Resectoscopic surgery may be an alternative to hysterectomy in high-risk women with atypical endometrial hyperplasia

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1 Journal of Minimally Invasive Gynecology (2007) 14, Resectoscopic surgery may be an alternative to hysterectomy in high-risk women with atypical endometrial hyperplasia Fawaz Edris, MD, George A. Vilos, MD, Awatif AL-Mubarak, MD, Helen C. Ettler, MB ChB, Jackie Hollett-Caines, MD, and Basim Abu-Rafea, MD From the Department of Obstetrics and Gynecology (Drs. Edris, Vilos, AL-Mubarak, Hollett-Caines, and Abu-Rafea), and Department of Pathology (Dr. Ettler), The University of Western Ontario, London, Ontario, Canada. KEYWORDS: Abnormal uterine bleeding; Atypia; Endometrial hyperplasia; Hysteroscopy; Resectoscopic surgery Abstract STUDY OBJECTIVE: Endometrial hyperplasia is found in 2% to 10% of women with abnormal uterine bleeding (AUB). Up to 43% of patients with cytologic atypia harbor coexisting adenocarcinoma, and approximately 20% to 52% of atypical hyperplasias, if untreated, progress to cancer. The objective of this study was to estimate the incidence of atypical endometrial hyperplasia encountered during routine resectoscopic surgery in women with AUB and to evaluate the role of resectoscopic surgery in the management of women with AUB and atypical endometrial hyperplasia who refused and/or were at high risk for hysterectomy. DESIGN: Prospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990 through December 2005, the senior author (GAV) performed primary resectoscopic surgery in 3401 women with AUB. Among these, there were 22 women with atypical (17 complex, 5 simple) endometrial hyperplasia. INTERVENTIONS: All women underwent hysteroscopic evaluation and partial (n 3) or complete (n 19) endometrial electrocoagulation and/or resection. Subsequently, 6 women had hysterectomy and bilateral salpingo-oophorectomy (BSO). MEASUREMENTS AND MAIN RESULTS: The median (range) for age, parity, and body mass index were 55 years (24 78 years), 2 (0 4), and 30.1 kg/m 2 ( kg/m 2 ), respectively. Among the 3401 women, there were 22 cases of atypical endometrial hyperplasia, 12 of which were incidentally diagnosed at the time of hysteroscopy (complex 10, simple 2, incidence 0.35%). After hysteroscopic diagnosis or confirmation of diagnosis, 6 women underwent hysterectomy and BSO. Of the remaining 16 women, followed for a median of 5 years (range years), 1 was lost to follow-up, 1 had only a biopsy to preserve fertility, 1 died from lung cancer after 4 years, and 1 died from colon cancer after 5 years. One patient developed endometrial cancer after 10.5 years with postmenopausal bleeding. She remains alive and well 3.5 years after hysterectomy and BSO. The remaining 11 patients are amenorrheic at a median follow-up of 6 years (range years). CONCLUSIONS: Resectoscopic surgery in 3391 women with AUB detected 12 incidental cases of atypical endometrial hyperplasia (incidence 0.35%). Skillful resectoscopic surgery may be an alternative to hysterectomy in women with AUB and atypical endometrial hyperplasia, who refuse or are at high-risk for hysterectomy and who are compliant with regular and long-term follow-up AAGL. All rights reserved. Corresponding author: George A. Vilos, MD, Department of Obstetrics and Gynecology, 268 Grosvenor Street, London, Ontario, Canada, N6A 4V2. george.vilos@sjhc.london.on.ca Submitted June 12, Accepted for publication August 13, /$ -see front matter 2007 AAGL. All rights reserved. doi: /j.jmig

2 Edris et al Hysteroscopy and atypical endometrial hyperplasia 69 Endometrial hyperplasia is a noninvasive proliferation of the stromal and epithelial components of the endometrial tissue. Based on a variety of cytologic and architectural changes, endometrial hyperplasia constitutes a heterogeneous group of lesions that vary from simple exaggeration of the normal proliferative state at one extreme to changes closely resembling adenocarcinoma at the other. The International Society of Gynecological Pathologists and the World Health Organization classify endometrial hyperplasia 1 4 as simple and complex, with or without atypia. Atypical hyperplasia designates proliferation of glands that is associated with cytologic atypia in which various degrees of nuclear atypia and loss of polarity are present. Abnormal uterine bleeding (AUB) is experienced by 5,6 10% to 30% of reproductive-aged women. Endometrial 7 11 hyperplasia is found in 2% to 10% of women with AUB. Traditionally, investigation of AUB included fractional dilatation and curettage (D&C) in the operating room under general anesthesia. It has been reported that D&C provides adequate sampling in 75% of women, and misses up to 10% of pathology. 12 Hysteroscopic endometrial ablation was introduced in the 1980s, while nonhysteroscopic or global endometrial ablation was introduced in the 1990s. Both were designed as alternatives to hysterectomy for treatment of women with 13 AUB of benign pathology. Before endometrial ablation, it is recommended that AUB be investigated in accordance 14 with established clinical practice guidelines. Such guidelines recommend that office endometrial biopsy or D&C in the operating room be performed in all women with postmenopausal bleeding and in premenopausal women with certain risk factors, such as irregular bleeding, age greater than 45 years, obesity (weight 90 kg or body mass index 27 kg/m 2 ), personal history of polycystic ovarian syndrome, infertility, nulliparity, or family history of endometrial or colon cancer. All of these have been shown to be 14 independent risk factors for endometrial hyperplasia and 11,15,16 carcinoma in women with AUB. Office endometrial biopsy is occasionally impossible to perform or provides an inadequate sample due to technical issues, cervical stenosis, or other patient conditions such as morbid obesity and discomfort. Under such circumstances, we have adopted the philosophy of performing hysteroscopic evaluation with directed biopsies or endometrial resection in the operating room under appropriate anesthesia and optimal medical conditions. Due to possible progression of atypical endometrial hyperplasia to endometrial carcinoma, or their coexistence, the most appropriate treatment for atypical endometrial hyperplasia is considered to be hysterectomy and bilateral salpingo-oophorectomy (BSO). In our current study, we present 22 women with AUB and atypical endometrial hyperplasia. In 12 women, prehysteroscopy office endometrial biopsy was inadequate; technically impossible; or reported as normal, proliferative or endometrial hyperplasia without atypia. Atypical endometrial hyperplasia was known preoperatively in 10 women. The purpose of the study was to estimate the frequency of atypical endometrial hyperplasia encountered during hysteroscopic endometrial ablation and to determine if hysteroscopic surgery can be used as an alternative to hysterectomy for patients with atypical endometrial hyperplasia when hysterectomy is difficult, risky, or refused. Material and methods From January 1990 through December 2005, the senior author (GAV) performed primary resectoscopic surgery using electrocoagulation with rollerball, resection with a loop electrode, or a combination of both in 3401 women with AUB. A 26F ( 9 mm) diameter resectoscope (Storz, Tuttlingen, Germany) and 3- to 5-mm rollerballs or 8-mm diameter loop electrodes were used to coagulate or cut tissue at W of power. The uterus was distended/ irrigated with 1.5% glycine solution at 100 cm H 2 O( 75 mm Hg) pressure with mm Hg suction to evacuate air bubbles, clots, and debris from the uterus. As a rule, resection rather than rollerball ablation of the entire was performed in the absence of a recent ( 6 months) negative endometrial biopsy; in the presence of intrauterine (s), myoma(s), or suspicious lesion(s); and in women with any of the risk factors for endometrial neoplasia, as described above. Having adopted the above principles, we incidentally identified 12 atypical endometrial hyperplasia cases (10 complex [Table 1] and 2 simple [Table 2]). Results The characteristics of the patients, preoperative endometrial biopsy, hysteroscopic findings and treatment, posthysteroscopy pathology and treatment, and clinical outcomes are also listed in the corresponding tables. Case histories of the first 7 patients of Table 1 and first 3 patients of Table 2 have been previously published. Table 1 includes 17 women with atypical complex endometrial hyperplasia. Seven of these were known to have atypical hyperplasia before hysteroscopic surgery. These women declined or were at high risk for hysterectomy and BSO. They consented only to hysteroscopic evaluation and possible endometrial resection. One of seven women (No. 11, TC) wished to preserve her fertility. Complete resection was done in 6 women, and the seventh (TC) had only a biopsy. Except in 1 woman (No. 7, SM), histopathologic evaluation confirmed atypical endometrial hyperplasia. Of the 6 women who had complete endometrial resection, 1 was lost to follow-up (No. 5, FH), and the other 5 remain amenorrheic after a median follow-up of 4 years (range years). The woman who wished to retain fertility also remains alive and well after 4 years of follow-up. She had 17

3 Table 1 Patient No./initials Atypical complex hyperplasia Age (yrs)/ parity BMI kg/m 2 Preoperative endometrial biopsy Hysteroscopic findings Hysteroscopic treatment Hysteroscopic pathology Post-hysteroscopic management Clinical outcome/years 1/CM 45/1 32 SH Thick *Rollerball/resection FACH Endometrial Ca/ 10.5 A&W/14 2/AC 65/4 38 SH 2-cm Resection ACH Amenorrheic but died of colon Ca/5 3/SL 57/ FSH Normal / *Rollerball/resection FACH/benign Amenorrheic/8 4/AS 65/ Unable to do Thick /large Resection FACH/benign Amenorrheic/7 5/FH 74/ FACH Thick Resection FACH Lost to follow-up 6/JD 56/ ACH Normal / Resection FACH Amenorrheic/6 7/SM 58/ ACH Normal Resection Normal Amenorrheic/6 8/BB 46/ Unable to do Thick oid *Rollerball/resection ACH TAH BSO/no residual 9/GP 54/ Proliferative 1 /2 myomas Resection FACH Amenorrheic/5 10/JM 46/ Normal Normal / myomas Resection FACH LAVH BSO/no residual hyperplasia 11/TC 24/ ACH Thick endometrial Biopsy only ACH Conceived after ART Normal biopsy/4 septum 12/HP 57/ ACH Thick /deep Resection FACH/adenomyosis Amenorrheic/4 glands 13/RH 52/ Proliferative Polypoid/septum Resection FACH Amenorrheic/4 14/CN 59/ ACH Thick Resection ACH Amenorrheic/4 15/CK 78/ Unable to do Thick / Partial resection/ ectomy Polyp with ACH TAH BSO/No residual hyperplasia 16/DF 41/ ACH Thick /deep Resection ACH Amenorrheic/1.5 glands 17/ML 52/ CH Thin / 3 s Resection ACH TAH BSO/CH A&W alive and well; ACH atypical complex hyperplasia; ART assisted reproductive technology; BMI body mass index; Ca cancer; CH complex hyperplasia; FACH focal atypical complex hyperplasia; FSH focal simple hyperplasia; LAVH laparoscopic-assisted vaginal hysterectomy; SH simple hyperplasia; TAH BSO total abdominal hysterectomy and bilateral salpingo-oophorectomy. *Rollerball of the cornua and fundus and resection of the remaining. On Tamoxifen. 70 Journal of Minimally Invasive Gynecology, Vol 14, No 1, January/February 2007

4 Edris et al Hysteroscopy and atypical endometrial hyperplasia 71 Table 2 Atypical simple hyperplasia Post-hysteroscopic management Clinical outcome/years Hysteroscopy findings Hysteroscopic treatment Hysteroscopic pathology Preoperative endometrial biopsy BMI kg/m 2 Age (yrs)/ parity Patient No./initials 1/IB 70/ FAH Polypoid Resection SH Amenorrheic/12 2/KH 50/ AH Thick Resection Proliferative Amenorrheic/8 FASH TAH BSO (2 y)/ endometriosis Partial resection/perforation 3/FW 46/ Hyperplasia Thick / oid/ 4/SW 64/ CH Cystic Resection FASH Amenorrheic but died of lung Ca/4 Resection FASH TAH BSO/focus of inactive 5/SZ 51/ ASF Thick / AH atypical hyperplasia; ASF atypical simple hyperplasia; BMI body mass index; Ca cancer; CH complex hyperplasia; FAH focal atypical hyperplasia; FASH focal atypical simple hyperplasia; SH simple hyperplasia; TAH BSO total abdominal hysterectomy and bilateral salpingo-oophorectomy. a twin pregnancy after assisted reproductive technology. She delivered the twins at 24 weeks. One twin survived and is doing well. She is currently being treated with progestins and followed regularly by endometrial biopsies, as she is trying to conceive again. Ten women were diagnosed with atypical endometrial hyperplasia after resectoscopic surgery. These women had complete endometrial resection with or without rollerball coagulation of the fundus and cornua, except 1 (No. 15, CK), who had only a ectomy and partial resection because of increased endomyometrial vascularity, intraoperative bleeding, and excessive fluid absorption. Four of these 10 women consented to hysterectomy and BSO including CK (No. 15). Histopathologic evaluation of the hysterectomy specimens confirmed absence of hyperplasia in 3 uteri and the presence of complex hyperplasia with no atypia in the fourth. Of the remaining 6 women, 4 are amenorrheic after a median follow-up of 6 years (range 4 8 years). One died from colon cancer after 5 years of amenorrhea. One patient developed endometrial carcinoma after 10.5 years. She presented with postmenopausal bleeding (age 57), and office biopsy indicated well-differentiated endometrial adenocarcinoma. The hysterectomy specimen indicated endometrioid adenocarcinoma (grade 1) with focal invasion of the outer half of myometrium, and cervical stroma. Complex atypical hyperplasia also was noted. She remains alive and well 3.5 years after hysterectomy, BSO, and adjuvant radiation therapy. Table 2 includes 5 women with atypical simple hyperplasia. Three of these women were known to have atypical hyperplasia. They declined or were at high-risk for hysterectomy and BSO. They consented to hysteroscopic evaluation and possible endometrial resection. Complete resection was done, and histopathologic evaluation confirmed focal atypical simple hyperplasia in 1 woman, simple hyperplasia with no atypia in the second, and normal proliferative in the third. The woman with focal atypical hyperplasia consented to hysterectomy and BSO. No endometrial pathology was found in the hysterectomy specimen. The other 2 women remain amenorrheic after 8 and 12 years of follow-up, respectively. Two women were diagnosed with focal atypical simple hyperplasia after resectoscopic surgery. One had complete endometrial resection, but died of lung cancer after 4 years of amenorrhea. The other woman had partial endometrial resection because of uterine perforation at hysteroscopy. Two years later, she consented to hysterectomy and BSO. Except for endometriosis, no endometrial pathology was found in the hysterectomy specimen. Frequency of atypical endometrial hyperplasia From Tables 1 and 2, the frequency of incidental atypical endometrial hyperplasia during hysteroscopic endometrial ablation is 0.35% (12/3391).

5 72 Journal of Minimally Invasive Gynecology, Vol 14, No 1, January/February 2007 Resectoscopic surgery in atypical endometrial hyperplasia Discussion The prevalence of endometrial hyperplasia in women 7 11 with AUB is 2% to 10%, and the prevalence of atypical hyperplasia in women with irregular menstrual cycles is 0.5% to 0.7%. 11,17 Previous reports showed that when untreated, 20% to 52% of atypical hyperplasias progress to cancer, compared 2,3,18 21 with 2% of hyperplasias lacking atypia. Furthermore, it has been shown that the majority of hyperplasias that progress into cancer do so in the first few years after the original diagnosis. 21 We cannot determine at what interval our patient with the initial diagnosis of focal atypical hyperplasia progressed to endometrial cancer. Following hysteroscopic endometrial ablation, our patient reported occasional spotting. Transvaginal ultrasonic measurement of endometrial thickness was reported as 6 mm and 4.5 mm at 6 and 9 years after ablation, respectively. Office endometrial biopsies were reported as insufficient tissue for diagnosis. At 10.5 years, the patient presented with postmenopausal bright red bleeding, and biopsy confirmed well-differentiated endometrial adenocarcinoma. It has also been reported that when hysterectomy was performed within 1 month of curettage, 17% to 43% of women diagnosed with atypical endometrial hyperplasia at the time of curettage were found to harbor well-differentiated adenocarcinoma. 1,22 25 It is of interest to note that none of the 6 women who had hysterectomy in our study harbored coexisting adenocarcinoma. This may be due to our small sample or interobserver variability amongst pathologists in the diagnosis of atypical endometrial hyperplasia and endometrial carcinoma. Several investigators have studied the significance, natural history, and association of atypical hyperplasia and endometrial adenocarcinoma. In a group of 48 women with untreated atypical hyperplasia, the frequency of regression, persistence, and progression to carcinoma over a mean period of 13.4 years was 60%, 17%, and 23%, respectively. 2 Similar findings were reported in 96 women with untreated hyperplasia for 1 to 13 years, in 18 whom 24% of those with atypia progressed to carcinoma. It remains uncertain whether endometrial hyperplasia forms a continuum of morphologic severity from simple to complex to atypical as the immediate precursor of endometrial cancer. In Tables 1 and 2, we list 16 women with atypicalhowever, the coexistence of hyperplasia and carcinoma in 26,27 endometrial hyperplasia who declined hysterectomy and some patients provides support for this theory. Also, be- BSO. Except for 1 woman who wanted to preserve her fertility, all women were treated with resectoscopic surgery. Eleven women remain amenorrheic after a median follow-up of 6 years (range years). One woman was lost to follow-up. Two other women were amenorrheic at 4 and 5 years of follow-up but died of unrelated causes. One developed endometrial carcinoma 10.5 years after hysteroscopic surgery. She remains alive and well 3.5 years after hysterectomy, BSO, and adjuvant radiation therapy. cause of the possibility of atypical hyperplasias progressing to cancer, 2,3,18 21 hysterectomy with BSO is considered the treatment of choice for atypical hyperplasia for those patients who have completed their families. Hysterectomy, however, may be difficult or risky for some patients and may be refused by others, especially those who wish to retain their fertility. Medical therapy with oral medroxyprogesterone acetate (MPA, Pfizer, New York, NY) may be an alternative to hysterectomy for women wishing to retain their uterus. However, ongoing surveillance is necessary, and long-term follow-up data are limited. In 1 study, out of 20 patients with atypical hyperplasia treated with oral MPA and followed for a mean of 7 years (range 2 12 years), 25% regressed, 50% persisted, and 25% progressed to carcinoma 5.5 years (range 2 7 years) after starting MPA. Our findings suggest that endometrial resection may be an alternative treatment for atypical endometrial hyperplasia, at least for those patients who decline or are at high-risk for hysterectomy and BSO. The lack of residual atypical hyperplasia in the 6 hysterectomy specimens of patients who underwent hysteroscopic endomyometrial resection provides additional support to this method of treatment and its potential role as an alternative to hysterectomy. However, patients should be compliant with long-term follow-up and intensive surveillance. Conclusion Atypical endometrial hyperplasia is found in approximately 0.35% of women undergoing hysteroscopic endometrial ablation for AUB. Routinely performing endometrial resection, rather than rollerball ablation, in women at high risk for hyperplasia/neoplasia will identify these cases of atypical hyperplasia. Skillful endometrial resection may be an alternative treatment for women with atypical endometrial hyperplasia when hysterectomy is difficult, risky, or refused. Editor s Comments It is important to note that the patients described here had endometrial resection rather than rollerball or global ablations in which endometrial sampling is not an integral part of the procedure (except for the thermal balloon as part of endometrial preparation ). Because adenomatous hyperplasia seen on preablation sampling is usually a contraindication to the procedure, this situation may arise infrequently as these newer procedures gain in popularity. While resec- 3

6 Edris et al Hysteroscopy and atypical endometrial hyperplasia 73 tion as viewed through the hysteroscope is much more dramatic than rollerball ablation, no difference in amenorrhea rates has been demonstrable in the literature over the past decade. One could argue that it s difficult to get endometrial cancer if the has been totally removed or destroyed, but, of course, that s the rub. We all know of individual patients in whom, years after total amenorrhea, menstruation reappears with either a benign or malignant. Keep in mind that postablation insertion of a medicated intrauterine device may be an excellent ancillary measure in these high-risk patients. References 1. Kurman RJ, Norris HJ. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer. 1982;49: Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long-term study of untreated hyperplasia in 170 patients. Cancer. 1985;56: Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol. 1989;160: Silverberg SG, Kurman RJ. Endometrial s and hyperplasias. In: Rosai J, ed. Tumors of the Uterine Corpus and Gestational Trophoblastic Disease. Washington, D.C.: Armed Forces Institute of Pathology; 1992: Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual blood loss: a population study variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45: Shapley M, Jordan K, Croft PR. An epidemiological survey of symptoms of menstrual loss in the community. Br J Gen Pract. 2004;54: MacKenzie IZ, Bibby JG. Critical assessment of dilatation and curettage in 1029 women. Lancet. 1978;2: Koss LG, Schreiber K, Oberlander SG, Moussouris HF, Lesser M. Detection of endometrial carcinoma and hyperplasia in asymptomatic women. Obstet Gynecol. 1984;64: Ash SJ, Farrell SA, Flowerdew G. Endometrial biopsy in DUB. J Reprod Med. 1996;41: Vercellini P, Cortesi I, Oldani S, Moschetta M, De Giorgi O, Crosignani PG. The role of transvaginal ultrasonography and outpatient diagnostic hysteroscopy in the evaluation of patients with menorrhagia. Hum Reprod. 1997;12: Farrell SC, Sampson SL, Ash S. Risk categories for abnormal endometrial biopsy in dysfunctional uterine bleeding. J Obstet Gynecol Can. 2000;22: Spencer CP, Whitehead MI. Endometrial assessment re-visited (Review). Br J Obstet Gynaecol. 1999;106: Vilos GA. Hysteroscopic and nonhysteroscopic endometrial ablation. Obstet Gynecol Clin North Am. 2004;31: , xi. 14. Vilos GA, Lefebvre G, Graves GR. Guidelines for the management of abnormal uterine bleeding: Society of Obstetrics and Gynaecology of Canada (SOGC) Clinical Practice Guidelines. J Obstet Gynaecol Can. 2001;23: Farquhar CM, Lethaby A, Sowter M, Verry J, Baranyai J. An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding. Am J Obstet Gynecol. 1999;181: Orr JJ, Chamberlain D, Kilgone L, Naumann W. Management of endometrial cancer. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin Number 65. August Obstet Gynecol. 2005;106: Vilos GA, Harding PG, Ettler HC. Resectoscopic surgery in 10 women with abnormal uterine bleeding and atypical endometrial hyperplasia. J Am Assoc Gynecol Laparosc. 2002;9: Huang SJ, Amparo E, Fu YS. Histologic classification and behavior of endometrial hyperplasia. Surg Pathol. 1988;23: Baak JP, Wisse-Brekelmans EC, Fleege JC, van der Putten HW, Bezemer PD. Assessment of the risk of endometrial cancer in hyperplasia, by means of morphological and morphometrical features. Pathol Res Pract. 1992;188: Terakawa N, Kigawa J, Taketani Y, et al. The behavior of endometrial hyperplasia: a prospective study Endometrial Hyperplasia Study Group. J Obstet Gynaecol Res. 1997;23: Horn LC, Schnurrbusch U, Bilek K, Hentschel B, Einenkel J. Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment. Int J Gynecol Cancer. 2004;14: Tavassoli F, Kraus FT. Endometrial lesions in uteri resected for atypical endometrial hyperplasia. Am J Clin Pathol. 1978;70: Janicek MF, Rosenshein NB. Invasive endometrial cancer in uteri resected for atypical endometrial hyperplasia. Gynecol Oncol. 1994; 52: Widra EA, Dunton CJ, McHugh M, Palazzo JP. Endometrial hyperplasia and the risk of carcinoma. Int J Gynecol Cancer. 1995;5: Trimble CL. Atypical endometrial hyperplasia: a tough call. Int J Gynecol Cancer. 2005;15: Beutler HK, Dockerty MB, Randall LM. Precancerous lesions of the. Am J Obstet Gynecol. 1963;86: Welch WR, Scully RE. Precancerous lesions of the. Hum Pathol. 1997;8: