INTRODUCTIONPrimary endometrial squamous cell carcinomas (PESCC) are rare entities, as less than 100 such cases involving only the endometrium have been reported to date. These tumors are majorly seen in post-menopausal women and conditions leading to chronic inflammation of the endometrium as pyometra, cervical stenosis, inflammatory diseases like ichthyosis, and very rarely foreign bodies like intra-uterine contraceptive device (IUCD). Although IUCD usage has been considered protective against the development of neoplasia, still sporadic cases of IUCD-associated uterine malignancies have been reported in the literature. We present a rare case of invasive pure endometrial SCC following 32 years of IUCD retention in a 66-year-old lady. Though there have been reports of endometrial SCC, to the best of our knowledge, pure endometrial (without any evidence of cervical involvement), invasive SCC, secondary to retained IUCD, is being reported for the first time.CASE REPORTWe present the case of a 66-year-old lady, with no comorbidities who presented to us in May 2020 with complaints of postmenopausal bleeding per vagina, on and off for 3 months. She attained menopause at the age of 58 years and gave a history of an IUCD -Copper T insertion 32-years ago, which was still in situ. Her BMI was 21.6. Per abdominal examination did not reveal any abnormality. Per-vaginal examination revealed a bulky uterus (8 weeks size), with the tip of IUCD felt at the level of external os, though per speculum examination had not revealed any abnormality. Bilateral parametria were free with no adnexal mass. On evaluation, her PAP smear examination was reported negative for malignancy and endometrial aspiration also showed only inflammatory changes with no malignancy. MRI of the pelvis was suggestive of irregular lobulated mass replacing the body of the uterus, involving >50% of the myometrium (Fig 1), extending up to serosa along with a linear opacity suggestive of a retained IUCD (Fig 1).The patient underwent surgical staging (Radical abdominal hysterectomy with bilateral salpingo-oophorectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling). Intraoperative findings revealed an enlarged uterus with the tumor in situ and breaching the uterine serosa to involve small bowel at 15cm from the ileo-caecal junction. Bilateral ovaries were atrophic. Bilateral parametrium was involved. There was no intra-abdominal metastatic disease present.On gross examination, a grey-white infiltrative tumor was identified occupying the entire uterine cavity (Fig1). The tumor measured 6.5cm in the greatest dimension and involved part of the isthmus. The tumor infiltrated the full thickness of the uterine wall to involve the adjacent small bowel segment. IUCD was found within the uterine cavity (Fig 1c). Histopathological examination from the grossly identified tumor showed invasive keratinizing SCC exhibiting moderate nuclear atypia with invading front arranged in chords and trabeculae (Fig2). The surface endometrial lining in the rest of the uterine cavity was replaced by squamous metaplasia (Fig 2) along with inflammation with no areas of dysplasia. Adequate sections studied from the uterine tumor showed no coexisting adenocarcinoma. The tumor infiltrated the isthmus, which too showed metaplastic changes in the surface epithelium. The cervix was largely unremarkable and showed only focal areas of squamous metaplasia (Fig2). Cervix and isthmus both submitted in entirety did not reveal any dysplastic squamous epithelium or invasive SCC arising from the native lining epithelium. Immunohistochemistry for p16 performed on representative sections from the tumor, isthmus, and cervix was negative.DISCUSSIONPure endometrial SCC is a rare entity. The largest series of these tumors was presented by Goodman in 1996.(1) Wherein, the majority of the patients had positive cervical smears as the involvement of the endometrial cavity by upward extension of primary SCC of the cervix is a common occurrence.(2) Glitches associated with establishing a preoperative diagnosis of PESCC are the relative rarity of these tumors and the presence of highly differentiated squamous cells in endometrial curettage specimen simulating chronic inflammatory response.(1) Though, considering the post-menopausal status of the majority of patients (98% in Goodman’s series), the probability of having pelvic inflammatory diseases decreases significantly and thus can guide the pathologist for thinking of a non-inflammatory pathology. Unlike SCC of the cervix, Human papilloma virus (HPV) has not been recognized as an important factor for PESCC pathogenesis.(3)PESCC is defined as a primary carcinoma of the endometrium composed of squamous cells with varying degrees of differentiation.(4) Fluhmann described the following strict pathological criteria to define any endometrial tumor as PESCC -(a) no evidence of a coexisting endometrial adenocarcinoma or primary cervical SCC; (b) no connection between the endometrial tumor and squamous epithelium of the cervix; or (c) no connection between any existing cervical in situ carcinoma and the independent endometrial neoplasm.(5) These criteria have been further modified by S Kay and Jeffers et al.(2)Abiding by the Fluhmann criteria, the tumor, in this case, was restricted to the endometrium with no coexisting adenocarcinoma. The cervix examined in entirety did not show any dysplasia or invasive malignancy. Intact IUCD and the total replacement of the surface endometrial lining with metaplastic squamous epithelium further indicate its temporal relationship with the invasive SCC. While the negative staining for p16 affirms the non-HPV pathway of tumorigenesis.It has been established that prolonged chronic inflammatory response can induce squamous metaplasia which later can transform to SCC.(6) Though rare, squamous metaplasia is but a known entity in the presence of IUCD for a very long time.(7) It has been also testified from population-based studies that endometrium is the main source of squamous metaplastic atypical cells in cervical smears in IUCD users, though epithelial atypia rapidly disappears upon removal of IUCD.(8) So, the progression of squamous metaplasia to dysplasia, to non-invasive and ultimately to invasive carcinoma is rare, and even in cases where it does occur, it is mostly adenocarcinomatous progression.(9) There are very few documentations of primary carcinoma in situ following the use of IUCD. (6) To the best of our knowledge, there is only one such case reported of invasive SCC of endometrium following retained IUCD. But even in this case, there was the involvement of cervical tissue (including ectocervix) by SCC in situ.(10)Considering the rarity of this pathological entity, there are no defined treatment options. In Goodman’s review of 64 cases, 48.4% were treated with surgery alone, while 39.1% of the patients were treated with surgery and radiation therapy. Very few patients were treated with surgery along with chemotherapy, radiation alone, or a trimodality treatment. The authors concluded that the early-stage tumors confined to the uterus regardless of grade and depth of invasion had a good prognosis while most of the patients with the advanced stage disease had a bad prognosis even after adjuvant treatment. Keneddy S. et al reviewed the treatment and survival pattern of all cases of primary endometrial SCC fulfilling Fluhmann’s criteria until 1995 and suggested the role of cisplatin-based chemoradiation.(4) Both Goodman and Kennedy suggested that unlike endometrial adenocarcinoma, chances of lymph nodal spread to pelvic lymph nodes are less common in PESCC while the involvement of vascular spaces (Parametrium) is more common with these tumors. Considering these facts and extrapolating the outcomes of cervical SCC, chemoradiation can be explored for locally advanced primary endometrial SCC.To date, no case of invasive PESCC has been reported in reference to retained IUCD, which fulfilled all Fluhmann’s criteria. The present case confirmed to Fluhmann’s criteria as there was no evidence of invasive or in situ SCC of the cervix or any other variant of endometrial carcinoma despite extensive sampling, though it has displayed sequential changes of squamous metaplasia. Although we were unable to perform in-situ hybridization for HPV confirmation, the negativity for its surrogate marker, p16 immunohistochemistry, affirms a non-HPV pathway in this case.CONCLUSION: Herein we present a unique case of PESCC secondary to retained IUCD. Prolonged retained IUCD may cause chronic inflammation of endometrium leading to metaplasia and carcinomatous changes.Conflict of Intrest: NilContribution to authorship:Anadi Pachaury – Conceptualization, Methodology, Investigation, Original draft writing, Review and editing.Akash Sali - Methodology, Investigation, Review and editing.Debashish Chaudhary - Conceptualization, Methodology, Investigation, Original draft writing, Review and editing.Consent for publication taken from patientFunding: NilREFERENCES1. Goodman A, Zukerberg LR, Rice LW, Fuller AF, Young RH, Scully RE. Squamous cell carcinoma of the endometrium: a report of eight cases and a review of the literature. Gynecol Oncol. 1996 Apr;61(1):54–60.2. 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