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Endometrial Adenocarcinoma in Pregnancy
Gynecologic Oncology 75, 298 –299 (1999) Article ID gyno.1999.5576, available online at http://www.idealibrary.com on
CASE REPORT Endometrial Adenocarcinoma in Pregnancy A. Ayhan, M.D., 1 S. Gunalp, M.D., C. Karaer, M.D., A. Gokoz, M.D., and U. Oz, M.D. Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Sihhiye-Ankara 06100, Turkey Received April 23, 1999
a soft, enlarged uterus. Complete blood count, urinanalysis, and coagulation studies were within normal limits. The blood chorionic gonadotropin level was 4130 mIU/ml. She underwent a suction curettage yielding 50 cc pinkish material. Pathological examination revealed chorionic villi and normal endometrium as well as an area of atypical hyperplasia and welldifferentiated endometrial adenocarcinoma with mucinous differentiation (Fig. 1). She consequently underwent a complete surgical staging procedure including total abdominal hysterectomy, bilateral salphingo-oopherectomy, omentectomy, and bilateral pelvic and paraaortic lymphadenectomy. Pathological examination of the specimen was consistent with grade 1 FIGO stage 1A endometrial adenocarcinoma. She was discharged with no additional treatment and is currently disease free.
Objective. The coexistence of endometrial adenocarcinoma and pregnancy is rare. Most cases are discovered in the first trimester due to irregular bleeding or spontaneous abortion. Case. A 44-year-old woman, gravida 3, para 2, was admitted due to abnormal vaginal bleeding. After complete history, physical examination, and laboratory evaluation, she was diagnosed with spontaneous abortion and underwent a suction curettage. Pathological examination of the tissue included chorionic villi and an area of atypical hyperplasia and endometrial cancer. Conclusion. Recent association between first-trimester spontaneous abortions and subsequent endometrial cancer makes these rare cases of concurrent endometrial cancer and first trimester of pregnancy attractive in that they may disclose insights into the pathophysiology of hormone-dependent cancers. © 1999 Academic Press
Key Words: endometrial adenocarcinoma; pregnancy.
DISCUSSION INTRODUCTION Gravidity and parity have strong inverse relationships with endometrial cancer occurrence. Similarly, women who bear children late in reproductive life may be at lower risk for endometrial cancer than those who complete their families early. Studies confirmed the protective effect of full term pregnancy in endometrial cancer [1]. The unopposed estrogen theory remains the most consistent explanation for hormonaldependent cancers of the female genital system. In the recent large survey for prediction of endometrial cancer, two additional factors remained statistically significant independent of gravidity: a history of ever having had an induced abortion and spontaneous abortions at a late age [1]. Interestingly, nearly all of the 24 cases of endometrial cancer and pregnancy in the literature were detected in first-trimester spontaneous abortions. In the recent case series four of five pregnancies were detected in the first trimester and one was associated with premature live birth [2]. In fact, a total of nine pregnancies were associated with live births since the first time the association was observed in 1927. The association between endometrial cancer and first trimester of pregnancy clashes with studies confirming the protective effect of full-term pregnancy.
Adenocarcinoma of the endometrium with intrauterine pregnancy is extremely rare. To our knowledge only five cases have been associated with a live fetus. Most cases were discovered by dilation and curettage for irregular vaginal bleeding in the first trimester. Ages ranged from 21 to 44 years, and parity, from 0 to 10. In almost all cases a well-differentiated endometrial adenocarcinoma with at most superficial invasion was discovered. CASE REPORT A 44-year-old woman, gravida 3, para 2, whose last menstrual period was 5 weeks ago, was admitted due to abnormal vaginal bleeding. She had menarche at 16 years and had an otherwise unremarkable personal history. She had never used oral contraceptives and had no endocrinologic disease including diabetes. Family history included a father who died of hepatocellular cancer. Physical examination disclosed a normotensive woman 165 cm in height and 60 kg in weight with 1
To whom correspondence should be addressed. Fax: (90) (312) 3116372.
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
298
299
CASE REPORT
FIG. 1. Concurrent endometrial adenocarcinoma and pregnancy, hematoxylin and eosin, 3100.
Human chorionic gonadotropin (hCG) dominates the picture in the first trimester of pregnancy. Besides its support of progesterone production by the corpus luteum, the antiproliferative properties of hCG especially in breast tissue with respect to differentiation are currently under investigation. One of the mechanisms observed in animal models is hCG mediation of its antiproliferative activity by downregulation of insulin-like growth factor 1 gene expression in liver and breast tissue [3]. In support of this hypothesis, it has been observed that hCG, as a differentiating agent and chemopreventive agent, inhibits DMBA-induced breast carcinogenesis in rat through an insulin-like growth factor-dependent mechanism [3]. Additionally, hCG influences gene expression in mammary epithelial cells, supporting its potential role in breast cancer prevention and therapy [4]. Endometrial cancer cell lines have local regulatory systems for their proliferation based on luteinizing hormone-releasing hormone and epidermal growth factor [5]. Tonic effects of hCG on these receptors due to its significantly longer half-life compared with luteinizing hormone may be another factor downregulating tumor proliferation in hormone-dependent tumors. In conclusion, the significant occurrence of endometrial can-
cer and pregnancy in the first trimester and the relationship between first-trimester abortions and future endometrial cancer may explain why the very rare coincidence of these two common conditions occurs mostly in the first trimester. It must, however, be emphasized that the number of live births associated with endometrial cancer is limited, which complicates easy conclusions. REFERENCES 1. McPherson CP, Sellers TA, Potter JD, Bostick RM, Folsom AR: Reproductive factors and risk of endometrial cancer: The Iowa Women’s Health Study. Am J Epidemiol 143:1195–1202, 1996 2. Schammel DP, Mittal KR, Kaplan K, Deligdisch L, Tavassoli FA: Endometrial adenocarcinoma associated with intrauterine pregnancy. A report of five cases and a review of the literature. Int J Gynecologic Pathol 17:327– 335, 1998 3. Huynh H: In vivo regulation of the insulin-like growth factor system of mitogens by human chorionic gonadotropin. Int J Oncol 13:571–575, 1998 4. Srivastava P, Silva ID, Russo J, Mgbonyebi OP, Russo IH: Identification of new genes differentially expressed in breast carcinoma cells treated with human chorionic gonadotropin. Int J Oncol 13:465– 469, 1998 5. Lamharzi N, Halmos G, Armatis P, Schally AV: Expression of mRNA for luteinizing hormone-releasing hormone receptors and epidermal growth factor receptors in human cancer cell lines. Int J Oncol 12:671– 675, 1998
CASE REPORT Endometrial Adenocarcinoma in Pregnancy A. Ayhan, M.D., 1 S. Gunalp, M.D., C. Karaer, M.D., A. Gokoz, M.D., and U. Oz, M.D. Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Sihhiye-Ankara 06100, Turkey Received April 23, 1999
a soft, enlarged uterus. Complete blood count, urinanalysis, and coagulation studies were within normal limits. The blood chorionic gonadotropin level was 4130 mIU/ml. She underwent a suction curettage yielding 50 cc pinkish material. Pathological examination revealed chorionic villi and normal endometrium as well as an area of atypical hyperplasia and welldifferentiated endometrial adenocarcinoma with mucinous differentiation (Fig. 1). She consequently underwent a complete surgical staging procedure including total abdominal hysterectomy, bilateral salphingo-oopherectomy, omentectomy, and bilateral pelvic and paraaortic lymphadenectomy. Pathological examination of the specimen was consistent with grade 1 FIGO stage 1A endometrial adenocarcinoma. She was discharged with no additional treatment and is currently disease free.
Objective. The coexistence of endometrial adenocarcinoma and pregnancy is rare. Most cases are discovered in the first trimester due to irregular bleeding or spontaneous abortion. Case. A 44-year-old woman, gravida 3, para 2, was admitted due to abnormal vaginal bleeding. After complete history, physical examination, and laboratory evaluation, she was diagnosed with spontaneous abortion and underwent a suction curettage. Pathological examination of the tissue included chorionic villi and an area of atypical hyperplasia and endometrial cancer. Conclusion. Recent association between first-trimester spontaneous abortions and subsequent endometrial cancer makes these rare cases of concurrent endometrial cancer and first trimester of pregnancy attractive in that they may disclose insights into the pathophysiology of hormone-dependent cancers. © 1999 Academic Press
Key Words: endometrial adenocarcinoma; pregnancy.
DISCUSSION INTRODUCTION Gravidity and parity have strong inverse relationships with endometrial cancer occurrence. Similarly, women who bear children late in reproductive life may be at lower risk for endometrial cancer than those who complete their families early. Studies confirmed the protective effect of full term pregnancy in endometrial cancer [1]. The unopposed estrogen theory remains the most consistent explanation for hormonaldependent cancers of the female genital system. In the recent large survey for prediction of endometrial cancer, two additional factors remained statistically significant independent of gravidity: a history of ever having had an induced abortion and spontaneous abortions at a late age [1]. Interestingly, nearly all of the 24 cases of endometrial cancer and pregnancy in the literature were detected in first-trimester spontaneous abortions. In the recent case series four of five pregnancies were detected in the first trimester and one was associated with premature live birth [2]. In fact, a total of nine pregnancies were associated with live births since the first time the association was observed in 1927. The association between endometrial cancer and first trimester of pregnancy clashes with studies confirming the protective effect of full-term pregnancy.
Adenocarcinoma of the endometrium with intrauterine pregnancy is extremely rare. To our knowledge only five cases have been associated with a live fetus. Most cases were discovered by dilation and curettage for irregular vaginal bleeding in the first trimester. Ages ranged from 21 to 44 years, and parity, from 0 to 10. In almost all cases a well-differentiated endometrial adenocarcinoma with at most superficial invasion was discovered. CASE REPORT A 44-year-old woman, gravida 3, para 2, whose last menstrual period was 5 weeks ago, was admitted due to abnormal vaginal bleeding. She had menarche at 16 years and had an otherwise unremarkable personal history. She had never used oral contraceptives and had no endocrinologic disease including diabetes. Family history included a father who died of hepatocellular cancer. Physical examination disclosed a normotensive woman 165 cm in height and 60 kg in weight with 1
To whom correspondence should be addressed. Fax: (90) (312) 3116372.
0090-8258/99 $30.00 Copyright © 1999 by Academic Press All rights of reproduction in any form reserved.
298
299
CASE REPORT
FIG. 1. Concurrent endometrial adenocarcinoma and pregnancy, hematoxylin and eosin, 3100.
Human chorionic gonadotropin (hCG) dominates the picture in the first trimester of pregnancy. Besides its support of progesterone production by the corpus luteum, the antiproliferative properties of hCG especially in breast tissue with respect to differentiation are currently under investigation. One of the mechanisms observed in animal models is hCG mediation of its antiproliferative activity by downregulation of insulin-like growth factor 1 gene expression in liver and breast tissue [3]. In support of this hypothesis, it has been observed that hCG, as a differentiating agent and chemopreventive agent, inhibits DMBA-induced breast carcinogenesis in rat through an insulin-like growth factor-dependent mechanism [3]. Additionally, hCG influences gene expression in mammary epithelial cells, supporting its potential role in breast cancer prevention and therapy [4]. Endometrial cancer cell lines have local regulatory systems for their proliferation based on luteinizing hormone-releasing hormone and epidermal growth factor [5]. Tonic effects of hCG on these receptors due to its significantly longer half-life compared with luteinizing hormone may be another factor downregulating tumor proliferation in hormone-dependent tumors. In conclusion, the significant occurrence of endometrial can-
cer and pregnancy in the first trimester and the relationship between first-trimester abortions and future endometrial cancer may explain why the very rare coincidence of these two common conditions occurs mostly in the first trimester. It must, however, be emphasized that the number of live births associated with endometrial cancer is limited, which complicates easy conclusions. REFERENCES 1. McPherson CP, Sellers TA, Potter JD, Bostick RM, Folsom AR: Reproductive factors and risk of endometrial cancer: The Iowa Women’s Health Study. Am J Epidemiol 143:1195–1202, 1996 2. Schammel DP, Mittal KR, Kaplan K, Deligdisch L, Tavassoli FA: Endometrial adenocarcinoma associated with intrauterine pregnancy. A report of five cases and a review of the literature. Int J Gynecologic Pathol 17:327– 335, 1998 3. Huynh H: In vivo regulation of the insulin-like growth factor system of mitogens by human chorionic gonadotropin. Int J Oncol 13:571–575, 1998 4. Srivastava P, Silva ID, Russo J, Mgbonyebi OP, Russo IH: Identification of new genes differentially expressed in breast carcinoma cells treated with human chorionic gonadotropin. Int J Oncol 13:465– 469, 1998 5. Lamharzi N, Halmos G, Armatis P, Schally AV: Expression of mRNA for luteinizing hormone-releasing hormone receptors and epidermal growth factor receptors in human cancer cell lines. Int J Oncol 12:671– 675, 1998