Intraneural Synovial Sarcoma of the Median Nerve in a 15-Year-Old Male: A Case Report and Review of Literature

Abstract

There have been 8 synovial sarcomas of the median nerve reported. We report a case of a 15-year-old male with synovial sarcoma of the right-hand median nerve. Patient presented with a 2-month history of enlarging mass at the base of the right thenar eminence associated with numbness in the median nerve distribution. Physical examination revealed a soft mass over the thenar eminence and paresthesia in the median nerve distribution. He underwent excision of the tumor, which revealed a well-encapsulated lesion encompassing the median nerve, involving the first, second, and radial aspect of the third web space as well as recurrent branches of the median nerve. Following excision of the tumor, a thorough metastatic workup was negative for metastatic disease. He was staged as III, T2b, N0, M0—poorly differentiated monophasic synovial sarcoma of the right median nerve. Postoperatively the patient was started on chemotherapy and radiation. Intraneural synovial sarcoma is extremely rare. Our case is the youngest with the longest follow-up. He is currently at a status of 3 years posttreatment with no signs of recurrence and excellent use of his right hand. This case is of particular interest due to the rarity of the disease along with this being the best outcome reported in the literature to-date.

Introduction

Synovial sarcoma (SS) is an aggressive soft tissue malignancy of mesenchymal origin and accounts for nearly 10% of all soft tissue sarcomas. ¹ Synovial sarcoma most commonly affects patients younger than 30 years of age, and is associated with a poor prognosis (50%-60% 5-year survival rate) despite radical surgical resection, local radiation therapy, and chemotheraphy.^2,3 However, prognosis is more favorable among younger patients and when the tumor affects the extremities.^1,2 Extremities are the most common site of origin, but these tumors have been known to arise for alternative site such as the heart, lung, and small intestines. In the rarest of occasions, the tumors may arise from peripheral nerves. ³

Synovial sarcoma is named after its resemblance to synovial cells on histopathologic examination; however, interestingly, it is not derived from synovial cells. A majority of SSs can be identified by the chromosomal translocation t(X;18)(p11.2;q11.2). The translocation breakpoint fuses the SS18 (previously “SYT”) on chromosome 18 with a homologous gene from chromosome X. The resultant fusion (SS18-SSX) is associated with either a monophasic or biphasic tumor containing a background of spindle cells with or without glandular epithelial differentiation. ⁴ The transducing-like enhancer-1 (TLE1) gene has shown to have good sensitivity, however limited specificity, for detecting SS, which allows for a confident preliminary diagnosis if positive. ⁵ Fluorescence in-situ hybridization (FISH), reverse transcription-polymerase chain reaction, or cytogenetic analysis is often used to confirm the diagnosis by identifying the t(X;18) translocation and resultant fusion gene. ⁴

Materials and Methods

A 15-year-old male presented with a 2-month history of an enlarging mass at the base of the right thenar eminence associated with numbness in the median nerve distribution. He denied previous trauma or surgery, and had no systemic symptoms. Physical exam revealed a soft mass over the thenar eminence and paresthesia in the median nerve distribution without motor weakness, and no lymphadenopathy was identified. Magnetic resonance imaging (MRI) of the hand revealed a T2 hyperintense brightly enhancing mass, measuring 6 x 4 millimeters within the palm (Figure 1). Based on the location of the mass, presence of median nerve palsy, and radiographic findings, it was initially diagnosed as a median nerve schwannoma.

Figure 1.

T1 MRI of intraneural median nerve sarcoma before excision (left and bottom right) and after excision (top right).

Note. MRI = magnetic resonance imaging.

He underwent excision of the tumor, which revealed a well-encapsulated lesion encompassing the median nerve, involving the first, second, and radial aspect of the third web space as well as recurrent branches of the median nerve (Figure 2). Due to the friable nature of the mass, it was removed in piecemeal fashion under the microscope, while preserving each of the median nerve fascicles.

Figure 2.

Median nerve before (left) and after (right) intraneural synovial sarcoma excision.

Microscopic analysis of the specimen reveals neoplastic cells with monotonously spindle cell, with relatively scant cytoplasm and architecturally distinct fascicle (Figure 3). Molecular study reveals SYT translocation by FISH. Immunohistochemistry is significant for strong and diffuse transducin-like enhancer-1 (TLE1) expression. Based on these pathological features, a diagnosis of monophasic synovial sarcoma of the median nerve was made.

Figure 3.

High power (200x—left; 400x—right) of the monophasic synovial sarcoma shows monotonously spindle-shaped nuclei which lack a nuclear “buckle” and relatively scant cytoplasm.

Note. Architecturally, distinct fascicle formation was noted. There was no interface identified with normal nerve or epithelial components, and no evidence of an admixture of axons within the neoplasm. However, there was a close association with and possible invasion of dense connective tissue, consistent with tendon.

Following excision of the tumor, a thorough metastatic workup was conducted. His repeat MRI of the right upper extremity reviewed no residual tumor. Computed tomography (CT) chest with contrast and positron emission tomography (PET) scan were normal, without evidence of metastatic disease. Based on these imaging studies, he was diagnosed as Stage III, T2b, N0, M0—poorly differentiated monophasic synovial sarcoma of the right median nerve.

Four weeks following surgical excision, patient started chemotherapy according to ARST 1321, Regimen A, which consisted of dexrazoxane, doxorubicin, ifosfamide, and pazopanib. Radiation therapy was started concurrently for total dose of 6660 cGy for positive margins.

Results

Posttreatment surveillance consisted of repeat MRI of the hand every 3 months for the 2 years, every 6 months thereafter. He also underwent repeat CT chest every 3 months for the first year, then every 12 months. At 3 years, he remains disease free with excellent use of his hand.

Discussion

Synovial sarcoma is a rare mesenchymal malignancy often presenting in the extremities, but can arise from heart, lung, small intestines, and, infrequently, peripheral nerves. Intraneural SSs are exceptionally rare malignancies with our case as only the sixth known case affecting the median nerve (Table 1). Four of the 6 cases (including ours) reported monophasic histologic findings.^3,6-9 However, interestingly the biphasic type is the most commonly reported histologic finding for all SSs. ⁹ Three cases reported patients that underwent total resection of the tumor and one who underwent extended resection. Only 2 cases were positive for the SS18-SSX fusion gene.^3,6-9

Table 1.

Cases of Synovial Sarcoma of the Median Nerve.

Authors	Sex/age	Hand	Radiation/chemotherapy	Surgery	Outcome
Rinehart et al 6	F/23	L	No/no	PR	Sensory loss in median nerve distribution immediately postoperatively, disease free at 7 months
Chesser et al 7	NA/16	NA	Yes/no	TR	No recurrence at 1 year
Uehara et al 8	F/33	R	Yes/no	TR	Recurred at 14 months, re-excision performed
Lipira et al 9	F/66	R	No/no	TR	Disease free at 6 months
Scheithauer et al 10	F/68	L	No/no	PR	Unstated
Tosi et al 11	F/59	R	No/no	TR	Unstated
Bhat et al 3	F/39	R	Yes/yes	TR	Multiple recurrences over 13 years, arm amputated below elbow.
Bhardwaj et al 12	F/15	L	Yes/no	TR	Unstated
Current study	M/15	R	Yes/yes	TR	No recurrences at 3 years

Note. PR = partial resection TR = total resection

The treatment of SSs is multifaceted, often incorporating surgical resection, local radiation therapy, and chemotherapy. Primary, localized SS is approached with wide, local surgical resection. ¹³ Radiotherapy is often added, particularly in patients with a high-risk tumor (eg, patient ≥25 years of age, tumor size ≥5 cm, poorly differentiated tumor).^13,14 While highly malignant, SSs are relatively chemosensitive compared to other soft tissue sarcomas. ¹⁵ Therefore, cytotoxic adjuvant or neoadjuvant chemotherapy is often considered in patients with advanced disease. ¹ SS is particularly sensitive to alkylating agents such as ifosfamide. ¹⁶ Furthermore, the Children’s Oncology Group study ARST1321 found pazopanib in combination with chemotherapy or radiation therapy alone was safe and showed significantly greater tumor response than chemotherapy or radiation therapy alone in children and adults with nonrhabdomyosarcoma soft tissue sarcomas. ¹⁷ Other options for treatment include adding on doxorubicin to the chemotherapy regiment and employing neoadjuvant instead of adjuvant chemotherapy.

Synovial sarcoma’s aggressive nature warrants combination surgical excision, chemotherapy, and radiation therapy with frequent monitoring for tumor recurrence after treatment. Despite aggressive treatment, the 5-year survival rate is a dismal 50% to 60% with death most commonly occurring from distant metastasis. ⁹ The most common site of metastasis is the lung. ⁹ Positive outcomes are associated with patient age < 25 years, distal tumor location, well differentiated tumor with low mitotic activity, tumor size < 5 cm, and localized tumor.^13,14 Magnetic resonance imaging is the preferred imaging modality when evaluating recurrence of SS of the extremities. ¹⁸ However, 1 multicenter, prospective study found no statistical difference in detecting recurrence of tumors affecting neurovascular structures. ¹⁹ Positron emission tomography is not routinely used to assess treatment response; however, it may be used at some institutions, and PET or CT may be used if there is clinical suspicion for recurrence of SS. ²⁰

Conclusion

Synovial sarcomas are particularly aggressive tumors that can occur in peripheral nerves, as in this case, but may occur anywhere in the body. Our case reports a SS with monophasic histologic findings, a positive SS18-SSX fusion gene, and TLE1 expression. This patient underwent total resection with adjuvant chemotherapy with ifosfamide and pazopanib and radiation. To our knowledge, this is the ninth case of intraneural SS of the median nerve reported in the literature. Our patient is the youngest reported and had a 3-year disease free follow-up.^3,6-9 This case is particularly notable for rarity of disease, age of the patient, tumor location, and extent of nerve involvement.