Eur. J. Epidemiol. 0392-2990 March 1992, p. 173-177

EUROPEAN JOURNAL

Vol. 8, No. 2

OF

EPIDEMIOLOGY

INCIDENCE OF GESTATIONALTROPHOBLASTICDISEASE IN STOCKHOLM COUNTY, 1975-1988 F. FLAM*1, V. LUNDSTRI3M-LINDSTEDT* and L.E. RUTQVIST** *Department o f Obstetrics a n d Gynecology. **Oncologic Centre - R a d i u m h e m m e t - Karolinska Hospital - S-104 01 Stockholm - Sweden.

Key words: Incidence - Trophoblastic disease - Sweden

An epidemiologicalstudy with the aim of establishing the incidence of hydatidiformmole, persistent trophoblastic disease and choriocarcinomain Stockholm County was performed. Based on the regional cancer registryand hospital registers, the incidencefor 1975-1988 was calculatedfor the number of deliveries as well as the total number of pregnancies. Of the molar pregnancies, 6% were treated with chemotherapy because of invasive mole or choriocarcinoma. Non-molar choriocarcinoma occurred in 1/33,717 deliveries. Difficulties in assessing the incidence of gestational trophoblastic disease are discussed.

INTRODUCTION

There is reportedly a marked variation in the incidence of gestational trophoblastic disease (GTD) between different parts of the world but also between studies performed within the same country describing different regions or time periods. Generally, there is greater consistency in studies performed in the western hemisphere. The highest frequencies for both the benign entity, hydatidiform mole, and the malignant forms - invasive mole and choriocarcinoma - have been reported from parts of Africa and from the Far East. The extreme values reported for hydatidiform mole are 12/1000 deliveries in Indonesia and 0.5/1000 deliveries in North America (6.7). The more recent and better performed studies from the Far East have documented a lower incidence that is approaching the numbers given for the western hemisphere. A nation-wide study performed in China found an incidence of 0.8/1000 pregnancies (5). There are many factors contributing to the difficulties in assessing incidence. All products of conception have the potential for developing into a trophoblastic Corresponding author.

disease. From this point of view follows the importance of reliable vital statistics. Abortions are not legal in many countries and the total number of pregnancies will be highly approximative. Many studies avoid this problem by providing GTD cases for the number of deliveries only. The hospital-based studies, especially those from under-developed countries, will tend to under-estimate the population at risk since many births, for example, take place at home. In hydatidiform mole there is always material for the histopathological diagnosis. However, there is no sharp distinction between hydatidiform mole and hydatidiform degeneration. The only Swedish report describing the incidence of GTD is from 1970 and covers patients treated between 1958 and 1965 (8). That report was based on the Swedish Cancer Registry. Recently, the reliability of this register with respect to GTD was evaluated (Flam & Rutqvist, unpublished data). Although reporting of all cases of hydatidiform mole to the Cancer Registry is mandatory for both the pathologist and the clinician involved, it was found that only 75% of the molar cases occurring in Stockholm County between 1971 and 1986 were reported to the register. The data presented in this paper cover all known

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Eur. J. Epidemiol.

cases of hydatidiform mole, persistent trophoblastic disease and chofiocarcinoma in a well-defined Swedish population, Stockholm County, from 1975 until 1988. Stockholm County is inhabited by 1.6 million people and constitutes approximately 20% of the Swedish population.

MATERIAL AND METHODS

The Regional Cancer Register and a computerized register covering nearly all hospital admissions in the region were used for ascertaining cases of hydatidiform mole. Basically, the inclusion criteria relied on the histopathological diagnosis by the pathologist at each hospital. The records of the cases identified only by the hospital registers were reviewed. When there was an equivocal histopathological diagnosis and the clinician decided to follow the case according to procedures for hydatidiform mole the case was included. For ascertaining the cases of persistent trophoblastic disease and choriocarcinoma, the same two registers used for hydatidiform mole were utilized. In addition, a register kept at the Department of Obstetrics and Gynecology at the Karolinskka Hospital where nearly all cases of the malignant forms were treated was used. All of these records were reviewed. All cases with a histopathological diagnosis of choriocarcinoma had been primarily diagnosed or reviewed at one pathology department. The criteria used were absence of villi, disorganized proliferation of cytotrophoblast and syncytiotrophoblast, cytologic atypicality, necrosis and hemorrhage. The total number of spontaneous, missed and legal abortions as well as ectopic pregnancies were obtained from the in-patient register for Stockholm

County which covers nearly all hospital admissions. Data on deliveries were abstracted from the Swedish Medical Birth Registry. RESULTS

The incidence of hydatidiform mole, persistent trophoblastic disease and gestational trophoblastic neoplasia not preceded by a molar pregnancy, by definition choriocarcinoma, were calculated from the available registers. These data were related to the number of deliveries as well as the total number of pregnancies. Hydatidiform mole

The regional Cancer Register of Stockholm County was the primary source of information. With the information obtained from the local hospital registers, the number of patients with hydatidiform mole for the years 1975-1988 was 393. Among these, 20 patients had an equivocal histopathological diagnosis but were included based on the opinion of the clinician. Table 1 demonstrates the total number of moles as well as the total number of pregnancies. Based on these data, the incidence of hydatidiform mole for both deliveries and pregnancies has been calculated as 1/686 and 1/1103, respectively. Table 1 provides data on the age distribution of hydatidiform mole. In the oldest age group, 45 years or older, the risk of a molar pregnancy in relation to deliveries was 1/11. In order to assess a time trend in the incidence of hydatidiform mole, patients were analyzed according to the year of diagnosis (Table 2). The study period was divided into three sections. There were no marked difference in incidence between the time periods.

TABLE 1. - Number of moles, by age of patient, for deliveries and pregnancies in Stockholm County, 1975-1988. Age (years)

15-19

20-24

25-29

30-34

35-39

40-44

45-

All ages

21

96

97

106

142

18

13

393

Spontaneous and missed abortions, ectopics

1,378

6,402

10,723

10,278

6,442

2,611

416

38,250

Legal abortions

19,981

32,399

26,453

21,941

17,047

7,048

795

125,664

Deliveries

10,487

60,577

96,933

71,348

26,109

4,138

142

269,734

Moles/delivery

1/499

1/631

1/999

1/673

1/622

1/230

1/11

1/686

2.0

1.6

1.0

1.5

1.6

4.4

91.0

1.5

1/1516

1/1035

1/1383

1/977

1/1181

1/767

1/104

1/1103

0.7

1.0

0.7

1.0

0.9

1.3

9.6

0.9

Moles

Rate/1000 deliveries Moles/pregnancy Rate/1000 pregnancies

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Incidence of trophoblastic disease in Stockholm County

TABLE 2. - Number of moles, by period of diagnosis, in relation to deliveries and pregnancies in Stockholm County 1975-1988. Time period

1975-1979

Moles Mole/delivery

119

152

122

1/777

1/606

1/698

1.3

1.7

1.4

1/1,1299

1/989

1/1,115

0.8

1.0

0.9

Rate/1000 deliveries Mole/pregnancy

1980-1984 1985-1988

Rate/1000 pregnancies

and the risk of persistent disease in different age groups are demonstrated in Table 3. Overall, 1/17 molar patients (6%) required chemotherapy. Table 4 shows the overall risk to deliveries (1/11,728) and pregnancies (1/18,854).

Choriocarcinoma There were 8 cases of choriocarcinoma, as seen in Table 3. Histopathological confirmation was obtained in all but one patient. The incidence in relation to deliveries is 1/33,717 and to pregnancies 1/54.206 (Table 4). The two patients with choriocarcinoma following a hydatidiform mole are not included.

DISCUSSION

Persistent trophoblastic disease There were 23 patients requiring chemotherapy in follow-up of a hydatidiform mole. Basically, treatment with chemotherapy was initiated when levels of hCG rose or reached a plateau for three consecutive weeks. Two of the patients did have a histopathological diagnosis of choriocarcinoma. The age distribution

In this study, the incidence of hydatiform mole and choriocarcinoma in relation to number of deliveries and pregnancies in the Stockholm area is presented. Almost all deliveries in Sweden are performed in a hospital. All spontaneous abortions, except very early ones (up to the 8th week of

TABLE 3. - Age distribution of hydatidiform mole, persistent trophoblastic disease and non-molar choriocarcinoma in Stockholm County, 1975-1988. Age (years)

15-19

20-24

25-29

30-34

35-39

40-44

45-

All ages

Moles

21

96

97

106

42

18

13

393

Persistent trophoblastic disease

-

7

3

6

4

-

3

23

Non-molar choriocarcinoma

-

2

1

-

2

-

3

8

Persistent trophoblastic disease/mole

-

1/14

1/32

1/18

1/11

-

1/4

1/17

Rate persistent trophoblastic disease/100 moles

-

7

3

6

9

-

25

6

TABLE 4. - Incidence of persistent trophoblastic disease and non-molar choriocarcinoma in Stockholm County, 1975-1988. Per delivery

Per 1000 deliveries

Per pregnancy

Per 1000 pregnancies

Persistent trophoblastic disease

1/11,728

0.09

1/18,854

0.05

Non-molar choriocarcinoma

1/33,717

0.03

1/54,206

0.02

Total

i/8,572

0.11

1/13,989

0.07

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Flam F. et aL

pregnancy), and patients undergoing a legal termination of pregnancy are admitted to hospitals. Abortion has been available on the woman's request since 1975, therefore illegal abortions are extremely rare. All hospital admissions are recorded and it can therefore be concluded that the figures for the number of deliveries and pregnancies are accurate. As mentioned previously, it is mandatory to report all cases of GTD to the Swedish Cancer Registry. No histopathological review of the molar cases was performed. Franke evaluated almost 400 cases of hydatidiform mole diagnosed in the Netherlands from 1978 to 1980 (3). By applying strict criteria he found the diagnosis to be incorrect in 25% of the cases. Seven percent were considered to be partial moles and 18% non-molar abortions. A similar review of molar cases in this data has not been carried out. On the other hand, there is reason to believe that many cases of molar pegnancies are not detected. There are false positive moles as well as false negative moles. The distinction between hydropic degeneration and molar pregnancy is not a very clear one. Furthemore, while it is routine that the material collected at a spontaneous abortion undergoes histopathological examination, this is not the case in patients with legal abortion. Most of the abortions are performed during the first trimester of pregnancy, where the incidence of hydatidiform mole could be as high as 1/600 (2). Since approximately 125,000 legal abortions were performed during the period of study, a thorough examination of the aborted material no doubt would have contributed to the number of moles. The incidence of hydatidiform mole, 1.46/1000 deliveries, in this study is twice that usually presented from the western world, including an earlier Swedish study (8). However, this figure comes close to the reported 1.54/1000 live births in 1983 for England and Wales (1). Whether the higher frequency of hydatidiform mole found in the present study in comparison to that of Ringertz represents a true increase in incidence or differences in methodology is difficult to assess. There are, however, several methodological factors supporting the latter conclusion. In the present study patients were identified not only by the National Cancer Registry but also by hospital records. In the present study, as mentioned above, patients clinically treated as cases of hydatidiform mole but without a certain histopathological diagnosis were also included. The study populations in the two studies were not identical. The present study describes conditions in Stockholm County, while the study by Ringertz included all of Sweden. In comparison to the rest of the country, the population of Stockholm County is more heterogenous due to the fact that many immigrants have been attracted to Stockholm. Data that relates to the ethnic background of pregnant women is not reported to the various registries. Therefore, an analysis containing information on possible ethnic differences in incidence was not carried out. Immigrants from Arab countries, for

Eur. J. Epidemiol.

example, tend to experience more pregnancies than do Swedish women. The correlation between reproductive variables and GTD prevalence has not been adequately studied. It is known that the risk for developing hydatidiform mole is much greater in younger and in older woman. Gravidity per se, however, seems not to be an independent risk factor although more data are needed on this issue. Possibly, the reguirements and accuracy of reporting to the Cancer Registry could differ between areas. In Ringertz' study the exact number of invasive mole and choriocarcinoma could be provided since hysterectomies were then performed as the primary treatment. Any study describing conditions after the introduction of chemotherapy as the basic treatment for both invasive mole and choriocarcinoma can only partly separate these entities. The number of patients with post-molar choriocarcinoma will be unknown. Certainly, at any center the majority of the patients with a pathological hCG regression curve will suffer from invasive mole, but a fair number of patients with choriocarcinoma will also be included. This number will, of course, be greater the stricter the criteria for initiating treatment are. Ringertz found in his study that 3.5% of the molar patients underwent subsequent hysterectomy, of these 2% were invasive moles and 1.5% choriocarcinomas. Other studies performed in the pre-chemotherapy time period indicate that the incidence of choriocarcinoma after a molar pregnancy does not exceed 3%. The figure for persistent trophoblastic disease reported here, 6%, is in accordance with other European centers where this number seldom exceeds 10% (9). American centers, however, treat around 25% of their molar patients (4). The cases of choriocarcinoma are few and the incidence found here, 1/54,206 pregnancies, is similar to figures already reported. It correlates well with Ringertz' study. It should again be emphasized that w e have not included the two cases of verified choriocarcinoma found in the group with persistent disease.

REFERENCES

Dent J. and Webb J. (1986): Hydatidiform mole in England and Wales 1973-1983. Lancet. 11: 673-677.

Bagshave K.D.,

. Cohen B.A., Burkman R.T., Rosenshein N.B., Atienza M.F., King T.M. and Parmely T.H. (1979): Gestational trophoblastic disease within an elective abortion population. - Am. J. Obstet. Gynecol. 135: 452-454. . Franke H.R. (1983): Gestational trophoblastic disease in the Netherlands. Thesis - Amsterdam - University of the Netherlands. . Morrow P.C. (1984): Postmolar trophoblastic disease: Diagnosis management and prognosis - Clin. Obstet. Gynecol. 27: 211-220. 176

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Incidence of trophoblastic disease in Stockholm County

Gynecol. I5: 735-739.

5. National Coordination Research Group of Chorioma (1980): Incidence of hydatidiform mole (a retrograde study of 2,023,621 women in 23 provinces) - Zhoghus Yixue Zazhi, 60: 641-644.

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6. Poen H.T. and Djojopranoto M (1986): The possible etiologic factors of hydatidiform mole and choriocarcinoma: preliminary report - Am. J. Obstet. Gynecol. 92: 510-513.

Ringertz N. (1970): Hydatidiform mole, invasive mole and choriocarcinoma in Sweden 1958-1965 - Acta Obstet. Gynecol, Scand. 49: 195-203.

. Stone M. and Bagshawe K.D. (1979): An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy - Br, J. Obstet. Gynaecol. 86: 782-792.

7. Reiner 1 and Dougherty C.M. (1960): Clinical and pathologic aspects of hydatidiform mole - Obstet.

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Incidence of gestational trophoblastic disease in Stockholm County, 1975-1988.

An epidemiological study with the aim of establishing the incidence of hydatidiform mole, persistent trophoblastic disease and choriocarcinoma in Stoc...
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