Acta Obstet Gynecol Scand 54: 303-305, 1975
RELATIONSHIP BETWEEN ENDOMETRIAL ARIAS-STELLA PHENOMENON AND CONCENTRATIONS OF URINARY CHORIONIC GONADOTROPIN AND SERUM HUMAN PLACENTAL LACTOGEN Olavi Ylikorkala and Matti Korhonen From the Department of Obstetrics and Gynecology (Head: Professor Peniii A . Jarvinen) and the Depariment of Pathology (Head: Professor Kai Dammert), University of Oulu, Oulu, Finland
Abstract. Serum placental lactogen (HPL) and urinary chorionic gonadotrophin (HCG) were measured in 14 patients with the endometrial Arias-Stella phenomenon and in 35 comparable patients without this reaction in order to explore a possible causative relationship between the hormonal levels and the endometrial changes. The concentrations of HPL and HCG were similar in both groups of patients, indicating a lack of correlation between the levels of these two hormones and endometrial changes.
Focal changes in endometrium from cases of uterine abortion, hydatidiform mole and chorionic carcinoma were first described by Arias-Stella (1). Similar endometrial changes have been reported in varying proportions of cases of these conditions and of ectopic pregnancy (2, 3, 6, 8). The cause of this reaction is disputed but Beswick & Gregory (3) speculated that the changes might result from alterations in hormonal balance due to disturbance of the trophoblast. The present study was designed to study the possibility that imbalance in the output of the two peptide hormones synthesized by syncytiotrophoblastic cells, plays a part in the etiology of the Arias-Stella phenomenon.
MATERIAL AND METHODS From 49 patients whose pregnancies ended unsuccessfully after vaginal bleeding, serum HPL and urinary HCG concentrations were measured on the first day in hospital. The mean duration of pregnancy, calculated from the first day of the last menstrual period, was 11.4 weeks with range of 7 to 16 weeks. Curettage was
performed 1-3 days after beginning of the vaginal bleeding. The tissue obtained at evacuation was fixed in buffered 10% formal-saline and 5 p thick paraffin sections were made and stained with haematoxylin and eosin. In 14 cases, including one ectopic pregnancy, focal endometrial changes as described by Arias-Stella ( I ) were observed (Fig. 1). In 35 cases the endometrium was normal or showed some pathology but no Arias-Stella reaction. The mean duration of pregnancy in patients with the Arias-Stella atypia was 9.5 weeks (range 7-16 weeks) and in patients without this atypia 12.1 weeks (range 8-16 weeks). Serum HPL was determined by a double antibody radioimmunoassay using the HCS Sclavo-Sorin kit (Saluggia, Italy) (4). The determinations were made in duplicate and the variation was 8.0%. Twenty-fourhour urinespecimens were collected during the first day in hospital. The HCG content was measured semiquantitatively by the test of Pregnosticon (Organon, Holland). The sensitivity limit of this test is I500 IU/l urine.
RESULTS The concentrations of HPL and HCG in each patient are shown in Fig. 2. The means of HPL and HCG levels in cases with or without the Arias-Stella phenomenon are not calculated because the durations of the pregnancies varied. The distribution of the patients with the Arias-Stella phenomenon was not different from the cases without this abnormality. The patients can be divided into two groups by a line where the relative increases in the concentrations of HPL and HCG were the same. (Fig. 2). Eight out of 28 cases above the line and six out of 21 cases below the line had the Arias-Stella reaction. Acta Obsrer Gynecol Scand 54 (1975)
0.Ylikorkala crnd M.Korhonen
304
Fig. I . Endometrial Arias-Stella reaction showing intraluminal budding, enlargement and vacuolation of
DISCUSSION The diagnosis of ectopic pregnancy before the occurrence of an abdominal catastrophe may be difficult partly because the pregnancy tests are often negative. Synthesis and release of HCG HPL
.
w/ml serum 0.40
-
0
0
0.20
-
010-
0
0
Fig. 2. Distribution of the patients kcording to the
concentrations of serum HPL and urinary HCG. Eight out of 28 cases above the line and six out of 21 cases below the line had the endometrial Arias-Stella reaction. Acta Obstet Gynecol Scand 54 (1975)
cells with slight nuclear hyperchromasia and hypertrophy. Haematoxylin and eosin, x 350.
from ectopic trophoblastic tissue is diminished (1 I), but maternal circulating HPL levels in ectopic pregnancies are normal (9). Because the AriasStella phenomenon is commonly associated with ectopic pregnancies (2, 3, 6), it might be thought that the dominance of HPL over HCG in ectopic pregnancy plays a part in the etiology of the phenomenon, but our results do not support this. In molar pregnancies, serum HPL levels have been reported to be lower but HCG output higher than normal (7, 10). We did not have any cases of molar pregnancy, but the dominance of HCG over HPL without hydatidiform degeneration was not related to the occurrence of Arias-Stella reaction. Infiltration of the cytoplasm with glycogen seems to be the cause for the appearance of cells in the Arias-Stella phenomenon (3). As HPL may play a role in the metabolism of carbohydrates and fats in pregnancy ( 5 ) it is possible, that glycogen infiltration and HPL levels are related to each other. However, in this study the AriasStella phenomenon was not related to the absolute HPL level.
Arias-Stella phenomenon ACKNOWLEDGEMENT m e authors gratefully acknowledge Dr Frej Stenback for his help. This study was supported by a P a n t from the Emil Aaltonen Foundation, Tampere, Finland.
7.
REFERENCES
8.
J.: Atypical endometrial changes associated with presence of chorionic tissue. Arch Path58: 112, 1954. Berthelsen, H. G.: Atypical endometrial changes in extra-uterine pregnancy: Arias-Stella’s phenomenon. Acta Obstet Gynecol Scand 36: 226, 1957. Beswick, I. P. & Gregory, M. M.: The AriasStella phenomenon and the diagnosis of pregnancy. J Obstet Gynaecol Br Comm 78: 143, 1971. Cocola, F., Genazzani, A. R. & Neri, P.: A critical evaluation of the double antibody radioimmunoassay of HCS for use in clinical practice. Folia Allergoll8: 518, 1971. Felber, J. P., Zaragoza, N., Benuzzi-Badoni, M. & Genazzani, A. R.: The double effect of human chorionic somatomammotropin (HCS) and pregnancy on lipogenesis and lipolysis in the isolated rat epidymal fat pad and fat cells. Horm Metab Resl: 293, 1972. Fredericksen, T.: The Arias-Stella reaction as an
1 . Arias-Stella,
2. 3. 4.
5.
6.
9. 10.
11.
305
aid in the diagnosis of ectopic pregnancy. Acta Obstet Gynecol Scand37: 86, 1958. Goldstein, D. p.: serum placental lactogen activity in patients molar pregnancy and trophob~astic tumors. A reliable index of malignancy. Am J Obstet GynecolllO: 583, 1971. Mackles, A., Wolfe, S. A. & Pozner, S. N.: Cellular atypia in endometrial glands (Arias-Stella reaction) as an aid in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol81: 1209, 1%1. Niven, P. A. R., Landon, J. & Chard, T.: Placental lactogen levels as guide to outcome of threatened abortion. Br Med J 3: 799, 1972. Saxena, B. N., Goldstein, D. P., Emerson, K. & Selenkow, H. A.: Serum placental lactogen levels in patients with molar pregnancy and trophoblastic tumors. Am J Obstet GynecollO2: 115, 1968. Wide, L.: An immunological method for the assay of human chorionic gonadotrophin. Acta Endocrinol (Kbh)4l: (Suppl. 70) I: 1 1 1 , 1%2.
Submitted for publication Febr. 22, 1974
Olavi Ylikorkala Department of Obstetrics and Gynecology University of Oulu Oulu Finland
Acta Obster Gynecol Scand 54 (1975)
RELATIONSHIP BETWEEN ENDOMETRIAL ARIAS-STELLA PHENOMENON AND CONCENTRATIONS OF URINARY CHORIONIC GONADOTROPIN AND SERUM HUMAN PLACENTAL LACTOGEN Olavi Ylikorkala and Matti Korhonen From the Department of Obstetrics and Gynecology (Head: Professor Peniii A . Jarvinen) and the Depariment of Pathology (Head: Professor Kai Dammert), University of Oulu, Oulu, Finland
Abstract. Serum placental lactogen (HPL) and urinary chorionic gonadotrophin (HCG) were measured in 14 patients with the endometrial Arias-Stella phenomenon and in 35 comparable patients without this reaction in order to explore a possible causative relationship between the hormonal levels and the endometrial changes. The concentrations of HPL and HCG were similar in both groups of patients, indicating a lack of correlation between the levels of these two hormones and endometrial changes.
Focal changes in endometrium from cases of uterine abortion, hydatidiform mole and chorionic carcinoma were first described by Arias-Stella (1). Similar endometrial changes have been reported in varying proportions of cases of these conditions and of ectopic pregnancy (2, 3, 6, 8). The cause of this reaction is disputed but Beswick & Gregory (3) speculated that the changes might result from alterations in hormonal balance due to disturbance of the trophoblast. The present study was designed to study the possibility that imbalance in the output of the two peptide hormones synthesized by syncytiotrophoblastic cells, plays a part in the etiology of the Arias-Stella phenomenon.
MATERIAL AND METHODS From 49 patients whose pregnancies ended unsuccessfully after vaginal bleeding, serum HPL and urinary HCG concentrations were measured on the first day in hospital. The mean duration of pregnancy, calculated from the first day of the last menstrual period, was 11.4 weeks with range of 7 to 16 weeks. Curettage was
performed 1-3 days after beginning of the vaginal bleeding. The tissue obtained at evacuation was fixed in buffered 10% formal-saline and 5 p thick paraffin sections were made and stained with haematoxylin and eosin. In 14 cases, including one ectopic pregnancy, focal endometrial changes as described by Arias-Stella ( I ) were observed (Fig. 1). In 35 cases the endometrium was normal or showed some pathology but no Arias-Stella reaction. The mean duration of pregnancy in patients with the Arias-Stella atypia was 9.5 weeks (range 7-16 weeks) and in patients without this atypia 12.1 weeks (range 8-16 weeks). Serum HPL was determined by a double antibody radioimmunoassay using the HCS Sclavo-Sorin kit (Saluggia, Italy) (4). The determinations were made in duplicate and the variation was 8.0%. Twenty-fourhour urinespecimens were collected during the first day in hospital. The HCG content was measured semiquantitatively by the test of Pregnosticon (Organon, Holland). The sensitivity limit of this test is I500 IU/l urine.
RESULTS The concentrations of HPL and HCG in each patient are shown in Fig. 2. The means of HPL and HCG levels in cases with or without the Arias-Stella phenomenon are not calculated because the durations of the pregnancies varied. The distribution of the patients with the Arias-Stella phenomenon was not different from the cases without this abnormality. The patients can be divided into two groups by a line where the relative increases in the concentrations of HPL and HCG were the same. (Fig. 2). Eight out of 28 cases above the line and six out of 21 cases below the line had the Arias-Stella reaction. Acta Obsrer Gynecol Scand 54 (1975)
0.Ylikorkala crnd M.Korhonen
304
Fig. I . Endometrial Arias-Stella reaction showing intraluminal budding, enlargement and vacuolation of
DISCUSSION The diagnosis of ectopic pregnancy before the occurrence of an abdominal catastrophe may be difficult partly because the pregnancy tests are often negative. Synthesis and release of HCG HPL
.
w/ml serum 0.40
-
0
0
0.20
-
010-
0
0
Fig. 2. Distribution of the patients kcording to the
concentrations of serum HPL and urinary HCG. Eight out of 28 cases above the line and six out of 21 cases below the line had the endometrial Arias-Stella reaction. Acta Obstet Gynecol Scand 54 (1975)
cells with slight nuclear hyperchromasia and hypertrophy. Haematoxylin and eosin, x 350.
from ectopic trophoblastic tissue is diminished (1 I), but maternal circulating HPL levels in ectopic pregnancies are normal (9). Because the AriasStella phenomenon is commonly associated with ectopic pregnancies (2, 3, 6), it might be thought that the dominance of HPL over HCG in ectopic pregnancy plays a part in the etiology of the phenomenon, but our results do not support this. In molar pregnancies, serum HPL levels have been reported to be lower but HCG output higher than normal (7, 10). We did not have any cases of molar pregnancy, but the dominance of HCG over HPL without hydatidiform degeneration was not related to the occurrence of Arias-Stella reaction. Infiltration of the cytoplasm with glycogen seems to be the cause for the appearance of cells in the Arias-Stella phenomenon (3). As HPL may play a role in the metabolism of carbohydrates and fats in pregnancy ( 5 ) it is possible, that glycogen infiltration and HPL levels are related to each other. However, in this study the AriasStella phenomenon was not related to the absolute HPL level.
Arias-Stella phenomenon ACKNOWLEDGEMENT m e authors gratefully acknowledge Dr Frej Stenback for his help. This study was supported by a P a n t from the Emil Aaltonen Foundation, Tampere, Finland.
7.
REFERENCES
8.
J.: Atypical endometrial changes associated with presence of chorionic tissue. Arch Path58: 112, 1954. Berthelsen, H. G.: Atypical endometrial changes in extra-uterine pregnancy: Arias-Stella’s phenomenon. Acta Obstet Gynecol Scand 36: 226, 1957. Beswick, I. P. & Gregory, M. M.: The AriasStella phenomenon and the diagnosis of pregnancy. J Obstet Gynaecol Br Comm 78: 143, 1971. Cocola, F., Genazzani, A. R. & Neri, P.: A critical evaluation of the double antibody radioimmunoassay of HCS for use in clinical practice. Folia Allergoll8: 518, 1971. Felber, J. P., Zaragoza, N., Benuzzi-Badoni, M. & Genazzani, A. R.: The double effect of human chorionic somatomammotropin (HCS) and pregnancy on lipogenesis and lipolysis in the isolated rat epidymal fat pad and fat cells. Horm Metab Resl: 293, 1972. Fredericksen, T.: The Arias-Stella reaction as an
1 . Arias-Stella,
2. 3. 4.
5.
6.
9. 10.
11.
305
aid in the diagnosis of ectopic pregnancy. Acta Obstet Gynecol Scand37: 86, 1958. Goldstein, D. p.: serum placental lactogen activity in patients molar pregnancy and trophob~astic tumors. A reliable index of malignancy. Am J Obstet GynecolllO: 583, 1971. Mackles, A., Wolfe, S. A. & Pozner, S. N.: Cellular atypia in endometrial glands (Arias-Stella reaction) as an aid in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol81: 1209, 1%1. Niven, P. A. R., Landon, J. & Chard, T.: Placental lactogen levels as guide to outcome of threatened abortion. Br Med J 3: 799, 1972. Saxena, B. N., Goldstein, D. P., Emerson, K. & Selenkow, H. A.: Serum placental lactogen levels in patients with molar pregnancy and trophoblastic tumors. Am J Obstet GynecollO2: 115, 1968. Wide, L.: An immunological method for the assay of human chorionic gonadotrophin. Acta Endocrinol (Kbh)4l: (Suppl. 70) I: 1 1 1 , 1%2.
Submitted for publication Febr. 22, 1974
Olavi Ylikorkala Department of Obstetrics and Gynecology University of Oulu Oulu Finland
Acta Obster Gynecol Scand 54 (1975)
