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Genitourinary Cancer

False-Positive Serum Human Chorionic Gonadotropin (hCG) in a Male Patient with a Malignant Germ Cell Tumor of the Testis: A Case Report and Review of the Literature

Departments of ^aClinical Chemistry and ^bClinical Oncology, Leiden University Medical Center, Leiden, The Netherlands

Key Words. Human chorionic gonadotropin • Germ cell neoplasms • Testicular neoplasms • Heterophilic antibodies • IgA deficiency • Tumor markers

Correspondence: S. Osanto, M.D., Ph.D., Department of Clinical Oncology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Telephone: 31-71-526-3464; Fax: 31-71-526-6760; e-mail: s.osanto{at}lumc.nl

Received July 24, 2008; accepted for publication September 30, 2008; first published online in THE ONCOLOGIST Express on November 4, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

	ABSTRACT

Top Abstract Introduction Case Report Review of the Literature Conclusions Author Contributions References

 
A 39-year-old male patient with a favorable prognosis stage IIB metastatic malignant germ cell tumor (GCT) and elevated pre- and postorchiectomy serum human chorionic gonadotropin (hCG) was treated with three courses of combination chemotherapy resulting in a rapid normalization of his serum hCG.

Within 2 months after the cessation of chemotherapy, his serum hCG increased again, suggesting tumor recurrence. Pathological examination of the resected residual retroperitoneal lymph nodes revealed no vital tumor cells. Based on the further rise in his serum hCG and enlargement of mediastinal lymph nodes on computed tomography scan, the patient underwent second- and third-line chemotherapy, which did not result in normalization of his serum hCG. Reanalysis of stored serum samples with other immunoassays revealed that the elevated serum hCG levels collected before first-line chemotherapy were indeed elevated, but those collected after first-line chemotherapy were all falsely positive. Currently, the patient is still alive and disease free.

This is the first report of a male cancer patient who received unneeded second- and third-line chemotherapy for relapse based on false-positive hCG results. We discuss the pitfalls of false-positive serum hCG measurements, including heterophilic antibodies, as in our IgA-deficient patient, and review the literature.

	INTRODUCTION

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Malignant germ cell tumors (GCTs) are rare tumors, accounting for 1% of all malignancies, and the commonest type of cancer in young men aged 15–35 years. Patients with metastatic GCTs have an excellent prognosis because of the chemosensitivity of these tumors. The majority of patients present with elevated serum markers, for example, human chorionic gonadotropin (hCG) and/or -fetoprotein (AFP), and their prechemotherapy levels have been integrated into the International Germ Cell Cancer Consensus Group consensus prognostic index for nonseminomatous GCT classification. Patients are stratified into good-, intermediate-, and poor-prognosis subgroups based on the primary tumor site, levels of serum tumor markers, and whether extrapulmonary visceral metastases are present.

Serum hCG levels are thus essential in both the diagnosis and follow-up of hCG-producing GCTs. Staging procedures with chest and abdominal computed tomography (CT) and evaluation of serum markers are used to detect subclinical residual or recurrent tumor, and patient management includes treatment with chemotherapy in cases of a rise in a serum marker. After orchiectomy, an increased level of hCG indicates persistent disease, whereas after chemotherapy-induced complete remission of metastatic disease, reappearance of hCG indicates the presence of a relapse.

	CASE REPORT

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In February 2003, a 39-year-old male patient underwent a unilateral orchiectomy because of a right testicular mass. He had an elevated serum hCG level of 30 U/l (upper normal value, 5 U/l), normal serum levels of AFP, and normal lactate dehydrogenase. Histological examination of the tumor showed an embryonal carcinoma. On an abdominal CT scan he had enlarged retroperitoneal lymph nodes of nearly 3 cm, and his postorchiectomy serum hCG level decreased but did not normalize, consistent with a stage IIB, favorable prognosis metastatic GCT. The patient was referred to our hospital, and systemic treatment consisted of three courses of chemotherapy with bleomycin, etoposide, and cisplatin (BEP) (March until April 2003). The prechemotherapy hCG of 13 U/l decreased to undetectable (<1 U/l) levels within 3 weeks after the start of chemotherapy (Fig. 1). Normalization of his serum hCG and the size of the enlarged retroperitoneal lymph nodes indicated that a complete remission was induced, requiring no further treatment.

View larger version (9K): [in this window] [in a new window]   Figure 1. hCG concentration (U/l) versus time. Serum hCG is plotted over the course of therapy. The BEP chemotherapy regimen was administered from March to April 2003. RPLND was performed on July 8, 2003. TIP chemotherapy was administered during September to October 2003. HDC, consisting of ifosfamide plus etoposide followed by high-dose cyclophosphamide, was administered during November to December 2003. Abbreviations: BEP, bleomycin, etoposide, and cisplatin; hCG, human chorionic gonadotropin; HDC, high-dose chemotherapy; RPLND, retroperitoneal lymph node dissection; TIP, paclitaxel, ifosfamide, and cisplatin.

Postoperatively, his hCG further increased to 280 U/l (Fig. 1). In August 2003, a CT scan of the chest showed two mediastinal lymph nodes of 11 mm diameter each, which were slightly larger than on previous CT scans. We diagnosed a relapse of the patient's hCG-producing GCT and decided to treat him with second-line chemotherapy. From September to October 2003, three courses of chemotherapy with paclitaxel, ifosfamide, and cisplatin were administered, upon which his hCG decreased to 55 U/l. However, thereafter his hCG increased again to 341 U/l (Fig. 1). The enlarged mediastinal nodes did not change in size. We subsequently planned to treat the patient with high-dose chemotherapy and autologous stem cell rescue. He received two courses of ifosfamide plus etoposide followed by high-dose cyclophosphamide in November and December 2003, but stem cell mobilization failed, while his serum hCG values decreased to 145 U/l.

Surprisingly, in January 2004, a normal serum hCG level (<0.5 U/l) was reported, coinciding with a switch to measurements of serum hCG samples on a Modular Analytics E 170 system (Roche Diagnostics, Mannheim, Germany) by our clinical chemistry laboratory. In 2003, the AxSym analyzer total β-hCG method (Abbott Diagnostics, Abbott Park, IL) was used. In all subsequent serum hCG samples collected in 2004, the hCG levels measured using the Modular Analytics E 170 system were undetectable, whereas measurements with the AxSym analyzer resulted in hCG values of approximately 255 U/l. Retesting of the serum samples of March 2003, collected prior to the first BEP chemotherapy, on the Modular Analytics E 170 showed measurable, although somewhat lower, serum hCG values of 9 U/l (upper normal value, 5 U/l), which gradually decreased toward undetectable in April 2003, confirming the initially elevated hCG results found using the AxSym analyzer. Using the AxSym analyzer, hCG was also found in urine samples from January 2004 (7.8 U/l), in the presence of just a trace of albumin in the same urine sample. However, analyses of both serum and urine samples of December 2003, and January 2004, on an Immulite® 2000 (Diagnostic Products Company [DPC], now Siemens Healthcare Diagnostics, Deerfield, IL), an Abbott Architect (Abbott Diagnostics), and using an in-house radioimmunoassay method in the Dutch hCG Reference Laboratory in Nijmegen indicated that the hCG level was undetectable in all samples. Interestingly, AFP was measured in parallel with the hCG assay on the AxSym analyzer. AFP concentrations 7–10 µg/l before, during, and after chemotherapy (upper reference limit, 10 µg/l). The switch to the Roche system did not result in any shift. Other assays for protein hormones, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), have shown no discrepant results.

Thus, our patient presented with a clinical stage IIB nonseminomatous GCT originating in the right testis with confirmed preorchiectomy as well as prechemotherapy elevated serum hCG levels. Following BEP chemotherapy, a pathologically confirmed complete remission was induced. However, he was later misdiagnosed with a relapse of the disease as a result of falsely elevated serum hCG concentrations.

We considered that the reappearance and rise in serum hCG levels following the cessation of curative first-line chemotherapy in this good-prognosis male GCT patient could be ascribed to the presence of heterophilic antibodies, which may interfere with serum two-sided immunometric assays. Heterophilic antibodies have been reported in IgA-deficient individuals. Serum IgA levels measured in January 2004 were below the detection level of 0.14 g/l, no anti-IgA antibodies could be detected in the patient's blood, whereas IgG levels were normal, consistent with an IgA deficiency. The medical history indicated that the patient indeed suffered from recurrent upper respiratory tract and middle ear infections during childhood, and IgA concentrations measured in 1993 were below the lower detection level of 0.1 g/l (normal value, 0.9–4.0 g/l). Various tests were subsequently performed by the clinical chemistry laboratory; the addition of a specific heterophilic antibody-blocking agent from Scantibodies Laboratory, Inc. (Santee, CA) to the AxSym analyzer hCG assay did not result in normal hCG measurements in the patient's serum samples. Dilution of the patient's serum with control serum or other diluents resulted in a nonlinear decrease in the patient' serum hCG concentration. Serum levels of testosterone, LH, FSH, and sex hormone–binding protein were found to be within normal limits in all serum samples prior to the start of first-line (March 2003) as well as after the cessation of third-line chemotherapy (February 2004).

In this young male patient with testicular cancer, measurements of the patient's serum samples resulted in false-positive hCG results as measured by the Abbott AxSym system, and the patient received treatment with high doses of chemotherapy for an erroneously diagnosed relapse of the disease. His history is remarkably misleading because of the initial presentation with an hCG-producing GCT, the prompt decline in serum hCG in parallel with a decrease in size of the enlarged lymph nodes following the institution of chemotherapy, the reappearance 2 months later consistent with an early and thus clinically unfavorable tumor relapse, followed again by a decline in his serum hCG during second-line and third-line treatment with cytotoxic agents. Currently, the patient is still alive and disease free.

	REVIEW OF THE LITERATURE

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hCG is mainly used for the detection and monitoring of pregnancy and pregnancy-related disorders, but it is also an extremely sensitive and specific marker for trophoblastic tumors of placental and germ cell origin. Thus, treatment of metastatic or recurrent testicular GCTs is often initiated on the basis of rising hCG levels, even in the absence of clinical, radiological, or histological evidence of a relapse.

False-positive serum hCG levels have mainly been reported in women suspected of (ectopic) pregnancy, molar gravidity, or gestational trophoblastic neoplasm (GTN). During the last two decades Cole and his coworkers from the USA hCG Reference Service identified a total of 71 women with false-positive hCG results (also called "phantom hCG"), mean 102 ± 152 IU/l (range, 6.1–900) [1–6]. In most of these patients, extensive imaging procedures revealed no measurable abnormal lesion. Forty-seven patients received unneeded chemotherapy. Twelve patients even underwent surgery without finding a malignancy in the operation specimen. Sera of these women were referred to the USA hCG Reference Service, where different hCG assay methods were applied, and the high levels of hCG were found to be falsely elevated. Also, other authors have published case reports on women in whom false-positive hCG results led to a wrong diagnosis and often to invasive diagnostic procedures and harmful treatment [7, 8].

Only a few case reports have dealt with falsely elevated hCG results in male patients with GCTs, in some cases leading to unnecessary surgical procedures [9–13]. However, to our knowledge, our index patient is the first male case who has received unneeded systemic chemotherapy for falsely elevated hCG.

Several causes for false-positive serum hCG levels have been reported in the literature (Table 1). Heterophilic antibodies, low affinity antibodies frequently found in human serum, are mentioned as the most frequent cause of false-positive hCG results [1–6, 14–19]. These antibodies may develop after infections or contact with animal tissues or constituents. They crossreact with immunoglobulins from different species, but their titer is generally low. Heterophilic antibodies are notably known to interfere with two-sided immunometric assays, widely used for the detection of serum proteins. Two-sided assays typically use a mouse monoclonal capture antibody bound to a vessel or bead, which immobilizes the serum analytes (e.g., hCG) by binding one epitope on hCG. A tracer antibody, polyclonal or monoclonal IgG of animal origin, is labeled with an enzyme or chemiluminescent agent and thereby marks the immobilized antibody by attaching to a distant epitope on the antigen. Interference with heterophilic antibodies can occur because of linkage of the animal capture antibody to the tracer antibody in the absence of antigen, resulting in a false-positive assay outcome. Using modern two-sided assays, the estimated amount of interference is on the order of 1 per 10,000 samples assayed [3]. However, interference may occur more frequently when using certain commercially available assays. The estimated interference rate leading to false-positive results of the Abbott AxSym total beta-hCG test, which is used in 28% of laboratories in the U.S., is estimated to be 1 in 1,430 samples assayed [3]. Heterophile interference is also reported to lead to falsely elevated or decreased tumor markers, for example, AFP, cancer antigen 125, carcinoembryonic antigen, thyroglobulin, and other proteins, in assays frequently used in the clinical setting [20–28].

IgA deficiency is the most common primary immunodeficiency, with a prevalence of 1 in 112 to 1 in 500 in the European and U.S. populations. Sera of patients with IgA deficiency often contain heterophilic antibodies, possibly related to increased mucosal antigen exposure of the systemic circulation. Up to 30% of IgA-deficient sera led to false-positive hCG results as measured in three different assays [29]. Despite the incorporation of nonspecific blocking antibodies (Scantibodies Laboratory, Inc.) in the DPC hCG assay, 7.4% of the sera of IgA-deficient women showed false-positive results, again illustrating the imperfect nature of this modified assay. In our IgA-deficient patient, heterophile interference is also likely to be the cause of his falsely elevated hCG results, although we did not establish the presence of heterophilic antibodies.

Irregular forms of hCG, produced by malignant GCTs and GTNs, for example, nicked hCG, hyperglycosylated hCG, and free hCG β subunit, may be another cause of a false-positive hCG result [30, 31]. Most commercial hCG assays indeed do not measure all hCG forms correctly, which may result in falsely elevated or decreased serum hCG concentrations [2]. Of six frequently used hCG immunometric assays, only the DPC assay detected all tested irregular forms of β-hCG correctly. Release of entrapped hCG from a large (necrotic) tumor mass after tumor regression during chemotherapy has also been suggested to explain false-positive serum hCG results [9, 10, 12]. Similarly, reinfusion of peripheral blood stem cells containing hCG at a high concentration, collected from a poor-risk testicular cancer patient when his serum hCG levels were remarkably elevated, resulted in false hCG surges [32]. Also, additives to blood collection tubes have been reported to interfere with immunometric assays, resulting in false test results of many frequently performed blood tests [27, 33].

Unexpected but truly elevated serum hCG levels can be observed in menopausal women because physiological low-level production of hCG by the pituitary is known to occur. This may be confirmed by the resolution of hCG levels after the administration of hormone-replacement therapy for 2 weeks [5]. Similarly, a moderate increase in serum hCG concentration resulting from a physiological pituitary reaction can be detected in men with hypogonadism [34]. Although we did not measure testosterone levels in our patient's serum during the course of chemotherapy, there were no clinical or biochemical signs of hypogonadism before and after the chemotherapy courses.

	CONCLUSIONS

Top Abstract Introduction Case Report Review of the Literature Conclusions Author Contributions References

 
In conclusion, elevated hCG levels are an essential and integral part of the international staging systems of GCTs, and initiation of systemic treatment in a patient with a history of a marker-positive GCT with a rise in a serum marker in the absence of any radiological abnormal lesion is a commonly adopted strategy [35–37]. However, if hCG is the sole elevated marker, clinicians should be aware that kits for the assay of serum hCG have been licensed in the U.S. and many other countries only as an aid to the detection of pregnancy and not for monitoring of GCTs (which may even produce irregular forms of hCG), and this is clearly stated in the accompanying kit assay information brochures. Although hCG is a very useful marker for the diagnosis and staging of GCTs, and monitoring of the therapeutic response and detection of tumor recurrence, our case report emphasizes the potential pitfalls of using serum tumor markers in the absence of a clinical correlate as the sole reason to start chemotherapy in patients with GCTs. Confirmation of elevated serum hCG levels by alternative serum hCG measurement methods, exclusion of other nonmalignant causes of elevated hCG levels, and optimal communication between clinical chemists and clinicians are essential to avoid unneeded medical interventions.

	AUTHOR CONTRIBUTIONS

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Conception/design: Susanne Osanto, Nir I. Weijl, Bart E.P.B. Ballieux

Administrative support: Susanne Osanto, Nir I. Weijl, Bart E.P.B. Ballieux

Provision of study materials: Susanne Osanto, Nir I. Weijl, Bart E.P.B. Ballieux

Collection/assembly of data: Susanne Osanto, Johannes van Pelt, Hans Gelderblom, Nir I. Weijl, Bart E.P.B. Ballieux

Data analysis: Susanne Osanto, Nir I. Weijl, Bart E.P.B. Ballieux

Manuscript writing: Susanne Osanto, Nir I. Weijl, Bart E.P.B. Ballieux

Final approval of manuscript: Susanne Osanto, Johannes van Pelt, Hans Gelderblom, Nir I. Weijl, Bart E.P.B. Ballieux

	REFERENCES

Top Abstract Introduction Case Report Review of the Literature Conclusions Author Contributions References

 

1. Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. Lancet 2000;355:712–715.[CrossRef][Medline]
2. Cole LA, Shahabi S, Butler SA et al. Utility of commonly used commercial human chorionic gonadotropin immunoassays in the diagnosis and management of trophoblastic diseases. Clin Chem 2001;47:308–315.[Abstract/Free Full Text]
3. Cole LA, Khanlian SA. Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total β-hCG test. Clin Biochem 2004;37:344–349.[Medline]
4. Cole LA, Khanlian SA. Inappropriate management of women with persistent low hCG results. J Reprod Med 2004;49:423–432.[Medline]
5. Cole LA, Sasaki Y, Muller CY. Normal production of human chorionic gonadotropin in menopause [letter]. N Engl J Med 2007;356:1184–1186.[Free Full Text]
6. USA hCG Reference Service. Heterophilic Antibodies and False Positive hCG Test. Available at http://www.hcglab.com/antibodies.htm. accessed July 15, 2008.
7. Olsen TG, Hubert PR, Nycum LR. Falsely elevated human chorionic gonadotropin leading to unnecessary therapy. Obstet Gynecol 2001;98:843–845.[CrossRef][Medline]
8. Esfandiari N, Goldberg JM. Heterophile antibody blocking agent to confirm false positive serum human chorionic gonadotropin assay. Obstet Gynecol 2003;101:1144–1146.[CrossRef][Medline]
9. van der Gaast A, Hoekstra JW, Croles JJ et al. Elevated serum tumor markers in patients with testicular cancer after induction chemotherapy due to a reservoir of markers in cystic differentiated mature teratoma. J Urol 1991;145:829–831.[Medline]
10. Mohler JL, Siami PF, Flanigan RC. False positive beta-human chorionic gonadotropin in testicular cancer. Urology 1987;30:252–254.[Medline]
11. Morris MJ, Bosl GJ. Recognizing abnormal marker results that do not reflect disease in patients with germ cell tumors. J Urol 2000;163:796–801.[CrossRef][Medline]
12. Beck SDW, Patel MI, Sheinfeld J. Tumor marker levels in post-chemotherapy cystic masses: Clinical implications for patients with germ cell tumors. J Urol 2004;171:168–171.[CrossRef][Medline]
13. Trojan A, Joller-Jemelka H, Stahel RA et al. False-positive human serum chorionic gonadotropin in a patient with a history of germ cell cancer. Oncology 2004;66:336–338.[Medline]
14. Bagshawe KD. Limitations of tests for human chorionic gonadotropin [comment]. Lancet 2000;355:671.[Medline]
15. Price A, Gillett G. Needless treatment for presumed malignancy [letter]. Lancet 2000;355:1724–1725.[Medline]
16. Hammond CB. False positive hCG [editorial]. Obstet Gynecol 2001;98:719–720.[Medline]
17. Levinson SS, Miller JJ. Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassays. Clin Chim Acta 2002;325:1–15.[CrossRef][Medline]
18. Bjerner J, Børmer OP, Nustad K. The war on heterophilic antibody interference [editorial]. Clin Chem 2005;51:9–11.[Free Full Text]
19. Preissner CM, Dodge LA, O'Kane DJ et al. Prevalence of heterophilic antibody interference in eight automated tumor marker immunoassays. Clin Chem 2005;51:208–210.[Free Full Text]
20. Touitou Y, Bogdan A. Tumor markers in non-malignant diseases. Eur J Cancer Clin Oncol 1988;24:1083–1091.[CrossRef][Medline]
21. Reinsberg J, Heydweiller A, Wagner U et al. Evidence for interaction of human anti-idiotypic antibodies with CA 125 determination in a patient after radioimmunodetection. Clin Chem 1990;36:164–167.[Abstract/Free Full Text]
22. Kuroki M, Matsumoto Y, Arakawa F et al. Reducing interference from heterophilic antibodies in a two-site immunoassay for carcinoembryonic antigen (CEA) by using a human/mouse chimeric antibody to CEA as the tracer. J Immunol Methods 1995;180:81–91.[CrossRef][Medline]
23. Reinsberg J. Different efficacy of various blocking reagents to eliminate interferences by human antimouse antibodies with a two-site immunoassay. Clin Biochem 1996;29:145–148.[CrossRef][Medline]
24. Morgan BR, Tarter TH. Serum heterophile antibodies interfere with prostate specific antigen test and result in over treatment in a patient with prostate cancer. J Urol 2001;166:2311–2312.[CrossRef][Medline]
25. Bertholf RL, Johannsen L, Guy B. False elevation of serum CA-125 level caused by human anti-mouse antibodies. Ann Clin Lab Sci 2002;32:414–418.[Abstract/Free Full Text]
26. Preissner CM, O'Kane DJ, Singh RJ et al. Phantoms in the assay tube: Heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003;88:3069–3074.[Abstract/Free Full Text]
27. Bowen RA, Chan Y, Cohen J et al. Effect of blood collection tubes on total triiodothyronine and other laboratory assays. Clin Chem 2005;51:424–433.[Abstract/Free Full Text]
28. Park S, Wians FH Jr, Cadeddu JA. Spurious prostate-specific antigen (PSA) recurrence after radical prostatectomy: Interference by human antimouse heterophile antibodies. Int J Urol 2007;14:251–253.[Medline]
29. Knight AK, Bingemann T, Cole L et al. Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency. Clin Exp Immunol 2005;141:333–337.[Medline]
30. Cole LA, Sutton J. Selecting an appropriate hCG test for managing gestational trophoblastic disease and cancer. J Reprod Med 2004;49:545–553.[Medline]
31. Cole LA. Hyperglycosylated hCG. Placenta 2007;28:977–986.[CrossRef][Medline]
32. Inoue M, Koga F, Kawakami S et al. False tumor marker surge evoked by peripheral blood stem cell transplantation. The Oncologist 2008;13:526–529.[Abstract/Free Full Text]
33. Bowen RA, Chan Y, Ruddel ME et al. Immunoassay interference by a commonly used blood collection tube additive, the organosilicone surfactant silwet L-720. Clin Chem 2005;51:1874–1882.[Abstract/Free Full Text]
34. Lempiäinen A, Hotakainen K, Blomqvist C et al. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma [letter]. Clin Chem 2007;53:1560–1561.[Free Full Text]
35. International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: A prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 1997;15:594–603.[Abstract/Free Full Text]
36. American Joint Committee on Cancer: AJCC Cancer Staging Manual. Greene FL, Page DL, Fleming ID et al, eds. Testis. Sixth Edition. New York: Springer, 2002:317-322.
37. Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II. Eur Urol 2008;53:497–513.[CrossRef][Medline]

This Article Abstract Full Text (PDF) All Versions of this Article: theoncologist.2008-0159v1 13/11/1149    most recent eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ballieux, B. E.P.B. Articles by Osanto, S. Search for Related Content PubMed PubMed Citation Articles by Ballieux, B. E.P.B. Articles by Osanto, S.