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Embryonal carcinoma of the ovary: a six-year survival
287
Int. J. Gynecol. Obstet., 1990,31: 287-292 International Federation of Gynecology and Obstetrics
Embryonal carcinoma of the ovary: a six-year survival G. Ueda, Y. Abe, M. Yoshida” and T. Fujiwara Department of Obstetrics and Gynecology, Osaka University Medical School and “Kitano Hospita& Osaka (Japan) (Received October 15th, 1988) (Revised and accepted Febmary 6th, 1989)
Abstract
Case report
We report a case of embryonal carcinoma, stage II, arising in the right ovary of an 18year-old woman. The elevated serum levels of alpha-fetoprotein (AFP) and urinary human chorionic gonadotropin (hCG) rapidly normalized after conservative surgery followed by combination chemotherapy. The tumor was composed of large primitive cells and some multinucleated giant cells. AFP and hCG were demonstrated immunohistochemically in each type of cells. She has been disease-free for 6 years.
An 1%year-old unmarried woman visited Kitano Hospita1 in Osaka complaining of a 4week history of lower abdominal pain and distension, in addition to a 3-month history of polymenorrhea. A hard tumor the size of a child’s head was palpated in the abdomen. The tumor was confirmed by sonography and computed tomography (CT), and suspected to be malignant. Laboratory studies showed elevated levels of urinary human chorionic gonadotropin (hCG) (2800 IU/I) and serum alpha-fetoprotein (AFP) (470 ng/ml). A laparotomy was performed on September 14, 1982. In the pelvic cavity there was a smal1 amount of clear yellow ascites, which was negative for malignant cells. The right ovary was occupied by a 23 x 22 x 16 cm tumor. It had a smooth unruptured capsule without adhesions to adjacent organs. The left ovary was slightly enlarged and multicystic. Several metastatic implants as large as 1 cm in diameter were found in the posterior serosa of the uterus and in the Douglas pouch. The right ovarian tumor together with the tube and the metastatic implants were removed. A wedge resection of the left ovary was also performed for a biopsy specimen. After the operation the patient was treated by a combination chemotherapy using
Keywords: Embryonal Case report.
carcinoma;
Ovary;
Introduction Embryonal carcinoma of the ovary is a rare ovarian tumor which should be differentiated from the relatively common endodermal sinus tumor in terms of clinical and histological differences. Kurman and Norris reviewed 15 such cases from the AFIP files between 1942 and 1972 [ll. Since then, however, only one case has been fully described [2]. Here we report a rare case who has been free of disease for about 6 years after conservative treatment. 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
Case Report
288
Ueda et al.
vincristine, actinomycin D, carboquone and tegafur. The serum AFP and urinary hCG leve18 decreased rapidly to within normal ranges. The patient was discharged on November 6, 1982, and has been free of disease for about 6 years, in addition to having a regular menstrual cycle. Pathology The right ovarian tumor was macroscopically covered with a smooth intact capsule, dark purple in color, 23 x 22 x 16 cm in size, and 4 kg in weight. In a cut section, the tumor was solid with some necrotic and hemorrhagic areas (Fig. 1). Microscopically, the tumor was mainly composed of large primitive pleomorphic cells appearing in solid sheet arrangements among the abundant mesenchymal tissues in addition to some multinucleated giant cells resembling syncytiotrophoblastic cells (Fig. 2). Under higher magnification, the cytoplasm of the primitive tumor cells was amphophilic and vacuolated. The nuclei were round and of various sizes with prominent nucleoli. Mitotic figures were numerous (Fig. 3). A few embryoid bodies
Fig. 1.
Macroscopic appearance of the tumor.
Znt J Gynecol Obstet 31
were also found (Fig. 4). Teratomatous components such as glandular epithelium and mature squamous epithelium were detected as only minor components (Fig. 5). AFP and hCG were identified by the immunoperoxidase method in some of the large primitive tumor cells forming solid sheets and al1 multinucleated giant cells, respectively (Figs. 6 and 7). Similar histology was observed in the metastases. However, no pathology was found in the biopsy specimen of the left ovary. Discussion Embryonal carcinoma of the ovary is listed separately from endodermal sinus tumor under WHO classification. However, the definition was unclear until the detailed description of Kurman and Norris [ll. According to them, the characteristics of embryonal carcinoma are abnormal hormonal manifestations such as precocious puberty, irregular genital bleeding, amenorrhea, and hirsutism; abnormal secretion of AFP and hCG, and their immunohistochemical localization in the tissues; and histological features consisting of
Embryonal carcinoma of the ovary
Fig. 2.
Shows the tumor cells arranged in solid sheets and a multinucleated giant cell. H-E, x 100.
large primitive cells arranged in solid sheets of nests, multinucleated giant cells, embryoid bodies, and/or cartilage or squamous epithelium reflecting a differentiation to teratoma. The present tumor had almost al1 of these features. APP and hCG were not only
Fig. 3.
289
identified immunohistochemically in the present tumor, but their elevated levels reduced rapidly after treatment as well, showing the production of these markers by the tumor. Some characteristics of embryonal carcinoma are similar to those of other germ cel1
The nuclei of tumor cells are of various sizes, with prominent nucleoli. Mitotic figures are numerous. H-E, x 400. Case Report
290
Fig. 4.
Ueda et al.
Shows an embryoid body. H-E, x 100.
tumors [3]. Dysgerminoma may contain syncytiotrophoblastic cells [4,5]. Nevertheless, even pure dysgerminoma is rarely reported to produce AFP and hCG [6]. When compared with an endodermal sinus tumor which produces AFP, the embryonal carci-
Fig. 5.
noma lacks the reticular, polyvesicular vitelline and festoon patterns [ 11. Polyembryoma has many embryoid bodies and secretes AFP and hCG [7]. Choriocarcinoma contains syncytiotrophoblastic cells and produces hCG [8,9]. Pure teratoma may produce AFP [ 101.
Shows glandular epithelium with squamous metaplasia. H-E, x 200.
Int J Gynecol Obstet 31
Embtyonal carcinoma of the ovary
Fig. 6.
Immunohistochemical
localization of hCG is demonstrated in a multinucleated giant cell. PAP, x 200.
On the other hand, embryonal carcinoma has occasionally been intermixed with other germ cel1 tumors such as dysgerminoma, choriocarcinoma, and teratoma [3,11]. The present tumor had a minor teratomatous component of squamous and glandular epithelium. Such an intermixture is oncoge-
Fig. 7
Immunohistochemical
291
netically interesting showing that embryonal carcinoma may be the neoplastic progenitor leading to endodermal sinus tumor and choriocarcinoma with extra-embryonic differentiation as wel1 as to teratoma with embryonic differentiation. Patients with embryo4 carinoma have a
localization of AFP is demonstrated in some of the tumor cells arranged in solid sheets. PAP, X 200. Case Report
292
Ueda et al.
better prognosis than those with endodermal sinus tumor, showing a 50% 5-year survival rate for Stage 1 disease [ 11. An 8-year survival case [2] had a Stage 1 tumor. However, two patients with stage 111 tumor [12] and two with recurrent tumor [13] were reported to be fatal. Since the present case was a stage 11disease showing the metastases to Douglas pouch, the initial prognosis was not considered to be very good. Contrary to this assumption, she has actually been free of disease for about 6 years, in addition to having a regular menstrual cycle. On this connection, some recent papers report that the survival has greatly improved in germ cel1 tumor mixed with embryonal carcinoma of the ovary [ 14,151 as wel1 as in embryonal carcinoma of the testis [16] as a result of the effectiveness of newer chemotherapies in the treatment of disseminated disease. Therefore, conservative surgery followed by multiagent chemotherapy may be the choice of treatment for this type of ovarian tumor in young patients, regardless of stages, to preserve fertility and ovarian function.
5
6
7
8
9 10
11
12
13
Ref erences 14 Kurman RJ, Norris HJ: Embryonal carcinoma of the ovary: a clinicopathologic entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testis. Cancer 38: 2420, 1976. Nakakuma K, Tashiro S, Uemura K et ah Alpha-fetoprotein and human chorionic gonadotropin in embryonal carcinoma of the ovary: An 8-year survival case. Cancer 52: 1470,1983. Scully RE: Tumors of the ovary and maldeveloped gonads. In: Atlas of Tumor Pathology, second series, fasc. 16. AFIP, 1979. Ueda G, Hamanaka N, Hayakawa K et al: Clinical, histochemical, and biochemical studies of an ovarian dysgerminoma with trophoblasts and Leydig cells. Am J Obstet Gynecol114: 748,1972.
Int J Gynecol Obstet 31
15
16
Zaloudek CJ, Tavassoli FA, Norris HJ: Dysgerminoma with syncytiotrophoblastic giant cells. A histologically and clinically distinctive subtype of dysgerminoma. Am J Surg Pathol 5: 361, 1981. Sekiya S, Inaba N, Takamizawa H et al: Human chorionic gonadotropin and alpha-fetoprotein in sera and tumor cells of a patient with pure dysgerminoma. Acts Obstet Gynecol Stand 66: 75, 1987. Takeda A, Ishizuka T, Goto T et al: Polyembryoma of ovary producing alpha-fetoprotein and hCG: immunoperoxidase and electron microscopic study. Cancer 49: 1878,1982. Vance RP, Geisinger R: Pure nongestational choriocarcinoma of the ovary. Report of a case. Cancer 56: 2321, 1985. Axe SR, Klein VR, Woodruff JD: Choriocarcinoma of the ovary. Obstet Gynecol66: 111,1985. Perrone T, Steeper TA, Dehner LP: Alpha-fetoprotein localization in pure ovarian teratoma. An immunohistochemical study of 12 cases. Am J Clin Pathol 88: 713, 1987. Kurman RJ, Norris HJ: Malignant mixed germ cel1 tumors of the ovary: A clinical and pathologie analysis of 30 cases. Obstet Gynecol48: 579, 1976. Slayton RE, Park RC, Silverberg SG et al: Vincristine, dactinomycin and cyclophosphamide in the treatment of malignant germ cel1 tumors of the ovary. A gynecologic oncology group study (a final report). Cancer 56: 243, 1985. Bradof JE, Hakes TB, Ochoa M et al: Germ cel1 malignancies of the ovary. Treatment with vinblastine, actinocisplatin bleomycin and containing mycin-D, chemotherapy combinations. Cancer 50: 1070, 1982. Raney RB, Jr, Sinclair L, Uri A et al: Malignant ovarian tumors in children and adolescents. Cancer 59: 1214, 1987. Germá JR, Piera JM, Barnadas A et al: Sequential combination chemotherapy for malignant germ cel1 tumors of the ovary. Cancer 61: 913, 1988. Vugrin D, Chen A, Feigl P et al: Embryonal carcinoma of the testis. Cancer 61: 2348, 1988.
Address for reprints: G. Ueda Depnrtment of Obstetrics and Gyaecology Osaka University Medical School 1-1-50, Fukushima Fukushimaku Osaka 553, Japan
Int. J. Gynecol. Obstet., 1990,31: 287-292 International Federation of Gynecology and Obstetrics
Embryonal carcinoma of the ovary: a six-year survival G. Ueda, Y. Abe, M. Yoshida” and T. Fujiwara Department of Obstetrics and Gynecology, Osaka University Medical School and “Kitano Hospita& Osaka (Japan) (Received October 15th, 1988) (Revised and accepted Febmary 6th, 1989)
Abstract
Case report
We report a case of embryonal carcinoma, stage II, arising in the right ovary of an 18year-old woman. The elevated serum levels of alpha-fetoprotein (AFP) and urinary human chorionic gonadotropin (hCG) rapidly normalized after conservative surgery followed by combination chemotherapy. The tumor was composed of large primitive cells and some multinucleated giant cells. AFP and hCG were demonstrated immunohistochemically in each type of cells. She has been disease-free for 6 years.
An 1%year-old unmarried woman visited Kitano Hospita1 in Osaka complaining of a 4week history of lower abdominal pain and distension, in addition to a 3-month history of polymenorrhea. A hard tumor the size of a child’s head was palpated in the abdomen. The tumor was confirmed by sonography and computed tomography (CT), and suspected to be malignant. Laboratory studies showed elevated levels of urinary human chorionic gonadotropin (hCG) (2800 IU/I) and serum alpha-fetoprotein (AFP) (470 ng/ml). A laparotomy was performed on September 14, 1982. In the pelvic cavity there was a smal1 amount of clear yellow ascites, which was negative for malignant cells. The right ovary was occupied by a 23 x 22 x 16 cm tumor. It had a smooth unruptured capsule without adhesions to adjacent organs. The left ovary was slightly enlarged and multicystic. Several metastatic implants as large as 1 cm in diameter were found in the posterior serosa of the uterus and in the Douglas pouch. The right ovarian tumor together with the tube and the metastatic implants were removed. A wedge resection of the left ovary was also performed for a biopsy specimen. After the operation the patient was treated by a combination chemotherapy using
Keywords: Embryonal Case report.
carcinoma;
Ovary;
Introduction Embryonal carcinoma of the ovary is a rare ovarian tumor which should be differentiated from the relatively common endodermal sinus tumor in terms of clinical and histological differences. Kurman and Norris reviewed 15 such cases from the AFIP files between 1942 and 1972 [ll. Since then, however, only one case has been fully described [2]. Here we report a rare case who has been free of disease for about 6 years after conservative treatment. 0020-7292/90/$03.50 0 1990 International Federation of Gynecology and Obstetrics Published and Printed in Ireland
Case Report
288
Ueda et al.
vincristine, actinomycin D, carboquone and tegafur. The serum AFP and urinary hCG leve18 decreased rapidly to within normal ranges. The patient was discharged on November 6, 1982, and has been free of disease for about 6 years, in addition to having a regular menstrual cycle. Pathology The right ovarian tumor was macroscopically covered with a smooth intact capsule, dark purple in color, 23 x 22 x 16 cm in size, and 4 kg in weight. In a cut section, the tumor was solid with some necrotic and hemorrhagic areas (Fig. 1). Microscopically, the tumor was mainly composed of large primitive pleomorphic cells appearing in solid sheet arrangements among the abundant mesenchymal tissues in addition to some multinucleated giant cells resembling syncytiotrophoblastic cells (Fig. 2). Under higher magnification, the cytoplasm of the primitive tumor cells was amphophilic and vacuolated. The nuclei were round and of various sizes with prominent nucleoli. Mitotic figures were numerous (Fig. 3). A few embryoid bodies
Fig. 1.
Macroscopic appearance of the tumor.
Znt J Gynecol Obstet 31
were also found (Fig. 4). Teratomatous components such as glandular epithelium and mature squamous epithelium were detected as only minor components (Fig. 5). AFP and hCG were identified by the immunoperoxidase method in some of the large primitive tumor cells forming solid sheets and al1 multinucleated giant cells, respectively (Figs. 6 and 7). Similar histology was observed in the metastases. However, no pathology was found in the biopsy specimen of the left ovary. Discussion Embryonal carcinoma of the ovary is listed separately from endodermal sinus tumor under WHO classification. However, the definition was unclear until the detailed description of Kurman and Norris [ll. According to them, the characteristics of embryonal carcinoma are abnormal hormonal manifestations such as precocious puberty, irregular genital bleeding, amenorrhea, and hirsutism; abnormal secretion of AFP and hCG, and their immunohistochemical localization in the tissues; and histological features consisting of
Embryonal carcinoma of the ovary
Fig. 2.
Shows the tumor cells arranged in solid sheets and a multinucleated giant cell. H-E, x 100.
large primitive cells arranged in solid sheets of nests, multinucleated giant cells, embryoid bodies, and/or cartilage or squamous epithelium reflecting a differentiation to teratoma. The present tumor had almost al1 of these features. APP and hCG were not only
Fig. 3.
289
identified immunohistochemically in the present tumor, but their elevated levels reduced rapidly after treatment as well, showing the production of these markers by the tumor. Some characteristics of embryonal carcinoma are similar to those of other germ cel1
The nuclei of tumor cells are of various sizes, with prominent nucleoli. Mitotic figures are numerous. H-E, x 400. Case Report
290
Fig. 4.
Ueda et al.
Shows an embryoid body. H-E, x 100.
tumors [3]. Dysgerminoma may contain syncytiotrophoblastic cells [4,5]. Nevertheless, even pure dysgerminoma is rarely reported to produce AFP and hCG [6]. When compared with an endodermal sinus tumor which produces AFP, the embryonal carci-
Fig. 5.
noma lacks the reticular, polyvesicular vitelline and festoon patterns [ 11. Polyembryoma has many embryoid bodies and secretes AFP and hCG [7]. Choriocarcinoma contains syncytiotrophoblastic cells and produces hCG [8,9]. Pure teratoma may produce AFP [ 101.
Shows glandular epithelium with squamous metaplasia. H-E, x 200.
Int J Gynecol Obstet 31
Embtyonal carcinoma of the ovary
Fig. 6.
Immunohistochemical
localization of hCG is demonstrated in a multinucleated giant cell. PAP, x 200.
On the other hand, embryonal carcinoma has occasionally been intermixed with other germ cel1 tumors such as dysgerminoma, choriocarcinoma, and teratoma [3,11]. The present tumor had a minor teratomatous component of squamous and glandular epithelium. Such an intermixture is oncoge-
Fig. 7
Immunohistochemical
291
netically interesting showing that embryonal carcinoma may be the neoplastic progenitor leading to endodermal sinus tumor and choriocarcinoma with extra-embryonic differentiation as wel1 as to teratoma with embryonic differentiation. Patients with embryo4 carinoma have a
localization of AFP is demonstrated in some of the tumor cells arranged in solid sheets. PAP, X 200. Case Report
292
Ueda et al.
better prognosis than those with endodermal sinus tumor, showing a 50% 5-year survival rate for Stage 1 disease [ 11. An 8-year survival case [2] had a Stage 1 tumor. However, two patients with stage 111 tumor [12] and two with recurrent tumor [13] were reported to be fatal. Since the present case was a stage 11disease showing the metastases to Douglas pouch, the initial prognosis was not considered to be very good. Contrary to this assumption, she has actually been free of disease for about 6 years, in addition to having a regular menstrual cycle. On this connection, some recent papers report that the survival has greatly improved in germ cel1 tumor mixed with embryonal carcinoma of the ovary [ 14,151 as wel1 as in embryonal carcinoma of the testis [16] as a result of the effectiveness of newer chemotherapies in the treatment of disseminated disease. Therefore, conservative surgery followed by multiagent chemotherapy may be the choice of treatment for this type of ovarian tumor in young patients, regardless of stages, to preserve fertility and ovarian function.
5
6
7
8
9 10
11
12
13
Ref erences 14 Kurman RJ, Norris HJ: Embryonal carcinoma of the ovary: a clinicopathologic entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testis. Cancer 38: 2420, 1976. Nakakuma K, Tashiro S, Uemura K et ah Alpha-fetoprotein and human chorionic gonadotropin in embryonal carcinoma of the ovary: An 8-year survival case. Cancer 52: 1470,1983. Scully RE: Tumors of the ovary and maldeveloped gonads. In: Atlas of Tumor Pathology, second series, fasc. 16. AFIP, 1979. Ueda G, Hamanaka N, Hayakawa K et al: Clinical, histochemical, and biochemical studies of an ovarian dysgerminoma with trophoblasts and Leydig cells. Am J Obstet Gynecol114: 748,1972.
Int J Gynecol Obstet 31
15
16
Zaloudek CJ, Tavassoli FA, Norris HJ: Dysgerminoma with syncytiotrophoblastic giant cells. A histologically and clinically distinctive subtype of dysgerminoma. Am J Surg Pathol 5: 361, 1981. Sekiya S, Inaba N, Takamizawa H et al: Human chorionic gonadotropin and alpha-fetoprotein in sera and tumor cells of a patient with pure dysgerminoma. Acts Obstet Gynecol Stand 66: 75, 1987. Takeda A, Ishizuka T, Goto T et al: Polyembryoma of ovary producing alpha-fetoprotein and hCG: immunoperoxidase and electron microscopic study. Cancer 49: 1878,1982. Vance RP, Geisinger R: Pure nongestational choriocarcinoma of the ovary. Report of a case. Cancer 56: 2321, 1985. Axe SR, Klein VR, Woodruff JD: Choriocarcinoma of the ovary. Obstet Gynecol66: 111,1985. Perrone T, Steeper TA, Dehner LP: Alpha-fetoprotein localization in pure ovarian teratoma. An immunohistochemical study of 12 cases. Am J Clin Pathol 88: 713, 1987. Kurman RJ, Norris HJ: Malignant mixed germ cel1 tumors of the ovary: A clinical and pathologie analysis of 30 cases. Obstet Gynecol48: 579, 1976. Slayton RE, Park RC, Silverberg SG et al: Vincristine, dactinomycin and cyclophosphamide in the treatment of malignant germ cel1 tumors of the ovary. A gynecologic oncology group study (a final report). Cancer 56: 243, 1985. Bradof JE, Hakes TB, Ochoa M et al: Germ cel1 malignancies of the ovary. Treatment with vinblastine, actinocisplatin bleomycin and containing mycin-D, chemotherapy combinations. Cancer 50: 1070, 1982. Raney RB, Jr, Sinclair L, Uri A et al: Malignant ovarian tumors in children and adolescents. Cancer 59: 1214, 1987. Germá JR, Piera JM, Barnadas A et al: Sequential combination chemotherapy for malignant germ cel1 tumors of the ovary. Cancer 61: 913, 1988. Vugrin D, Chen A, Feigl P et al: Embryonal carcinoma of the testis. Cancer 61: 2348, 1988.
Address for reprints: G. Ueda Depnrtment of Obstetrics and Gyaecology Osaka University Medical School 1-1-50, Fukushima Fukushimaku Osaka 553, Japan