Intracranial metastasis from synovial sarcoma

Synovial sarcomas comprise between 5% to 10% of all soft tissue sarcomas in adults. It has a predilection for young adults and is one of the more frequently misdiagnosed soft tissue sarcomas. It is not unusual for synovial sarcoma to present initially after a traumatic event. It most commonly occurs in close proximity to a large joint. The most common site for metastasis is the lung, followed by lymph node involvement. Synovial sarcoma rarely metastasizes to the skeleton and when it occurs, it most commonly involves the long bones.¹

Cranial metastasis is rare and has only been described in 2 previously reported cases.^2,3 Reports of other sarcomas having intracranial metastasis include rhabdomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, Ewing’s sarcoma, and clear cell sarcoma from the kidney.^4-10 The synchronous or metachronous development of >2 primary soft tissue sarcomas has been reported.^11-13 These are primary soft tissue sarcomas occurring at multiple soft tissue sites without pulmonary or lymphatic involvement. It is often difficult to distinguish between the synchronous or metachronous appearance of a second primary and soft tissue sarcoma metastasis. This article presents a case of a 17-year-old adolescent boy who presented with simultaneous enlarging masses involving the skull and thigh. Open biopsies confirmed synovial sarcoma in both regions. Staging studies, including computed tomography (CT) of his chest, abdomen/pelvis and bone scan were otherwise negative for metastasis.

Case Report

A 17 year-old adolescent boy presented with simultaneously enlarging masses in his right posterior, proximal thigh and skull. The patient sustained an injury 3 months prior while playing football and was undergoing treatment by his local physician for a presumed hamstring tear. He was referred to an orthopedic oncologist because the swelling about his right thigh continued to increase and he began developing a mass on the left side of his cranium.

The thigh mass was evaluated with conventional radiographs and magnetic resonance imaging (MRI). Magnetic resonance imaging showed a large, 17×12-cm heterogenous mass within the deep soft tissue of the posterior aspect of the right thigh. The adductor muscles and the biceps femoris were displaced posteromedially and posterolaterally, respectively. The mass abutted the femur, but no definite cortical destruction was identified. The marrow signal appeared within normal limits. The sciatic nerve abutted the mass and was displaced posteromedially (Figure 1).

Figure 1: T-2 weighted axial image of right proximal thigh. A deep seated, large heterogenous mass adjacent to the posterior femoral cortex is noted. No intraosseous extension is seen.

Computed tomography of the skull (Figure 2) showed cortical disruption with compression of underlying brain tissue. Open biopsies of the cranium and thigh confirmed monophasic spindle cell synovial sarcoma at both sites (Figure 3).

Figure 2: CT of skull. An intracortical, expansile mass compressing the right side of the patient’s brain is seen. Figure 3: Hematoxylin-eosin stained (100) biopsy of the thigh mass showing a monophasic synovial sarcoma. The biopsy from the skull demonstrated identical histopathology.

Staging studies, which included a CT of the chest, abdomen, and pelvis were negative for metastasis. Bone scan showed subtle increased uptake in the soft tissue of the thigh and an area of increased tracer in the skull; otherwise there was no evidence of metastasis (Figure 4).

The patient was treated with neoadjuvant chemotherapy and external beam radiation to each site. Repeat imaging studies showed no progression of the cranial mass, a slightly diminished size of the thigh mass and negative staging studies for other areas of involvement.

Figure 4: Full body bone scan. Subtle uptake is seen in the soft tissues of the right thigh. On the anterior view, a small area of uptake is seen on the right side of the cranium. No other bone involvement is seen (A). Lateral view of a bone scan showing the head and neck region. Increased uptake is clearly seen in the superior aspect of the skull (B).

The patient underwent resection of the thigh mass with the closest margin being approximately 2 mm. The tumor extended to the periosteum, however there was no evidence of invasion. A subperiosteal dissection was performed; therefore the margin was close to the underlying proximal femur. The patient was then treated with additional postoperative chemotherapy. At the completion of chemotherapy he was restaged every 3 months.

At 6-month post chemotherapy evaluation, MRI showed a recurrent lesion in the femur directly adjacent to the previously resected tumor. Needle biopsy confirmed a recurrence of synovial sarcoma, and a wide resection was performed of the femoral lesion.

Six months following this resection the patient was noted to have a recurrent buttock mass, which was encasing his sciatic nerve. At this time, his staging studies indicated no progression of his skull lesion and no other evidence of metastasis. The patient underwent an external hemipelvectomy with a minimum of 2 cm margins. He did well until 9 months after the procedure when he developed new intraabdominal and pulmonary lesions. He died 2 months later, approximately 2 years after his initial presentation.

Discussion

Synovial sarcoma has a unique metastatic pattern. Unlike many other sarcomas, it is not uncommon for it to metastasize to the lymph nodes, other soft tissues, and on occasion, bone. Regional lymph node involvement has been reported in 3% to 10% of patients, and some have suggested performing sentinel lymph node biopsy to assist in staging.^14,15

Several cases of head and neck metastasis are reported in the literature; however brain metastasis is exceptionally rare.^8-10 A delay in diagnosis is also common with synovial sarcoma, because of their insidious onset, periarticular location and often benign appearing imaging features. Additionally, intralesional calcification may be seen on radiographs in up to 20% of synovial sarcoma. This finding may be confused with such entities as myositis ossificans, extraskeletal osteosarcoma, mesenchymal chondrosarcoma and sclerosing lipoma.

Presentation after a traumatic event is common, and suspicion of an underlying tumor should be raised if the swelling does not resolve in a timely fashion. Imaging studies are performed prior to biopsy to avoid artifact from hematoma and postsurgical edema. Ideally, the biopsy should be performed or supervised by the surgeon who will do the surgery if it proves to be malignant. Errors in biopsy track placement and unplanned surgical excisions may result in difficulty obtaining local control and lead to wound complications or amputation.

The mainstay of treatment for synovial sarcoma is wide surgical resection.¹⁶ This involves removal of the tumor with a cuff of normal tissue circumferentially around the mass. The centripetal growth pattern along soft tissue planes creates a false pseudocapsule, which often contain satellites of malignant cells. The addition of adjuvant treatments is not universally agreed on. Radiation has been shown to have beneficial effects in reducing local recurrence, and chemotherapy has shown a trend toward improved prognosis in some studies.¹⁵

In patients presenting with multiple sites of involvement, chemotherapy is generally recommended. Poor prognostic factors include: tumor >5 cm in diameter, deep, subfascial location, advanced age, neurovascular invasion, and high grade. In this high risk subgroup, chemotherapy may have more of a benefit.¹⁷

Radiotherapy should be considered for high-grade and intermediate-grade tumors with close or positive histologic margins. Optimal timing for radiation remains unclear, however many factors should be considered, including tumor size, location, type of resection and type of reconstruction. A lower dose is required when given prior to surgery (50 Gy) versus postoperative. A higher dose (60-66 Gy) is required after surgery to maximize tumor kill in a hypoxic environment.¹⁸ Other options include brachytherapy and intraoperative radiation. The advantages of these modalities include a reduction of the required dose and less toxicity to the overlying skin and adjacent soft tissue.

Since two-thirds of all recurrences occur within the first 2 years, follow up should be most intense during this period. Addressing recurrences early may allow for successful limb preservation. However, there is little evidence that early detection of recurrence has a major influence on survival.

Our patient presented with two simultaneous lesions without other evidence of metastases. The cranial lesion appeared to respond well to neoadjuvant chemotherapy and external beam radiation. Following treatment there was no imaging or clinical evidence of disease in this region. The thigh also responded to adjuvant therapy, but not as dramatically as the cranial mass. The margins were close, particularly at the underlying bone interface. However because the preoperative MRI did not show underlying bone involvement, the periosteum was used as a margin (~2mm).

The patient received maximal radiation to the region and eventually underwent an external hemipelvectomy in attempt to obtain local control. He soon thereafter developed wide spread metastases and succumbed to his disease. There was no evidence of recurrence in the cranial region at the time of his death. Kaufman³ reported a case of cerebral metastasis from synovial sarcoma in a 32-year-old man treated with radiation and noted complete remission. However, at the time of autopsy residual tumor was found in the brain. The impact of local recurrence on the likelihood of metastatic spread remains unclear.

Przkora et al² reported a 74-year-old woman who was being anticoagulated for recurrent thrombosis due to compression of her right popliteal vein that was thought to be a Baker’s cyst. She began experiencing progressive headache and vomiting. An intracranial hemorrhage was found, and at the time of evacuation, tissue sent to pathology showed synovial sarcoma. The mass thought to be the Baker’s cyst was then biopsied and showed a similar finding, synovial sarcoma. This patient died from her disease within 1 year.

Except for rhabdomyosarcoma, osteosarcoma, and Ewing’s sarcoma, the use of adjuvant chemotherapy generally does little to influence the natural history of sarcoma. A meta-analysis of adjuvant chemotherapy used to treat soft tissue sarcomas did not demonstrate an overall survival advantage, although progression free survival improved. Synovial sarcoma remains a challenge, both diagnostically and therapeutically. The focus for future developments will be identifying molecular therapeutic targets and the inhibition of angiogenesis.

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Authors

Drs Siegel and Dunham are from the Division of Orthopedic Surgery, Dr Lopez-Ben is from the Department of Radiology, and Dr Siegal is from the Department of Pathology, University of Alabama at Birmingham, Alabama.

Drs Siegel, Dunham, Lopez-Ben, and Siegal have no relevant financial relationships to disclose.

Correspondence should be addressed to Herrick J. Siegel, MD, University of Alabama at Birmingham, FOT 920, 1530 3rd Ave S, Birmingham, AL 35294.