Surgical Science, 2013, 4, 345-349
http://dx.doi.org/10.4236/ss.2013.48068 Published Online August 2013 (http://www.scirp.org/journal/ss)
High-Grade Extremity Myxofibrosarc oma with
Synchronous Mesenteric Leiomyosarcoma:
Double Primary Sarcomas
Milljae Shin, Sung-Joo Kim
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Received May 30, 2013; revised July 1, 2013; accepted July 9, 2013
Copyright © 2013 Milljae Shin, Sung-Joo Kim. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Here, we report the case of a 47-year-old male who presented with a painless palpable mass in the right shoulder. This
extremity tumor was diagnosed as a high-grade myxofibrosarcoma after a wide excision. Simultaneously, a synchro-
nous mesenteric mass was discovered, which proved to be a leiomyosarcoma.
Keywords: Double Primary; Leiomyosarcoma; Myxofibrosarcoma; Synchronous Sarcoma
Soft tissue sarcomas are a heterogeneous group of ma-
lignancies that arise from primitive mesenchymal cells
. Soft tissue sarcomas may be associated with the de-
velopment of other malignancies in several genetic con-
ditions including neurofibromatosis , familial adeno-
matous polyposis , retinoblastoma , and Li-Frau-
meni syndrome [4,5]. Aside from patients with family
histories, it is extremely rare to see two distinct sarcomas
of different histological types simultaneously and spo-
radically presenting in one individual.
Here, we report a case in which a mesenteric leiomyo-
sarcoma (LMS) was discovered during treatment for an
extremity myxofibrosarcoma (MFS). We speculate on
the possibility of a concurrent LMS mimicking the me-
tastasis of a primary high-grade MFS. To our knowledge,
this is the first published case report in the English lit-
erature of a patient with synchronous development of a
mesenteric LMS and an extremity MFS.
2. Case History
A 47-year-old man presented with a palpable mass in the
right shoulder, which had been present for two months
and had doubled in size during that time. He had under-
gone endoscopic mucosal resection for early gastric can-
cer six years before. He had no other significant medical
history and his family history was unremarkable. He had
experienced an obvious weight loss (3 kg/1 month, BMI
24.5 kg/m2). During the physical examination, we found
a palpable mobile mass that was firm, painless, and
non-tender to the touch. He was otherwise well. All
blood laboratory tests were within normal limits.
Since the clinical features were diagnostic of extremity
soft tissue sarcoma, a wide excision of the pathologic
lesion was performed in August 2011. Visible and palpa-
ble tissue was resected in an en bloc fashion. All in-
volved muscle bundles and overlying skin were included
in the resection. The tumor measured about 6 × 4.5 × 3
cm and did not seem to have an infiltrative growth pat-
tern. The lesion was identified as a high-grade MFS
which was categorized as 3/3 according to the French
Federation of Cancer Centers Sarcoma Group (FNCLCC)
grading system. The sample showed conspicuous solid
and hypercellular components with high pleomorphism,
numerous atypical mitotic figures (20 per 10 high-power
field), and confluent areas of necrosis in over half of the
sample (Figure 1). The surrounding skeletal muscle and
skin were not involved. According to the immunohisto-
chemistry report, tumor cells were positive for p53 and
vimentin but negative for cytokeratin (CK), S-100 pro-
tein, CD68 and alpha-smooth muscle actin (SMA). The
Ki-67 index was 50%.
To investigate the high-grade soft tissue extremity sar-
coma, whole-body 18F-2-fluoro-2-deoxy-D-glucose
(18FDG) positron emission tomography (PET) scan was
performed to determine the patient’s stage. The scan
showed a hypermetabolic mass (SUVmax = 15.1) in the
opyright © 2013 SciRes. SS
M. SHIN, S.-J. KIM
Figure 1. Microscopic view of the high-grade extremity
myxofibrosarcoma (hematoxylin-eosin staining; magnifica-
right lower quadrant of abdomen, which was suspicious
for malignancy (Figure 2(a)). There was no evidence of
increased FDG uptake in the right shoulder area or in
both lungs. A second CT scan of the abdomen revealed
the presence of a well-demarcated solid sized 4.7 × 5.0
cm and a cystic mass in mesentery of the right lower
quadrant (Figure 2(b)). At this point, metastasis was
suspected but no diagnosis was made. Because MFS is
known for its chemo-sensitivity, we decided to proceed
with the upfront palliative chemotherapy, and if the tu-
mor remained stable, would follow with a surgical me-
tastatectomy for the intra-abdominal mass.
From October 2011 to January 2012, the patient re-
ceived four cycles of chemotherapy. His regimen in-
cluded 50 mg/m2/4 days of doxorubicin in conjunction
with two-hour infusions of 2.0 g/m2/day ifosfamide [6,7].
Mesna equimolar to the ifosfamide was administered
immediately before and four hours after the ifosfamide.
Each cycle of chemotherapy was followed by G-CSF
prophylaxis. Radiologic images of the metastatic lesion,
both 18FDG-PET and abdominal CT scans, were taken
after the final cycle. The malignant mass in the right low-
er abdomen had no significant changes in size (5.2 × 5.0
cm) or FDG uptake (SUVmax = 15.3) from what was pre-
viously noted. There was no evidence of any abnormal
FDG uptake or a definite new lesion, which would have
suggested metastasis. After these four cycles of chemo-
therapy, the patient’s performance status was 1 (symp-
tomatic; fully ambulatory) and he was judged to have
stable disease. The patient was scheduled to complete
chemotherapy after surgical resection.
Figure 2. Images of intra-abdominal mass discovered: (a)
Whole-body 18F-2-fluoro-2-deoxy-D-glucose positron emis-
sion tomography, red arrow; (b) Abdominal computed to-
mography, yellow arrow.
The mesenteric mass on the right lower quadrant of the
abdomen was treated by surgical excision followed by an
incidental appendectomy at the department of surgery in
February 2012. During the laparotomy, we identified a
round encapsulated mass measuring 5.3 × 4.5 × 4.0 cm
rising from the mesentery of the terminal ileum. There
was no evidence of invasion into the small intestine or
adjacent tissues. The mass was removed via a simple
excision. The cut surface of this smooth mass was rub-
bery, pale yellow in color, myxoid, and nodular without
evidence of hemorrhagic necrosis (Figure 3).
Histopathologic examination of the mass revealed an
undifferentiated pleomorphic sarcoma (Figure 4(a)).
Besides high cellularity, it was composed of highly pleo-
morphic and spindle-shaped cells arranged in an inter-
lacing fascicular pattern, showing bizarre nuclei and in-
creased mitotic figures (10 per 10 high-power field). The
surgical margins were tumor-free. Immunohistochemical
samples stained with alpha-smooth muscle actin (SMA)
and desmin were diffuse and strongly positive (Figures
4(b) and (c)). The tumor cells demonstrated a negative
reaction for S-100 protein, CD68, c-MET and nestin. The
Ki-67 index was 35%. The results are summarized in
Table 1. Accordingly, immunohistochemistry of the me-
senteric mass established the diagnosis of LMS, which
was categorized as 3/3 according to the FNCLCC grad-
The patient had an unremarkable recovery and was
discharged within one week. The patient subsequently
received adjuvant radiation therapy four weeks after sur-
gery in March 2012. He was tolerable at the time of the
submission of this article.
Copyright © 2013 SciRes. SS
M. SHIN, S.-J. KIM 347
Figure 3. Bulk of the sarcoma manifested by a mesenteric
Figure 4. Microscopic view of the mesenteric mass (hema-
toxylin-eosin staining and immunohistochemical staining;
magnification ×100): Histological section (a) and immune-
reactivity for SMA (b) and desmin (c).
Table 1. Immunohistochemistry results between extremity
mass and mesenteric mass.
Antigen Extremity mass Mesenteric mass
p53 + ND
Vimentin + ND
CK (cytokeratin) − ND
S-100 protein − −
SMA (a-smooth muscle actin)− +
CD68 − −
Desmin ND +
c-MET ND −
Nestin ND −
Ki-67 + (50%) + (35%)
Final confirmed diagnosis Myxofibrosarcoma Leiomyosarcoma
−, negative; +, positive; ND, not done.
MFS is one of the most common sarcomas in the ex-
tremities of elderly patients . It arises more frequently
in subcutaneous tissues than in deep soft tissues . Dis-
tinctive histological features vary from a hypocellular,
mainly myxoid, and purely spindle-cell appearance (low-
grade neoplasm) to high-grade, pleomorphic (malignant
fibrous histiocytoma-like) lesions with multinucleated
giant cells, high mitotic activity, and areas of necrosis .
Because of morphological resemblances, high-grade
MFS is known as the myxoid variant of malignant fi-
brous histiocytoma . MFS has been reported to have
significantly higher recurrence rates, more than other soft
tissue sarcomas do, ranging from 32% to 60% [9,11,12].
Mentzel et al.  reported that 55.0% of MFS cases had
local recurrences and 21.7% developed metastases. They
also demonstrated that the local recurrence rate was in-
dependent of histological grade and tumor depth. DNA
aneuploidy is associated with histological grade but not
with the clinical course.
LMS is a malignant cancer of smooth muscle. LMS is
a relatively rare tumor, accounting for 5% to 10% of all
soft tissue sarcomas . LMS occurs mostly in the re-
troperitoneum and other intra-abdominal lesions, includ-
ing the mesentery. It is very difficult to accurately predict
the clinical behavior of LMS. LMS can remain dormant
for long periods and recur many years later. Massi et al.
 provided evidence that LMS has an aggressive bio-
logic activity. Early surgery, with margins of removal
that are as wide as possible, is the most effective inter-
vention . Advanced age, vascular invasion, DNA
aneuploidy, high mitotic rate, large tumor size, and
Copyright © 2013 SciRes. SS
M. SHIN, S.-J. KIM
American Joint Committee on Cancer (AJCC) staging
may have prognostic value [13,14,16].
Here, we report a case of high-grade extremity MFS
with a synchronous mesenteric LMS. The synchronous
development of multiple primary sarcomas of different
histopathology is extremely rare  and very few cases
have been reported in the literature [4,18,19]. In their
review of 5505 sarcomas, Grobmyer et al.  reported
only for 2 patients (0.04%) who presented with synchro-
nous soft tissue sarcomas of distinct pathology. This was
also the case for sarcomas associated with other malign-
nant neoplasms, such as lymphoma [21,22] or adenocar-
cinoma [23,24]. Both Merimsky et al.  and Geva et
al.  have respectively shown that 7.5% of soft tissue
sarcoma patients developed other malignant neoplasms
either before or after the initial sarcoma diagnosis. They
presented that the incidence of second primary sarcomas
in patients who were diagnosed previously with soft tis-
sue sarcoma was 7.5 to 12.5 times greater than the inci-
dence of primary soft tissue sarcoma in the general
How multiple primary tumors occur in the same indi-
vidual is unclear. Several explanations have been pro-
posed. One of the greatest contributing factors is genetic
susceptibility. Fon et al.  provided a novel hypothesis
that common genetic factors, such as germ-line P53 mu-
tations or mutations in checkpoint kinase-2, predispose
patients to developing multiple synchronous tumors. Us-
ing array-based comparative genomic hybridization
techniques, Wa et al.  demonstrated that LMS was
characterized by frequent loss of 13q, loss of 10q and
gain of 17p. Hernando et al.  found that mice carry-
ing homozygous deletion of Pten alleles developed
widespread smooth muscle cell hyperplasia and abdomi-
nal LMS. Little is known about the genetic association
between MFS and LMS. Congyang et al.  proposed
that histiocytic sarcoma have shared common clonal ori-
gins with diffuse large B cell lymphoma, or transdiffer-
entiation theory. Other possible mechanisms included
alkylating agents provoking chromosomal translocations
of normal mesenchymal tissue , radiation  and
persistent dysregulation of the immune system .
High-grade, advanced or malignant soft tissue sarco-
mas are aggressive diseases with poor prognosis and are
usually invasive and metastasize . Complete en bloc
surgical resection is the single most important factor for
better prognosis. Our case highlights the importance of
thorough surgical and pathologic examination for all
masses in a patient with synchronously detected sarco-
mas. Assuming that a mass is detected by radiological
imaging in a patient with malignancy, the lesion might be
interpreted as metastasis when a specific primary malig-
nancy has a great tendency for distant metastasis. In our
case, the mesenteric mass was initially misdiagnosed as
metastasis of the coexistent primary tumor, thus preclud-
ing its staging. However, our histological result showed
two obviously different synchronous sarcomas. In con-
clusion, both metastasis and multiple primary tumors
should always be taken into consideration in the differen-
tial diagnosis when synchronous sarcomas are encoun-
tered. Recently, Park et al.  emphasized performing
adequate pre-surgical evaluation and a comprehensive
biopsy, even though a painless, movable soft tissue sar-
coma of the extremity is likely a benign tumor. Take-
moto et al.  emphasized the necessity of using im-
munohistochemistry in the differential diagnosis of sar-
All authors of this manuscript have no financial conflicts
of interest to disclose.
 E. G. Demicco and A. J. Lazar, “Clinicopathologic Con-
siderations: How Can We Fine Tune Our Approach to
Sarcoma?” Seminars in Oncology, Vol. 38, Suppl. 3,
2011, pp. S3-18. doi:10.1053/j.seminoncol.2011.09.001
 D. G. Hope and J. J. Mulvihill, “Malignancy in Neurofi-
bromatosis,” Advances in Neurology, Vol. 29, 1981, pp.
 D. H. Abramson, M. R. Melson, I. J. Dunkel and C. M.
Frank, “Third (Fourth and Fifth) Nonocular Tumors in
Survivors of Retinoblastoma,” Ophthalmology, Vol. 108,
No. 10, 2001, pp. 1868-1876.
 P. Aurello, C. Cicchini, R. De Angelis, et al., “Synchro-
nous and Metachronous Retroperitoneal Sarcomas: Two
Case Reports,” Anticancer Research, Vol. 22, No. 4,
2002, pp. 2409-2412.
 F. P. Li, J. F. Fraumeni, J. J. Mulvihill, et al., “A Cancer
Family Syndrome in Twenty-Four Kindreds,” Cancer
Research, Vol. 48, No. 18, 1988, pp. 5358-5362.
 S. Sleijfer, C. Seynaeve and J. Verweij, “Using Sin-
gle-Agent Therapy in Adult Patients with Advanced Soft
Tissue Sarcoma Can Still Be Considered Standard Care,”
Oncologist, Vol. 10, No. 10, 2005, pp. 833-841.
 M. Tascilar, W. J. Loos, C. Seynaeve, J. Verweij and S.
Sleijfer, “The Pharmacologic Basis of Ifosfamide Use in
Adult Patients with Advanced Soft Tissue Sarcomas,”
Oncologist, Vol. 12, No. 11, 2007, pp. 1351-1360.
 R. W. Mutter, S. Singer, Z. Zhang, M. F. Brennan and K.
M. Alektiar, “The Enigma of Myxofibrosarcoma of the
Extremity,” Cancer, Vol. 118, No. 2, 2012, pp. 518-527.
 T. Mentzel, E. Calonje, C. Wadden, et al., “Myxofi-
brosarcoma. Clinicopathologic Analysis of 75 Cases with
Emphasis on the Low-Grade Variant,” The American
Journal of Surgical Pathology, Vol. 20, No. 4, 1996, pp.
Copyright © 2013 SciRes. SS
M. SHIN, S.-J. KIM
Copyright © 2013 SciRes. SS
 S. W. Weiss and F. M. Enzinger, “Myxoid Variant of
Malignant Fibrous Histiocytoma,” Cancer, Vol. 39, No. 4,
1977, pp. 1672-1685.
 L. Angervall, L. G. Kindblom and C. Merck, “Myxofi-
brosarcoma. A Study of 30 Cases,” Acta Pathologica Mi-
crobiologica Scandinavica Section A Pathology, Vol.
85A, No. 2, 1977, pp. 127-140.
 A. Gronchi, S. Lo Vullo, C. Colombo, et al., “Extremity
Soft Tissue Sarcoma in a Series of Patients TREATED at
a Single Institution: Local Control Directly Impacts Sur-
vival,” Annals of Surgery, Vol. 251, No. 3, 2010, pp.
 P. Gustafson, H. Willen, B. Baldetorp, et al., “Soft Tissue
Leiomyosarcoma. A Population-Based Epidemiologic and
Prognostic Study of 48 Patients, Including Cellular DNA
Content,” Cancer, Vol. 70, No. 1, 1992, pp. 114-119.
 D. Massi, G. Beltrami, M. M. Mela, et al., “Prognostic
Factors in Soft Tissue Leiomyosarcoma of the Extremi-
ties: A Retrospective Analysis of 42 Cases,” European
Journal of Surgical Oncology, Vol. 30, No. 5, 2004, pp.
 G. D. Demetri, S. Antonia, R. S. Benjamin, et al., “Soft
Tissue Sarcoma,” Journal of the National Comprehensive
Cancer Network, Vol. 8, No. 6, 2010, pp. 630-674.
 K. Miyajima, Y. Oda, Y. Oshiro, et al., “Clinicopatho-
logical Prognostic Factors in Soft Tissue Leiomyosar-
coma: A Multivariate Analysis,” Histopathology, Vol. 40,
No. 4, 2002, pp. 353-359.
 A. Tsang, J. R. Nash, M. V. Fordham, M. N. Hartley and
G. J. Poston, “The Management of Retroperitoneal Li-
posarcoma with Synchronous Intra-Duodenal Sarcoma,”
European Journal of Surgical Oncology, Vol. 29, No. 6,
2003, pp. 515-518. doi:10.1016/S0748-7983(03)00050-7
 A. Hadidy, A. Alsharif, R. Sheikh-Ali, et al., “Odonto-
genic Myxofibroma Synchronous with Primary Angio-
sarcoma of the Spleen,” British Journal of Radiology, Vol.
83, No. 985, 2010, pp. e10-13. doi:10.1259/bjr/14078580
 K. Tsutsumi, Y. Aida, T. Ohno and M. Ookura, “Primary
cardiac Rhabdomyosarcoma Following a Uterine Leio-
myosarcoma: Double Primary Sarcomas,” Japanese Jour-
nal of Thoracic and Cardiovascular Surgery, Vol. 53, No.
8, 2005, pp. 458-462. doi:10.1007/s11748-005-0086-7
 S. R. Grobmyer, N. Luther, C. R. Antonescu, S. Singer
and M. F. Brennan, “Multiple Primary Soft Tissue Sar-
comas,” Cancer, Vol. 101, No. 11, 2004, pp. 2633-2635.
 L. Congyang, W. Xinggui, L. Hao and H. Weihua, “Syn-
chronous Histiocytic Sarcoma and Diffuse Large B Cell
Lymphoma Involving the Stomach: A Case Report and
Review of the Literature,” International Journal of He-
matology, Vol. 93, No. 2, 2011, pp. 247-252.
 A. Cossu, A. Deiana, A. Lissia, et al., “Synchronous In-
terdigitating Dendritic Cell Sarcoma and B-Cell Small
Lymphocytic Lymphoma in a Lymph Node,” Archives of
Pathology & Laboratory Medicine, Vol. 130, No. 4, 2006,
 M. Rettenmaier, H. D. Epstein, L. N. Abaid, K. A. Bech-
tol and B. H. Goldstein, “Leiomyosarcoma with Syn-
chronous Clear Cell Ovarian Carcinoma,” Onkologie, Vol.
33, No. 12, 2010, pp. 695-697. doi:10.1159/000322216
 Y. Takemoto, M. Kawahara, S. Yamamoto, et al., “Syn-
chronous Primary Adenocarcinoma of the Lung and
Leiomyosarcoma of the Small Intestine,” Internal Medi-
cine, Vol. 39, No. 8, 2000, pp. 655-658.
 O. Merimsky, Y. Kollender, J. Issakov, et al., “Multiple
Primary Malignancies in Association with Soft Tissue
Sarcomas,” Cancer, Vol. 91, No. 7, 2001, pp. 1363-1371.
 R. Geva, I. Jiveliouk, M. Inbar, et al., “The Co-Occur-
rence of Breast Cancer and Soft Tissue Sarcoma in a Sin-
gle Cohort Series,” American Journal of Clinical Oncol-
ogy, Vol. 32, No. 1, 2009, pp. 34-37.
 A. Fon, L. Mileshkin, J. Slavin, et al., “Synchronous Di-
agnosis of Hodgkin Lymphoma and Osteosarcoma,” In-
ternal Medicine Journal, Vol. 37, No. 10, 2007, pp. 731-
 C. V. Wa, S. DeVries, Y. Y. Chen, F. M. Waldman and E.
S. Hwang, “Clinical Application of Array-Based Com-
parative Genomic Hybridization to Define the Relation-
ship between Multiple Synchronous Tumors,” Modern
Pathology, Vol. 18, No. 4, 2005, pp. 591-597.
 E. Hernando, E. Charytonowicz, M. E. Dudas, et al., “The
AKT-mTOR Pathway Plays a Critical Role in the Devel-
opment of Leiomyosarcomas,” Nature Medicine, Vol. 13,
No. 6, 2007, pp. 748-753. doi:10.1038/nm1560
 V. de Giorgi, R. Santi, M. Grazzini, et al., “Synchronous
Angiosarcoma, Melanoma and Morphea of the Breast
Skin 14 Years after Radiotherapy for Mammary Carci-
noma,” Acta Dermato-Venereologica, Vol. 90, No. 3,
2010, pp. 283-286.
 N. Ally, D. Kumar and F. M. Wodajo, “Synchronous
Fibrosarcoma and Medullary Thyroid Cancer in a Man
with AIDS,” American Journal of Clinical Oncology, Vol.
29, No. 5, 2006, pp. 532-533.
 J. H. Park, C. H. Kang, C. H. Kim and I. J. Chae, “Highly
Malignant Soft Tissue Sarcoma of the Extremity with a
Delayed Diagnosis,” World Journal of Surgical Oncology,
Vol. 8, 2010, p. 84. doi:10.1186/1477-7819-8-84