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Not so benign endometrial hyperplasia: Endometrial cancer after endometrial ablation
August 1997, Vd. 4, No. 4
TheJournal of the American Association of Gynecologic Laparoscopists
Not So Benign Endometrial Hyperplasia: Endometrial Cancer after Endometrial Ablation Richard J. Gimpelson, M.D.
Abstract The masking or development of endometrial cancer after endometrial ablation is a concern often alluded to in discussions of complications of endometrial ablation. It is necessary to look for a common factor when this complication occurs. Six cases published in peer-reviewed literature were collected to establish a link between the development of endometrial cancer and endometrial ablation. Preexisting endometrial hyperplasia seems to be the common denominator, and should be considered a contraindication to endometrial ablation until more data are collected.
(l Am Assoc Gynecol Laparosc 4(4):507-511, 1997)
cinoma in women who undergo this form of minimally invasive surgery.
Numerous articles have been published on endometrial ablation or variations since the first reports appeared in the 1980s. 1-4 Various medical methods have been used to make the endometrium easier to ablate or excise?, 6 These contributed to a lower complication rate and helped establish ablation as an excellent alternative to hysterectomy. 7 Of primary concern, however, is the potential for the procedure to mask the presence or delay the diagnosis of endometrial cancer. 8Two proposals to minimize this complication are mechanical preparation of the endometrium 9 and endomyometrial resection.l~ I reviewed six cases of endometrial cancer that appeared in peer-reviewed literature 11-16in an attempt to identify common risk factor(s). Avoiding endometrial ablation in the group with these factors should reduce the frequency of subsequent endometrial car-
Case Reports Patient No. 1 At the time of endometrial resection a 38-year-old, obese, diabetic woman with a 4-year history of menorrhagia was found to have a moderately differentiated adenocarcinoma without myometrial involvement. 11 Hysteroscopy and endometrial curettage performed 3 months before endometrial resection revealed a normal cavity in secretory phase. Total abdominal hysterectomy was performed 4 weeks after resection. Histologic examination revealed granulation tissue and no residual carcinoma. The authors suggested that outpatient biopsy using a
From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine, St. Louis, and private practice in Gynecology, Chesterfield, Missouri. Address reprint requests to Richard J. Gimpelson, M.D., 222 South Woods Mill Road, Suite 400, Chesterfield, MO 63017; fax 314 878 7661. Presented at the World Congress of Hysteroscopy, Miami, Florida, February 9-11, 1996.
507
Endometrial Carcinoma after Endometrial Ablation Gimpelson
resectoscope to obtain a full-thickness sample should be considered in high-risk women. Some confusion exists about this patient because a later article by the same authors 17 stated that she was readmitted for hysterectomy 6 weeks after resection, and that histologic examination of curettings 4 months before resection revealed only cystic hyperplasia.
Patient No. 3 A 39-year-old woman with a 15-year history of polycystic ovary disease was diagnosed with stage Ia, grade I endometrial adenocarcinoma 8 months after endometrial ablation with the rollerball electrode. 13 Curettage 8 years earlier revealed moderate to severe endometrial hyperplasia, and the woman was prescribed megestral acetate 80 mg/day. After 4 months of drug therapy, curettage revealed secretory and decidual endometrium, and the dosage of megestral acetate was reduced to 40 mg/day. Nine months later, a third curettage demonstrated scanty endometrium with sparse glands and stroma with decidual changes. At this time, the patient began cyclic therapy with medroxyprogesterone acetate 20 mg/day for 14 days/month. Two and one-half years later she discontinued the drug on her own and did not return for 3 years, 4 months before ablation. A fourth curettage at that time revealed proliferative endometrium with small areas of cystic endometrial hyperplasia. The woman took leuprolide acetate microspheres 3 to 4 months before ablation. At ablation, the endometrium was slightly thicker than expected after gonadotropin-releasing hormone agonist suppression, but with no visible areas of proliferation. Definitive surgery consisted of total abdominal extrafascial hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and pelvic and peritoneal lymph node dissection with peritoneal washings. Although hysteroscopy performed before ablation was not reported, the authors concluded that the neoplasm was missed by both curettage and hysteroscopic visualization.
Patient No. 2 A 56-year-old woman had moderately differentiated, superficially invasive adenocarcinoma of the endometrium 5 years after resectoscopic ablation of the endometrium using a coagulation electrode.12 Additional atypical glandular hyperplasia and adenomyosis were present in the surgical specimen. Three years before ablation the patient was diagnosed with adenomatous hyperplasia without atypia and treated with medroxyprogesterone acetate. One year before ablation a biopsy specimen revealed mild adenomatous hyperplasia, and cyclic progesterone therapy was continued. Abiopsy specimen 1 to 2 months before ablation revealed breakdown changes and exogenous progestin effect. The patient was lost to follow-up for 5 years, and then returned with complaints of heavy menses, at which time endometrial biopsy was consistent with well-differentiated adenocarcinoma. Treatment consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node sampling, and vaginal cuff irradiation. It should be noted that this woman's medical history was significant for hypertension, diabetes, obesity, and Duke stage B colon cancer (negative margins). In the discussion of this case, the authors expressed concern about masking adenocarcinoma because of blood pockets and synechiae that form after endometrial ablation. They also suggested that adenocarcinoma might develop in deep rests of adenomyosis. The authors stated that use of the resectoscope may have caused less scarring than the Nd:YAG laser and thus resulted in the patient experiencing early vaginal bleeding. In addition, the authors suggested adding progesterone to estrogen replacement in postmenopausal women after endometrial ablation. It should be noted that this woman's medical history was significant for hypertension, diabetes, obesity, and Duke stage B colon cancer (negative margins).
Patient No. 4 A 52-year-old diabetic, hypertensive, markedly obese (5 ft 4 in., 310 lbs) woman was diagnosed with well-differentiated adenocarcinoma confined to the uterine cavity with superficial myometrial invasion, 6 months after endometrial ablation with the rollerball electrode. TM She experienced menopause 3.5 years before ablation. Eighteen months before ablation she underwent fractional dilatation and curettage (D&C), with curettings revealing a small focus of benign adenomatous hyperplasia. Four months before ablation, the patient experienced persistent vaginal bleeding with increased uterine depth from 9 to 10 cm.
508
August 1997, Vol. 4, No. 4
TheJournal of the American Association of Gynecologic Laparoscopists
Hysteroscopic examination was unsuccessful, and D&C revealed only atrophic endometrial tissue. Four months later the woman underwent endometrial ablation. She subsequently underwent exploratory laparotomy with pelvic washings, and total abdominal hysterectomy with bilateral salpingo-oophorectomy. The authors concluded that adequate preoperative sampling revealed benign endometrium that did not interdict performance of hysteroscopic ablation. They further concluded that at-risk patients should be followed carefully after ablation with regular endometrial sampling procedures (brush, Pipelle or Novak curette).
a 1-cm, hypoechoic lesion in the endometrial cavity, and an endometrial biopsy specimen revealed adenomatous hyperplasia with focal architectural atypia, but not cytologic atypia. After 4 weeks of danazol, endometrial ablation and polypectomy were performed. The pathology report was secretory endometrium and fragments of focally ulcerated endometrial polyp. Two and one-half years later the patient underwent total abdominal hysterectomy, bilateral salpingooophorectomy, and Marshall-Marchetti-Krantz procedure for stress urinary incontinence. Grade I, focal grade II adenocarcinoma of the endometrium was discovered on pathology evaluation. The authors emphasized the importance of patient selection, education, and definitive preoperative work-up involving more than endometrial sampling and ultrasound examination, in addition to careful postoperative surveillance.
Patient No. 5 A 04-year-old woman was diagnosed with metastatic endometrial adenocarcinoma 15 months after endometrial ablation with a resectoscope. 15 She was morbidly obese, was hypertensive, and had diabetes mellitus. Menopause occurred 8 years before ablation. Two years before ablation she underwent D&C for postmenopausal bleeding. The curettings revealed benign endometrial tissue (specific histopathologic interpretation not described). Medroxyprogesterone acetate was prescribed but was unsuccessful in controlling the bleeding. The patient refused hysterectomy, and endometrial ablation was offered as an alternative. Two months of danocrine therapy preceded ablation. Before danocrine therapy began, endometrial biopsy revealed adenomatous hyperplasia. At the time of ablation, curettage revealed an endometrial polyp and hyperplastic endometrium with focal atypia. Although bleeding recurred 1 month after ablation, she refused hysterectomy until 15 months later. Treatment consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, and excision of umbilical mass, followed by two courses of doxoorubicin and cisplatin. Uterine and umbilical histopathology was consistent with poorly differentiated endometrial adenocarcinoma.
Discussion
Close patient follow-up including evaluation for abnormal bleeding is vital to patients who may be at high risk for developing adenocarcinoma after endometrial ablation. This would include evaluation of abnormal bleeding occurring after endometrial ablation. However, it is not clear what constitutes abnormal bleeding after endometrial ablation, or what is the best way to evaluate it. Should one do aspiration biopsy, sharp curettage, suction curettage, or repeat hysteroscopy with biopsy and possible curettage? Is ultrasound valuable in the follow-up of patients at risk of hyperplasia? These are questions that at the present time do not have answers. In my practice, women who report an increase in flow 6 months after endometrial ablation, or who report any vaginal bleeding after 1 year of postablation amenorrhea, undergo hysteroscopic examination with biopsy or curettage. At the time of writing, no cases of endometrial hyperplasia or uterine cancer have been found in my series of patients. This leads me to conclude that some other factor may contribute to the risk of developing adenocarcinoma of the endometrium. All six patients described in the literature were obese. Five of them were diabetics. Four obese diabetics were also hypertensive. The one nondiabetic woman had polycystic ovary syndrome. Thus, all of these women had histories placing them at risk for developing uterine cancer. Authors of the second report concluded that the use of the resectoscope caused less scarfing than the Nd:YAG laser and led to early vaginal bleeding. There are no
Patient No. 6 A 58-year-old, obese, hypertensive, diabetic woman was diagnosed with stage I endometrial cancer 2.5 years after rollerball endometrial ablation and resection of endometrial polyp with the loop electrode. 16 Five years before ablation she had an endometrial biopsy for intermittent spotting. The pathologist reported proliferative endometrium, and the patient subsequently agreed to begin progesterone therapy. Two months before ablation transvaginal ultrasound revealed
509
Endometrial Carcinoma after Endometrial Ablation Gimpelson
scientific data to support this statement, and in fact all six patients had uterine adenocarcinoma after endometrial ablation by resectoscope. At the present time, to my knowledge, no case of adenocarcinoma of the endometrium has been reported in a woman who underwent endometrial ablation with the Nd:YAG laser. Several authors commented on adenomyosis as a possible cause on the basis of buried rests of endometrium, but it is likely that many women undergoing endometrial ablation, both successful and unsuccessful, have adenomyosis. It should be noted that hysteroscopy was performed before endometrial ablation in only one of the six patients. Only one common link can place these women at risk for developing adenocarcinoma of the endometrium: they all were reported to have benign hyperplasia before endometrial ablation. Although simple benign or cystic hyperplasia was not thought to be a risk factor in the past, a recent study presents a very different view of that risk. Eleven of 31 women diagnosed with endometrial adenocarcinoma were diagnosed with hyperplasia from 4 months to 8 years earlier, and 6 of those 11 had only simple benign or cystic hyperplasia. 19Thus the potential risk to develop the malignancy was already present in their uteri at the time they were evaluated before ablation. It could be argued that none of the six women should have undergone endometrial ablation because of preexisting hyperplasia. Lentz and I reported atypical hyperplasia found during endometrial ablation. 2~ Although directed hysteroscopic biopsy at the time of ablation found the lesion, a biopsy 5 months before ablation revealed mild cystic hyperplasia. Thus this woman's history is consistent with those of the six patients described here, and if atypical hyperplasia had not been discovered during ablation, she may have become the seventh case report. Suggestions to reduce the risk of developing adenocarcinoma of the endometrium by picking up precursors at the time of ablation include mechanical preparation of the endometrium by suction curettage 9 and endomyometrial resection in the unprepared endometrium. However, both methods would give retrospective results in that the patient would have already undergone endometrial ablation and incurred the small surgical risk and not so small surgical costs, and would still require additional definitive treatment. The best way to avoid the development of adenocarcinoma is to screen patients carefully by hysteroscopy and directed biopsy if indicated, or hysteroscopy and curettage 21to
pick up endometrial hyperplasia before ablation, and then treat by means other than endometrial ablation.
Summary Benign hyperplasia is not so benign in women who undergo endometrial ablation. It should be considered a contraindication to the procedure and remain such until appropriate studies are carried out to assess the value and risk of ablation in the presence of benign endometrial hyperplasia. References
510
1. Goldrath MH, Fuller TA, Segal S: Laser photovaporization of the endometrium for the treatment of menorrhagia. Am J Obstet Gynecol 140:14-19, 1981 2. Loffer FD: Hysteroscopic endometrial ablation with the Nd:YAG laser using a non-touch technique. Obstet Gynecol 69:679-682, 1987 3. DeCherney AH, Desmond MC, Lavy G, et al: Endometrial ablation for intractable uterine bleeding: Hysteroscopic resection. Obstet Gynecol 70:668-670, 1987 4. Vancaillie TG: Electrocoagulation of the endometrium with the ball end resectoscope. Obstet Gynecol 74:425-427, 1989 5. Goldrath MH: Use of danazol in hysteroscopic surgery for menorrhagia. J Reprod Med 35:91-96, 1990 6. Brooks PG, Serden SP, Davos I: Hormonal inhibition of the endometrium for resectoscopic endometrial ablation. Am J Obstet Gynecol 164:1601-1606, 1991 7. Hulka JF, Peterson HB, Phillips JM, et al: Operative hysteroscopy: American Association of Gynecologic Laparoscopists' 1993 membership survey. J Am Assoc Gynecol Laparosc 2:131-132, 1995 8. Loffer FD: Complications of hysteroscopy~Their cause, prevention, and correcton. J Am Assoc Gynecol Laparosc 3:11-26, 1995 9. Gimpelson RJ, Kaigh J: Mechanical preparation of the endometrium before endometrial ablation. J Reprod Med 37:691, 1992 10. Wortman M, Daggett A: Hysteroscopic endomyometrial resection: A new technique for the treatment of menorrhagia. Obstet Gynecol 83:295-299, 1994
August ] 997, Vd. 4, No. 4
The Journal of the American Association of Gynecologic Laparoscopists
11. Dwyer NA, Stirrat GM: Early endometrial carcinoma: An incidental finding after endometrial ablation for dysfunctional uterine bleeding. Br J Obstet Gynaecol 98:733-734, 1991
16. Margolis MT, Thoen LD, Boike GM, et al: Asymptomatic endometrial carcinoma after endometrial ablation. Int J Gynaecol Obstet 51:255-258, 1995 17. Dwyer N, Hutton J, Stirrat GM: Randomized controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia. Br J Obstet Gynaecol 100:237-243, 1993
12. Copperman AB, DeCberney AH, Olive DL: A case of endometrial cancer after endometrial ablation for dysfunctional uterine bleeding. Obstet Gyneco183:640-642, 1993
18. Gusberg SB: The individual at high risk for endometrial carcinoma.Am J Obstet Gyneco1126:535-542, 1976
13. Ramey JW, Koonings PP, Given FT, et al: The process of carcinogenesis for endometrial adenocarcinoma could be short: Development of a malignancy after endometrial ablation.Am J Obstet Gyneco1170:1370-1371, 1994
19. Gambrell RD: The "red queen" and endometrial hyperplasia [letter]. Fertil Steril 61:401, 1994
14. Baggish MS, Ringgenberg E, Sze EHM: Adenocarcinoma of the corpus uteri after endometrial ablation. J Gynecol Surg 11:91-94, 1995
20. Gimpelson RJ, Lentz RD: Endometrial ablation: A report of four cases. J Reprod Med 38:592-594, 1993
15. Horowitz IR, Copas PR, Aaronoff M, et al: Endometrial adenocarcinoma following endometrial ablation for postmenopausal bleeding: A case report. Gynecol Oncol 56:460-463, 1995
21. Gimpelson RJ, Rappold HO: A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. Am J Obstet Gynecol 185:489--492, 1988
511
TheJournal of the American Association of Gynecologic Laparoscopists
Not So Benign Endometrial Hyperplasia: Endometrial Cancer after Endometrial Ablation Richard J. Gimpelson, M.D.
Abstract The masking or development of endometrial cancer after endometrial ablation is a concern often alluded to in discussions of complications of endometrial ablation. It is necessary to look for a common factor when this complication occurs. Six cases published in peer-reviewed literature were collected to establish a link between the development of endometrial cancer and endometrial ablation. Preexisting endometrial hyperplasia seems to be the common denominator, and should be considered a contraindication to endometrial ablation until more data are collected.
(l Am Assoc Gynecol Laparosc 4(4):507-511, 1997)
cinoma in women who undergo this form of minimally invasive surgery.
Numerous articles have been published on endometrial ablation or variations since the first reports appeared in the 1980s. 1-4 Various medical methods have been used to make the endometrium easier to ablate or excise?, 6 These contributed to a lower complication rate and helped establish ablation as an excellent alternative to hysterectomy. 7 Of primary concern, however, is the potential for the procedure to mask the presence or delay the diagnosis of endometrial cancer. 8Two proposals to minimize this complication are mechanical preparation of the endometrium 9 and endomyometrial resection.l~ I reviewed six cases of endometrial cancer that appeared in peer-reviewed literature 11-16in an attempt to identify common risk factor(s). Avoiding endometrial ablation in the group with these factors should reduce the frequency of subsequent endometrial car-
Case Reports Patient No. 1 At the time of endometrial resection a 38-year-old, obese, diabetic woman with a 4-year history of menorrhagia was found to have a moderately differentiated adenocarcinoma without myometrial involvement. 11 Hysteroscopy and endometrial curettage performed 3 months before endometrial resection revealed a normal cavity in secretory phase. Total abdominal hysterectomy was performed 4 weeks after resection. Histologic examination revealed granulation tissue and no residual carcinoma. The authors suggested that outpatient biopsy using a
From the Department of Obstetrics and Gynecology, St. Louis University School of Medicine, St. Louis, and private practice in Gynecology, Chesterfield, Missouri. Address reprint requests to Richard J. Gimpelson, M.D., 222 South Woods Mill Road, Suite 400, Chesterfield, MO 63017; fax 314 878 7661. Presented at the World Congress of Hysteroscopy, Miami, Florida, February 9-11, 1996.
507
Endometrial Carcinoma after Endometrial Ablation Gimpelson
resectoscope to obtain a full-thickness sample should be considered in high-risk women. Some confusion exists about this patient because a later article by the same authors 17 stated that she was readmitted for hysterectomy 6 weeks after resection, and that histologic examination of curettings 4 months before resection revealed only cystic hyperplasia.
Patient No. 3 A 39-year-old woman with a 15-year history of polycystic ovary disease was diagnosed with stage Ia, grade I endometrial adenocarcinoma 8 months after endometrial ablation with the rollerball electrode. 13 Curettage 8 years earlier revealed moderate to severe endometrial hyperplasia, and the woman was prescribed megestral acetate 80 mg/day. After 4 months of drug therapy, curettage revealed secretory and decidual endometrium, and the dosage of megestral acetate was reduced to 40 mg/day. Nine months later, a third curettage demonstrated scanty endometrium with sparse glands and stroma with decidual changes. At this time, the patient began cyclic therapy with medroxyprogesterone acetate 20 mg/day for 14 days/month. Two and one-half years later she discontinued the drug on her own and did not return for 3 years, 4 months before ablation. A fourth curettage at that time revealed proliferative endometrium with small areas of cystic endometrial hyperplasia. The woman took leuprolide acetate microspheres 3 to 4 months before ablation. At ablation, the endometrium was slightly thicker than expected after gonadotropin-releasing hormone agonist suppression, but with no visible areas of proliferation. Definitive surgery consisted of total abdominal extrafascial hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and pelvic and peritoneal lymph node dissection with peritoneal washings. Although hysteroscopy performed before ablation was not reported, the authors concluded that the neoplasm was missed by both curettage and hysteroscopic visualization.
Patient No. 2 A 56-year-old woman had moderately differentiated, superficially invasive adenocarcinoma of the endometrium 5 years after resectoscopic ablation of the endometrium using a coagulation electrode.12 Additional atypical glandular hyperplasia and adenomyosis were present in the surgical specimen. Three years before ablation the patient was diagnosed with adenomatous hyperplasia without atypia and treated with medroxyprogesterone acetate. One year before ablation a biopsy specimen revealed mild adenomatous hyperplasia, and cyclic progesterone therapy was continued. Abiopsy specimen 1 to 2 months before ablation revealed breakdown changes and exogenous progestin effect. The patient was lost to follow-up for 5 years, and then returned with complaints of heavy menses, at which time endometrial biopsy was consistent with well-differentiated adenocarcinoma. Treatment consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node sampling, and vaginal cuff irradiation. It should be noted that this woman's medical history was significant for hypertension, diabetes, obesity, and Duke stage B colon cancer (negative margins). In the discussion of this case, the authors expressed concern about masking adenocarcinoma because of blood pockets and synechiae that form after endometrial ablation. They also suggested that adenocarcinoma might develop in deep rests of adenomyosis. The authors stated that use of the resectoscope may have caused less scarring than the Nd:YAG laser and thus resulted in the patient experiencing early vaginal bleeding. In addition, the authors suggested adding progesterone to estrogen replacement in postmenopausal women after endometrial ablation. It should be noted that this woman's medical history was significant for hypertension, diabetes, obesity, and Duke stage B colon cancer (negative margins).
Patient No. 4 A 52-year-old diabetic, hypertensive, markedly obese (5 ft 4 in., 310 lbs) woman was diagnosed with well-differentiated adenocarcinoma confined to the uterine cavity with superficial myometrial invasion, 6 months after endometrial ablation with the rollerball electrode. TM She experienced menopause 3.5 years before ablation. Eighteen months before ablation she underwent fractional dilatation and curettage (D&C), with curettings revealing a small focus of benign adenomatous hyperplasia. Four months before ablation, the patient experienced persistent vaginal bleeding with increased uterine depth from 9 to 10 cm.
508
August 1997, Vol. 4, No. 4
TheJournal of the American Association of Gynecologic Laparoscopists
Hysteroscopic examination was unsuccessful, and D&C revealed only atrophic endometrial tissue. Four months later the woman underwent endometrial ablation. She subsequently underwent exploratory laparotomy with pelvic washings, and total abdominal hysterectomy with bilateral salpingo-oophorectomy. The authors concluded that adequate preoperative sampling revealed benign endometrium that did not interdict performance of hysteroscopic ablation. They further concluded that at-risk patients should be followed carefully after ablation with regular endometrial sampling procedures (brush, Pipelle or Novak curette).
a 1-cm, hypoechoic lesion in the endometrial cavity, and an endometrial biopsy specimen revealed adenomatous hyperplasia with focal architectural atypia, but not cytologic atypia. After 4 weeks of danazol, endometrial ablation and polypectomy were performed. The pathology report was secretory endometrium and fragments of focally ulcerated endometrial polyp. Two and one-half years later the patient underwent total abdominal hysterectomy, bilateral salpingooophorectomy, and Marshall-Marchetti-Krantz procedure for stress urinary incontinence. Grade I, focal grade II adenocarcinoma of the endometrium was discovered on pathology evaluation. The authors emphasized the importance of patient selection, education, and definitive preoperative work-up involving more than endometrial sampling and ultrasound examination, in addition to careful postoperative surveillance.
Patient No. 5 A 04-year-old woman was diagnosed with metastatic endometrial adenocarcinoma 15 months after endometrial ablation with a resectoscope. 15 She was morbidly obese, was hypertensive, and had diabetes mellitus. Menopause occurred 8 years before ablation. Two years before ablation she underwent D&C for postmenopausal bleeding. The curettings revealed benign endometrial tissue (specific histopathologic interpretation not described). Medroxyprogesterone acetate was prescribed but was unsuccessful in controlling the bleeding. The patient refused hysterectomy, and endometrial ablation was offered as an alternative. Two months of danocrine therapy preceded ablation. Before danocrine therapy began, endometrial biopsy revealed adenomatous hyperplasia. At the time of ablation, curettage revealed an endometrial polyp and hyperplastic endometrium with focal atypia. Although bleeding recurred 1 month after ablation, she refused hysterectomy until 15 months later. Treatment consisted of total abdominal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, and excision of umbilical mass, followed by two courses of doxoorubicin and cisplatin. Uterine and umbilical histopathology was consistent with poorly differentiated endometrial adenocarcinoma.
Discussion
Close patient follow-up including evaluation for abnormal bleeding is vital to patients who may be at high risk for developing adenocarcinoma after endometrial ablation. This would include evaluation of abnormal bleeding occurring after endometrial ablation. However, it is not clear what constitutes abnormal bleeding after endometrial ablation, or what is the best way to evaluate it. Should one do aspiration biopsy, sharp curettage, suction curettage, or repeat hysteroscopy with biopsy and possible curettage? Is ultrasound valuable in the follow-up of patients at risk of hyperplasia? These are questions that at the present time do not have answers. In my practice, women who report an increase in flow 6 months after endometrial ablation, or who report any vaginal bleeding after 1 year of postablation amenorrhea, undergo hysteroscopic examination with biopsy or curettage. At the time of writing, no cases of endometrial hyperplasia or uterine cancer have been found in my series of patients. This leads me to conclude that some other factor may contribute to the risk of developing adenocarcinoma of the endometrium. All six patients described in the literature were obese. Five of them were diabetics. Four obese diabetics were also hypertensive. The one nondiabetic woman had polycystic ovary syndrome. Thus, all of these women had histories placing them at risk for developing uterine cancer. Authors of the second report concluded that the use of the resectoscope caused less scarfing than the Nd:YAG laser and led to early vaginal bleeding. There are no
Patient No. 6 A 58-year-old, obese, hypertensive, diabetic woman was diagnosed with stage I endometrial cancer 2.5 years after rollerball endometrial ablation and resection of endometrial polyp with the loop electrode. 16 Five years before ablation she had an endometrial biopsy for intermittent spotting. The pathologist reported proliferative endometrium, and the patient subsequently agreed to begin progesterone therapy. Two months before ablation transvaginal ultrasound revealed
509
Endometrial Carcinoma after Endometrial Ablation Gimpelson
scientific data to support this statement, and in fact all six patients had uterine adenocarcinoma after endometrial ablation by resectoscope. At the present time, to my knowledge, no case of adenocarcinoma of the endometrium has been reported in a woman who underwent endometrial ablation with the Nd:YAG laser. Several authors commented on adenomyosis as a possible cause on the basis of buried rests of endometrium, but it is likely that many women undergoing endometrial ablation, both successful and unsuccessful, have adenomyosis. It should be noted that hysteroscopy was performed before endometrial ablation in only one of the six patients. Only one common link can place these women at risk for developing adenocarcinoma of the endometrium: they all were reported to have benign hyperplasia before endometrial ablation. Although simple benign or cystic hyperplasia was not thought to be a risk factor in the past, a recent study presents a very different view of that risk. Eleven of 31 women diagnosed with endometrial adenocarcinoma were diagnosed with hyperplasia from 4 months to 8 years earlier, and 6 of those 11 had only simple benign or cystic hyperplasia. 19Thus the potential risk to develop the malignancy was already present in their uteri at the time they were evaluated before ablation. It could be argued that none of the six women should have undergone endometrial ablation because of preexisting hyperplasia. Lentz and I reported atypical hyperplasia found during endometrial ablation. 2~ Although directed hysteroscopic biopsy at the time of ablation found the lesion, a biopsy 5 months before ablation revealed mild cystic hyperplasia. Thus this woman's history is consistent with those of the six patients described here, and if atypical hyperplasia had not been discovered during ablation, she may have become the seventh case report. Suggestions to reduce the risk of developing adenocarcinoma of the endometrium by picking up precursors at the time of ablation include mechanical preparation of the endometrium by suction curettage 9 and endomyometrial resection in the unprepared endometrium. However, both methods would give retrospective results in that the patient would have already undergone endometrial ablation and incurred the small surgical risk and not so small surgical costs, and would still require additional definitive treatment. The best way to avoid the development of adenocarcinoma is to screen patients carefully by hysteroscopy and directed biopsy if indicated, or hysteroscopy and curettage 21to
pick up endometrial hyperplasia before ablation, and then treat by means other than endometrial ablation.
Summary Benign hyperplasia is not so benign in women who undergo endometrial ablation. It should be considered a contraindication to the procedure and remain such until appropriate studies are carried out to assess the value and risk of ablation in the presence of benign endometrial hyperplasia. References
510
1. Goldrath MH, Fuller TA, Segal S: Laser photovaporization of the endometrium for the treatment of menorrhagia. Am J Obstet Gynecol 140:14-19, 1981 2. Loffer FD: Hysteroscopic endometrial ablation with the Nd:YAG laser using a non-touch technique. Obstet Gynecol 69:679-682, 1987 3. DeCherney AH, Desmond MC, Lavy G, et al: Endometrial ablation for intractable uterine bleeding: Hysteroscopic resection. Obstet Gynecol 70:668-670, 1987 4. Vancaillie TG: Electrocoagulation of the endometrium with the ball end resectoscope. Obstet Gynecol 74:425-427, 1989 5. Goldrath MH: Use of danazol in hysteroscopic surgery for menorrhagia. J Reprod Med 35:91-96, 1990 6. Brooks PG, Serden SP, Davos I: Hormonal inhibition of the endometrium for resectoscopic endometrial ablation. Am J Obstet Gynecol 164:1601-1606, 1991 7. Hulka JF, Peterson HB, Phillips JM, et al: Operative hysteroscopy: American Association of Gynecologic Laparoscopists' 1993 membership survey. J Am Assoc Gynecol Laparosc 2:131-132, 1995 8. Loffer FD: Complications of hysteroscopy~Their cause, prevention, and correcton. J Am Assoc Gynecol Laparosc 3:11-26, 1995 9. Gimpelson RJ, Kaigh J: Mechanical preparation of the endometrium before endometrial ablation. J Reprod Med 37:691, 1992 10. Wortman M, Daggett A: Hysteroscopic endomyometrial resection: A new technique for the treatment of menorrhagia. Obstet Gynecol 83:295-299, 1994
August ] 997, Vd. 4, No. 4
The Journal of the American Association of Gynecologic Laparoscopists
11. Dwyer NA, Stirrat GM: Early endometrial carcinoma: An incidental finding after endometrial ablation for dysfunctional uterine bleeding. Br J Obstet Gynaecol 98:733-734, 1991
16. Margolis MT, Thoen LD, Boike GM, et al: Asymptomatic endometrial carcinoma after endometrial ablation. Int J Gynaecol Obstet 51:255-258, 1995 17. Dwyer N, Hutton J, Stirrat GM: Randomized controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia. Br J Obstet Gynaecol 100:237-243, 1993
12. Copperman AB, DeCberney AH, Olive DL: A case of endometrial cancer after endometrial ablation for dysfunctional uterine bleeding. Obstet Gyneco183:640-642, 1993
18. Gusberg SB: The individual at high risk for endometrial carcinoma.Am J Obstet Gyneco1126:535-542, 1976
13. Ramey JW, Koonings PP, Given FT, et al: The process of carcinogenesis for endometrial adenocarcinoma could be short: Development of a malignancy after endometrial ablation.Am J Obstet Gyneco1170:1370-1371, 1994
19. Gambrell RD: The "red queen" and endometrial hyperplasia [letter]. Fertil Steril 61:401, 1994
14. Baggish MS, Ringgenberg E, Sze EHM: Adenocarcinoma of the corpus uteri after endometrial ablation. J Gynecol Surg 11:91-94, 1995
20. Gimpelson RJ, Lentz RD: Endometrial ablation: A report of four cases. J Reprod Med 38:592-594, 1993
15. Horowitz IR, Copas PR, Aaronoff M, et al: Endometrial adenocarcinoma following endometrial ablation for postmenopausal bleeding: A case report. Gynecol Oncol 56:460-463, 1995
21. Gimpelson RJ, Rappold HO: A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage. Am J Obstet Gynecol 185:489--492, 1988
511