Abstract
A testicular tumor is one of the rare malignant diseases. Moreover, it is one of the few malignancies that can be cured in early stages and, in the majority of cases, in more advanced stages as well. In addition to germ cell tumors, which usually arise from germ cell neoplasia in situ, the rare Leydig cell and Sertoli cell tumors, which belong to the gonadal stromal tumors, are obligately endocrine active. In this chapter, the genesis, risk factors, diagnosis and subsequent therapy, and impact on fertility of germ cell and gonadal stromal tumors are presented.
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References
AWMF S3-Leitlinie Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF (Leitlinienprogramm Onkologie): S3-Leitlinie Diagnostik, Therapie und Nachsorge der Keimzelltumoren des Hodens, Langversion 1.1, 2020, AWMF-Registernummer: 043/049OL. https://www.leitlinienprogramm-onkologie.de/leitlinien/hodentumoren. Zugegriffen: 21. February 2022
AWMF S2k Leitlinie der DGGG, DGU, DGRM (2017): Fertilitätserhalt bei Patienten mit onkologischen Erkrankungen (S2k-Level, AWMF Registry No.015/082, November 2017). http://www.awmf.org/leitlinien/detail/ll/015-082.html
Banerji JS, Odem-Davis K, Wolff EM, Nichols CR, Porter CR (2016) Patterns of care and srvival outcomes for malignant sex cord stromal testicular cancer: Results from the National Cancer Data Base. J Urol 196:1117–1122. https://doi.org/10.1016/j.juro.2016.03.143
Bois JI, Vagni RL, de Badiola FI, Moldes JM, Losty PD, Lobos PA (2021) Testis-sparing surgery for testicular tumors in children: a 20 year single center experience and systematic review of the literature. Pediatr Surg Int 37:607–616. https://doi.org/10.1007/s00383-020-04850-6
Bosl GJ, Motzer RJ (1997) Testicular germ-cell cancer. NEJM 337:242–253. https://doi.org/10.1056/NEJM199707243370406
Bremmer F, Schweyer S (2016) Leydig-Zell-, Sertoli-Zell- und adulte Granulosazelltumoren. Pathologe 37:71–77. https://doi.org/10.1007/s00292-015-0131-y
Chang B, Borer JG, Tan PE, Diamond DA (1998) Large-cell calcifying sertoli cell tumor of the testis: case report and review of the literature. Urology 52:520–522. https://doi.org/10.1016/S0090-4295(98)00246-5
Classen J, Dieckmann K, Bamberg M, Souchon R, Kliesch S, Kuehn M, Loy V (2003) Radiotherapy with 16 Gy may fail to eradicate testicular intraepithelial neoplasia: preliminary communication of a dose-reduction trial of the German Testicular Cancer Study Group. Br J Cancer 88:828–831. https://doi.org/10.1038/sj.bjc.6600771
Cools M, Drop SLS, Wolffenbuttel KP, Oosterhuis JW, Looijenga LHJ (2006) Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev 27:468–484. https://doi.org/10.1210/er.2006-0005
de Souza RF, da Silva JP, Vieira Balla B, Neves Ferreira R, Chambô Filho A (2017) Bilateral Sertoli cell tumors in a patient with androgen insensitivity syndrome. Case Rep Obstet Gynecol 2017:8357235.1–8357235.4. https://doi.org/10.1155/2017/8357235
Dieckmann K-P, Kulejewski M, Pichlmeier U, Loy V (2007) Diagnosis of contralateral testicular intraepithelial neoplasia (TIN) in patients with testicular germ cell cancer: systematic two-site biopsies are more sensitive than a single random biopsy. Eur Urol 51:175–183. https://doi.org/10.1016/j.eururo.2006.05.051
Dieckmann K-P, Wilken S, Loy V, Matthies C, Kleinschmidt K, Bedke J, Martinschek A, Souchon R, Pichlmeier U, Kliesch S (2013) Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group. Ann Oncol 24:1332–1337. https://doi.org/10.1093/annonc/mds628
Dieckmann K-P, Radtke A, Spiekermann M, Balks T, Matthies C, Becker P, Ruf C, Oing C, Oechsle K, Bokemeyer C, Hammel J, Melchior S, Wosniok W, Belge G (2017) Serum levels of microRNA miR-371a-3p: a sensitive and specific new biomarker for germ cell tumours. Eur Urol 71:213–220. https://doi.org/10.1016/j.eururo.2016.07.029
Donner J, Kliesch S, Brehm R, Bergmann M (2004) From carcinoma in situ to testicular germ cell tumour. APMIS 112:79–88. https://doi.org/10.1111/j.1600-0463.2004.apm1120201.x
Engels M, Gehrmann K, Falhammar H, Webb EA, Nordenström A, Sweep FC, Span PN, van Herwaarden AE, Rohayem J, Richter-Unruh A, Bouvattier C, Köhler B, Kortmann BB, Arlt W, Roeleveld N, Reisch N, Stikkelbroeck NMML, Claahsen-van der Grinten HL (2018) Gonadal function in adult male patients with congenital adrenal hyperplasia. Eur J Endocrinol 178:285–294. https://doi.org/10.1530/EJE-17-0862
Fankhauser CD, Grogg JB, Hayoz S, Wettstein MS, Dieckmann KP, Sulser T, Bode PK, Clarke NW, Beyer J, Hermanns T, Fankhauser CD, Grogg JB, Wettstein MS, Dieckmann K-P, Bode P-K, Clarke NW (2020) Risk factors and treatment outcomes of 1,375 patients with testicular Leydig cell tumors: analysis of published case series data. J Urol 203:949–956. https://doi.org/10.1097/JU.0000000000000705
Freeman DA (1986) Steroid hormone-producing tumors in man. Endocr Rev 7:204–220. https://doi.org/10.1210/edrv-7-2-204
Gabrilove JL, Freiberg EK, Leiter E, Nicolis GL (1980) Feminizing and non-feminizing Sertoli cell tumors. J Urol 124:757–767. https://doi.org/10.1016/S0022-5347(17)55652-9
Gemeinsamer Bundesausschuß (G-BA) (2021) Richtlinie zur Kryokonservierung von Ei- oder Samenzellen oder Keimzellgewebe sowie entsprechende medizinische Maßnahmen wegen keimzellschädigender Therapie. Bundesanzeiger BAnz AT 19.02.2021 B7
Giwercman A, Thomsen JK, Hertz J, Jensen V, Skakkebæk NE, Meinecke B, Berthelsen JG, Thormann L, Storm HH (1997) Prevalence of carcinoma in situ of the testis in 207 oligozoospermic men from infertile couples: prospective study of testicular biopsies. BMJ 315:989–991. https://doi.org/10.1136/bmj.315.7114.989
Ham S, Meachem SJ, Choong CS, Charles AK, Baynam GS, Jones TW, Samarajeewa NU, Simpson ER, Brown KA (2013) Overexpression of aromatase associated with loss of heterozygosity of the STK11 gene accounts for prepubertal gynecomastia in boys with Peutz-Jeghers syndrome. J Clin Endocrinol Metab 98:E1979–E1987. https://doi.org/10.1210/jc.2013-2291
Hansen PV, Trykker H, Svennekjæ IL, Hvolby J (1990) Long-term recovery of spermatogenesis after radiotherapy in patients with testicular cancer. Radiother Oncol 18:117–125. https://doi.org/10.1016/0167-8140(90)90137-L
Heidenreich A, Weißbach L, Höltl W, Albers P, Kliesch S, Köhrmann KU, Dieckmann KP, Köhrmann K (2001) Organ sparing surgery for malignant germ cell tumor of the testis. J Urol 166:2161–2165. https://doi.org/10.1016/S0022-5347(05)65526-7
Heidenreich A, Albers P, Hartmann M, Kliesch S, Köhrmann KU, Krege S, Ph L, Weißbach L, for the German Testicular Cancer Study Group (2003) Complications of primary nerve-sparing retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors of the testis: experience of the German Testicular Cancer Study Group. J Urol 169:1710–1714
Hiester A, Fingerhut A, Niegisch G, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, Kwasny P, Pechoel M, Lehmann J, Kliesch S, Köhrmann KU, Fimmers R, Loy V, Wittekind C, Hartmann M, Albers P (2021) Late toxicities and recurrences in patients with clinical stage I nonseminomatous germ cell tumor after 1 cycle of adjuvant BEP vs. primary retroperitoneal lymph node dissection – a 13-years follow-up analysis of a phase-III trial cohort. Eur J Cancer 155:64–72
Horwich A, Shipley J, Huddart R (2006) Testicular germ-cell cancer. Lancet 367:754–765. https://doi.org/10.1016/S0140-6736(06)68305-0
Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, Berney D, Srigley JR, Epstein JI, Tickoo SK (2017) The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 70:513–521. https://doi.org/10.1111/his.13115
IGCCCG (1997) International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15(2):594–603
Kier MG, Lauritsen J, Mortensen MS, Bandak M, Andersen KK, Hansen MK, Agerbaek M, Holm NV, Dalton SO, Johansen C, Daugaard G (2017) Prognostic factors and treatment results after bleomycin, etoposide, and cisplatin in germ cell cancer: a population-based study. Eur Urol 71:290–298. https://doi.org/10.1016/j.eururo.2016.09.015
Kliesch S (1998) Tumoren und Fehlbildungen des Nebenhodens und des Samenstranges. In: Krause W, Weidner W (eds) Andrologie. Krankheiten der männlichen Geschlechtsorgane : 252 Einzelabbildungen, 102 Tabellen. Ferdinand Enke Verlag, Stuttgart, pp S220–S223
Kliesch S (2004) Diagnostik und Primärtherapie des Hodentumors. Urologe 43:1494–1499. https://doi.org/10.1007/s00120-004-0727-y
Kliesch S (2021) Diagnose und Therapie des Leydig-Zell-Tumors. Urologe 60:880–885. https://doi.org/10.1007/s00120-021-01576-8
Kliesch S (2022) Hodentumor Survivorship und Langzeittoxizität. In: Michel MS, Thüroff J, Janetschek G, Wirth M (eds) Die Urologie, 2nd edn. Springer, Cham. im Druck
Kliesch S, Behre HM, Jürgens H, Nieschlag E (1996) Cryopreservation of semen from adolescent patients with malignancies. Med Pediatr Oncol 26:20–27. https://doi.org/10.1002/(SICI)1096-911X(199601)26:1<20::AID-MPO3>3.0.CO;2-X
Kliesch S, Bergmann M, Hertle L, Nieschlag E, Behre HM (1997) Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies. Hum Reprod 12:2830–2835. https://doi.org/10.1093/humrep/12.12.2830
Kliesch S, Thomaidis T, Schutte B, Puhse G, Kater B, Roth S, Bergmann M (2003) Update on the diagnostic safety for detection of testicular intraepithelial neoplasia (TIN). APMIS 111:70–74.; discussion 75. https://doi.org/10.1034/j.1600-0463.2003.11101101.x
Kliesch S, Schmidt S, Wilborn D et al (2021a) Management of germ cell tumours of the testis in adult patients. German Clinical Practice Guideline Part I: Epidemiology, classification, diagnosis, prognosis, fertility preservation, and treatment recommendations for localized stages. UIN 105:169–180. https://doi.org/10.1159/000510407
Kliesch S, Schmidt S, Wilborn D et al (2021b) Management of germ cell tumours of the testes in adult patients: German Clinical Practice Guideline, Part II: Recommendations for the treatment of advanced, recurrent, and refractory disease and extragonadal and sex cord/stromal tumours and for the management of follow-up, toxicity, quality of life, palliative care, and supportive therapy. UIN 105:181–191. https://doi.org/10.1159/000511245
Klonisch T, Ivell R, Balvers M, Kliesch S, Fischer B, Bergmann M, Steger K (1999) Expression of relaxin-like factor is down-regulated in human testicular Leydig cell neoplasia. Mol Hum Reprod 5:104–108. https://doi.org/10.1093/molehr/5.2.104
Latif T, Kold Jensen T, Mehlsen J, Holmboe SA, Brinth L, Pors K, Skouby SO, Jørgensen N, Lindahl-Jacobsen R (2017) Semen quality as a predictor of subsequent morbidity: a Danish cohort study of 4,712 men with long-term follow-up. Am J Epidemiol 186:910–917. https://doi.org/10.1093/aje/kwx067
Liu G, Duranteau L, Carel JC, Monroe J, Doyle DA, Shenker A (1999) Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med 341:1731–1736. https://doi.org/10.1056/NEJM199912023412304
Lottrup G, Belling K, Leffers H, Nielsen JE, Dalgaard MD, Juul A, Skakkebæk NE, Brunak S, Rajpert-De Meyts E (2017) Comparison of global gene expression profiles of microdissected human foetal Leydig cells with their normal and hyperplastic adult equivalents. Mol Hum Reprod 23:339–354. https://doi.org/10.1093/molehr/gax012
Loy V, Linke J (2003) Endokrine Tumoren des Hodens. Pathologe 24:308–313. https://doi.org/10.1007/s00292-003-0620-2
Luckie TM, Danzig M, Zhou S, Wu H, Cost NG, Karaviti L, Venkatramani R (2019) A multicenter retrospective review of pediatric Leydig cell tumor of the testis. J Pediatr Hematol/Oncol 41:74. https://doi.org/10.1097/MPH.0000000000001124
Mesa H, DaScott G, Smith S, Dachel S, Larson W, Manivel C (2015) The mystery of the vanishing Reinke crystals. Hum Pathol 46:600–606. https://doi.org/10.1016/j.humpath.2015.01.004
Miao X, Li Y, Zhou T, Lv M (2021) Testis-sparing surgery in children with testicular tumors: a systematic review and meta-analysis. Asian J Surg 44:1503–1509. https://doi.org/10.1016/j.asjsur.2021.03.016
Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs—Part A: Renal, poryenile, and testicular tumours. Eur Urol 70:93–105. https://doi.org/10.1016/j.eururo.2016.02.029
Nason GJ, Redmond EJ, Considine SW, Omer SI, Power D, Sweeney P (2018) The natural history of Leydig cell testicular tumours: an analysis of the National Cancer Registry. Ir J Med Sci 187:323–326. https://doi.org/10.1007/s11845-017-1662-4
Necchi A, Bratslavsky G, Shapiro O, Elvin JA, Vergilio J-A, Killian JK, Ngo N, Ramkissoon S, Severson E, Hemmerich AC, Ali SM, Chung JH, Reddy P, Miller VA, Schrock AB, Gay LM, Ross JS, Jacob JM (2019) Genomic features of metastatic testicular sex cord stromal tumors. Eur Urol focus 5:748–755. https://doi.org/10.1016/j.euf.2019.05.012
Petersen PM, Skakkebaek NE, Vistisen K, Rørth M, Giwercman A (1999) Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J Clin Oncol 17:941–947. https://doi.org/10.1200/JCO.1999.17.3.941
Pozza C, Gianfrilli D, Fattorini G, Giannetta E, Barbagallo F, Nicolai E, Cristini C, Di Pierro GB, Franco G, Lenzi A, Sidhu PS, Cantisani V, Isidori AM (2016) Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions. Andrology 4:1193–1203. https://doi.org/10.1111/andr.12260
Pühse G, Secker A, Kemper S, Hertle L, Kliesch S (2005) Early androgen deficiency in testicular germ cell cancer patients. Exp Clin Endocrinol Diabetes 113. https://doi.org/10.1055/s-2005-863040
Pühse G, Wachsmuth JU, Kemper S, Husstedt IW, Kliesch S, Evers S (2010) Phantom testis syndrome: prevalence, phenomenology and putative mechanisms. Int J Androl 33:e216–e220. https://doi.org/10.1111/j.1365-2605.2009.00994.x
Raman JD, Nobert CF, Goldstein M (2005) Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. JUrol 174:1819–1822. https://doi.org/10.1097/01.ju.0000177491.98461.aa
Rassam Y, Gromoll J, Kliesch S, Schubert M (2020) Testicular microlithiasis is associated with impaired spermatogenesis in patients with unexplained infertility. UIN 104:610–616. https://doi.org/10.1159/000508584
Rives N, Perdrix A, Hennebicq S, Saïas-Magnan J, Melin M-C, Berthaut I, Barthélémy C, Daudin M, Szerman E, Bresson J-L, Brugnon F, Bujan L (2012) The semen quality of 1158 men with testicular cancer at the time of cryopreservation: results of the French National CECOS Network. J Androl 33:1394–1401. https://doi.org/10.2164/jandrol.112.016592
RKI (2019) Krebs in Deutschland 2015/2016. https://www.krebsdaten.de/Krebs/SiteGlobals/Forms/Datenbankabfrage/datenbankabfrage_stufe2_form.html
RKI (2021). https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Hodenkrebs/hodenkrebs_node.html
Rohayem J, Bäumer LM, Zitzmann M, Fricke-Otto S, Mohnike K, Gohlke B, Reschke F, Jourdan C, Müller HL, Dunstheimer D, Weigel J, Jorch N, Müller-Rossberg E, Lankes E, Gätjen I, Richter-Unruh A, Hauffa BP, Kliesch S, Krumbholz A, Brämswig J (2021) Semen quality and testicular adrenal rest tumour development in 46,XY congenital adrenal hyperplasia: the importance of optimal hormonal replacement. Eur J Endocrinol 184:487–501. https://doi.org/10.1530/eje-20-1154
Ruf CG, Isbarn H, Wagner W, Fisch M, Cord M, Dieckmann KP (2014) Changes in epidemiologic features of testicular germ cell cancer: Age at diagnosis and relative frequency of seminoma are constantly and significantly increasing. Urol Oncol 32:33.e1–33.e6. https://doi.org/10.1016/j.urolonc.2012.12.002
Schrader M, Weissbach L, Hartmann M, Krege S, Albers P, Miller K, Heidenreich A (2010) Burden or relief: do second-opinion centers influence the quality of care delivered to patients with testicular germ cell cancer? Eur Urol 57:867–872. https://doi.org/10.1016/j.eururo.2009.10.032
Schrader M, Zengerling F, Hakenberg OW, Protzel C (2016) Nationale Zweitmeinungsnetzwerke Hodentumoren und Peniskarzinom: Zwei “Evidenz-Pipelines”. Urologe 55:1192–1198. https://doi.org/10.1007/s00120-016-0201-7
Skakkebæk NE (1972) Possible carcinoma-in-situ of the testis. Lancet 300:516–517. https://doi.org/10.1016/S0140-6736(72)91909-5
Skakkebaek NE, Berthelsen JG, Giwercman A, Müller J (1987) Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 10:19–28. https://doi.org/10.1111/j.1365-2605.1987.tb00161.x
Suardi N, Strada E, Colombo R, Freschi M, Salonia A, Lania C, Cestari A, Carmignani L, Guazzoni G, Rigatti P, Montorsi F (2009) Leydig cell tumour of the testis: presentation, therapy, long-term follow-up and the role of organ-sparing surgery in a single-institution experience. BJU Int 103:197–200. https://doi.org/10.1111/j.1464-410x.2008.08016.x
Ulbright TM, Amin MB, Young RH (2007) Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. American J Surg Pathol 31:827–835. https://doi.org/10.1097/PAS.0b013e3180309e33
van der Kaaij MAE, Heutte N, van Echten-Arends J, Raemaekers JMM, Carde P, Noordijk EM, Fermé C, Thomas J, Eghbali H, Brice P, Bonmati C, Henry-Amar M, Kluin-Nelemans HC (2009) Sperm quality before treatment in patients with early stage Hodgkin’s lymphoma enrolled in EORTC-GELA Lymphoma Group trials. Haematologica 94:1691–1697. https://doi.org/10.3324/haematol.2009.009696
Villares Fragoso MCB, Latronico AC, Carvalho FM, Zerbini MCN, Marcondes JAM, Araujo LMB, Lando VS, Frazzatto ET, Mendonca BB, Villares SMF (1998) Activating mutation of the stimulatory G protein (gsp) as a putative cause of ovarian and testicular human stromal Leydig cell tumors. J Clin Endocrinol Metab 83:2074–2078. https://doi.org/10.1210/jcem.83.6.4847
von Amsberg G, Sehovic M, Hartmann M, Bokemeyer C (2021) Diagnose und Therapie seltener Hodentumoren am Beispiel des malignen Mesothelioms der Tunica vaginalis testis und Sertoli-Zell-Tumoren. Urologe 60:872–879. https://doi.org/10.1007/s00120-021-01575-9
Williams DH, Karpman E, Sander JC, Spiess PE, Pisters LL, Lipshultz LI (2009) Pretreatment semen parameters in men with cancer. J Urol 181:736–740. https://doi.org/10.1016/j.juro.2008.10.023
Young RH (2005) Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol 18:S81–S98. https://doi.org/10.1038/modpathol.3800311
Zengerling F, Krege S, Schrader AJ, Schrader M (2014) Nationales Zweitmeinungsnetzwerk Hodentumoren - ein System zum Evidenztransfer! Aktuelle Urologie 45:454–456. https://doi.org/10.1055/s-0034-1395624
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Kliesch, S., Schubert, M. (2023). Testicular Tumors. In: Nieschlag, E., Behre, H.M., Kliesch, S., Nieschlag, S. (eds) Andrology. Springer, Cham. https://doi.org/10.1007/978-3-031-31574-9_24
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