Well differentiated endometrioid adenocarcinoma of the uterus: a cancer unit or centre case?

Objective: The purpose of this study was to investigate what proportion of cases showing a well differentiated endometrioid endometrial adenocarcinoma in the hysterectomy specimen removed at two UK cancer centres had adverse pathological features or advanced stage disease at the time of presentation. Study Design:Ninety-eight patients who were operated on at either the South East London Cancer Centre, London or the Kent Oncology Centre. Maidstone had a histological diagnosis of well differentiated (grade 1) endometrioid adenocarcinoma in their hysterectomy specimen. These were identified using the Multidisciplinary meeting database as well as the respective pathology department databases. The histology reports for these patients were examined and analysed for the purpose of this study. Results: Of the initial 98 cases, 65 patients (66.3%) were referred with a preoperative curettage showing it well differentiated endometrioid adenocarcinoma, 25 cases (25.5%) were referred with atypical endometrial hyperplasia, seven patients (7.1%) were referred with a moderately differentiated endometrioid adenocarcinoma, and one case (1.0%) was referred with a possible malignant mixed Mullerian tumour. Subsequent histological examination of the hysterectomy specimens revealed that all of these cases had it well I differentiated endometrioid adenocarcinoma. In 20 of the 98 cases (20.4%) there was no myometrial invasion, 56 cases (57.1%) showed invasion of the inner half of the myornetriurn and 22 cases (22.4%) showed cuter half involvement. There was no cervical involvement in 78 cases (79.6%). endocervical gland involvement in eight patients (8.2%) and cervical stromal involvement in 12 patients (12.2%). The total percentage of cases with cervical involvement was 20.4%. Thirty-eight cases (Out of the 98) underwent a bilateral pelvic lymphadenectomy. Of these 38 cases. four cases had locoregional nodal metastases (10.5% of the patients who underwent lymphadenectomy). There were ovarian metastases in one case and metastasis to one fallopian tube in another. From our study, 33.6% of cases with a well differentiated endometrioid adenocarcinoma of the uterus were Stage Ic or more at the time of presentation; 12.2% were at least FIGO Stage Ic. eight patients (8.2%) were FIGO Stage IIa, seven patients (7.1%) were Stage IIb and six patients (6.1%) were Stage III. In these patients a full surgical staging operation with a pelvic lymphadenectomy was indicated according to FIGO recommendation. Conclusion: A significant proportion (33.6%) of well differentiated tumours in a hysterectomy were found to have Stage Ic disease or more at the time of presentation. and thus full surgical staging including a lymphadenectomy should have been carried out in these cases. Cases with a preoperative biopsy showing atypical hyperplasia or well differentiated adenocarcinoma should have a preoperative MRI scan or preferably an intraoperative frozen section examination to identify those cases with adverse pathological features which need to be fully staged with pelvic and paraaortic lymphadenectomy.

Well differentiated endometrial adenocarcinoma; Staging; Prognostic factors.

[1] Jemal A., Tiwari R.C., Murray T., Ghafour A., Samuels A., Ward E. et al.: Cancer Statistics, 2004. CA Cancer J. Clin. , 2004, 54, 8.

[2] Quinn M., Wood H., Cooper N., Rowan S. (eds.): Cancer Atlas of the UK and Ireland 1991-2000. Basingstoke, Palgrave MacMillan, 2005, 239.

[3] Fisher B., Constantino J.P., Redmond C.K., Fisher E.R., Wickerham D.L., Cronin W.M.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project B-14. J. Natl. Cancer Inst., 1994, 86, 527.

[4] Assikis V.J., Neven P., Jordan V.C., Vergote I.: A realistic clinical perspective on tamoxifen and endometrial carcinogenesis. Eur. J. Cancer, 1996, 32A, 1464.

[5] Calman Hine Report: A policy framework for commissioning cancer services: A report by the Expert Advisory Group on Cancer to the Chief Medical Officers of England and Wales. Department of Health Publication, 1995.

[6] Kurman R.J., Kaminski P.F., Norris H.J.: The behaviour of endometrial hyperplasia: a long-term study of 'untreated' hyperplasia in 170 patients. Cancer, 1985, 56, 403.

[7] Silverberg S.G.: Hyperplasia and carcinoma of the endometrium. Semin. Diagn. Pathol. , 1988, 135.

[8] Huang S.J., Amparo E.G., Yu Y.S.: Endometrial hyperplasia: histologic classification and behaviour. Surg. Pathol. , 1988, 1, 215.

[9] Widra E.A., Dunton C.J., McHugh M., Palazzo J.P.: Endometrial hyperplasia and the risk of carcinoma. Int. J. Gynaecol. Cancer,1995, 5, 233.

[10] Ferenczy A., Gelfand M.: The biologic significance of cytologic atypia in progestin treated endometrial hyperplasia. Am. J.Obstet. Gynaecol. , 1989, 160, 126.

[11] Kurman R.J., Norris H.J.: Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer, 1982, 49, 2547.

[12] Janicek M.F., Rosenshein N.B.: Invasive endometrial cancer in uteri resected for atypical endometrial hyperplasia. Gynaecol.Oncol. , 1994, 52, 373.

[13] FIGO. Staging classification and clinical practice. Guidelines for Gynaecological Cancers. www.figo.org.

[14] Creasman W.T., Morrow C.P., Bundy B.N., Homesley H.D., Graham J.E., Heller P.B.: Surgical pathologic spread patterns of endometrial cancer. Cancer, 1987, 60, 2035.

[15] Sartori E., Gadducci A., Landoni F., Lissoni A., Maggino T., Zola P. et al.: Clinical behaviour of 203 Stage II endometrial cancer cases: the impact of primary surgical approach and of adjuvant radiation therapy. Int. J. Gynecol. Cancer, 2001, 11, 430.

[16] Cornelison T.L., Trimble E.L., Kosary C.L.: SEER data, corpus uteri cancer: treatment trends versus survival for FIGO Stage II,1988-1994, 74, 350.

[17] Mariani A., Webb M.J., Keeney G.L., Calori G., Podratz K.C.: Role of wide radical hysterectomy and pelvic lymph node dissection in endometrial cancer with cervical involvement. Gynecol.Oncol. , 2001, 83, 72.

[18] Look K.: Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the role of surgery and adjuvant radiation. Int. J, Gynecol. Cancer 2002, 12, 237.

[19] Jolly S., Vargas C.E., Kumar T., Weiner S.A., Brabbins D.S., Chen P.Y., Floyd W., Martinez A.A.: Gynecol. Oncol. , 2006, 103, 87.

[20] Citron J.R., Sutton H., Yamada S.D., Mehta N., Mundt A.J.: Int. J.Radiat. Oncol. Biol. Phys. , 2004, 59, 1432.

[21] Dvalishvili I., Charkviani L., Turashvili G., Burkadze G.: Clinical characteristics of prognostic factors in uterine endometrioid adenocarcinoma of various grade. Georgian Med. News, 2006, 132, 24.

[22] Eltabbakh G.H., Shamonki J., Mount S.L.: Gynecol Oncol. , 2005, 99,309.

[23] Dzvincuk P., Pilka R., Kudela M., Duskova M.: Histological grade in the management of carcinoma of the endometrium. Ceska Gynekol. , 2005, 70, 201.

[24] Mitchard J., Hirschowitz L.: Concordance of FIGO grade of endometrial adenocarcinomas in biopsy and hysterectomy specimens. Histopathology, 2003, 42, 372.

[25] Petersen R.W., Quinlivan J.A., Casper G.R., Nicklin J.L.: Aust NZ.J. Obstet. Gynaecol. , 2000, 40, 191.

[26] Cowles T.A., Magrina J.F., Masterson B.J., Capen C.V.: Comparison of clinical and surgical staging in patients with endometrial cancer. Obstetrics Gynecol. , 1985, 66, 413.

[27] Soothill P.W., Alcock C., MacKenzie I.Z.: Discrepancy between curettage and hysterectomy histology in patients with stage 1 uterine malignancy. Br. J. Obstet. Gynaecol. , 1989, 96, 478.

[28] Oakley G., Nahhas W.A.: Endometrial adenocarcinoma: therapeutic impact of preoperative histopathologic examination ofendometrial tissue. Eur. J. Gynaecol. Oncol. , 1989, 10, 255.

[29] Manfredi R., Mirk P., Maresca G., Margariti P.A., Testa A., ZannoniG.F. et al.: Local regional staging of endometrial carcinoma: role of MRI in surgical planning. Radiology, 2004, 231, 372.

[30] Shibutani O., Joja I., Shiraiwa M., Asakawa T., Miyagi Y., KudoT. , Hiraki Y.: Endometrial carcinoma: efficacy of thin section oblique axial MR images for evaluating cervical invasion.Abdom. Imaging, 1999, 24, 520.

[31] Cunha T.M., Felix A., Cabral I.: Preoperative assessment of deep myometrial and cervical invasion in endometrial carcinoma: comparison of MRI and gross visual inspection. Int. J. Gynecol. Cancer, 2001, 11, 130.

[32] Frei K.A., Kinkel K.: Staging endometrial cancer: role of MRI. Review article. J. MRI, 2001, 13, 850.

[33] Quinlivan J.A., Petersen R.W., Nicklin J.L.: Accuracy of frozen section for the operative management of endometrial cancer. BJOG, 2001, 108, 798.

[34] Zorlu C.G., Kuscu E., Ergun Y., Aydogdu T., Cobanoglu O., ErdasO. : Intraoperative evaluation of prognostic factors in Stage I endometrial cancer by frozen section: how reliable?. Acta Obstet. Gynecol. Scand. , 1993, 72, 382.

[35] Badia J., Chuaqui R., Hamed F, Wild R., Barrena N., MayersonD. , Oyarzun E.: An intraoperative anatomicopathological study of myometrial penetration in endometrial cancer: its usefulness in making decisions on extending the primary surgical treatment.Rev. Chil. Obstet. Ginecol. , 1992, 57, 420.

[36] Kayikcioglu F., Boran N., Meydanli M.M., Tulunay G., KoseF.M. , Bulbul D.: Is frozen section diagnosis a reliable guide in surgical treatment of Stage I endometrial cancer?. Acta Oncol. ,2002, 41, 444.

[37] Kir G., Kir M., Cetiner H., Karateke A., Gurbuz A.: Diagnostic problems on frozen section examination of myometrial invasion in patients with endometrial carcinoma. Eur. J. Gynaecol. Oncol. ,2004, 25, 211.

[38] Homesley H.D., Boike G., Spiegel G.W.: Feasibility of laparoscopic management of presumed Stage I endometrial carcinoma and assessment of accuracy of myoinvasion estimates by frozen section: a gynecologic oncology group study. Int. J. Gynecol. Cancer, 2004, 14, 341.

[39] Malviya V.K., Deppe G., Malone J.M., Sundareson A.S., Lawrence W.D.: Reliability of frozen section examination in identifying poor prognostic indicators in Stage I endometrial adenocarcinoma. Gynecol. Oncol. , 1989, 34, 299.

[40] Frumovitz M., Slomovitz B.M., Singh D.K., Broaddus R.R., Abrams J., Sun C.C., Bevers M., Bodurka D.C.: Frozen section analyses as predictors of lymphatic spread in patients with early stage uterine cancer. J. Am. Coll. Surg., 2004, 199, 388.

[41] Kucera E., Kainz C., Reinthaller A., Sliutz G., Leodolter S.,Kucera H., Breitenecker G.: Accuracy of intraoperative frozen section diagnosis in Stage I endometrial adenocarcinoma. Gynecol. Obstet. Inv., 2000, 49, 62.

[42] Fanning J., Tsukada Y., Piver M.S.: Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma. Gynecol. Oncol. , 1990, 37, 47.

[43] Shim J.U., Rose P.G., Reale F.R., Soto H., Tak W.K., Hunter R.E.: Accuracy of frozen section diagnosis at surgery in clinical Stage I and II endometrial carcinoma. Am. J. Obstet. Gynecol. , 1992, 166.1335.