Myxoid liposarcoma: a rare soft-tissue tumor with a misleading benign appearance
© Loubignac et al. 2009
Received: 26 November 2008
Accepted: 22 April 2009
Published: 22 April 2009
Lipoma is by far the most common of all benign soft-tissue tumors which far outnumber malignant tumors. Soft-tissue sarcomas are malignant tumors and are usually named for the type of tissue in which they begin. Liposarcoma (LPS), which arises in the fatty tissue, is rather an uncommon soft-tissue tumor. Multiple histologic subtypes of liposarcoma are recognized, including myxoid liposarcoma, and correspond to tumors of very different prognosis. In two-third of the cases, this tumor occurs in the muscle while often demonstrating a misleading benign appearance as observed in the majority of soft-tissue sarcomas.
We report the case of a 50-year-old man operated on for a fat tumor of the thigh initially diagnosed as lipoma but revealing to be a myxoid liposarcoma after histopathological examination. The initial incomplete tumor excision required the need for a re-excision with adjuvant chemotherapy and complementary radiotherapy.
When any suspicious soft-tissue tumor is diagnosed, the combined information gathered from accurate preoperative radiographic planning and X-rays or surgical biopsy is of tremendous value for establishing the most appropriate therapeutic program, highly adapted to the histopathological findings.
Lipomas account for 50% of all benign soft-tissue tumors. Malignant tumors or sarcomas comprise approximately 1% of all soft-tissue tumors. They are also rare among the malignant tumors that occur in adult, reporting a prevalence lower than 1% and an incidence of 30 cases per million population [1, 2]. Liposarcoma itself (LPS) comprises about 15% of all soft-tissue sarcomas in the adult and its prognosis is highly related to the location, and more particularly to the histologic pattern of the tumor [3–5]. This fat tumor, of ubiquitous localization, commonly appears as a slowly enlarging mass with a misleadingly benign appearance . However, any soft-tissue tumor requires the need for a thorough preoperative X-Ray investigation [1, 7] and a biopsy should be performed if of more than five centimeters diameter .
Mr A. Oma, a patient aged 50 years, with a 5-year history of a small tumorous lesion, and regularly followed after a polytraumatism, presents on 23 December 2003, with the complaint of a gradually growing mass in his thigh for three months. This small tumor involving the antero-lateral aspect of the thigh within the upper one-third, has a soft consistency, no adherences to the surrounding structures and is well circumscribed. Neither functional nor general symptoms are associated and routine blood tests are normal. Such features suspects a common adipose tumor of lipoma type and its excision is scheduled on 27 January 2004. This simple and rapid surgical procedure includs the excision of an intramuscular, subaponeurosis tumor, very well defined within the vast external of the crural quadriceps. The tumor of approximately 8 cm is sent to the laboratory of pathological anatomy. The excised specimen is a 7.5-cm, well defined, flexible, ovoid tumor of gelatinous aspect and brownish appearance, with some more fleshy zones, without necrotic or hemorrhagic changes.
Postoperative management is simple: from March to July 2004, the patient is treated with adjuvant chemotherapy consisting of six cycles of MAID-type [Doxorubicine (20 mg/m2), Ifosfamide (2500 mg/m2), Dacarbazine (300 mg/m2) and Mesna (6000 mg)] combined with radiotherapy delivering 50 Gy on the left thigh followed by 10 Gy focused on the operating site.
In November 2004, the clinical and paraclinic post-therapeutic follow-up (MRI scan and CT-Scan) reveal normal with minor orthopedic sequelas; a schedule of radio-clinical follow-up is established (MRI Scan and TAP-CT-Scan); the patient is in clinical remission at five years.
Despite the misleading benign appearance of this malignant tumor, complete preoperative X-Ray investigations and biopsy should have been performed since any deep tumor of soft tissues and/or which size exceeds five centimeters is considered as being suspect and requires biopsy prior to any excision procedure. Biopsy plays a crucial role in accurate histopathological diagnosis, and proper staging would enable the oncology committee to implement the most appropriate therapeutic protocol . The first biopsy must be guided by ultrasound or CT-Scan; in case of failure, a surgical biopsy will be indicated and performed through a suitable surgical approach to avoid compromising the subsequent conservative management. In the present case, the evidence of positive excision margins increases the risk of tumor recurrence (around 60%) in the absence of re-excision . This resumption must be scheduled from the results of a MRI Scan which looks for potential tumor anatomical residue and should be performed once proper healing of the initial surgery has been achieved. The re-excision procedure takes place at the initial site of resection and is performed with a wider margin of at least two centimeters of healthy tissue. All tissue potentially exposed to viable tumor cells at the initial procedure should be removed at that time, including the surgical scar and the orifices of drainage. A complementary radiation therapy should be implemented on the operating site, with a minimal safety margin of five centimeters, combined with adjuvant chemotherapy [10, 11]. Lipomas and liposarcomas are of adipose origin according to the histogenetic classification of the World Health Organization [8, 9, 12]. Soft-tissue sarcomas are malignant tumors that originate in the soft tissues of the body which include muscle, fat, fibrous tissue, blood vessels or peripheral nerves.
The genesis of soft-tissue sarcomas has not yet been clearly defined but several contributing factors that increase the likelihood of developing these tumors have been identified: external radiation therapy and genetic factors are the most well-established risk factors for soft tissue sarcomas. Approximately 1% of patients treated with radiation therapy for a malignant tumor, might develop, in previously irradiated tissues, an osseous or soft tissue "radiation-induced sarcoma", which may appear from three to ten years later . Some genetic diseases (neuromatosis, retinoblastoma, L-Fraumeni syndrome) may lead to the development of soft-tissue sarcomas. Lipoma is a very common tumor, generally, of a small size (less than 5 cm) and of superficial aspect whereas liposarcoma is a much rarer tumor of large (more than 5 cm) deep-seated connective tissue spaces, most commonly originating (three out of four times) under the superficial fascia . Three main histological sub-types of LPS are recognized, which differ in their morphological aspect and evolution: well-differentiated LPS (the most frequent), Myxoid LPS and\or with round cells (40% of the LPS), and the anaplastic LPS, a rarer category of bad prognosis [3, 8]. Myxoid LPS and round-cell LPS represent the same entity since they share a key genetic defect (t12; 16), (q13; p11). This genetic abnormality results in fusion of the transcription factor gene CHOP with FUS, and might be discovered through specific techniques (RT-PCR or FISH) while playing a critical role in the differential diagnosis [12, 13]. Actually, the myxoid LPS may contain a variable number of round cells which determines the degree of differentiation and affects the prognosis . There is still no consensus on the percentage of round cells which would help in the grading of such tumors; nevertheless, any myxoid LPS containing more than 10% of round cells should conduct to a cautious prognosis due to the risk of metastases occurrence [4, 8]. The myxoid liposarcoma occurs predominantly at the level of the muscular chamber of the limbs and more specifically in the thigh in more than 2/3 of the cases; it rarely occurs in the retroperitoneum or the subcutaneous tissue.
The operative specimen must be located and oriented, to accurately define the margins of the excision. It is sent to the pathologist, in a fresh state, along with a thorough clinical information mandatory for proper histological analysis (age, extent, location and depth of the tumor, date of appearance, and previous treatment); the type and objective of the surgical procedure are detailed . The myxoid LPS has a well-defined macroscopic aspect with no signs of malignancy. The histological examination reveals a myxoid tumor, of misleading benign appearance, since it is free from cyto-nuclear atypias and demonstrates a very low mitotic activity; the diagnosis is based on the particular aspect of vascularization on the one hand, and on the thorough detection of lipoblasts, on the other hand, typically encountered in malignant tumors of adipose origin . Diagnosis of subaponeurotic tumors of the thigh are easily performed in adults over 40 years old; Nevertheless, it is advisable to eliminate benign tumors of myxoid aspect and more specifically intramuscular myxomas and, in a post-traumatic context, lipomas presenting myxoid degenerative changes or reactional tumor-like lesions such as proliferating myositis [3, 5, 6]. The presence of areas of round cell dense proliferation might result in an uneasy differential diagnosis with other malignant tumors (melanoma, carcinoma, lymphoma); the diagnosis is dependent upon accurate detection of lipoblasts, possibly helped by immunohistochemical markers (S100 protein) [3, 5]. There is a great variety of histopronostic scoring systems; the National Union of Cancer Centers grading system (NUCCGS) is widely used in Europe; it was first described by Trojani and al. then was revised by Guillou and Coindre . This rating system is based on three histological criteria: differentiation, number of mitoses and presence of a tumor necrosis. The prognostic value of cytogenetic analysis determines the risk for local recurrence which is first conditioned by the quality of the surgical excision and, in a lesser measure, the histological grading of the lesion. The analysis of the excision margins is critical; excision margins that exceed one centimeter might be considered as negative; margins under this value are considered as " suspicious " or positive (intra-tumors) . The risk of metastasis and thus the global survival rate mostly depend on the histological pattern [8, 10]. In the present case (histopronostic grade 2 featuring more than 10% of round cells), the presence of a great number of round cells is considered as the major predicting factor for prognosis, and prevails over the histological grade, as well as the presence of positive or negative excision margins. Myxoid LPS have a high risk of local recurrence (50%) whereas pure myxoid LPS report a 20% rate of metastasis. At the other extremity of the spectrum of disease, the LPS featuring a majority of round cells, metastasizes in 70% of the cases. These metastases arise in lungs and bone but, also, in serous membranes (pleura, pericardium and peritoneum) . The average survival rate is 80% at 5 years and 50% at 10 years, strongly determined by the quality of the local excision [7, 10]. The local reference treatment for soft-tissue sarcomas of the extremities includes the combination of surgery and radiation therapy. The indication should be discussed by a committee of multidisciplinary oncologists; Surgery is usually completed by an adjuvant radiation therapy and, sometimes, by a complementary chemotherapy according to the results of the pathology examination and the general extension of tumor [2, 11]. Once the course of treatment has been completed, a necessary schedule of follow-up begins. Clinical examinations, imaging (MRI Scan and TAP-Scan) are performed every six months for five years after treatment, then annually for at least 5 years after this. Since sarcomas are exceedingly rare tumors, our review of the world literature provided very few studies on liposarcomas and even less on myxoid LPS [3, 7, 10]; The published series include all types of liposarcoma and soft-tissue sarcomas, with a therapeutic protocol based on the histological grade and potential metastases [2, 7, 10, 15]. Despite the reassuring clinical aspect of his tumor, our patient should have benefited from an X-ray investigation and a preoperative biopsy. Moreover, his tumor was voluminous, deep and intramuscular. The histopathologic examination of the operative specimen confirmed the malignancy with positive margins of excision. Dujardin  confirms that the isolated excision of a soft-tissue sarcoma exposes the patient to a risk of local recurrence from 50 to 93% according to the type of tumour. The prognosis for this patient is thus reserved since it presented with a myxoid LPS which survival rate is 60% at 5 years  which, furthermore, was initially handled by a margin excision. Taking into account the tumor size (7.5 cm), the histological features (number of round cells = 30%), the initial margin excision and the young age of the patient (50 years), re-excision followed by adjuvant radiation therapy and implementation of a complementary chemotherapy was recommended by the oncology committee in order to decrease the risk of local recurrence and metastasis [2, 7, 10]. Staging studies comprising MRI Scan of the thigh and an abdo-thoracic TAP-Scan, followed by a tumor biopsy should have been undertaken for accurate histological diagnosis. These elements would have helped the oncology committee to suggest a wide surgical excision of the voluminous tumor completed by adjuvant radiotherapy .
The present case clearly illustrates the problems associated with the management of these rare tumors and which might be encountered by any surgeon, whatever the surgical field. Any soft-tissue tumor diagnosed in the adult, particularly when its size exceeds five centimeters and/or when of subaponeurotic origin, typically requires the need for a careful preoperative X-ray investigation combined with a diagnostic biopsy. In case of malignancy, an early accurate medico-surgical treatment should be implemented, associated with a systematic histopathological examination. The prognosis for patients with soft tissue sarcoma largely depends on the quality and coherence of the initial management protocol based on a close multidisciplinary cooperation within the oncology committee.
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