Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.
Humans ; Male ; Female ; Young Adult ; Adult ; Adolescent ; Sarcoma, Ewing/pathology* ; Proto-Oncogene Protein c-fli-1 ; Immunohistochemistry ; Biomarkers, Tumor/genetics* ; Central Nervous System/pathology*

BACKGROUNDEwing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is often difficult to distinguish from other small round cell tumors. The EWS-Ets gene fusions that result from chromosomal translocations in this tumor provide potential molecular diagnostic markers. To apply these molecular markers to commonly available archival materials, we evaluated the feasibility of detecting EWS-Ets including EWS-Fli1 and EWS-ERG fusion transcripts in paraffin-embedded tissues and its diagnostic value for detecting ES/pPNET.

METHODSThirteen paraffin-embedded samples of ES/pPNETs were retrieved from archives. Thirteen cases of other tumors with small round cell features (including rhabdomyosarcoma, neuroblastoma, lymphoma, small cell carcinoma, and desmoplastic small round cell tumor) were used as negative controls. Beta-actin and beta2-microglobulin were used as internal controls. A nested reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay was performed to detect the EWS-Fli1 and EWS-ERG fusion transcripts.

RESULTSBeta-actin and beta2-microglobulin were detected in 10/13 and 13/13 ES/pPNETs, respectively. EWS-Fli1 fusion transcripts were detected in 11 of 13 (85%) ES/pPNETs. Three chimeric transcripts, all EWS-Fli1, were detected in ES/pPNET samples. Among 11 EWS-Fli1-positive cases, 7 cases had a type I fusion transcript involving fusion of EWS exon 7 with Fli1 exon 6, 2 cases had a type II fusion transcript involving EWS exon 7 with Fli1 exon 5, and 2 cases expressed fusion transcripts involving EWS exon 7 and Fli1 exon 8. Type I EWS-Fli1 fusion predominated over other types. Fusion types could not be distinguished in the remaining 2 cases. Thirteen negative controls did not show detectable chimeric messages. There was a significant relationship between EWS-Fli1 fusion transcripts and CD99 expression.

CONCLUSIONSMolecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.

Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Neuroectodermal Tumors, Primitive, Peripheral ; genetics ; pathology ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; Proto-Oncogene Protein c-fli-1 ; RNA, Messenger ; analysis ; RNA-Binding Protein EWS ; Sarcoma, Ewing ; genetics ; pathology ; Transcription Factors ; genetics

Base Sequence ; Formaldehyde ; chemistry ; Humans ; Molecular Sequence Data ; Oncogene Proteins, Fusion ; genetics ; Paraffin Embedding ; Proto-Oncogene Protein c-fli-1 ; genetics ; RNA, Neoplasm ; genetics ; metabolism ; RNA-Binding Protein EWS ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Rhabdomyosarcoma ; genetics ; Sarcoma, Ewing ; genetics ; Sarcoma, Synovial ; genetics ; Soft Tissue Neoplasms ; genetics ; Tissue Fixation

OBJECTIVETo investigate the expression of EWS-FLI1/ERG fusion transcript resulting from t(11;12)(q24;12) in paraffin-embedded tissues and its diagnostic implication for Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET).

METHODSOne-step reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect a characteristic EWS-FLI1/ERG fusion transcript in 25 cases of ES/pPNET and 15 cases of other small round cell tumors (including 8 cases of rhabdomyosarcoma, 4 cases of synovial sarcoma, 2 cases of neuroblastoma and 1 case of lymphoma) using formalin-fixed and paraffin-embedded tissues.

RESULTSEWS-FLI1/ERG fusion transcript was detected in 20 of the 25 ES/pPNET cases (80%). The 15 non-ES/pPNET control cases were negative for EWS-FLI1/ERG fusion transcript.

CONCLUSIONSDetection of EWS-FLI1/ERG fusion transcript is a reliable index for molecular diagnosis of ES/pPNET. One-step RT-PCR is a practical method for such analysis in routine paraffin-embedded tumor tissues.

Adolescent ; Adult ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Neuroectodermal Tumors, Primitive, Peripheral ; diagnosis ; metabolism ; Oncogene Proteins, Fusion ; metabolism ; Paraffin Embedding ; Proto-Oncogene Protein c-fli-1 ; RNA-Binding Protein EWS ; Reverse Transcriptase Polymerase Chain Reaction ; Rhabdomyosarcoma ; diagnosis ; metabolism ; Sarcoma, Ewing ; diagnosis ; metabolism ; Sarcoma, Synovial ; diagnosis ; metabolism ; Transcription Factors ; metabolism

OBJECTIVETo study the clinicopathologic features and differential diagnosis of epithelioid sarcoma-like hemangioendothelioma (ES-H).

METHODSThe clinical, radiologic and pathologic features of three cases of ES-H were analyzed.

RESULTSAll the 3 cases occurred in male adults. The age ranged from 44 to 53 years. The presentations included left neck mass, iliac pain and bilateral shoulder masses. Histologically, ES-H was composed of a mixture of spindle and epithelioid tumor cells. Transition between the two cell types was demonstrated. The tumor cells were arranged in compact sheets, vague nodules or intersecting fascicles, amongst a collagenous stroma. Central coagulative necrosis was identified in one case, reminiscent the morphology that seen in epithelioid sarcoma. There was no evidence of angiogenesis, though focal presence of intracytoplasmic vacuoles was seen in one case, as in classic examples of epithelioid hemangioendothelioma. Immunohistochemical study showed that the tumor cells expressed both epithelial (AE1/AE3, CAM5.2 and epithelial membrane antigen) and endothelial (CD31, Fli-1 and factor VIII-related antigen) markers. Two of the cases were also positive for CD34. All of the patients were treated by surgical resection. Two patients remain well at 14-month and 9-month follow up, respectively. The remaining patient had repeated local recurrences during a 6-year period.

CONCLUSIONSES-H represents a rare morphologic type of hemangioendothelioma. It has some overlapping histologic features with epithelioid sarcoma and epithelioid hemangioendothelioma. The endothelial nature of ES-H is difficult to be verified on the basis of morphologic examination alone. Confirmation of the diagnosis with immunohistochemistry is necessary. ES-H is likely related to epithelioid hemangioendothelioma and may represent a cellular spindle cell variant of epithelioid hemangioendothelioma.

Adult ; Antigens, CD34 ; metabolism ; Biomarkers ; metabolism ; Diagnosis, Differential ; Follow-Up Studies ; Hemangioendothelioma ; metabolism ; pathology ; surgery ; Hemangioendothelioma, Epithelioid ; metabolism ; pathology ; Humans ; Ilium ; Immunohistochemistry ; Keratins ; metabolism ; Lymphatic Metastasis ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Neck ; Neoplasm Recurrence, Local ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Proto-Oncogene Protein c-fli-1 ; metabolism ; Reoperation ; Retrospective Studies ; Sarcoma ; metabolism ; pathology ; surgery ; Shoulder ; von Willebrand Factor ; metabolism

Extraskeletal Ewing's sarcoma (EES) is a rare soft tissue tumor morphologically indistinguishable from the more common Ewing's sarcoma of bone. We report a case of EES arising in the hard palate of 34-yr-old male patient. Microscopically, the monotonous small round cells without neuronal differentiation showed membranous positive immunoreactivity for MIC2/CD99 and vimentin. Ultrastructurally, the tumor cells showed a few intracytoplasmic organelles without evidence of neurosecretory granules or neurofilaments. The EWS-FLI1 chimeric gene was identified using the nested reverse transcriptase-polymerase chain reaction.
Adult ; Antigens, CD/analysis ; Cell Adhesion Molecules/analysis ; Humans ; Immunohistochemistry ; Male ; Oncogene Proteins, Fusion/genetics ; Palatal Neoplasms/genetics/metabolism/*pathology ; Palate, Hard/metabolism/*pathology ; Proto-Oncogene Protein c-fli-1/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma, Ewing's/genetics/metabolism/*pathology ; Transcription, Genetic ; Vimentin/analysis

OBJECTIVETo compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen.

METHODSSeventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review.

RESULTSThe male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases.

CONCLUSIONSSCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

12E7 Antigen ; Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Biopsy, Large-Core Needle ; Bone Neoplasms ; diagnosis ; metabolism ; pathology ; Carcinoma, Small Cell ; diagnosis ; metabolism ; pathology ; Cell Adhesion Molecules ; metabolism ; Child ; Female ; Humans ; Lymphoma ; diagnosis ; metabolism ; pathology ; Male ; Middle Aged ; Neuroectodermal Tumors, Primitive, Peripheral ; diagnosis ; metabolism ; pathology ; Oncogene Proteins, Fusion ; metabolism ; Osteosarcoma ; diagnosis ; metabolism ; pathology ; Plasmacytoma ; diagnosis ; metabolism ; pathology ; Proto-Oncogene Protein c-fli-1 ; metabolism ; RNA-Binding Protein EWS ; metabolism ; Retrospective Studies ; Sarcoma, Ewing ; diagnosis ; metabolism ; pathology ; Vimentin ; metabolism ; Young Adult

OBJECTIVETo study the clinicopathologic features of primitive neuroectodermal tumor (PNET) in female genital tract.

METHODSSix cases of PNET arising in female genital tract were retrospectively reviewed. The clinicopathologic features, immunohistochemical findings and EWS gene translocation study results were analyzed.

RESULTSThe age of patients ranged from 10 to 27 years (mean = 20 years). The sites of involvement included ovary (1 case), uterus (1 case), vulva (2 cases) and vagina (2 cases). The greatest diameter of the tumor ranged from 2 to 10 cm (mean = 5.4 cm). The tumor had nodular appearance and showed grayish-pink fleshy cut surface, accompanied by foci of hemorrhage and necrosis. Histologically, the tumor was composed of malignant small round cells with indistinct cell borders, hyperchromatic nuclei, dense chromatin, tiny nucleoli and scanty cytoplasm. The tumor cells were arranged in sheets or lobules. Homer-Wright rosettes were identified in 1 case. Immunohistochemical study showed that the tumor cells were positive for CD99, FLI-1 and CD56 (6/6). Focal expression of vimentin (5/6), NSE (5/6), nestin (4/6), synaptophysin (4/6), S-100 protein (2/6) and chromogranin A (1/6) was also demonstrated. EWS gene translocation was detected in 5 cases studied. Follow-up information was available in 2 patients (7 and 17 months of follow up, respectively). One of them died of tumor metastasis 17 months after diagnosis. The other patient was still alive.

CONCLUSIONSPNET arising in female genital tract is rare. It mainly involves ovary, uterus, vulva and vagina. Immunohistochemical study using a panel of antibodies and fluorescence in-situ hybridization play an important role in definitive diagnosis of this rare malignancy.

12E7 Antigen ; Adolescent ; Adult ; Antigens, CD ; metabolism ; CD56 Antigen ; metabolism ; Cell Adhesion Molecules ; metabolism ; Child ; Female ; Follow-Up Studies ; Genital Neoplasms, Female ; genetics ; metabolism ; pathology ; surgery ; Humans ; Neuroectodermal Tumors, Primitive, Peripheral ; genetics ; metabolism ; pathology ; surgery ; Ovarian Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Proto-Oncogene Protein c-fli-1 ; metabolism ; RNA-Binding Protein EWS ; genetics ; Retrospective Studies ; Translocation, Genetic ; Uterine Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vaginal Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; Vulvar Neoplasms ; genetics ; metabolism ; pathology ; surgery ; Young Adult

OBJECTIVETo observe the expression of FLI-1 in primitive neuroectodermal tumors (PNET), explore the value of immunohistochemical staining of FLI-1 in combination with other neural markers in diagnosis of PNET, and analyze the prognostic factors in PNET patients.

METHODS35 cases of PNET, of which 33 cases with complete clinical data, were included in this study. Immmunohistochemistry (The En Vision method) was applied to detect the expression of FLI-1, CD99, Syn, NSE, S-100, NF, Vim in the tumor tissues. The clinicopathological data of 33 cases were analyzed by Cox regression.

RESULTSThe positive expression rate of FLI-1 were 51.4% and that of CD99 was 88.6%. The sensitivity of FLI-1 combined with CD99 was up to 100%. The positive rates of Vim, Syn, NSE, s-100 and NF were 91.4%, 48.6%, 45.7%, 22.9% and 0, respectively. Cox regression analysis showed that the impact of primary location and treatment modality were of statistical significance (P < 0.05), but the age, sex, stage or size of tumors did not (P > 0.05).

CONCLUSIONImmunohistochemical detection of FLI-1 and neural markers is a preferred method for clinical diagnosis of PNET. The main factors affecting the prognosis are the primary location of PNET and treatment modality.

12E7 Antigen ; Adolescent ; Adult ; Antigens, CD ; metabolism ; Brain Neoplasms ; metabolism ; pathology ; therapy ; Cell Adhesion Molecules ; metabolism ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Middle Aged ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; therapy ; Neuroectodermal Tumors, Primitive, Peripheral ; metabolism ; pathology ; therapy ; Pelvic Neoplasms ; metabolism ; pathology ; therapy ; Phosphopyruvate Hydratase ; metabolism ; Proportional Hazards Models ; Proto-Oncogene Protein c-fli-1 ; metabolism ; S100 Proteins ; metabolism ; Survival Rate ; Synaptophysin ; metabolism ; Vimentin ; metabolism ; Young Adult