Human chorionic gonadotropin is a hormone normally produced by the developing placenta. The protein can be detected in serum or urine and is the basis of pregnancy testing. It is particularly valuable in the diagnosis of ovarian and testicular tumors and in monitoring responses to chemotherapy.
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DISEASE ASSOCIATIONS CHARACTERIZATION Common Associations Mixed germs cell tumors or pure choriocarcinoma of the ovary or testis
Extragonadal mixed germ cell tumors or pure choriocarcinoma
Gestational trophoblastic disease
Less Common Poorly differentiated carcinomas-rare
FALSE POSITIVES CHARACTERIZATION
False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations.
Rotmensch S, Cole LA.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, USA.
Lancet 2000 Feb 26;355(9205):712-5 Abstract quote
BACKGROUND: 12 women were diagnosed of having postgestational choriocarcinoma on the basis of persistently positive human chorionic gonadotropin (hCG) test results in the absence of pregnancy. Most of the women had extirpative surgery or chemotherapy, or both, without significant diminution in hCG titre. Our aim was to assess whether the hCG concentrations were false-positive test results.
METHODS: Samples were tested for hCG, hCG free beta subunit, and hCG beta-core fragment. Assay kinetics were also assessed, and samples were tested independently by competitive RIA. False-positive hCG concentrations were identified by two criteria: detection of hCG in serum and lack of detection of hCG and its degradation products in urine; and wide variations in results for different hCG assays. We corroborated false-positive hCG values by the lack of parallel changes in hCG results when serum was diluted, by false detection of other antigens, and by failure to detect hCG with in-house assays.
FINDINGS: All 12 women met both criteria for false-positive hCG, and all had corroborating findings. In all 12 cases, a false diagnosis had been made, and most of the women had been subjected to needless surgery or chemotherapy. Assay kinetics indicated that heterophilic antibodies were responsible for the false-positive results. As a result of our findings all further therapy was stopped.
INTERPRETATION: Current protocols for the diagnosis and treatment of choriocarcinoma should be modified to include a compulsory test for hCG in urine.
ENDOMETRIAL CARCINOMA Endometrial Adenocarcinoma Associated With Elevated Serum Concentrations of the Free b Subunit of Human Chorionic Gonadotropin
David G. Grenache, PhD, Karen A. Moller, MD, and Pamela M. Groben, MD
Am J Clin Pathol 2004;121:748-753 Abstract quote
We report a case of a histologic grade II endometrial adenocarcinoma without trophoblastic differentiation in a 24-year-old woman with an elevated serum concentration of human chorionic gonadotropin (hCG) and with no evidence of pregnancy. Serum and urine specimens were used to study the hCG immunoreactivity.
Qualitative tests performed on serum and urine using 5 different assays produced conflicting results. The hCG concentration in serum and urine was quantified using assays designed to detect different molecular forms of the molecule; analysis revealed that serum hCG immunoreactivity was due entirely to the presence of the free b subunit. Immunohistochemical analysis performed on tissue samples showed strong cytoplasmic staining for hCG.
While hCG is a well-recognized tumor marker in gynecologic malignant neoplasms, immunoreactivity most often is due to the presence of both intact molecule and the free b subunit. To our knowledge, this is the first report of an endometrial adenocarcinoma producing only the free b subunit of hCG.
MULTIPLE MYELOMA Positive Pregnancy Tests in a Nongravid, Premenopausal Woman Due to hCG b-Chain Production by Multiple Myeloma
Stephen P. Slone, MD, etal.
Am J Clin Pathol 2005;124:108-112 Abstract quote
Positive pregnancy test results occurred in a nongravid, premenopausal woman while she was receiving chemotherapy for multiple myeloma.
We tested 2 hypotheses to account for this finding: (1) Heterophil antibodies caused positive interference in the immunoassays. (2) Genuine human chorionic gonadotropin (hCG) originated from a nonsyncytiotrophoblastic source. Paraprotein was eliminated as a source of positive interference because 3 different instruments with unique capture and signal antibodies gave similar results (83, 90, and 97 mIU/mL [83, 90, and 97 IU/L]). Human antimouse antibodies (HAMAs) were unlikely to cause positive interference because immunoreactivity was maintained after serum was treated to neutralize heterophil antibodies. Immunoassays performed after gel filtration of serum indicated that immunoreactivity was due to genuine hCG. The high-molecular-weight fraction (heterophil antibody) had 6 mIU/mL (6 IU/L) of hCG. The low-molecular-weight fraction (hCG) had 86 mIU/mL (86 IU/L) of hCG.
Immunohistochemical stains revealed that myeloma cells expressed immunoreactive hCG. Hence, multiple myeloma caused positive pregnancy test results in a nongravid woman.
Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases.
Cole LA, Shahabi S, Butler SA, Mitchell H, Newlands ES, Behrman HR, Verrill HL. USA
hCG Reference Service, Obstetrics and Gynecology, University of New Mexico, Albuquerque, NM 87131, USA.
Clin Chem 2001 Feb;47(2):308-15 Abstract quote
BACKGROUND: Patients with trophoblastic diseases produce ordinary and irregular forms of human chorionic gonadotropin (hCG; e.g., nicked hCG, hCG missing the beta-subunit C-terminal segment, hyperglycosylated hCG, and free beta subunit) that are recognized to differing extents by automated immunometric hCG (or hCG beta) assays. This has led to low or false-negative results and misdiagnosis of persistent disease. False-positive hCG immunoreactivity has also been detected, leading to needless therapy for trophoblastic diseases. Here we compare seven commonly used hCG assays.
METHODS: Standards for five irregular forms hCG produced in trophoblastic diseases, serum samples from 59 patients with confirmed trophoblastic diseases, and serum samples from 12 women with previous false-positive hCG results (primarily in the Abbott AxSYM assay) were blindly tested by commercial laboratories in the Beckman Access hCG beta, the Abbott AxSYM hCG beta, the Chiron ACS:180 hCG beta, the Baxter Stratus hCG test, the DPC Immulite hCG test, the Serono MAIAclone hCG beta tests, and in the hCG beta RIA.
RESULTS: Only the RIA and the DPC appropriately detected the five irregular hCG standards. Only the Beckman, DPC, and Abbott assays gave results similar to the RIA in the patients with confirmed trophoblastic diseases (values within 25% of RIA in 49, 49, and 54 of 59 patients, respectively). For samples that were previously found to produce false-positive hCG results, no false-positive results were detected with the DPC and Chiron tests (5 samples, median <2 IU/L), but up to one-third of samples were false positive (>10 IU/L) in the Beckman (1 of 5), Serono (2 of 9), and Baxter assays (1 of 5), and the hCG beta RIA (3 of 9; median for all assays, <5 IU/L). These samples, which produced false-positive results earlier in the Abbott AxSYM assay, continued to produce high values upon reassessment (median, 81 IU/L).
CONCLUSIONS: Of six frequently used hCG immunometric assays, only the DPC detected the five irregular forms of beta hCG, agreed with the RIA, and avoided false-positive results in the samples tested. This assay, and similarly designed assays not tested here, seem appropriate for hCG testing in the diagnosis and management of trophoblastic diseases.
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