European Journal of Obstetrics & Gynecology and Reproductive Biology, 45 (1992) 63-66 0 1992 Elsevier Science Publishers B.V. All rights resewed 0028-2243/92/$05.00
EUROBS
63
01345
Synchronous primary malignancies of the female genital tract Ali Ayhan ‘, bmer T. Yalp
a, Z. Selquk Tuncer ‘, Timur Giirgan a and Tiirkan KiiQikall b
Departments of ’ Obstetrics and ’ Pathology, Division of Gynecologic Oncology, School of Medicine, Hacettepe University, Ankara, Turkey Accepted
for publication
7 January
1992
Summary This study includes 29 patients with synchronous primary malignancies of the female genital tract. These patients constituted 1.7% of all genital malignancies. The most frequently observed synchronous neoplasms were those of the ovary together with the endometrium (51.7%). Most patients had early-stage and low-grade disease. Stage I disease was observed in 68.1% of patients with ovarian cancer. Patients with synchronous ovarian and endometrial cancer had a 73.3% 5-year survival rate, suggesting a favorable prognosis. Synchronous
genital
malignancy;
Endometrial
cancer;
Ovarian
Introduction Synchronous primary tumors of the female genital tract are relatively rare, comprising only 1% to 6% of all genital neoplasms. Endometrial cancer synchronous with ovarian cancer is the most common occurrence [ 1,2]. While the etiology of this phenomenon remains unclear, it has been postulated that embriologically similar tissues of the female genital tract, when simultaneously subjected to carcinogens may develop synchronous neoplasms [3,4]. Others suggest that these neoplasms represent metaplasia occurring in similar histological epithelium of the genital tract and peritoneum [5]. In terms of the etiology it is quite likely that estrogens are important in synchronous endomeCorrespondence: Dr. Ah Ayhan, Hacettepe oniversitesi TIP Fakiiltesi, Kadm Hastahklarl Ve Dogum Anabilim Dal], 06100, Ankara, Turkey.
cancer
trial and ovarian carcinoma; in cervical and vaginal lesions human papilloma virus could be of importance. The prognosis of the patients with synchronous malignancies was reported to be more favorable when compared to the survival of patients harboring the same neoplasms individually
h71. The aim of this study was to evaluate the clinicopathologic features of synchronous genital malignancies. Material and Methods This study includes 29 patients with synchronous primary genital malignancies diagnosed and treated at the Hacettepe University, School of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology between 1967 and 1986. Data were obtained from the patients’ files, oncology follow-up forms and pathology reports.
64
All patients fullfilled the criteria of multiple primary neoplasms proposed by Warner and Gates [8]. Recurrent, metastatic, extragenital and metachronousiy occurring tumors were excluded from the study. Only second or third primary neoplasms which were either diagnosed concurrent with the primary neoplasm, discovered at the primary surgical procedure, or diagnosed within 6 months of the primary tumor were included in this study. All surgical specimens were re-examined by the coauthor pathologist. Epithelial ovarian neoplasms were classified according to the WHO criteria [5]. All patients were staged using FIG0 recommendations. Results
Twenty-nine patients diagnosed as having synchronous tumors constituted 1.7% of all patients with genital malignancies (29/1690X Two concurrent neoplasms were observed in 28 patients, while one had three separate simultaneous tumors. The mean age of the patients at diagnosis was 48.4 years (range 24-70). Nine patients were nulliparous and six were postmenopausal. The most common complaint was irregular vaginal bleeding (51.7%). The most common cancer was that of the ovary concomitant with other gynecological malignancies (Table I). The endometrial and ovarian cancer group consisted of 15 patients and the most common histological subtypes were adenocarcinoma of the endometrium and serous or TABLE I Synchronous malignancies Site I
Site II
No.
Ovary Ovary Vagina Endometrium Ovary Vulva
Endometrium Cervix Cervix Cervix Ovary Vagina
15 * 5 3 3 2 1
Total * One patient had CIS of the cervix.
29
TABLE II Endometrium
and ovary group
Endometrium
Ovary
No.
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma MMMT **
Serous Mutinous Endometrioid Clear cell Granulosa cell Serous
5 5* 2 1 1 1
* * = Malign mixed mesodermal tumor. * One patient had CIS of the cervix.
mutinous adenocarcinoma of the ovary (Table II>. The majority of the patients with cervical, vaginal and vulvar neoplasms had squamous carcinoma. Of the 22 cases with ovarian cancer, 15 had stage I, 4 had stage II and 3 had stage III disease There were 14, 6 and 2 patients with grade I, II and III tumors, respectively. Of the 18 patients with uterine malignancy, 14 had stage I, 13 had stage II and 1 had stage III disease. There were 14 patients with grade I and 4 patients with grade II neoplasms. Eight patients with cervical cancer had stage I and grade I lesions. One patient with cervical mutinous adenocarcinoma had a stage III and grade III tumor. All patients with vaginal cancer had stage I and grade I disease. One patient with vulvar carcinoma had a stage III and grade III disease. The patients with ovarian and endometrial cancer underwent total abdominal hysterectomy, bilateral salpingooopherectomy, omentectomy and bilateral pelvic and paraaortic lymphadenectomy. Postoperatively, five patients received multiagent chemotherapy (CHAD = Cyclophosphamide + hexametylmelamine + adriamycine + platinum), 2 patients received external irradiation, and one patient was given intraperitoneal radioactive colloidal chromic phosphate. One patient had carcinoma in situ of the cervix in addition to the endometrial and ovarian cancer. She received postoperative chemotherapy but died of metastatic disease 28 months after the diagnosis. The overall 5-year survival in patients with endometrial and ovarian cancer, including the one
65 TABLE
III
Synchronous tumors other than endometrium and ovary group A. Ovary-cervix group Ovary
Cerviu
No.
Anaplastic Endometrioid Serous Clear cell
Epidermoid Epidermoid Epidermoid Epidermoid
1 2 1 1
Cervix
No. 1 1 1
B. Vagina-Cervix Vagina
group
Epidermoid Epidermoid Epidermoid
Epidermoid Mutinous Adenoacanthoma
C. Endometrium-Cervix Endometrium
group Cervix
Adenocarcinoma Endometrioid
Epidermoid Epidermoid
D. Ovary-Ovary group Ovary
Ovary
Brenner Granulosa cell
Clear cell Serous
E. Vulva-Vagina Vulva
Epidermoid
No. 2 1 No. 1 1
group Vagina
Epidermoid
No. 1
patient with in situ cervical cancer, was 73.3%. The patients with synchronous malignancies other than endometrium and ovary were also treated primarily by surgery (Table III). The ovary and cervix group consisted of 5 patients and while four of the patients are still alive, with an average of 40 months, one patient with an anaplastic carcinoma of the ovary died 32 months after the diagnosis. Three patients had primary neoplasms of the vagina and cervix. One patient with a mutinous adenocarcinoma of the cervix died in the 12th month of diagnosis. The other two patients are alive and free of disease with a mean survival of 40 months. Two patients had concomittant ovarian malignancies of different histological types. One patient had a malignant Brenner tumor in her left ovary together with a clear-cell carcinoma in her right ovary. She is free of disease in the eighth year of surgical treatment and adjuvant chemotherapy. The other patient had a granulosa
cell tumor in her left ovary and a serous carcinoma in her right ovary. She received combination chemotherapy following surgery and survived 36 months. Discussion Primary malignancies of the genital tract seem to occur synchronously more often than one would expect by chance. A patient with a genital malignancy appears to be at a significantly increased risk for a second malignancy [8,10].The reports indicate l-6% incidence of multiple primary tumors among the cancer patient population. Recently, Reisner et al showed an incidence of 0.7% among 3863 patients [3]. The 1.7% incidence in our report is in accordance with the literature. The most commonly reported synchronous malignancies was the coexistence of endometrial and ovarian cancers [3,7]. This group comprised 51.7% of all patients in this series. The incidence of patients with endometrial carcinoma who had simultaneous ovarian cancer was reported to be 2-4% whereas this was 4% in this report [4,7]. Most of the neoplasms were in the early stages and low-grade. Stage I disease was detected in 68.1% of patients with ovarian cancer This finding is in contrast to the 70% primary ovarian carcinoma patients whose disease has spread beyond the pelvis at the time of diagnosis [3,11]. Similarly, only one patient had stage III disease among patients with endometrial carcinoma. The association of early stage and low histological grade indicates that they may have arisen as synchronous separate multifocal primary lesions rather than metastases. The prognoses in these patients were reported to be more favorable when compared to metastatic lesions of individual tumors [1,12]. The 5year survival of 73.3% in the most frequently observed endometrial and ovarian cancer group also suggests that these patients had a better survival than the patients with a single primary genital malignancy. Similarly favorable outcomes were observed in other synchronous tumor groups. Surgical treatment should be the treatment of choice as it contributes to the diagnosis of synchronous lesions. Most of the patients were sub-
66
jetted to adjuvant chemotherapy which appears to improve the efficacy of surgery. However, due to the limited number of patients, it is difficult to draw conclusions regarding the optimal treatment choice. In conclusion, patients with primary genital malignancies are at increased risk for synchronous tumors.The most frequent lesions were ovarian and endometrial carcinomas. Most lesions were early stage and low grade. Surgery and adjuvant chemotherapy appears to be the treatment of choice.
4 5 6
7
8
9
References 10 1 Matloch DL, Salem FA, Charles EH, Save EW. Synchronous multiple primary neoplasms of the upper female genital tract. Gynecol Oncol 1982;13:271. 2 Scoenberg BS, Greenberg RA, Eisenberg H. Occurrence of certain multiple primary cancers in females. J Natl Cancer Inst 1969;43:15. 3 Eisner RF, Nieberg RK, Berek JS. Synchronous primary
11 12
neoplasms of the female reproductive tract. Gynecol Oncol 1989;33:335. Woodruff JD, Solomon D, Sullivant H. Multifocal disease in the upper genital canal. Obstet Gynecol 1985;65:965. Laughan S. The secondary mullerian system. Obstet Gynecol Sun, 1972;27:133. Ulbright TM, Roth LM. Metastatic and independent cancers of the endometrium and ovary. Hum Pathol 1985;16:28. Zaino RJ, Unger ER, Whitney CW. Synchronous carcinomas of the uterine corpus and ovary. Gynecol Oncol 1984;19:329. Rose PG, Herterick EE, Boutselis JG, Moeshberger M, Sachs L. Multiple Primary gynecologic neoplasms. Am J Obstet Gynecol 1987;157:261. Hart WR, Morrow CP. The Ovaries. In: Gynecology and obstetrics: the health care of women. New York: McGraw-Hill, 1981. Axelford J, Fruchter R, Boyce J. Multiple primaries among gynecologic malignancies. Gynecol Oncol 1984;18:359. Beck W. Pelvic malignancies. In Obstetrics and gynecology. New York: Wiley & Sons 1986;229. Eifel P, Henricksen M, Ross W, Ballon S, Martines A, Kempson R. Simultaneous presentation of carcinoma involving the ovary and the uterine corpus. Cancer 1982;50:163.
EUROBS
63
01345
Synchronous primary malignancies of the female genital tract Ali Ayhan ‘, bmer T. Yalp
a, Z. Selquk Tuncer ‘, Timur Giirgan a and Tiirkan KiiQikall b
Departments of ’ Obstetrics and ’ Pathology, Division of Gynecologic Oncology, School of Medicine, Hacettepe University, Ankara, Turkey Accepted
for publication
7 January
1992
Summary This study includes 29 patients with synchronous primary malignancies of the female genital tract. These patients constituted 1.7% of all genital malignancies. The most frequently observed synchronous neoplasms were those of the ovary together with the endometrium (51.7%). Most patients had early-stage and low-grade disease. Stage I disease was observed in 68.1% of patients with ovarian cancer. Patients with synchronous ovarian and endometrial cancer had a 73.3% 5-year survival rate, suggesting a favorable prognosis. Synchronous
genital
malignancy;
Endometrial
cancer;
Ovarian
Introduction Synchronous primary tumors of the female genital tract are relatively rare, comprising only 1% to 6% of all genital neoplasms. Endometrial cancer synchronous with ovarian cancer is the most common occurrence [ 1,2]. While the etiology of this phenomenon remains unclear, it has been postulated that embriologically similar tissues of the female genital tract, when simultaneously subjected to carcinogens may develop synchronous neoplasms [3,4]. Others suggest that these neoplasms represent metaplasia occurring in similar histological epithelium of the genital tract and peritoneum [5]. In terms of the etiology it is quite likely that estrogens are important in synchronous endomeCorrespondence: Dr. Ah Ayhan, Hacettepe oniversitesi TIP Fakiiltesi, Kadm Hastahklarl Ve Dogum Anabilim Dal], 06100, Ankara, Turkey.
cancer
trial and ovarian carcinoma; in cervical and vaginal lesions human papilloma virus could be of importance. The prognosis of the patients with synchronous malignancies was reported to be more favorable when compared to the survival of patients harboring the same neoplasms individually
h71. The aim of this study was to evaluate the clinicopathologic features of synchronous genital malignancies. Material and Methods This study includes 29 patients with synchronous primary genital malignancies diagnosed and treated at the Hacettepe University, School of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology between 1967 and 1986. Data were obtained from the patients’ files, oncology follow-up forms and pathology reports.
64
All patients fullfilled the criteria of multiple primary neoplasms proposed by Warner and Gates [8]. Recurrent, metastatic, extragenital and metachronousiy occurring tumors were excluded from the study. Only second or third primary neoplasms which were either diagnosed concurrent with the primary neoplasm, discovered at the primary surgical procedure, or diagnosed within 6 months of the primary tumor were included in this study. All surgical specimens were re-examined by the coauthor pathologist. Epithelial ovarian neoplasms were classified according to the WHO criteria [5]. All patients were staged using FIG0 recommendations. Results
Twenty-nine patients diagnosed as having synchronous tumors constituted 1.7% of all patients with genital malignancies (29/1690X Two concurrent neoplasms were observed in 28 patients, while one had three separate simultaneous tumors. The mean age of the patients at diagnosis was 48.4 years (range 24-70). Nine patients were nulliparous and six were postmenopausal. The most common complaint was irregular vaginal bleeding (51.7%). The most common cancer was that of the ovary concomitant with other gynecological malignancies (Table I). The endometrial and ovarian cancer group consisted of 15 patients and the most common histological subtypes were adenocarcinoma of the endometrium and serous or TABLE I Synchronous malignancies Site I
Site II
No.
Ovary Ovary Vagina Endometrium Ovary Vulva
Endometrium Cervix Cervix Cervix Ovary Vagina
15 * 5 3 3 2 1
Total * One patient had CIS of the cervix.
29
TABLE II Endometrium
and ovary group
Endometrium
Ovary
No.
Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma MMMT **
Serous Mutinous Endometrioid Clear cell Granulosa cell Serous
5 5* 2 1 1 1
* * = Malign mixed mesodermal tumor. * One patient had CIS of the cervix.
mutinous adenocarcinoma of the ovary (Table II>. The majority of the patients with cervical, vaginal and vulvar neoplasms had squamous carcinoma. Of the 22 cases with ovarian cancer, 15 had stage I, 4 had stage II and 3 had stage III disease There were 14, 6 and 2 patients with grade I, II and III tumors, respectively. Of the 18 patients with uterine malignancy, 14 had stage I, 13 had stage II and 1 had stage III disease. There were 14 patients with grade I and 4 patients with grade II neoplasms. Eight patients with cervical cancer had stage I and grade I lesions. One patient with cervical mutinous adenocarcinoma had a stage III and grade III tumor. All patients with vaginal cancer had stage I and grade I disease. One patient with vulvar carcinoma had a stage III and grade III disease. The patients with ovarian and endometrial cancer underwent total abdominal hysterectomy, bilateral salpingooopherectomy, omentectomy and bilateral pelvic and paraaortic lymphadenectomy. Postoperatively, five patients received multiagent chemotherapy (CHAD = Cyclophosphamide + hexametylmelamine + adriamycine + platinum), 2 patients received external irradiation, and one patient was given intraperitoneal radioactive colloidal chromic phosphate. One patient had carcinoma in situ of the cervix in addition to the endometrial and ovarian cancer. She received postoperative chemotherapy but died of metastatic disease 28 months after the diagnosis. The overall 5-year survival in patients with endometrial and ovarian cancer, including the one
65 TABLE
III
Synchronous tumors other than endometrium and ovary group A. Ovary-cervix group Ovary
Cerviu
No.
Anaplastic Endometrioid Serous Clear cell
Epidermoid Epidermoid Epidermoid Epidermoid
1 2 1 1
Cervix
No. 1 1 1
B. Vagina-Cervix Vagina
group
Epidermoid Epidermoid Epidermoid
Epidermoid Mutinous Adenoacanthoma
C. Endometrium-Cervix Endometrium
group Cervix
Adenocarcinoma Endometrioid
Epidermoid Epidermoid
D. Ovary-Ovary group Ovary
Ovary
Brenner Granulosa cell
Clear cell Serous
E. Vulva-Vagina Vulva
Epidermoid
No. 2 1 No. 1 1
group Vagina
Epidermoid
No. 1
patient with in situ cervical cancer, was 73.3%. The patients with synchronous malignancies other than endometrium and ovary were also treated primarily by surgery (Table III). The ovary and cervix group consisted of 5 patients and while four of the patients are still alive, with an average of 40 months, one patient with an anaplastic carcinoma of the ovary died 32 months after the diagnosis. Three patients had primary neoplasms of the vagina and cervix. One patient with a mutinous adenocarcinoma of the cervix died in the 12th month of diagnosis. The other two patients are alive and free of disease with a mean survival of 40 months. Two patients had concomittant ovarian malignancies of different histological types. One patient had a malignant Brenner tumor in her left ovary together with a clear-cell carcinoma in her right ovary. She is free of disease in the eighth year of surgical treatment and adjuvant chemotherapy. The other patient had a granulosa
cell tumor in her left ovary and a serous carcinoma in her right ovary. She received combination chemotherapy following surgery and survived 36 months. Discussion Primary malignancies of the genital tract seem to occur synchronously more often than one would expect by chance. A patient with a genital malignancy appears to be at a significantly increased risk for a second malignancy [8,10].The reports indicate l-6% incidence of multiple primary tumors among the cancer patient population. Recently, Reisner et al showed an incidence of 0.7% among 3863 patients [3]. The 1.7% incidence in our report is in accordance with the literature. The most commonly reported synchronous malignancies was the coexistence of endometrial and ovarian cancers [3,7]. This group comprised 51.7% of all patients in this series. The incidence of patients with endometrial carcinoma who had simultaneous ovarian cancer was reported to be 2-4% whereas this was 4% in this report [4,7]. Most of the neoplasms were in the early stages and low-grade. Stage I disease was detected in 68.1% of patients with ovarian cancer This finding is in contrast to the 70% primary ovarian carcinoma patients whose disease has spread beyond the pelvis at the time of diagnosis [3,11]. Similarly, only one patient had stage III disease among patients with endometrial carcinoma. The association of early stage and low histological grade indicates that they may have arisen as synchronous separate multifocal primary lesions rather than metastases. The prognoses in these patients were reported to be more favorable when compared to metastatic lesions of individual tumors [1,12]. The 5year survival of 73.3% in the most frequently observed endometrial and ovarian cancer group also suggests that these patients had a better survival than the patients with a single primary genital malignancy. Similarly favorable outcomes were observed in other synchronous tumor groups. Surgical treatment should be the treatment of choice as it contributes to the diagnosis of synchronous lesions. Most of the patients were sub-
66
jetted to adjuvant chemotherapy which appears to improve the efficacy of surgery. However, due to the limited number of patients, it is difficult to draw conclusions regarding the optimal treatment choice. In conclusion, patients with primary genital malignancies are at increased risk for synchronous tumors.The most frequent lesions were ovarian and endometrial carcinomas. Most lesions were early stage and low grade. Surgery and adjuvant chemotherapy appears to be the treatment of choice.
4 5 6
7
8
9
References 10 1 Matloch DL, Salem FA, Charles EH, Save EW. Synchronous multiple primary neoplasms of the upper female genital tract. Gynecol Oncol 1982;13:271. 2 Scoenberg BS, Greenberg RA, Eisenberg H. Occurrence of certain multiple primary cancers in females. J Natl Cancer Inst 1969;43:15. 3 Eisner RF, Nieberg RK, Berek JS. Synchronous primary
11 12
neoplasms of the female reproductive tract. Gynecol Oncol 1989;33:335. Woodruff JD, Solomon D, Sullivant H. Multifocal disease in the upper genital canal. Obstet Gynecol 1985;65:965. Laughan S. The secondary mullerian system. Obstet Gynecol Sun, 1972;27:133. Ulbright TM, Roth LM. Metastatic and independent cancers of the endometrium and ovary. Hum Pathol 1985;16:28. Zaino RJ, Unger ER, Whitney CW. Synchronous carcinomas of the uterine corpus and ovary. Gynecol Oncol 1984;19:329. Rose PG, Herterick EE, Boutselis JG, Moeshberger M, Sachs L. Multiple Primary gynecologic neoplasms. Am J Obstet Gynecol 1987;157:261. Hart WR, Morrow CP. The Ovaries. In: Gynecology and obstetrics: the health care of women. New York: McGraw-Hill, 1981. Axelford J, Fruchter R, Boyce J. Multiple primaries among gynecologic malignancies. Gynecol Oncol 1984;18:359. Beck W. Pelvic malignancies. In Obstetrics and gynecology. New York: Wiley & Sons 1986;229. Eifel P, Henricksen M, Ross W, Ballon S, Martines A, Kempson R. Simultaneous presentation of carcinoma involving the ovary and the uterine corpus. Cancer 1982;50:163.
