Primary Endometrial Primitive Neuroectodermal Tumors with EWSR Gene Rearrangement
Primitive Neuroectodermal Tumors are rare tumors of the female genital tract. They are even rarer in the endometrium. Endometrial cancers with poorly differentiated sheets of non-cohesive cells should prompt a pathologist to exclude several main differential diagnosis including small cell carcinoma, undifferentiated uterine carcinoma, and PNET. The most sensitive marker for PNET is known to be CD99, however this immunostain is not very specific. Ninety five percent (95%) of PNETs have EWSR1 gene on 22q12 rearranged with FLI1 gene on 11q24 (80-90%), the remaining majority of the cases have rearrangement with ERG gene on 21q22. Less frequent partner genes discovered are ETV1 on 7p22, E1AF gene on 17q12, FEV gene on 2q33. Less than 50 cases of uterine tumors with neuroectodermal differentiation are described in the literature (Hendrickson et al., 1986, Sinkre et al., 2000, Ng et al., 2002, Odunsi et al., 2004, Peres et al., 2005, Park et al., 2007, Akbayir et al., 2008, Euscher et al., 2008, Majeed et al., 2009, Bartosch et al., 2011, Kathuria et al., 2011, Xiao et al., 2014). However, only four (4) of these cases have been documented to show EWSR-FLI1 gene rearrangement (Sinkre et al., 2000, Kathuria et al., 2011). All of the cases in the biggest case series of 17 cases were negative for EWSR1 by in-situ hybridization (Euscher et al., 2008). Here we describe 2 cases of primary uterine PNETs with FISH proven EWSR1 gene rearrangement. Our cases show uneventful clinical outcome when uterine PNET is limited to the uterus, but limited therapeutic efficacy of treatment modalities with more widespread disease. Uterine tumors suspected to be PNET should be confirmed by RT-PCR or FISH for EWSR1 gene rearrangement for appropriate systemic therapy.
- Bartosch C, Vieira J, Teixeira MR et al. 2011. Endometrial endometrioid adenocarcinoma associated with primitive neuroectodermal tumours of the uterus: a poor prognostic subtype of uterine tumours. Medical Oncology 28:1488-1494.
- Euscher ED, Deavers MT, Lopez-Terrada D, Lazar AJ, Silva EG, Malpica A. 2008. Uterine tumors with neuroectodermal differentiation. A series of 17 cases and review of the literature. American Journal of Surgical Pathology 32:219-228.
- Hendrickson MR, Scheithauer BW. 1986. Primitive neuroectodermal tumor of the endometrium: report of two cases, one with electron microscopic observations. International Journal of Gynecological Pathology 5:249-259.
- Kathuria K, Gupta S, Maheshwari A et al. 2011. Primary primitive neuroectodermal tumor of the uterus: A case report with an unusual molecular pathology finding. Journal of Cancer Research and Therapeutics 7: 488-490.
- Majeed U, Ilyas MA, Uddin N et al. 2009. Primary Ewing's sarcoma- primitive neuroectodermal tumor of uterus. Journal of Obstetrics and Gynaecology 29: 73-74.
- Ng SB, Sirrampalam K, Chuah KL. 2002. Primitive neuroectodermal tumours of the uterus: a case report with cytological correlation and review of the literature. Pathology 34:455-461.
- Odunsi K, Olatinwo M, Collins Y et al. 2004. Primary primitive neuroectodermal tumor of the uterus: a report of two cases and review of the literature. Gynecologic Oncology 92:689-696.
- Park JY, Kang HJ, Kim HS et al. 2007. Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: A case report and literature review. Gynecologic Oncology 106:427-432.
- Sinkre P, Albores-Saavedra J, Miller DS. 2000. Endometrial endometrioid carcinoma associated with Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor. International Journal of Gynecological Pathology 19:127-132.
- Xiao C, Zhao J, Guo P, Wang D, Zhao D, Ren T et al. 2014. Clinical analysis of primary primitive neuroectodermal tumors in the female genital tract. International Journal of Gynecological Cancer 24:404-409.
Contributed by Binara Assylbekova, MD and Octavia M. Peck-Palmer, PhD