Keimzelltumoren des Hodens: Klassifikation, Schnellschnittdiagnostik, Sentinel-Lymphknoten-Biopsie und biologische Sonderformen

Zusammenfassung

Die Keimzelltumoren (KZT) sind die häufigsten Neoplasien im Hoden und lassen sich in Abhängigkeit vom Manifestationsalter, der Molekularbiologie und der Histomorphologie in Typ-I-, Typ-II- und Typ-III-Tumoren einteilen. Insgesamt gibt es dabei 6 histologische Subtypen, die unterschiedlich innerhalb dieser 3 Gruppen verteilt sind: Seminome, embryonale Karzinome, Chorionkarzinome, Dottersacktumoren, Teratome und spermatozytäre Tumoren. Am häufigsten sind die malignen Typ-II-KZT, die primär meist durch eine radikale Orchiektomie therapiert werden. In Fällen kleiner Tumoren, bei denen z.B. aufgrund negativer Serumtumormarker unklar ist, ob ein maligner oder benigner Hodentumor (z.B. Epidermiszyste, Keimstranggonadenstromatumor, Adenomatoidtumor, andere testikuläre Adnextumoren) vorliegt, kann zunächst eine Enukleation mit anschließender Schnellschnittuntersuchung erfolgen, da für benigne Tumoren eine hodenerhaltende Tumorresektion ausreicht. Die genaue Einteilung der KZT erfolgt dann histopathologisch durch die morphologischen Charakteristika der KZT-Subtypen und kann unter gewissen Umständen durch immunhistochemische Analysen ergänzt werden. Bei der Untersuchung von Resektaten aus Metastasen (z.B. retroperitoneale Lymphknoten) können auch biologische Sonderformen, wie eine somatische Malignität oder das sogenannte „Growing-Teratoma“-Syndrom detektiert werden. Sollten histomorphologisch Anteile der typischen KZT-Subtypen in somatischen Malignitäten fehlen, kann der KZT-Ursprung molekularpathologisch durch Nachweis des Isochromosoms 12p oder einer Vermehrung chromosomalen Materials auf Chromosom 12 bestätigt werden.

Abstract

Germ cell tumours (GCTs) are the most common testicular neoplasms and are classified into type I, type II, and type III tumours depending on age of onset, molecular biology, and histomorphology. There are six histological subtypes, whose distribution varies among the three groups: seminomas, embryonal carcinomas, choriocarcinomas, yolk-sac tumours, teratomas, and spermatocytic tumours. The most common are malignant type II GCTs, typically treated with radical orchiectomy. In cases of small tumours where tumour dignity is uncertain – such as when serum markers are negative – initial enucleation followed by frozen section examination can be performed. This approach is particularly useful when benign tumours are suspected, including epidermal cysts, sex cord gonadal stromal tumours, adenomatoid tumours, or other testicular adnexal tumours, since testis-sparing tumour resection is sufficient for small benign tumours. The precise classification of GCTs is based on the histopathological assessment of morphological characteristics of the GCT subtypes and, in certain cases, is supplemented by immunohistochemical analyses. When examining resected specimens from metastatic sites (e.g., retroperitoneal lymph nodes), special biological variants of type II tumours, such as somatic malignancies or the so-called growing teratoma syndrome, may also be encountered. If somatic malignancies lack the characteristic histomorphological features of the typical GCT subtypes, the GCT origin can be confirmed molecular-pathologically by detecting isochromosome 12p or an amplification of chromosomal material on chromosome 12.

Schlüsselwörter

Hoden - Keimzelltumoren - somatische Malignität - Growing Teratoma Syndrom - Isochromosom 12p

Keywords

testis - germ cell tumour - somatic-type malignancy - growing teratoma syndrome - isochromosome 12p

Publication History

Received: 15 May 2025

Accepted: 07 July 2025

Article published online:
23 September 2025

• Literatur

• 1 Sung H, Ferlay J, Siegel RL. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021; 71: 209-249
• 2 Park JS, Kim J, Elghiaty A. et al. Recent global trends in testicular cancer incidence and mortality. Medicine (Baltimore) 2018; 97: e12390
• 3 WHO Classification of Tumours Editorial Board. Urinary and male genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2023 09 23]. (WHO classification of tumours series, 5th ed.; vol. 8). Accessed September 23, 2023 at: https://tumourclassification.iarc.who.int/chaptercontent/36/333
• 4 Oosterhuis JW, Looijenga LHJ. Human germ cell tumours from a developmental perspective. Nat Rev Cancer 2019; 19: 522-537
• 5 Honecker F, Aparicio J, Berney D. et al. ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment and follow-up. Ann Oncol 2018; 29: 1658-1686
• 6 Oosterhuis JW, Looijenga LHJ. Testicular germ-cell tumours in a broader perspective. Nat Rev Cancer 2005; 5: 210-222
• 7 Zhou G, Sun F, Yu X. et al. Clinical characteristics and long-term management of prepubertal testicular teratomas: a retrospective, multicenter study. Eur J Pediatr 2023; 182: 1823-1828
• 8 Pow-Sang J, Sánchez J, Benavente V. et al. Testicular yolk sac carcinoma in infants: natural history in 56 consecutive patients. Prog Clin Biol Res 1985; 203: 623-637
• 9 Rajpert-De Meyts E, Bartkova J, Samson M. et al. The emerging phenotype of the testicular carcinoma in situ germ cell. APMIS 2003; 111: 267-278
• 10 Nettersheim D, Heimsoeth A, Jostes S. et al. SOX2 is essential for in vivo reprogramming of seminoma-like TCam-2 cells to an embryonal carcinoma-like fate. Oncotarget 2016; 7: 47095-47110
• 11 Nettersheim D, Vadder S, Jostes S. et al. TCam-2 Cells Deficient for SOX2 and FOXA2 Are Blocked in Differentiation and Maintain a Seminoma-Like Cell Fate In Vivo. Cancers (Basel) 2019; 11: 728
• 12 Nettersheim D, Jostes S, Sharma R. et al. BMP Inhibition in Seminomas Initiates Acquisition of Pluripotency via NODAL Signaling Resulting in Reprogramming to an Embryonal Carcinoma. PLoS Genet 2015; 11: e1005415
• 13 Wruck W, Bremmer F, Kotthoff M. et al. The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours. J Cell Mol Med 2021; 25: 1-12
• 14 Kotthoff M, Skowron MA, Bremmer F. et al. Induction of SOX17 with stimulation of WNT, TGF-beta, and FGF signaling drives embryonal carcinomas into the yolk-sac tumor lineage resulting in increased cisplatin resistance. Int J Cancer 2025; 156: 2210-2224
• 15 Fichtner A, Richter A, Filmar S. et al. The detection of isochromosome i(12p) in malignant germ cell tumours and tumours with somatic malignant transformation by the use of quantitative real-time polymerase chain reaction. Histopathology 2021; 78: 593-606
• 16 Talerman A. Spermatocytic seminoma: clinicopathological study of 22 cases. Cancer 1980; 45: 2169-2176
• 17 Carrière P, Baade P, Fritschi L. Population based incidence and age distribution of spermatocytic seminoma. J Urol 2007; 178: 125-128
• 18 Hu R, Ulbright TM, Young RH. Spermatocytic Seminoma: A Report of 85 Cases Emphasizing Its Morphologic Spectrum Including Some Aspects Not Widely Known. Am J Surg Pathol 2019; 43: 1-11
• 19 Gupta S, Farooq A, Rowsey RA. et al. Cytogenetics of spermatocytic tumors with a discussion of gain of chromosome 12p in anaplastic variants. Hum Pathol 2022; 124: 85-95
• 20 Fichtner A, Nettersheim D, Bremmer F. Histopathological analysis of germ cell tumours: aspects to consider. Aktuelle Urol 2024; 55: 528-536
• 21 S3-Leitlinie Keimzelltumoren des Hodens AWMF-Registernummer: 043/049OL. https://www.leitlinienprogramm-onkologie.de/leitlinien/hodentumoren 2020
• 22 Elert A, Olbert P, Hegele A. et al. Accuracy of frozen section examination of testicular tumors of uncertain origin. Eur Urol 2002; 41: 290-293
• 23 Fankhauser CD, Roth L, Kranzbühler B. et al. The Role of Frozen Section Examination During Inguinal Exploration in Men with Inconclusive Testicular Tumors: A Systematic Review and Meta-analysis. Eur Urol Focus 2021; 7: 1400-1402
• 24 Vermeulen-Spohn MS, Pongratanakul P, Thy S. et al. RAISN: Robot-assisted Indocyanine Green-guided Sentinel Node Biopsy in Clinical Stage I Germ Cell Tumor. Eur Urol Open Sci 2024; 66: 55-59
• 25 Groll RJ, Warde P, Jewett MAS. A comprehensive systematic review of testicular germ cell tumor surveillance. Crit Rev Oncol Hematol 2007; 64: 182-197
• 26 Ulbright TM, Loehrer PJ, Roth LM. et al. The development of non-germ cell malignancies within germ cell tumors. A clinicopathologic study of 11 cases. Cancer 1984; 54: 1824-1833
• 27 Bremmer F, Pongratanakul P, Skowron M. et al. Characterizing the mutational burden, DNA methylation landscape, and proteome of germ cell tumor-related somatic-type malignancies to identify the tissue-of-origin, mechanisms of therapy resistance, and druggable targets. Br J Cancer 2023; 129: 1580-1589
• 28 Magers MJ, Kao C-S, Cole CD. et al. „Somatic-type“ malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin. Am J Surg Pathol 2014; 38: 1396-1409
• 29 Flood TA, Ulbright TM, Hirsch MS. „Embryonic-type Neuroectodermal Tumor“ Should Replace „Primitive Neuroectodermal Tumor“ of the Testis and Gynecologic Tract: A Rationale for New Nomenclature. The American journal of surgical pathology 2021; 45: 1299-1302
• 30 Logothetis CJ, Samuels ML, Trindade A. et al. The growing teratoma syndrome. Cancer 1982; 50: 1629-1635
• 31 Pongratanakul P, Bremmer F, Pauls S. et al. Assessing the risk to develop a growing teratoma syndrome based on molecular and epigenetic subtyping as well as novel secreted biomarkers. Cancer Lett 2024; 585: 216673