Myxofibrosarcoma: Christina L. Roland,, Wei-Lien Wang,, Alexander J. Lazar,, Keila E. Torres

M y x o f i b ro s a rc o m a
Christina L. Roland, MDa,*, Wei-Lien Wang, MDb,

Alexander J. Lazar, MD, PhDb, Keila E. Torres, MD, PhDa
KEYWORDS
Myxofibrosarcoma Surgery MRI Recurrence
KEY POINTS
Myxofibrosarcoma is a unique subtype of soft tissue sarcoma with a locally infiltrative
behavior and a predilection for local recurrence.
Histology reveals a highly myxoid neoplasm with a distinctly hypocellular appearance,
although some lesions have more cellular areas and can be higher grade.
Patients presenting with a diagnosis of myxofibrosarcoma should undergo high-quality
T1- and T2-weighted MRI with pre- and postgadolinium imaging to accurately define
the extent of the disease.
Wide surgical resection with a 2 cm soft tissue margin encompassing the entire area of
increased signal on T2-weighted MRI is required, which can require complex vascular
and plastic surgery reconstruction.
A subset of patients with higher-grade lesions will develop distant metastases.
INTRODUCTION: NATURE OF THE PROBLEM
Myxofibrosarcoma (MFS) is a unique subtype of soft tissue sarcoma often characterized

by a diffusely infiltrative pattern. This represents approximately 5% of soft tissue
sarcoma diagnoses (Fig. 1). With the introduction of more stringent morphologic and
immunohistochemical criteria in 2002 and reaffirmed in 2013, the World Health Organi-
zation (WHO) renamed the myxoid variant of malignant fibrous histiocytoma (MFH) with
a predominant myxoid component (>50%) myxofibrosarcoma.1,2 Series of MFS and
myxoid MFH studies describe these tumors as having a significant propensity for local
recurrence, while exhibiting an overall better prognosis when compared with other com-
plex karyotype sarcomas such as leiomyosarcoma.3–5 Given its relatively recent recog-
nition as a distinct pathologic entity, the clinical behavior and outcomes for patients with
MFS are uncertain, and there are no randomized trials to guide treatment protocols.
Disclosure: The authors have nothing to disclose.

a
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400
Pressler Street, Unit 1484, Houston, TX 77030, USA; b Department of Pathology, University of
Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0085, Houston, TX
77030, USA
* Corresponding author.
E-mail address: clroland@mdanderson.org
Surg Oncol Clin N Am 25 (2016) 775–788

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776 Roland et al
Fig. 1. Frequency by histology for patients with soft tissue sarcoma treated at MD Anderson
Cancer Center (MDACC) between 2008 to 2013 (n 5 3574). UPS/MFH undifferentiated
pleomorphic sarcoma, GIST gastrointestinal stromal tumor, MPNST malignant peripheral
nerve sheath tumor.
Therefore, treatment decisions and understanding of this disease are based on case–
control and retrospective studies.
PATHOPHYSIOLOGY
Myxofibrosarcoma was first formally described in 1977.6 Diagnostic terminology has

evolved over the years and thus merits some further discussion. In the original 1977
description in the journal Cancer, Enzinger and Weiss used the terminology “myxoid
variant of malignant fibrous histiocytoma.” They noted that the myxoid variant of
MFH had extensive, distinct myxoid features and exhibited less aggressive behavior
than storiform or pleomorphic MFH.6 Use of the term myxofibrosarcoma extends
back to at least 1951.7 However, it was only in the late 1970s that this terminology
was applied to this specific entity.8 In the 1990s, MFH attracted attention as a poten-
tially problematic and possibly nonspecific diagnostic category likely contaminated
with multiple entities.9–11 Among the multiple histologic types of MFH, attempts
were made to help better distinguish myxofibrosarcoma as a separate diagnostic
category.10 Malignant fibrous histiocytoma (MFH) was renamed undifferentiated pleo-
morphic sarcoma (UPS) and was defined as a diagnosis of exclusion in both the 2002
and 2013 WHO Classification of Tumors of Soft Tissue and Bone.1,2 Given the use of
modern methods including immunohistochemistry and molecular studies, UPS is now
better defined and much less likely to be contaminated by mimics such as poorly
differentiated carcinoma or spindle cell melanoma. Under the current WHO classifica-
tion, the preferred diagnostic terminology for tumors formerly referred as myxoid ma-
lignant fibrous histocytoma is myxofibrosarcoma.
Not surprisingly, given the alterations in diagnostic terminology, the diagnostic
criteria for myxofibrosarcoma have also evolved over the years. The original 1977
description detailed a grossly multilobular tumor with mucoid features on cut surface
(Fig. 2). Histology reveals a highly myxoid neoplasm with a distinctly hypocellular
appearance (Fig. 3A). The myxoid areas are sparsely populated spindle cells or some-
times pleomorphic cells embedded in a matrix of the acid mucopolysaccharides
(Fig. 3B, C). Due to the myxoid features, the vasculature is distinct. Areas of more
diffuse cellularity are often present (Fig. 3D), and these areas often have conspicuous
Myxofibrosarcoma 777
Fig. 2. Gross appearance of myxofibrosarcoma. The tumor is composed of lobulated areas of

myxoid and nonmyxoid areas.
mitotic activity that is not usually a feature of the highly myxoid areas. Sometimes
pseudo-lipoblasts (multivacuolated cells filled with mucin rather than lipid, see inset
Fig. 3E) are apparent in myxoid areas. It was recognized early on that areas of this
myxofibrosarcoma may show much higher degrees of cellularity that were indistin-
guishable from malignant fibrous histiocytoma or what is now called undifferentiated
pleomorphic sarcoma.6,12,13 The original 1997 article demonstrated that the degree of
hypercellularity was related to the ultimate metastatic potential of these neoplasms.6
Rarely, myxofibrosarcoma can show epithelioid cellularity rather than spindle cells
admixed within the myxoid areas or growing as a diffusely cellular proliferation
(Fig. 4). These epithelioid myxofibrosarcomas appear to behave more aggressively
than their traditional spindle cell counterparts.14
Although the hypocellular myxoid component of myxofibrosarcoma is relatively
easy to recognize, there has been debate in the field over how much of
the neoplasm must be comprised of this hypocellular myxoid component in order
to diagnose this entity. Opinions vary widely, with requirements of as much as
75% to as little as 5% hypercellular myxoid content.3,6,8,13,15,16 Furthermore,
myxofibrosarcoma can progress to a completely cellular neoplasm devoid of a
myxoid component that is indistinguishable from UPS (see Fig. 3D). There is a ten-
dency for myxofibrosarcomas to become more cellular over time and with local
recurrence, suggesting this is a form of tumor progression in at least some cases.
Neoplasms composed mainly of the hypocellular myxoid component tend to show
local recurrence rather than distant metastasis.3 A recent paper by Singer and col-
leagues indicates that even a minimal hypocellular myxoid component of at least
5% confers a better prognosis for myxofibrosarcoma relative to undifferentiated
pleomorphic sarcoma lacking this myxoid component.15 They thus suggest
defining myxofibrosarcoma as having at least a 5% hypocellular myxoid compo-
nent, while anything with less than 5% myxoid is best considered as undifferenti-
ated pleomorphic sarcoma. Given the virtually complete morphologic overlap of
the hypercellular and generally nonmyxoid portions of myxofibrosarcoma with un-
differentiated pleomorphic sarcoma, distinguishing these 2 entities can be chal-
lenging when only a minimal myxoid component is present. At the authors’
institution, a cut-off of roughly 20% characteristic myxoid component is used for
the diagnosis of myxofibrosarcoma.
Myxofibrosarcoma can be graded under the FNCLCC (Fédération Nationale des
Centres de Lutte Contre le Cancer) system.17 Hypocellular cases tend have low
mitotic activity and no necrosis and are thus considered low-grade when the entire
lesion is composed of this characteristic component. Areas of increased cellularity
778 Roland et al
Fig. 3. Histologic appearance of myxofibrosarcoma. (A) Low power reveals lobular architec-
ture with myxoid areas and less myxoid, more cellular areas. (B, C) Higher-power examination
of myxoid areas reveals the prominent myxoid stroma, spindle cells with mild-to-moderate
atypia, thin-walled vessels; mitotic activity is generally very low. (D) More cellular areas
have less myxoid stroma, often composed of more atypical spindled-to-pleomorphic cells.
These areas are reminiscent of undifferentiated pleomorphic sarcoma and often demonstrate
prominent mitotic activity. (E) Scattered pseudolipoblasts are sometimes encountered in the
myxoid areas (arrow). These cells have a vacuolated appearance but are filled with mucin and
not lipids and should not be interpreted as evidence of lipogenic differentiation.
with mitotic activity result in designation of a higher grade. Many of these neoplasms
turn out to be intermediate- rather than high-grade, as the tumor differentiation score
for myxofibrosarcoma is 2, in contrast to undifferentiated pleomorphic sarcoma,
which is assigned a differentiation score of 3. Thus, myxofibrosarcoma must exhibit
both high mitotic rate and necrosis to achieve a designation of high-grade under
the FNCLCC system. However, many institutions and the American Joint Committee
Fig. 4. Histologic appearance of myxofibrosarcoma with epithelioid features. (A) Low power
reveals myxoid and more cellular areas. (B) Myxoid areas can be prominent and relatively devoid
of atypical cellularity. (C) More cellular areas contain epithelioid cells that can become diffuse.
on Cancer (AJCC), group intermediate- and high-grade tumors into 1 category for pur-
poses of staging given that intermediate sarcomas have some potential for distant
metastasis.18 Given the challenges and debate in the literature regarding the diag-
nostic criteria and grading, management approaches vary for the more cellular and
higher-grade myxofibrosarcomas.
780 Roland et al
CYTOGENETICS AND MOLECULAR FINDINGS
Most cases of MFS demonstrate a highly complex karyotype, often with tripoid or tet-
rapoid alterations.6 Willems and colleagues19 demonstrated that most cases have
complex cytogenetic anomalies, and such alterations were observed in tumors of all
grades. Furthermore, this group observed that the tumors that locally recurred had
more complex cytogenetic aberrations when compared with those that did not recur.
Based on this observation, the authors proposed the concept of MFS progression as a
multistep genetic process that is lead by genetic instability. MFS is among the sar-
coma subtypes currently being characterized by The Cancer Genome Atlas (TCGA)
for sarcoma, and this collaborative project should provide additional insights into
the relatively uncharacterized genomic landscape of this tumor.
CLINICAL PRESENTATION/EXAMINATION
MFS usually affects older patients (Table 1).6,13,16 Although the age range is broad,
most patients are in their fifth to seventh decades of life, and men are affected slightly
more often than women. The most common sites of presentation are the extremities
(77%), with a predilection for the lower extremities (Fig. 5A). MFS tumors can also
be located on the trunk (12%) and head and neck region (3%), but to a lesser extent.13
MFS is uncommon in the abdominal cavity and retroperitoneum. It has been reported
in the skin, breast, heart, and paratesticular region.
The tumor most commonly arises as a slowly enlarging, painless mass. It may pre-
sent as a predominantly deep or subcutaneous multinodular growth (Fig. 5B). Mentzel
and colleagues16 classified MFS into 2 groups: superficial (dermal/subcutaneous) and
deep (intramuscular/mainly subfascial). The superficial group tends to infiltrate
through the fascia, whereas the deep lesions tend to form a single discrete mass.
The superficial lesions may involve the dermal layer and present as a cutaneous lesion
as well. Deep-seated lesions tend to be less nodular and can demonstrate an infiltra-
tive growth pattern. Usually, they are larger than their superficial counterparts.
DIAGNOSTIC PROCEDURES
One of the major challenges of myxofibrosarcoma is to define the boundaries of the

tumor. As with other soft tissue sarcomas of the extremity, MRI is the diagnostic mo-
dality of choice. MFS has low attenuation on computed tomography (CT) and shows
low-to-intermediate signal on T1-weighted MRI (Fig. 6A). The solid and myxomatous
components both show high signal on T2-weighted MRI, with the myxoid component
showing higher signal intensity similar to that of fluid (Figs. 6B–D). Nodular and periph-
eral enhancement is often seen in the solid components.
MFS often show abnormal signal infiltration along the facial plan on MRI that corre-
spond to an infiltrative growth pattern histologically, named the “tail sign (Figs. 6B
and D).”5,20 One of the first groups to evaluate the diagnostic value of the tail sign in
Table 1
Clinical features of myxofibrosarcoma
Features Low-Grade Myxofibrosarcoma

Peak age Elderly
Depth Subcutaneous tissue
Stroma Usually uniformly myxoid
Atypia Present
Fig. 5. Distribution of myxofibrosarcoma tumors by (A) site and (B) tumor depth. (Data from
Refs.3,13,16)
a large number of patients with MFS was Kaya and colleagues.20 Eighty-one percent
of MFS tumors had a multidirectional signal spreading along the facial plane (tail sign)
on T2-weighted MRI. Interestingly, the authors found histologic infiltrative growth
pattern on patients with focal growth pattern on MRI. The discrepancy may be due
to the use of T2-weighted images instead of gadolinium-enhanced images that can
depict tumor infiltration more accurately. Lefkowitz and colleagues21 sought to deter-
mine whether the tail sign is helpful in distinguishing myxofibrosarcoma from other
myxoid-containing neoplasms. In a group of 44 MFS, the tail sign was observed by
3 radiologists, with a sensitivity of 64% to 77% and a specificity of 79% to 90% among
myxoid-predominant lesions. In addition, this group also found that the lesions
demonstrated an infiltrative growth pattern histologically regardless of the MRI char-
acteristics, emphasizing the importance of clearly defining the extent of disease
with imaging prior to resection. Yoo and colleagues22 observed that tumors that
had a focal growth pattern on T2-weighted images would also demonstrate a tail
sign on postcontrast images. Tails at MRI are not unique to MFS; they are also
observed in other soft tissue tumors such as unclassified sarcomas.22 Waters and col-
leagues5 evaluated the features of recurrent low-grade myxofibrosarcoma lesions on
CT and MRI imaging and found the tail sign was present in recurrent disease as well.
The infiltrative growth pattern of low-grade myxofibrosarcoma can result in anatom-
ically deceptive boundaries at surgery because of microscopic extension into the
dermis and skeletal muscles.5,23 A completely infiltrative growth pattern along facial
planes without the formation of a discrete nodular lesion has been described in
some cases. Given the various clinical and histopathologic appearances of this tumor,
the potential for diagnostic and staging errors highlights the importance of multidisci-
plinary, preoperative planning. As part of the preoperative imaging, it is critical that pa-
tients presenting with a diagnosis of MFS undergo high-quality T1- and T2-weighted
MRI with pre-and postgadolinium imaging.
THERAPEUTIC OPTIONS/SURGICAL TECHNIQUE
Margin-negative surgical resection is the cornerstone of treatment for patients with

soft tissue sarcoma, including MFS. In the 1970s, half of patients presenting with
782 Roland et al
Fig. 6. A 54-year-old man with 7.3 cm myxofibrosarcoma of the right thigh. (A–C) Axial
views. (D) Coronal view demonstrates a fusiform intramuscular soft tissue tumor in the
rectus femoris muscle in the right midthigh. The lobulated intramuscular tumor is isointense
on T1 (A), heterogeneously hyperintense on T2 (B), and shows nonhomogeneous enhance-
ment on the postcontrast images (C). On T2-weighted images with fat suppression (B, D),
the tail sign can be seen extending along the facial planes (white arrows).
extremity sarcomas were treated with amputation for local control of their tumors.
Radical resection was defined as complete removal of an entire anatomic compart-
ment, including nerves, vessels, and any involved bone. Often, amputation was the
only possible procedure for adequate compartmental resection. Disappointingly, it
was noted that although local recurrence rates were less than 10% following radical
surgery, a significant proportion of patients continued to die from metastatic dis-
ease.24 This realization led to the establishment of limb salvage surgery combined
with radiation therapy. However, for patients whose tumor cannot be grossly resected
with a limb-sparing procedure that leaves a functional extremity (rare, at < 5%), ampu-
tation remains the treatment of choice.25
MFS presents a unique challenge due multidirectional spread along the facial
planes. Therefore, obtaining negative margins may be challenging despite careful
preoperative planning (Fig. 7).20 As described previously, a high-quality T1- and
Fig. 7. Preoperative planning algorithm for patients with myxofibrosarcoma.
T2-weighted MRI with pre-and postgadolinium imaging is part of the preoperative

planning for a patient with a diagnosis of MFS. Clinical, pathologic, and radiographic
data should be reviewed by an experienced multidisciplinary team in a specialized
referral center. The input of an experienced sarcoma multidisciplinary team (surgical
oncologist, radiation oncologist, medical oncologist, sarcoma pathologist, and radiol-
ogist) is critical to the planning and implementation of these complex resections. Wide
resection should include a 2 cm margin of soft tissue surrounding the tumor, with
planned resection of the entire area on increased signal on T2-weighted images.
The biopsy tract or incision should be removed en bloc with the resection specimen.
Although evidence of major vascular, bony, or nerve involvement may be indications
for amputation, en bloc resection of the tumor with vascular structures, bone, or seg-
ments of nerve can be performed with reconstruction and interposition grafting. Often,
the superficial and infiltrative nature of MFS results in large surgical resection beds that
require complex reconstruction for wound closure. Consultation with plastic surgeons
for local tissue advancement flaps, rotational flap, and free-flaps are sometimes
necessary. The complexity of this type of excision may require a multidisciplinary sur-
gical team including a vascular surgeon, neurosurgeon, and a reconstructive plastic
surgeon in addition to a sarcoma surgical oncologist. The authors highly recommend
for the patient to have the opportunity to meet and discuss the surgical plan with each
of the surgical specialties involved in the case and understand and be prepared for the
resection and the necessary vascular and/or reconstructive procedures.
Intraoperative margin assessment with frozen section is notoriously difficult and
unreliable.
CLINICAL OUTCOMES
Overall survival for patients with localized MFS ranges from 61% to 77% at 5-year
(Table 2).3,26 Resection margin status at initial operation remains the most important
factor associated with survival.3,27,28
MFS are locally aggressive tumors that have a propensity for local recurrence
(LR) (Table 3). LR rates range from 16% to 57%, with a significant proportion of
784 Roland et al
Table 2
Disease-specific and overall survival rates for myxofibrosarcoma
Number of 5-y Disease-Specific 5-y Overall

Reference, Study Year Patients Survival (%) Survival (%)
Lin et al,27 2006 61 73 —
Huang et al,28 2010 49 96 —
Sanfilippo et al,3 2011 158 — 77
Lee et al,15 2016 197 51 —
Look Hong et al,26 2013 69 — 61
Haglund et al,30 2012 36 — 65 (4 y)
patients developing multiple recurrences (25%–52%).3,15,26–30 Median time to LR

is approximately 8 to 27 months but can occur up to 8 years after initial treatment.3
Margin status at initial resection is the most important predictor of LR, as patients
with a microscopically negative margin are less likely to recur than those
with microscopically positive margins.3,30 Further, Haglund and colleagues30
demonstrated reduced local recurrence rates for patients with wider microscopic
margins. Among patients with negative margins, 6 of 15 patients with less than
1 cm margin had an LR, whereas none of the patients with a margins of at least
1 cm had an LR.
Tumor grade has also been evaluated in relationship to LR.8,13,16,31 As discussed
previously, various grading systems have been used, making it difficult to compare be-
tween studies (Table 4). However, the risk of recurrence ranged from approximately
48% for low-grade tumors to 62% for high-grade tumors.
Interestingly, Huang and colleagues31 found that when low-grade tumors recur, they
often recur at a higher grade, demonstrating evidence of tumor progression. Further-
more, of those who demonstrated tumor progression, up to 50% of patients devel-
oped distant metastases compared with only 17% of patients who did not have
histologic progression.
The tendency for local recurrences makes limb salvage difficult. MFS amputation
rates are as high 17% to 41%,30,32 as compared with approximately 5% for all other
soft tissue sarcoma histologies, highlighting the importance of optimal, multimodal
therapy at initial presentation.
Table 3
Local recurrence rates for myxofibrosarcoma
Number of Local Recurrence Multiple

Reference, Study Year Patients Rate Number Recurrences Number 5 Year RFS
Lin et al,27 2006 61 27 (44%) 13 (48%) 30%
Huang et al,28 2010 49 28 (57%) 7/28 (25%) 40%
Sanfilippo et al,3 2011 158 20 (17%) 14/27 (52%) 82%
Haglund et al,30 2012 36 11 (31%) 4/11 (45%) 60% (4 y)
Lee et al,15 2016 197 54 (27%) — 25%
Dewan et al,29 2012 172 27 (17%) — —
Look Hong et al,26 2013 69 11 (16%) 4/11 (36%) 72%
16%–57% 25%–52% 25%–82%
Table 4
Relationship between histologic grade and local recurrence for myxofibrosarcoma
Study, Year Grade 1 Grade 2 Grade 3 Grade 4

Mentzel et al,16 1996 6/12 (50%) 9/13 (69%) 18/33 (55%) —
Angervall et al,8 1977 0/2 2/7 (29%) 6/10 (60%) 7/11 (64%)
Merck et al,13 1983 3/8 (38%) 13/27 (48%) 21/41 (51%) 17/28 (61%)
Huang et al,31 2004 28/49 (57%) — — —
w48% w49% 55% 62%
Like other soft tissue sarcomas, a proportion of patients with initially

localized disease will develop distant metastases (Tables 5 and 6). Overall
5-year metastasis-free survival is 47% to 90% and varies by tumor grade
(Table 7).8,13,15,16,31
ROLE OF RADIATION
Given that local recurrence is a critical problem in patients with MFS, the potential for
adjuvant therapies is appealing to reduce potential local and distant recurrences.
Based on randomized trials including a multitude of sarcoma subtypes, there is
assumed to be an improvement in local control with radiation therapy in the treatment
of MFS.33,34 However, there are no randomized data specific to MFS evaluating the
role of radiation therapy (XRT). Several retrospective cohort studies3,26,32 have evalu-
ated the association of XRT and recurrence (see Table 7). Unfortunately, these studies
are small and likely underpowered to demonstrate a significant difference. Currently,
the use of XRT for patients with MFS varies by institution and should be based on an
individualized patient basis.
ROLE OF CHEMOTHERAPY
The role of chemotherapy in the treatment of MFS is less clear. There are no random-
ized clinical trials evaluating chemotherapy in the treatment of MFS. Several cohort
studies3,26,32 have evaluated overall survival of patients with primary resected MFS,
some of whom were treated with chemotherapy (Table 8). None of these studies
demonstrated a benefit in distant metastases or overall survival with the use of chemo-
therapy. Therefore, the use of chemotherapy should be used in the setting of a clinical
trial.
Table 5
Relation between histologic grade and rate of metastasis for myxofibrosarcoma
Reference, Study Year Grade 1 Grade 2 Grade 3 Grade 4

Mentzel et al,16 1996 0/12 5/13 (38%) 10/33 (29%) —
Angervall et al,8 1977 0/2 2/7 (29%) 2/11 (18%) 3/11 (27%)
Merck et al,13 1983 0/8 6/27 (21%) 21/45 (47%) 11/29 (38%)
Huang et al,31 2004 — 7/49 (14%) — —
26% 31% 33%
786 Roland et al
Table 6
Impact of radiation therapy on local recurrence in myxofibrosarcoma
Reference, Study Year # Patients Radiation Tx (%) Local Recurrence HR (95% CI)
Sanfilippo et al,3 2011 158 35% (RT) 1.1 (0.5–2.6)b
14% CRT
Look Hong et al,26 2013 69 77% 0.43 (0.12–1.51)a
32
Mutter et al, 2012 114 80% 0.6 (0.29–1.27)a
Abbreviations: CRT, chemoradiation therapy; RT, radiation therapy.

a
Univariate analysis.
b
Multivariable analysis.
Table 7
Five-year metastasis-free-survival for myxofibrosarcomas
Reference, Study Year Number of Patients 5-Year Metastasis-Free Survival (%)

Lin et al,27 2006 61 60
Huang et al,28 2010 49 90
Sanfilippo et al,3 2011 158 85
Lee et al,15 2016 197 47
Look Hong et al,26 2013 69 82
47–90
Table 8
Impact of chemotherapy on overall survival in myxofibrosarcoma
Number Chemo Overall Survival HR

Reference, Study Year of Patients Tx (%) (95% Confidence Interval)
Sanfilippo et al,3 2011 158 14% CRT 0.8 (0.3–2.2)b
26
Look Hong et al, 2013 69 12% CRT 0.92 (0.27–3.14)a
18% CTx
Mutter et al,32 2012 114 11% 1.31 (0.71–2.4)a
Abbreviations: CRT, chemoradiation therapy; CTx, chemotherapy only.

a
Univariate analysis.
b
Multivariable analysis.
SUMMARY
Myxofibrosarcoma is a unique subtype of soft tissue sarcoma with a locally infiltrative

behavior. High-quality MRI imaging is critical for preoperative planning. Wide surgical
resection with 2 cm soft tissue margin is the mainstay of treatment and can require
complex vascular and plastic surgery reconstruction. Local recurrence is common,
and a subset of patients with high-grade lesions will develop distant metastases.
Radiation may be beneficial in reducing local recurrence
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M y x o f i b ro s a rc o m a

Christina L. Roland, MDa,*, Wei-Lien Wang, MDb,

INTRODUCTION: NATURE OF THE PROBLEM

Myxofibrosarcoma (MFS) is a unique subtype of soft tissue sarcoma often characterized

Disclosure: The authors have nothing to disclose.

Surg Oncol Clin N Am 25 (2016) 775–788

Myxofibrosarcoma was first formally described in 1977.6 Diagnostic terminology has

Fig. 2. Gross appearance of myxofibrosarcoma. The tumor is composed of lobulated areas of

CYTOGENETICS AND MOLECULAR FINDINGS

One of the major challenges of myxofibrosarcoma is to define the boundaries of the

Features Low-Grade Myxofibrosarcoma

THERAPEUTIC OPTIONS/SURGICAL TECHNIQUE

Margin-negative surgical resection is the cornerstone of treatment for patients with

Fig. 7. Preoperative planning algorithm for patients with myxofibrosarcoma.

T2-weighted MRI with pre-and postgadolinium imaging is part of the preoperative

Number of 5-y Disease-Specific 5-y Overall

patients developing multiple recurrences (25%–52%).3,15,26–30 Median time to LR

Number of Local Recurrence Multiple

Study, Year Grade 1 Grade 2 Grade 3 Grade 4

Like other soft tissue sarcomas, a proportion of patients with initially

Reference, Study Year Grade 1 Grade 2 Grade 3 Grade 4

Abbreviations: CRT, chemoradiation therapy; RT, radiation therapy.

Reference, Study Year Number of Patients 5-Year Metastasis-Free Survival (%)

Number Chemo Overall Survival HR

Abbreviations: CRT, chemoradiation therapy; CTx, chemotherapy only.

Myxofibrosarcoma is a unique subtype of soft tissue sarcoma with a locally infiltrative

2. Fletcher C, Unni K, Mertens F. Pathology and genetics of tumours of soft tissue

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