Image Quiz

Thigh Mass in a Fifty-five-Year-Old Woman (continued)

Answer: Atypical lipoma (also known as well-differentiated liposarcoma) with dedifferentiated liposarcoma.


Fig. 1		 Fig. 1 Coronal T1-weighted (A and B) and corresponding fat-suppressed T2-weighted (C and D) magnetic resonance images of the left thigh, showing a well-differentiated liposarcoma (thick arrow, Fig. 1, A) saturating out in the corresponding fat-suppressed T2-weighted image (Fig. 1, C). The anterosuperior portion of the lesion has both fatty and nonfatty components (thin arrows, Fig. 1, B), while the most inferior portion of the lesion is composed solely of dedifferentiated liposarcoma with no visible fatty component (arrowheads).

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Fig. 2		 Fig. 2 Axial T1-weighted (A, B, and C) and corresponding fat-suppressed T2-weighted (D, E, and F) magnetic resonance images of the left thigh. The most proximal images (A and D) show the predominantly fatty, well-differentiated liposarcoma, which saturates on the T2-weighted image (Fig. 2, D). The most distal images (C and F) show the dedifferentiated liposarcoma without a fatty component, corresponding to the area of the lesion marked by the arrowheads in Figure 1. The central images (B and E) show a "mixed" area of the lesion, comprised of both well-differentiated and dedifferentiated liposarcoma, corresponding to the area denoted by the thin black arrows in Figure 1, B.

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Fig. 3		 Fig. 3 Low-power photomicrograph of the central area of the tumor, showing the transition from well-differentiated (left) to dedifferentiated (right) liposarcoma (hematoxylin and eosin, original magnification ×100).

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Fig. 4		 Fig. 4 Photomicrograph of the proximal, well-differentiated liposarcomatous portion of the tumor. Note the occasional lipoblasts, the variation in the size and shape of the fatty vacuoles, and the fibrous septa showing nuclear atypia, all of which are characteristic features of this lesion (hematoxylin and eosin; original magnification, ×200).

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Fig. 5		 Fig. 5 Photomicrograph of the distal dedifferentiated liposarcomatous portion of the lesion. Note the irregular spindle cells and lack of fatty differentiation (hematoxylin and eosin; original magnification, ×200).

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Discussion

Because of the atypical pleomorphic nuclei that could be seen in so-called atypical lipomas, these tumors were initially believed to be low-grade malignant neoplasms and were designated as well-differentiated liposarcoma1 and grade-I lipogenic liposarcoma2. The name atypical lipoma was suggested by Kindblom et al.3 in recognition of the lack of metastatic potential of these lesions. More recently, these lesions were reassessed by Evans et al.4, who proposed the following nomenclature reflecting the drastically different clinical behavior of the lesion in its various locations: atypical lipomas occur in the subcutaneous space and are thought not to recur even with marginal excision; atypical intramuscular lipomas are those within or between muscles and often recur but do not metastasize; and well-differentiated liposarcomas occur solely within the retroperitoneum and may cause death from local disease. The orthopaedic community generally prefers to use the term atypical lipoma to differentiate lesions in the extremities and limb girdles from those with lethal potential.

Atypical lipoma usually affects adults, with a peak incidence in the fifth and sixth decades and with a slight male predominance5,6. Common extremity locations of this tumor are deep in the thigh and buttock, and it often presents clinically as a painless slow-growing mass5,7. The typical appearance of atypical lipoma on magnetic resonance imaging is that of a fatty mass, generally larger than a simple lipoma, with thick septations8,9. The fatty lobules show typical fat characteristics and appear bright on T1-weighted magnetic resonance images and dark on fat-suppressed T2-weighted magnetic resonance images (Figs. 1-A, 2-A, and 2-D). The septa, however, appear dark on T1-weighted images and bright on fat-suppressed T2-weighted images and can comprise 25% or more of the lesion by volume9. Enhancement of the septa with gadolinium is often seen. It is these characteristics that distinguish these lesions from benign lipomas, which typically have a uniform fat density on magnetic resonance imaging (Fig. 3). Benign lipomas may have thin areas of linear enhancement rather than frank septations10, with these thin areas generally amounting to less than 5% of the tumor by volume9. Mature adipocytes of varying sizes, intermixed with occasional lipoblasts, are present on histological evaluation of atypical lipoma, with atypical multinucleated stromal cells in the septa showing nuclear hyperchromasia (Fig. 4)5,8,11. The adipocytic portion of these tumors also shows S-100-protein positivity on immunohistochemistry5.

Dedifferentiated liposarcoma appears as a typical soft-tissue sarcoma, namely, dark on T1-weighted magnetic resonance images and generally heterogeneously bright on fat-suppressed T2-weighted images (Figs. 1-B, 1-D, 2-B, 2-C, 2-E, and 2-F). The identifiable fat content in these lesions, on the basis of the results of imaging studies, is generally <25%8, even reaching the level of no identifiable fat in some series9. A lipomatous mass in close juxtaposition to a nonspecific soft-tissue mass suggests the presence of dedifferentiated liposarcoma5,12. On histological examination, a dedifferentiated liposarcoma may show areas that have the characteristics of a well-differentiated liposarcoma, but it will also demonstrate atypical spindle-cell proliferations with a high mitotic index, resembling malignant fibrous histiocytoma in more than 60% of tumors (Fig. 5)5. These areas can be consistent with low-grade, intermediate-grade, or high-grade sarcoma.

Although thought to be generally benign with negligible rates of metastasis, atypical lipoma must be closely followed because of the possibility of transformation into dedifferentiated liposarcoma7. Dedifferentiation rates for atypical lipoma have been cited in the literature, albeit in small series, as 3% to 19% in the extremities6,7,11,12, with rates of 17% to 24% in the retroperitoneum11,13 and up to 29% in the groin11. Dedifferentiation generally occurs in large, long-standing tumors, occurring, on the average, five years or more after identification of the primary tumor5,7,11. Dedifferentiation is also noted to occasionally occur in the setting of recurrence of a previous atypical lipoma7,11, although recurrences of dedifferentiated lesions can show any phenotype, from low grade to high grade, including a well-differentiated phenotype.

Treatment for atypical lipoma is complete surgical resection. However, while some of these tumors are easily resectable, excision is often difficult or impractical for many tumors because these lesions can permeate into the surrounding tissues, especially when the lesions are recurrent ones. There are no data to support the use of radiation or chemotherapy for lesions that occur in the extremities or limb girdles, despite the fact that marginal or intralesional resection is performed in the majority of patients. However, the presence of microscopic disease and satellite lesions is thought to contribute to the high local recurrence rate5,7. The rates of recurrence have been reported in the literature to be 15% to 52% for the extremities7,11-13 and anywhere from 30% to 91% for the more aggressive retroperitoneal lesions11,14-16, but these rates are based only on small series and the wide range of percentiles gives an idea of the variability of behavior of this tumor. Atypical lipoma has an extremely low metastatic potential and is associated with a near 100% patient survival rate at ten to twenty years17.

For dedifferentiated liposarcoma, wide resection and radiation are the most commonly employed treatment combination. Chemotherapy may be used for higher-grade lesions, but data concerning the effectiveness of this treatment are lacking. The overall recurrence rate in the extremities can be as high as 57%17 but has been reported to be even higher for retroperitoneal lesions, approximately 71% to 100%16,18. Metastases from dedifferentiated liposarcoma do occur, but death from disease occurs in only a minority of patients6. The metastatic potential of these lesions is dependent on tumor grade, size, type, degree of histologic differentiation, and location (i.e., retroperitoneal or in an extremity, superficial or deep)5. The overall chance of the development of distant metastatic lesions may range from 20% to 57%16,17,19. In the few longer-term studies that are available, there is a reported five-year disease-specific survival rate of 59% to 71% that is associated with all dedifferentiated lesions, with 14% to 17% of patients dying of disease beyond the initial five-year interval5. It has been reported that retroperitoneal lesions may have a five-year survival rate as low as 8% to 42%5,15,16,18, but those data derived from studies with small numbers and short periods of follow-up.

The lesion in this Image Quiz represents a dedifferentiated recurrence fifteen years after an initial atypical lipoma was resected from the pelvis, nine years after the onset of dedifferentiation, three years after the discovery of pulmonary metastatic disease, and fifteen months after excision of an atypical lipoma at the same location in the same (left) thigh. Although such a diffuse, multifocal involvement with atypical lipoma is extremely unusual, it is important that the surgeon recognize the characteristic imaging features of both atypical lipoma and dedifferentiated liposarcoma.

Note: The authors acknowledge Brendan C. Dickson, MD, for his assistance in obtaining photomicrographs of the surgical pathology specimen.

*In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Stryker Orthopaedics. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits of less than $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Stryker Orthopaedics).

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