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Partial hydatidiform mole with diploid karyotype: Report of three cases
Partial hydatidiform mole with diploid karyotype: Report of three cases Nelson N. H. Teng, M.D., Ph.D., and Samuel C. Ballou, M.D. Stanford, California Recent studies suggest that a partial mole with a triploid karyotype has little tendency to invade and metastasize and usually requires no therapy other than evacuation. This report describes three patients with a mole of normal diploid karyotype coexisting with a living fetus. Each patient had persistent elevation of human chorionic gonadotropin. Two patients required chemotherapy; one of these had invasive mole. The partial mole with normal diploid karyotype is a distinct clinical entity with the potential for malignant sequelae. The possibility of twin gestation cannot be excluded. (AM J OBSTET GvNECOL 1984;150:961-4.)
Traditionally, the classic or complete hydatidiform mole has no associated embryo or fetus and has a 46,XX or 46,XY karyotype of paternal derivation whereas the partial or incomplete mole is accompanied by a fetus and has a triploid 69,XXY karyotype. 1 The reported incidence of hydatidiform mole coexisting with a fetus varies from 1 of 10,000 to 1 of 100,000 pregnancies; however, histologic reevaluation has revealed that up to 35% of moles have coexisting embryonal or fetal parts. 2 Ten to 20% of patients with complete mole require chemotherapy for persistent serum elevation of human chorionic gonadotropin, a rise or plateau in human chorionic gonadotropin titer, or metastases. In general, incomplete mole is not associated with the development of persistent gestational trophoblastic neoplasia; however, myometrial invasion and a malignant evolution with a fatal outcome rarely have been reported. This report describes three cases of hydatidiform mole with a coexisting living fetus. All three patients had persistent elevation of human chorionic gonadotropin, and two required chemotherapy. The karyotype of the mole, placenta, and fetus was normal diploid in each case.
Case histories Case 1. A 30-year-old woman, gravida 4, para 2, abortus 1, with an estimated 15-week gestation developed intermittent vaginal spotting, hypertension (190/ 110 mm Hg), and proteinuria. A sonogram revealed a single fetus with the biparietal diameter of a 13V2-week From the Section of Gynecologic Oncology, Department of Gynecology and Obstetrics, Stanford University School of Medicine. Presented at the Eleventh Annual Meeting of the Western Association of Gynecologic Oncologists, Colorado Springs, Colorado, May 2629, 1983. Received for publication December 14, 1983; accepted June 29, 1984. Reprint requests: Nelson N. H. Teng, M.D., Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305.
gestation, a 12 x 12 em mixed echogenic mass consistent with a molar pregnancy, and bilateral cystic adnexal masses. Physical findings included hyperthyroidism, high-output congestive cardiac failure, and a fundal height of 22 em with audible fetal heart tones. A quantitative human chorionic gonadotropin determination was 270,000 miU/ml. A suction curettage produced 400 gm of molar tissue and a 50 gm fetus and placenta. Thyroid function tests returned to normal 48 hours after evacuation. One month after curettage the patient was readmitted because of vaginal bleeding and elevation of the serum human chorionic gonadotropin titer to 303,000 miU/ mi. The uterus was enlarged to 16 em. No metastases were noted on physical examination or chest roentgenogram. Treatment consisted of four courses of actinomycin D (Fig. 1). A hysterectomy performed during the second course of chemotherapy revealed extensive myometrial invasion by hydropic molar villi with exuberant proliferation of both cytotrophoblastic and syncytiotrophoblastic elements. The clinical and laboratory manifestations of hyperthyroidism paralleled the rise and subsequent decline of serum human chorionic gonadotropin to undetectable levels. The karyotype of the fetus, mole, and placenta was 46,XX. Case 2. A 22-year-old woman, gravida 2, para 1, abortus 0, presented with a first-trimester uterus larger than expected and vaginal bleeding. A sonogram revealed a living fetus, coexistent molar gestation, and bilaterally enlarged, cystic ovaries. All other radiographic and laboratory examinations were normal. Following an unsuccessful induction with intravaginal prostaglandin, a 300 gm normal male fetus and abundant molar tissue were evacuated. The serum human chorionic gonadotropin level was determined weekly and was persistently elevated 10 weeks after termination of the pregnancy. A prompt response to actinomycin D therapy was obtained and no elevation of titer has been noted during the succeeding 8 months (Fig. 2). The karyotype of the mole, fetus, and normal placental tissue was 46,XY.
961
962 Teng and Bailon
December 15, 1984 Am J Obstet Gynecol
1,000,000 TAH
100,000
10,000
1,000
100
t t
t r Act D
10
Time (months)
Fig. 1. Clinical course of Case 1. TAH, Total abdominal hysterectomy. Act D, Actinomycin D.
Case 3. A 24-year-old woman, gravida 2, para I, abortus 0, presented with vaginal bleeding at 20 weeks' gestation. The uterus was not enlarged. Fetal heart tones were audible. A sonogram revealed a viable ISweek fetus and a large placenta with multiple areas of coexistent hydatidiform mole. The serum level of human chorionic gonadotropin was 878,000 miU/ml. Hypertension (1401100 mm Hg), proteinuria, and hyperreflexia were noted. A suction curettage yielded a grossly normal male fetus, normal placenta, and approximately 300 gm of molar tissue. The serum level of human chorionic gonadotropin slowly regressed to undetectable levels 5 months after termination of the pregnancy (Fig. 3). The karyotype of the fetus, molar tissue, and placenta was 46,XY.
Comment The malignant potential of partial or incomplete hydatidiform mole remains controversial. In part, this controversy reflects lack of uniform diagnostic criteria. Szulman and Surti' require identification of a coexistent fetus, a functioning villous vasculature, and focal hyperplasia of the trophoblast. In addition, virtually all incomplete moles in their series are triploid. In contrast, Vassilakos et al.' make the diagnosis of incomplete hydatidiform mole whenever there is visible swelling of the villi irrespective of the degree or extent of trophoblastic hyperplasia. Several patients have developed malignant sequelae after the diagnosis of incomplete hydatidiform mole.
Partial hydatidiform mole
Volume 150 Number 8
963
1,000,000
100,000
10,000
\
;::; s
';; >:
1,000
\ \ Act D
l
100
r
l
10
Time (months)
Fig. 2. Clinical course of Case 2. Act D, Actinomycin D.
All of these patients required chemotherapy after evacuation. One patient succumbed to widespread choriocarcinoma. Only one of these patients had fetal and molar tissues subjected to chromosomal analysis that revealed triploidy. Each of the three patients described in this report had a hydatidiform mole with coexistent living fetus. In each case, the mole was diploid and demonstrated hypertrophic villi with focal atypical trophoblastic proliferation consistent with the diagnosis of incomplete hydatidiform mole. Each patient had a persistent serum elevation of human chorionic gonadotropin. Invasion was noted in the hysterectomy specimen of the first patient.
The possibility of twin gestations cannot be excluded but would not alter the clinical management. Patients with hydatidiform mole and coexistent fetus require evacuation of the products of conception followed by a search for metastases and weekly monitoring of the serum level of human chorionic gonadotropin. Karyotyping of the products of gestation might be of prognostic importance but is not readily applicable to this patient population. As with the complete hydatidiform mole, absence of metastases should be associated with a virtual 100% survival even if chemotherapy is required. The coexistent fetus is normal by gross morphologic and cytogenetic analysis and does not appear to be a high-risk factor for patients with hydatidiform
964 Teng and Bailon
December 15, 1984 Am J Obstet Gynecol
1,000,000
\ 100,000
10' 000
1,000
100
10
Time
(months)
Fig. 3. Clinical course of Case 3.
mole. More data are needed to further delineate this interesting but rare condition. We wish to acknowledge Drs. William Dworsky and Sheldon Schein for their participation in the care of these patients.
REFERENCES I. Szu1man AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. AM J 0BSTET GYNECOL 1978;131:665-71.
2. Czernobilsky B, Barash A, Lancet M. Partial moles: A clinicopathologic study of 25 cases. Obstet Gynecol 1982; 59:75-7. 3. Szulman AE, Surti U. The syndromes of hydatidiform mole. II. Morphologic evolution of the complete and partial mole. AMJ 0BSTET GYNECOL 1978;132:20-7. 4. Vassilakos P, Riotton G, Kajii T. Hydatidiform mole-two entities: a morphologic and cytogenetic study with some clinical considerations. AM J 0BSTET GYNECOL 1977; 127: 167~70.
Traditionally, the classic or complete hydatidiform mole has no associated embryo or fetus and has a 46,XX or 46,XY karyotype of paternal derivation whereas the partial or incomplete mole is accompanied by a fetus and has a triploid 69,XXY karyotype. 1 The reported incidence of hydatidiform mole coexisting with a fetus varies from 1 of 10,000 to 1 of 100,000 pregnancies; however, histologic reevaluation has revealed that up to 35% of moles have coexisting embryonal or fetal parts. 2 Ten to 20% of patients with complete mole require chemotherapy for persistent serum elevation of human chorionic gonadotropin, a rise or plateau in human chorionic gonadotropin titer, or metastases. In general, incomplete mole is not associated with the development of persistent gestational trophoblastic neoplasia; however, myometrial invasion and a malignant evolution with a fatal outcome rarely have been reported. This report describes three cases of hydatidiform mole with a coexisting living fetus. All three patients had persistent elevation of human chorionic gonadotropin, and two required chemotherapy. The karyotype of the mole, placenta, and fetus was normal diploid in each case.
Case histories Case 1. A 30-year-old woman, gravida 4, para 2, abortus 1, with an estimated 15-week gestation developed intermittent vaginal spotting, hypertension (190/ 110 mm Hg), and proteinuria. A sonogram revealed a single fetus with the biparietal diameter of a 13V2-week From the Section of Gynecologic Oncology, Department of Gynecology and Obstetrics, Stanford University School of Medicine. Presented at the Eleventh Annual Meeting of the Western Association of Gynecologic Oncologists, Colorado Springs, Colorado, May 2629, 1983. Received for publication December 14, 1983; accepted June 29, 1984. Reprint requests: Nelson N. H. Teng, M.D., Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305.
gestation, a 12 x 12 em mixed echogenic mass consistent with a molar pregnancy, and bilateral cystic adnexal masses. Physical findings included hyperthyroidism, high-output congestive cardiac failure, and a fundal height of 22 em with audible fetal heart tones. A quantitative human chorionic gonadotropin determination was 270,000 miU/ml. A suction curettage produced 400 gm of molar tissue and a 50 gm fetus and placenta. Thyroid function tests returned to normal 48 hours after evacuation. One month after curettage the patient was readmitted because of vaginal bleeding and elevation of the serum human chorionic gonadotropin titer to 303,000 miU/ mi. The uterus was enlarged to 16 em. No metastases were noted on physical examination or chest roentgenogram. Treatment consisted of four courses of actinomycin D (Fig. 1). A hysterectomy performed during the second course of chemotherapy revealed extensive myometrial invasion by hydropic molar villi with exuberant proliferation of both cytotrophoblastic and syncytiotrophoblastic elements. The clinical and laboratory manifestations of hyperthyroidism paralleled the rise and subsequent decline of serum human chorionic gonadotropin to undetectable levels. The karyotype of the fetus, mole, and placenta was 46,XX. Case 2. A 22-year-old woman, gravida 2, para 1, abortus 0, presented with a first-trimester uterus larger than expected and vaginal bleeding. A sonogram revealed a living fetus, coexistent molar gestation, and bilaterally enlarged, cystic ovaries. All other radiographic and laboratory examinations were normal. Following an unsuccessful induction with intravaginal prostaglandin, a 300 gm normal male fetus and abundant molar tissue were evacuated. The serum human chorionic gonadotropin level was determined weekly and was persistently elevated 10 weeks after termination of the pregnancy. A prompt response to actinomycin D therapy was obtained and no elevation of titer has been noted during the succeeding 8 months (Fig. 2). The karyotype of the mole, fetus, and normal placental tissue was 46,XY.
961
962 Teng and Bailon
December 15, 1984 Am J Obstet Gynecol
1,000,000 TAH
100,000
10,000
1,000
100
t t
t r Act D
10
Time (months)
Fig. 1. Clinical course of Case 1. TAH, Total abdominal hysterectomy. Act D, Actinomycin D.
Case 3. A 24-year-old woman, gravida 2, para I, abortus 0, presented with vaginal bleeding at 20 weeks' gestation. The uterus was not enlarged. Fetal heart tones were audible. A sonogram revealed a viable ISweek fetus and a large placenta with multiple areas of coexistent hydatidiform mole. The serum level of human chorionic gonadotropin was 878,000 miU/ml. Hypertension (1401100 mm Hg), proteinuria, and hyperreflexia were noted. A suction curettage yielded a grossly normal male fetus, normal placenta, and approximately 300 gm of molar tissue. The serum level of human chorionic gonadotropin slowly regressed to undetectable levels 5 months after termination of the pregnancy (Fig. 3). The karyotype of the fetus, molar tissue, and placenta was 46,XY.
Comment The malignant potential of partial or incomplete hydatidiform mole remains controversial. In part, this controversy reflects lack of uniform diagnostic criteria. Szulman and Surti' require identification of a coexistent fetus, a functioning villous vasculature, and focal hyperplasia of the trophoblast. In addition, virtually all incomplete moles in their series are triploid. In contrast, Vassilakos et al.' make the diagnosis of incomplete hydatidiform mole whenever there is visible swelling of the villi irrespective of the degree or extent of trophoblastic hyperplasia. Several patients have developed malignant sequelae after the diagnosis of incomplete hydatidiform mole.
Partial hydatidiform mole
Volume 150 Number 8
963
1,000,000
100,000
10,000
\
;::; s
';; >:
1,000
\ \ Act D
l
100
r
l
10
Time (months)
Fig. 2. Clinical course of Case 2. Act D, Actinomycin D.
All of these patients required chemotherapy after evacuation. One patient succumbed to widespread choriocarcinoma. Only one of these patients had fetal and molar tissues subjected to chromosomal analysis that revealed triploidy. Each of the three patients described in this report had a hydatidiform mole with coexistent living fetus. In each case, the mole was diploid and demonstrated hypertrophic villi with focal atypical trophoblastic proliferation consistent with the diagnosis of incomplete hydatidiform mole. Each patient had a persistent serum elevation of human chorionic gonadotropin. Invasion was noted in the hysterectomy specimen of the first patient.
The possibility of twin gestations cannot be excluded but would not alter the clinical management. Patients with hydatidiform mole and coexistent fetus require evacuation of the products of conception followed by a search for metastases and weekly monitoring of the serum level of human chorionic gonadotropin. Karyotyping of the products of gestation might be of prognostic importance but is not readily applicable to this patient population. As with the complete hydatidiform mole, absence of metastases should be associated with a virtual 100% survival even if chemotherapy is required. The coexistent fetus is normal by gross morphologic and cytogenetic analysis and does not appear to be a high-risk factor for patients with hydatidiform
964 Teng and Bailon
December 15, 1984 Am J Obstet Gynecol
1,000,000
\ 100,000
10' 000
1,000
100
10
Time
(months)
Fig. 3. Clinical course of Case 3.
mole. More data are needed to further delineate this interesting but rare condition. We wish to acknowledge Drs. William Dworsky and Sheldon Schein for their participation in the care of these patients.
REFERENCES I. Szu1man AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. AM J 0BSTET GYNECOL 1978;131:665-71.
2. Czernobilsky B, Barash A, Lancet M. Partial moles: A clinicopathologic study of 25 cases. Obstet Gynecol 1982; 59:75-7. 3. Szulman AE, Surti U. The syndromes of hydatidiform mole. II. Morphologic evolution of the complete and partial mole. AMJ 0BSTET GYNECOL 1978;132:20-7. 4. Vassilakos P, Riotton G, Kajii T. Hydatidiform mole-two entities: a morphologic and cytogenetic study with some clinical considerations. AM J 0BSTET GYNECOL 1977; 127: 167~70.