a 54-year - old woman with gravidity 3 and parity 1 , who had been postmenopausal for two years , presented with a 6-month history of vaginal bleeding and general weakness . the patient looked generally anemic and fatigued , and had no past history of taking estrogen replacement therapy . in addition , the patient had a body mass index of 24.5 kg / m and a blood cancer antigen 125 level of 24.2 u / ml ( normal range , 0 to 35 u / ml ) . the patient had a normal papanicolaou smear but no notable gynecological history . transvaginal ultrasound showed a 7-cm protruding mass in the endometrial cavity with an endometrial thickness of 22.3 mm . in addition , the mass was surrounded by echogenic blood flow and it showed an ill - defined margin with the myometrium . the patient underwent total hysterectomy with a bilateral salpingo - oophorectomy under the laparoscopic guidance under a provisional diagnosis of submucosal leiomyoma . the tumor did not involve the serosal surface of the uterus or the abdominal cavity . grossly , there was an ill - defined , relatively solid endometrial mass with a spotty necrosis , measuring 765 cm . in addition , it involved the myometrium at the fundus and body but not its serosal tissue . following a careful examination , the entire uterine cervix was divided into 12 sections in total from the 12 o'clock position . microscopically , the tumor showed a clear evidence of squamous differentiation , such as presence of intercellular bridges and keratinization ( fig . 1a , b ) , thus confirming a well - differentiated , invasive scc of the endometrium . the tumor involved more than 80% of the myometrial thickness and it showed a vascular invasion to the myometrium . in the adjacent non - neoplastic endometrium , there were glands with both a pseudostratification and a ciliary change and their stroma was infiltrated by inflammatory cells , plasma cells and neutrophils in particular ( fig . there were no evidences demonstrating the presence of squamous metaplasia of the endometrium , endometrial adenocarcinoma , cervical scc and a connection between the endometrial tumor and the squamous epithelium of the cervix . on immunohistochemistry , there was a positive immunoreactivity for cytokeratin 7 , p63 ( fig . 1d ) , but not for cytokeratin 20 and estrogen receptor ( er ) and progesterone receptor ( pr ) . but hpv was not detected on either in situ hybridization ( ish ) or hpv dna chip analysis . the patient showed a disease - free course during a 13-month follow - up period . the connection between the endometrium and the cervix should therefore be ruled out in making a diagnosis of pescc . squamous differentiation of an endometrioid adenocarcinoma must also be excluded.2 several theories regarding the cellular origin of pescc have been proposed : 1 ) reserve or stem cells located between the glandular basement membrane and the endometrial columnar cell layer;4 2 ) squamous metaplasia of the normal endometrium;5 and 3 ) heterotopic cervical tissue.6 it has been reported that vitamin a deficiency , anti - estrogen treatment , pyometra , chronic infection , uterine prolapse , myoma , intrauterine device , history of pelvic irradiation and curettage are associated with squamous metaplasia of the endometrium.2,5,7,8 hpv infection plays a key role in the pathogenesis of squamous neoplasms of the uterine cervix,9 whose role in that of pescc remains controversial . of note , kataoka et al.10 demonstrated the presence of hpv type 31 by the polymerase chain reaction ( pcr ) in one patient with pescc . but there were no other reports demonstrating a clear association between hpv and pescc.11 - 13 horn et al.11 performed an hpv analysis with general primers and hpv typing in eight patients with pescc . giordano et al.12 failed to detect hpv dna by pcr in one patient with pescc . in addition , i m et al.13 could not detect hpv by ish in three patients with pescc . according to review of literatures about five korean women with pescc ( table 1 ) , there were one positive case for hpv 16/18 in the cervix but not the endometrium by ish and pcr assay14 and another negative case for hpv 16/18 by pcr assay.15 moreover , we did not find any evidence of hpv in our patient . we therefore suggest that hpv may not be the primary causative factor for pescc . a cyclin - dependent kinase-4 inhibitor involved in the prb pathway , p is a surrogate marker for hpv infection in cervical neoplasms.9 it has been reported that p is expressed in some cases of endometrial carcinoma.11,16 to date , however , fewer attempts have been made to evaluate both the hpv status and p expression . ansari - lari et al.16 reported that p expression is moderate to strong and diffuse in endocervical adenocarcinoma and weak and patchy in endometrial adenocarcinoma . these findings suggest that p immunohistochemistry may be helpful for distinguishing endocervical adenocarcinoma from endometrial adenocarcinoma . according to horn et al.,11 50% of the cases showed a positive p immunoreactivity but there was only one positive case for hpv . these reports suggest that alterations of the p pathway may play a role in the pathogenesis of some cases of pescc , if any , without an hpv involvement . similarly , our case showed weak and patchy p expression and negative results for hpv by both ish and dna chip analysis . our case therefore indicates that p overexpression may be involved in the development of pescc with no respect to hpv infection . the clinical applicability of the er and pr status as a prognostic indicator of pescc is still uncertain . considering that most patients are postmenopausal , however , a loss of estrogen can not be completely ruled out as an etiologic factor . this is not only because most cases of pescc occur in postmenopausal women but also because one of the most frequent presenting symptoms is vaginal bleeding . the average duration of symptoms before diagnosis is 11.5 months.8 total hysterectomy with a bilateral salpingo - oophorectomy is the first line of choice for menopausal women . the effectiveness of radiotherapy and chemotherapy as adjuvant treatments remains highly controversial.7,8 pescc has a poor prognosis compared with endometrial adenocarcinoma . that is , it is well documented that the 5-year survival rates in endometrial adenocarcinoma at stages i , ii , iii , and iv are 89.1% , 78.8% , 57.8% , and 22.8% , respectively.17 however , the 5-year survival rate of pescc is difficult to assess because of its rarity . with a survival period ranging from 14 to 36 months , it has been reported that the 1-year survival rates in pescc at stages i , iii , and iv are 80% , 20% , and 0% , respectively.7,8 the mean age of the six korean patients ( table 1 ) , including our case , was 62 years ( range , 54 to 68 years ) , all of whom were postmenopausal.14,15,18 - 20 most of the korean women with pescc are multiparous , which is contradictory to the report , by goodman et al.,8 made from nulliparous women . in addition , vaginal bleeding is one of the typical symptoms that occur in korean women . in summary , there was positive p immunoreactivity with no evidence of hpv by ish and dna chip analysis in our case . our case highlights the significant role of p overexpression , regardless of the hpv status in the pathogenesis of pescc . henceforth , however , further large - scale studies are warranted to gain a deeper insight into its characteristics of pescc .
primary endometrial squamous cell carcinoma ( pescc ) is an extremely rare tumor with unclear pathogenesis . 
 a 54-year - old postmenopausal woman presented with a 6-month history of vaginal bleeding . 
 the patient was provisionally diagnosed with uterine submucosal leiomyoma . 
 this was followed by total hysterectomy with a bilateral salpingo - oophorectomy under the laparoscopic guidance . 
 histopathologically , the tumor was pescc which was accompanied by a lack of the tumor in the uterine cervix . 
 the tumor showed positive immunoreactivity for p16ink4a . 
 but there was no evidence of human papillomavirus ( hpv ) on in situ hybridization and hpv dna chip analysis . 
 we also present a review of the relevant literature on korean women .