去分化脂肪肉瘤和多形性脂肪肉瘤：细针抽吸细胞学形态学和 MDM2/CDK4 表达的比较研究。
Dedifferentiated liposarcoma and pleomorphic liposarcoma: a comparative study of cytomorphology and MDM2/CDK4 expression on fine-needle aspiration.
机构信息
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
出版信息
Cancer Cytopathol. 2014 Feb;122(2):128-37. doi: 10.1002/cncy.21362. Epub 2013 Nov 12.
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.
背景
去分化脂肪肉瘤（DDLPS）和多形性脂肪肉瘤（PLPS）是两种不同的高级别脂肪肉瘤。DDLPS 是一种非脂性肉瘤，其特征是 MDM2 和 CDK4 的扩增。PLPS 是一种含有脂肪母细胞的高级别肉瘤，其特征是复杂的核型和更具侵袭性的临床病程。罕见情况下，DDLPS 表现出脂母细胞分化，类似于 PLPS。DDLPS 和 PLPS 的细胞形态特征以及辅助研究的实用性尚未得到系统分析。
方法
回顾性分析了 25 例 DDLPS 和 13 例 PLPS 的细胞学标本，所有病例均经组织学证实，并结合临床和细胞遗传学数据进行分析。比较了两种肿瘤的细胞密度、血管结构、背景物质、主要细胞形态、细胞质质量和核多形性。对细胞块和/或核心针活检进行了 MDM2 和 CDK4 的免疫组织化学染色。
结果
来自 DDLPS 和 PLPS 的细针抽吸涂片的细胞数量不同，由细胞簇和非黏附细胞组成。大约 25%的 DDLPS 和 PLPS 病例中存在丰富的黏液样基质，而分支状曲线血管在 DDLPS 中比在 PLPS 中更常见（25 例中有 7 例，而 13 例中有 2 例）。肿瘤由主要梭形（25 例中的 18 例 DDLPS 与 13 例中的 3 例 PLPS）或上皮样细胞（25 例中的 7 例 DDLPS 与 13 例中的 6 例 PLPS）组成。3 例 PLPS 以多形性细胞为主，在两种肿瘤中均较为常见（25 例中的 13 例 DDLPS 与 13 例中的 10 例 PLPS）。细胞质大多呈纤维状，常有空泡。其他特征包括坏死、有丝分裂和明显的炎症浸润。主要的细胞学差异是存在明显的多形性、丰富的脂肪母细胞和大多数 PLPS 中具有微空泡的细胞质细胞。24 例（96%）DDLPS 分别表达 MDM2 和 CDK4，20 例（80%）表达 MDM2，而无 PLPS 表达这两种标志物。6 例 DDLPS 的荧光原位杂交检测到环状或巨大标记染色体和/或 MDM2 扩增；2 例 PLPS 具有复杂的核型。
结论
DDLPS 和 PLPS 表现出可变的、偶尔重叠的细胞学特征。脂肪母细胞、具有微空泡的细胞质细胞和明显的多形性更提示为 PLPS，但这些特征也可能存在于 DDLPS 中。MDM2 和 CDK4 的共表达可将 DDLPS 与 PLPS 区分开来。
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