Kadir K. Bas, Visiting Surgical Research Fellow, Department of Surgery; Anil M. Bahadursingh, Assistant Professor of Surgery, Department of Surgery, St. Louis University School of Medicine, St. Louis, MO
Kadir K. Bas, MD
Visiting Surgical Research Fellow
Department of Surgery
Anil M. Bahadursingh, MD
Assistant Professor of Surgery
Department of Surgery
St. Louis University
School of Medicine
St. Louis, MO
Soft tissue sarcomas are very rare. Approximately 5,000 to 6,000 new cases are diagnosed annually in the United States, and these tumors account for 1% of adult malignancies.1 Malignant cartilaginous tumors that are not connected to bone are called extraskeletal chondrosarcomas. These lesions are extremely rare and comprise 1% to 2% of all malignant soft tissue tumors.2 This neoplasm differs from other forms of chondrosarcoma in that the preponderance of occurrences are in young adults, generally those between the ages of 15 and 35 years, with a slightly higher incidence in women.3 Although multiple predisposing factors have been identified such as genetic diseases, radiation exposure, certain chemical agents, lymphedema, and trauma, no specific etiology has been found.1
Clinical symptoms depend on the tumor's location. Distant metastases are usually observed in the lungs.3 Computed tomography (CT) scans, plain radiographs, and magnetic resonance imaging (MRI) are used to outline the mass before surgery. Angiography and bone scintigraphy may be used to determine whether bones and vessels have been affected.
Treatment is radical wide excision of the mass and adjuvant chemotherapy.4,5 Radiation therapy is recommended if the tumor cannot be completely removed.6 Because extraskeletal chondrosarcomas are highly malignant, the 2-year rate of survival is around 50%.7
A 75-year-old woman presented with a 6-month history of a mass in her right thigh. There was no history of trauma or radiation exposure, and the patient thought the mass was a hematoma that might resolve. The lesion, however, continued to enlarge and started to cause discomfort. On clinical examination, a firm, nontender, 20 x 15-cm mass was palpated in the left medial thigh. The mass was mobile and was not fixed to the skin. There was no edema, erythema, ecchymosis, lymphadenopathy compromise in peripheral circulation, or other significant clinical findings. The patient's only symptom was minimal discomfort because of the size of the mass.
The CT scan and MRI revealed no bony involvement (Figure 1). A CT scan of the chest showed multiple bilateral pulmonary nodules; the largest one was in the postero-basilar segment of the left lower lobe and measured 17 mm (Figure 2). These nodules were considered to be metastatic disease from the patient's primary tumor in her left thigh. Coronal and axial T1- and T2-weighted fast-spin-echo MRIs without fat suppression were taken of the lower extremities and showed a large mass in the adductor compartment of the left thigh, measuring approximately 13.4 cm and with a transverse diameter of 11 x 9.6 cm (Figure 3). Craniocaudal views, which were heterogeneous in T1 and T2 signals and showed T2 hyperintensity, suggested necrosis with no bone abnormality or involvement of the adjacent muscles in the posterior or anterior compartments of the thigh. No bone marrow signal abnormality was seen.
Radical excision of the mass was performed with 2-cm margins all around. No breach of the tumor capsule was noted and good margins were present. Histologically, all margins were confirmed to be tumor-free. Microscopic evaluation revealed a biomorphic pattern composed of undifferentiated round or oval cells resembling embryonal mesenchyme and well-differentiated cartilaginous tissue, which is a characteristic finding of extraskeletal mesenchymal chondrosarcoma (Figure 4). Immunohistochemically the cells in the chondroid areas were positive for S100 protein, but the tumor cells were negative for cytokeratin, actin, desmin, CD34, and factor VIII. The patient did not undergo adjuvant therapy.
Lightenstein and Bernstein first described mesenchymal chondrosarcomas in 1959, and Dowling reported the first case of an extraskeletal mesenchymal chondrosarcoma in 1964.8,9 Extraskeletal mesenchymal chondrosarcomas are extremely rare, fully malignant tumors with an obscure etiology. It is commonly thought that a history of trauma could be a predisposing factor for soft tissue sarcomas. Extraskeletal mesenchymal chondrosarcomas involve muscles or the central nervous system.5,10 These tumors usually occur intracranially in the spinal meninx and orbita. Occasionally they occur in unexpected organs, such as the abdominal wall, thyroid perineum, and heart.11-14 Clinical symptoms depend on the tumor's location. Intracranial or spinal processes may cause vomiting, headache, and various sensory and motor symptoms. Intraorbital tumors may cause exophthalmus and visual impairment. Intramuscular processes cause a slow painless swelling.
Diagnosis of extraskeletal mesenchymal chondrosarcomas is often delayed because these tumors are generally painless. The most common differential diagnosis includes hematoma or pulled muscle.1 The physician must consider the size of the mass and its relationship to other structures. In adults, any soft tissue mass of the extremities that is symptomatic, larger than 5 cm, or enlarging, and any new mass that persists beyond 4 weeks, should be studied carefully, preferably using imaging studies followed by incisional biopsy.15 Fine-needle aspiration biopsy has no role in diagnosis.1 True-cut core biopsies have been found to have accuracy rates of 98% for diagnosing malignancy and 94% for diagnosing sarcoma.16 Foci of calcifications of the mass typically can be seen on plain radiography and CT scans. MRI is usually performed because it provides three-dimensional images that help in planning surgical management. The lungs are the prime site for metastasis for extremity lesions, and a CT scan of the chest is useful to detect possible metastasis in the early period of the disease. Angiography is not recommended because it does not change the treatment strategy.1
The differential diagnosis of extraskeletal mesenchymal chondrosarcoma should include extraskeletal chondroma, synovial sarcoma, extraosseous osteosarcoma, and extraosseous myxoid chondrosarcoma. Currently, an extraskeletal chondrosarcoma is morphologically classified as either an extraskeletal myxoid chondrosarcoma or an extraskeletal mesenchymal chondrosarcoma. It is generally agreed that the mesenchymal variety carries a worse prognosis than its myxoid counterpart because it is metastatic in most cases.17
Pathologically, the main difference between extraskeletal myxoid chondrosarcoma and extraskeletal mesenchymal chondrosarcoma is that myxoid lesions include variable amounts of mucoid material in a myxoid stroma, and mesenchymal lesions include undifferentiated mesenchymal cells and cartilaginous tumor cells.3 Our patient's extraskeletal chondrosarcoma was the mesenchymal type. Grossly, on cut surface, the tumor will show a mixture of soft gray tissue and irregularly sized cartilage and in some cases, bone. Microscopically, it is composed of undifferentiated mesenchymal cells and well-differentiated cartilaginous tissue, usually with central calcification. Immunohistochemically, S100 protein is often found to be positive, but the tumor cells do not express desmin, actin, or cytokeratin.
S100 protein is a calcium-binding protein and is commonly expressed in peripheral nerve tumors, such as schwannomas, neurofibromas, neurogenic sarcomas, and some carcinoid tumors. Nakajima and associates also found S100 expressed by some other tumors, including chondrosarcomas, salivary gland pleomorphic adenomas, and Langerhans cell granulomatosis. Their study shows that S100 protein is not strictly specific to nervous tissue and its associated tumors; however, S100 positivity still can be useful in diagnosing extraskeletal mesenchymal chondrosarcomas.18
Recommended treatment is complete excision of the mass and systemic chemotherapy with or without local radiotherapy. When possible, the tumor must be excised with 2- to 3-cm margins of normal tissue, and meticulous attention must be taken to avoid major neurovascular injury during the dissection. There is a high rate of local recurrence if there is a positive margin after resection.19-21 For extremity tumors, extrapulmonary metastases are uncommon, but regional lymph node metastasis may be observed.3 Patients should undergo thoracotomy with the intent of resecting all disease if they have controllable primary tumors, no extrathoracic disease, are medically fit for thoracotomy, and have lung disease that appears to be completely resectable.22,23 Patients with unresectable pulmonary metastases or extrapulmonary metastatic sarcoma are best treated with systemic chemotherapy
Despite optimal multimodal therapy, at least one third of patients develop recurrent disease after a median disease-free interval of 18 months. Prognosis depends on several factors, including size, histological grade, and localization of the tumor; the presence of distant metastasis; and the sufficiency of the operation.24 The 10-year survival rate has been determined to be 28% with resection.25 Because local recurrence or metastases may be observed many years after a patient is rendered disease-free, long-term follow-up is necessary. It is recommended that follow-up include CT scans of the lungs and MRIs of the area of resection every 4 months for the first 3 years and then with decreasing frequency for as many as 20 years.26
Extraskeletal mesenchymal chondrosarcoma is a rare form of sarcoma that is not connected to bone, but typically involves the muscles or central nervous system. These tumors are generally painless, contributing to the frequent delays in their diagnosis. CT scanning, MRI, and plain radiographs may identify these lesions. Complete excision of the mass is recommended along with systemic chemotherapy and possible local radiotherapy. Frequent and thorough follow-up examinations are required because of the highly malignant nature of extraskeletal mesenchymal chondrosarcomas.