High-Grade Extremity Myxofibrosarcoma with Synchronous Mesenteric Leiomyosarcoma: Double Primary Sarcomas

doi:10.4236/ss.2013.48068

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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

Email: [email protected]

Received May 30, 2013; revised July 1, 2013; accepted July 9, 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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

1. Introduction

Soft tissue sarcomas are a heterogeneous group of ma-

lignancies that arise from primitive mesenchymal cells

[1]. Soft tissue sarcomas may be associated with the de-

velopment of other malignancies in several genetic con-

ditions including neurofibromatosis [2], familial adeno-

matous polyposis [2], retinoblastoma [3], 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

M. SHIN, S.-J. KIM

346

Figure 1. Microscopic view of the high-grade extremity

myxofibrosarcoma (hematoxylin-eosin staining; magnifica-

tion ×100).

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.

(a) (b)

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-

ing system.

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.

M. SHIN, S.-J. KIM 347

Figure 3. Bulk of the sarcoma manifested by a mesenteric

mass.

(a)

(b)

(c)

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.

3. Discussion

MFS is one of the most common sarcomas in the ex-

tremities of elderly patients [8]. It arises more frequently

in subcutaneous tissues than in deep soft tissues [9]. 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 [9].

Because of morphological resemblances, high-grade

MFS is known as the myxoid variant of malignant fi-

brous histiocytoma [10]. 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. [9] 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 [13]. 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.

[14] 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 [15]. Advanced age, vascular invasion, DNA

aneuploidy, high mitotic rate, large tumor size, and

M. SHIN, S.-J. KIM

348

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 [17] and very few cases

have been reported in the literature [4,18,19]. In their

review of 5505 sarcomas, Grobmyer et al. [20] 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. [25] and Geva et

al. [26] 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

population [20,25].

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. [27] 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. [28] demonstrated that LMS was

characterized by frequent loss of 13q, loss of 10q and

gain of 17p. Hernando et al. [29] 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. [21] 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 [19], radiation [30] and

persistent dysregulation of the immune system [31].

High-grade, advanced or malignant soft tissue sarco-

mas are aggressive diseases with poor prognosis and are

usually invasive and metastasize [17]. 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. [32] 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. [24] emphasized the necessity of using im-

munohistochemistry in the differential diagnosis of sar-

comas.

4. Acknowledgements

All authors of this manuscript have no financial conflicts

of interest to disclose.

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