Forearm Mass in an Adolescent

Abstract

HISTORY AND PHYSICAL EXAMINATION A 17-year-old, right-hand-dominant man presented to our clinic and had a mass over the volar aspect of his right distal forearm that was growing for the past 2 months. The patient had a 2-year history of mild right wrist discomfort, which had recently worsened. He also complained of a new onset of paresthesias throughout his hand. He denied any fever, chills, night sweats, or weight loss. The patient was otherwise healthy with no previous injuries or major illnesses. A congenital chest wall cyst was removed at age 11 years with no complications. Otherwise, he had no major medical or surgical history. Social and family histories were noncontributory. On physical examination, the patient was a well-appearing adolescent male who reported pain in his right wrist region. He had full range of motion (ROM) of his shoulder, elbow, and fingers. Supination of the wrist was limited to 40°; otherwise the rest of the examination was within normal limits. He had normal motor function throughout his right upper extremity. Neurologic examination was normal in axillary, radial, musculocutaneous, median, and ulnar nerve distributions. He had a 2+ radial pulse and a normal Allen test. He had no adenopathy or peripheral edema. Examination revealed a 5 × 4-cm elliptical firm mass on the volar aspect of his right distal forearm. Based on the history, physical examination, and imaging studies, what is the differential diagnosis? IMAGING INTERPRETATION Plain radiographs of the forearm and wrist showed secondary changes and deformity of the distal ulna, suggestive of a soft tissue mass (Fig 1). Magnetic resonance imaging (MRI) scans revealed a large, well-circumscribed mass along the volar margin of the distal forearm extending distally to the level of the radiocarpal joint. The mass measured 4 cm × 3 cm × 6 cm. The mass was homogeneous and slightly hyperintense to muscle on axial T1-weighted images and hyperintense on corresponding axial T2-weighted images (Fig 2). Although the ulna was remodeled by the adjacent mass, there was no marrow involvement or periosteal reaction to suggest an aggressive nature. Hematologic studies were all normal.Fig 1.: A plain radiograph of the forearm and wrist shows secondary changes and deformity of the distal ulna with scalloping of the ulnar cortex.Fig 2. A–C.: Magnetic resonance images of the forearm and wrist are shown. (A) An axial view shows a well-circumscribed soft tissue mass measuring 4.1 x 2.9 x 6.2 cm extending between the radius and ulna in the pronator quadratus muscle. (B) A sagittal view shows the mass extending distally, just volar to the radiocarpal joint. (C) An axial image study with intravenous contrast view shows uptake throughout the lesion.DIFFERENTIAL DIAGNOSIS Juvenile aponeurotic fibroma Extra-abdominal desmoid tumor Schwannoma Lymphoma Ewing’s sarcoma Fibrosarcoma Synovial sarcoma Leiomyosarcoma Hemangiopericytoma An open incisional biopsy was done. At the time of the biopsy, the mass appeared sharply circumscribed, round, and multilobular. The mass appeared to be completely surrounded by a pseudocapsule. Based on the history and physical examination, radiographic studies, and histologic picture, what is the diagnosis and how should this lesion be treated? See page 305 for diagnosis and treatment. Continuation of ORP Conference from page 304. HISTOLOGY INTERPRETATION Gross evaluation after sectioning showed a gray-white mass measuring 5 cm in diameter with focal areas of hemorrhage. The histology specimens contained predominately spindle cells of uniform appearance, with small amounts of indistinct cytoplasm and oval dark-staining nuclei (Fig 3). There were also some tumor cells with an epithelioid appearance. Immunostains showed trace reactivity of keratins and a lack of reactivity for S100 protein, actins, desmin, and CD34.Fig 3. A–B.: (A) A low-power slide shows predominately spindle cells with surrounding fibrous septa. (B) A high-power slide shows mostly well-oriented, rather plump, spindle-shaped cells of uniform appearance, with small amounts of indistinct cytoplasm and oval dark-staining nuclei.DIAGNOSIS The findings were suggestive of a synovial sarcoma with monophasic morphology. Molecular analysis of the tumor using RT-PCR showed the neoplasm to be positive for SYT-SSX2 fusion transcripts associated with chromosomal translocation t (X; 18). The final diagnosis was monophasic synovial sarcoma, spindle cell type. DISCUSSION AND TREATMENT The current case is unusual for an aggressive soft tissue sarcoma. The plain radiographs showed the distal ulna was eroded by a slow-growing soft tissue mass, with gradual remodeling resulting in a deformed bone. There was no evidence on the MRI scans of active invasion into the bone, and there was no periosteal reaction. Common tumors that may have these characteristics include a large benign nerve tumor, juvenile aponeurotic fibroma, or (less likely) a slow-growing ganglion. The images with the contrast-enhanced view showed uptake throughout the lesion, ruling out a ganglion. Other differential diagnoses, based on the radiographs, could be eliminated by viewing the histologic sections. These included desmoid tumor and juvenile aponeurotic fibroma. The histologic sections contained intersecting fascicles of spindle cells. Based on this, the histologic differential diagnosis included schwannoma, Ewing’s sarcoma, lymphoma, fibrosarcoma, leiomyosarcoma, hemangiopericytoma, and synovial sarcoma.10 Two basic tissue types characterize schwannomas. Antoni Type A tissue has fascicles of spindle-shaped schwann cells streaming around numerous acellular, eosinophilic areas surrounded by paralleled or palisaded nuclei of spindle cells (Verocay bodies). Antoni Type B tissue consists entirely of less cellular and more randomly arranged spindle cells in a loose, myxomatous stroma.7 The lack of S-100 proteins on immunostaining also indicated that the current case was not a schwannoma. Ewing’s sarcomas usually show neural differentiation and have neural features. Ewing’s sarcomas also typically express microneme protein 2 antigen (cell surface glycoprotein) and more than 85% contain chromosomal translocation at the t (11;22) (q24;q12).7 Microneme protein 2 antigen is not specific to Ewing’s sarcoma and occasionally also is found in synovial sarcoma. Similarly, staining for T and B cells ruled out lymphoma (CD34). Synovial sarcoma can be distinguished from fibrosarcoma by its irregular and often multilobular growth pattern, the plump appearance of the nuclei, and the focal whorled arrangement of the spindle cells. In general, mitotic figures are less common than in fibrosarcoma.18 Additional factors that suggest a synovial sarcoma are the presence of mast cells, foci of calcification, the presence of hemangiopericytomatous vasculature, and, most importantly, the appearance of cytokeratin or epithelial membrane antigen in the neoplastic cells.18 Leiomyosarcomas typically have cells arranged in well-defined fascicles that intersect at right angles to each other. The nuclei are blunt-ended and the cytoplasm is more densely eosinophilic. Virtually all of these tumors stain strongly for smooth muscle actin.18 Hemangiopericytoma is a rare tumor and by definition a diagnosis of exclusion. Many synovial sarcomas exhibit a focal, prominent hemangiopericytomatous vascular pattern. However, hemangiopericytomas have this vasculature throughout the entire neoplasm, including myxoid and hyalinized zones. Hemangiopericytomas also lack immunohistochemical evidence of epithelial differentiation and express CD-34 in as many as 80% of cases, a marker typically absent in synovial sarcoma.18 Synovial sarcoma is the fourth most common histologic type of soft tissue sarcoma and occurs with maximal frequency in the second through fifth decades of life.4,14 Approximately 800 new cases of synovial cell sarcoma are diagnosed each year in the United States.7 Synovial sarcomas arise from pluripotential mesenchymal cells and occur primarily in the arms and legs, where they tend to arise adjacent to large joints, especially the knee region. The majority of synovial sarcomas occur in the lower limb, while up to 1/3 occur in the upper limb.8 In an upper extremity, synovial sarcoma tends to affect the wrist and forearm more often than the elbow or shoulder. Most synovial sarcomas are found within 5 cm of a joint. However, only a small percentage of cases are actually intra-articular. Infrequently, the disease develops in the head and neck and in the trunk.11,14 This cancer occurs mostly in adolescents and young adults, and it affects men more than women. Invasion of adjacent bone is seen in 10 to 20% of patients.11 Adjacent periosteal reaction can be seen in as many as 20% of patients. Distant metastases to bone usually are of the lytic-mixed variety.4 As in the current case, the most common symptom of synovial sarcoma is a deep-seated mass that is often accompanied by pain or tenderness. Synovial sarcoma is known to appear as an indolent lesion present for many years before presentation. In a few cases, pain or tenderness is present for several years even though a mass cannot be felt. These cases can be easily mistaken for synovitis, bursitis, or arthritis.14,15 In larger joints, such as the knee, vague symptoms of pain can go undiagnosed for months without a mass being observed. The radiographic findings in ½ of patients with synovial sarcoma are interpreted as normal. If an abnormality is present, the radiograph may reveal a well-defined round or lobulated soft tissue mass. Osseous erosion is observed in 5% to 20% of synovial sarcomas. Approximately 30% of patients have calcifications observed during imaging analysis. Calcification may be focal or diffuse and may appear fine, stippled, or dense.7 On MRI scans, the lesion may show cystic and solid components, areas of hemorrhage, and even fluid-fluid levels. Magnetic resonance imaging has proven to be valuable in the detection and staging of soft tissue tumors and also for surgical planning. However, MRI signal characteristics usually are nonspecific for histologic diagnosis. Histologic analysis of tissue is usually required for definitive diagnosis. Approximately ¼ of synovial sarcomas are associated with pulmonary metastases at the time of initial presentation.9,17,20 Gross specimens are usually well-demarcated, whitish-pink, fleshy masses with a heterogeneous appearance, and specimens may display solid, hemorrhagic, or cystic components when sectioned. These tumors can occasionally interdigitate with muscles and tendons or encase neurovascular structures.11 Calcified foci occasionally are observed. Heavy calcification tends to indicate less aggressive lesions and offers a more favorable prognosis.16 Depending on which cell type predominates, overall histologic appearances can be described as biphasic (epithelioid and spindle cell), monophasic spindle cell, or monophasic epithelioid. The biphasic subtype contains both epithelial and spindle cell components, whereas the monophasic fibrous type is a fibrosarcomalike spindle cell without an epithelial component.5,7,16,17 Marked cellular pleomorphism and atypia are uncommon, and when present, their appearance overlaps with that of high-grade malignant fibrous histiocytoma and fibrosarcoma.5 Synovial sarcoma is most frequently misdiagnosed as benign.2 More than 90% of patients with synovial sarcoma have a t (X:18) translocation mutation, which is not associated with other sarcomas. The translocation involves the SYT gene on chromosome 18 (at 18q11) and the SSX1 or SSX2 gene on the X chromosome (at Xp11). These genes appear to be transcription regulators, which either activate proto-oncogenes or inhibit tumor suppressor genes. Subtypes of these translocations have been shown to correlate with the distinct histologic subtypes and potential prognostic differences.1 Biphasic tumors, containing epithelial and spindle cell components, express the SYT-SSX1 transcript, although monophasic tumors with only a spindle cell component may express either transcript. Other than molecular diagnostic tests, no laboratory studies are specific for this diagnosis. The current case shows the diagnostic value of cytogenetics in distinguishing among various soft tissue sarcomas. These tumors are treated aggressively with limb-sparing surgery when possible. The recommended treatment is wide resection. If negative margins cannot be obtained during planning for limb salvage surgery, then amputation may be the other option. Local recurrence was shown to be high after a marginal resection (excision leaving positive margins).13,20 Wide resection is supplemented with radiation either preoperatively or postoperatively to reduce the recurrence.3 Multidrug adjuvant chemotherapy protocols are currently offered because synovial sarcomas have been shown to be chemosensitive, although controversy exists over its actual survival benefit in patients. 7,12 Previous studies indicate that younger age, smaller tumor size (< 5 cm), distal limb location, and negative resection margins correlate with improved outcomes. Adjuvant radiation therapy also correlates with improved outcomes.3,6,13 The natural history of synovial sarcoma includes local recurrence, usually within 2 years of initial treatment. This particularly is true when postoperative margins are positive. Although local control of sarcomas has improved with curative resections and adjuvant radiation, metastases develop eventually in most patients; the sites most commonly involved are the lung and skeleton. Regional lymph nodes are involved in 10 to 25% of patients.4,10,17 In the current patient, CT scans of his chest, abdomen, and pelvis revealed no abnormality. The Musculoskeletal Tumor Society classification of the tumor was Stage IIA (tumor contained within the pronator quadratus muscle without invasion into the adjacent bones). The patient had limb-sparing surgery that consisted of radical resection of distal forearm sarcoma, median nerve neurolysis, and ulnar nerve neurolysis, with resection of the distal ulna.3,9,19 This was followed by chemotherapy and radiation therapy. Although there was a marked decrease in flexion and extension of the wrist, the patient retained adequate functional use of the hand. Controversy exists about the prognostic implications of histologic subtypes; some have suggested that the epithelioid subtype is associated with lower risks of early metastasis and improved long-term survival rates.17Similarly, the monophasic subtype has been associated with a longer relapse-free period.18 Invasion of bone and neurovascular structures, marked cellular atypia, and distant metastases are associated with a poor prognosis.9,17,20 Synovial sarcoma has an approximately 50% survival rate at 5 years.12 Followup of our patient has involved clinical examination, MRI of the surgical site, and CT scans of the chest to check for any evidence of recurrence. This has been done at frequent intervals over the past 2 years without evidence of recurrence. At latest followup, there was no evidence of tumor recurrence.