vascular Anoma-
lies (ISSVA) classification system, most recently updated in
2018, and summarized in Table 2 [3].
In part one of this two-part review, we discussed pediat-
ric tumor-like lesions, adipocytic tumors, fibroblastic and
myofibroblastic tumors, and perivascular tumors. In part
two, we focus on vascular lesions, fibrohistiocytic tumors,
muscle tumors, peripheral nerve sheath tumors, tumors of
uncertain differentiation, and undifferentiated small round
cell sarcomas.
lesion location or the vessel type that comprises the majority
of the lesion [4–6].
Vascular tumors are considered neoplastic, characterized
by increased proliferation of endothelial and other vascular
cells, while vascular malformations are congenital vascular
lesions, grow commensurately with the child, cannot invo-
lute, and have the ability to expand hemodynamically [5].
The ISSVA includes numerous tumors in their classifi-
cation (Table 2). We discuss selected subtypes of heman-
giomas, tufted angioma and kaposiform hemangioendothe-
lioma, as well as retiform hemangioendothelioma.

Vascular lesions Tumors

Vascular lesions can be separated into vascular tumors and Hemangiomas

vascular malformations, as divided in the classification
system of the International Society for the Study of Vas-
cular Anomalies (ISSVA), most recently updated in 2018,
and presented below [3]. Alternatively, the World Health
Organization classification does not differentiate between
vascular tumors and vascular malformations, and relies on
Hemangiomas are a benign proliferation of blood vessels,
often characterized by a rapid early proliferative stage and
a later involuting stage. In contrast, vascular malformations
arise from dysplastic vascular channels and exhibit normal
endothelial turnover, growing commensurate with the child

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Skeletal Radiology
Table 2  The International Society for the Study of Vascular Anoma-
lies classification of vascular tumors [3]
Benign vascular tumors
Infantile hemangioma
Congenital hemangioma
- Rapidly involuting
- Non-involuting
- Partially involuting
Tufted angioma
Spindle cell hemangioma
Epitheloid hemangioma
Pyogenic granuloma
Others
Locally aggressive or borderline vascular tumors
Kaposiform hemangioendothelioma
Retiform hemangioendothelioma
Papillary intralymphatic angioendothelioma (PILA), Dabska tumor
Composite hemangioendothellioma
Pseudomyogenic hemangioendothelioma
Polymorphous hemangioendothelioma
Hemangioendothelioma not otherwise specified
Kaposi sarcoma
Others
Malignant vascular tumors
Angiosarcoma
Epitheloid hemangioendothelioma
Others
and without regression, and represent an error of vascular
morphogenesis.
Infantile hemangiomas are the most common benign
tumor of childhood, occurring in up to 5% of infants [7–9].
This is a benign neoplasm of the endothelial cells [10]. They
grow rapidly during the first months of life, and regress
thereafter, typically achieving relative stability and some
degree of remnant scarring by 3–4 years of age [7]. At birth,
they are usually small and inconspicuous. They appear as a
subcutaneous bluish red mass resembling the surface of a
strawberry when involving the skin. A proliferative phase
occurs during the first year of life, where the tumor grows
rapidly, and represents a high-flow vascular tumor, as evi-
denced by a bruit, pulsatility, and warmth, and with a firm,
raised, and noncompressible lesion on examination. During
the involuting phase, which occurs over the next 1–5 years,
there is slow regression of what becomes a softer and more
pale tumor, and with complete regression often occurring
by 5–7 years [10].
Histologically, in the early proliferative phase, the infan-
tile hemangioma is made of hyperplastic endothelial cells
with increased numbers of mast cells, while during the invo-
lution phase, there is progressive perivascular deposition of
fibrofatty tissue and thinning of the endothelial lining [10].
On MRI, proliferating infantile hemangiomas are lobu-
lated and mass-like, isointense to muscle on T1-weighted
imaging, hyperintense on T2-weighted imaging, and with
central and peripheral flow vessels/voids. Diffuse enhance-
ment is present during this phase. Despite the high-flow
nature of the lesion, there is no arteriovenous shunting. Dur-
ing the involuting phase, infantile hemangiomas appear as
a heterogeneous mass with less contrast enhancement and
with areas of increased signal on T1 corresponding to fibro-
fatty deposition [10] (Fig. 1).
Conversely, the more rare congenital hemangioma is
noted at birth as a true mass (rather than just precursor
skin discoloration, which can be seen at birth in up to 30%
of infantile hemangiomas) or on pre-natal ultrasound and
can be divided into rapidly involuting (typically involutes
by 8–14 months), partially involuting, and non-involuting
based on biologic behavior over time [11]. Infantile and
congenital hemangiomas share similar imaging character-
istics, with failure of regression noted of the non-involuting
congenital hemangioma [10]. When compared to infantile
hemangiomas, congenital hemangiomas are more likely to
have calcifications, adjacent fat stranding, and less well-
defined borders [12].
The diagnosis of infantile and congenital hemangioma
is clinical—established by the appearance of raspberry-red
cutaneous stains with a sharp margin, typically not requiring
imaging or biopsy [13]. If biopsied, GLUT1 immunohis-
tochemical marker positivity is a distinguishing feature of
infantile hemangiomas [11]. For patients with unclear clini-
cal history and exam, greater than 5 cutaneous lesions, or
suspected associated anatomic abnormalities, imaging can
be helpful. Ultrasound with Doppler interrogation is gener-
ally preferred for imaging evaluation and MRI may also be
helpful in select cases [7].
Although most commonly seen in isolation within the
subcutaneous tissues, infantile hemangiomas can occur
in the context of PHACE (Posterior fossa and supratento-
rial brain malformations, Hemangioma of face and neck,
Arterial abnormalities, Cardiovascular defects, Eye abnor-
malities, supraumbilical raphe, and sternal clefts/defects) or
LUMBAR (Lower body infantile hemangiomas and other
cutaneous defects, Urogenital anomalies and ulceration,
Myelopathy, Bony deformities, Anorectal malformations,
Arterial anomalies, Renal anomalies) syndromes [7]. These
associations should be more strongly considered if multiple
are present, and with large (often greater than 5 cm)/seg-
mental lesions at facial (PHACE) or lumbosacral/perineal
locations (LUMBAR) [7]. For suspected syndromic cases,
MRI is the optimal imaging modality to define underlying
structural abnormalities and vascular components [7, 14]
(Fig. 2). When at least 5 cutaneous infantile hemangiomas
are present, screening ultrasound exam is recommended
by the American Academy of Pediatrics to evaluate for the
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 Skeletal Radiology

Fig. 1  Intramuscular heman-
gioma. 12-year-old female (A) (B)
with 2-day history of left knee
pain with concern for soft
tissue mass. Axial T1 (A),
T2-fat-suppressed (B), and
coronal T2-fat-suppressed
(C) MR images of the thigh
demonstrate a lobulated and
mass-like intramuscular lesion
isointense to muscle on T1
and hyperintense in signal on
T2 with linear and lacelike
areas of low or intermediate
interspersed signal intensity. (C)
There is subtle fat signal within
the periphery of the lesion on
the T1 sequence (arrow). The
mass was resected, and the
patient remained asymptomatic
for 5 years, at which time she (D)
experienced recurrent, mild,
localized pain at the site of the
lesion. Repeat MRI (D and E)
demonstrated recurrent heman-
gioma, as evidenced by a small
enhancing mass in the resection
bed (axial T1-fat-suppressed
images following intravenous
contrast administration with
arrow denoting enhancing
mass). Grossly (F), the mass
is ill defined and exhibits
spongy, yellow to red-brown
cut surfaces with variably sized
blood-filled cavities (arrows). (E) (F)
Microscopic examination (G)
demonstrates variably sized,
thin-walled, ectatic (*), and slit-
like (arrow) vessels infiltrating
between skeletal muscle fibers

(G)

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Skeletal Radiology
presence of hepatic infantile hemangiomas [7]. On ultra-
sound, congenital and infantile hemangiomas classically
show heterogenous echogenicity, hypervascularity, occa-
sional calcifications (more common in congenital heman-
giomas), and high-flow waveforms on Doppler interrogation
[12, 15]. In later phase involuting lesions, tortuous, com-
pressible channels with venous waveform on Doppler inter-
rogation become a dominant feature [16].
Rarely, congenital and infantile hemangiomas may be
complicated by potentially life-threatening airway obstruc-
tion, bleeding, and ulceration, as well as cardiac failure and
severe hypothyroidism (classically with liver lesions) [7].
The presence of prominent venous ectasia and venous lakes
on ultrasound was associated with these complications in
one small series [17].
Tufted angioma and kaposiform hemangioendothelioma
Tufted angioma and kaposiform hemangioendothelioma are
considered a spectrum of the same disease. Tufted angiomas
are characterized by superficial, dermal/subdermal, discrete
lobules of capillaries within dermal collagen. The involved
skin typically demonstrates violaceous patches and plaques
on physical exam. Kaposiform hemangioendothelioma tends
to involve deeper soft tissues, with ill-defined, coalescent
nodules of spindled endothelial cells and dilated lymphatic
channels with surrounding fibrotic stroma. Both entities
have a wide anatomic distribution. In combination, they are
responsible for most cases of the platelet-trapping syndrome
referred to as Kasabach-Merritt phenomenon, although this
is more frequently seen with kaposiform hemangioendothe-
lioma [5, 18–21].
Most cases present in children younger than 5 years, and
kaposiform hemangioendothelioma occurs most commonly
within the first weeks of life. On MRI, both tufted angiomas
and kaposiform hemangioendotheliomas have ill-defined/
irregular margins. Although it is not always present, a char-
acteristic “reticular” pattern of T1 iso-to-hypointense and
T2-hyperintense signal, reminiscent of the inflammatory
changes seen in the context of cellulitis, can help to distin-
guish kaposiform hemangioendothelioma from tufted angi-
oma on MRI [22, 23]. In addition, tufted angiomas are typi-
cally localized to less than 1 cm in maximum depth from the
skin surface, whereas kaposiform hemangioendothelioma
extends to more than 1 cm maximum depth from the skin
surface, often diffusely permeating the soft tissues without
respecting tissue planes [23]. Osseous involvement may be
present in cases of kaposiform hemangioendothelioma, and
vascular flow voids may be visualized on T2-weighted imag-
ing, with arterial feeding vessels and dilated draining veins
often apparent on MRA [5, 10, 23]. Both tufted angiomas
and kaposiform hemangioendotheliomas tend to be isoin-
tense to slightly hyperintense to muscle on T1, hyperintense
on T2-weighted imaging, and demonstrate enhancement fol-
lowing intravenous contrast administration [24].
Untreated lesions can partially regress but will recur, and
large lesions can be life threatening due to associated throm-
bocytopenia complications such as disseminated intravascu-
lar coagulation or visceral involvement. Medical treatment,
such as vincristine, steroids, or mTOR inhibitors (e.g., siroli-
mus), is typically initiated first line for Kasaback-Merritt
phenomenon. Wide local excision, when possible, can be
curative [25, 26]. Of note, differential considerations for the
tufted angioma/kaposiform hemangioendothelioma spec-
trum of disease include infantile fibrosarcoma and infantile
myofibromatosis (both discussed in Part 1)—large tumors
seen in infants that can both cause consumptive coagulopa-
thy, mimicking the Kasabach-Merritt phenomenon. Imaging
and clinical presentation cannot always reliably distinguish
these entities, and biopsy is often necessary if there is diag-
nostic dilemma, as there are therapeutic implications. Infan-
tile fibrosarcoma often harbors an NTRK gene fusion that
is targetable with selective inhibitors, as discussed in Part
1 of the manuscript and the “NTRK-rearranged spindle cell
neoplasm” section below.
Retiform hemangioendothelioma
Retiform hemangioendothelioma is an uncommon, locally
aggressive, rarely metastasizing vascular lesion most com-
monly involving the skin and subcutaneous tissue of the dis-
tal lower extremities of children and young adults [4, 27]. It
presents as a red/blue slow-growing nodule or plaque, and
on histopathology demonstrates arborizing branching vas-
cular channels with bland endothelial cells with prominent
nuclei. First-line treatment, when feasible, is wide local exci-
sion [27]. MRI features of this tumor in children have rarely
been reported. Typical lesions are centered at the level of
the superficial dermis/subcutaneous fat, and are described as
similar to other subtypes of hemangioendotheliomas—with
low to isointense signal on T1-weighted sequences, iso to
hyperintensity on T2-weighted sequences, and hypervascu-
larity on post-gadolinium sequences [28].
Vascular malformations
Vascular malformations represent congenital anomalies or
errors of development of the vascular system and are not
neoplasms. They are composed of dysplastic vessels with-
out cellular proliferation. They are thought to be a result of
errant vascular morphogenesis in utero with arrest of normal
vascular development and failed or incomplete resorption
of primitive vascular elements. There is a resultant imma-
ture non-involuted vascular structure, or vascular malfor-
mation. They can be divided into high-flow and low-flow
lesions based on hemodynamic characteristics at dynamic
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(B)
(A)

(C) (D)

(E)

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 Skeletal Radiology
◂ Fig. 2  LUMBAR syndrome with infantile hemangioma. 1-month-old
female, without any skin abnormalities at birth, developed redness
and ulceration in sacral area. Initially evaluated in the emergency
department, where an ultrasound (A) revealed a broad, heterogenous,
hypervascular mass along the gluteal cleft with high-flow spectral
waveforms on Doppler interrogation, suggestive of infantile heman-
gioma. Dermatology was consulted, and recommended an MRI of
the spine, abdomen, and pelvis with suspicion for associated struc-
tural abnormalities given the location of the lesion. MRI at 3 months
of age demonstrates a multilobulated lesion with interweaving low
signal and fatty septae, predominantly isointense on axial T1-fat-
suppressed images (B), hyperintense on axial T2-fat-suppressed
images (C), and avidly, homogeneously enhancing on axial T1-fat-
suppressed images following intravenous administration of gadolin-
ium contrast (D). The lesion spanned up to 4.5 cm within the super-
ficial subcutaneous fat and extended to the skin surface. In addition,
on sagittal T1-weighted images (E), a low lying spinal cord conus is
present, terminating at the L3 vertebral body level, with an associ-
ated intraspinal lipoma extending from the conus medullaris to the
thecal sac terminus. The right kidney (not pictured) was also noted
to be 1 cm asymmetrically smaller than the left, with abnormal pos-
teromedial rotation of its lower pole. The patient received propranolol
treatment for her presumed ulcerated infantile hemangioma, which
responded clinically with significant decrease in size. The patient
had normal neurologic exam on neurosurgery evaluation, and parents
deferred prophylactic de-tethering procedure, with plan to follow up
with repeat MRI in 2 years. The patient had no clinical manifestation
of the noted renal anomaly on nephrology consultation, with plan for
follow-up renal ultrasound to monitor kidney growth
time-resolved contrast-enhanced MR angiography. These
lesions are present at birth and grow commensurate with the
child. They do not spontaneously involute or regress [9, 29].
Distinguishing high from low flow has important clini-
cal implications, in that low-flow vascular malformations
are often treated with percutaneous sclerotherapy; however,
this approach is ineffective with high-flow lesions, where the
agents are rapidly washed away from the endothelial lining.
High-flow lesions are treated with transarterial embolization,
with possible surgical resection [10].
High‑flow vascular malformations
Arteriovenous malformation  The arteriovenous malforma-
tion contains a nidus comprised of an abnormal network of
tortuous and dysplastic vascular channels residing between
feeding arteries and draining veins, and without a normal
capillary bed [8, 9, 30, 31]. Shunting at the nidus results in
high blood flow across the lesion, and accounts for asym-
metric overgrowth, trophic changes due to ischemia from
arterial steal, hemorrhage, and high output cardiac failure.
On MRI, they demonstrate high flow, enlarged feeding
arteries and draining veins, which appear as tortuous signal
void patterns. There may be perilesional edema and adja-
cent tiny vessels creating the appearance of an ill-defined
mass, although the lesion is often nonmass like with tissue
infiltration that does not respect tissue planes. Numerous
interspersed punctate areas of high signal may be present
as a result of hemorrhage and thrombosis. There is early
enhancement with early venous shunting, in contrast to
venous malformations, which demonstrate delayed enhance-
ment and no venous shunting [9, 10, 30].
Arteriovenous fistula  Arteriovenous fistulas reflect a single
large vascular channel between artery and vein, either con-
genital, typically at the head and neck, or acquired, such as
with penetrating injury. On MRI, the arterial and venous
elements of the mass may be apparent as large signal voids,
without a well-defined mass [9].
Low‑flow vascular malformations
Venous  Venous malformations are the most common vas-
cular malformation, found at the head and neck, extremities,
and trunk [9, 30]. They are formed of dilated venous chan-
nels of varying sizes with a paucity of smooth muscle and
may show adventitial fibrosis, thrombi, and phleboli. They
may be small and localized or diffuse and infiltrating. They
may be isolated or multiple [10].
Venous malformations are soft, compressible, and non-
pulsatile. There is usually a bluish discoloration when they
involve the skin or subcutaneous tissues, but there is no
bruit or thrill. They expand with Valsalva and decompress
with elevation of the extremity or compression. While often
asymptomatic, there may be stiffness and discomfort from
hemorrhage with ecchymosis, thrombophlebitis, or hemar-
throsis. Peripheral lesions may lead to bone thinning, dem-
ineralization with possible pathologic fracture, and limb
underdevelopment. They may also cause skeletal hypertro-
phy or muscle contracture from infiltration of the malforma-
tion or secondary to sclerotherapy. Additionally, they may
cause muscle atrophy and subcutaneous fat prominence [10].
MRI demonstrates a lobulated septated lesion with low to
intermediate T1 and increased T2 signal, which correlates to
single or multiple venous lakes containing stagnant blood.
There is frequently interspersed fat within the lesion. Clas-
sically, they are infiltrating, nonmass-like lesions that do
not push borders and do not respect tissue planes. Venous
malformations often extend from the skin through the subcu-
taneous tissue and infiltrate muscle, bone, and joint compart-
ments. Their infiltrative and nonmass-like appearance helps
to distinguish from aggressive soft tissue tumors. Signal
voids are usually absent secondary to a lack of hypertro-
phied feeding arteries and enlarged draining veins. Those
voids that are occasionally present are related to thrombosed
vessels, phleboliths, or fibrous striations in cross section.
Hemorrhagic or proteinaceous content may cause fluid/
fluid levels within the mass. Dynamic contrast-enhanced
MR shows gradual delayed contrast filling without enlarged
arteries or arteriovenous shunting [10] (Fig. 3).
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 Skeletal Radiology

Fig. 3  Venous malformation.
9-year-old female with history (A) (B)
of developmental dysplasia of
the hip and with right knee pain.
Axial T1 (A), T2-fat-suppressed
(B), T1-fat-suppressed (C),
T1-fat-suppressed post intra-
venous gadolinium (D), and
sagittal T2-fat-suppressed (E)
MR images of the knee dem-
onstrate a large late-enhancing
intramuscular lesion with high
signal on T2 consistent with a
low-flow venous malformation.
This lesion is lobulated and sep-
tated, corresponding to venous
lakes containing stagnant (C) (D)
blood. It appears infiltrating and
nonmass-like, with distribu-
tion that does not respect tissue
planes, in contrast to hemangi-
oma. Microscopic examination
(F) demonstrates an aggregate
of abnormally dilated vascular
spaces with thin walls (arrow)

(E)

(F)

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Skeletal Radiology
Lymphatic  Although often referred to as a cystic hygroma or
lymphangioma, these are slow-flow vascular malformations,
and the suffix “-oma” should be reserved for lesions exhibit-
ing cellular proliferation [9]. Nevertheless, these terms are
seen ubiquitously throughout the literature and in clinical
practice, and have been used in sub-classifying descrip-
tion of this malformation. For instance, lymphangioma has
been described as a benign, localized collection of dilated
lymphatic channels, commonly seen in children, and often
in the context of somatic PIK3CA mutations [32]. When
multicentric or diffusely infiltrating across multiple tissue
planes or involving more than one organ, the same process
has been referred to as lymphangiomatosis. When located
superficially, these lesions have been labeled lymphangi-
oma circumscritum, and when involving deep tissues have
been referred to as cavernous lymphangioma [4]. “Cystic
hygroma” is a term that has been used to describe a large,
cystic lymphangioma in the neck, axilla, or groin of infants,
and can be seen in patients with Turner syndrome as well as
lethal karyotypes [33–35].
Lymphatic malformations are the result of sequestered
lymphatic sacs, and may be comprised of multiple small
cystic spaces or of larger cystic spaces, giving them their
MRI appearance, as a multiseptated cystic mass, hypoin-
tense on T1 and hyperintense on T2-weighted imaging. The
lesion may be more heterogenous depending on protein or
hemorrhage content. There may be enhancement of the septa
following contrast. Notably, in the microcystic form, the
individual cysts may not be perceptible. These lesions are
often seen in combination with other vascular malformations
[9, 30] (Fig. 4).
Although they most frequently occur in the head and
neck, they are also present elsewhere throughout the body
anywhere lymphatic vessels are present, including the lower
extremities [9, 30].
Capillary  Also referred to as port-wine stains, capillary
malformations are characterized by a collection of vascular
channels in the dermis, and diagnosis traditionally does not
require imaging. On MRI, the lesion is typically not per-
ceptible [9].
Combined  When vascular malformations are comprised
of more than one type of vessel wall, they are considered
combined type.
Fibrohistiocytic tumors
Plexiform fibrohistiocytic tumor
Plexiform fibrohistiocytic tumor is a rare neoplasm centered
at the dermal-subcutaneous junction that typically presents
in the limbs of children and young adults and rarely metasta-
sizes [36, 37]. It typically presents as a slow-growing, poorly
defined plaque or nodule measuring up to 3 cm [37]. On his-
topathology, plexiform architecture, nodules of histiocytoid
epithelioid cells and osteoclast-like giant cells, and fasci-
cles of myofibroblastic spindle cells are seen [4]. On MRI,
tumors are plaque like or infiltrative in morphology, isoin-
tense on T1-weighted imaging, hyperintense on T2-weighted
imaging, and enhance on T1-weighted fat-suppressed images
following administration of intravenous gadolinium [38].
Treatment is surgical resection.
Muscle tumors
EBV‑associated smooth muscle tumor
Epstein-Barr virus (EBV)–associated smooth muscle tumors
are a new classification within the WHO’s 5­ th edition [4].
Although they are seen across a wide age range, they merit
discussion in the pediatric population, where they can be
seen in patients with primary immunodeficiency, post-
transplant, or HIV/AIDS who have EBV infection [39,
40]. These tumors demonstrate smooth muscle differentia-
tion on pathology, distinguishing them from EBV-positive
lymphoproliferative disorders, as well as EBV-encoded
small RNA (EBER) positivity, and both can occur months
to years after the onset of immunodeficiency or transplant.
EBV-associated smooth muscle tumors can occur anywhere
in the body including the skin and subcutaneous soft tis-
sues, although are most commonly seen in the liver in post-
transplant patients. The tumors are often multicentric, and
range in size from below 1 cm to over 20 cm. Prognosis
depends on the condition of the patient’s immune system.
Imaging description of these rare tumors in the pediatric
population is limited. On MRI, one review of 29 pediat-
ric cases identified EBV-associated smooth muscle tumors
in the liver of a post-kidney transplant 11-year-old-boy as
circumscribed, hypointense on T1-weighted images, hyper-
intense on T2-weighted images, and with peripheral “rim”
enhancement on T1-weighted fat-suppressed images post
intravenous gadolinium administration in portal venous
phase [41]. This appearance is non-specific, and notably
similar to described MRI characteristics of EBV-associated
lymphoproliferative disease and other malignancies [42].
Fetal rhabdomyoma
Fetal rhabdomyoma is a rare, benign neoplasm comprised
of immature skeletal muscle fibers that occurs in associa-
tion with basal cell nevus syndrome due to loss-of-function
mutations in the tumor suppressor gene PTCH1 [43]. Car-
diac rhabdomyomas, as are classically seen in the context
13
 Skeletal Radiology

Fig. 4  Lymphatic malforma-
tion with hematoma. 9-year-old (A)
female with expanding soft
tissue mass at the left clavicle
after being hit by a ball to
the region. Ultrasound (A)
demonstrates a heterogenous
multiseptated mass with internal
echogenic material. Frontal
radiograph (B) demonstrates
a soft tissue density overlying
the mid clavicle (arrow). Axial
T1-fat-suppressed (C), T2-fat-
suppressed (D), and T1-fat-
suppressed post intravenous
gadolinium (E) MR images (B)
of the clavicle demonstrate a
non-enhancing multiloculated
mass with heterogenous signal
and fluid–fluid levels related to
internal hemorrhage. Grossly
(F), the specimen is red-brown
and focally surrounded by
muscle (*). Sectioning reveals
a multiloculated cystic cavity
(arrow) containing a small
amount of blood and sur-
rounded by muscle and fibrous
tissue. Microscopic examina-
tion (G) demonstrates vascular
channels lined by a monolayer (C) (D)
of bland endothelial cells that
display oval, hyperchromatic
nuclei (arrow) and overlie a
fibrous wall with focal hemor-
rhage (*)

(E)

(F) (G)

13
Skeletal Radiology
of tuberous sclerosis, are classified separately by the WHO
[4]. Fetal rhabdomyomas are typically slow-growing, pain-
less masses, affect children with mean age of 2.1 years, and
have a postauricular predilection [4]. On MRI, they gen-
erally demonstrate isointense signal to muscle on T1- and
T2-weighted imaging and enhance on T1-weighted fat-
suppressed images following administration of intravenous
contrast [44].
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common soft tissue sarcoma
in children, arising from primitive, undifferentiated mesen-
chymal cells committed to develop into striated muscle.
Almost all pediatric cases are of the alveolar or embryonal
subtypes, and a minority of cases involve the spindle cell/
sclerosing subtype, which was added to the WHO’s ­5th edi-
tion classification. Spindle cell/sclerosing rhabdomyosar-
coma also has three new subtypes, on the basis of genetic
abnormalities: (1) congenital spindle cell with VGLL2/
NCOA2/CITED2 rearrangements (favorable prognosis),
(2) MYOD1-mutant spindle cell/sclerosing, (3) intraosse-
ous spindle cell RMS with TFCP2/NCOA2 rearrangements
[4, 45]. The pleomorphic variant occurs almost exclusively
in adults. The two most common subtypes of rhabdomyo-
sarcoma in pediatric patients have distinct anatomic predi-
lections, syndromic associations, and genetic alterations.
While the embryonal type most commonly occurs in the
head and neck, retroperitoneum, and genitourinary tract,
the alveolar type has a predilection for the extremities and
trunk [1, 46–49]. Embryonal rhabdomyosarcoma is associ-
ated with several syndromes that involve the RAS signaling
pathway, including neurofibromatosis type 1 (NF1), Noo-
nan syndrome, and Costello syndrome, and has also been
reported in Beckwith-Wiedemann syndrome (dysregulation
of the 11p15.5 region), DICER1 syndrome (specifically
uterine embryonal rhabdomyosarcoma), and Li-Fraumeni
syndrome (TP53 mutations) [50]. On molecular analysis of
rhabdomyosarcomas, FOX01 gene fusion is typically seen
in alveolar rhabdomyosarcoma, and helps to distinguish this
subtype from the embryonal subtype [4].
MRI features are nonspecific, with low or intermediate
signal on T1, intermediate to high signal on T2-weighted
imaging, and with variable enhancement following intrave-
nous contrast. There are often areas of necrosis which appear
hyperintense on fluid-sensitive sequences. Prominent high-
flow vessels may be present in the alveolar subtype [46–48,
51] (Fig. 5).
Ectomesenchymoma
Ectomesenchymoma is an exceedingly rare composite
tumor with elements resembling rhabdomyosarcoma as
well as neuroblastic tumors. Of the approximately 50 cases
reported, most affected patients are infants and children
[4, 52]. This tumor has been reclassified from a periph-
eral nerve sheath tumor to a skeletal muscle tumor in the
2020 WHO classification as trisomies of chromosomes 2,
8, and 11, and frequent HRAS mutations suggest that the
tumor is more closely related to rhabdomyosarcoma than
to a neural crest neoplasm [53]. Most commonly involved
sites include the pelvis, intra-abdominal, and retroperito-
neal soft tissues, although reported anatomic distribution
is widespread. On MRI, these masses are reported to be
hypointense on T1-weighted images, heterogeneous on
T2-weighted images, and show patchy contrast enhance-
ment [54]. Patients are treated with multimodality strate-
gies, including rhabdomyosarcoma protocols, with com-
parable outcomes [52, 55].
Peripheral nerve sheath tumors
Schwannoma
Schwannoma, also known as neurilemoma, is a benign,
encapsulated nerve sheath tumor comprised of neoplastic
Schwann cells [4, 46]. Most cases are diagnosed in the third
to fifth decades [56]. Schwannomas tend to be solitary and
present as a slow-growing, solitary, sporadic, painless mass
in 90% of cases. Patients with neurofibromatosis type 2
(NF2) or schwannomatosis often develop multiple schwan-
nomas related to underlying somatic NF2 mutation or often
other germline chromosome 22 mutations [57]. In addition
to occurring along the flexor aspects of the upper and lower
extremities, schwannomas commonly occur along the spinal
and sympathetic nerve roots of the head and neck, classically
from the vestibular division of the bilateral ­8th cranial nerves
in NF2, and can also affect the posterior mediastinum and
retroperitoneum [29, 46].
Schwannomas are histologically eccentric and separate
from the nerve, which is why they are surgically excisa-
ble from the nerve [29, 46]. They are often nonspecific on
MRI, hypointense on T1, and hyperintense on T2-weighted
imaging, with variable contrast enhancement [29]. Large
“ancient” schwannomas may undergo cystic degeneration
and show areas of hemorrhage, necrosis, and calcification
[58]. Plexiform schwannomas are comprised of more infil-
trative or thinly separated nodules that appear more conflu-
ent on MRI, and are seen most commonly sporadically but
have also been reported in patients with NF2 and schwanno-
matosis, and tend to come to clinical attention in childhood
or at birth [59, 60]. Schwannomas rarely undergo malignant
transformation [46]. See further description of overlapping
MR imaging features in the “Neurofibroma” section below.
13
 Skeletal Radiology

Fig. 5  Alveolar rhabdomyosar-
(A) (B)
coma. 3-year-old female with a
palpable lump in her right lower
leg. Axial T1 (A), T2-fat-sup-
pressed (B), T1-fat-suppressed
(C), T1-fat-suppressed post
intravenous gadolinium (D),
and coronal T2-fat-suppressed
(E) MR images through the leg
demonstrate a large intramus-
cular T1 hypointense and T2
hyperintense lesion (arrows)
with avid enhancement on
post-contrast imaging within the (C) (D)
posterolateral lower leg. Grossly
(F), the tumor is well circum-
scribed and displays a tan-
white, firm, and nodular cut sur-
face. The tumor is surrounded
by tan-brown skeletal muscle
(arrow). Microscopic examina-
tion (G) reveals monotonous,
rounded tumor cells arranged
in solid and alveolar nests, with
evidence of skeletal muscle
infiltration (arrow). Molecular
evaluation by FISH showed (E) (F)
evidence of FOXO1 rearrange-
ment supporting the diagnosis
of alveolar rhabdomyosarcoma
(not shown)

(G)

13
Skeletal Radiology
Neurofibroma
The neurofibroma is also a benign peripheral nerve sheath
tumor consisting mainly of Schwann cells [4, 46]. Neurofi-
bromas are most commonly sporadic and solitary (cutaneous
or deeper nerves affected), but can also be diffuse (subcu-
taneous nerves of the head and neck affected), or plexiform
(diffuse tumor extending along branches of a nerve) [29, 30,
46]. In 10% of cases, neurofibromas are seen in the context
of NF1. Most patients with NF1 exhibit neurofibromas in
childhood, before the age of 20 years, while sporadic neu-
rofibromas tend to affect young adults [56]. Multiple neurofi-
bromas and plexiform neurofibromas almost always occur in
the context of NF1 [56].
NF1 patients have also been found to develop a newly
WHO-classified subtype of neurofibroma termed atypical
neurofibroma/atypical neurofibromatous neoplasm of uncer-
tain biological potential. This subtype is associated with
specific genetic deletions and at least two of the following:
cytological atypia, hypercellularity, and/or loss of neurofi-
broma architecture, < 1.5 mitoses/mm^2. They are consid-
ered premalignant or early malignant stage falling short of
diagnostic criteria for malignant peripheral nerve sheath
tumor, but at risk for progression to this tumor [53, 61–64].
The neurofibroma is intermixed with and inseparable
from the nerve; therefore, surgical excision must include the
parent nerve [29, 46]. Similar to the schwannoma, neurofi-
bromas exhibit often nonspecific imaging features on MRI,
hypointense on T1, hyperintense on T2-weighted imaging,
and with variable intravenous contrast enhancement [29].
Plexiform neurofibromas are usually large at presentation
with a multilobulated appearance and with diffuse thicken-
ing of the involved nerve and its branches [56] (Fig. 6).
Although often nonspecific on MRI, both schwannomas
and neurofibromas may exhibit several characteristic signs.
These include the “fascicular sign” (multiple small ring-like
structures with peripheral higher signal intensity represent-
ing fascicular bundles on T2-weighted imaging), “split fat
sign” (the lesion is surrounded by a rim of fat), “string sign”
(entering and exiting nerve roots are apparent at both ends
of the lesion), and “target sign” (high signal peripheral rim
related to myxomatous tissue and lower signal central zone
on T2 related to fibrocollagenous signal; notably, the fibro-
collagenous tissue will enhance following contrast admin-
istration) ([29, 46] (Fig. 7).
Benign triton tumor/neuromuscular choristoma
Benign triton tumor/neuromuscular choristoma is an
extremely rare intraneural proliferation of mature skeletal
muscle interposed with nerve fibers of the endoneurium
that presents mostly in infancy or childhood, and classi-
cally involves the sciatic nerve or brachial plexus [65–67].
Patients often have progressive pain or peripheral neuropa-
thy, including atrophy of the limb involved, and superim-
posed desmoid fibromatosis is seen in up to 80% of cases
[65, 66]. Most reported cases of neuromuscular choristoma
have been described in the presence of CTNNB1-mutated
fibroblasts/myofibroblasts, similar to sporadic desmoids
[65].
On MRI, neuromuscular choristoma manifests as fusiform
enlargement of the associated nerve, T1- and T2-weighted
sequence signal isointense to muscle, typically with less
than 50% intralesional fat (helping to distinguish from lipo-
matosis of the nerve), and with minimal enhancement on
post-gadolinium T1-weighted fat-suppressed sequences.
More hypointense T1- and T2-weighted signal, as well as
more avid contrast enhancement, is seen as superimposed
fibromatosis component increases [67, 68].
Malignant peripheral nerve sheath tumor
Malignant peripheral nerve sheath tumors are of neuroec-
todermal origin, often arising in benign plexiform neurofi-
bromas, but can occur in preexisting isolated neurofibromas.
While the lifetime risk of developing a malignant periph-
eral nerve sheath tumor is 0.001% in the general population,
those with NF1 have an 8–26% risk [46, 47].
The question of whether malignant degeneration of a
peripheral nerve sheath tumor has occurred is answered
correctly clinically approximately 72% of the time. Factors
that are associated with malignant transformation include
increasing size, large size, persistent pain, neurologic defi-
cits, location deep to the fascia, or within an extremity [46,
47].
On MRI, factors that suggest malignant peripheral nerve
sheath tumor include tumor growth, central cystic changes
often caused by necrosis or hemorrhage, peripheral contrast
enhancement, and a feathery perilesional edema. Although
potentially only meaningful in those with NF1, intralesional
heterogeneity on T1-weighted imaging may correlate with
malignancy [46, 47, 69]. These tumors are often nonspecific
in appearance otherwise iso to slightly hyperintense to mus-
cle on T1, and heterogeneously hyperintense on T2-weighted
imaging. In a study by Wasa et al., the authors found four
statistically significant MRI features that helped to dis-
tinguish a malignant peripheral nerve sheath tumor from
a neurofibroma: increased largest dimension of the mass,
presence of peripheral enhanced pattern, presence of per-
ilesional edema-like zone, and presence of an intra-tumoral
cystic lesion [70] (Fig. 8).
However, both benign and malignant lesions have over-
lapping clinical manifestations, and morphologic imaging
cannot reliably differentiate benign from malignant trans-
formed lesions, in particular in tumors with heterogeneity.
Conversely, PET can be used as an imaging discriminator
13
 Skeletal Radiology

Fig. 6  Plexiform neurofi-
broma. 16-year-old female with (A) (B)
history of neurofibromatosis
type 1 and leg mass. Axial T1
(A), T2-fat-suppressed (B),
T1-fat-suppressed (C), T1-fat-
suppressed post intravenous
gadolinium (D), and sagittal
T1-fat-suppressed post-gado-
linium (E) MR images through
the foot demonstrate a large,
ill-defined, infiltrative het-
erogeneously enhancing lesion
with heterogenous signal on
T1 and T2 imaging, consistent
with plexiform neurofibroma,
involving the superficial and
deep soft tissues of the left
(C) (D)
lower extremity (*). On gross
examination (F), the mass is
rubbery with a fibrous, tan-
grey cut surface. Microscopic
examination (G) demonstrates a
diffuse and haphazard prolifera-
tion of loosely arranged spindle
cells with small, wavy nuclei
(arrows) in a myxo-collagenous
stroma. The lesional cells have
benign cytologic features and
lack significant mitotic activity

(E) (F)

(G)

13
Skeletal Radiology
Fig. 7  Plexiform neurofibroma with target sign. 17-year-old male
with history of neurofibromatosis type 1 and painful mass at the
popliteal fossa. Axial T2-fat-suppressed MR image through the knee
demonstrates a lobulated mass within the posterior soft tissues of the
knee. Many of the rounded components of the mass that comprise the
tumor exhibit a hyperintense T2 halo, with central hypointense sig-
nal, compatible with the target sign described with peripheral nerve
sheath tumors
for benign neurofibroma and malignant peripheral nerve
sheath tumor in those with NF1 utilizing a combination
of qualitative and quantitative assessment, with an under-
standing that rare false positive and false negative results
will occur (Fig. 8). Additionally, diffusion-weighted imag-
ing-derived parameters for differentiation of benign from
malignant peripheral nerve sheath tumors in the context of
NF1 have demonstrated improved sensitivity and specific-
ity compared with evaluation of morphologic MRI features
[71, 72].
Tumors of uncertain differentiation
NTRK‑rearranged spindle cell neoplasm
NTRK-rearranged spindle cell neoplasm (emerging) is a new
entity described in the 2020 WHO classification within the
category of tumors of uncertain differentiation. A growing
body of literature has recognized “variant” NTRK rear-
rangements in a subset of pediatric mesenchymal tumors
[53, 73–76] (Table 3). These genetic variations differ from
the “classic” EVT6-NTRK fusion that is commonly seen
in infantile fibrosarcoma, which was discussed in Part 1,
but otherwise share many similar clinicopathologic features.
“Classic” and “variant” NTRK-rearranged tumors are most
commonly seen in children less than 2 years old but can
present through adolescence. Both tumor subtypes tend
to occur in the extremities and the trunk but can affect the
viscera. On pathology, both tumor subtypes have a similar
morphologic pattern of haphazardly arranged primitive cells
in variably myxoid stroma and/or spindled cells arranged in
fascicles [74].
Some of the cases described in series of NTRK variant
tumors including children have had clinicopathologic simi-
larities to lipofibromatosis, dermatofibrosarcoma protuber-
ans, and peripheral nerve sheath tumors. MRI features of
these tumors are only just emerging in the published litera-
ture. In one case described as lipofibromatosis-like neural
tumor, the tumor showed predominant T1 signal isointensity,
internal fat signal (unlike typical descriptions of dermatofi-
brosarcoma protuberans), and predominant T2 hyperinten-
sity [74–79].
Recognition of NTRK translocations has clinical impor-
tance, as aberrantly expressed oncogenic receptor tyrosine
kinases in NTRK-rearranged neoplasms are medically tar-
getable. Recent clinical trials have shown promising results
for larotrectinib therapy in pediatric patients with NTRK-
rearranged tumors [79].
Synovial sarcoma
Synovial sarcoma is the most common non-rhabdomyo-
sarcomatous soft tissue sarcoma in children, and the sec-
ond most common malignant soft tissue tumor in pediatric
patients [1, 46–48]. Despite the name, the tumor does not
arise from synovium, but from primitive mesenchymal tissue
and is named for its histologic resemblance to synovium.
Synovial sarcoma is often characterized on molecular
pathology by a specific SS18-SSX1/2/4 fusion gene [80].
The lesion often occurs near joints, particularly the popliteal
fossa [29, 46, 81]. The tumor can occur at any age, but most
commonly occurs in adolescence [81].
The MRI appearance is variable, with the most com-
mon appearance being a heterogeneous multilocular, well-
defined, cystic-appearing lesion with internal septations.
Fluid–fluid levels as a result of layering blood products are
common. Margins are typically sharp, but larger lesions
may be ill defined and infiltrative. As with other sarcomas,
the lesion is usually isointense to muscle on T1, heteroge-
neously isointense or hyperintense to subcutaneous fat on
T2-weighted imaging, and with heterogeneous intravenous
contrast enhancement. Notably, the lesion may appear
deceptively benign (small, homogeneous, well defined, and
13

(A)
(C)
(E)
(F)
Fig. 8  Malignant peripheral nerve sheath tumor arising from a plexi-
form neurofibroma. 12-year-old female with neurofibromatosis type
1 and increasingly painful left groin mass. Axial T1 (A), T2-fat-sup-
pressed (B), T1-fat-suppressed (C), T1-fat-suppressed post intrave-
nous gadolinium (D), and coronal T1-fat-suppressed post intravenous
gadolinium (E) MR images through the pelvis and upper thighs dem-
onstrate a large heterogenous T2 hyperintense and T1 isointense left
pelvic mass extending into the thigh through the femoral canal, asso-
ciated with the left femoral nerve. The mass was increasingly pain-
ful and resides within deep soft tissues, including the pelvis. FDG/
PET image through the intrapelvic portion of the mass (F) demon-
strates an FDG avid mass along the left pelvis, with excreted tracer
with a growth pattern that displaces rather than infiltrates
adjacent structures). Fifty percent are contiguous with bone
and 21% exhibit cortical thinning or medullary invasion [29,
46–48, 81] (Fig. 9).
Several features may aid in making a prospective imag-
ing diagnosis. These imaging features include the pres-
ence of dystrophic calcification, fluid–fluid levels as a
result of intralesional hemorrhage (18%), hemorrhage
13
Skeletal Radiology
(B)
(D)
within the urinary bladder. On gross examination (G), the soft tis-
sue mass displays a multinodular cut surface that ranges from soft,
white, and glistening (*) to firm, yellow-white, and gelatinous (**).
The mass abuts the peripheral inked margin (arrow). Low-power
view (H) shows a plexiform neurofibroma with multiple nerve fas-
cicles expanded by the tumor, leading to a multinodular appearance
(*). There is one dominant nodule (**). High-power view (I) of this
dominant nodule demonstrates increased cellularity and nuclear pleo-
morphism (arrow) suggesting transformation to malignant peripheral
nerve sheath tumor. The tumor cells were positive for S100 and dis-
played increased Ki-67 index
which appears bright on T1- and T2-weighted imaging
(present in over 40%), triple-signal intensity (areas hyper-
intense, isointense, and hypointense relative to fat as a
result of hemorrhage, fibrous tissue, and cystic and solid
regions; present in 35%), a “bowl of grapes sign” which
describes large cystic areas with prominent hemorrhagic
foci, and a relative lack of T2-weighted hyperintensity
[29, 46–48, 81].
Skeletal Radiology

(G) (H)

(I)

Fig. 8  (continued)

Table 3  NTRK rearrangements in pediatric soft tissue tumors
Genetic rearrangement Tumor nomenclature
“Classic” (ETV6-NTRK fusion) Infantile fibrosarcoma
“Variant” (Non-ETV6-NTRK fusion) Lipofibromatosis-like
neural tumors
Tumors resembling
peripheral nerve sheath
tumors
Spindle cell tumors
Epithelioid sarcoma
Epithelioid sarcoma was first recognized in 1970 as a dis-
tinct tumor with multidirectional differentiation, predomi-
nately epithelial, but of uncertain histogenesis. Since that
time, the histomorphopathology, immunophenotype, and
ultrastructure suggest it is of mesenchymal origin. The
tumor is rare, with variable biologic behavior, accounting
for less than 1% of all soft tissue tumors [82]. It consists of a
multinodular proliferation of spindle-shaped and epithelioid
cells, typically characterized by a deletion on chromosome
22 resulting in almost complete loss of SMARCB1 (INI1)
nuclear protein expression [4]. Notably, the tumor manifests
as a painless, slow-growing mass that may have been present
for a long period of time, simulating a benign, inflammatory
process [47].
Pathologically, the tumor has been classified as either
classic type (previously, distal type) or proximal type. The
classic type often arises in extremities, such as the arm and
hand, as subcutaneous or deep soft tissue nodules with pos-
sible ulceration. The proximal type has been described to
occur more commonly in older adults. These tumors have
a high recurrence rate and a poor prognosis in those with
distant metastases, with a median survival of 8 months [82].
Epithelioid sarcoma occurs most often during adoles-
cence, has a male predominance, and is the most common
soft tissue sarcoma of the wrist and hand. The smaller
lesions may be well circumscribed or ill defined. Larger
lesions are often multilobulated. Collectively, tumor mar-
gins are frequently lobulated and infiltrative, and the tumor
is often partially or predominately necrotic in appearance.
Peritumoral edema/increased T2 signal is a common find-
ing on MRI, and reportedly correlates with the histologic
finding of an intense inflammatory response and/or edema
about the tumor. Lesions can arise in superficial or deep
soft tissues, with a propensity to spread along fascial planes,
aponeuroses, and tendon sheaths. Hemorrhagic necrosis may
result in increased T1-weighted signal, and T2 signal is often
heterogeneous. Contrast enhancement is also heterogenous,

13
 Skeletal Radiology

Fig. 9  Synovial sarcoma.
16-year-old female with a (A) (B)
one-year history of an increas-
ingly painful left hip, and
recent palpable mass. Axial
T1 (A), T2-star-fat-suppressed
(B), T1-fat-suppressed (C),
and T1-fat-suppressed post
intravenous gadolinium (D)
MR images through the left
hip demonstrate a well-circum-
scribed mass within the superfi-
cial soft tissues adjacent to the
left femoral greater trochanter.
The periphery of the mass
exhibits increased T1 signal
compatible with blood products. (C) (D)
Centrally, there is a soft tissue
component that appears hypoin-
tense on T1, hyperintense on
T2, and with enhancement
following intravenous contrast
administration. The patient
had image-guided biopsy with
pathology consistent with
synovial sarcoma, which was
later resected

depending upon cellularity and degeneration. Overall, the
MRI appearance can be quite variable, and is nonspecific.
[46, 47, 82] (Fig. 10).
Alveolar soft part sarcoma
The alveolar soft part sarcoma is rare and of uncertain cell
origin, characterized by a specific chromosomal translo-
cation that results in ASPSCR1-TFE3 gene fusion [47].
Although the exact histogenesis is unknown, the name is
derived from the presence of nests of eosinophilic cells
that contain abundant precrystalline cytoplasmic granules
organized in a fashion-resembling respiratory alveoli, and
separated by a rich vascular blood supply [46]. The tumor
primarily affects adolescents and young adults, mainly in the
trunk and lower extremities [46, 83, 84].
It is well circumscribed on MRI, and, unlike many other
soft tissue sarcomas, exhibits moderate to high signal inten-
sity on T1-weighted imaging potentially related to an abun-
dance of slow capillary blood flow through tumor vessels.
The tumor is heterogenously hyperintense on T2-weighted
imaging with moderate to intense contrast enhancement
(Fig. 11). Notably, dilated vessels in and around the lesion
may be present with associated serpentine flow voids. A
prominent feeding artery and draining vein may be present,
which may mimic an arteriovenous malformation, rhabdo-
myosarcoma, or fibrosarcoma [46, 47, 83, 84].
Target lesions may be present within the tumor associ-
ated with nodular/lobular internal architecture, in which
there are components of the tumor that appear peripherally
hyperintense surrounding a centrally hypointense focus on
T2-weighted imaging (Fig. 11). These target lesions tend to
be small, multiple, and similar in size. This helps to distin-
guish them from the “target signs” described with peripheral
nerve sheath tumors which are larger and variable in size
[84].
Desmoplastic small round cell tumor
Desmoplastic small round cell tumor is characterized by
nests of small round cells on a desmoplastic stroma, spe-
cific immunocytochemical staining, and commonly EWSR1-
WT1 gene fusion [85, 86]. It primarily arises in children
and young adults with widespread abdominal and peritoneal
involvement. Location outside the abdominal cavity is rare,
but cases involving the thoracic cavity, paratesticular region,
head and neck, limbs, kidney, and brain have been reported
[87–89].
Although computed tomography is typically the pre-
ferred imaging modality for both diagnosis and follow-up,

13
Skeletal Radiology
(A)
(B)
(D)
(C)
(E)
Fig. 10  Epithelioid sarcoma. 13-year-old male presented with left
foot and ankle swelling for 3  years with intermittent pain. Axial
T2-fat-suppressed (A) and sagittal T1-weighted (B) MR imaging
demonstrate a rounded mass along the extensor tendons that appears
hypointense on T1 and hyperintense on T2. There is surrounding
soft tissue increased T2 signal and regional marrow signal changes.
Complete resection was required for the diagnosis of epithelioid sar-
coma. 12-month follow-up MRI (C) demonstrates recurrence with
a peripherally enhancing mass present on the sagittal T1-weighted
fat-suppressed sequence following intravenous gadolinium. Disease
recurrence was resected and radiated. Follow-up PET/CT at 6 months
demonstrates locally recurrent (D) and metastatic (E) disease that is
FDG avid
MRI is also employed on occasion. In both instances, the
tumor typically manifests as multiple bulky masses scat-
tered throughout the abdominal cavity, without a clear
parenchymal organ of origin, and with a dominant mass in
the rectovesical or rectouterine pouch [90–93]. On MRI,
(A) (B)
(C) (D)
Fig. 11  Alveolar soft part sarcoma. 12-year-old male with an enlarg-
ing right thigh mass over several months. On MRI, the mass is pre-
dominately, slightly hyperintense to muscle on axial T1-weighted
imaging (A), demonstrates a predominantly hyperintense, sharply
circumscribed appearance on T2-fat-suppressed images (B), with a
few, thin, low signal internal septations and punctate foci. The mass
enhances avidly on axial T1-weighted fat-suppressed images follow-
ing administration of intravenous gadolinium contrast (C). On the
sagittal T2-weighted fat-suppressed image, there are multiple small,
relatively uniformly sized internal nodules/tumor lobules, and small
target lesions with bright periphery and dark centers (D). The patient
underwent excisional biopsy, and pathology was consistent with alve-
olar soft part sarcoma, with re-excision achieving negative margins.
The patient has since been observed for 5 years without evidence of
recurrence
desmoplastic small round cell tumors are heterogeneous
to isointense on T1-weighted images (patchy foci of inter-
nal T1 hyperintensity may reflect internal tumoral hemor-
rhage or necrosis), typically heterogeneously hyperintense
on T2-weighted images (with low T2 areas corresponding
to more cellularly dense desmoplastic response), and have
heterogeneous enhancement following administration of
intravenous gadolinium contrast [90, 94–97].
Extrarenal rhabdoid tumor
Extrarenal rhabdoid tumor is an exceedingly rare, highly
malignant neoplasm that is predominantly seen in infants
and children. It is characterized by primitive undifferenti-
ated or rhabdoid cell morphology, and typically has loss of
expression of the SMARCB1 gene [98]. The tumor seems
to arise most commonly in deep midline locations—such as
the neck, paraspinal region, abdominal and retroperitoneal,
13

pelvic and perineal locations [99–102]; however, reported
anatomic distribution is widespread and includes extrarenal
viscera, most commonly the liver [103, 104]. Regardless of
tumor location, patient outcomes are poor, with reported
overall 5-year survival rate of < 15% [105, 106].
On MRI, extrarenal rhabdoid tumors demonstrate hypo-
to isointense signal on T1-weighted images, heterogeneously
hyperintense signal on T2-weighted images, enhancement
on T1-weighted fat-suppressed images following intravenous
gadolinium contrast administration, and sometimes with low
signal central regions corresponding to areas of necrosis or
hemorrhage [51, 107, 108].
Undifferentiated small round cell sarcomas
Advances in knowledge of the genetic alterations of pre-
viously described “undifferentiated round cell sarcomas”
have led the WHO to create a new chapter in their 2020
classification covering “undifferentiated small round cell
sarcomas of bone and soft tissue tumors.” This new cat-
egory includes Ewing sarcoma (previously classified as a
miscellaneous tumor of bone) as well as the entities listed
in Table 1, and of these we discuss extraskeletal Ewing sar-
coma and sarcoma with BCOR genetic alterations in greater
detail below. Although seen at all ages, round cell sarcoma
with EWSR1-non-ETS fusions is a rare tumor that even
more rarely manifests within the soft tissues, rather than
bone [109]. CIC-rearranged sarcomas similarly can present
in all age groups, but have a predilection for young adults,
with < 25% of cases seen in children [110]. CIC-rearranged
sarcomas are highly aggressive and frequently metastasize to
the lungs, with significantly worse 5-year survival rate than
Ewing sarcoma [111].
Extraskeletal Ewing sarcoma
Ewing’s sarcoma is a malignant small, round blue cell tumor
associated with FET-ETS fusion genes that is most com-
monly seen in patients less than 20 years of age [112]. In
about 12% of cases, the tumor is extraosseous—arising in
soft tissue as opposed to bone, with a wide anatomic distri-
bution [113]. MRI demonstrates a well-circumscribed mass
iso or hypointense to muscle on T1-weighted images, hetero-
geneously hyperintense on T2-weighted images, with vari-
able enhancement on T1-weighted fat-suppressed images
following intravenous administration of gadolinium contrast.
There may be regions of internal hemorrhage with intrinsic
T1-weighted hyperintensity, as well as internal fluid lev-
els. Focal areas of necrosis appear low on T1 and high on
T2-weighted imaging. Serpentine high-flow vascular chan-
nels, exhibiting low signal on conventional pulse sequences,
are frequently present [46, 47, 114–116].
13
Skeletal Radiology
Sarcoma with BCOR alterations
Relatively recently, several rare subsets of primitive
round cell sarcomas have been identified with BCOR
genetic alterations on immunohistochemical testing,
and are now given their own classification by the WHO
[4]. These include BCOR gene fusions, most commonly
BCOR-CCNB3 which is typically seen in patients less
than 20 years old, as well as sarcomas with BCOR-internal
tandem duplication and primitive myxoid mesenchymal
tumors of infancy that occur within the first year of life
and may be present at birth [117–120]. BCOR-CCNB3
sarcomas are relatively evenly spread between bone and
soft tissue origin, most commonly seen in the pelvis, lower
extremity, and paraspinal regions, although reported ana-
tomic distribution is wide [121, 122]. BCOR-internal
tandem duplication sarcomas and primitive myxoid mes-
enchymal tumors of infancy occur mainly in soft tissues
at the trunk, head and neck, and retroperitoneum [120].
Patients most commonly present with pain and swelling
[123].
The MRI features of BCOR-internal tandem duplication
and primitive myxoid mesenchymal tumors of infancy have
not yet been well described in medical imaging literature.
Two case reports describe the tumors to be predominantly
cystic lesions, with high signal intensity on T2-weighted
images, low signal intensity on T1-weighted images, and
minimal peripheral contrast enhancement [124, 125]. These
tumors are typically treated with complete resection to avoid
recurrent growth [124].
On MRI, BCOR-CCNB3 sarcomas are aggressive-
appearing tumors, similar in appearance to the above
description of extraskeletal Ewing sarcoma—they are
reported to have internal necrosis, flow voids, perilesional
edema, and avid enhancement following administration of
intravenous gadolinium [126] (Fig. 12). BCOR-CCNB3 sar-
comas are treated similarly to Ewing sarcoma, with similar
5-year survival rates (72–80%) [117, 122, 123]. Metastatic
disease is identified on presentation in many cases—most
commonly to the lungs.
Conclusion
There are numerous soft tissue tumors and tumor-like condi-
tions in the pediatric population. The recently updated WHO
classification scheme for these tumors provides a useful
standardized nomenclature in the context of evolving under-
standing of underlying genetic aberrations and emerging
targeted therapies. MRI is widely employed when imaging
these soft tissue lesions due to its superior soft tissue con-
trast and characterization, ability to identify any underlying
Skeletal Radiology
(A)
(C)
(E)
Fig. 12  BCOR-CCNB3 sarcoma. 7-year-old female presented with
chest pain. Frontal chest radiograph (A) demonstrates a right chest
wall mass. MRI was obtained. On coronal T2-weighted image with
fat suppression (B), a hyperintense mass is seen in similar distribu-
tion, centered within the soft tissues between the right 2nd and 3rd
ribs along the lateral chest wall, extending outward to the overlying
soft tissues, and inward to the pleural space, with a small hyperin-
tense pleural effusion present. On axial fat-suppressed T1-weighted
image (C), the mass demonstrates heterogenous signal intensity,
with low-intensity regions likely corresponding to areas of necrosis
and a few focal hyperintense regions likely corresponding to areas
of hemorrhage. On axial fat-suppressed T1-weighted image follow-
ing administration of intravenous contrast (D), there is heterogene-
ous enhancement—primarily at the peripheral and central portions of
bone marrow signal abnormalities, and in select instances
provide quantitative or semi-quantitative data. While certain
soft tissue lesions may exhibit conventional MRI features
(B)
(D)
the mass. Abnormal enhancement is also noted about the thickened
ipsilateral parietal and visceral pleura, as well as within the marrow
of the 3rd rib. Axial image from a subsequent whole body PET/CT
(E) demonstrates heterogeneous FDG uptake greater than the medi-
astinal blood pool within the mass, with non-FDG avid areas likely
corresponding to necrosis, as well as FDG avidity along the thickened
pleura and the pleural effusion, favoring malignant extension. Physio-
logic FDG uptake is noted along the anterior mediastinum within the
thymus. Needle biopsy revealed largely necrotic tissue, interspersed
with viable areas of tumor showing primitive small, round to spindled
cells on a myxoid background with patchy pseudocyst formation (not
shown). Immunohistochemistry demonstrated strong, diffuse positiv-
ity to CCNB3, supporting the diagnosis of BCOR-CCNB3 rearranged
sarcoma
characteristic of a specific diagnosis without biopsy, most
lesions are often indeterminate based on clinical examina-
tion and MRI, and biopsy is required.
13

Declarations  17. Waelti SL, Rypens F, Damphousse A, Powell J, Soulez G, Mes-
Conflict of interest  Author Andrew Haims, MD discloses a financial
relationship with Pfizer.
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