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• W2041956179 abstract "Primitive neuroectodermal tumor of the uterine corpus (PNET) is rare and appears to have an aggressive clinical course. We report on a postmenopausal woman with optimal surgically cytoreduced advanced-stage PNET in which adjuvant combination chemotherapy with platinum and taxane agents was unsuccessful in extending her disease-free survival. Primitive neuroectodermal tumor of the uterine corpus (PNET) is rare and appears to have an aggressive clinical course. We report on a postmenopausal woman with optimal surgically cytoreduced advanced-stage PNET in which adjuvant combination chemotherapy with platinum and taxane agents was unsuccessful in extending her disease-free survival. Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the Ewing sarcoma family of tumors originally described by Hart and Earle in 1973.1Hart M.N. Earle K.M. Primitive neuroectodermal tumors of the brain in children.Cancer. 1973; 32: 890-897Crossref PubMed Scopus (453) Google Scholar Rarely, PNET has been reported to originate in the female genital tract.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar As of 2007, there are only 22 published cases of PNET of the uterus.It is difficult to derive from the current literature any conclusion regarding the optimal treatment of these tumors. Overall, Ewing sarcoma tumors have a high relapse rate and high mortality rate.3Kushner B.H. Meyers P.A. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.J Clin Oncol. 2001; 19: 870-880Crossref PubMed Scopus (112) Google Scholar The majority of PNET of the uterine corpus is diagnosed at an advanced stage, highlighting its aggressive nature. In an effort to gain a better understanding of potential therapeutic options, we report on a case of PNET of the uterine corpus treated with a platinum and taxane combination chemotherapy following optimal cytoreductive surgery.Case ReportA 59-year-old white woman presented with postmenopausal vaginal bleeding. A pelvic ultrasound revealed a myometrial mass and thickened endometrium (11 mm). Curettage specimen was interpreted as endometrial stromal sarcoma. After referral, a gynecologic oncologist performed an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node sampling, and infracolic omentectomy. Surgical findings included an enlarged uterus and a necrotic 3 cm right pelvic lymph node. At the completion of the tumor reductive surgery, there was no grossly visible residual disease.Pathologic examination of the surgical specimen described an International Federation of Gynecology and Obstetrics (FIGO) stage IIIC based on pelvic and paraaortic lymph node involvement, high-grade malignant epithelial neoplasm, with features most compatible with peripheral PNET. Immunohistochemical studies revealed tumor cells with positive staining for WT-1, synaptophysin, CD10, and Ewing sarcoma marker CD99 (FIGURE 1, FIGURE 2).FIGURE 2Immunohistochemistry with CD99 (Ewing marker) showing membranous and cytoplasmic expression.Show full captionShah. Primitive neuroectodermal tumor. Am J Obstet Gynecol 2009.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Three weeks after surgery, the patient was initiated on chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks. No growth factors were used and no treatment delays occurred. A computed tomography (CT) scan 1 week after completing chemotherapy revealed evidence of disease, with metastatic cystic lesions measuring 4 cm near the vagina cuff, 3 cm at the left pelvic sidewall, and 2 cm along the paraaortic lymph nodes. The patient subsequently underwent palliative 4-field pelvic radiotherapy and paraaortic boost image modulated radiotherapy for a total of 50 Gy over 6 weeks. She also received concomitant cisplatin therapy at 40 mg/m2 for 4 weekly cycles.A follow-up, 12-month CT scan showed significant increase in the neoplastic process, with significant mediastinal lymphadenopathy. Multiple pulmonary and hepatic nodules were also identified. She is currently alive with persistent disease after 12 months and is considering further palliative chemotherapy.CommentPrimitive neuroectodermal tumor is a rare tumor. PNET of the uterus usually presents with abnormal vaginal bleeding and uterine mass. There is a bimodal age distribution, with PNET presenting either in the second decade or in the postmenopausal period.The striking similarity between extraskeletal Ewing's sarcoma and PNET provides insight into these rare tumors. The identification of a common translocation t(11;22)(q24;12) in Ewing sarcoma and nearly 85% of PNET suggests that these tumors share a common histogenesis.4Delattre O. Zucman J. Melot T. et al.The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts.N Engl J Med. 1994; 331: 294-299Crossref PubMed Scopus (906) Google Scholar This understanding, along with identification of the fusion gene, EWS-FL11, may aid in the understanding of this disease and the identification of more targeted therapies.5Mittal S. Sumana G. Gupta M. Gupta B. Primitive neuroectodermal tumor of the uterus: a case report.Int J Gynecol Cancer. 2007; 17: 524-527Crossref PubMed Scopus (16) Google ScholarThe differential diagnosis of PNET of the uterine corpus includes uterine lymphoma, poorly differentiated endometrioid carcinoma, high-grade endometrial stromal sarcoma or undifferentiated sarcoma, and small cell neuroendocrine carcinoma.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar In addition to the histologic pattern, immunohistochemical staining with CD99 or MIC2, vimentin, synaptophysin, and neuron-specific enolase assists in making the diagnosis of PNET of the uterine corpus.7Akbayir O. Gungorduk K. Rafioglu G. et al.Primary primitive neuroectodermal tumor of the uterus: a case report.Arch Gynecol Obstet. 2008; 277: 345-348Crossref PubMed Scopus (17) Google ScholarThere is no consensus of the optimal treatment for patients with PNET of the uterus, because the majority of published patients had surgery, chemotherapy, and/or radiotherapy (Table). From these cases it appears that advancing age and advancing stage correlate with a poorer prognosis. The 2-year survival of younger patients and postmenopausal patients was 75% and 32%, respectively.8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google ScholarTABLEClinical features of primary primitive neuroectodermal tumors of the uterine corpusCaseAge, yFIGO stageSurgeryRadiationChemotherapyFollow-upHendrickson and Scheithauer13Hendrickson M.R. Scheithauer B.W. Primitive neuroectodermal tumor of the endometrium: report of two cases, one with electron microscopic observations.Int J Gynecol Pathol. 1986; 5: 249-259Crossref PubMed Scopus (48) Google Scholar12IVBTAH, LSOYesCyclophosphamidePelvic recurrence, 12 monthsdoxorubicinDOD, 2 yvincristineHendrickson and Scheithauer13Hendrickson M.R. Scheithauer B.W. Primitive neuroectodermal tumor of the endometrium: report of two cases, one with electron microscopic observations.Int J Gynecol Pathol. 1986; 5: 249-259Crossref PubMed Scopus (48) Google Scholar57IIBTAH, BSO, PALNDYesCisplatinLung metastasis, 5 monthsvinblastineDOD, 2 ybleomycinDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar67IIICSAH, BSOYesCisplatinPersistentdoxorubicinDOD, 6 monthscarboplatin5-FUDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar68IVBTAH, BSO, PLNDYesCisplatinPersistentDOD, 12 monthsDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar69ITAH, BSO, PLNDYesNot doneNED, 6 yDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar68ITAH, BSOYesNot doneNED, 5 yMolyneux et al14Molyneux A.J. Deen S. Sundaresan V. Primitive neuroectodermal tumour of the uterus.Histopathology. 1992; 21: 584-585Crossref PubMed Scopus (27) Google Scholar72ITAH, BSONot doneNot doneDOD, 8 monthsFukunaga et al15Fukunaga M. Nomura K. Endo Y. Ushigome S. Aizawa S. Carcinosarcoma of the uterus with extensive neuroectodermal differentiation.Histopathology. 1996; 29: 565-570Crossref PubMed Scopus (52) Google Scholar54NRTAH, BSONot doneCyclophosphamidePersistentcisplatinAWD, 3 monthsdoxorubicin5-FUSorensen et al16Sorensen J.B. Schultze H.R. Madsen E.L. Holund B. Primitive neuroectodermal tumor (PNET) of the uterine cavity.Eur J Obstet Gynecol Reprod Biol. 1998; 76: 181-184Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar62ITAH, BSOYesVincristineRecurrent ascites, 6 monthscyclophosphamideDOD, 18 monthscisplatinTaieb et al17Taieb S. Cabaret V. Bonodeau F. Leblanc E. Besson P. MRI of primitive neuroectodermal tumor of the uterus.J Comput Assist Tomogr. 1998; 22: 896-898Crossref PubMed Scopus (25) Google Scholar36IRH, BSO, PLNDYesNot doneNRRose et al18Rose P.G. O'Toole R.V. Keyhani-Rofagha S. Qualman S. Boutselis J.G. Malignant peripheral primitive neuroectodermal tumor of the uterus.J Surg Oncol. 1987; 35: 165-169Crossref PubMed Scopus (37) Google Scholar17IIICRH, PLND, bilateral ovarian wedge biopsyNot doneVincristineNED, > 10 yWard et al19Ward B.S. Hitchcock C.L. Keyhani S. Primitive neuroectodermal tumor of the uterus A case report.Acta Cytol. 2000; 44: 667-672Crossref PubMed Scopus (19) Google ScholarcisplatindoxorubicindactinomycincyclophosphamideetoposideKarseladze et al20Karseladze A.I. Filipova N.A. Navarro S. Llombart-Bosch A. Primitive neuroectodermal tumor of the uterus A case report.J Reprod Med. 2001; 46: 845-848PubMed Google Scholar16ITAH, BSO, omentectomyYesCyclophosphamideNED, 4 yvincristinedoxorubicinNg et al21Ng S.B. Sirrampalam K. Chuah K.L. Primitive neuroectodermal tumours of the uterus: a case report with cytological correlation and review of the literature.Pathology. 2002; 34: 455-461Crossref PubMed Scopus (24) Google Scholar48IIICTAH, BSONot doneNot doneNED, 6 monthsOdunsi et al8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google Scholar66ITAH, BSO, PLND, PALND, omentectomyNot doneNot doneNED, 2 yOdunsi et al8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google Scholar65IIICTAH, BSO, omentectomy, PLND, PALND, upper vaginectomyYesCisplatinLung metastasis, 3 monthsdoxorubicinAWD, 12 monthsetoposidepaclitaxelVenizelos et al22Venizelos I.D. Zafrakas M. Dragoumis K. Tzevelekis P. Kellartzis D. Bontis J. Primitive neuroectodermal tumor (PNET) of the uterine isthmus.Eur J Gynaecol Oncol. 2004; 25: 384-386PubMed Google Scholar68ITAH, BSOYesNot doneNED, 10 monthsPeres et al23Peres E. Mattoo T.K. Poulik J. Warrier I. Primitive neuroectodermal tumor (PNET) of the uterus in a renal allograft patient: a case report.Pediatr Blood Cancer. 2005; 44: 283-285Crossref PubMed Scopus (23) Google Scholar15ITAH, PLNDNot doneCarboplatinNED, 12 monthsetoposideVarghese et al24Varghese L. Arnesen M. Boente M. Primitive neuroectodermal tumor of the uterus: a case report and review of literature.Int J Gynecol Pathol. 2006; 25: 373-377Crossref PubMed Scopus (25) Google Scholar43IIICTAH, BSO, PLNDNot doneCyclophosphamideNED, 2 monthsdoxorubicinvincristineetoposideBlattner et al2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar26IIIRH, PLND, bilateral ovarian transpositionYesVincristineNED, 16 monthsdoxorubicincyclophosphamideifosfamideetoposideMittal et al5Mittal S. Sumana G. Gupta M. Gupta B. Primitive neuroectodermal tumor of the uterus: a case report.Int J Gynecol Cancer. 2007; 17: 524-527Crossref PubMed Scopus (16) Google Scholar24IITAH, BSO, omentectomyNot doneVincristinePersistentdoxorubicinAWD, 1 monthcyclophosphamideifosfamideetoposidePark et al25Park J.Y. Lee S. Kang H.J. Kim H.S. Park S.Y. Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.Gynecol Oncol. 2007; 106: 427-432Crossref PubMed Scopus (42) Google Scholar30IVBNot doneNot doneVincristineDOD, 16 monthsdoxorubicinifosfamidecarboplatinetoposideAkbayir et al7Akbayir O. Gungorduk K. Rafioglu G. et al.Primary primitive neuroectodermal tumor of the uterus: a case report.Arch Gynecol Obstet. 2008; 277: 345-348Crossref PubMed Scopus (17) Google Scholar22ITAH, BSO, PLND, PALND, omentectomyNot doneCisplatinNED, 10 monthsdoxorubicinPresent case59IIICTAH, BSO, PLND, PALND, omentectomyYesPaclitaxelPersistentcarboplatinAWD, 12 monthsAWD, alive with disease; BSO, bilateral salpingo-oophorectomy; DOD, died of disease; LSO, left salpingo-oophorectomy; NED, no evidence of disease; NR, not reported; PALND, paraaortic lymphadenectomy; PLND, pelvic lymphadenectomy; RH, radical hysterectomy; SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy.Shah. Primitive neuroectodermal tumor. Am J Obstet Gynecol 2009. Open table in a new tab Although multimodality treatment may achieve disease-free survival in about 60%, those patients treated only with local control measures (surgery and radiation) have a relapse rate approaching 90%.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 3Kushner B.H. Meyers P.A. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.J Clin Oncol. 2001; 19: 870-880Crossref PubMed Scopus (112) Google Scholar Multiple chemotherapy regimens are reported. Chemotherapy agents used include cyclophosphamide (C), cisplatin, dactinomycin, doxorubicin (A), etoposide (E), ifosfamide (I), and vincristine (V). One suggested regimen is VAC/IE. This is based on a randomized trial from the Children's Oncology Group, involving patients with Ewing sarcoma or primitive neuroectodermal tumors of the bone, which showed the addition of I and E to standard VAC improved outcomes only in patients with nonmetastatic disease.9Miser J.S. Krailo M.D. Tarbell N.J. et al.Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a Children's Cancer Group and Pediatric Oncology Group study.J Clin Oncol. 2004; 22: 2873-2876Crossref PubMed Scopus (153) Google ScholarRandomized trials from the Gynecologic Oncology Group in advanced-stage uterine adenocarcinoma and epithelial ovarian cancers have shown the combination of paclitaxel with a platinum agent as a doublet or triplet may be an effective approach with a tolerable side-effect profile.10Fleming G.F. Brunetto V.L. Cella D. et al.Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.J Clin Oncol. 2004; 22: 2159-2166Crossref PubMed Scopus (478) Google Scholar, 11McGuire W.P. Hoskins W.J. Brady M.F. et al.Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.N Engl J Med. 1996; 334: 1-6Crossref PubMed Scopus (2747) Google Scholar, 12Ozols R.F. Bundy B.N. Greer B.E. et al.Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.J Clin Oncol. 2003; 21: 3194-3200Crossref PubMed Scopus (1751) Google Scholar In this postmenopausal patient with advanced-stage disease, concerns about her quality-of-life superseded any curative-intent chemotherapy. Therefore, although the biologic nature of the tumor often outweighs the organ of tumor origin in selecting chemotherapy, this patient received 6 cycles of carboplatin and paclitaxel.Her lack of response to this regimen may further support the utility of the VAC with or without the IE regimen for PNET of the uterine corpus. The overall poor prognosis for all patients with PNET of the uterine corpus highlights the need for the introduction of novel therapies before making any substantial beneficial impact on prognosis. Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the Ewing sarcoma family of tumors originally described by Hart and Earle in 1973.1Hart M.N. Earle K.M. Primitive neuroectodermal tumors of the brain in children.Cancer. 1973; 32: 890-897Crossref PubMed Scopus (453) Google Scholar Rarely, PNET has been reported to originate in the female genital tract.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar As of 2007, there are only 22 published cases of PNET of the uterus. It is difficult to derive from the current literature any conclusion regarding the optimal treatment of these tumors. Overall, Ewing sarcoma tumors have a high relapse rate and high mortality rate.3Kushner B.H. Meyers P.A. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.J Clin Oncol. 2001; 19: 870-880Crossref PubMed Scopus (112) Google Scholar The majority of PNET of the uterine corpus is diagnosed at an advanced stage, highlighting its aggressive nature. In an effort to gain a better understanding of potential therapeutic options, we report on a case of PNET of the uterine corpus treated with a platinum and taxane combination chemotherapy following optimal cytoreductive surgery. Case ReportA 59-year-old white woman presented with postmenopausal vaginal bleeding. A pelvic ultrasound revealed a myometrial mass and thickened endometrium (11 mm). Curettage specimen was interpreted as endometrial stromal sarcoma. After referral, a gynecologic oncologist performed an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node sampling, and infracolic omentectomy. Surgical findings included an enlarged uterus and a necrotic 3 cm right pelvic lymph node. At the completion of the tumor reductive surgery, there was no grossly visible residual disease.Pathologic examination of the surgical specimen described an International Federation of Gynecology and Obstetrics (FIGO) stage IIIC based on pelvic and paraaortic lymph node involvement, high-grade malignant epithelial neoplasm, with features most compatible with peripheral PNET. Immunohistochemical studies revealed tumor cells with positive staining for WT-1, synaptophysin, CD10, and Ewing sarcoma marker CD99 (FIGURE 1, FIGURE 2).Three weeks after surgery, the patient was initiated on chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks. No growth factors were used and no treatment delays occurred. A computed tomography (CT) scan 1 week after completing chemotherapy revealed evidence of disease, with metastatic cystic lesions measuring 4 cm near the vagina cuff, 3 cm at the left pelvic sidewall, and 2 cm along the paraaortic lymph nodes. The patient subsequently underwent palliative 4-field pelvic radiotherapy and paraaortic boost image modulated radiotherapy for a total of 50 Gy over 6 weeks. She also received concomitant cisplatin therapy at 40 mg/m2 for 4 weekly cycles.A follow-up, 12-month CT scan showed significant increase in the neoplastic process, with significant mediastinal lymphadenopathy. Multiple pulmonary and hepatic nodules were also identified. She is currently alive with persistent disease after 12 months and is considering further palliative chemotherapy. A 59-year-old white woman presented with postmenopausal vaginal bleeding. A pelvic ultrasound revealed a myometrial mass and thickened endometrium (11 mm). Curettage specimen was interpreted as endometrial stromal sarcoma. After referral, a gynecologic oncologist performed an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node sampling, and infracolic omentectomy. Surgical findings included an enlarged uterus and a necrotic 3 cm right pelvic lymph node. At the completion of the tumor reductive surgery, there was no grossly visible residual disease. Pathologic examination of the surgical specimen described an International Federation of Gynecology and Obstetrics (FIGO) stage IIIC based on pelvic and paraaortic lymph node involvement, high-grade malignant epithelial neoplasm, with features most compatible with peripheral PNET. Immunohistochemical studies revealed tumor cells with positive staining for WT-1, synaptophysin, CD10, and Ewing sarcoma marker CD99 (FIGURE 1, FIGURE 2). Three weeks after surgery, the patient was initiated on chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks. No growth factors were used and no treatment delays occurred. A computed tomography (CT) scan 1 week after completing chemotherapy revealed evidence of disease, with metastatic cystic lesions measuring 4 cm near the vagina cuff, 3 cm at the left pelvic sidewall, and 2 cm along the paraaortic lymph nodes. The patient subsequently underwent palliative 4-field pelvic radiotherapy and paraaortic boost image modulated radiotherapy for a total of 50 Gy over 6 weeks. She also received concomitant cisplatin therapy at 40 mg/m2 for 4 weekly cycles. A follow-up, 12-month CT scan showed significant increase in the neoplastic process, with significant mediastinal lymphadenopathy. Multiple pulmonary and hepatic nodules were also identified. She is currently alive with persistent disease after 12 months and is considering further palliative chemotherapy. CommentPrimitive neuroectodermal tumor is a rare tumor. PNET of the uterus usually presents with abnormal vaginal bleeding and uterine mass. There is a bimodal age distribution, with PNET presenting either in the second decade or in the postmenopausal period.The striking similarity between extraskeletal Ewing's sarcoma and PNET provides insight into these rare tumors. The identification of a common translocation t(11;22)(q24;12) in Ewing sarcoma and nearly 85% of PNET suggests that these tumors share a common histogenesis.4Delattre O. Zucman J. Melot T. et al.The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts.N Engl J Med. 1994; 331: 294-299Crossref PubMed Scopus (906) Google Scholar This understanding, along with identification of the fusion gene, EWS-FL11, may aid in the understanding of this disease and the identification of more targeted therapies.5Mittal S. Sumana G. Gupta M. Gupta B. Primitive neuroectodermal tumor of the uterus: a case report.Int J Gynecol Cancer. 2007; 17: 524-527Crossref PubMed Scopus (16) Google ScholarThe differential diagnosis of PNET of the uterine corpus includes uterine lymphoma, poorly differentiated endometrioid carcinoma, high-grade endometrial stromal sarcoma or undifferentiated sarcoma, and small cell neuroendocrine carcinoma.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar In addition to the histologic pattern, immunohistochemical staining with CD99 or MIC2, vimentin, synaptophysin, and neuron-specific enolase assists in making the diagnosis of PNET of the uterine corpus.7Akbayir O. Gungorduk K. Rafioglu G. et al.Primary primitive neuroectodermal tumor of the uterus: a case report.Arch Gynecol Obstet. 2008; 277: 345-348Crossref PubMed Scopus (17) Google ScholarThere is no consensus of the optimal treatment for patients with PNET of the uterus, because the majority of published patients had surgery, chemotherapy, and/or radiotherapy (Table). From these cases it appears that advancing age and advancing stage correlate with a poorer prognosis. The 2-year survival of younger patients and postmenopausal patients was 75% and 32%, respectively.8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google ScholarTABLEClinical features of primary primitive neuroectodermal tumors of the uterine corpusCaseAge, yFIGO stageSurgeryRadiationChemotherapyFollow-upHendrickson and Scheithauer13Hendrickson M.R. Scheithauer B.W. Primitive neuroectodermal tumor of the endometrium: report of two cases, one with electron microscopic observations.Int J Gynecol Pathol. 1986; 5: 249-259Crossref PubMed Scopus (48) Google Scholar12IVBTAH, LSOYesCyclophosphamidePelvic recurrence, 12 monthsdoxorubicinDOD, 2 yvincristineHendrickson and Scheithauer13Hendrickson M.R. Scheithauer B.W. Primitive neuroectodermal tumor of the endometrium: report of two cases, one with electron microscopic observations.Int J Gynecol Pathol. 1986; 5: 249-259Crossref PubMed Scopus (48) Google Scholar57IIBTAH, BSO, PALNDYesCisplatinLung metastasis, 5 monthsvinblastineDOD, 2 ybleomycinDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar67IIICSAH, BSOYesCisplatinPersistentdoxorubicinDOD, 6 monthscarboplatin5-FUDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar68IVBTAH, BSO, PLNDYesCisplatinPersistentDOD, 12 monthsDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar69ITAH, BSO, PLNDYesNot doneNED, 6 yDaya et al6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar68ITAH, BSOYesNot doneNED, 5 yMolyneux et al14Molyneux A.J. Deen S. Sundaresan V. Primitive neuroectodermal tumour of the uterus.Histopathology. 1992; 21: 584-585Crossref PubMed Scopus (27) Google Scholar72ITAH, BSONot doneNot doneDOD, 8 monthsFukunaga et al15Fukunaga M. Nomura K. Endo Y. Ushigome S. Aizawa S. Carcinosarcoma of the uterus with extensive neuroectodermal differentiation.Histopathology. 1996; 29: 565-570Crossref PubMed Scopus (52) Google Scholar54NRTAH, BSONot doneCyclophosphamidePersistentcisplatinAWD, 3 monthsdoxorubicin5-FUSorensen et al16Sorensen J.B. Schultze H.R. Madsen E.L. Holund B. Primitive neuroectodermal tumor (PNET) of the uterine cavity.Eur J Obstet Gynecol Reprod Biol. 1998; 76: 181-184Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar62ITAH, BSOYesVincristineRecurrent ascites, 6 monthscyclophosphamideDOD, 18 monthscisplatinTaieb et al17Taieb S. Cabaret V. Bonodeau F. Leblanc E. Besson P. MRI of primitive neuroectodermal tumor of the uterus.J Comput Assist Tomogr. 1998; 22: 896-898Crossref PubMed Scopus (25) Google Scholar36IRH, BSO, PLNDYesNot doneNRRose et al18Rose P.G. O'Toole R.V. Keyhani-Rofagha S. Qualman S. Boutselis J.G. Malignant peripheral primitive neuroectodermal tumor of the uterus.J Surg Oncol. 1987; 35: 165-169Crossref PubMed Scopus (37) Google Scholar17IIICRH, PLND, bilateral ovarian wedge biopsyNot doneVincristineNED, > 10 yWard et al19Ward B.S. Hitchcock C.L. Keyhani S. Primitive neuroectodermal tumor of the uterus A case report.Acta Cytol. 2000; 44: 667-672Crossref PubMed Scopus (19) Google ScholarcisplatindoxorubicindactinomycincyclophosphamideetoposideKarseladze et al20Karseladze A.I. Filipova N.A. Navarro S. Llombart-Bosch A. Primitive neuroectodermal tumor of the uterus A case report.J Reprod Med. 2001; 46: 845-848PubMed Google Scholar16ITAH, BSO, omentectomyYesCyclophosphamideNED, 4 yvincristinedoxorubicinNg et al21Ng S.B. Sirrampalam K. Chuah K.L. Primitive neuroectodermal tumours of the uterus: a case report with cytological correlation and review of the literature.Pathology. 2002; 34: 455-461Crossref PubMed Scopus (24) Google Scholar48IIICTAH, BSONot doneNot doneNED, 6 monthsOdunsi et al8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google Scholar66ITAH, BSO, PLND, PALND, omentectomyNot doneNot doneNED, 2 yOdunsi et al8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google Scholar65IIICTAH, BSO, omentectomy, PLND, PALND, upper vaginectomyYesCisplatinLung metastasis, 3 monthsdoxorubicinAWD, 12 monthsetoposidepaclitaxelVenizelos et al22Venizelos I.D. Zafrakas M. Dragoumis K. Tzevelekis P. Kellartzis D. Bontis J. Primitive neuroectodermal tumor (PNET) of the uterine isthmus.Eur J Gynaecol Oncol. 2004; 25: 384-386PubMed Google Scholar68ITAH, BSOYesNot doneNED, 10 monthsPeres et al23Peres E. Mattoo T.K. Poulik J. Warrier I. Primitive neuroectodermal tumor (PNET) of the uterus in a renal allograft patient: a case report.Pediatr Blood Cancer. 2005; 44: 283-285Crossref PubMed Scopus (23) Google Scholar15ITAH, PLNDNot doneCarboplatinNED, 12 monthsetoposideVarghese et al24Varghese L. Arnesen M. Boente M. Primitive neuroectodermal tumor of the uterus: a case report and review of literature.Int J Gynecol Pathol. 2006; 25: 373-377Crossref PubMed Scopus (25) Google Scholar43IIICTAH, BSO, PLNDNot doneCyclophosphamideNED, 2 monthsdoxorubicinvincristineetoposideBlattner et al2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar26IIIRH, PLND, bilateral ovarian transpositionYesVincristineNED, 16 monthsdoxorubicincyclophosphamideifosfamideetoposideMittal et al5Mittal S. Sumana G. Gupta M. Gupta B. Primitive neuroectodermal tumor of the uterus: a case report.Int J Gynecol Cancer. 2007; 17: 524-527Crossref PubMed Scopus (16) Google Scholar24IITAH, BSO, omentectomyNot doneVincristinePersistentdoxorubicinAWD, 1 monthcyclophosphamideifosfamideetoposidePark et al25Park J.Y. Lee S. Kang H.J. Kim H.S. Park S.Y. Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.Gynecol Oncol. 2007; 106: 427-432Crossref PubMed Scopus (42) Google Scholar30IVBNot doneNot doneVincristineDOD, 16 monthsdoxorubicinifosfamidecarboplatinetoposideAkbayir et al7Akbayir O. Gungorduk K. Rafioglu G. et al.Primary primitive neuroectodermal tumor of the uterus: a case report.Arch Gynecol Obstet. 2008; 277: 345-348Crossref PubMed Scopus (17) Google Scholar22ITAH, BSO, PLND, PALND, omentectomyNot doneCisplatinNED, 10 monthsdoxorubicinPresent case59IIICTAH, BSO, PLND, PALND, omentectomyYesPaclitaxelPersistentcarboplatinAWD, 12 monthsAWD, alive with disease; BSO, bilateral salpingo-oophorectomy; DOD, died of disease; LSO, left salpingo-oophorectomy; NED, no evidence of disease; NR, not reported; PALND, paraaortic lymphadenectomy; PLND, pelvic lymphadenectomy; RH, radical hysterectomy; SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy.Shah. Primitive neuroectodermal tumor. Am J Obstet Gynecol 2009. Open table in a new tab Although multimodality treatment may achieve disease-free survival in about 60%, those patients treated only with local control measures (surgery and radiation) have a relapse rate approaching 90%.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 3Kushner B.H. Meyers P.A. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.J Clin Oncol. 2001; 19: 870-880Crossref PubMed Scopus (112) Google Scholar Multiple chemotherapy regimens are reported. Chemotherapy agents used include cyclophosphamide (C), cisplatin, dactinomycin, doxorubicin (A), etoposide (E), ifosfamide (I), and vincristine (V). One suggested regimen is VAC/IE. This is based on a randomized trial from the Children's Oncology Group, involving patients with Ewing sarcoma or primitive neuroectodermal tumors of the bone, which showed the addition of I and E to standard VAC improved outcomes only in patients with nonmetastatic disease.9Miser J.S. Krailo M.D. Tarbell N.J. et al.Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a Children's Cancer Group and Pediatric Oncology Group study.J Clin Oncol. 2004; 22: 2873-2876Crossref PubMed Scopus (153) Google ScholarRandomized trials from the Gynecologic Oncology Group in advanced-stage uterine adenocarcinoma and epithelial ovarian cancers have shown the combination of paclitaxel with a platinum agent as a doublet or triplet may be an effective approach with a tolerable side-effect profile.10Fleming G.F. Brunetto V.L. Cella D. et al.Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.J Clin Oncol. 2004; 22: 2159-2166Crossref PubMed Scopus (478) Google Scholar, 11McGuire W.P. Hoskins W.J. Brady M.F. et al.Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.N Engl J Med. 1996; 334: 1-6Crossref PubMed Scopus (2747) Google Scholar, 12Ozols R.F. Bundy B.N. Greer B.E. et al.Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.J Clin Oncol. 2003; 21: 3194-3200Crossref PubMed Scopus (1751) Google Scholar In this postmenopausal patient with advanced-stage disease, concerns about her quality-of-life superseded any curative-intent chemotherapy. Therefore, although the biologic nature of the tumor often outweighs the organ of tumor origin in selecting chemotherapy, this patient received 6 cycles of carboplatin and paclitaxel.Her lack of response to this regimen may further support the utility of the VAC with or without the IE regimen for PNET of the uterine corpus. The overall poor prognosis for all patients with PNET of the uterine corpus highlights the need for the introduction of novel therapies before making any substantial beneficial impact on prognosis. Primitive neuroectodermal tumor is a rare tumor. PNET of the uterus usually presents with abnormal vaginal bleeding and uterine mass. There is a bimodal age distribution, with PNET presenting either in the second decade or in the postmenopausal period. The striking similarity between extraskeletal Ewing's sarcoma and PNET provides insight into these rare tumors. The identification of a common translocation t(11;22)(q24;12) in Ewing sarcoma and nearly 85% of PNET suggests that these tumors share a common histogenesis.4Delattre O. Zucman J. Melot T. et al.The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcripts.N Engl J Med. 1994; 331: 294-299Crossref PubMed Scopus (906) Google Scholar This understanding, along with identification of the fusion gene, EWS-FL11, may aid in the understanding of this disease and the identification of more targeted therapies.5Mittal S. Sumana G. Gupta M. Gupta B. Primitive neuroectodermal tumor of the uterus: a case report.Int J Gynecol Cancer. 2007; 17: 524-527Crossref PubMed Scopus (16) Google Scholar The differential diagnosis of PNET of the uterine corpus includes uterine lymphoma, poorly differentiated endometrioid carcinoma, high-grade endometrial stromal sarcoma or undifferentiated sarcoma, and small cell neuroendocrine carcinoma.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 6Daya D. Lukka H. Clement P.B. Primitive neuroectodermal tumors of the uterus: a report of four cases.Hum Pathol. 1992; 23: 1120-1129Abstract Full Text PDF PubMed Scopus (90) Google Scholar In addition to the histologic pattern, immunohistochemical staining with CD99 or MIC2, vimentin, synaptophysin, and neuron-specific enolase assists in making the diagnosis of PNET of the uterine corpus.7Akbayir O. Gungorduk K. Rafioglu G. et al.Primary primitive neuroectodermal tumor of the uterus: a case report.Arch Gynecol Obstet. 2008; 277: 345-348Crossref PubMed Scopus (17) Google Scholar There is no consensus of the optimal treatment for patients with PNET of the uterus, because the majority of published patients had surgery, chemotherapy, and/or radiotherapy (Table). From these cases it appears that advancing age and advancing stage correlate with a poorer prognosis. The 2-year survival of younger patients and postmenopausal patients was 75% and 32%, respectively.8Odunsi K. Olatinwo M. Collins Y. Withiam-Leitch M. Lele S. Spiegel G.W. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature.Gynecol Oncol. 2004; 92: 689-696Crossref PubMed Scopus (25) Google Scholar AWD, alive with disease; BSO, bilateral salpingo-oophorectomy; DOD, died of disease; LSO, left salpingo-oophorectomy; NED, no evidence of disease; NR, not reported; PALND, paraaortic lymphadenectomy; PLND, pelvic lymphadenectomy; RH, radical hysterectomy; SAH, subtotal abdominal hysterectomy; TAH, total abdominal hysterectomy. Shah. Primitive neuroectodermal tumor. Am J Obstet Gynecol 2009. Although multimodality treatment may achieve disease-free survival in about 60%, those patients treated only with local control measures (surgery and radiation) have a relapse rate approaching 90%.2Blattner J.M. Gable P. Quigley M.M. McHale M.T. Primitive neuroectodermal tumor of the uterus.Gynecol Oncol. 2007; 106: 419-422Crossref PubMed Scopus (25) Google Scholar, 3Kushner B.H. Meyers P.A. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.J Clin Oncol. 2001; 19: 870-880Crossref PubMed Scopus (112) Google Scholar Multiple chemotherapy regimens are reported. Chemotherapy agents used include cyclophosphamide (C), cisplatin, dactinomycin, doxorubicin (A), etoposide (E), ifosfamide (I), and vincristine (V). One suggested regimen is VAC/IE. This is based on a randomized trial from the Children's Oncology Group, involving patients with Ewing sarcoma or primitive neuroectodermal tumors of the bone, which showed the addition of I and E to standard VAC improved outcomes only in patients with nonmetastatic disease.9Miser J.S. Krailo M.D. Tarbell N.J. et al.Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a Children's Cancer Group and Pediatric Oncology Group study.J Clin Oncol. 2004; 22: 2873-2876Crossref PubMed Scopus (153) Google Scholar Randomized trials from the Gynecologic Oncology Group in advanced-stage uterine adenocarcinoma and epithelial ovarian cancers have shown the combination of paclitaxel with a platinum agent as a doublet or triplet may be an effective approach with a tolerable side-effect profile.10Fleming G.F. Brunetto V.L. Cella D. et al.Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.J Clin Oncol. 2004; 22: 2159-2166Crossref PubMed Scopus (478) Google Scholar, 11McGuire W.P. Hoskins W.J. Brady M.F. et al.Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.N Engl J Med. 1996; 334: 1-6Crossref PubMed Scopus (2747) Google Scholar, 12Ozols R.F. Bundy B.N. Greer B.E. et al.Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study.J Clin Oncol. 2003; 21: 3194-3200Crossref PubMed Scopus (1751) Google Scholar In this postmenopausal patient with advanced-stage disease, concerns about her quality-of-life superseded any curative-intent chemotherapy. Therefore, although the biologic nature of the tumor often outweighs the organ of tumor origin in selecting chemotherapy, this patient received 6 cycles of carboplatin and paclitaxel. Her lack of response to this regimen may further support the utility of the VAC with or without the IE regimen for PNET of the uterine corpus. 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