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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Solid Tumour Section Mini Review Testis: Spermatocytic seminoma Ewa Rajpert-De Meyts Dept. of Growth & Reproduction, Copenhagen University Hospital, Rigshospitalet, Section GR-5064, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark (ERDM) Published in Atlas Database: November 2003 Online updated version : http://AtlasGeneticsOncology.org/Tumors/SpermatSeminID5119.html DOI: 10.4267/2042/38059 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2004 Atlas of Genetics and Cytogenetics in Oncology and Haematology Identity Clinics and pathology Alias: Spermatocytoma Note: Spermatocytic seminoma is a rare testicular neoplasm derived from germ cells. It was first described by Masson in 1946. This tumour occurs exclusively in the testes, in relatively older men. There is no female (ovarian) equivalent. Disease Spermatocytic seminoma has a relatively mild clinical course. Most patients present with a painless swelling of one testis, but in some cases tenderness was reported. Metastases are very rare and have been basically reported only in cases with sarcomatous transformation. Classification Phenotype / cell stem origin Note Classification of germ cell tumours has not been adapted uniformly in the world. Two classifications most commonly used are the modified WHO classification and the British Testicular Panel (BTTP) classification. In addition Grigor proposed in 1993 a new classification based on biological features, and it was suggested in the AFIP Atlas of Tumor Pathology a modified classification of testicular and paratesticular tumours and tumour-like lesions. Spermatocytic seminoma is classified in these four systems as follows: Atlas Genet Cytogenet Oncol Haematol. 2004; 8(1) The origin of spermatocytic seminoma from the germ cell lineage has been clearly demonstrated by a number of studies, however the cell of origin have been a matter of debate. The initial hypothesis suggested that the spermatocyte was the progenitor cell and the tumour might contain post-meiotic haploid cells. Subsequent studies failed to find haploid DNA values, thus arguing against a true meiotic-phase tumour. 57 Testis: Spermatocytic seminoma Rajpert-De Meyts E En example of spermatocytic seminoma, HE-stained. A high power image showing characteristic polymorphism of the cell nucleus size of spermatocytic seminoma. Other hypotheses stipulated that spermatocytic seminoma might be a better differentiated variant of classical seminoma (composed of cells differentiating in the direction of spermatocytes but which have not yet reached this stage) or may originate from type B (dark) spermatogonia, which are committed to enter meiosis. Finally, some researchers suggested that spermatocytic seminoma might be derived from primordial germ cells or gonocytes. The current consensus, based on comparative studies of the phenotypes of spermatocytic seminoma, normal germ cells and other germ cell derived tumours, is that spermatocytic seminoma is derived from spermatogonia that are committed to enter meiosis but have not yet done so. Importantly, spermatocytic seminoma is not derived from carcinoma in situ (CIS), the gonocytes-like Atlas Genet Cytogenet Oncol Haematol. 2004; 8(1) intratubular precursor lesion for germ cell tumours of adolescents and young adults (classical seminoma and non-seminoma). Etiology Aetiology of spermatocytic seminoma is unknown. Epidemiology Spermatocytic seminoma is rare and represents around 2-5% of seminomas. It occurs in patients at 45-80 years of age, and is extremely rare in young men under than 35. This is in contrast to the classical seminoma, which demonstrates the peak of age-specific incidence around 35 years of age. Cytology A characteristic feature of spermatocytic seminoma is the presence of three types of cells with different 58 Testis: Spermatocytic seminoma Rajpert-De Meyts E nuclear size: large, small and intermediate. Some nuclei may exhibit a presence of nuclear thread-like chromatin. Evolution Some cases of spermatocytic seminoma may undergo sarcomatous transformation and spread outside the testis. An anaplastic variant was also described. Pathology There is no specific marker for spermatocytic seminoma. Proteins/antigens that are highly expressed in spermatogonia (most of them also present in gonocytes and primary spermatocytes), such as SSX (synovial sarcoma on X chromosome), NSE (neuronspecific enolase), CHK2, MAGE-A4, NY-ESO-1, VASA are present in spermatocytic seminoma. Antigens expressed in embryonic germ cells but not in the normal adult testis, e.g. PLAP (placental-like alkaline phosphatase), TRA-1-60, or KIT are usually undetectable in spermatocytic seminoma. High expression of p53 protein in a subset of cells was demonstrated in approximately 80% of cases. Proteins highly abundant in post-meiotic spermatids, e.g. p19INK4d, are usually not present in spermatocytic seminoma. The expression of telomerase (the RNA component) in spermatocytic seminoma was found to be moderate: lower than in classical seminomas but higher than in mature teratomas. Genetics Note No specific germ-line chromosomal aberration or gene mutations were reported in patients with spermatocytic seminoma. Cytogenetics Note Cytogenetic studies demonstrated variable ploidy of the different cell populations in spermatocytic seminoma, with prevalence of diploid and polyploid cells. No haploid values were found. Cytogenetics Molecular Only one molecular study of 4 spermatocytic seminomas was performed to date. A uniform gain of chromosome 9, and less consistent gains of chromosomes 1 and 20, and loss of chromosome 22 material were found by comparative genomic hybridisation. Treatment Spermatocytic seminoma (orchiectomy). is treated by surgery MAGE-A4 antigen is abundant is spermatocytic seminoma (visible in a lower part of the picture). Note that MAGE-A4 is also present in spermatogonia (visible in the upper part) (from Rajpert-De Meyts et al. Histopathology 2003). Atlas Genet Cytogenet Oncol Haematol. 2004; 8(1) 59 Testis: Spermatocytic seminoma Rajpert-De Meyts E Delgado R, Rathi A, Albores-Saavedra J, Gazdar AF. Expression of the RNA component of human telomerase in adult testicular germ cell neoplasia. Cancer. 1999 Nov 1;86(9):1802-11 References Rosai J, Silber I, Khodadoust K. Spermatocytic seminoma. I. Clinicopathologic study of six cases and review of the literature. Cancer. 1969 Jul;24(1):92-102 Kraggerud SM, Berner A, Bryne M, Pettersen EO, Fossa SD. Spermatocytic seminoma as compared to classical seminoma: an immunohistochemical and DNA flow cytometric study. APMIS. 1999 Mar;107(3):297-302 Pugh RC. Testicular tumours - Introduction. In: Pugh RC (ed.) Pathology of the testis. Blackwell Scientific, Oxford 1976, 139159 Ulbright TM, Amin MB, Young RH. Tumors of the testis, adnexa, spermatic cord, and scrotum. In: Atlas of Tumor Pathology. Third Series, Fascicle 25. Armed Forces Institute of Pathology, Washington DC, 1999, 1-375 Mostofi FK. Comparison of various clinical and pathological classifications of tumors of testes. Semin Oncol. 1979 Mar;6(1):26-30 Romanenko AM, Persidskiĭ IuV. [Ultrastructure and histogenesis of spermatocytic seminoma]. Vopr Onkol. 1983;29(7):60-6 Stoop H, van Gurp R, de Krijger R, Geurts van Kessel A, Köberle B, Oosterhuis W, Looijenga L. Reactivity of germ cell maturation stage-specific markers in spermatocytic seminoma: diagnostic and etiological implications. Lab Invest. 2001 Jul;81(7):919-28 Müller J, Skakkebaek NE, Parkinson MC. The spermatocytic seminoma: views on pathogenesis. Int J Androl. 1987 Feb;10(1):147-56 Satie AP, Rajpert-De Meyts E, Spagnoli GC, Henno S, Olivo L, Jacobsen GK, Rioux-Leclercq N, Jégou B, Samson M. The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma in situ. Lab Invest. 2002 Jun;82(6):775-80 Dekker I, Rozeboom T, Delemarre J, Dam A, Oosterhuis JW. Placental-like alkaline phosphatase and DNA flow cytometry in spermatocytic seminoma. Cancer. 1992 Feb 15;69(4):993-6 Grigor KM. A new classification of germ cell tumours of the testis. Eur Urol. 1993;23(1):93-100; discussion 101-3 Rajpert-De Meyts E, Jacobsen GK, Bartkova J, Aubry F, Samson M, Bartek J, Skakkebaek NE. The immunohistochemical expression pattern of Chk2, p53, p19INK4d, MAGE-A4 and other selected antigens provides new evidence for the premeiotic origin of spermatocytic seminoma. Histopathology. 2003 Mar;42(3):217-26 Eble JN. Spermatocytic seminoma. Hum Pathol. 1994 Oct;25(10):1035-42 Albores-Saavedra J, Huffman H, Alvarado-Cabrero I, Ayala AG. Anaplastic variant of spermatocytic seminoma. Hum Pathol. 1996 Jul;27(7):650-5 This article should be referenced as such: Rosenberg C, Mostert MC, Schut TB, van de Pol M, van Echten J, de Jong B, Raap AK, Tanke H, Oosterhuis JW, Looijenga LH. Chromosomal constitution of human spermatocytic seminomas: comparative genomic hybridization supported by conventional and interphase cytogenetics. Genes Chromosomes Cancer. 1998 Dec;23(4):286-91 Atlas Genet Cytogenet Oncol Haematol. 2004; 8(1) Rajpert-De Meyts E. Testis: Spermatocytic seminoma. Atlas Genet Cytogenet Oncol Haematol. 2004; 8(1):57-60. 60