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Endometrial adenocarcinoma in teenagers
Adolesc Pediatr Gynecol (1989) 2: 157 -159
Adolescent and Pediatric Gynecology © 1989 Springer-Verlag New York Inc.
Endometrial Adenocarcinoma in Teenagers Dale W. Stovall, M.D., Ralph 1. Anderson, M.D., and Frank D. De Leon, M.D. Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, Texas
Abstract. Adenocarcinoma of the endometrium is an extremely rare finding in the teenage population. Two case reports of 17-year-old teenagers with endometrial carcinoma are presented. Both patients have a history of prolonged periods of anovulation which supports the association between unopposed prolonged estrogen effect and the development of endometrial carcinoma.
Key Words. Endometrial carcinoma-Chronic anovulation-Endometrial biopsy
Introduction Adenocarcinoma of the endometrium commonly afflicts female patients over 40 years of age, with the diagnosis most frequently made between the ages of 50 and 65. Only about 5% of the women affected are under 40, and the disease is extremely rare in the teenage population. 1 Because of this rarity, we present two cases of endometrial adenocarcinoma in 17year-old women diagnosed within a 6-month period at the Texas Tech University Health Science Center in Lubbock. The clinical presentation, as well as the need for histology screening in the teenager who has a prolonged history of unopposed estrogen exposure, is discussed.
Case Reports The first patient, a 17 -year-old nulligravida, presented with a chief complaint of heavy and. irregular menstrual bleeding of 3 years duration. She was preAddress reprint requests to: F.D. De Leon, M.D., Department of Obstetrics and Gynecology, Texas Tech Health Sciences Center, Lubbock, Texas 79430, USA. Presented in part at the Third Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology held in Houston, TX, September, 1988.
viously diagnosed as having precocious puberty. She had experienced menarche at age 9 and thelarche and adrenarche at age 8. Her evaluation for precocious puberty included skull films, computed tomography scan of the abdomen and pelvis, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH), testosterone, and dehydroepiandrosterone sulfate (DHEAS), all within normal limits. Hand-wrist films revealed an advanced bone age and all other test findings were consistent with constitutional, true sexual precocity. Her physical examination was remarkable for short stature (4'4"), and the presence of situs inversus. Pelvic examination revealed a lO-week sized uterus, which sounded to 9 cm. A dilatation and curettage was performed, which revealed crowding of the endometrial glands and hyperchromatic nuclei with irregular nuclear contours. There were 35 mitotic figures noted in 50 high power fields and the diagnosis of stage IBGI adenocarcinoma was made (Fig. 1). Her treatment consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy. Peritoneal cytologic sampling revealed no tumor spread. The ovaries were polycystic on gross examination and the histologic examination, confirming the diagnosis, showed numerous small cortical cysts lined by granulosa cells with stromal luteinization. There was no evidence of corpus lutea, corpora albicans, or ovarian stromal tumor. The second patient is a 17-year-old nulligravida, who presented with a 2-year history of menometrorrhagia requiring dilatation and curettage for control. She had menarche at age 13. Her physical examination was remarkable for obesity (266 pounds), which was at the 95th percentile for her age. She also demonstrated mild hirsutism by the Ferriman and Gallwey scoring system with Grade II terminal hair on the upper lip and chin areas, and Grade I on the chest. Pelvic examination revealed a slightly enlarged uterus, which sounded to 8 cm. Histologic examination of the endometrium revealed a well-differentiated adenocarcinoma with obvious superficial myometrial invasion.
158
Stovall et al.:
Teenage Endometrial Adenocarcinoma
Fig. 1. Uterine endometrium reveals well-differentiated adenocarcinoma. Architecturally there are "back to back" glands and there is evidence of nuclei stratification.
Focal areas of squamous metaplasia were seen, and a diagnosis of stage lAG 1 adenoacanthoma was made. Total abdominal hysterectomy with bilateral salpingooophorectomy was performed and the superficial myometrial invasion was confirmed (Fig. 2). No enlarged lymph nodes were palpable in the pelvic or periaortic areas, and the peritoneal washings were negative. The ovaries were enlarged and polycystic in appearance and their histology was again confirmatory. The slides from both patients were reviewed at another institution which confirmed our findings.
Discussion Adenocarcinoma of the endometrium is most commonly found in the postmenopausal woman, with the
Fig. 2. Section from the endometrium reveals carcinomatous glands invading the smooth muscle cells of the myometrium. Arrows reveal area of invasion.
peak incidence occurring between 50 and 65 years of age. 2 Risk factors in this population include onset of menopause after the age of 49, obesity, race, parity, and estrogen intake. 3 Another major group at risk are those patients in the reproductive years who have a history of chronic anovulation, such as in Stein-Leventhal syndrome with its characteristic obesity, hirsutism, irregular menses, and infertility. 4 Although the etiology of the chronic anovulation syndrome is not known, it is believed to be multifactorial in origin, and in many instances begins in adolescence. The 2 patients presented emphasize the importance of recognizing chronic anovulation in a young population. Despite their young age, these patients had a history of chronic, unopposed estrogen exposure. A history of precocious puberty, early follicular function, and chronic anovulation characterized the first patient. The second patient also had risk factors, including a history of chronic anovulation and morbid obesity. Adipose tissue is a known source for peripheral conversion of androgens to estrogens. 5 Endometrial sampling, an accepted procedure to detect endometrial cancer in patients 35 years and older with persistent anovulatory bleeding may need to be extended to younger patients under very special circumstances; however, it is difficult to select which patients in the adolescent age group may benefit from this procedure. We have described two adolescents who were unique in their age group and who had significant risk factors for prolonged and/or increased unopposed estrogen exposure. It is this group of adolescents that may benefit from endometrial sampling. Factors that affect prognosis in endometrial carcinoma include the stage of the disease, degree of differentiation, depth of myometrial invasion, and the histologic pattern. 6- 8 Each of these variables was carefully considered in the final decision for treatment. Histologically, the first case revealed adenocarcinoma and the second, adenocarcinoma with squamous metaplasia both of which have more favorable prognosis than other patterns including adenosquamous, clear cell carcinoma, and papillary. Both carcinomas were highly differentiated tumors and therefore Grade I. Nevertheless, the remaining two categories, stage and myometrial invasion, give an indication of the total tumor volume. The first patient had Stage IB disease with a 9 cm uterus and the second had evidence of myometrial invasion which was confirmed by histology. Therefore, with evidence of an increased tumor volume, surgical therapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy were performed. Although our patients were treated with definitive surgical therapy, a more conservative approach consisting of curettage and pro-
Stovall et al.:
Teenage Endometrial Adenocarcinoma
gesterone therapy has been reported for treatment of Grade I, Stage lA, noninvasive adenocarcinoma. 9 - 1l This form of treatment would preserve ovarian function and future fertility in these young patients. The two patients presented were not candidates for this form of therapy, however, due to the more aggressive nature of their disease. In conclusion, teenagers with risk factors for adenocarcinoma including obesity, estrogen intake, and chronic anovulation, especially when associated with precocious puberty, should be considered for endometrial sampling as part of their evaluation to rule out the possibility of an endometrial malignancy.
References
4.
5.
6.
7.
8. 9.
1. Elwood JM, Cole P, Rothman KJ, et al: Epidemiology of endometrial cancer. J Natl Cancer Inst 1977; 59: 1055 2. Koss LG, Schreiber K, Oberlander SG, et al: Detection of endometrial carcinoma and hyperplasia in asymptomatic women. Obstet Gynecol 1984; 64: 1 3. Faguer C, Maghioracus P, Fai R: Epidemiology study of endometrial adenocarcinoma from 74 cases seen at
10.
11.
159
the Saint-Anthoine Maternity Hospital. Sem Hop Paris 1983; 59:43 Jeffery JD, Taylor R, Robertson DE, et al: Endometrial carcinoma occurring in patients under the age of 45 years. Am J Obstet Gynecol 1987; 156:2 Ackerman GE, Smith ME, Mendelson CR, et al: Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 1981; 53:412 Petterson F, Kolstad P, Ludwig H, et al: Annual report on the results of treatment in gynecologic cancer. International Federation of Gynecology and Obstetrics 1985; 19 Connelly PJ, Alberhasky RC, Christopherson WM, et al: Carcinoma of the endometrium. Obstet Gynecol 1982; 59:569 Christopherson WM, Connelly PJ, Alberhasky RC: Carcinoma of the endometrium. Cancer 1983; 51: 1705 Farhi DC, Nosanchuk J, Silverberg SG: Endometrial adenocarcinoma in women under 25 years of age. Obstet Gynecol 1986; 68:741 Eddy WA: Endometrial carcinoma in Stein-Leventhal syndrome treated with hydroxyprogesterone caproate. Am J Obstet Gynecol 1978; 131:581 Fechner RE, Kaufman HK: Endometrial adenocarcinoma in Stein-Leventhal syndrome. Cancer 1974; 34:444
Adolescent and Pediatric Gynecology © 1989 Springer-Verlag New York Inc.
Endometrial Adenocarcinoma in Teenagers Dale W. Stovall, M.D., Ralph 1. Anderson, M.D., and Frank D. De Leon, M.D. Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, Texas
Abstract. Adenocarcinoma of the endometrium is an extremely rare finding in the teenage population. Two case reports of 17-year-old teenagers with endometrial carcinoma are presented. Both patients have a history of prolonged periods of anovulation which supports the association between unopposed prolonged estrogen effect and the development of endometrial carcinoma.
Key Words. Endometrial carcinoma-Chronic anovulation-Endometrial biopsy
Introduction Adenocarcinoma of the endometrium commonly afflicts female patients over 40 years of age, with the diagnosis most frequently made between the ages of 50 and 65. Only about 5% of the women affected are under 40, and the disease is extremely rare in the teenage population. 1 Because of this rarity, we present two cases of endometrial adenocarcinoma in 17year-old women diagnosed within a 6-month period at the Texas Tech University Health Science Center in Lubbock. The clinical presentation, as well as the need for histology screening in the teenager who has a prolonged history of unopposed estrogen exposure, is discussed.
Case Reports The first patient, a 17 -year-old nulligravida, presented with a chief complaint of heavy and. irregular menstrual bleeding of 3 years duration. She was preAddress reprint requests to: F.D. De Leon, M.D., Department of Obstetrics and Gynecology, Texas Tech Health Sciences Center, Lubbock, Texas 79430, USA. Presented in part at the Third Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology held in Houston, TX, September, 1988.
viously diagnosed as having precocious puberty. She had experienced menarche at age 9 and thelarche and adrenarche at age 8. Her evaluation for precocious puberty included skull films, computed tomography scan of the abdomen and pelvis, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH), testosterone, and dehydroepiandrosterone sulfate (DHEAS), all within normal limits. Hand-wrist films revealed an advanced bone age and all other test findings were consistent with constitutional, true sexual precocity. Her physical examination was remarkable for short stature (4'4"), and the presence of situs inversus. Pelvic examination revealed a lO-week sized uterus, which sounded to 9 cm. A dilatation and curettage was performed, which revealed crowding of the endometrial glands and hyperchromatic nuclei with irregular nuclear contours. There were 35 mitotic figures noted in 50 high power fields and the diagnosis of stage IBGI adenocarcinoma was made (Fig. 1). Her treatment consisted of total abdominal hysterectomy with bilateral salpingo-oophorectomy. Peritoneal cytologic sampling revealed no tumor spread. The ovaries were polycystic on gross examination and the histologic examination, confirming the diagnosis, showed numerous small cortical cysts lined by granulosa cells with stromal luteinization. There was no evidence of corpus lutea, corpora albicans, or ovarian stromal tumor. The second patient is a 17-year-old nulligravida, who presented with a 2-year history of menometrorrhagia requiring dilatation and curettage for control. She had menarche at age 13. Her physical examination was remarkable for obesity (266 pounds), which was at the 95th percentile for her age. She also demonstrated mild hirsutism by the Ferriman and Gallwey scoring system with Grade II terminal hair on the upper lip and chin areas, and Grade I on the chest. Pelvic examination revealed a slightly enlarged uterus, which sounded to 8 cm. Histologic examination of the endometrium revealed a well-differentiated adenocarcinoma with obvious superficial myometrial invasion.
158
Stovall et al.:
Teenage Endometrial Adenocarcinoma
Fig. 1. Uterine endometrium reveals well-differentiated adenocarcinoma. Architecturally there are "back to back" glands and there is evidence of nuclei stratification.
Focal areas of squamous metaplasia were seen, and a diagnosis of stage lAG 1 adenoacanthoma was made. Total abdominal hysterectomy with bilateral salpingooophorectomy was performed and the superficial myometrial invasion was confirmed (Fig. 2). No enlarged lymph nodes were palpable in the pelvic or periaortic areas, and the peritoneal washings were negative. The ovaries were enlarged and polycystic in appearance and their histology was again confirmatory. The slides from both patients were reviewed at another institution which confirmed our findings.
Discussion Adenocarcinoma of the endometrium is most commonly found in the postmenopausal woman, with the
Fig. 2. Section from the endometrium reveals carcinomatous glands invading the smooth muscle cells of the myometrium. Arrows reveal area of invasion.
peak incidence occurring between 50 and 65 years of age. 2 Risk factors in this population include onset of menopause after the age of 49, obesity, race, parity, and estrogen intake. 3 Another major group at risk are those patients in the reproductive years who have a history of chronic anovulation, such as in Stein-Leventhal syndrome with its characteristic obesity, hirsutism, irregular menses, and infertility. 4 Although the etiology of the chronic anovulation syndrome is not known, it is believed to be multifactorial in origin, and in many instances begins in adolescence. The 2 patients presented emphasize the importance of recognizing chronic anovulation in a young population. Despite their young age, these patients had a history of chronic, unopposed estrogen exposure. A history of precocious puberty, early follicular function, and chronic anovulation characterized the first patient. The second patient also had risk factors, including a history of chronic anovulation and morbid obesity. Adipose tissue is a known source for peripheral conversion of androgens to estrogens. 5 Endometrial sampling, an accepted procedure to detect endometrial cancer in patients 35 years and older with persistent anovulatory bleeding may need to be extended to younger patients under very special circumstances; however, it is difficult to select which patients in the adolescent age group may benefit from this procedure. We have described two adolescents who were unique in their age group and who had significant risk factors for prolonged and/or increased unopposed estrogen exposure. It is this group of adolescents that may benefit from endometrial sampling. Factors that affect prognosis in endometrial carcinoma include the stage of the disease, degree of differentiation, depth of myometrial invasion, and the histologic pattern. 6- 8 Each of these variables was carefully considered in the final decision for treatment. Histologically, the first case revealed adenocarcinoma and the second, adenocarcinoma with squamous metaplasia both of which have more favorable prognosis than other patterns including adenosquamous, clear cell carcinoma, and papillary. Both carcinomas were highly differentiated tumors and therefore Grade I. Nevertheless, the remaining two categories, stage and myometrial invasion, give an indication of the total tumor volume. The first patient had Stage IB disease with a 9 cm uterus and the second had evidence of myometrial invasion which was confirmed by histology. Therefore, with evidence of an increased tumor volume, surgical therapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy were performed. Although our patients were treated with definitive surgical therapy, a more conservative approach consisting of curettage and pro-
Stovall et al.:
Teenage Endometrial Adenocarcinoma
gesterone therapy has been reported for treatment of Grade I, Stage lA, noninvasive adenocarcinoma. 9 - 1l This form of treatment would preserve ovarian function and future fertility in these young patients. The two patients presented were not candidates for this form of therapy, however, due to the more aggressive nature of their disease. In conclusion, teenagers with risk factors for adenocarcinoma including obesity, estrogen intake, and chronic anovulation, especially when associated with precocious puberty, should be considered for endometrial sampling as part of their evaluation to rule out the possibility of an endometrial malignancy.
References
4.
5.
6.
7.
8. 9.
1. Elwood JM, Cole P, Rothman KJ, et al: Epidemiology of endometrial cancer. J Natl Cancer Inst 1977; 59: 1055 2. Koss LG, Schreiber K, Oberlander SG, et al: Detection of endometrial carcinoma and hyperplasia in asymptomatic women. Obstet Gynecol 1984; 64: 1 3. Faguer C, Maghioracus P, Fai R: Epidemiology study of endometrial adenocarcinoma from 74 cases seen at
10.
11.
159
the Saint-Anthoine Maternity Hospital. Sem Hop Paris 1983; 59:43 Jeffery JD, Taylor R, Robertson DE, et al: Endometrial carcinoma occurring in patients under the age of 45 years. Am J Obstet Gynecol 1987; 156:2 Ackerman GE, Smith ME, Mendelson CR, et al: Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 1981; 53:412 Petterson F, Kolstad P, Ludwig H, et al: Annual report on the results of treatment in gynecologic cancer. International Federation of Gynecology and Obstetrics 1985; 19 Connelly PJ, Alberhasky RC, Christopherson WM, et al: Carcinoma of the endometrium. Obstet Gynecol 1982; 59:569 Christopherson WM, Connelly PJ, Alberhasky RC: Carcinoma of the endometrium. Cancer 1983; 51: 1705 Farhi DC, Nosanchuk J, Silverberg SG: Endometrial adenocarcinoma in women under 25 years of age. Obstet Gynecol 1986; 68:741 Eddy WA: Endometrial carcinoma in Stein-Leventhal syndrome treated with hydroxyprogesterone caproate. Am J Obstet Gynecol 1978; 131:581 Fechner RE, Kaufman HK: Endometrial adenocarcinoma in Stein-Leventhal syndrome. Cancer 1974; 34:444