IM may enter the differential diagnosis on gross inspection. Microscopically, however, it is composed of bland spindle and stellate cells with small nuclei that are separated by abundant myxoid matrix with minimal vascularity. Some cases, named “cellular myxoma,” show increased cellularity. IM may be encapsulated or may show some infiltration in the surrounding skeletal muscle. It stains for vimentin and variably for CD34, actin, and desmin. S100 protein is negative. IM myxomas, of either usual or increased cellularity type, lack cytologic atypia, mitotic activity, and necrosis and simple excision is curative.
Myxoid lipoma is characterized by a lipoma in which the adipocytes are embedded in abundant stromal mucin. Neither lipoblasts nor plexiform vascular network is seen.
WDLS has typical multivacuolated lipoblasts and thickened septa containing large hyperchromatic spindle cells, and lacks the plexiform vascular network characteristic of myxoid liposarcoma (MLS). Univacuolated lipoblasts and small primitive mesenchymal cells are usually not observed.
Lipoblastoma is a lesion of early childhood with a distinct lobular architecture, and may closely resemble MLS. The exclusive occurrence in early childhood excludes the diagnosis of liposarcoma.
MLS is the second most common type of liposarcoma (LS), and comprises 30% to 40% of all LS and 10% of all adult soft tissue sarcomas. A subset of MLS is characterized by progression to round cell morphology, and is known as round cell liposarcoma (RCLS). Although still separately classified by the WHO, the two types of LS are the extremes of the same entity, and share the same translocation, t(12; 16) (q13; p11). MLS and RCLS affect the muscles of the extremities, with the thigh involved in approximately 70% of the cases, and the remaining cases originating in calf, popliteal region, and upper extremity. The retroperitoneum and the subcutis are only rarely affected. The two subtypes have a different prognosis, since RCLS tends to metastasize more frequently than the myxoid type. Both subtypes may metastasize to soft tissue and bone, often many years after the excision of the primary tumor. Deep visceral metastases are less frequent. Grossly MLS is typically gelatinous and may contain areas of hemorrhage or necrosis. MLS with a significant round cell component may contain visible foci with a white, fleshy appearance, which becomes predominant in pure RCLS. Pure MLS is multinodular with increased cellularity at the growing edge of the nodules, reminiscent of fetal fat. The tumor cells are evenly dispersed in an abundant myxoid matrix, rich in hyaluronic acid, and vary from small spindle cells with inconspicuous cytoplasm to multi- and univacuolated lipoblasts. The univacuolated lipoblasts, characteristic of MLS, are more frequently seen at the periphery of the lobules. There is a delicate and regular network of delicate vessels (“chicken-wire” pattern). MLS may assume different patterns: lymphangioma-like, trabecular, and spindle. Sometimes it can show increased cellularity, characterized by a mixture of spindle and round cells that should not to be confused with round cell component, because it is not associated with an increased risk of metastasis. When present, the round cell component may be focal or extensive. To be defined as RCLS, the neoplastic cells have to proliferate back-to-back in sheets or cohesive clusters that, in small biopsies, may be confused with lymphoma or malignant small round blue cell tumors. Immunohistochemistry is of limited value. The S100 protein may be positive in the round cell component, suggesting adipocytic differentiation. CD34 is generally negative. As mentioned above, MLS is characterized by a t(12; 16) (q13; p11) translocation that is seen in more than 90% of the cases, and that fuses the CHOP gene on chromosome 12q13 and the FUS gene on chromosome 16p11. A minority of cases has a variant t (12; 22) (q13; q12) translocation that fuses the EWS gene on chromosome 22 with the CHOP gene on chromosome 12. Factors adversely affecting the prognosis are >5% of round cell component, presence of necrosis, and TP53 overexpression.
