Annual Meeting of the Arab Division of the AIP
Alep, December 08th, 2007
Lecture
Myxofibrosarcoma, fibromyxoid sarcoma, or myxofibro-something Refinement or redundancy in soft tissue tumor pathology ?
Louis Guillou, M.D.
University Institute of Pathology, Lausanne, Switzerland
Introduction
mitotically inactive spindle cells, although some
Many soft tissue lesions may show alternating
fibrotic and myxoid areas on microscopic
examination.
Superficial
acral
fibromyxoma,
cutaneous myxoma, cellular myxoma, and ossifying
fibromyxoid tumor are the most common in the
benign tumor category, whereas myxofibrosarcoma
(low and intermediate variants), low-grade
fibromyxoid sarcoma (Evans’s tumor), and
inflammatory
myxohyaline
tumor
(myxoinflammatory fibroblastic sarcoma) are the
most frequent among malignancies.
The aim of this presentation is to highlight the
similarities and differences that exist between those
lesions displaying fibromyxoid areas, and to give
some clues that may be of help in the differential
diagnostic approach.
Salient clinicopathologic features of the most
relevant entities
Superficial acral fibromyxoma
Fig. 1. Superficial acral fibromyxoma. A small benign
fibromyxoid nodule occurring in the vicinity of a nail.
lesions may display significant cellular atypia
(especially hyperchromatic nuclei). The lesion is
often highly vascular, containing numerous short
Clinical features
First described in 2001 by Fetsch et al. in a series
of 37 cases, superficial acral fibromyxoma is a
benign, slow-growing solitary lesion which typically
occurs in the superficial soft tissues of distal
extremities (fingers, palm, toes) of middle-aged
adults, with a tendency to involve the nail region.
The lesion is generally small (1-2 cm on average),
asymptomatic, and is often present for years before
the patient seeks medical attention. Recurrences
following complete surgical excision are rare (5% of
cases).
Pathologic features
Grossly, superficial acral fibromyxoma is soft to
firm. Cut section shows a gray-white to gelatinous
well-demarcated nodule. Microscopic examination
reveals cellular, myxoid, and fibrous areas. The
cellular areas are composed of bland, usually
Fig. 2. Superficial acral fibromyxoma. Alternating presence
of collagenous and myxoid areas.
2
curvilinear
vessels
resembling
those
of
myxofibrosarcoma. Interstitial mast cells are
common. Spindle cells usually express CD34 (90%
of cases), CD99 (80%), and less frequently EMA
(70%). They are negative for smooth muscle actin,
desmin, keratins, and S100 protein.
Differential diagnosis
Superficial acral fibromyxoma must be distinguished
from a low-grade sarcoma, especially a low-grade
myxofibrosarcoma, a low grade fibromyxoid
sarcoma, a low-grade malignant peripheral nerve
sheath tumor, an acral myxoinflammatory
fibroblastic sarcoma, or a myxoid variant of
dermatofibrosarcoma protuberans. Among benign
lesions,
acquired
(digital
or
periungueal)
fibrokeratoma, the myxoid variant of fibrous
histiocytoma, cutaneous myxoma, superficial
angiomyxoma, and sclerosing perineurioma are the
most likely to be confused with a superficial acral
fibromyxoma.
Cellular myxoma
Clinical features
Conventional myxoma of soft tissues (intramuscular
myxoma) is a non recurring soft tissue lesion which
typically occurs in middle-aged adults with a female
predominance. Most common locations include the
thigh, buttock, arm, and forearm. Tumor size varies
from a few centimeters to masses up to 10 cm, with
larger tumors being observed in the thigh. 5% to
10% of patients may develop mutiple myxomas
together with polyostotic fibrous dysplasia of
adjacent bone (Mazabraud's syndrome).
Fig. 3. Cellular myxoma. Absence of cellular atypia or
nuclear pleomorphism in cellular areas.
Cellular myxomas tend also to be solitary, deepseated, and to predominate in middle-aged women
(female to male ratio: 1.6;1, mean age: 52 years).
They commonly develop in the thigh (70% of cases)
but may also be observed in the upper extremity,
especially upper arm (deltoïd muscle). The average
tumor size is 5.5 cm. An association with fibrous
dysplasia has not been reported. Cellular myxoma
does not portend a higher recurrence risk than
conventional intramuscular myxoma. However,
incompletely excised cellular myxomas might have
some capacity for local recurrence (9% of the
lesions recur after marginal excison in the series of
van Roggen et al.). This tumor does not
metastasize.
Pathologic features
On section, the tumor is gelatinous and lobulated
with a glistening surface. Central cystic changes
may be present. Grossly, it is well demarcated but
on microscopic examination, it commonly infiltrates
between the skeletal muscle fibers or into the
adjacent adipose tissue, especially at the periphery
of the lesion. Conventional myxomas are
paucicellular and hypovascular lesions, containing
few fibrous streaks. The myxoid matrix
predominates and the tumor cells have sometimes
a vacuolated cytoplasm. Cellular myxomas contain,
in addition, areas of high cellularity and
hypervascular foci. In many cases, hypercellular
areas account for more than 50% of tumor amount.
The lesional cells are bland, stellate or spindle
shaped, without cytonuclear pleomorphism or
hyperchromasia, separated by a myxoid stroma
containing abundant collagen fibers. Mitoses and
necrosis are absent. Intratumoral vessels are either
thick-walled and muscular or curvilinear resembling
those observed in low-grade myxofibrosarcoma.
Myxoma, including the cellular variant is negative
for S100 protein and desmin. CD34 reactivity is
observed in about 50% of cases, especially in
cellular areas. Focal reactivity for smooth muscle
actin can also be observed in cellular areas.
Differential diagnosis
Cellular intramuscular myxoma should be
differentiated first from myxoid low grade sarcomas
including
low-grade
myxofibrosarcoma
(hyperchromatic cells, cellular pleomorphism,
perivascular increase in cellularity), low-grade
malignant
peripheral
nerve
sheath
tumor
(attachement
to
large
nerve,
cellular
hyperchromasia, S100 protein reactivity in half of
cases), low-grade fibromyxoid sarcoma (alternating
myxoid and collagenous areas, whorling pattern,
varying presence of giant rosettes, EMA reactivity,
t(7;16) reciprocal translocation), and myxoid
liposarcoma (plexiform vasculature, presence of
adipocytes and/or lipoblasts, round cells around
vessels and at the periphery of tumor lobules,
t(12;16) or t(12;22) translocations). Among benign
lesions,
myxoid
perineurioma,
myxoid
neurofibroma, and juxta-articular myxoma (a
recurring lesion situated in close proximity to large
joints) might be confused with cellular myxoma of
soft tissue.
Ossifying fibromyxoid tumor
Clinical features
This neoplasm was described in 1989 by Enzinger
and Weiss in a series of 59 cases. It occurs in
middle-aged adults (median age: 50 years) with a
slight male predominance, as a well-demarcated,
slowly growing painless mass, usually situated in
the subcutaneous tissue of proximal limbs, limbs
girdles, and trunk. 20-30% of cases occur in deep
soft tissues. Most lesions are solitary and remain
asymptomatic for years before coming to medical
attention. Most OFMT are characterized by a
benign clinical course. However, local recurrence is
common (15-20% of cases), mostly due to
incomplete excision (often related to the presence
of overlooked satellite micronodules). Atypical and
malignant variants of OFMT are also prone to local
3
recurrence (especially if marginally excised ) and
may also metastasize. About 5% of all OFMT
metastasize. Lesions with high cellularity, high
nuclear grade and/or high mitotic activity (>2
mitoses/50 hpf) show increased local-recurrence
and metastatic rates.
Fig. 4. Ossifying fibromyxoid tumor. A bone shell is readily
visible at the periphery of the mass.
Pathologic features
Grossly, OFMT are well circumscribed, firm, often
multinodular, and may have a discernibly osssified
periphery. The median size is 4 cm (range: 2-15
cm). The lesion is surrounded by a dense hyaline
pseudocapsule containing a variable amount of
mature lamellar bone, resulting in the appearance
of peripheral bony shell. Up to 20% of OFMT are
non ossifying lesions. Frequently, nodules of tumor
extend through and beyond the pseudocapsule
(satellite micronodules). The lesion is composed of
lobules of small round-to spindle-shaped cells with
pale eosinophilic cytoplam and uniform bland
nuclei, set in a fibromyxoid to hyalinized matrix.
Nuclei are uniform, non hyperchromatic and often
vesicular. Mitoses are very rare (usually <2 per 50
hpf). In some areas, tumor cells may be arranged in
ribbons, cords, or show a lace-like pattern similar to
that observed in pleomorphic adenoma of salivary
glands. Frank chondroid diifferentiation is
uncommon.
Fig. 5. Ossifying fibromyxoid tumor. Cords and ribbons of
cytologically bland tumor cells, set in a fibromyxoid matrix.
Atypical/malignant variants of OFMT show
cytological features of malignancy in terms of
increased
cellularity,
increased
nuclear
pleomorphism and increased mitotic activity (>2
mitoses / 50 hpf) and they often contain atypical
osteoid islands in the center of the lesion,
resembling
osteosarcomatous
foci,
raising
differential
diagnostic
problems
with
an
extraskeletal osteosarcoma or a malignant
schwannoma.
Immunohistochemically, most OFMT express S100
protein (60-80%) and GFAP (suggesting some
neural origin), and 15-40% of them show focal
reactivity for desmin. They are usually negative for
CD34. Occasional reactivity for keratins (10%) and
smooth muscle actin (5%) may be observed.
Differential diagnosis
Conventional OFMT resemble a mixed tumor or a
myoepithelioma of soft tissue with which it may be
confused. As opposed to OFMT, myoepithelioma
usually express epithelial markers (cytokeratins
and/or EMA). It should also be differentiated from
low-grade fibromyxoid sarcoma (positivity for EMA,
negativity for S100 protein), low-grade MPNST
(attachement
to
large
nerve,
nuclear
hyperchromasia, focal reactivity for S100, negativity
for desmin), perineurioma (positivity for EMA,
negativity for S100 protein), neurofibroma
(consistent negativity for desmin), and epithelioid
smoooth muscle tumors. Lesions showing extensive
hyalinization may be confused with a desmoid
tumor, whereas those showing extensive chondroid
differentiation should be distinguished from an
extraskelaetal myxoid chondrosarcoma. Atypical
and malignant variants of OFMT may resemble
extraskeletal osteosarcoma, sclerosing epithelioid
fibrosarcoma,
MPNST
with
heterologous
differentiation and low-grade dedifferentiated
liposarcoma with heterologous differentiation.
Myxofibrosarcoma
Clinical features
Myxofibrosarcoma, previously called myxoid
malignant fibrous histiocytoma, is a relatively
common sarcoma of older patients (median age: 60
years), mostly found in the deep dermis and
subcutaneous fat of limbs (especially lower limbs)
and limb girdles. 30 to 60% of the cases are deepseated, developing in fascia and skeletal muscle.
Fig.
6.
Gross
appearance
of
a
low-grade
myxofibrosarcoma. The lesion develops into deep dermis
and subcutis and shows a characteristic multinodular
growth pattern.
This is a slow-growing, often painless tumor
affecting men and women equally. Clinical behavior
depends on histologic grade and on extent of
resection. Local recurrences occur in about 50% of
4
cases, often because of inadequate initial excisions.
It is not unusual for recurrences to show signs of
upgrading with an increase in cellularity,
pleomorphism and mitotic activity, and, conversely,
a reduction of the myxoid component. Metastases
to lungs and bone are mostly observed in highgrade, deep-seated tumors (20-35%); they are rare
in low-grade lesions. The overall 5-year survival
rate is 60-70%.
vessels and vacuolated cells. However, myxoma,
nodular fasciitis and low-grade fibromyxoid sarcoma
all occur in young to middle-aged adults and lack
cellular atypia and hyperchromatic nuclei. Highgrade lesions may be confused with any
pleomorphic sarcoma; in this context, occurrence in
the elderly, subcutaneous location and the
presence of small myxoid areas in an otherwise
pleomorphic tumor should suggest the diagnosis.
Low-grade fibromyxoid sarcoma
Clinical features
Low-grade fibromyxoid sarcoma (LGFMS) is an
unusual variant of fibrosarcoma that was not
recognized as a malignant neoplasm until 1987. It
usually presents as a long-standing, painless mass
which occurs preferentially in the deep soft tissues
of the limbs (thigh), limb girdles (shoulder), and
trunk of young adults (median age: 35 years), with a
slight predilection for males. For those tumors
Fig. 7. Low-grade myxofibrosarcoma. Enlarged tumor cells
with hyperchromatic nuclei are evident.
Pathologic features
Grossly, myxofibrosarcoma is typically ill-defined,
heterogeneous, often multinodular, located in the
subcutaneous fat, growing along fibrous septa and
forming more or less gelatinous nodules. Large
tumors are often deep-seated, and partially necrotic
and/or hemorrhagic. On microscopic examination,
this is a multinodular, variably myxoid lesion. There
is unfortunately no consensus on the extent of the
myxoid areas required for the diagnosis of
myxofibrosarcoma: whereas some authors require
at least 50%, 10% is enough for some others. Low-,
intermediate- and high-grade tumors have been
described, depending on the respective proportions
of myxoid and nonmyxoid components (the latter
showing morphologic features of storiformpleomorphic malignant fibrous histiocytoma). Lowgrade myxofibrosarcomas are predominantly
myxoid; the tumor is hypocellular and contains
distinctive curvilinear vessels. Tumor cells, which
have enlarged hyperchromatic nuclei, tend to
aggregate around vessels. Vacuolated cells
containing acid mucin and resembling lipoblasts are
also found. Mitotic figures are rare. In high-grade
lesions, the malignant fibrous histiocytoma-like
component predominates: nuclear pleomorphism is
evident, multinucleated giant cells and necrosis
common, and mitotic figures, including abnormal
mitoses, readily visible. Subcutaneous cases of
myxofibrosarcoma can grow quite a way along
subcutaneous fibrous septa from the main lesion.
Immunohistochemically, tumor cells stain diffusely
for vimentin and occasionally for smooth muscle
actin. They are negative for S100 protein, CD34,
and CD68.
Differential diagnosis
Low-grade myxofibrosarcoma may be confused
with myxoma and nodular fasciitis but also with lowgrade
fibromyxoid
sarcoma
and
myxoid
liposarcoma owing to the presence of plexiform
Fig. 8. Gross appearance of a low-grade fibromyxoid
sarcoma. The lesion is well-demarcated, multilobulated,
firm and whitish, resembling a desmoid tumor.
adequately resected ab initio, the local recurrence is
close to 10%. The metastatic rate varies according
to follow-up duration. It varies between 5 and 10%
for a follow-up period shorter than 5 years whereas
it is close to 70% for patients followed for more than
7 years. Less than 5% of patients have died
Fig. 9. Low-grade fibromyxoid sarcoma. Alternating
presence of collagenous and myxoid areas.
of their tumor with a median follow-up of 2 years.
Metastases are mainly to lungs and pleura, also to
bone, and can occur late in the course of the
disease (15-25 years after initial excision). The
presence of high-grade areas in an otherwise lowgrade lesion is not currently believed to be
5
prognostically significant. Wide excision with tumorfree margins is the optimal surgical treatment.
Adjuvant radiation therapy is recommended by
some authors.
Pathologic features
LGFMS are well-demarcated, sometimes lobulated
tumors. Cut section shows a fibrous or fibromyxoid,
whitish,
glistening
mass,
bearing
some
resemblance to a uterine leiomyoma. Cystic
changes are occasionally observed. In its classic
form, LGFMS consists of spindle-shaped tumor
cells forming sweeping fascicles or whorls, in a
piebald collagenous and myxoid background. The
cells have pale eosinophilic cytoplasm and
deceptively bland, ovoid or tapered nuclei with one
or two small nucleoli, and occasional nuclear
inclusions. Mitotic figures are rare and there is no
necrosis. The stroma is focally very collagenous; in
the myxoid areas, curvilinear or plexiform vessels
resembling those of myxofibrosarcoma or myxoid
liposarcoma are readily visible. Although grossly
well-circumscribed, the tumor often infiltrates the
surrounding tissues on microscopic examination.
Some tumors may contain clusters of large rosettes,
consisting of cores of hyalinized collagen
surrounded by rounded, epithelioid-looking tumor
cells. When they are numerous, the lesion has been
described as hyalinizing spindle cell tumor with
giant rosettes (HSTGR). Foci of epithelioid-looking
cells can also be found in varying proportions in
LGFMS, overlaping morphologically with sclerosing
epithelioid fibrosarcoma. 15-20% of low-grade
fibromyxoid sarcomas contain intermediate- or highgrade,
densely
cellular
areas
resembling
conventional fibrosarcoma. Recurrent tumors also
tend to be more cellular and mitotically active, at
least focally.
Immunohistochemically, 80% of LGFMS express
Fig. 10. Low-grade fibromyxoid sarcoma showing a
whorled growth pattern. Tumor cell nuclei are bland.
EMA, CD99 and bcl2, at least focally. With rare
exceptions, they are consistently negative for CD34,
S100 protein, smooth muscle actin, desmin, and
keratins.
Cytogenetically, 80% of LGFMS bear a t(7;16)
(q33;p11) reciprocal translocation, or contain
supernumerary ring chromosomes composed of
material from chromosomes 7 and 16. Chimeric
FUS/CREB3L2 or FUS-CREB3L1 fusion transcripts
can be detected in this tumor type, using RT-PCR
Differential diagnosis
Classic low-grade fibromyxoid sarcoma may
resemble benign lesions such as fibroma,
neurofibroma, perineurioma, and desmoid tumor.
However, neurofibroma and perineurioma are
positive for S100 protein and EMA, respectively.
Deep fibromatoses (desmoid tumors) are more
uniform, lack myxoid nodules, have a more
fascicular growth pattern and are usually reactive
for smooth muscle actin, and often focally for
desmin.
Among malignant tumors, low-grade
malignant peripheral nerve sheath tumor (focal
S100
positivity),
the
myxoid
variant
of
dermatofibrosarcoma (CD34 positivity), and the lowgrade variant of myxofibrosarcoma (subcutaneous
location, greater degree of nuclear pleomorphism)
are most likely to be confused with low grade
fibromyxoid sarcoma. When giant rosettes are
present,
leiomyoma,
neuroblastoma-like
schwannoma,
and
metastatic
low-grade
endometrial stromal sarcoma must also be
considered, but can easily be excluded on
immunohistochemical grounds.
Inflammatory myxohyaline tumor
(Myxoinflammatory fibroblastic sarcoma)
Clinical features
Inflammatory
myxohyaline
tumor
/
myxoinflammatory fibroblastic sarcoma is a low
grade sarcoma which is mostly (but not exclusively)
observed in the distal extremities: fingers, hands,
wrist, toes, feet and ankles. This entity was
described simultaneously in 1998 by two different
groups
under
two
different
appellations:
"inflammatory myxohyaline tumor of distal
extremities with virocyte or Reed-Sternberg-like
cells" (Montgomery EA et al.) and "acral
myxoinflammatory fibroblastic sarcoma" (JM Meis-
Fig. 11. Inflammatory myxohyaline tumor. Coexistence of
cellular/pleomorphic areas and myxoid areas containing
vacuolated (lipoblast-like) cells.
Kindblom & LG Kindblom). It usually presents as a
slowly-growing neoplasm of middle-aged adults
(median age: 40-55 years), with no sex predilection.
Half of the cases are observed in hands and
fingers; less frequently, they can be seen in the
toes, feet, ankles, lower legs, knees, wrists or lower
arms. This neoplasm, which bears striking
resemblance to myxofibrosarcoma (myxoid MFH),
develops in the subcutis, in deep soft tissues or
along tendon sheaths, and may be accompanied by
symptoms of chronic synovitis/tenosynovitis. Local
6
recurrences are observed in about 20% of cases;
metastases are exceedingly rare. The high (67%)
recurrence rate reported by Meis-Kindblom &
Kindblom is probably related to the fact that many
patients had had incomplete initial excisions, often
following mistaken diagnoses of benignity
multivacuolated cells (bubbly cells) with scalloped
nuclei resembling lipoblasts are commonly found.
Occasional multinucleated Touton giant cells or
Reed-Sternberg-like cells are also seen, as well as
hemosiderin deposits. Blood vessels may be
curvilinear, resembling those of myxofibrosarcoma,
Fig. 12. Inflammatory myxohyaline tumor. Admixture of
hyalinized collagenous matrix and inflammation.
Fig. 14. Inflammatory myxohyaline tumor. Large tumor cell
with viral-like inclusion.
Pathologic features
but this is not the rule. Mitotic activity is usually low
and tumor necrosis infrequent. Local recurrences
and metastases tend to be more cellular and
mitotically
active
than
primaries.
Immunohistochemically, tumor cells may express
CD34 and CD68, at least focally. Occasional
reactivity for keratins and/or smooth muscle actin
has also been observed. S100 protein , EMA,
desmin, and HMB45 are generally not expressed.
On
gross
examination,
inflammatory
myxohyaline tumors measure 3-4 cm on
average and present as whitish, firm,
multinodular, often ill-defined neoplasms. The
cut suface may be gelatinous due to marked
myxoid changes. Many tumors develop
Fig. 13. Inflammatory myxohyaline tumor showing giant
tumor cells with prominent nucleoli and pseudolipoblastic
vacuolated cells.
in the subcutis, although they tend to grow along
the
underlying
tendon
sheaths
and/or
aponeuroses ; skeletal muscle is seldom involved.
On
microscopic
examination,
this
tumor
characteristically contains numerous inflammatory
elements (lymphocytes, plama cells, neutrophils)
which tend to obscure the neoplastic cells. The
latter are either spindle-shaped or epithelioid, often
frankly atypical and/or pleomorphic, and set in a
stroma which varies from densely hyaline to focally
myxoid. Some tumor cells have copious
eosinophilic cytoplasm, enlarged vesicular nuclei
and macronucleoli, thus resembling ganglion cells
or virocytes. These cells tend to cluster in hyalinized
areas whereas, in myxoid areas, uni or
Differential diagnosis
Inflammatory myxohyaline tumor should be
differentiated first from an inflammatory or an
infectious
processs
(chronic
tenosynovitis,
inflammatory pseudotumor, inflamed ganglion cyst,
myxoma
with
superimposed
inflammation,
proliferative fasciitis, etc…). Myxofibrosarcoma
(myxoid MFH) is the second most important
differential diagnosis to consider, but pleomorphic
liposarcoma (for those tumors containing numerous
vacuolated
« bubbly »
cells),
inflammatory
fibrosarcoma, or giant cell tumor of tendon sheath
(for those lesions that contain numerous Touton
giant cells) also enter the differential. The lesion is
less likely to be confused with a lymphoma or
Hodgkin disease.
Although described as a distinct entity, inflammatory
myxohyaline tumor may possibly be an
inflammatory
variant
of
low-grade
myxofibrosarcoma with a predilection for hands and
feet.
Helpful clues in the differential
diagnostic approach
Superficial
acral
fibromyxoma
versus
something else
In favor of superficial acral fibromyxoma:
 tumor location: distal extremities especially
nail bed
 small size (1-2 cm)
 superficial
 no mitoses
 no cellular atypia
7

positivity for CD34, CD99, EMA
Low-grade myxofibrosarcoma versus low-grade
fibromyxoid sarcoma
In favor of low-grade myxofibrosarcoma and against
low-grade fibromyxoid sarcoma:
 occurrence in elderly
 dermal and/or subcutaneous location
 multinodularity and ill-defined (infiltrative)
borders
 alternating presence of myxoid (with
abundant myxoid matrix) and solid areas
with spindle-shaped/pleomorphic cells
 absence of whorled growth pattern
 cellular atypia, hyperchromatic nuclei and/or
monstruous cells
 vacuolated, lipoblast-like cells
 mitoses and abnormal mitoses readily visible
Inflammatory myxohyaline tumor versus low- to
intermediate grade myxofibrosarcoma
This is a difficult situation. Sometimes, it is virtually
impossible to separate these two lesions on
morphologic grounds only. Nevertheless, the
following features would favor a diagnosis of
inflammatory myxohyaline tumor over that of
myxofibrosarcoma:







tumor location in distal extremities (fingers)
involvement of subcutis, tendon sheaths,
and synovium
numerous
inflammatory
elements
(lymphocytes and plasmocytes) admixed
with the tumor cell component
large (sometimes giant) tumor cells with
viral-like intranuclear inclusions
binucleated
(Reed-Sternberg-like)
or
multinucleated tumor cells
low mitotic activity
areas with abundant myxoid substance
containing vacuolated (pseudolipoblastic)
cells alternating with paucicellular fibrotic
and hyalinized areas
Low-grade
fibromyxoid
sarcoma
versus
ossifying fibromyxoid tumor
Some LGFMS which contain epithelioid-looking
cells may ressemble ossifying fibromyxoid tumors
as well as sclerosing epithelioid fibrosarcomas. The
following features would favor a diagnosis of
ossifying fibromyxoid tumor over that of LGFMS:
 occurrence in middle-aged adults (rather
than young adults)
 superficial location (subcutis +++)
 low-power magnification: homogeneous
appearance; absence of whorled growth
pattern and absence of readily visible
myxoid nodules
 tumor cells more rounded than spindleshaped
 bone shell at the periphery of the lesion
and/or bone production within the tumor
 absence of giant rosettes
 S100 and/or desmin reactivity
 lack of t(7;16) translocation
Cellular myxoma versus low-grade fibromyxoid
sarcoma
This is a common and difficult problem in soft tissue
tumor pathology. In this situation, it is wise to
examine the tumor for the presence of the t(7;16)
translocation (using RT-PCR or FISH). Morphologic
features that would weigh in favor of a cellular
myxoma are the following:
 occurrence in middle-aged females
 ill-defined
borders
at
low-power
magnification
and
lack
of
fibrous
pseudocapsule
 absence of whorled growth pattern
 presence of areas with abundant myxoid
substance containing curvilinear vessels and
few scattered, slightly hyperchromatic nuclei
 myofibroblastic rather than fibroblastic
appearance of spindle cells
 presence of vacuolated (pseudolipoblastic)
cells in myxoid foci
 absence of giant rosettes
Cellular
myxoma
versus
low-grade
myxofibrosarcoma
This is another common problem in soft tissue
tumor pathology. Sometimes, it is impossisble to
separate one entity from the other. The following
features, however, would weigh in favor of a lowgrade myxofibrosarcoma over a cellular myxoma:
 occurrence in elderly people
 occurrence in male rather than female
patients
 superficial location (dermis and subcutis)
 multinodular growth pattern
 admixture of myxoid and solid/pleomorphic
areas
 large cells with hyperchromatic atypical
nuclei
 mitoses and abnormal mitoses
 (CD34 negativity)
References
Superficial acral fibromyxoma
Fetsch JF, Laskin WB, Miettinen M. Superficial acral
fibromyxoma:
a
clinicopathologic
and
immunohistochemical analysis of 37 cases of a distinctive
soft tissue tumor with a predilection for the fingers and
toes. Hum Pathol. 2001, 32:704-714.
Andre J, Theunis A, Richert B, de Saint-Aubain N.
Superficial acral fibromyxoma: clinical and pathological
features. Am J Dermatopathol. 2004, 26:472-474.
Cellular myxoma
van Roggen JFG, McMenamin ME, Fletcher CD. Cellular
myxoma of soft tissue: a clinicopathological study of 38
cases
confirming
indolent
clinical
behaviour.
Histopathology. 2001; 39:287-297.
Catroppo JF, Olesnicky L, Ringer P, Goldenkranz R,
Casas V, Wright T. Intramuscular low-grade myxoid
neoplasm with recurrent potential (cellular myxoma) of the
lower extremity: case report with cytohistologic correlation
and review of the literature. Diagn Cytopathol. 2002;
26:301-305.
Charron P, Smith J. Intramuscular myxomas: a
clinicopathologic study with emphasis on surgical
management. Am Surg. 2004; 70:1073-1077.
8
Allen PW. Myxoma is not a single entity: a review of the
concept of myxoma. Ann Diagn Pathol 2000, 4: 99-123.
van Roggen JFG, Hogendoorn PCW, Fletcher CD. Myxoid
tumours of soft tissue. Histopathology 1999, 35: 291.312.
Meis JM, Enzinger FM. Juxta-articular myxoma. A clinical
and pathologic study of 65 cases. Hum pathol 1992, 23:
639-646.
SJ, Cooper K, Suster S, Lamovec J. Myxoinflammatory
fibroblastic sarcoma: a tumor not restricted to acral sites.
Ann Diagn Pathol. 2002, 6:272-280.
Lambert I, Debiec-Rychter M, Guelinckx P, Hagemeijer A,
Sciot R. Acral myxoinflammatory fibroblastic sarcoma with
unique clonal chromosomal changes. Virchows Arch.
2001, 438:509-512.
Myxofibrosarcoma
Nielsen GP, O’Connell JX, Rosenberg AE. Intramuscular
myxoma. A clinicopathologic study of 51 cases with
emphasis on hypercellular and hypervascular variants. Am
J Surg Pathol. 1998, 22: 1222-1227.
Enzinger FM. Intramuscular myxoma. A review and followup study of 34 cases. Am J Clin Pathol 1965, 43: 104-113.
Hashimoto H, Tsuneyoshi M, Damairu Y, Enjoji M,
Shinohara N. Intramuscular myxoma. A clinicopathologic,
immunohistochemical and electron microscopic study.
Cancer 1986,58: 740-747.
Miettinen M, Höckerstedt K, Reitamo J, Tötterman S.
Intramuscular myxoma. A clinicopathological study of 23
cases. Am J Clin Pathol 1985, 84: 265-272.
Ossifying fibromyxoid tumor
Enzinger FM Weiss SW, Liang CY.. Ossifying fibromyxoid
tumor of soft parts. A clinicopathological analysis of 59
cases. Am J Surg Pathol 1989; 13: 817-827.
Kilpatrick SE, Ward WG, Mozes M, Miettinen M, Fukunaga
M, Fletcher CDM. Atypical and malignant variants of
ossifying fibromyxoid tumor. Clinicopathologic analysis of
six cases. Am J Surg Pathol 1995; 19: 1039-1046.
Zamecnik M, Michal M, Simpson RHW, Lamovec J,
Hlavcak P, Kinkor Z, Mukensnabl P, Matejovsky Z,
Betlach J. Ossifying fibromyxoid tumor of soft parts: a
report of 17 cases with emphasis on unusual histological
features. Ann Diagn Pathol 1997; 1: 73-81.
Holck S, Pedersen JG, Ackermann T, Daugaard S.
Ossifying fibromyxoid tumour of soft parts, with focus on
unusual clinicopathological features. Histopathology 2003;
42: 599-604.
Folpe AL, Weiss SW. Ossifying fibromyxoid tumor of soft
parts. A clinicopathologic study of 70 cases with emphasis
on atypical and malignant variants. Am J Surg Pathol
2003; 27: 421-431.
Inflammatory myxohyaline tumor
(Myxoinflammatory fibroblastic sarcoma)
Montgomery EA, Devaney KO, Giordano TJ, Weiss SW.
Inflammatory myxohyaline tumor of distal extremities with
virocyte or Reed-Sternberg-like cells: a distinctive lesion
with features simulating inflammatory conditions,
Hodgkin's disease, and various sarcomas. Mod Pathol
1998; 11: 384-391.
Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory
fibroblastic sarcoma: a low-grade tumor of the hands and
feet. Am J Surg Pathol 1998; 22: 911-924.
Michal M. Inflammatory myxoid tumor of the soft parts with
bizarre giant cells. Pathol Res Pract 1998; 194: 529-533.
Sakaki M, Hirokawa M, Wakatsuki S, Sano T, Endo K,
Fujii Y, Ikeda T, Kawaguchi S, Hirose T, Hasegawa T.
Acral myxoinflammatory fibroblastic sarcoma: a report of
five cases and review of the literature. Virchows Arch.
2003, 442:25-30.
Jurcic V, Zidar A, Montiel MD, Frkovic-Grazio S, Nayler
Weiss SW, Enzinger FM. Myxoid variant of malignant
fibrous histiocytoma. Cancer 1977; 39: 1672-1685
Merck C, Angervall L, Kindblom LG, Oden A.
Myxofibrosarcoma. A malignant soft tissue tumor of
fibroblastic-histiocytic origin. A clinicopathologic and
prognostic study of 110 cases using multivariate analysis.
Acta Pathol Microbiol Immunol Scand Suppl 1983; 282: 140.
Mentzel T, Calonje E, Wadden C, Camplejohn RS, Beham
A, Smith MA, Fletcher CD. Myxofibrosarcoma:
Clinicopathologic analysis of 75 cases with emphasis on
the low grade variant. Am J Surg Pathol 1996; 20: 391405.
Huang HY, Lal P, Qin J, Brennan MF, Antonescu CR.
Low-grade myxofibrosarcoma: a clinicopathologic analysis
of 49 cases treated at a single institution with
simultaneous assessment of the efficacy of 3-tier and 4tier grading systems. Hum Pathol 2004; 35: 612-621.
Oda Y, Takahira T, Kawaguchi K, Yamamoto H, Tamiya
S, Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M. Lowgrade
fibromyxoid
sarcoma
versus
low-grade
myxofibrosarcoma in the extremities and trunk. A
comparison
of
clinicopathological
and
immunohistochemical features. Histopathology 2004; 45:
29-38.
Antonescu CR, Baren A. Spectrum of low-grade
fibrosarcomas: a comparative ultrastructural analysis of
low-grade myxofibrosarcoma and fibromyxoid sarcoma.
Ultrastruct Pathol 2004; 28: 321-332
Low-grade fibromyxoid sarcoma
Hyalinizing spindle cell tumor with giant rosettes
Evans HL. Low-grade fibromyxoid sarcoma: a report of
two metastasizing neoplasms having a deceptively benign
appearance. Am J Clin Pathol 1987; 88: 615-619.
Evans HL. Low-grade fibromyxoid sarcoma: a report of 12
cases. Am J Surg Pathol 1993; 17: 595-600.
Lane KL, Shannon, RJ, Weiss, S.W. Hyalinizing spindle
cell tumor with giant rosettes: a distinctive tumor closely
resembling low-grade fibromyxoid sarcoma. Am J Surg
Pathol 1997; 21: 1481-1488.
Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade
fibromyxoid sarcoma and hyalinizing spindle cell tumor
with giant rosettes: a clinicopathologic study of 73 cases
supporting their identity and assessing the impact of highgrade areas. Am J Surg Pathol 2000; 24: 1353-1360.
Zamecnik M, Michal M. Low-grade fibromyxoid sarcoma: a
report
of
eight
cases
with
histologic,
immunohistochemical, and ultrastructural study. Ann
Diagn Pathol 2000; 4: 207-217.
Mezzelani A, Sozzi G, Nessling M, Riva C, Della Torre G,
Testi MA, Azzarelli A, Pierotti MA, Lichter P, Pilotti S. Low
grade fibromyxoid sarcoma: a further low-grade soft tissue
malignancy characterized by a ring chromosome. Cancer
Genet Cytogenet 2000;122:144-148.
9
Reid R, Chandu de Silva MV, Paterson L, Ryan E, Fisher
C: Low-grade fibromyxoid sarcoma and hyalinizing spindle
cell tumor with giant rosettes share a common
t(7;16)(q34;p11) translocation. Am J Surg Pathol 2003; 27:
1229-1236.
Panagopoulos I, Storlazzi CT, Fletcher CD, Fletcher JA,
Nascimento A, Domanski HA, Wejde J, Brosjö O,
Rydholm A, Isaksson M, Mandahl N, Mertens F. The
chimeric FUS/CREB3L2 gene is specific for low-grade
fibromyxoid sarcoma. Genes Chromosomes Cancer.
2004; 40: 218-228.
Mertens F, Fletcher C, Antonescu CR, Coindre JM,
Colecchia M, Domanski HA, Downs-Kelly E, Fisher C,
Goldblum JR, Guillou L, Reid R, Rosai J, Sciot R, Mandahl
N, Panagopoulos I. Clinicopathologic and molecular
genetic characterization of low-grade fibromyxoid
sarcoma, and cloning of a novel FUS/CREB3L1 fusion
gene. Lab Invest 2005; 85: 408-415.
Billings SD, Giblen G, Fanburg-Smith JC. Superficial lowgrade
fibromyxoid
sarcoma
(Evans
tumor):
a
clinicopathological analysis of 19 cases with a unique
observation in the pediatric population. Am J Surg Pathol,
2005; 29: 204-210.
Oda Y, Takahira T, Kawaguchi K, Yamamoto H, Tamiya S,
Matsuda S, Tanaka K, Iwamoto Y, Tsuneyoshi M. Lowgrade
fibromyxoid
sarcoma
versus
low-grade
myxofibrosarcoma in the extremities and trunk. A
comparison
of
clinicopathological
and
immunohistochemical features. Histopathology 2004; 45:
29-38.
Guillou L, Benhattar J, Gengler C, Gallagher G, RanchèreVince D, Collin F et al. Translocation-positive low-grade
fibromyxoid sarcoma: clinicopathologic and molecular
analysis of a series expanding the morphologic spectrum
and suggesting potential relationship to sclerosing
epithelioid fibrosarcoma. A study from the French
Sarcoma Group. Am J Surg Pathol 2007, in press
Louis Guillou, M.D. Institut Universitaire de Pathologie, rue
du Bugnon 25, CH-1011 Lausanne (Suisse). tél : +41 21
314 72 16 / 71 11 ; fax : +41 21 314 72 07 ; e-mail :
louis.guillou @ chuv.hospvd.ch
Table 1. Neoplasms with a “myxo-fibro” appearance (nonexhaustive list)
“Myxo-fibro” areas observed frequently
Superficial acral fibromyxoma
Cutaneous myxoma / Superficial angiomyxoma
Cellular myxoma / Juxta-articular myxoma
Ossifying fibromyxoid tumor
Myxofibrosarcoma (low- and intermediate-grade variants)
Low grade fibromyxoid sarcoma / hyalinizing spindle cell tumor with giant rosettes
Inflammatory myxohyaline tumor (myxoinflammatory fibroblastic sarcoma)
“Myxo-fibro” areas observed occasionally
Soft tissue perineurioma (myxoid variant)
Desmoplastic fibroblastoma (collagenous fibroma)
Myxoid neurofibroma
Myxoid spindle cell lipoma (dendritic fibromyxolipoma)
Ancient fibro-hyalinized nodular fasciitis
Giant cell fibroblastoma
Deep "aggressive" angiomyxoma
Desmoid tumor
Solitary fibrous tumor (myxoid variant)
Low-grade malignant peripheral nerve sheath tumor
Dedifferentiated liposarcoma
Pleomorphic liposarcoma
Sclerosing epithelioid fibrosarcoma
10
Table. 2. Relevant differences between low-grade myxofibrosarcoma (Low-grade MFS), low-grade fibromyxoid sarcoma (LGFMS), ossifying fibromyxoid tumor (OFMT),
inflammatory myxohyaline tumor (IMHT), and cellular myxoma (CM)
Clinical features
Median age
Sex
Tumor location
Size (median)
Depth
Morphology
Multinodular growth pattern
Extensive infiltrative borders
Whorled growth pattern
Bone shell/bone production
Hyperchromatic atypical nuclei
Pseudolipoblasts
Intranuclear inclusions
Mitoses (median counts/10 hpf))
Atypical mitoses
Plexiform/curvilinear vessels
Perivascular cell condensation
Giant rosettes
Epithelioid-looking cells
Solid pleomorphic (high-grade) areas
Numerous inflammatory elements
Immunohistochemistry
EMA
CD34
Smooth muscle actin
Desmin
S100 protein
Average MIB1 labelling index (500 cells)
Cytogenetics
Chromosomal abnormalities
Outcome
Local recurrence rate
Metastatic rate
5-year DSS rate3
Low-grade MFS
LGFMS
OFMT
IMHT
CM
60 yrs
M>F
limbs (lower extremity)
limb girdles
5-7 cm
superficial (60%)
30-35 yrs
M=F
limbs (thigh)
trunk
5-7 cm
deep (90%)
50 yrs
M>F
limbs, trunk
limb girdles
4 cm
superficial (70-80%)
50 yrs
M=F
distal extremities (90%)
3-4 cm
superficial & deep
50 yrs
F>M
limbs
(thigh: 70%)
5-6 cm
deep (>90%)
yes (50%)
yes (50%)
no
no/no
yes
yes
no
yes (2)
yes
yes
yes
no
no
limited (<20%)
no
occasional
no
yes
no/rare
no1
no
yes
very rare (2)1
no
in myxoid foci only
rare
occasional
occasional
no
no
occasional
no
no
yes/yes
no
no
no
rare1
no
no
no
no
no
no
no
yes
yes
no
no/no
yes
yes
yes (viral-like)
rare
rare
yes
yes
no
no
yes
yes
no
occasional
no
no/no
no
yes
no
absent
no
yes
yes
no
no
no
occasional
neg
neg
pos focal
neg
neg
152
pos focal (80%)
neg
neg
neg
neg
52
neg
neg
pos (5%)
pos (15-40%)
pos (60-80%)
neg
pos focal
rarely pos
neg
neg
neg
pos (50%)
occasional
neg
neg
non specific
t(7;16)
non specific
non specific
non specific
50%
5-15% (after x recurrences)
>95%
10%
10-70%
>95%
15-20%
5%
>95%
20%
exceptional
>95%
10%
0%
100%
1. except in cellular areas. 2. in : Oda Y et al. Histopathology 2004 ; 45 : 29-38. 3. DSS : disease specific survival