Liposarcoma is the second most frequent soft-tissue malignancy in adults. These tumors are relatively rare, comprising approximately 10% to 20% of soft-tissue sarcomas and less than 1% of all malignancies. 1-4 The lung is the organ most commonly involved by metastases, whereas central nervous system (CNS) involvement has been considered rare. 1,5,6 This report will review the case of a recurrent liposarcoma from an uncommon primary location presenting as a brain metastasis and will attempt to briefly review the patterns of CNS involvement in metastatic liposarcoma.
A 54-year-old woman sought treatment 9 years previously with a growth in the nail bed of the right thumb. This was thought to be a fungus, and the nail was removed. She experienced a recurrence 2 years later, and the nail was again removed. Pathological analysis revealed liposarcoma with a mixture of myxoid, round cell, and pleomorphic patterns (Fig. 1A). She underwent a right thumb distal phalangectomy at that time. Computed tomography (CT) of the chest and abdomen showed no evidence of metastatic disease, and no retroperitoneal primary. No chemotherapy or radiation was given.
The patient’s current complaints began approximately 5 months before her admission. She reported new onset of left lower extremity numbness and weakness. A brain CT scan at that time was reported as showing no abnormalities. Further evaluation included magnetic resonance imaging of the lumbar spine, which also was unrevealing. The symptoms progressed slowly to include the upper extremity. She was referred to a neurologist. Electromyographic testing was not helpful. Four months after the onset of these neurologic symptoms, a magnetic resonance scan of the brain demonstrated a single large right parafalcine mass (Fig. 2A–C). The tumor was dural based and enhanced with contrast material.
Craniotomy was performed and the mass was removed. Pathological analysis revealed a high grade myxoid sarcoma pattern (Fig. 1B,C). Chest and abdominal CT showed multiple pulmonary nodules but no disease in the abdomen or pelvis. The patient received palliative whole-brain radiotherapy and then cytotoxic systemic therapy. At 6 months after craniotomy, the patient has improved strength of the left lower extremity. She does not report any other symptoms referable to the cancer. Despite chemotherapy with paclitaxel (Taxol: Bristol-Myers Squibb Co., Princeton, NJ, U.S.A.), topotecan, and VP-16 (EtopoTax: Bristol-Myers Squibb), CT of the chest has documented progression of metastatic disease.
As with all sarcomas, liposarcomas arise from tissues derived from the primitive mesenchyme. The characteristic cells of this tumor, which display fatty degenerative changes, are lipoblasts. Of the 4,500 to 5,000 newly diagnosed cases of sarcoma in the United States each year, 10% to 20% are liposarcomas. 1,7 The peak incidence of these tumors is in the fifth to seventh decades. They are uncommon in childhood. Liposarcomas typically arise in the deep soft tissues of the proximal extremities and retroperitoneum. The low incidence of liposarcomas has made the discovery of their metastatic patterns, especially to the CNS, a slow process.
Liposarcoma are divided into four histologic subtypes. These are well differentiated, myxoid, pleomorphic, and round cell. Also, 10% to 20% will show mixed characteristics. The well-differentiated variety resembles the benign lipoma with some atypical nuclei. The myxoid variant shows myxoid changes of the ground substance with an abundance of mitotic figures. Many small cells define the round cell type, and numerous atypical nuclei and multinucleated giant cells are seen with pleomorphic liposarcoma. Some authors will include a fifth subtype—dedifferentiated. 8,9 This is characterized by the coexistence of well-differentiated and poorly differentiated areas in the same tumor, or in the tumor and the recurrence or metastasis. This was the situation with the present case (Fig. 1A–C). The natural history is strongly influenced by the grade and type.
Liposarcomas can be found at any site. However, they almost always extend in the deep structures such as the intermuscular facial planes. The retroperitoneum and deep thigh are the most frequent locations. Involvement of the hands or feet is uncommon. In the Armed Forces Institute of Pathology series of 1,067 cases, 42% involved the trunk and retroperitoneum, 42% the lower extremity, 10% the upper extremity, and 6% the head and neck. 9 No cases involving the hand were observed. Treatment is wide local excision when possible. 10 Radiation therapy is often used, especially with incomplete resection.
Tumor behavior depends on several factors. Recurrence rates are variable, but are most strongly influenced by location of tumor and accessibility for surgical excision. Not unexpectedly, recurrence is most common for deep-seated lesions, especially when incompletely excised. Local recurrence rates from 57%14 to 78%11 are seen with liposarcomas from all locations. Recurrence rates of up to 100% are seen with groups of retroperitoneal tumors. 4,12 Histology is also important, with myxoid and well-differentiated varieties demonstrating a lesser tendency to recur. 13,14
Metastases are frequent. Distant metastases were seen in 45% of patients in a series of 51, 11 and 51% in a series of 236 patients, which included 22 postmortem examinations. 15 Rates of metastasis are related to tumor subtype and degree of differentiation, and to a lesser degree on tumor size, location, and mode of therapy. Again, a much lower rate is observed for the myxoid and well-differentiated subtypes. Frequency of metastases has been found to be as high as 86% in nonmyxoid varieties. 16
Sarcoma metastatic to the CNS is less well described than metastatic carcinoma. Hematogenous spread is seen with sarcomas. This appears to be the method of spread to the CNS as well. Metastatic sarcoma is seen in a widespread distribution throughout the CNS and can be multiple. However, single CNS metastases are disproportionately higher in sarcomas than in carcinoma. 17,18
Early reports of metastatic sarcoma revealed brain metastases only rarely, 0% to 3%. 6,19 Some more recent reports have given estimates of brain metastases as high as 1.6% to 9.6%—possibly attributable to prolonged survival or the more widespread use of chemotherapeutic agents. 18,19 Autopsy reports provide yet a higher rate of brain involvement—3% to 15% of patients with sarcoma. 17
A 1983 study from Vezeridis et al. 7 looked at 242 patients with recurrent soft-tissue sarcomas between 1960 and 1978. This group included 43 patients with liposarcoma. The recurrence patterns were examined. First recurrences of sarcomas were most commonly local, followed by lung metastases. Brain involvement was found in 1.2%. A similar pattern was seen for second recurrence, but CNS involvement reached 3.9%. For subsequent recurrences, local disease dropped significantly, but brain metastases were seen in 14.3% by the fourth recurrence.
There are several studies looking exclusively at patients with liposarcoma. The findings are summarized in Table 1. These studies consistently demonstrate that liposarcoma spread to the brain is an uncommon finding.
It has been reported that the myxoid subtype shows no radiographic evidence of fat in up to 58% of cases and may resemble a cystlike abnormality on imaging studies. Such findings were noted in the noncontrasted images of our patient. Myxoid tumors are homogeneous on T1- and T2-weighted images, and have been reported to show enhancement of any nonmyxoid components on the tumor on magnetic resonance and CT scans. 21-23 There was enhancement of much of the tumor in our patient (Fig. 2A–C).
A primary tumor initially developed under the right thumbnail in the patient in our report. This is an extremely uncommon location, and not a site that one would generally associate with having a higher rate of recurrence. Despite treatment with wide local excision and despite negative chest and abdominal CT scans, widely metastatic disease developed. This second recurrence presented as a single, symptomatic brain mass.
Metastatic liposarcoma to the brain is a rarely encountered tumor. Recurrence and distant spread are related to histologic type and grade, location of primary, and completeness of surgical excision. 24,25 Frequency of brain involvement increases with subsequent recurrences. Even in view of all these generalizations, CNS involvement must be considered in any patient with a history of liposarcoma who presents with new neurologic complaints.
Acknowledgment: The authors thank Ms. Ester Vallejo for help in preparing the manuscript.
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