Primary vulvar Ewing's sarcoma/primitive neuroectodermal tumor in a post-menopausal woman: A case report

Ewing's sarcomas/peripheral primitive neuroectodermal tumors (ES/pPNETs) are high-grade malignant neoplasms rarely found outside the skeletal system. Only 12 cases of vulvar ES/pPNET have so far been reported, all involving children or women of child-bearing age. We describe the case of a 52-year-old woman who was admitted to our hospital for the local excision of a 4 cm vulvar mass, originally thought to be a Bartholin's gland cyst. It was subsequently found to consist of small round cells positive for anti-CD99 antibody, thus suggesting a diagnosis of ES/pPNET. The demonstration of EWSR1 gene translocations by means of fluorescent in situ hybridization excluded small-cell carcinoma, squamous cell carcinoma of the small type, Merkel cell carcinoma, and lymphoblastic lymphoma. After surgery, the patient received six cycles of polychemotherapy and radiotherapy; she is still alive and well after 1 year of follow-up. Our findings underline the crucial role of molecular biology techniques in the differential diagnosis of small round cell tumors in these unusual locations.     

外周原始神经外胚肿瘤／尤因肉瘤临床病理学

目的：研究原始神经外胚叶瘤（PNET）／尤因肉瘤的（EWS）的诊断,鉴别诊断。方法：41例病人按传统病理学分为3类,并用免疫组织化学两步法检测CD99,NSE,S－100蛋白,Syn,VIm,LCA,Des,Myo抗体的表达。结果：（1）41例病人有27例PNET,8例EWS和6例Askin瘤。（2）免疫表型,CD99有87．8％强阳性表达,NSE53．7％,S－100蛋白22％,Syn4.9%,vim41.5%,统计结果显示CD99强阳性表达与NSE,S-100蛋白,Syn,Vim强阳性表达差异有显著性（P＜0．01）。（3）,PNET,EWS,Askin瘤对各种抗体的阳性表达差异无显著性（P＞0．05）,结论：（1）PNET,EWS,Askin瘤属同一肿瘤家族,（2）用组织学,免疫组织化学可与其他小圆细胞肿瘤进行鉴别诊断。     

骨外Ewing肉瘤/外周原始神经外胚叶肿瘤的临床病理分析

目的探讨骨外Ewing肉瘤／外周原始神经外胚叶肿瘤的临床病理特征及诊断、鉴别诊断依据。方法18例骨外Ewing肉瘤／外周原始神经外胚叶肿瘤行常规病理检查及免疫组化染色,其中2例进行电镜检查。结果光镜显示肿瘤组织主要由小圆形或卵圆形细胞组成,免疫组化染色显示肿瘤细胞膜CD99强阳性,电镜显示肿瘤细胞质内有神经内分泌颗粒。结论骨外Ewing肉瘤/外周原始神经外胚叶肿瘤的诊断依赖病理特征,并需要与其他小细胞恶性肿瘤进行鉴别。     

Expression of a new human THY-1 related antigen in Ewing's sarcoma and peripheral neuroectodermal tumors

Ewing's sarcoma (ES), peripheral neuroectodermal tumor (PNET) and Askin's tumor of the chest wall share a reciprocal chromosomal translocation between the long arms of chromosomes 11 and 22 (q23-24; q12). In the absence of other distinguishing features this specific translocation is regarded as marker of a common and neuroectodermal origin for these rare tumors. A monoclonal antibody (HBA-71) developed in our laboratory has been found to recognize an unique ES and PNET associated antigen, which is also expressed in some normal tissues, including thymus, bone marrow, islets of Langerhans, ependyma and adenohypophysis. It is shown in this study that this HBA-71 antigen is closely related to the murine THY-1 antigens, major cell surface glycoproteins of thymocytes and brain in mice and rat. Both antigens have similar molecular ratios (18,000), amino acid compositions and sensitivity to tryptic digestion, show high cell surface expression, and binding of the appropriate antibodies to HBA-71 antigen triggers proliferation in thymocytes. The HBA-71 epitope may represent a primitive neuroectodermal marker of ES/PNET, or its expression may be directly linked to the reciprocal translocation invariably associated with HBA-71-positive ES and PNET tumors, which maps to the same region of chromosome 11 (q23-24) as the human Thy-1 gene.     

Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors.

Diagnostic classification of poorly differentiated, round cell, primitive neuroectodermal neoplasms, including Ewing's sarcoma, peripheral neuroepithelioma, Askin's tumor, and esthesioneuroblastoma, is challenging to the surgical pathologist using conventional histopathologic approaches because of very similar and overlapping morphologic and cytologic features. Furthermore, distinguishing these neoplasms from neuroblastoma, embryonal rhabdomyosarcoma, small cell osteogenic sarcoma, and non-Hodgkin's lymphoma can be difficult. This paper describes and reviews the cytogenetic and molecular genetic changes in these tumors and demonstrates how the ability to detect these changes has enabled a greater understanding of the histogenesis, classification, diagnosis, and prognosis of these neoplasms.     

石蜡包埋尤文瘤/外周原始神经外胚瘤中EWS-FLI1融合基因的表达

目的 运用逆转录聚合酶链反应(RT-PCR)技术检测石蜡包埋尤文瘤／外周原始神经外胚瘤(ES／pPNET)组织中特异性染色体易位融合基因EWS-FLI1／ERGmRNA的表达并探讨其诊断意义。方法 运用一步法RT-PCR技术检测25例石蜡包埋ES／pPNETs和15例其他小圆细胞肿瘤(包括8例胚胎型和腺泡型横纹肌肉瘤、4例低分化滑膜肉瘤、2例神经母细胞瘤和1例淋巴瘤)组织中EWS-FLI1／ERG的表达。结果 25例ES／pPNET中20例检测到EWS-FLI1／ERG融合基因的表达(8056),15例对照组均未检出EWS-FLI1的表达。结论 EWS-FLI1／ERGmRNA的表达是ES／pPNETs分子诊断的可靠指标,一步法RT-PCR是一种适用于临床常规石蜡包埋组织EWS-FLI1融合基因表达的检测方法。     

原发椎管内外周型原始神经外胚层肿瘤2例

目的探讨椎管内原发外周型原始神经外胚层肿瘤的临床特点、诊断、病理表现和治疗进展。方法分析2例经影像学、手术和病理检测证实的椎管内原始神经外胚层肿瘤,回顾相关文献,总结其临床特点。结果 2例病变术前行MRI检查呈等T1WI和等T2WI信号,增强后明显强化;镜下部分切除病变,术后病理检查提示均为外周型原始神经外胚层肿瘤,术后行放疗和化疗,分别随访13和10个月。结论椎管内原始神经外胚层肿瘤发病率低,好发于青少年,影像学无明显特异性,病理检查是可靠的诊断依据,预后较差。     

Peripheral primitive neuroectodermal tumor/Ewing's sarcoma of the craniospinal vault: case reports and review

The peripheral primitive neuroectodermal tumor/Ewing's sarcoma family tumor (pPNET/ESFT) group includes small round cell tumors of the bone, soft tissue, and nerve with morphological attributes of the germinal neuroepithelium. Peripheral PNETs/ESFTs also occur within the craniospinal vault, a region including the central nervous system, the meninges, and the cranial and spinal nerve roots. Gene rearrangements between the EWS gene on chromosome 22q12 and members of the ETS gene family are common in and specific to pPNETs/ESFTs. Another defining characteristic of pPNETs/ESFTs is their membranous expression of the MIC2 gene product. We describe 2 cases of pPNETs within the craniospinal vault. An intradural tumor arising from the nerve roots of the cauda equina was discovered in a 32-year-old man presenting with radiculopathic back pain and lower-extremity weakness. An intracranial pPNET that mimicked a meningioma was found in a 21-year-old man presenting with headache and visual disturbances. MIC2 gene product expression and EWS/ETS gene rearrangement were detected in both case patients. The literature with regard to pPNETs/ESFTs arising within the craniospinal vault is reviewed.     

Detection of recurrent chromosome abnormalities in Ewing's sarcoma and peripheral neuroectodermal tumor cells using bivariate flow karyotyping.

Bivariate flow karyotyping can be used for the detection of recurrent chromosome abnormalities in tumor cells. For this purpose 2 cell lines originally derived from Ewing's sarcomas and 4 cell lines from peripheral neuroectodermal tumors were used. The characteristic t(11;22) was known to be present in 5 cell lines. The remaining cell line was known to have a variant t(2;11;22;21) translocation. Metaphase chromosomes were stained with the fluorescent dyes Hoechst 33258 and Chromomycin A3 and analyzed subsequently using bivariate flow cytometry. The resulting bivariate flow karyotypes of the tumor cells were normalized by a standardized procedure using a computerized method and compared with a reference flow karyotype of normal chromosomes. In 5 cell lines two recurring abnormal chromosome peaks were identified at positions expected for the der(11) and der(22) chromosomes characteristic for the reciprocal t(11;22)(q24;q12). In the remaining cell line with the variant t(2;11;22;21), only the peak representing the der(22) was identifiable. It is concluded that bivariate flow karyotyping can be used for the semiautomated detection of recurrent translocations and the assessment of their variability among different tumors.     

Primary skeletal Ewing's sarcoma in Down syndrome

Primary skeletal Ewing's sarcoma that occurred in two teenage patients with Down syndrome are reported. Cytogenetic analysis of one of these tumors showed the 11;22 translocation characteristic of Ewing's sarcoma as well as other complex karyotypic changes. The possible role of constitutional trisomy 21 in development of these sarcomas is discussed.     

Secretogranin II expression in Ewing's sarcomas and primitive neuroectodermal tumors.

Production of chromogranins, the acidic components of the chromaffin granules regarded as specific neuroendocrine markers, was analyzed by immunocytochemistry and hybridization (Northern blotting and in situ hybridization) in primary lesions and cell lines of Ewing's sarcomas, primitive neuroectodermal tumors (PNETs), and neuroblastomas. Antibodies and probes specific for chromogranin A (CgA), chromogranin B (CgB), and secretogranin II (SgII) were used. Ewing's sarcomas and PNETs, unlike neuroblastomas, were negative for CgA and CgB. Two primary Ewing's sarcomas, one primary PNET (an Askin tumor), and one PNET cell line (TC32) were found to strongly express the SgII gene, as shown by the presence of specific mRNA. This result supports the hypothesis that some Ewing's sarcomas represent a most primitive form of neuroectodermal tumor; in addition, it indicates a diagnostic role of SgII in cases of Ewing's sarcomas and PNETs.     

Primary Ewing sarcoma/primitive neuroectodermal tumor in the adrenal gland

Primary Ewing sarcoma or primitive neuroectodermal tumor (PNET) of the adrenal gland is extremely rare. We report a case of Ewing sarcoma or PNET of the adrenal in a 48‐year‐old Chinese woman. The patient was hospitalized with left upper quadrant abdominal pain and swelling that had been present for 1 year. Computed tomography (CT) images revealed a circumscribed mass in the left adrenal region measuring 12 cm in its greatest dimension, and the mass was surgically resected. Macroscopically, the mass (13 × 10 × 8 cm³) in the left adrenal gland was encapsulated, soft, appearing grayish white and yellow, and with foci of cystic degeneration, necrosis, and hemorrhage on cross‐sectional. Non‐tumorous adrenal tissue was compressed, but identifiable at the periphery of the specimen. Histologically, compact short spindle and oval tumor cells were arranged in sheets. Tumor cells tested positive for vimentin, CD99, Bcl‐2, NKX2.2, EMA, and CD117, and weakly positive for FLI‐1 on immunohistochemical analysis and showed rearrangement of the EWSR1 on fluorescence in situ hybridization analysis. Post‐adrenalectomy, after being recurrence free for 4.5 years, the patient relapsed and a localized recurrence was detected on a follow‐up CT scan.     

Cytological diagnosis and prognosis in Ewing's sarcoma in children

143 cytological studies of the material obtained from 98 children aged from 2 to 18 years with tentative diagnosis of Ewing's sarcoma were made. Histocytological correlations showed 96.2% cases to be of informative value, 87% of them with precise cytological diagnosis of the above sarcoma. The analysis of images specified mean values of square (S) and ploidity (P) of tumor cell nuclei in 21 children with a good (10), and bad (11) outcome of the disease. It was established that if ploidy is higher than expected one (p = 0.0357 S), bad prognosis can be supposed and a good prognosis in the opposite case. In case of good prognosis differentiated tumor cells with large clear nuclei are seen in the smears, and poorly differentiated cells with hyperchromic nuclei are observed in cases with bad prognosis.