Atypical evolution of a synovial sarcoma: case report [605224]

Atypical evolution of a synovial sarcoma: case report
Nitipir Cornelia1,2, Popa Ana Maria1,Olaru Mihaela1,Orlov Cristina1
1”Elias” University Emergency Hospital, Medical Oncology Department, Bucharest, Romania
2”Carol Davila” University of Medicine and Pha rmacy, Bucharest, Romania
[anonimizat] , [anonimizat] , [anonimizat]

Abstract
Synovial sarcoma represents almost 1/10 of all soft tissue neoplasms, and half of patients
diagnosed will develop metastases in the course of the disease. In most cases, cancer cells spread
to the lungs as a first site of metastasis [1]. In this paper we present a rare case of a synovial
sarcoma in a young female. The patient was diagnosed with a biphasic synovial sarcoma located
in the upper left thigh, for which s he underwent surgery – with clear margins and adjuvant
radiotherapy. She was disease free for 12 months until s he developed multiple bone metastases
(including to the clivus). Whole body computer tomography scan showed no visceral
involvement. Multiple courses of systemic therapy were used, including pazopanib, under which
she had progression free survival of 11 mo nths. Progression, however, was still limited to the
bones. Although skeletal lesions without pulmonary involvement are uncommon in synovial
sarcomas and cranial metastases are extremely rare, further research is needed regarding
treatment decisions in the se situations.
Keywords: clival metastasis, bone metastases, synovial sarcoma
Introduction
Synovial sarcoma represents approximately 7-10% of all soft tissue neoplasms and it usually
affects young adults between 20 and 40 years of age and adolescents. Desp ite the name, the
tissue of origin remains unknown, although some authors consider that primitive muscle cells
may play a role in the tumor development. Between the different histological subtypes,
monophasic synovial sarcoma accounts for more than half of all diagnosed lesions, followed by
the biphasic subtype. On imagistic findings they are often calcified and usually arise near joints.
At diagnosis, 20% of patients have positive lymph nodes. In advanced stages, cancer cells
frequently disseminate to the lungs (~80%) [1,2] .
Case report
We present the case of a female patient, 28 years old, non -smoker, with no significant past
medical history and no family history of cancer, who was admitted in the Orthopedics
Department of a private hospital in Bucharest on March 2015, accusing pain and a progressively
increasing swelling in the left proximal thigh. Magnetic resonance imaging (MRI) showed a
tumor mass in the left Sartorius muscle (Fig. 1, 2) , infiltrative in the subcutaneous tissue at its
distal end, with sm all left inguinal adenopathies and superficial thrombosis of the great
saphenous vein. Whole body computer tomography (CT) scan was negative for disseminated
disease.

(a) (b)
Figure 1. Cross sectional MRI images show ing a tumor mass in the left Sartorius muscle on T1 –
weighted (a) and T2 -weighted (b) images.

(a) (b)
Figure 2. MRI images sho wing a tumor mass in the left Sartorius muscle on T2 -weighted sagittal
(a) and T1 -weighted coronal (b) images.
The orthopedics team recommended surgery and the patient underwent wide, oncological
margin -free local excision of the mass, en bloc with the Sar torius muscle and a loco -regional
lymph node. Histologically, the mass showed characteristic features of a malignant vascular and
atypical endothelial proliferation. The inguinal lymph node dissected and surgical margins were
free of tumor cells. Immunohis tochemistry (IHC) findings were consistent with a biphasic
synovial sarcoma. Cancer cells were positive for vimentin, EMA and bcl2 and had a proliferative
index of 30%. Genetic testing was positive for SS18 rearrangements. Post -operative MRI

showed no resi dual disease. The patient underwent adjuvant radiotherapy with a total dose of 60
Gy prescribed to the target volume, well tolerated. No adjuvant chemotherapy was needed.
Following radiotherapy, she was diagnosed with primary ovarian insufficiency and was referred
to a fertility clinic. IHC testing was repeated and the tissue samples were negative for estrogen
and progesterone receptors. Thus, the patient was started on hormone replacement therapy.
She was disease free for 12 months until multiple bone met astases were identified following a
PET-CT (Fig. 3) . She had mixed lesions to her vertebrae, pelvis and ribs and the brain MRI
showed clival osteolytic metastasis. Besides mild headaches she did not accuse any other
symptoms. The case was assessed in a mul tidisciplinary team including an oncologist and a
radiotherapist and was decided to initiate systemic therapy with anthracyclines and zoledronic
acid, along with stereotactic radiotherapy targeting the clivus (25 Gy were administered divided
in 5 fractions ). After cardiac assessment, given the anthracycline cardiotoxicity, the patient
underwent 6 cycles of doxorubicine 75 mg/m2 administered every 3 weeks and zoledronic acid
every 4 weeks, which was well tolerated. Follow up imagistic findings showed regress ion of the
irradiated clivus lesion, but unfortun ately she had progressive bone disease with the appearance
of new osteolytic lesions.

Figure 3. 18F-FDG PET/CT showing intense FDG uptake in multiple vertebrae .
The oncology team decided to change systemi c treatment with ifosfamide 1g/m2 per day for a 14
day continuous infusion, uromitexan equidose and zoledronic acid, cycle repeated every 28 days.
After 6 cycles, imagistic evaluation showed stationary disease. The patient then continued with
Pazopanib 800 mg p.o. daily and zoledronic acid and had stable disease for 11 months until
progression of bone metastases.
Discussion
Most of synovial sarcomas (70%) arise in the extremities, and in localized disease they have a
better overall survival outcome than thos e that arise in other parts of the body. The 5 year
survival rate is approximately 50%, and half of the patients diagnosed will develop metastases at
some point in time. In metastatic cases, 80 -90% of patients have pulmonary dissemination,

followed by lymp h node involvement (~20%) and rarely, 8 -10% of patients develop bone
metastases [2, 3]. A retrospective study published in 2013 analysed the distribution of bone
metastases amongst soft tissue sarcoma subtypes, and concluded that leiomyosarcomas,
undiffere ntiated pleomorphic sarcomas and angiosarcomas were the most common subtypes that
developed skeletal lesions, whereas synovial sarcomas accounted for 5% [4] . It is quite unusual
to diagnose bone metastases without pulmonary involvement, as it happened in the case
presented. Time to metastasis in this patient was 12 months, compared to a median of 16 -20
months according to published data [5]. Although no visceral metastases, the patient was treated
in accordance with the international guidelines for metasta tic disease, and showed stationary
disease under treatment with ifosfamide for 6 months and under treatment with pazopanib for 11
months, until prog ression. Progression, however , was still limited to the bones.
Another unique aspect about this case is the clival metastasis found on MRI. To date, few cases
were reported with metastatic disease involving the clivus, from different types of cancer. In
2013, a review of literature (from Medline database) was published investigating clival
metastases, where the authors reported a total of ~50 cases published from 1950 to 2013; the
most common types of primary cancer were prostate and hepatocellular carcinoma , no synovial
sarcomas were noted [6]. Although specific signs and symptoms were observed in these cases
related to the cranial nerves affected by the lesions, our patient accused only mild headaches. She
underwent stereotactic radiotherapy, with regression of the clival metastasis and alleviation of
symptoms.
To conclude, atypical cases of synovial sarcomas s hould be treated in specialized centers and
treatment decisions should always be made by a multidisciplinary team. Although uncommon,
bone metastases without any visceral involvement must be carefully assessed, due to the fact that
the course of the diseas e can be unpredictable. Further research is needed regarding treatment
decisions in these situations.

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