Abstract：
OBJECTIVE: The aim of the present investigation was to characterize the growth pattern and antigen profile of peripheral nerve sheath tumors (PNST) in a large series of tumors obtained from patients with Neurofibromatosis type 1 (NF1) focusing on morphological characteristics of diffuse plexiform neurofibroma (DPNF).
METHODS: Tissue micro-array (TMA) analysis was applied to study 520 formalin-fixed, paraffin-embedded human PNST of 385 patients with confirmed NF1 diagnosis. PNST originated from all areas of the body and were classified as cutaneous neurofibroma (CNF, n=114), diffuse neurofibroma (DNF, n=109), DPNF (n=108), plexiform neurofibroma (PNF, n=110), and malignant peripheral nerve sheath tumor (MPNST, n=22). Histomorphology and antigen expression patterns of the tumors were determined [S100, epithelial membrane antigen (EMA), CD90, mast cell tryptase, and neurofilament].
RESULTS: Benign PNST showed significantly more S100-positive tumor cells than MPNST (p<0.001). EMA expression was most pronounced in perineurium of DPNF. The number of mast cells in CNF, DNF and DPNF was significantly higher compared to PNF and MPNST (p<0.001 for both comparisons, Mann-Whitney U-test).
CONCLUSIONS: DPNF show some distinct cellular characteristics. A high number of EMA positive cells possibly indicates the dissemination of perineural cells to the surrounding tissue. Concerning mast cell density, DPNF resemble DNF and CNS rather than PNF. Close contact of tumor cells in DPNF, DNF and CNF with the immune system is a prerequisite for permanent immunological reactions in contrast to PNF in which tumor cells are partitioned from the immune system by the perineurium and blood-nerve barrier of blood vessels. It is assumed that these morphological distinctions may reflect in part the biological differences between the entities. While PNF is a known precancerous stage in NF1 patients, DPNF are not rated as such. Furthermore, the morphologic differences between benign nerve sheath tumors may be important for the efficacy of drugs to access tumor cells.
METHODS: Tissue micro-array (TMA) analysis was applied to study 520 formalin-fixed, paraffin-embedded human PNST of 385 patients with confirmed NF1 diagnosis. PNST originated from all areas of the body and were classified as cutaneous neurofibroma (CNF, n=114), diffuse neurofibroma (DNF, n=109), DPNF (n=108), plexiform neurofibroma (PNF, n=110), and malignant peripheral nerve sheath tumor (MPNST, n=22). Histomorphology and antigen expression patterns of the tumors were determined [S100, epithelial membrane antigen (EMA), CD90, mast cell tryptase, and neurofilament].
RESULTS: Benign PNST showed significantly more S100-positive tumor cells than MPNST (p<0.001). EMA expression was most pronounced in perineurium of DPNF. The number of mast cells in CNF, DNF and DPNF was significantly higher compared to PNF and MPNST (p<0.001 for both comparisons, Mann-Whitney U-test).
CONCLUSIONS: DPNF show some distinct cellular characteristics. A high number of EMA positive cells possibly indicates the dissemination of perineural cells to the surrounding tissue. Concerning mast cell density, DPNF resemble DNF and CNS rather than PNF. Close contact of tumor cells in DPNF, DNF and CNF with the immune system is a prerequisite for permanent immunological reactions in contrast to PNF in which tumor cells are partitioned from the immune system by the perineurium and blood-nerve barrier of blood vessels. It is assumed that these morphological distinctions may reflect in part the biological differences between the entities. While PNF is a known precancerous stage in NF1 patients, DPNF are not rated as such. Furthermore, the morphologic differences between benign nerve sheath tumors may be important for the efficacy of drugs to access tumor cells.
摘要：
目的：本研究的目的是表征从1型神经纤维瘤病（NF1）患者获得的一系列肿瘤中周围神经鞘瘤（PNST）的生长方式和抗原分布，重点是弥漫性丛状神经纤维瘤（DPNF）的形态学特征。
方法：组织微阵列（TMA）分析用于研究520福尔马林固定，石蜡包埋的人PNST385例确诊为NF1。PNST起源于身体的所有区域，被归类为皮肤神经纤维瘤（CNF，n=114),弥漫性神经纤维瘤（DNF，n=109)，DPNF（n=108），丛状神经纤维瘤（PNF，n=110),和恶性周围神经鞘瘤（MPNST，n=22）。确定肿瘤的组织形态学和抗原表达模式[S100，上皮膜抗原（EMA），CD90肥大细胞类胰蛋白酶,和神经丝]。
结果：良性PNST显示S100阳性肿瘤细胞明显多于MPNST（p<0.001）。EMA在DPNF的神经鞘膜中表达最明显。CNF中肥大细胞的数量,DNF和DPNF显著高于PNF和MPNST(p<0.001,曼-惠特尼U检验)。
结论：DPNF显示出一些明显的细胞特征。大量的EMA阳性细胞可能表明神经周细胞散布到周围组织。关于肥大细胞密度，DPNF类似于DNF和CNS而不是PNF。肿瘤细胞在DPNF、与PNF相比,具有免疫系统的DNF和CNF是永久性免疫反应的先决条件,在PNF中,肿瘤细胞通过神经周和血管的血神经屏障与免疫系统分开。假定这些形态学差异可以部分地反映实体之间的生物学差异。虽然PNF是NF1患者中已知的癌前阶段，DPNF没有这样评级。此外，良性神经鞘瘤之间的形态学差异对于药物进入肿瘤细胞的疗效可能很重要。
方法：组织微阵列（TMA）分析用于研究520福尔马林固定，石蜡包埋的人PNST385例确诊为NF1。PNST起源于身体的所有区域，被归类为皮肤神经纤维瘤（CNF，n=114),弥漫性神经纤维瘤（DNF，n=109)，DPNF（n=108），丛状神经纤维瘤（PNF，n=110),和恶性周围神经鞘瘤（MPNST，n=22）。确定肿瘤的组织形态学和抗原表达模式[S100，上皮膜抗原（EMA），CD90肥大细胞类胰蛋白酶,和神经丝]。
结果：良性PNST显示S100阳性肿瘤细胞明显多于MPNST（p<0.001）。EMA在DPNF的神经鞘膜中表达最明显。CNF中肥大细胞的数量,DNF和DPNF显著高于PNF和MPNST(p<0.001,曼-惠特尼U检验)。
结论：DPNF显示出一些明显的细胞特征。大量的EMA阳性细胞可能表明神经周细胞散布到周围组织。关于肥大细胞密度，DPNF类似于DNF和CNS而不是PNF。肿瘤细胞在DPNF、与PNF相比,具有免疫系统的DNF和CNF是永久性免疫反应的先决条件,在PNF中,肿瘤细胞通过神经周和血管的血神经屏障与免疫系统分开。假定这些形态学差异可以部分地反映实体之间的生物学差异。虽然PNF是NF1患者中已知的癌前阶段，DPNF没有这样评级。此外，良性神经鞘瘤之间的形态学差异对于药物进入肿瘤细胞的疗效可能很重要。
