Elevated Serum Alpha-fetoprotein Levels Research Articles

A Normal Ultrasound Does Not Obviate the Need for Amniocentesis in Patients With Elevated Serum Alpha-Fetoprotein

Elevated levels of maternal serum alpha-fetoprotein (MSAFP) will identify a population at increased risk for specific congenital malformations, which are accurately diagnosed by amniotic fluid AFP and acetylcholinesterase. The risk for spontaneous abortion related to amniocentesis, combined with increasing confidence in the accuracy of ultrasound diagnosis, has caused us to question the need for amniocentesis in the diagnostic workup of pregnancies complicated by elevated levels of AFP in maternal serum. A retrospective study of 257 pregnancies evaluated for elevated serum AFP levels revealed 16 fetal malformations diagnosed by amniotic fluid AFP and acetylcholinesterase. Only 12 of these malformations were diagnosed on the initial ultrasound study. All malformations were diagnosed when ultrasound examination was repeated for increased acetylcholinesterase activity. Earlier gestational age at scanning, smaller defects, and pure technical failure were implicated as causes of misdiagnosis. The rate of fetal malformations identified in this high-risk population (6.23%) and the rate of ultrasound misdiagnosis (1.5% of the population with elevated levels of MSAFP) imply that amniocentesis should still be considered an essential part of the diagnostic workup in these situations.

Localization of an ataxia-telangiectasia gene to chromosome 11q22-23.

Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes. Furthermore, heterozygous females are at an increased risk of breast cancer. These findings, when coupled with an estimated carrier frequency of 0.5-5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.

Easurements of placental, decidual, and fetal proteins before and after chorionic villus sampling

Circulating placental [human chorionic gonadotrophin (hCG), Schwangerschafts protein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), decidual (pregnancy protein 12 (PP12), and fetal alphafetoprotein (AFP)] proteins were measured immediately before and within 1 h in 18 women undergoing diagnostic chorionic villus sampling (CVS) in the first trimester. An elevation of serum AFP levels was consistently seen, while fluctuations in excess of 10 per cent of the pre-CVS levels of SP1 and PP12 were seen in the majority of patients. Fluctuations in hCG and PAPP-A were consistently less than 10 per cent of pre-CVS values. Post-CVS changes in levels were not apparently associated with any feature of the technique, the pregnancy, or its outcome (one missed abortion). As feto-maternal haemorrhage is a common event, anti-D should be offered to rhesus-negative women undergoing CVS. In the prediction of subsequent miscarriage, only hCG and PAPP-A measurements should be considered.

Elevated alpha-fetoprotein and a normal fetal sonogram: association with placental abnormalities

This report documents the outcome of 25 pregnancies with elevated serum alpha-fetoprotein levels on two separate samplings despite normal anatomic appearance of the fetus on a detailed "consultative" sonographic examination. Six of these also had elevated amniotic fluid alpha-fetoprotein. All fetuses in this series were anatomically normal at time of delivery; one aborted fetus was triploid. Of the 25 pregnancies, 16 had sonographically demonstrable placental hemorrhage, eight retroplacental and eight subchorionic. One had hydropic changes in the placenta associated with triploidy. Of the subgroup of six pregnancies in which both serum and amniotic fluid values were elevated, one had a retroplacental hemorrhage, one had a subchorionic hemorrhage, and one had diffuse hydropic changes in the placenta. A control group of 112 patients with normal alpha-fetoprotein levels yielded four with small (less than 2 cm3) subchorionic hemorrhage. The occurrence rate of placental hemorrhage in women with elevated alpha-fetoprotein and normal fetus was 64%, whereas the control group of patients with normal alpha-fetoprotein had a 3.6% occurrence rate of placental hemorrhage. Sonographically detectable placental abnormalities may be associated with elevated alpha-fetoprotein in serum and/or amniotic fluid samples. Such abnormalities may occur because of fetomaternal admixture associated with placental hemorrhage and/or intraamniotic bleeding resulting from subchorionic hemorrhage.

Outcome of Pregnancy in Relation to Maternal Serum Alpha-Fetoprotein Levels in the Second Trimester

120 women with elevated alpha-fetoprotein (AFP) in pregnancy week 16-17 were subsequently supervised every 4th week until a few days postpartum. A group of 102 women with normal (n = 78) or low (n = 24) serum AFP concentrations in pregnancy week 16-17 were studied in the same way. In the last week before parturition the AFP serum level declined and the decrease was more pronounced with increasing gestational duration up to pregnancy week 41. The AFP level relationship between the women was stable on average throughout the pregnancies. Smoking was found to be related to elevated maternal serum AFP levels in pregnancy week 16-17. Among mothers younger than 25 years, 72% of those with high or very high AFP serum levels in pregnancy week 16-17 were smokers. Among women with elevated or much elevated maternal serum AFP levels in pregnancy week 16-17, male fetuses predominated. But only those carrying female fetuses gave premature birth to small-for-date children. Further analysis of the data revealed that if such a woman was a multipara, there was a 54% risk of a small-for-date premature female baby. Other data indicate that this risk may be increased by smoking and maternal age. It is recommended that this category of mothers with elevated AFP in pregnancy week 16-17 is continuously supervised during pregnancy.

Ovarian yolk sac tumor arising from an endometrioid carcinoma

A yolk sac tumor that arose within an ovarian endometrioid adenocarcinoma in a 50-year-old woman is described. The tumor had typical microscopic features, stained immunohistochemically for alpha-fetoprotein, and was associated with an elevated serum alpha-fetoprotein level when metastases appeared. This is the fourth case in which a yolk sac tumor has been reported to develop from a somatic carcinoma and the second in which this tumor has been associated with epithelium of endometrioid type. Tumor heterogeneity or neometaplasia may account for the origin of a tumor of germ cell type from a carcinoma of somatic origin.

Intrapericardial yolk sac tumor in an infant girl

This article is a report on the first known case of an intrapericardial yolk sac (endodermal sinus) tumor discovered in a 14-month-old girl. The patient presented with a systolic murmur, cardiomegaly, and manifestations of cardiac failure. At surgery a large, friable, intrapericardial mass with no evidence of extrapericardial spread was found. Histologic and immunohistochemical findings were diagnostic of yolk sac tumor. Following initial resection, chemotherapy, and a second resection 13 months after the first, the patient died 24 months after diagnosis. Tumor enlargement was associated with elevated serum alpha-fetoprotein levels.

Maternal Floor Infarction of the Placenta Associated with Elevated Second Trimester serum Alpha-Fetoprotein

Maternal floor infarction is a recurring placental disease of ubiquitous perivillous fibrin deposition with obliteration of normal placental architecture. In this case, elevated levels of maternal serum alpha-fetoprotein (AFP) were found as well as a small fetal-maternal bleed. The association between placental disease and elevated maternal serum AFP is discussed.

Alpha-Fetoprotein Associated with Islet Cell Tumors

Elevated serum levels of alpha-fetoprotein (AFP) (100-1,000 ng/ml) were found in three patients with islet cell tumors. Serial levels correlated with progression of disease, suggesting that AFP could be a useful tumor marker substance for islet cell tumors. Survey sera from an expanded pool of 23 patients with islet cell tumors and nine with carcinoid tumors did not identify additional cases, however, suggesting that elevated AFP levels in these classes of Apudomas are uncommon. Nonetheless, the distinction from other AFP-producing tumors such as hepatocellular carcinoma is clinically important and warrants an awareness of the rare association of AFP with these tumors.

Human Chorionic Gonadotropin and Alpha‐Fetoprotein in Sera and Tumor Cells of a Patient with Pure Dysgerminoma of the Ovary: A case report with radio‐immunoassay and immunoperoxidase

One of 7 patients with pure dysgerminoma had slightly elevated serum human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) levels as determined by radio-immunoassay before operation. The values returned to the normal range after the removal of the tumor. The cells that produced the HCG or AFP were identified by immunohistochemical staining of the tumor tissues. HCG proved positive both in the multinucleated giant cells with eosinophilic cytoplasm and in the spindle-shaped cells with a hyperchromatic nucleus. AFP was positively stained in the round cells. These results suggest that HCG and AFP are produced by the cells which constitute pure dysgerminoma.

Elevated maternal α-fetoprotein levels with subsequent fetal exsanguination

Presented is a case with persistently elevated maternal serum alpha-fetoprotein and normal amniotic fluid alpha-fetoprotein values associated with subsequent fetal-maternal bleeding and fetal death. Fetal-maternal bleeding, with potential for rhesus sensitization and fetal death, should be considered in the presence of elevated serum alpha-fetoprotein levels.

Epididymal melanotic neuroectodermal tumor of infancy

Six melanotic neuroectodermal tumors of infancy arising in the epididymis were reported previously. Each followed a benign clinical course. In the seventh case of such a tumor, reported herein, an elevated serum alpha-fetoprotein level returned to normal following excision of the tumor. Urinary and serum tumor markers may be useful for following the course of these tumors in the future.

Intrapleural endodermal sinus tumor arising from the diaphragm

We report a primary endodermal sinus tumor (EST) of the right hemidiaphragm, presenting as a right-sided hemothorax in an 18-month-old female. Four operations were performed, the last three being indicated solely by an elevated level of serum alpha-fetoprotein (AFP). Cyclic chemotherapy with varying drug combinations together with irradiation therapy were not effective in controlling the disease. To our knowledge, this is the first instance of a primary EST arising from the diaphragm.

Testicular tumour markers in tissue correlated to serum levels and clinical stage.

Clinical investigation of 11 patients with testicular tumour included tests for the marker substances AFP (alpha fetoprotein) and HCG (human chorionic gonadotropin) in serum and in tumour tissue, using an indirect immunoperoxidase technique. In one case of pure seminoma, neither AFP nor HCG was detectable in tissue or in serum. In eight of ten patients with non-seminomatous germ cell tumour there was AFP-immunoreactivity in tumour tissue, and seven of them also had elevated serum levels of AFP. Five patients showed HCG-immunoreactivity in tumour tissue and the same number had elevated serum levels of HCG. The findings indicated good correlation between immunoreactivity of tumour tissue, serum level of the tumour markers and clinical stage of the neoplastic disease.

Tumour markers in testicular germ cell tumours. Five-year experience from the DATECA Study 1976-1980.

Since Jan. 1, 1976, nearly all new cases of testicular germ cell tumours have been included in the Danish Testicular Carcinoma Study (DATECA), and have been monitored by the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). During the first five years, 1058 patients participated in the investigation, but only 603 of these patients were followed by preoperative as well as postoperative marker determinations in serum. The overall prevalence of marker positivity, i.e. elevated preoperative values for AFP and/or HCG, was 8 per cent for seminoma patients and 60 per cent for non-seminoma patients. Elevated levels of serum AFP and HCG were correlated to the presence of endodermal sinus tumour and choriocarcinoma elements, respectively, in the primary tumour. The presence of increased marker concentration in serum was correlated stage (higher percentage in higher stages) and to prognosis (marker negative patients had a better prognosis than marker positive patients). Marker production by seminoma patients seems to indicate a poor prognosis, especially for HCG producing seminomas.

Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer

We used an indirect immunoperoxidase technique to localize alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.

Elevated maternal serum alpha-fetoprotein, second-trimester oligohydramnios, and pregnancy outcome.

Although the primary purpose of maternal serum alpha-fetoprotein (AFP) screening is to detect open neural tube defects, the technique is of value in the diagnosis of other fetal abnormalities. Six patients from the Alpha-Fetoprotein Screening Program, Perinatal Region IV, were found to have twice elevated maternal serum AFP levels associated with severe early second-trimester oligohydramnios. Five of the fetuses were found to have urinary tract abnormalities. The source of the elevated maternal serum AFP is not clear. Pregnancy prognosis appears poor. These cases should be thoroughly studied so that patients may be accurately informed of the recurrence risk.

Psychological reactions experienced by pregnant women with an elevated serum alpha-fetoprotein level

Repeated semistructured interviews with 66 singleton-pregnant women disclosed that when they were notified that they had an elevated serum AFP level, 47 per cent reacted with panic, 35 per cent with reasonable concern, and 18 per cent with denial. Three days later, these proportions had changed to 14, 21, and 65 per cent, respectively. On the latter occasion an interviewer judged that 74 per cent of the women were severely or considerably anxious about fetal malformations.Twenty-five women who required extended investigation did not experience more strain during this period than women for whom one control serum assay sufficed. After completion of the total investigation 56 of the women did not regret that they had undergone the serum AFP test.The present findings show that being informed about abnormal serum AFP test results induces immediate and severe though temporary emotional distress that can be alleviated by adequate medical information and reasonable psychological support.

Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: histologic and immunohistochemical analyses of 35 cases.

By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.

Prenatal diagnosis of exstrophy of the cloaca.

While screening for neural tub defects, three cases of exstrophy of the cloaca were found through elevated second-trimester maternal serum alphafetoprotein levels. Measurement of amniotic fluid alphafetoprotein and examination of the structure of rapidly adhering cells confirmed the abnormalities, and the pregnancies were terminated. Subsequent studies of cholinesterase isozymes by acrylamide electrophoresis showed an abnormal acetylcholinesterase band in each of the three amniotic fluids. During the same period, two more cases of exstrophy of the cloaca were identified in spontaneous abortions and another one in a stillbirth. It is suggested that the condition is more common than has been previously suspected and is often misclassified as omphalocele.