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Metastatic choriocarcinoma complicated by term pregnancy
GYNECOLOGIC
ONCOLOGY
34, 122-124 (1989)
CASE REPORT Metastatic Choriocarcinoma Complicated by Term Pregnancy’ GREGORY SUTTON, Department
M.D.,* MICHAEL HOGAN, M.D.,3 NORMAN ROSENBLUM, M.D.,3
of Obstetrics
and Gynecology,
University
of Pennsylvania,
AND
JOHN
3400 West Spruce Street, Philadelphia,
J. MIKUTA, JR., M.D. Pennsylvania
19104
Received March 21. 1988
Malignant gestational trophoblastic disease arising after term pregnancy is associated with a poorer prognosis than postmolar trophoblastic disease [l]. Choriocarcinoma coexistent with intrauterine pregnancy has also been reported [2]. The case described herein represents the rare occurrence of a term pregnancy in a patient with preexisting metastatic choriocarcinoma and serves to underscore the need for adequate contraception in the follow-up of patients treated for malignant gestational trophoblastic disease. CASE REPORT A 19-year-old unmarried black female was referred to the Hospital of the University of Pennsylvania at 20 weeks gestation in April 1982 with the history of having spontaneously aborted a hydatidiform mole in February 1980 (see Fig. 1). She had a postabortal curettage which produced tissue containing focal atypia. A second curettage, performed for plateauing hCG levels, contained histologic changes consistent with choriocarcinoma. Two courses of Actinomycin D were given and hCG titers became undetectable. Nine months later, she became pregnant and underwent an elective abortion at 12 weeks gestation; normal gestational products were identified with no evidence of trophoblastic disease. Oral contraceptives were started, but hCG levels began to rise and she was treated with alternating methotrexate and folinic acid. A chest radiograph at this time revealed a 2-cm left lower lobe metastatic nodule and she received 3 l/2 ’ Supported in part by the American Cancer Society Career Developmental Award 86-74. * To whom reprint requests should be addressed at Department of Obstetrics and Gynecology, Indiana University Medical School, 926 West Michigan Street, Indianapolis, IN 46223. 3 Present address: Lankenau Hospital, Medical Science Building, Suite 3305, Philadelphia, PA 19151. 122 OWO-8258/89
$1.50
Copyright 0 1989by AcademicPress,Inc. All rights of reproduction in any form reserved.
courses of chemotherapy with methotrexate/Actinomycin D/chlorambucil, achieving negative titers before refusing further treatment in September 1981. in April of the following year, she presented to the Hospital of the University of Pennsylvania at 20 weeks gestation with pleuritic chest pain and cough. The pulmonary nodule now measured 4.3 cm in diameter and fine needle aspiration confirmed the diagnosis of metastatic choriocarcinoma. HCG titer was 8600 mIU/ml. Pelvic ultrasound confirmed the presence of a normal 20 week gestation and hepatic ultrasound and brain CT scan disclosed no metastases. Pregnancy termination was recommended, but declined by the patient. She initially refused hospitalization or further therapy. She finally consented to thoracotomy and resection of the lung metastasis, but consented only to methotrexate chemotherapy. Following surgery, the patient attended the follow-up clinic sporadically, but hCG titers decreased from 6370 to 3 100 mIU/ml. At 34 l/2 weeks gestation she was seen at another institution and noted to have an hCG in excess of 10,000 mIU/ml. She was persuaded to undergo metastatic workup. Chest x ray and hepatic ultrasound were again negative, but a l-cm left frontal metastasis was identified on brain CT. Only after a grand ma1seizure at 36 weeks gestation did the patient consent to wholebrain radiotherapy and delivery of an 1820-gmale infant, apgars 6 and 8, by cesarean section. Modified Bagshawe chemotherapy was initiated and hCG titers returned to baseline after two cycles of this treatment and completion of 3000 rad of whole-brain therapy. Two additional courses of modified Bagshawe therapy were given. At 3 years after therapy, both mother and infant were alive and well. Although the antifolinics aminopterin and methotrexate both have the ability to produce deformities in the human fetus when administered in the first trimester of pregnancy [3,4], aggressive chemotherapy given after the
123
CASE REPORT
100,000
II
10,000
Pulm
km1
t Y A
2.0
1.5
4180 6/80
1960
Y 0
3161 s/al 7161 9181 1981
00 5.5
7.0
L-7
t
1
0’ 2fao
a 4.3
Ultrasound “20 Weeks”
Resection Pulmonary Metastasis
k------------‘4162 5182
*6/82
7182
a/a2
9162
IO/62
1/k
i 982 FIGURE
first trimester of gestation does not preclude normal births in most cases. In a study by Blatt et al. [5], growth and development and subsequent school performance of offspring treated after the first trimester were shown to be unaffected by such chemotherapy. Although other agents such as Actinomycin-D or Sfluorouracil might have been employed with success in the management of the patient presented, neither has a demonstrated advantage over methotrexate. In addition to illustrating the deleterious effect of partial compliance by patient upon a management scheme, this case summary highlights the importance of adequate contraception and sufficient duration of surveillance hCG titers in patients treated for malignant gestational trophoblastic disease. Goldstein ef al. [6] have suggested that a 6-month follow-up period is adequate after evacuation of a hydatidiform mole lacking such ominous features as uterine size exceeding that of a 20 week gestation, serum titer greater than 40,000 mIU, theta lutein cysts over 5 cm in diameter, or pulmonary complications at the time of evacuation. Malignant trophoblastic disease may recur at intervals of greater than 1 year following remission, but such occurrences are rare [71. After treatment of malignant trophoblastic disease or evacuation of a mole with ominous features, a full year of monitoring is crucial. Another point illustrated in this case is the fact that a
I
substantial rise of tumor-related hCG was detectable given the stable baseline hCG of late pregnancy. Had brain metastases arisen during the first trimester hCG peak, diagnosis may have been delayed. An additional observation from the case presented is the risk of brain metastases associated with the presence of pulmonary lesions. Bagshawe [8] has recommended that all patients with pulmonary metastases receive prophylactic intrathecal methotrexate to obviate the risk of central nervous system spread. Such an aggressive approach has not gained acceptance in this country. Solitary resistant pulmonary metastases may be surgically resected for cure [9], but such an approach is most successful with lesions less than 5 cm [IO] and must never be performed without adequate perioperative chemotherapeutic coverage.
REFERENCES 1. Miller, J. M., Smwit, E. A., and Hammond, C. B. Choriocarcinoma following term pregnancy, Obstet. Gynecol. 53, 207-212 (1979). 2. Kuhn, R. J. P., Long, A. R., and Fortune, D. W. Choriocarcinoma coexistent with intrauterine pregnancy, Aust. NZ J. Obstet. Gynecol. 20, 94-98 (1980). 3. Milunsky, A., Graef, J. W., and Graynor, M. F. Methotrexateinduced congenital malformations, J. Pediatr. 72, 790-795 (1968).
124
SUTTON ET AL.
4. Powell, H. R., and Ekert, H. Methotrexate-induced congenital malformations, Med. J. Aust. 2, 1076 (1971). 5. Blatt, J., Mulvihill, J. J., Ziegler, J. L., et al. Pregnancy outcome following cancer chemotherapy of Hodgkin’s disease, Amer. J. Med. 69, 828-832 (1980). 6. Goldstein, D. P., and Berkowitz, R. S. Gestational trophoblastic neoplusms, Saunders, Philadelphia (1982). 7. Surwit, E. A., and Hammond, C. B. Recurrent gestational trophoblastic disease, Gynecol. Oncol. 12, 177-183 (1981).
8. Bagshawe, K. D. Treatment of high-risk choriocarcinoma, J. Reprod. Med. 29, 813-818 (1984). 9. Sink, J. D., Hammond, C. B., and Young, W. G. Pulmonary resection in the management of metastases from gestational choriocarcinoma, J. Thorac. Cardiovasc. Surg. 81, 830-834 (1981). 10. Xu, L. T., Sun, F. S., Wang, Y. E., et al. Resection of pulmonary metastatic choriocarcinoma in 43 drug-resistant patients, Ann. Thorac. Surg. 39, 257-259 (1985).
ONCOLOGY
34, 122-124 (1989)
CASE REPORT Metastatic Choriocarcinoma Complicated by Term Pregnancy’ GREGORY SUTTON, Department
M.D.,* MICHAEL HOGAN, M.D.,3 NORMAN ROSENBLUM, M.D.,3
of Obstetrics
and Gynecology,
University
of Pennsylvania,
AND
JOHN
3400 West Spruce Street, Philadelphia,
J. MIKUTA, JR., M.D. Pennsylvania
19104
Received March 21. 1988
Malignant gestational trophoblastic disease arising after term pregnancy is associated with a poorer prognosis than postmolar trophoblastic disease [l]. Choriocarcinoma coexistent with intrauterine pregnancy has also been reported [2]. The case described herein represents the rare occurrence of a term pregnancy in a patient with preexisting metastatic choriocarcinoma and serves to underscore the need for adequate contraception in the follow-up of patients treated for malignant gestational trophoblastic disease. CASE REPORT A 19-year-old unmarried black female was referred to the Hospital of the University of Pennsylvania at 20 weeks gestation in April 1982 with the history of having spontaneously aborted a hydatidiform mole in February 1980 (see Fig. 1). She had a postabortal curettage which produced tissue containing focal atypia. A second curettage, performed for plateauing hCG levels, contained histologic changes consistent with choriocarcinoma. Two courses of Actinomycin D were given and hCG titers became undetectable. Nine months later, she became pregnant and underwent an elective abortion at 12 weeks gestation; normal gestational products were identified with no evidence of trophoblastic disease. Oral contraceptives were started, but hCG levels began to rise and she was treated with alternating methotrexate and folinic acid. A chest radiograph at this time revealed a 2-cm left lower lobe metastatic nodule and she received 3 l/2 ’ Supported in part by the American Cancer Society Career Developmental Award 86-74. * To whom reprint requests should be addressed at Department of Obstetrics and Gynecology, Indiana University Medical School, 926 West Michigan Street, Indianapolis, IN 46223. 3 Present address: Lankenau Hospital, Medical Science Building, Suite 3305, Philadelphia, PA 19151. 122 OWO-8258/89
$1.50
Copyright 0 1989by AcademicPress,Inc. All rights of reproduction in any form reserved.
courses of chemotherapy with methotrexate/Actinomycin D/chlorambucil, achieving negative titers before refusing further treatment in September 1981. in April of the following year, she presented to the Hospital of the University of Pennsylvania at 20 weeks gestation with pleuritic chest pain and cough. The pulmonary nodule now measured 4.3 cm in diameter and fine needle aspiration confirmed the diagnosis of metastatic choriocarcinoma. HCG titer was 8600 mIU/ml. Pelvic ultrasound confirmed the presence of a normal 20 week gestation and hepatic ultrasound and brain CT scan disclosed no metastases. Pregnancy termination was recommended, but declined by the patient. She initially refused hospitalization or further therapy. She finally consented to thoracotomy and resection of the lung metastasis, but consented only to methotrexate chemotherapy. Following surgery, the patient attended the follow-up clinic sporadically, but hCG titers decreased from 6370 to 3 100 mIU/ml. At 34 l/2 weeks gestation she was seen at another institution and noted to have an hCG in excess of 10,000 mIU/ml. She was persuaded to undergo metastatic workup. Chest x ray and hepatic ultrasound were again negative, but a l-cm left frontal metastasis was identified on brain CT. Only after a grand ma1seizure at 36 weeks gestation did the patient consent to wholebrain radiotherapy and delivery of an 1820-gmale infant, apgars 6 and 8, by cesarean section. Modified Bagshawe chemotherapy was initiated and hCG titers returned to baseline after two cycles of this treatment and completion of 3000 rad of whole-brain therapy. Two additional courses of modified Bagshawe therapy were given. At 3 years after therapy, both mother and infant were alive and well. Although the antifolinics aminopterin and methotrexate both have the ability to produce deformities in the human fetus when administered in the first trimester of pregnancy [3,4], aggressive chemotherapy given after the
123
CASE REPORT
100,000
II
10,000
Pulm
km1
t Y A
2.0
1.5
4180 6/80
1960
Y 0
3161 s/al 7161 9181 1981
00 5.5
7.0
L-7
t
1
0’ 2fao
a 4.3
Ultrasound “20 Weeks”
Resection Pulmonary Metastasis
k------------‘4162 5182
*6/82
7182
a/a2
9162
IO/62
1/k
i 982 FIGURE
first trimester of gestation does not preclude normal births in most cases. In a study by Blatt et al. [5], growth and development and subsequent school performance of offspring treated after the first trimester were shown to be unaffected by such chemotherapy. Although other agents such as Actinomycin-D or Sfluorouracil might have been employed with success in the management of the patient presented, neither has a demonstrated advantage over methotrexate. In addition to illustrating the deleterious effect of partial compliance by patient upon a management scheme, this case summary highlights the importance of adequate contraception and sufficient duration of surveillance hCG titers in patients treated for malignant gestational trophoblastic disease. Goldstein ef al. [6] have suggested that a 6-month follow-up period is adequate after evacuation of a hydatidiform mole lacking such ominous features as uterine size exceeding that of a 20 week gestation, serum titer greater than 40,000 mIU, theta lutein cysts over 5 cm in diameter, or pulmonary complications at the time of evacuation. Malignant trophoblastic disease may recur at intervals of greater than 1 year following remission, but such occurrences are rare [71. After treatment of malignant trophoblastic disease or evacuation of a mole with ominous features, a full year of monitoring is crucial. Another point illustrated in this case is the fact that a
I
substantial rise of tumor-related hCG was detectable given the stable baseline hCG of late pregnancy. Had brain metastases arisen during the first trimester hCG peak, diagnosis may have been delayed. An additional observation from the case presented is the risk of brain metastases associated with the presence of pulmonary lesions. Bagshawe [8] has recommended that all patients with pulmonary metastases receive prophylactic intrathecal methotrexate to obviate the risk of central nervous system spread. Such an aggressive approach has not gained acceptance in this country. Solitary resistant pulmonary metastases may be surgically resected for cure [9], but such an approach is most successful with lesions less than 5 cm [IO] and must never be performed without adequate perioperative chemotherapeutic coverage.
REFERENCES 1. Miller, J. M., Smwit, E. A., and Hammond, C. B. Choriocarcinoma following term pregnancy, Obstet. Gynecol. 53, 207-212 (1979). 2. Kuhn, R. J. P., Long, A. R., and Fortune, D. W. Choriocarcinoma coexistent with intrauterine pregnancy, Aust. NZ J. Obstet. Gynecol. 20, 94-98 (1980). 3. Milunsky, A., Graef, J. W., and Graynor, M. F. Methotrexateinduced congenital malformations, J. Pediatr. 72, 790-795 (1968).
124
SUTTON ET AL.
4. Powell, H. R., and Ekert, H. Methotrexate-induced congenital malformations, Med. J. Aust. 2, 1076 (1971). 5. Blatt, J., Mulvihill, J. J., Ziegler, J. L., et al. Pregnancy outcome following cancer chemotherapy of Hodgkin’s disease, Amer. J. Med. 69, 828-832 (1980). 6. Goldstein, D. P., and Berkowitz, R. S. Gestational trophoblastic neoplusms, Saunders, Philadelphia (1982). 7. Surwit, E. A., and Hammond, C. B. Recurrent gestational trophoblastic disease, Gynecol. Oncol. 12, 177-183 (1981).
8. Bagshawe, K. D. Treatment of high-risk choriocarcinoma, J. Reprod. Med. 29, 813-818 (1984). 9. Sink, J. D., Hammond, C. B., and Young, W. G. Pulmonary resection in the management of metastases from gestational choriocarcinoma, J. Thorac. Cardiovasc. Surg. 81, 830-834 (1981). 10. Xu, L. T., Sun, F. S., Wang, Y. E., et al. Resection of pulmonary metastatic choriocarcinoma in 43 drug-resistant patients, Ann. Thorac. Surg. 39, 257-259 (1985).