Chiang Sarah, Snuderl Matija, Kojiro-Sanada Sakiko, Quer Pi-Sunyer Ariadna, Daya Dean, Hayashi Tohru, Bosincu Luisanna, Ogawa Fumihiro, Rosenberg Andrew E, Horn Lars-Christian, Wang Lu, Iafrate A John, Oliva Esther
*Department of Pathology, Memorial Sloan Kettering Cancer Center †Department of Pathology, New York University Langone Medical Center, New York, NY ‡Department of Pathology, Kurume University School of Medicine, Fukuoka ¶Department of Pathology, Junwakai Memorial Hospital, Miyazaki **Department of Diagnostic Pathology, Sainokuni Higashiomiya Medical Center, Saitama, Japan §Department of Anatomic Pathology, Germans Trias I Pujol Hospital, Badalona, Spain ∥Department of Pathology, McMaster University, Juravinski Hospital, Hamilton, ON, Canada #Department of Pathology, University of Sassari, Sassari, Italy ††Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL ‡‡Division of Gynecologic, Breast and Perinatal Pathology, University Hospital Leipzig, Leipzig, Germany §§Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2017 Jun;41(6):761-772. doi: 10.1097/PAS.0000000000000831.
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.
女性生殖道原发性原始神经外胚层肿瘤（PNET）较为罕见，其确切分类仍不明确。本文报告了19例妇科PNET的临床、组织学、免疫表型特征以及EWSR1重排状态，其中包括10例卵巢肿瘤、8例子宫肿瘤和1例外阴肿瘤。患者年龄在12至68岁之间，卵巢PNET患者的中位年龄为20岁，子宫PNET患者的中位年龄为51岁。15例PNET具有中枢神经系统（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，符合中枢性PNET。其余4例PNET完全由未分化的小圆形蓝细胞组成，被归类为尤因肉瘤/外周性PNET。8例PNET与另一种肿瘤类型相关，包括5例卵巢成熟囊性畸胎瘤、2例子宫内膜低级别子宫内膜样癌和1例子宫癌肉瘤。免疫组化显示，17例PNET表达至少1种神经分化标志物，其中10例、8例、14例、8例和1例分别表达突触素、神经元特异性烯醇化酶、CD56、S100和嗜铬粒蛋白。4例PNET中GFAP呈阳性，均为中枢型。10例和16例肿瘤分别可见膜性CD99和核Fli-1染色，中枢性和尤因肉瘤/外周性PNET中均可见两种标志物的同时表达。所有肿瘤均表达波形蛋白，而角蛋白混合物（CAM5.2、AE1/AE3）染色仅在4例PNET中局灶性出现。荧光原位杂交在所有病例中均成功，4例具有尤因肉瘤/外周性PNET形态学特征且同时表达CD99和Fli-1的肿瘤中有2例证实存在EWSR1重排。总之，女性生殖道可出现中枢性和尤因肉瘤/外周性PNET，中枢性PNET更为常见。中枢性PNET表现出一系列与CNS肿瘤重叠的形态学特征，但缺乏EWSR1重排。GFAP表达支持中枢性PNET的形态学印象，在尤因肉瘤/外周性PNET中不存在。尤因肉瘤/外周性PNET缺乏CNS肿瘤的形态学特征。
