Departments of 1Pathology and 2Obstetrics & Gynaecology, Hamdard Institute of Medical Sciences & Research, New Delhi, India *Corresponding Author e-mail: jaseemamu@gmail.com سرطان اخلاليا احلرشفية األويل يف موقع بطانة الرحم تقرير تشخيص نادر �سوجاتا جيتلي، زيبا �ساميم، حممد جا�سم ح�سن، جارميا مادان، رينا جاين abstract: Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year’s duration. A total abdominal hysterectomy with a bilateral salpingo- oophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up. Keywords: Squamous Cell Carcinoma; Endometrium; Pyometra; Case Report; India. امللخ�ص: �رسطان اخلاليا احلر�سفية )SCC( لبطانة الرحم، �سواء كان اأويل اأو ثانوي ل�رسطان عنق الرحم، نادر احلدوث. و�رسطان اخلاليا احلر�سفية الأ�سا�سي النا�سيء يف موقع بطانة الرحم نف�سه اأكرث ندرة. وعادة ما يحدث يف الن�ساء بعد �سن الياأ�ض، وله عالقة قوية مع تقيح الرحم. نعر�ض حالة امراأة يف �سن الياأ�ض ،متعددة الولدات تبلغ من العمر 60 عاما قدمت اإىل م�ست�سفى الذكرى املئوية حلكيم عبد احلميد، نيو دلهي، الهند، مايو 2014 ومعها تورم اأ�سفل البطن ي�سابه حمل 26 اأ�سبوعا وافرازات مهبلية ملدة �سنة واحدة. مت اإجراء ا�ستئ�سال كلي للرحم مع قناتي فالوب واملبي�سني، وكان الرحم مت�سخما مع تقيح واأظهر الت�رسيح اأنه قد مت ا�ستبدال خاليا بطانة الرحم باأكملها بخاليا حر�سفية خبيثة دون انت�سار اىل الن�سيج الع�سلي. وك�سف فح�ض الن�سيج املناعي اأن اخلاليا ال�رسطانية كانت ايجابية لp63 مع ارتفاع قيا�ض موؤ�رسKi-67. مل يكن العالج امل�ساعد مطلوبا واأ�سبحت املري�سة خالية من الأمرا�ض عند متتبعتها بعد �سبعة اأ�سهر. مفتاح الكلمات: خاليا ال�رسطان احلر�سفية؛ بطانة الرحم؛ تقيح الرحم؛ تقرير حالة؛ الهند. Primary Endometrial Squamous Cell Carcinoma In Situ Report of a rare disease Sujata Jetley,1 Zeeba S. Jairajpuri,1 *Mohammad J. Hassan,1 Garima Madaan,1 Reena Jain2 online case report Hospital, New Delhi, India, in May 2014 with abdominal swelling and vaginal discharge which had been occurring for the past year. There was no history of vaginal bleeding, the obstetric history was uneventful and the patient had been postmenopausal for 16 years. An abdominal examination revealed a soft and non- tender lump corresponding to the size of a pregnancy of 26 gestational weeks. A speculum examination showed a healthy cervix. Ultrasonography revealed a mass in the pelvic region measuring 14.2 x 10.8 cm, suggestive of a postmenopausal simple ovarian cyst. Contrast-enhanced computed tomography of the lower abdomen showed a large pelvic-abdominal cystic lesion, likely of left adnexal origin. A Papanicolaou smear of the cervix was suggestive of atrophy and was negative for intraepithelial lesions or invasive cancers. An exploratory laparotomy and total abdominal hysterectomy with bilateral salpingo-oophorectomy Cancer of the endometrium is acommon gynaecological malignancy in the developed world and is second only to cervical cancer in the developing world.1 Most endometrial cancers are adenocarcinomas. Primary endometrial squamous cell carcinomas (PESCCs) are extremely rare although the exact prevalence is not yet known. The majority of squamous cell carcinoma (SCC) cases represent an extension from the cervix, where SCC spreads superficially to the inner surface of the uterus and replaces the endometrium with carcinoma cells.2 However, whether primary or secondary, endometrial SCC is rare and PESCC in situ even rarer. Case Report A 60-year-old multiparous postmenopausal woman presented to Hakeem Abdul Hameed Centenary Sultan Qaboos University Med J, November 2015, Vol. 15, Iss. 4, pp. e559–562, Epub. 23 Nov 15 Submitted 13 Jan 15 Revisions Req. 16 Jun & 13 Jul 15; Revisions Recd. 30 Jun & 20 Aug 15 Accepted 27 Aug 15 doi: 10.18295/squmj.2015.15.04.021 Primary Endometrial Squamous Cell Carcinoma In Situ Report of a rare disease e560 | SQU Medical Journal, November 2015, Volume 15, Issue 4 was performed. On gross examination, the uterus was enlarged and the uterine cavity was filled with approximately 1,500 mL of pus. The inner surface of the cavity had a slightly irregular appearance [Figure 1]. The cervix had thinned but showed no growth. Microscopy of multiple sections from different areas of the uterine wall revealed that the entire endometrial lining had been replaced by sheets of atypical squamous cells with marked pleomorphism and bizarre forms [Figure 2]. The changes were limited to the epithelial lining and extensive sampling did not reveal any invasion into the myometrium. In view of the chronic pyometra, the presence of ichthyosis uteri was suspected but samples taken from multiple sections did not yield evidence of the condition. Despite extensive sampling, no evidence of normal endometrial glandular epithelium was found. Sections from the cervix did not show any abnormalities and there was no evidence of atypia or dysplasia. Both ovaries and the myometrium were unremarkable. Positive immunohistochemical staining for p63 confir- med the squamous nature of the lesion and a high Ki- 67 labelling index was noted [Figure 3]. A diagnosis of PESCC in situ was made. The patient was not given any adjuvant therapy and was disease-free during the seven-month follow-up period. Discussion Endometrial SCC usually occurs in postmenopausal women (mean age: 67 years).2 The condition has been strongly associated with pyometra, cervical stenosis, multiparity and chronic inflammation.2 Clinically, the majority of patients present with vaginal bleeding. Endometrial SCC usually originates from the uterine cervix and extends in a superficial spreading pattern.3 An extensive review of the literature by Marwah et al. revealed 26 cases of cervical carcinoma with endometrial surface involvement; Ishida et al. reported two more cases the following year.3,4 In all of these cases, the women were over the age of 50 years and presented with vaginal bleeding.3,4 PESCC is defined as a primary carcinoma of the endometrium composed of squamous cells with varying degrees of differentiation.5 Although a few reports of PESCC are available in the literature, the prevalence of this condition is unknown. While the exact pathogenesis is unclear, the cellular origin of PESCC has been proposed to be “reserve or stem cells located between the glandular basement membrane and the endometrial columnar cell layer, squamous metaplasia of the normal endometrium, or heterotopic cervical tissue”.6 Further research supports this finding.7–9 Human papilloma virus is known to have a definite role in the pathogenesis of SCC of the uterine cervix; however, its role in endometrial SCC is still to be determined.6 In cases of PESCC, it is important to exclude cervical SCC extension into the endometrium and squamous differentiation of an endometrioid adenocarcinoma.6,10 It is also essential to differentiate PESCC from endometrial SCC involvement based on the following strict pathological criteria recommended by Fluhmann: (1) no evidence of a coexisting endometrial adenocarcinoma or primary cervical SCC; (2) no connection between the endometrial tumour and squamous epithelium of the cervix; or Figure 1: Cut-open hysterectomy specimen showing the greyish-yellow irregular uterine cavity of a patient with primary endometrial squamous cell carcinoma in situ. No cervical growth was seen. Figure 2A & B: Haematoxylin and eosin stains at (A) x40 and (B) x400 magnification showing extensive replacement of the entire endometrial lining by sheets of atypical squamoid cells with marked pleomorphism in a patient with primary endometrial squamous cell carcinoma in situ. No invasion of the myometrium was seen. Figure 3A & B: Immunohistochemistry stains at x100 magnification showing (A) tumour cells positive for p63 and (B) a high Ki-67 labelling index in a patient with primary endometrial squamous cell carcinoma in situ. Sujata Jetley, Zeeba S. Jairajpuri, Mohammad J. Hassan, Garima Madaan and Reena Jain Online Case Report | e561 labelling index has also been reported, demonstrating the aggressive and malignant nature of the lesion.18 Lee et al. found a positive immunoreactivity for the cytokeratin 7, p63 and p16INK4a proteins, but not for cytokeratin 20 or the oestrogen and progesterone receptors.6 As a prognostic indicator of PESCC, the role of these receptors is still uncertain; however, lack of oestrogen cannot be completely ruled out as an aetiological factor since most patients diagnosed with PESCC are postmenopausal.6 The prognosis for patients with SCC depends mainly on the stage of the tumour. PESCC has been reported to show a poorer prognosis than endometrioid carcinomas.18 Management for this condition usually consists of a surgical hysterectomy with adnexectomy and radiotherapy.2 Conclusion Few cases of PESCC have been reported in the literature. As the disease usually presents with vaginal bleeding and is most commonly seen in postmenopausal women, PESCC should be considered (3) no connection between any existing cervical in situ carcinoma and the independent endometrial neoplasm.10 These criteria were later modified by other authors.11,12 The present case conformed to Fluhmann’s criteria and also displayed sequential changes of dysplasia and carcinoma in situ, although there were no signs of an invasive carcinoma despite extensive sampling. To the best of the authors’ knowledge, only five cases of PESCC in situ have been reported to date [Table 1].13–17 Radhika et al. reported a case of PESCC in situ associated with a prolapsed uterus, while Mitchell et al. noted an association with the long-term use of intrauterine devices.13,14 Zidi et al. described a case of PESCC in situ with extensive squamous metaplasia and dysplasia along with a serous cystadenoma of the right ovary.15 PESCC in situ was also reported by Kairys et al., while a rare case with extensive ichthyosis uteri was described by Pailoor et al. in a postmenopausal woman with pyometra.16,17 The role of immunohistochemistry is limited, with most studies demonstrating a mutation of the p53 tumour suppressor gene.18,19 A high Ki-67 Table 1: Comparative analysis of cases of endometrial squamous cell carcinoma in situ in the literature Author and year of report Patient age in years Clinical presentation Gross findings Microscopy findings Associated pathology Kairys et al.16 1964 57 Asymptomatic pelvic mass which appeared 3.5 years after undergoing apparently success- ful radiation therapy for stage II SCC of the cervix Multiple myomas with replacement of the endometrium by a pyogenic membrane Endometrial SCC in situ Multiple leiomyomas with pyometra Radhika et al.13 1993 50 Complete prolapse of the uterus Normal uterine cavity with wall thickness of 1.3 cm PESCC in situ Squamous metaplasia of the surface mucosal lining and involvement of some of the superficial glands by SCC in situ Mitchell et al.14 1999 65 Vaginal bleeding Haemorrhagic and granular endometrium Endometrial SCC in situ Extensive squamous metaplasia of the endometrium and in situ carcinoma of the cervix uteri Zidi et al.15 2003 75 Pelvic pain and vaginal discharge Thickened and epidermalised endometrium with pyometra PESCC in situ Extensive squamous metaplasia of the endometrium with foci of dysplasia and pyometra Pailoor et al.17 2014 52 Pelvic pain Widened endometrial cavity lined by irregular, shaggy, membrane-like material PESCC in situ Extensive ichthyosis uteri Present case 60 Abdominal swelling and vaginal discharge Irregular appearance of the endometrial surface with pyometra PESCC in situ Pyometra and replacement of the endometrial lining with atypical squamous cells without invasion of the myometrium SCC = squamous cell carcinoma; PESCC = primary endometrial squamous cell carcinoma. Primary Endometrial Squamous Cell Carcinoma In Situ Report of a rare disease e562 | SQU Medical Journal, November 2015, Volume 15, Issue 4 in the differential diagnosis for these patients, despite its rarity. The exact pathogenesis is unclear and diagnosis is based on strict pathological criteria. This report presents a case of PESCC in situ in a 60-year-old multiparous postmenopausal woman with pyometra and without invasion of the myometrium. References 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61:69–90. doi: 10.3322/caac.20107. 2. Bagga PK, Jaswal TS, Datta U, Mahajan NC. Primary endometrial squamous cell carcinoma with extensive squamous metaplasia and dysplasia. Indian J Pathol Microbiol 2008; 51:267–8. doi: 10.4103/0377-4929.41686. 3. Marwah N, Garg M, Singh S, Sethi D, Sen R. Unusual form of squamous cell carcinoma of the cervix extending in situ into the endometrium: Three case reports and review of literature. Int J Appl Basic Med Res 2012; 2:139–41. doi: 10.4103/2229- 516X.106359. 4. Ishida M, Okabe H. Superficial spreading squamous cell carcinoma of the uterine cervix involving the endometrium: Report of two cases with emphasis on the likely molecular mechanism. Oncol Lett 2013; 5:31–4. doi: 10.3892/ol.2012.953. 5. Kennedy AS, DeMars LR, Flannagan LM, Varia MA. Primary squamous cell carcinoma of the endometrium: A first report of adjuvant chemoradiation. Gynecol Oncol 1995; 59:117–23. doi: 10.1006/gyno.1995.1277. 6. Lee SJ, Choi HJ. Primary endometrial squamous cell carcinoma: A case report and review of relevant literature on Korean women. Korean J Pathol 2012; 46:395–8. doi: 10.4132/ KoreanJPathol.2012.46.4.395. 7. Baggish MS, Woodruff JD. The occurrence of squamous epithelium in the endometrium. Obstet Gynecol Surv 1967; 22:69–115. doi: 10.1097/00006254-196702000-00008. 8. Seltzer VL, Klein M, Beckman EM. The occurrence of squamous metaplasia as a precursor of squamous cell carcinoma of the endometrium. Obstet Gynecol 1977; 49:34–7. 9. Yamamoto Y, Izumi K, Otsuka H, Kishi Y, Mimura T, Okitsu O. Primary squamous cell carcinoma of the endometrium: A case report and a suggestion of new histogenesis. Int J Gynecol Pathol 1995; 14:75–80. doi: 10.1097/00004347-199501000- 00013. 10. Fluhmann CF. The histogenesis of squamous cell metaplasia of the cervix and endometrium. Surg Gynecol Obstet 1953; 97:45–58. 11. Kay S. Squamous cell carcinoma of the endometrium. Am J Clin Pathol 1974; 61:264–9. 12. Jeffers MD, McDonald GS, McGuinness EP. Primary squamous cell carcinoma of the endometrium. Histopathology 1991; 19:177–9. doi: 10.1111/j.1365-2559.1991.tb00010.x. 13. Radhika S, Dey P, Gupta SK. Primary squamous cell carcinoma- in-situ of the endometrium: A case report. Indian J Cancer 1993; 30:92–5. 14. Mitchell S, Fletcher H, Williams NP, Coard K. In situ squamous cell carcinoma of the endometrium associated with long-term intrauterine device (Dalkon Shield) usage. J Obstet Gynaecol 1999; 19:88–9. doi: 10.1080/01443619966119. 15. Zidi YS, Bouraoui S, Atallah K, Kchir N, Haouet S. Primary in situ squamous cell carcinoma of the endometrium, with extensive squamous metaplasia and dysplasia. Gynecol Oncol 2003; 88:444–6. doi: 10.1016/S0090-8258(02)00105-1. 16. Kairys LR, Dougherty CM, Mickal A. Squamous cell carcinoma in situ of the endometrial cavity. Am J Obstet Gynaecol 1964; 88:548–9. doi: 10.1016/0002-9378(64)90516-2. 17. Pailoor K, Pai MR, Gatty RC, Fernandes H, Jayaprakash CS, Marla NJ. A rare case of primary insitu squamous cell carcinoma of the endometrium with extensive icthyosis uteri. Online J Health Allied Sci 2014; 13:10. 18. Terada T, Tateoka K. Primary pure squamous cell carcinoma of the endometrium: A case report. Int J Clin Exp Pathol 2013; 6:990–3. 19. Giordano G, D’Adda T, Merisio C, Gnetti L. Primary squamous cell carcinoma of the endometrium: A case report with immunohistochemical and molecular study. Gynecol Oncol 2005; 96:876–9. doi: 10.1016/j.ygyno.2004.11.019. http://dx.doi.org/10.3322/caac.20107 http://dx.doi.org/%2010.4103/0377-4929.41686 http://dx.doi.org/10.4103/2229-516X.106359 http://dx.doi.org/10.4103/2229-516X.106359 http://dx.doi.org/10.3892/ol.2012.953 http://dx.doi.org/10.1006/gyno.1995.1277 http://dx.doi.org/10.4132/KoreanJPathol.2012.46.4.395 http://dx.doi.org/10.4132/KoreanJPathol.2012.46.4.395 http://dx.doi.org/10.1097/00006254-196702000-00008 http://dx.doi.org/10.1097/00004347-199501000-00013 http://dx.doi.org/10.1097/00004347-199501000-00013 http://dx.doi.org/10.1111/j.1365-2559.1991.tb00010.x http://dx.doi.org/10.1080/01443619966119 http://dx.doi.org/10.1016/S0090-8258%2802%2900105-1 http://dx.doi.org/10.1016/0002-9378%2864%2990516-2 http://dx.doi.org/10.1016/j.ygyno.2004.11.019