间充质梭形细胞肿瘤与激酶融合,通常出现在浅表或深层软组织位置,很少发生在骨骼中。在这里,我们从我们的档案中描述了8个以各种激酶融合为特征的骨肿瘤的临床病理和分子数据,并将这些发现与先前报道的7例病例结合起来。以单例报告为主。在当前系列中,除一名患者外,所有患者都是幼儿或青少年,年龄范围从新生儿到59岁(平均19岁)。大多数肿瘤(n=5)出现在头颈部区域(颅底,乳突,上颌骨,和下颌骨),剩下三个在胫骨,骨盆骨,和胸壁。融合包括NTRK1(n=3),RET(n=2),NTRK3(n=2),和BRAF(n=1)。在组合序列中(n=15),大多数肿瘤(73%)发生在儿童和年轻人(<30岁),并表现为颌骨和颅骨(40%),其次是长和小管状骨(33%)。融合跨越了大量的激酶基因,包括降序的NTRK3(n=6),NTRK1(n=4),RET(n=2),BRAF(n=2),和RAF1(n=1)。通过靶向RNA测序确认的所有融合都在框内并且将激酶结构域保留在融合癌蛋白内。类似于软组织对应物,该系列中大多数NTRK3阳性骨肿瘤表现为高级别形态(5/6),而大多数NTRK1肿瘤为低级别(3/4)。值得注意的是,在老年人中出现的所有四个肿瘤都是高级别梭形细胞肉瘤,成人纤维肉瘤(FS)样,恶性周围神经鞘瘤(MPNST)样和MPNST表型。总的来说,10个肿瘤有高级形态,从婴儿和成人类型FS,像MPNST一样,MPNST,而5例显示良性/低度组织学(MPNST样和粘液瘤样)。免疫组织化学(IHC),S100和CD34阳性分别为57%和50%,分别,而在43%的病例中S100和CD34共表达。三分之一的肿瘤(4个高级别和粘液瘤样)对S100和CD34均为阴性。Pan-TRK的IHC在所有8个测试的NTRK融合阳性肿瘤中均为阳性,而在两个具有其他激酶融合的肿瘤中均为阴性。临床随访太有限,无法得出一般性结论。
Mesenchymal spindle cell tumors with kinase fusions, often presenting in superficial or deep soft tissue locations, may rarely occur in bone. Herein, we describe the clinicopathologic and molecular data of eight bone tumors characterized by various kinase fusions from our files and incorporate the findings with the previously reported seven cases, mainly as single case reports. In the current series all but one of the patients were young children or teenagers, with an age range from newborn to 59 years (mean 19 years). Most tumors (n = 5) presented in the head and neck area (skull base, mastoid, maxilla, and mandible), and remaining three in the tibia, pelvic bone, and chest wall. The fusions included NTRK1 (n = 3), RET (n = 2), NTRK3 (n = 2), and BRAF (n = 1). In the combined series (n = 15), most tumors (73%) occurred in children and young adults (<30 years) and showed a predilection for jaw and skull bones (40%), followed by long and small tubular bones (33%). The fusions spanned a large spectrum of kinase genes, including in descending order NTRK3 (n = 6), NTRK1 (n = 4), RET (n = 2), BRAF (n = 2), and RAF1 (n = 1). All fusions confirmed by targeted RNA sequencing were in-frame and retained the kinase domain within the fusion oncoprotein. Similar to the soft tissue counterparts, most NTRK3-positive bone tumors in this series showed high-grade morphology (5/6), whereas the majority of NTRK1 tumors were low-grade (3/4). Notably, all four tumors presenting in the elderly were high-grade spindle cell sarcomas, with adult fibrosarcoma (FS)-like, malignant peripheral nerve sheath tumor (MPNST)-like and MPNST phenotypes. Overall, 10 tumors had high-grade morphology, ranging from infantile and adult-types FS, MPNST-like, and MPNST, whereas five showed benign/low-grade histology (MPNST-like and myxoma-like). Immunohistochemically (IHC), S100 and CD34 positivity was noted in 57% and 50%, respectively, while co-expression of S100 and CD34 in 43% of cases. One-third of tumors (4 high grade and the myxoma-like) were negative for both S100 and CD34. IHC for Pan-TRK was positive in all eight NTRK-fusion positive tumors tested and negative in two tumors with other kinase fusions. Clinical follow-up was too limited to allow general conclusions.