Annals of Surgical Oncology, 6(4):389 –394

Published by Lippincott Williams & Wilkins © 1999 The Society of Surgical Oncology, Inc.

Myxoid Liposarcoma—The Frequency and the Natural History

of Nonpulmonary Soft Tissue Metastases

Andrew J. Spillane, FRACS, Cyril Fisher, MD, FRCPath, and

J. Meirion Thomas, MS, MRCP, FRCS

Background: Myxoid liposarcomas (ML) make up the major subset of liposarcomas, which in
most series represent the second or third most common type of soft tissue sarcoma. The tendency
for ML to metastasize to other soft tissues (STM) in preference to lung parenchyma has been
previously described; however, the natural history of this tumor’s behavior is poorly documented.
Our intent was to analyze the natural history of ML and further quantify the incidence of STM,
concentrating on their significance in terms of survival.
Methods: We reviewed the experience at the Royal Marsden Hospital over a 10-year period,
documenting the clinicopathological behavior of ML, including the frequency of STM.
Results: There were 50 patients, with a median follow-up of 43 months. The actuarial 5-year soft
tissue metastasis rate was 31%, and the most common sites of STM were the retroperitoneum,
abdominal wall, and abdominal cavity. In those 12 patients who had STM there was a median
interval of 23 months after original diagnosis to the time the first metastasis became apparent (range,
0 –142 months). Median survival following first metastasis was 35 months; 6 of the 12 patients died
between 6 and 50 months. Four patients who had STM remain disease free at 15 to 59 months after their
first STM. Any round cell component of the ML was associated with a significantly greater chance of
metastatic disease (P ⫽ .02). In this series, the overall 5-year and 7-year survival rates were 85% and
68%. Patients with STM had an 11 times greater chance of dying than those who did not.
Conclusions: ML usually is an indolent disease, but there is a subset of patients who develop
STM and have a significantly worse prognosis. STM can occur years after the initial diagnosis and
can be associated with medium-long–term survival after they occur. STM should be managed
aggressively because of this.
Key Words: Soft tissue sarcoma—Myxoid liposarcoma—Survival—Soft tissue metastasis.

Soft tissue sarcomas (STS) most commonly metasta-
size to the lungs.1 Follow-up in STS patients, therefore,
primarily involves surveillance for local recurrence and
pulmonary metastases. Liposarcomas are the second or
third most common histological type of STS, represent-
ing between 8% and 17.8% of these sarcomas in most
series.1–3 Myxoid liposarcoma with or without a round
cell component (ML) is the major subtype of liposar-
coma, representing 45% to 55% of cases.2 Well-differ-
entiated, pleomorphic, and dedifferentiated liposarcoma
Received October 16, 1998; accepted January 21, 1999.
From the Melanoma and Sarcoma Unit (AJS, JMT) and Department
of Anatomical Pathology (CF), Royal Marsden Hospital, London,
United Kingdom.
Address correspondence to: J. Meirion Thomas, Melanoma and Sar-
coma Unit, Royal Marsden Hospital, Fulham Rd, London SW3 6JJ, UK;
Fax: 0171–351-5410; E-mail: joseph.thomas@rmh.nthames.nhs.uk
make up the other subtypes.4,5 ML and, less commonly,
other subtypes of liposarcoma have been reported to
demonstrate the phenomenon of nonpulmonary soft tis-
sue metastases (STM), which also has been described as
multicentric involvement of the retroperitoneum or op-
posite limb.1,2,5– 8 It is our experience that only ML has a
propensity to STM compared to other STS, and the
natural history of the behavior of this unusual sarcoma is
not obvious from the literature. We aim to give a chro-
nological overview and to verify the incidence and prog-
nostic significance of STM in a large series.
MATERIALS AND METHODS
We conducted a retrospective review of the Royal
Marsden Hospital (RMH) records and private patient
notes covering the period from January 1988 through

389
390 A. J. SPILLANE ET AL.
March 1998. The list of patients was obtained from the
Department of Anatomical Pathology database. The pa-
tients were all managed primarily by the senior author.
Some patients were referred to the RMH with recurrent
disease, but in all cases the histology of the primary
tumor was reviewed by one pathologist (CF). Follow-up
information was added to the database up to September
1, 1998. Exclusions from analysis were made on the
basis of inadequate information being available.
Definitions
Survival data were calculated from date of first histo-
logical diagnosis of ML to the date of last review or
death. In the metastatic group, survival was calculated
from the date of first histologically proven metastatic
disease or date of compelling radiological evidence of
metastatic disease.
Disease at knee or elbow level was included in the
distal limb group.
Myxoid liposarcoma was defined as that variant of
liposarcoma with lipoblasts that often are signet-ring
type, plexiform capillary pattern, and pools of myxoid
material or myxoid matrix with hyaluronidase-sensitive
acid mucopolysaccharides. If present, areas of round cell
differentiation were noted.
Soft tissue metastases included all nonpulmonary pa-
renchymal soft tissue and visceral metastases but ex-
cluded lymph node and bone metastases, which were to
be separately identified.
Survival data were calculated using the Kaplan-Meier
method.9 Cox’s proportional hazards regression model
was used to assess the importance of the round cell
component, and a time-dependent covariate10 was used
to assess the prognostic importance of STM.
RESULTS
Fifty-five patients were identified who had a patho-
logical diagnosis of myxoid liposarcoma (ML) during
this period of time. Five patients were excluded from the
analysis, three who were lost to follow-up and two who
were referred for opinion only. The median age at reg-
istration at the RMH was 43.5 years (range, 21–77
years). The male-to-female ratio was 0.92. Follow-up
ranged from 5–117 months, with a median of 43 months
in the patients still alive.
The sites of primary ML are documented in Table 1. In
one case there were two lesions at presentation (left thigh
and right shoulder), and we were unable to state which
was the primary. It is possible, but not likely, that they
were synchronous primaries. Thirty-one patients pre-
sented with a painless lump. Twelve patients were re-
Ann Surg Oncol, Vol. 6, No. 4, 1999
TABLE 1. Primary sites of myxoid liposarcomas
Site of primary No. cases
Proximal upper limb 2a
Distal upper limb 1
Proximal lower limb 27a
Distal lower limb 7
Buttock 5
Retroperitoneum 5
Posterior chest wall 1
Soft palate 1
Abdominal wall 2
a
1 patient had 2 synchronously detected tumors.
ferred to RMH with recurrent disease—10 with local
recurrence, one with a locally recurrent STM and a liver
metastasis, and one with a supraclavicular STM. The
pathological characteristics of the primary tumors were
typical ML in 34 cases and ML with areas of round cell
differentiation in 16 cases (32%).
Overall surgery was the primary therapy used in 48 of
the patients, and radiotherapy was used in 2 cases. Pri-
mary surgical intervention was performed at the RMH in
27 cases and at other institutions in 23 cases. Eleven of
these latter 23 cases required further local surgery to
achieve adequate clearance. Adjuvant radiotherapy was
given after surgery for the primary tumor in 20 cases.
Following management at the RMH there were six
cases of local recurrence, ranging from 5 to 38 months
after referral at a median of 20 months. At assessment,
three of these patients were disease-free, two had died,
and one was alive with residual disease. Three local
recurrences occurred in the STM group. One of those
patients had multiple local recurrences before referral.
The actuarial 5- and 7-year local recurrence rate after
treatment at the RMH was 16%.
Overall there were 12 cases with soft tissue metasta-
ses. These are summarized in Table 2, including the
chronological history of disease events and therapies.
The actuarial 5-year STM rate was 31%. The presence of
a round cell component on histopathology was predictive
of a 5-year metastasis rate of 58%, whereas those without
a round cell component had a 5-year metastasis rate of
16% (P ⫽ .02). The median interval after the primary
was diagnosed to the time the first metastasis became
apparent was 23 months (range, 0 –142 months). Median
survival following the first metastasis was 35 months.
Six patients were still alive at between 25 and 67 months
after their first metastasis, four of whom were disease-
free. There were six deaths in the STM group, all dis-
ease-related, ranging from 43 to 148 months (median, 63
months) after first diagnosis and from 6 to 50 months
after first metastasis. Figure 1 shows the survival plot of

Date of diagnosis ⫹
Primary site ⫹ treatment
Patient
1 12/92. R Posterolateral
chest wall; surgery
2 6/93. R Quadriceps;
surgery ⫹ RT
3 9/91. R knee area;
surgery
4 8/96. L thigh and R
shoulder; surgery
5 11/94. R hamstring;
surgery ⫹ RT
6 10/92. R buttock; surgery
7 2/91. R soft palate;
surgery ⫹ RT
Ann Surg Oncol, Vol. 6, No. 4, 1999
TABLE 2. Case descriptions of the patients with soft tissue metastases
Outcome to 9/98
Time post-diagnosis
Metastatic site(s) Treatment (Time after 1st met)
6/94 Axillary ⫹ retroperitoneal mass 7/94 Ifosfamide 9 g/m2 ⫻5, Doxorubicin DOD 8/98
1/98 Adductor compartment ⫹ intraabdominal 75 mg/m2 ⫻4 -⬎ SD 68 months
⫹ abdominal wall
6/98 Intra-abdominal ⫹ lung mets ⫹ pleural 2/95 Axillary surgery (50 months)
effusions 2/96 Abdominal surgery
5/97 Radiotherapy abdomen
2/98 Debulked abdomen
1/95 Retroperitoneal mass 1/95 Surgery ⫹ RT AWD
10/96 Supraclavicular mass 1/97 Surgery ⫹ (supraclavicular) RT 63 months
1/97 Lower posterior chest wall lesion 6/97 Surgery (44 months)
6/97 Recurrent retroperitoneal mass with 7/97 Doxorubicin 75 mg/m2 ⫻3 -⬎ PD
several transperitoneal sites
4/98 Progression chest wall mass 9/97 Ifosfamide 9 g/m2 ⫻6 -⬎ PR
4/98 RT to posterior chest wall
8/98 Gemcitabine 1250 mg/m2 ⫻4
12/93 Perineal ⫹ sigmoid mesocolon mets 12/93 Surgery (both sites) DOD 9/96
8/94 Paraspinal mass 9/94 Surgery ⫹ RT 60 months
4/95 Abdominal wall metastases 6/95 Debulking surgery (33 months)
9/95 Adrenal metastases 7/95 Ifosfamide 9 g/m2 ⫻2 -⬎PD
5/96 Further retroperitoneal disease 9/95 Doxorubicin 75 mg/m2 ⫻7 -⬎ GPR
5/96 Debulking surgery
6/97 Rectus sheath ⫹ L elbow ⫹ R thigh ⫹ L 6/97 Ifosfamide 12 g/m2 ⫻2 -⬎ SD ADF
gluteus maximus
10/97 R lung metastasis 8/97 Surgery 25 months
12/97 R thigh 10/97 Pulmonary metastasectomy (25 months)
12/97 Surgery
5/96 L flank ⫹ R lobe liver 6/96 Ifosfamide 5 g/m2 ⫹ doxorubicin 50 mg/m2 ⫻6 DOD - 8/98
(12/96) -⬎ PR (flank)/SD (liver)
1/97 Disease progression flank 9/97 Surgery abdominal wall 43 months
8/97 R supraclavicular ⫹ R infrascapular mets 11/97 Surgery neck & back (25 months)
9/97 L flank, R pleural apex (STM) 2/98 Carboplatin 610 mg ⫹ Etoposide 120 mg/m2 -
⬎PD
2/98 Local recurrence R thigh
12/94 2 large mets abdomen ⫹ LR 12/94 Surgery buttock AWD
3/95 LR–R buttock ⫹ abdominal mets 3/95 Surgery buttock & abdomen 61 months
MYXOID LIPOSARCOMA—FREQUENCY OF SOFT TISSUE METASTASES
8/97 R buttock recurrence 4/95 Ifosf 5 g/m2 ⫹ Doxo 50 mg/m2 ⫻4-adjuvant (35 months)
11/97 Abdominal recurrences ⫻ 7 8/97 Surgery on buttock recurrence
11/97 Debulking surgery
1/93 Lung met (PM) 1/93 Pulmonary metastasectomy DOD 6/96
2/94 Ascites, pelvic wall ⫹ ovarian mets 5/93 RT Lumbar vertebra 64 months
4/93 Probable bone met L4 vertebra 9/94 Debulking surgery (41 months)
8/94 Recurrent retroperitoneal masses 12/94 ifosfamide ⫹ doxorubicin ⫻3 -⬎ PD
4/95 R lumbar ⫹ increase retroperitoneal 5/95 surgery back
391
392 A. J. SPILLANE ET AL.

ADF, alive and disease-free; AWD, alive with disease; DOD, dead of disease; L, left; mets, metastases; R, right; RT, radiotherapy; SD, stable disease; PD, progressive disease; PR, partial
the 12 cases following first STM. Four patients in this
series had both pulmonary and soft tissue metastatic
(67 months)

(45 months)

(33 months)

(35 months)
117 months

148 months
(6 months)
62 months

57 months

DOD 4/95

DOD 8/95
62 months
disease. In Case 7, lung parenchyma was the first site of
metastatic disease, and in Case 12 the lung metastasis
ADF

ADF

ADF was detected synchronously with a STM. The other two

parenchymal lung metastases occurred after STM. Only
one case had a liver metastasis (Case 5), and there was
one presumed case of a bone metastasis (Case 7). Eight
of the patients with STM had chemotherapy during their
treatment. Further details of the chemotherapy regimens,
timing, and responses are given in Table 2. Six of the

Etoposide 75 mg/d - initial PR then PD

patients with STM had adjuvant radiotherapy at the time
Till Referral 12/86 surgery only; 2/87 RT

10/94 Laminectomy ⫹ excisional surgery

12/94 Thoracotomy excision pleural mets

9/92 Epirubicin 150 mg/m2 ⫻8 -⬎ GPR

of treatment of their primary, with 7 having radiotherapy

Debulking surgery abdomen
to metastatic disease sites. All 12 patients had between
one and four further surgical procedures for treatment of
Ifosfamide 5 g/m2 -⬎ PD

their metastatic disease.

response; GPR, good partial response; Doxo, doxorubicin; Ifosf, ifosfamide; PM, pulmonary metastasis; STM, soft tissue metastasis.
Among the other 38 patients in the series, there have
2/90 Resection of scar

11/87-⬎ 1/94 Surgery

been three deaths, all resulting from myxoid liposar-

2/93 Surgery ⫹ RT

1/96 Surgery ⫹ RT

9/92 Surgery axilla

coma. Two patients died from incompletely excised ret-

roperitoneal sarcomas, 3 and 12 months after diagnosis,
12/95 Surgery
5/95 Surgery

9/96 Surgery

Surgery

and one patient, an elderly woman, died at 19 months

after diagnosis following incompletely excised extensive
3/94
4/94
6/94
4/95

abdominal wall and groin disease.

At the time of analysis there were four patients alive
with clinically or radiologically apparent residual dis-
ease. Two of these were from the group with STM.
9/92 Axillary mass ⫹ pulmonary metastases

Patients with STM were 11 times more likely to die than

12/85, 8/86, 12/86, 11/87, 1/91, 2/92 LR

were patients without STM (hazard ratio 10.8, 95% CI:

10/94 Cord comp ⫹ erector spinae mass

3/94 Sternal subcutaneous metastasis ⫹

2.0 –59; P ⫽ .006). For the whole series of 50 cases, the

10/95 R supraclavicular fossa mass
12/94 Parietal pleural mets (STM)

overall 5-year and 7-year survival rates were 85% and

11/95 Abdominal wall metastasis
5/95 L gluteus max. metastasis

abdominal cavity metastasis

68%.
11/95 L ant abdominal wall
5/96 Chest wall metastasis
2/93 L thigh metastasis

DISCUSSION
1/94 Amputation

Soft tissue sarcomas typically metastasize to the lungs.

If metastases are resectable, there is potential for long-
term survival with pulmonary metastasectomy.4 There-
fore, surveillance for local recurrence and lung metasta-
sis forms the basis of follow-up. Liposarcomas are the
second or third most common STS in most series, rep-
resenting between 8% and 17.8% of the total.1–3 Lipo-
11/93. L buttock; surgery
7/93. R thigh; surgery ⫹

sarcomas have been reported to metastasize in 19% to

12/82. R thigh; surgery
fossa; surgery ⫹ RT

6/90. L thigh; surgery

12/88. L ischiorectal

37% of patients5,7,8,11 and may metastasize to soft tissues

rather than the lungs.5– 8,12 MLs form the major subset of
liposarcomas and usually are described as being of low
grade with low metastatic potential, similar to well-
⫹ RT
RT

differentiated liposarcoma.8 A round cell component to

ML is considered a higher grade version of ML and is
thought to have increased potential for metastasis.12 Ple-
omorphic and dedifferentiated liposarcomas also are
high grade, and when they metastasize, they mostly do so
8

10

11

12

to lung. It has been our experience that, compared to

Ann Surg Oncol, Vol. 6, No. 4, 1999

 MYXOID LIPOSARCOMA—FREQUENCY OF SOFT TISSUE METASTASES
other subtypes, only ML has a tendency to metastasize to
nonpulmonary soft tissue sites, and does so more often
than to lung parenchyma. The restriction of this phenom-
enon to ML has been observed by several other au-
thors,2,13 but not by all.8 Cheng et al. reported no asso-
ciation with histological subtype of liposarcoma, but
review of their data shows that 10 of 13 cases with
first-site metastases other than the lung were either myx-
oid or round cell subtypes. In the other three cases of
STM from other subtypes of liposarcoma, metastases
were to liver in two patients and bone in one patient.8 In
our series the most common sites of STM were the
retroperitoneum, abdominal wall, and abdominal cavity,
but there was a wide range of sites to both trunk and
limbs. With time, metastasis to multiple sites often oc-
curs (see Table 2). There have been case reports of
several unusual sites of metastasis.5,14 Enzinger and
Weiss suggest that for unknown reasons ML tend to
produce secondary lesions on the serosal surfaces of the
pleura, pericardium, and diaphragm, sometimes alone or
in combination with metastases to the viscera.2
Not surprisingly, metastatic disease was associated
with a significantly higher chance of dying (P ⫽ .006).
Of interest, however, is the median survival of 35 months
following first metastasis, with half the patients still
alive. The characteristic of first metastasis occurring
years after diagnosis previously has been reported,1,2,5,7
but from our data it is apparent that patients can enjoy
medium-long survival after developing metastatic dis-
ease. The median survival of 35 months after first me-
tastasis in this series contrasts with figures reported by
393
FIG. 1. Survival following first soft
tissue metastasis (n ⫽ 12).
Vezeridis et al. for a cohort of 242 STS, suggesting that
if lung was the first site of metastasis, the median sur-
vival is only 9.8 months.1 The three deaths in the group
with no STM were from unresectable gross disease, and
all died within 20 months of diagnosis.
The frequency of areas of round cell differentiation in
this cohort (32%) is similar to that previously reported in
series of myxoid liposarcoma. Kilpatrick et al. identified
43% of cases with round cell areas.6 They argued, like
Evans,5 that round cell liposarcoma should be regarded
as the poorly differentiated form of ML. This argument is
strengthened by the demonstration of the same chromo-
somal translocation of t12,15 (q13;p11) in both subtypes.16
It has been demonstrated that patients with ML contain-
ing more than 5% round cell differentiation had a higher
risk of death,12 whereas others state that a level more
than 25% is an adverse factor.6 In our study, the presence
of any round cell areas was associated with significantly
greater chance of metastasis at 5 years and, hence, a
worse prognosis.
In our series, eight patients received chemotherapy,
which, in one case, was adjuvant. There are too few patients
from whom to calculate a response rate; however, four of
seven patients who had chemotherapy for advanced disease
had a significant response to chemotherapy, and another
enjoyed prolonged disease stabilization. It seems reasonable
to conclude that myxoid liposarcoma is relatively chemo-
sensitive compared with STS as a group, given that pub-
lished response rates in phase III trials usually are in the
area of 25%.15 This series demonstrates that good palliation
can be achieved with chemotherapy for STM and that there
Ann Surg Oncol, Vol. 6, No. 4, 1999
394 A. J. SPILLANE ET AL.
may not be cross-resistance between ifosfamide and doxo-
rubicin, in either direction, as seen in Cases 2 and 3 (see
Table 2). This finding has not been widely reported in other
types of sarcoma.
In conclusion, ML is a distinct subtype of liposarcoma
that has a frequency of STM not seen in other types of
STS. In this series, 12 of 50 patients developed STM.
The median time to first metastasis was 23 months, and
median survival after first metastasis was 35 months,
demonstrating that even after metastatic disease there is
a good chance of medium-long–term survival. Therefore,
aggressive treatment, most often involving further sur-
gery, is warranted. When a patient with ML presents
originally, and if metastatic disease occurs, it is prudent
to include abdominal and pelvic computed tomography
scans in the staging work-up. When following up pa-
tients with ML it is sensible to investigate carefully what
may initially seem quite odd symptomatology for a STS
because of the unpredictable sites of recurrent disease.
Acknowledgment: The authors thank Dr R. A’Hern for his
assistance with the statistical analysis and Dr I. Judson for his
review of and comments on the chemotherapy data.
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