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Primitive Neuroectodermal Tumors of the Female Genital Tract: A Morphologic, Immunohistochemical, and Molecular Study of 19 Cases.

19例女性生殖道原始神经外胚层肿瘤形态学、免疫表型和分子学研究

Chiang S,Snuderl M,Kojiro-Sanada S,Quer Pi-Sunyer A,Daya D,Hayashi T,Bosincu L,Ogawa F,Rosenberg AE,Horn LC,Wang L,Iafrate AJ,Oliva E

Abstract

Primary primitive neuroectodermal tumor (PNET) of the female genital tract is rare, and its proper classification remains unclear. The clinical, histologic, and immunophenotypic features as well as EWSR1 rearrangement status of 19 gynecologic PNETs, including 10 ovarian, 8 uterine, and 1 vulvar tumors, are herein reported. Patient age ranged from 12 to 68 years, with a median age of 20 and 51 years among those with ovarian and uterine PNETs, respectively. Morphologic features of central nervous system (CNS) tumors were seen in 15 PNETs, including 9 medulloblastomas, 3 ependymomas, 2 medulloepitheliomas, and 1 glioblastoma, consistent with central PNET. The remaining 4 PNETs were composed entirely of undifferentiated small round blue cells and were classified as Ewing sarcoma/peripheral PNET. Eight PNETs were associated with another tumor type, including 5 ovarian mature cystic teratomas, 2 endometrial low-grade endometrioid carcinomas, and a uterine carcinosarcoma. By immunohistochemistry, 17 PNETs expressed at least 1 marker of neuronal differentiation, including synaptophysin, NSE, CD56, S100, and chromogranin in 10, 8, 14, 8, and 1 tumors, respectively. GFAP was positive in 4 PNETs, all of which were of central type. Membranous CD99 and nuclear Fli-1 staining was seen in 10 and 16 tumors, respectively, and concurrent expression of both markers was seen in both central and Ewing sarcoma/peripheral PNETs. All tumors expressed vimentin, whereas keratin cocktail (CAM5.2, AE1/AE3) staining was only focally present in 4 PNETs. Fluorescence in situ hybridization was successful in all cases and confirmed EWSR1 rearrangement in 2 of 4 tumors demonstrating morphologic features of Ewing sarcoma/peripheral PNET and concurrent CD99 and Fli-1 expression. In conclusion, central and Ewing sarcoma/peripheral PNETs may be encountered in the female genital tract with central PNETs being more common. Central PNETs show a spectrum of morphologic features that overlaps with CNS tumors but lack EWSR1 rearrangements. GFAP expression supports a morphologic impression of central PNET and is absent in Ewing sarcoma/peripheral PNET. Ewing sarcoma/peripheral PNETs lack morphologic features of CNS tumors.

摘要

发生在女性生殖道的原始神经外胚层肿瘤(PNET)罕见,确切分类尚不清楚。本文作者报道19例女性生殖道PNET的临床表现、组织学、免疫表型特征和EWSR1基因重排情况,发生在卵巢10例、子宫8例、会阴1例。患者年龄范围12-68岁,发生在卵巢和子宫的PNET中位年龄分别为20岁和51岁。 15例PNET中可见中枢神经系统 (CNS)肿瘤的形态学特征。包括9例髓母细胞瘤、3例室管膜瘤,2例髓上皮瘤和1例胶质母细胞瘤,与中枢神经系统的PNET较一致。剩余4例PNETs完全由未分化的小圆蓝细胞组成,被归类为尤文肉瘤或外周PNET。8例PNET与其他类型肿瘤有关,包括5例卵巢成熟性囊性畸胎瘤,2例子宫内膜的低级别内膜样癌和1例子宫癌肉瘤。免疫组化研究表明,其中17例PNET至少表达一种神经分化标记物,包括Syn(10/17)、NSE(8/17)、CD56(14/17)、S100(8/17)和CgA(1/17)。4例PNET中GFAP阳性,且均属于中枢型。10例瘤细胞膜阳性表达CD99,16例核阳性表达Fli-1。中枢和外周尤文肉瘤/PNET可同时共表达CD99和Fli-1。所有肿瘤均表达vimentin,而仅4例PNET局灶表达细胞角蛋白(CAM5.2,AE1/AE3)。所有病例均进行了FISH检测,具有尤文肉瘤/外周PNET形态学特征且同时具有CD99 与Fli-1表达的4例肿瘤中有2例检出了EWSR1重排。总之,女性生殖道可发生中枢和尤文肉瘤/外周PNET,中枢型PNET可能更常见。中枢型PNET显示了与CNS肿瘤重叠的形态学谱系特征,但缺乏EWSR1基因重排。GFAP的表达支持中枢型PNET,而在尤文肉瘤/外周PNET中不表达GFAP,且尤文肉瘤/外周PNET缺乏CNS肿瘤的形态学特征。

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