Dedifferentiated liposarcoma and pleomorphic liposarcoma: a comparative study of cytomorphology and MDM2/CDK4 expression on fine-needle aspiration.
BACKGROUND
Dedifferentiated liposarcoma (DDLPS) and pleomorphic liposarcoma (PLPS) are distinct high-grade liposarcomas. DDLPS is a nonlipogenic sarcoma characterized by amplification of MDM2 and CDK4. PLPS is a high-grade sarcoma containing lipoblasts, characterized by a complex karyotype and a more aggressive clinical course. Rarely, DDLPS shows lipogenic differentiation, mimicking PLPS. The cytomorphologic features of DDLPS and PLPS and the utility of ancillary studies have not been systemically analyzed.


METHODS
Cytologic preparations of 25 DDLPS and 13 PLPS, all histologically confirmed, were retrospectively reviewed along with clinical and cytogenetic data. Sample cellularity, vascular architecture, background material, predominant cell morphology, quality of the cytoplasm, and nuclear pleomorphism were compared for both tumor types. Immunohistochemistry for MDM2 and CDK4 was performed on cell blocks and/or core needle biopsies.


RESULTS
Fine-needle aspirate smears from both DDLPS and PLPS were variably cellular, composed of cellular clusters and noncohesive cells. Abundant myxoid stroma was present in ∼25% of DDLPS and PLPS cases, whereas branching curvilinear vessels were more common in DDLPS than in PLPS (7 of 25 versus 2 of 13). Tumors were composed of predominantly spindled (18 of 25 DDLPS versus 3 of 13 PLPS) or epithelioid cells (7 of 25 DDLPS versus 6 of 13 PLPS). Pleomorphic cells were predominant in 3 PLPS, and were frequent in both (13 of 25 DDLPS versus 10 of 13 PLPS). The cytoplasm was mostly fibrillary and often vacuolated in both entities. Other features included necrosis, mitoses, and a prominent inflammatory infiltrate. The main cytologic differences were the presence of marked pleomorphism, abundant lipoblasts, and cells with microvacuolated cytoplasm in most PLPS. A total of 24 (96%) and 20 (80%) cases of DDLPS expressed MDM2 and CDK4, respectively, whereas none of the PLPS expressed both markers. Six DDLPS tested showed ring or giant marker chromosomes and/or MDM2 amplification by fluorescence in situ hybridization; 2 PLPS had complex karyotypes.


CONCLUSIONS
DDLPS and PLPS exhibit variable and occasionally overlapping cytologic features. The presence of lipoblasts, cells with microvacuolated cytoplasm, and marked pleomorphism are more suggestive of PLPS, but these characteristics can be present in DDLPS. Coexpression of MDM2 and CDK4 distinguishes DDLPS from PLPS.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Adrián
A
Mariño-Enríquez
Jason L
JL
Hornick
Paola
P
Dal Cin
Edmund S
ES
Cibas
Xiaohua
X
Qian
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods*; D002869:Chromosome Aberrations; D051358:Cyclin-Dependent Kinase 4 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008080:Liposarcoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis*; D012189:Retrospective Studies
D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
CDK4; MDM2; adipocytic; cytology; dedifferentiated liposarcoma; fine-needle aspirate; lipoblast; pleomorphic liposarcoma; sarcoma; soft tissue