Background: Pure testicular seminoma does not express alpha fetoprotein (AFP). However, seminoma patients with mildly elevated serum AFP levels are increasingly reported. As this finding may prompt unwarranted treatment measures, we reviewed our experience with AFP levels in seminoma. Patients and Methods: We retrospectively registered AFP levels in 254 consecutive seminoma patients, and in 196 male controls with non-malignant diseases. In those with elevated AFP levels, we re-examined the orchiectomy specimens histologically. We reviewed the clinical course and looked for hepatic disorders. Results: Elevated AFP levels were found in 5 patients (1.97%, 95% CI 0.19-3.68) and in 4 controls (2.04%, 95% CI 0.06-4.02). The elevations were modest and kept elevated throughout the clinical course. No hepatic disorders were recorded. Histologically, pure seminoma was confirmed. Conclusion: Unspecific AFP elevations occur in about 2% of seminoma patients. Care-givers should be aware of this particular subgroup of seminoma patients to avoid unwarranted treatment burden.

1.
Mir MC, Pavan N, Gonzalgo ML: Current clinical applications of testicular cancer biomarkers. Urol Clin North Am 2016;43:119-125.
2.
Murray MJ, Nicholson JC: α-Fetoprotein. Arch Dis Child Educ Pract Ed 2011;96:141-147.
3.
Smith JB: Alpha-fetoprotein: occurrence in certain malignant diseases and review of clinical applications. Med Clin North Am 1970;54:797-803.
4.
Kim CY, Kim BR, Lee SS, Jeon DH, Lee CM, Kim WS, Cho HC, Kim JJ, Lee JM, Kim HJ, Ha CY, Kim HJ, Kim TH, Jung WT, Lee OJ: Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma. Medicine (Baltimore) 2017;96:e5844.
5.
Yoon YM, Kang DY, Kim DY, Seo JW, Lim HJ, Lee HJ, Park SG: Extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without malignancy: a case report. J Med Case Rep 2016;10:140.
6.
Talerman A, van der Pompe WB, Haije WG, Baggerman L, Boekestein-Tjahjadi HM: Alpha-foetoprotein and carcinoembryonic antigen in germ cell neoplasms. Br J Cancer 1977;35:288-291.
7.
Scardino PT, Cox HD, Waldmann TA, Mcintire KR, Mittemeyer B, Javadpour N: The value of serum tumor markers in the staging and prognosis of germ cell tumors of the testis. J Urol 1977;118:994-999.
8.
Doherty AP, Bower M, Christmas TJ: The role of tumour markers in the diagnosis and treatment of testicular germ cell cancers. Br J Urol 1997;79:247-252.
9.
Fong ZV, Tanabe KK: The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer 2014;120:2824-2838.
10.
Gilligan TD, Seidenfeld J, Basch EM, Einhorn LH, Fancher T, Smith DC, Stephenson AJ, Vaughn DJ, Cosby R, Hayes DF: American society of clinical oncology clinical practice guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol 2010;28:3388-3404.
11.
Stang A, Bray F, Dieckmann KP, Lortet-Tieulent J, Rusner C: Mortality of testicular cancer in East and West Germany 20 years after reunification: a gap not closed yet. Urol Int 2015;95:160-166.
12.
Javadpour N: Significance of elevated serum alphafetoprotein (AFP) in seminoma. Cancer 1980;45:2166-2168.
13.
Lamm DL, Wepsic HT, Feldman P, Richie JP: Importance of alpha-fetoprotein in patients with seminoma. Urology 1977;10:233-235.
14.
Ehrlich Y, Beck SD, Foster RS, Bihrle R, Einhorn LH: Serum tumor markers in testicular cancer. Urol Oncol 2013;31:17-23.
15.
Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MP, Nicolai N, Oldenburg J: Guidelines on testicular cancer: 2015 update. Eur Urol 2015;68:1054-1068.
16.
Lange PH, Nochomovitz LE, Rosai J, Fraley EE, Kennedy BJ, Bosl G, Brisbane J, Catalona WJ, Cochran JS, Comisarow RH, Cummings KB, deKernion JB, Einhorn LH, Hakala TR, Jewett M, Moore MR, Scardino PT, Streitz JM: Serum alpha-fetoprotein and human chorionic gonadotropin in patients with seminoma. J Urol 1980;124:472-478.
17.
Dieckmann KP, Düe W, Bauer HW: Seminoma testis with elevated serum beta-HCG - a category of germ-cell cancer between seminoma and nonseminoma. Int Urol Nephrol 1989;21:175-184.
18.
Vazeille C, Massard C, Loriot Y, Albiges L, Troalen F, Escudier B, Fizazi K: Nonfamilial chronic serum alpha-fetoprotein increase in a patient with clinical stage I seminoma. Clin Genitourin Cancer 2016;14:e91-e93.
19.
Wymer KM, Daneshmand S, Pierorazio PM, Pearce SM, Harris KT, Eggener SE: Mildly elevated serum alpha-fetoprotein (AFP) among patients with testicular cancer may not be associated with residual cancer or need for treatment. Ann Oncol 2017;28:899-902.
20.
Motzer RJ, Jonasch E, Agarwal N, Beard C, Bhayani S, Bolger GB, Chang SS, Choueiri TK, Costello BA, Derweesh IH, Gupta S, Hancock SL, Kim JJ, Kuzel TM, Lam ET, Lau C, Levine EG, Lin DW, Michaelson MD, Olencki T, Pili R, Plimack ER, Rampersaud EN, Redman BG, Ryan CJ, Sheinfeld J, Shuch B, Sircar K, Somer B, Wilder RB, Dwyer M, Kumar R: Testicular cancer, version 2.2015. J Natl Compr Canc Netw 2015;13:772-799.
21.
Dieckmann KP, Dralle-Filiz I, Heinzelbecker J, Matthies C, Bedke J, Ellinger J, Sommer J, Haben B, Souchon R, Anheuser P, Pichlmeier U: Seminoma clinical stage 1 - patterns of care in Germany. Urol Int 2016;96:390-398.
22.
Light PA: Tumour markers in testicular cancer. J R Soc Med 1985;78:19-24.
23.
Coppack S, Newlands ES, Dent J, Mitchell H, Goka G, Bagshawe KD: Problems of interpretation of serum concentrations of alpha-foetoprotein (AFP) in patients receiving cytotoxic chemotherapy for malignant germ cell tumours. Br J Cancer 1983;48:335-340.
24.
Grem JL, Trump DL: Reversible increase in serum alpha-fetoprotein content associated with hepatic dysfunction during chemotherapy for seminoma. J Clin Oncol 1986;4:41-45.
25.
Germà JR, Llanos M, Tabernero JM, Mora J: False elevations of alpha-fetoprotein associated with liver dysfunction in germ cell tumors. Cancer 1993;72:2491-2494.
26.
Bussar-Maatz R, Weissbach L, Dahlmann N, Mann K: [The ‘false positive' tumor marker in malignant testicular tumor]. Urologe A 1993;32:177-182.
27.
Funahashi M, Tuchiya F, Makiyama K, Sugiura S, Miyoshi Y, Kishida T, Ogawa T, Uemura H, Yao M, Kubota Y: [Two cases of testicular tumors with high alpha-fetoprotein levels: a case report]. Hinyokika Kiyo 2005;51:133-137.
28.
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.
29.
Schefer H, Mattmann S, Joss RA: Hereditary persistence of alpha-fetoprotein. Case report and review of the literature. Ann Oncol 1998;9:667-672.
30.
Houwert AC, Giltay JC, Lentjes EG, Lock MT: Hereditary persistence of alpha-fetoprotein (HPAF P): review of the literature. Neth J Med 2010;68:354-358.
31.
Chierigo P, Puccetti O, Visonà A, Bassan F, Rahmati M, Lazzarotto M, Franzolin N: [High alpha-fetoprotein persistence after orchiectomy. On a case of uncommon etiology]. Urologia 2010;77(suppl 17):27-31.
32.
Kuber W, Tang X, Bussar-Maatz R: Krankheitsverlauf bei Patienten mit HCG-aktivem Seminom; in Weissbach L, Hildenbrand G (eds): Register und Verbundstudie für Hodentumoren - Bonn. Ergebnisse einer prospektiven Untersuchung. Munich, W. Zuckschwerdt Verlag, 1982, pp 275-286.
33.
Nørgaard-Pedersen B, Schultz HP, Arends J, Brincker H, Krag Jacobsen G, Lindeløv B, Rørth M, Svennekjaer IL: Tumour markers in testicular germ cell tumours. Five-year experience from the DATECA study 1976-1980. Acta Radiol Oncol 1984;23:287-294.
34.
Nazeer T, Ro JY, Amato RJ, Park YW, Ordonez NG, Ayala AG: Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic study of ten cases. Oncol Rep 1998;5:1425-1429.
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