Department of Pathology, Nuffield Dept of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Nuffield Orthopaedic Centre, Headington, Oxford, OX3 7LD, UK.
Virchows Arch. 2010 Mar;456(3):317-23. doi: 10.1007/s00428-010-0882-z. Epub 2010 Feb 2.
Giant cell-rich leiomyosarcoma of soft tissues is an unusual variant of malignant smooth muscle tumor characterized by the presence of numerous multinucleated giant cells (MNGCs). The nature of MNGCs and the cellular mechanisms underlying their accumulation in this tumor are poorly understood. Analysis of the expression of osteoclast, macrophage, and smooth muscle markers in two cases of giant cell-rich leiomyosarcoma revealed that the MNGCs in giant cell-rich leiomyosarcoma were negative for smooth muscle markers and that these cells expressed an osteoclast-like phenotype, being positive for CD45, CD68, tartrate-resistant acid phosphatase, and CD51 but negative for CD14 and HLA-DR. Scattered tumor-associated macrophages (TAMs) also expressed this phenotype. Leiomyosarcoma tumor cells strongly reacted for CD51 but were negative for CD14, CD45, and CD68. An analysis of 25 conventional (nongiant cell-containing) leiomyosarcomas found isolated CD68(+) MNGCs in three cases (12%), all of which were grade II/III leiomyosarcomas containing a prominent TAM infiltrate. Leiomyosarcoma-derived TAMs in the presence of receptor activator for nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor were capable of differentiating into osteoclast-like cells capable of resorbing bone. Reverse transcription polymerase chain reaction studies showed that RANKL, osteoprotegerin, and TNF-related apoptosis-inducing ligand were expressed by leiomyosarcoma cells. Our findings indicate that the giant cells found in leiomyosarcomas are osteoclast-like and that they are formed from TAMs by a RANKL-dependent mechanism.
富含巨细胞的软组织平滑肌肉瘤是一种罕见的恶性平滑肌肿瘤变异型，其特征是存在大量多核巨细胞（MNGCs）。MNGCs 的性质以及其在这种肿瘤中积累的细胞机制尚未得到充分理解。对两例富含巨细胞的平滑肌肉瘤中破骨细胞、巨噬细胞和平滑肌标志物的表达分析表明，富含巨细胞的平滑肌肉瘤中的 MNGCs 不表达平滑肌标志物，这些细胞表达破骨细胞样表型，对 CD45、CD68、抗酒石酸酸性磷酸酶和 CD51 呈阳性，但对 CD14 和 HLA-DR 呈阴性。散在的肿瘤相关巨噬细胞（TAMs）也表达这种表型。平滑肌肉瘤肿瘤细胞强烈表达 CD51，但不表达 CD14、CD45 和 CD68。对 25 例常规（不含巨细胞）平滑肌肉瘤的分析发现，3 例（12%）存在孤立的 CD68（+）MNGCs，均为 II/III 级含有明显 TAM 浸润的平滑肌肉瘤。在核因子 kappa B 配体（RANKL）和巨噬细胞集落刺激因子存在的情况下，源自平滑肌肉瘤的 TAMs 能够分化为能够吸收骨的破骨细胞样细胞。逆转录聚合酶链反应研究表明，RANKL、骨保护素和 TNF 相关凋亡诱导配体均由平滑肌肉瘤细胞表达。我们的研究结果表明，在平滑肌肉瘤中发现的巨细胞是破骨细胞样的，并且它们是通过 RANKL 依赖的机制从 TAMs 形成的。
