Many Postchemotherapy Sarcomatous Tumors in Patients With Testicular Germ Cell Tumors Are Sarcomatoid Yolk Sac Tumors A Study of 33 Cases
Many Postchemotherapy Sarcomatous Tumors in Patients With Testicular Germ Cell Tumors Are Sarcomatoid Yolk Sac Tumors A Study of 33 Cases
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DOI：
10.1097/pas.0000000000000322
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发表时间：
2015-02-01
影响因子：
5.6
通讯作者：
Ulbright, Thomas M.
中科院分区：
文献类型：
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作者：
Howitt, Brooke E.;Magers, Martin J.;Ulbright, Thomas M.
睾丸生殖细胞肿瘤（TGCT）患者的肉瘤样肿瘤可能表现出不同的谱系，通常归因于畸胎瘤的“转化”，尽管也有人认为起源于卵黄囊瘤（YST）。我们对23例TGCT患者的33个肉瘤样肿瘤进行了评估，这些肿瘤缺乏特定肉瘤亚型的一些特征，包括：肉瘤（轻度、中度、重度）、细胞构成、肿瘤坏死、有丝分裂指数、间质血管分布、细胞分布（梭形或上皮样）和间质质量（粘液样和/或纤维样）。进行针对细胞角蛋白（AE 1/AE 3）、SALL 4、磷脂酰肌醇蛋白聚糖-3（GPC 3）、甲胎蛋白（AFP）、p63、胶质细胞酸性蛋白（GFAP）、CD 34、MUC 4、平滑肌肌动蛋白（SMA）、结蛋白、钙调蛋白和肌生成素的免疫组织化学染色分析。对染色强度（0 =阴性，1 =弱，2 =中等，3 =强）和程度（0 = <1%，1 = 1%至10%，2 = 10%至50%，3 = > 50%）进行评分。根据法国肉瘤分级系统评估肿瘤分级，2-3级视为高级别。AE 1/AE 3和GPC 3的强度至少为中等且细胞均> 10%（+）的肿瘤被认为是肉瘤样YST（SYST）;来自14名患者（年龄18至38岁，平均27岁）的22个肿瘤符合这些标准，是本研究的重点。所有肿瘤均发生于化疗后（TGCT诊断后3 ~ 132个月，平均42.5个月，中位30.5个月）。在粘液样至纤维样间质中，梭形细胞（100%; 19个占优势）和上皮样细胞（77%; 3个占优势）。13例表现出至少局灶性严重的核分裂症。独特的肿瘤“小环”和细胞间基底膜沉积（壁YST分化）是常见的。除AE 1/AE 3和GPC 3阳性外，15/22例为SALL 4（+），10/22例至少为局灶性CD 34（+），2/22例为局灶性p63（+）。50%显示平滑肌分化，如结蛋白（8/19）、钙调蛋白（2/4）和/或SMA（4/6）反应性所证明。AFP、MUC 4、GFAP、myogenin均为阴性。随访时，8/14例患者在首次SYST诊断后7至217个月（平均58个月）死于疾病，而5/14例患者在1至259个月（平均83个月）时存活且无疾病证据（ANED）。1例患者在39个月时死于不相关原因。在11例高级别肿瘤患者中，8例死于疾病，1例死于无关原因，2例为ANED;所有3例低级别肿瘤患者均在41至262个月（平均128个月）时发生ANED。我们的结论是，高比例的肉瘤样肿瘤化疗后切除的TGCT患者是恶性的。这些通常发生在诊断后几年，并在高级别时表现出侵略性。
Sarcomatoid neoplasms in patients with testicular germ cell tumors (TGCTs) may show diverse lineages and are usually attributed to "transformation" of teratoma, although origin from yolk sac tumor (YST) has also been suggested. We evaluated 33 sarcomatoid tumors from 23 TGCT patients that lacked specific features of a defined sarcoma subtype for a number of features, including: atypia (mild, moderate, severe), cellularity, tumor necrosis, mitotic index, stromal vascularity, cell profile (spindle or epithelioid), and stromal quality (myxoid and/or fibrous). Immunohistochemical staining analyses directed against cytokeratin (AE1/AE3), SALL4, glypican-3 (GPC3), alpha-fetoprotein (AFP), p63, glial fibrillary acidic protein (GFAP), CD34, MUC4, smooth muscle actin (SMA), desmin, caldesmon, and myogenin were performed. Staining intensity (0 = negative, 1 = weak, 2 = moderate, 3 = strong) and extent (0 = < 1%, 1 = 1% to 10%, 2 = 10% to 50%, 3 = > 50%) were scored. Tumor grade based on the French sarcoma grading system was assessed, with grades 2-3 considered high grade. Tumors with at least moderate intensity and > 10% (+) cells for both AE1/AE3 and GPC3 were considered to be sarcomatoid YST (SYST); 22 tumors from 14 patients (ages 18 to 38 y, mean 27 y) met these criteria and were the focus of this study. All SYSTs occurred after chemotherapy (3 to 132mo after TGCT diagnosis; mean 42.5 mo, median 30.5 mo). They had spindled (100%; 19 predominant) and epithelioid cells (77%; 3 predominant) in myxoid to fibrous stroma. Thirteen exhibited at least focally severe nuclear atypia. Distinctive tumor "ringlets" and intercellular basement membrane deposits (parietal YST differentiation) were common. In addition to positivity for AE1/AE3 and GPC3, 15/22 were SALL4 (+), 10/22 were at least focally CD34 (+), and 2/22 were focally p63 (+). Fifty percent exhibited smooth muscle differentiation as evidenced by desmin (8/19), caldesmon (2/4), and/or SMA (4/6) reactivity. AFP, MUC4, GFAP, and myogenin were negative in all cases. On follow-up, 8/14 patients died of disease at 7 to 217 months (mean 58 mo) after the initial SYST diagnosis, whereas 5/14 were alive and had no evidence of disease (ANED) at 1 to 259 months (mean 83 mo). One patient died of unrelated causes at 39 months. Of the 11 patients with high-grade tumors, 8 were dead of disease, 1 died of an unrelated cause, and 2 were ANED; all 3 patients with low-grade tumors were ANED at 41 to 262 months (mean 128 mo). We conclude that a high proportion of sarcomatoid tumors in postchemotherapy resections of TGCT patients are SYSTs. These typically occur several years after diagnosis and behave aggressively when high grade.