Pleomorphic Liposarcoma

The American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) TNM staging systems can be applied.

The molecular profiles of pleomorphic liposarcomas more closely resemble those of other pleomorphic sarcomas than those of atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, or myxoid liposarcoma. Metaphase cells show high chromosomal counts and complex structural rearrangements. This complexity is represented by unidentifiable marker chromosomes, non-clonal aberrations, polyploidy, and intercellular heterogeneity. No pathognomonic structural rearrangement, such as recurrent translocation or consistent presence of supernumerary ring chromosomes, has been identified. Studies using array comparative genomic hybridization have shown complex profiles with numerous chromosomal imbalances. The most frequent mutations involve TP53 and NF1. It has been noted that the genomic profiles of pleomorphic liposarcoma and myxofibrosarcoma are similar. Amplification of the 12q14-q15 region is absent in pleomorphic liposarcoma.

Most tumors are large, with a median size of 8–10 cm. They are well demarcated but non-encapsulated, or ill-defined and infiltrative and sometimes multinodular. On sectioning, most tumors are white to yellow. Myxoid changes (jelly-like areas) and foci of necrosis (tissue death) are often observed.

Histologically, most cases have infiltrative margins, and all tumors contain a varying proportion of pleomorphic lipoblasts in a background of a high-grade, usually pleomorphic, undifferentiated sarcoma. The presence of lipoblasts is necessary for the diagnosis, but their number varies considerably between cases and between areas within the same tumor, emphasizing the importance of adequate sampling. In most cases, the non-lipogenic component resembles undifferentiated pleomorphic sarcoma with spindle and multinucleated giant cells arranged in short fascicles, with some notable features: namely, the presence of extremely large tumor cells often showing clear or vacuolated cytoplasm, and the presence of extracellular and occasionally intracellular eosinophilic hyaline droplets. Almost half of cases contain at least focal areas similar to intermediate- to high-grade myxofibrosarcoma-like zones associated with pleomorphic lipoblasts. This myxofibrosarcoma-like component is predominant in some cases. Epithelioid morphology is seen in about one quarter of cases with areas resembling poorly differentiated carcinoma, renal clear cell carcinoma, adrenocortical carcinoma, or melanoma. Necrosis is present in more than half of cases.

Unlike in dedifferentiated liposarcoma with homologous differentiation, staining for MDM2 and CDK4 is typically negative in pleomorphic liposarcoma. The epithelioid subtype may be positive for keratins and melan-A.

There are few reports, but cytology is likely to be challenging.

Pleomorphic liposarcomas are aggressive sarcomas exhibiting local recurrence and metastatic rates of 30–50%, with an overall 5-year survival rate of about 60%. Metastases occur mostly in the lungs and pleura. Central location, increased tumor depth, greater size, and higher mitotic count have been associated with a worse prognosis.

Absence of amplification of MDM2 can help distinguish pleomorphic liposarcoma from dedifferentiated liposarcoma.

Essential: pleomorphic spindle cell sarcoma containing a variable number of pleomorphic lipoblasts; myxofibrosarcoma-like morphology with pleomorphic lipoblasts; epithelioid subtype with sheets of carcinoma-like epithelioid cells with pleomorphic lipoblasts; tumors may consist only of pleomorphic lipoblasts.