IML may be considered in the differential diagnosis because of their frequent large size and deep location; however, the neoplasm depicted in the images contains significant cytologic atypia that is not seen in lipomas. IML is most common in middle-aged and older individuals (fifth to seventh decade) and usually affects the large muscles of the proximal extremities. It may reach a large size (>20cm) and has either circumscribed or infiltrative margins. It is composed of lobules of mature appearing adipose tissue lacking cytologic atypia. The majority of lipomas harbor chromosomal aberrations involving genes encoding members of the high mobility group of proteins (such as HMGA2 and HMGA1B). The most consistent structural rearrangements involve band 12q13-15, followed by 6p21-23, 13q11-22, and 12q22-24. These aberrations are not seen in liposarcoma.
Pleomorphic liposarcoma (PLS) is a neoplasm with features of pleomorphic high-grade sarcoma. The neoplasm in the picture, on the other hand, is mainly composed of mature appearing adipose tissue with scattered adipocytic atypia. PLS is the rarest subtype of liposarcoma (5% of the total). It affects older individuals and is most commonly seen in the deep soft tissue of the lower extremity, followed by the upper extremity and retroperitoneum. It resembles a pleomorphic malignant fibrous histiocytoma (MFH) with bona fide lipomatous differentiation, including lipoblasts. It is not related cytogenetically with the group of atypical lipoma/well-differentiated liposarcoma (WDLS), but shows complex and variable structural aberrations that make this neoplasm closer to pleomorphic sarcomas than liposarcomas.
The gross image shows a large intramuscular fatty tumor that microscopically is composed of variably sized adipocytes with scatted atypical lipoblasts with pleomorphic, hyperchromatic nuclei, consistent with WDLS. WDLS is the most common type of liposarcoma (more than 50% of cases), the remaining types includes the myxoid/round cell type, the pleomorphic, and the dedifferentiated types. WDLS affects adults, with a peak incidence in the sixth and seventh decades of life. The majority of cases (75%) affect the deep muscles of the extremities, and the remaining cases are seen in the retroperitoneum and contiguous areas (inguinal canal and paratesticular region). WDLS may arise in the subcutaneous fat, where the terms atypical lipoma or atypical lipomatous tumor (ALT) of the subcutis are preferred due to the indolent course and minimal risk for dedifferentiation or metastasis. In general, WDLS of the extremities has low disease related mortality because surgery can be curative, differently from retroperitoneal tumors, where local control is difficult or impossible to achieve. WDLS may dedifferentiate to a high-grade nonlipogenic sarcoma and, in doing so, it acquires a metastatic potential. Dedifferentiation may occur in approximately 20% of the retroperitoneal tumors, but in less than 2% of the neoplasms of the extremity. WDLS is usually large, lobulated, and yellow to white in color. The gross appearance is that of mature fat, but it is usually firmer in view of thick fibrous septa and areas of fibrosis. Several types are recognized: lipoma-like, sclerosing, inflammatory, and spindle cell, but different patterns may coexist in the same tumor. The lipomalike type is similar grossly and microscopically to mature white fat but shows thickened, hypercellular fibrous septa containing large hyperchromatic spindle cells. Lipoblasts may be present within the tumor lobules, but are not necessary for diagnosis. The sclerosing type is characterized by atypical cells, which may include lipoblasts, embedded in a fibrous to myxoid matrix. The inflammatory variant is characterized by a diffuse inflammatory infiltrate composed of lymphocytes, which often form germinal centers. The spindle cell type is characterized by a proliferation of bland spindle cells embedded in fibrous to myxoid stroma and associated with an atypical lipomatous component and, occasionally, shows metaplastic bone formation and a smooth or striated muscle component. The surrounding matrix is fibrous to myxoid and sparse lipoblasts are present. Immunohistochemistry is of limited value; WDLS is positive for CD34 and variably for the S100 protein. Supernumerary ring and giant marker chromosomes are characteristic of WDLS. They are composed of interspersed amplified sequences origination from the region 12q14-15, where the MDM2 gene is located. Neighboring genes, such as SAS, CDK4, and HMGIC, are also amplified. The 12q14-15 amplification is never found in lipoma.
Although areas of WDLS are usually present in well-sampled specimens of dedifferentiated liposarcoma (DDLS), the image contains only WDLS without evidence of dedifferentiation. DDLS is a liposarcoma that shows sharp or gradual transition from WDLS to a nonadipocytic sarcoma. Dedifferentiation may be present either in the primary sarcoma or, less commonly, in the recurrence. By convention, to be classified as DDLS, a liposarcoma should contain at least a 1cm
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focus of dedifferentiation. The dedifferentiated component shows variable features, ranging from low to high-grade sarcomas. Lower grade dedifferentiation may resemble solitary fibrous tumor (SFT), fibrosarcoma, or, in rare cases, may contain meningotheliallike whorls and metaplastic bone; at the other hand of the spectrum, high-grade dedifferentiation may resemble pleomorphic or inflammatory MFH. Heterologous differentiation in the form of osteosarcoma, chondrosarcoma, rhabdomyosarcoma (RMS) or leiomyosarcoma may occur, without change in the overall prognosis. DDLS affects adult patients, 50 years or older. It follows the same anatomical distribution of WDLS, but it does not share its indolent behavior. Once dedifferentiation occurs, the neoplasm acquires a more aggressive biological potential, including a faster tempo on recurrences (overall recurrence rate around 40%) and a capacity for metastatic dissemination. The metastatic rate is variable (varying between 10% and 20% of all cases) and depends on several factors, with tumor grade, necrosis, and mitotic activity being the most important. Prognosis is also related to the tumor site, with retroperitoneal and proximal tumors doing worse than tumors in distal extremities. The genetics of DDLS is still limited. Amplification of 12q13-21 with coamplification of other regions has been identified in some DDLS and is shared by WDLS. MDM2 amplification has been identified in DDLS of retroperitoneum.
Pleomorphic lipoma does not occur in the deep soft tissue of the thigh. Pleomorphic lipoma is a variant of spindle cell lipoma with scattered multinucleated giant cells. It affects older individuals and is significantly more common in males (M:F = 9:1). It is almost exclusively seen in the subcutaneous tissue of the posterior neck, shoulder region, and back. Spindle cell and pleomorphic lipomas are small ovoid, well-circumscribed masses that appear white to yellow, depending on the relative proportion of spindle cell component and mature adipose tissue. Histologically, pleomorphic lipoma contains a mixture of small uniform spindle cells embedded in myxoid stroma with dense collagen fibers and mature adipocytes, which is diagnostic of spindle cell lipoma. In addition, however, it contains variable amounts of giant cells with peripherally oriented nuclei (“floret-like” giant cells). Spindle cell/pleomorphic lipomas have more complex cytogenetic aberrations than usual lipomas and usually are hypodiploid, following partial loss of genetic material, most commonly affecting chromosome 13 and/or 16. Balanced rearrangements have also been reported. Pleomorphic lipoma is benign and simple excision is curative.
