Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Carolinas HealthCare System, Charlotte, NC, USA.
Mod Pathol. 2019 Feb;32(2):242-251. doi: 10.1038/s41379-018-0129-0. Epub 2018 Sep 11.
We present our experience with ten well-characterized malignant tenosynovial giant cell tumors, including detailed immunohistochemical analysis of all cases and molecular cytogenetic study for CSF1 rearrangement in a subset. Cases occurred in 7 M and 3 F (mean age: 52 years; range: 26-72 years), and involved the ankle/foot (n = 1), finger/toe (n = 3), wrist (n = 1), pelvic region (n = 3), leg (n = 1), and thigh (n = 1). There were eight primary and two secondary malignant tenosynovial giant cell tumors. Histologically, all cases showed definite areas of typical tenosynovial giant cell tumor. The malignant areas varied in appearance. In some cases, isolated malignant-appearing large mononuclear cells with high nuclear grade and mitotic activity were identified within otherwise-typical tenosynovial giant cell tumor, as well as forming larger masses of similar-appearing malignant cells. Occasionally, these nodules of malignant large mononuclear cells showed transition to pleomorphic spindle cell sarcoma, with varying degrees of collagenization and myxoid change. One malignant tenosynovial giant cell tumor was composed of sheets of monotonous large mononuclear cells with high nuclear grade, growing in a hyalinized, osteoid-like matrix, with areas of heterologous osteocartilaginous differentiation. Mitotic activity ranged from 2 to 34 mitoses per 10 HPF (mean 18/10 HPF). Geographic necrosis was observed in four cases. The malignant-appearing large mononuclear cells were consistently positive for clusterin and negative for CD163, CD68, and CD11c. Desmin was positive in a small minority of these cells. Areas in malignant tenosynovial giant cell tumor resembling pleomorphic spindle cell sarcoma or osteo/chondrosarcoma showed loss of clusterin expression. RANKL immunohistochemistry was positive in the large mononuclear cells in eight cases. Two cases showed an unbalanced rearrangement of the CSF1 locus. Follow-up (nine patients; range 0.5-66 months; mean 20 months) showed three patients dead of disease, with three other living patients having lung and lymph node metastases; three patients were disease-free. We conclude that malignant tenosynovial giant cell tumors are highly aggressive sarcomas with significant potential for locally destructive growth, distant metastases, and death from disease. The morphologic and immunohistochemical features of these tumors and the presence of CSF1 rearrangements support origin of malignant tenosynovial giant cell tumor from synoviocytes.
我们介绍了 10 例特征明确的恶性腱鞘巨细胞瘤，包括所有病例的详细免疫组织化学分析和部分病例的 CSF1 重排的分子细胞遗传学研究。7 例为男性，3 例为女性（平均年龄：52 岁；范围：26-72 岁），涉及踝/足部（n=1）、手指/脚趾（n=3）、腕部（n=1）、骨盆（n=3）、腿部（n=1）和大腿（n=1）。8 例为原发性，2 例为继发性恶性腱鞘巨细胞瘤。组织学上，所有病例均显示明确的典型腱鞘巨细胞瘤区域。恶性区域表现不同。在一些病例中，在典型的腱鞘巨细胞瘤内可识别孤立的恶性表现的大单核细胞，核分级高，有丝分裂活性高，以及形成类似表现的恶性细胞的较大肿块。偶尔，这些恶性大单核细胞结节向多形性梭形细胞肉瘤转化，伴有不同程度的胶原化和黏液样变。1 例恶性腱鞘巨细胞瘤由单调的大单核细胞组成，核分级高，生长在玻璃样、类骨样基质中，有异型骨/软骨分化区。有丝分裂活性范围为每 10HPF 2-34 个（平均 18/10HPF）。4 例观察到地理性坏死。恶性表现的大单核细胞始终对聚集素呈阳性，对 CD163、CD68 和 CD11c 呈阴性。这些细胞中有一小部分 desmin 阳性。在恶性腱鞘巨细胞瘤中类似于多形性梭形细胞肉瘤或骨肉瘤的区域表现出聚集素表达缺失。RANKL 免疫组化在 8 例中的大单核细胞中呈阳性。2 例显示 CSF1 基因座的不平衡重排。随访（9 例患者；范围 0.5-66 个月；平均 20 个月）显示 3 例患者死于疾病，3 例其他患者出现肺和淋巴结转移；3 例患者无病。我们得出结论，恶性腱鞘巨细胞瘤是高度侵袭性肉瘤，具有显著的局部破坏性生长、远处转移和疾病相关死亡的潜力。这些肿瘤的形态学和免疫组织化学特征以及 CSF1 重排的存在支持恶性腱鞘巨细胞瘤起源于滑膜细胞。
