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Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

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Abstract

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord–stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical “square off” quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff (PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohistochemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1–AE3 by paranuclear dot-like or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immunohistochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical “square off” quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohistochemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of 12p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon–intron junctions in c-kit and PDFGRA genes.

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References

  1. Arroyo JG, Harris W, Laden A (1998) Recurrent mixed germ cell–sex cord stromal tumor of the ovary in an adult. Int J Gynecol Pathol 17:281–283

    PubMed  CAS  Google Scholar 

  2. Baker PM, Oliva E (2005) Immunohistochemistry as a tool in the differential diagnosis of ovarian tumors: An update. Int J Gynecol Pathol 24:39–55

    PubMed  Google Scholar 

  3. Bolen JW (1981) Mixed germ cell–sex cord stromal tumor. A gonadal tumor distinct from gonadoblastoma. Am J Clin Pathol 75:565–573

    PubMed  CAS  Google Scholar 

  4. Bosl GJ, Ilson DH, Rodriguez E, Motzer RJ, Reuter VE, Chaganti RS (1994) Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86:349–355

    Article  PubMed  CAS  Google Scholar 

  5. Cabanne F (1971) Gonadoblastomes et tumeurs de l’ebauche gonadique. Ann Anat Pathol (Paris) 16:387–404

    CAS  Google Scholar 

  6. Cheng L (2004) Establishing a germ cell origin for metastatic tumors using OCT4 immunohistochemistry. Cancer 101:2006–2010

    Article  PubMed  Google Scholar 

  7. Cheville JC, Rao S, Iczkowski KA, Lohse CM, Pankratz VS (2000) Cytokeratin expression in seminoma of the human testis. Am J Clin Pathol 113:583–588

    Article  PubMed  CAS  Google Scholar 

  8. Cummings OW, Ulbright TM, Eble JN, Roth LM (1994) Spermatocytic seminoma: An immunohistochemical study. Hum Pathol 25:54–59

    Article  PubMed  CAS  Google Scholar 

  9. Daum O, Klecka J, Ferda J, Treska V, Vanecek T, Sima R, Mukensnabl P, Michal M (2005) Gastrointestinal stromal tumor of the pancreas: case report with documentation of kit gene mutation. Virchows Arch 446:470–472

    Article  PubMed  Google Scholar 

  10. Denk H, Moll R, Weybora W, Lackinger E, Vennigerholz F, Beham A, Franke WW (1987) Intermediate filaments and desmosomal plaque proteins in testicular seminomas and non-seminomatous germ cell tumours as revealed by immunohistochemistry. Virchows Arch A Pathol Anat Histopathol 410:295–307

    Article  PubMed  CAS  Google Scholar 

  11. Floyd C, Ayala AG, Logothesis CJ, Silva EG (1988) Spermatocytic seminoma with associated sarcoma of the testis. Cancer 61:409–414

    Article  PubMed  CAS  Google Scholar 

  12. Hattab EM, Pang-Hsien T, Wilson DJ, Cheng L (2005) OCT4 immunohistochemistry is superior to placental alkaline phosphatase (PLAP) in the diagnosis of central nervous system germinoma. Am J Surg Pathol 29:368–371

    Article  PubMed  Google Scholar 

  13. Hughesdon PE, Kumarasamy T (1970) Mixed germ cell tumours (gonadoblastomas) in normal and dysgenetic gonads. Case reports and review. Virchows Arch A Pathol Pathol Anat 349:258–280

    Article  PubMed  CAS  Google Scholar 

  14. Jacobsen GK, Braendstrup O, Talerman A (1991) Bilateral mixed germ cell sex–cord stroma tumour in a young adult woman. APMIS 23:132–137

    CAS  Google Scholar 

  15. Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L (2004) OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol 28:935–940

    Article  PubMed  Google Scholar 

  16. Kemmer K, Corless CL, Fletcher JA, McGreevey L, Haley A, Griffith D, Cummings OW, Wait C, Town A, Heinrich M (2004) KIT mutation common in testicular seminomas. Am J Pathol 164:305–313

    PubMed  CAS  Google Scholar 

  17. Kernek KM, Brunelli M, Ulbright TM, Eble JN, Martignoni G, Zhang S, Michael H, Cummings OW, Cheng L (2004) Fluorescence in situ hybridization analysis of chromosome 12p in paraffin-embedded tissue is useful for establishing germ cell origin of metastatic tumors. Mod Pathol 17:1309–1313

    Article  PubMed  CAS  Google Scholar 

  18. Kurman RJ (2002) In: Talerman A (ed) Germ cell tumors of the ovary. Blaustain’s Pathology of the Female Genital Tract, 5th edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  19. Lacson AG, Gillis DA, Shawwa A (1988) Malignant mixed germ cell sex cord stromal tumors of the ovary associated with isosexual precocious puberty. Cancer 61:2122–2133

    Article  PubMed  CAS  Google Scholar 

  20. Looijenga LHJ, Zafarana G, Grygalewicz B, Summersgill B, Debiec-Rychter M, Veltman J, Schoenmakers EFPM, Rodriguez S, Jafer O, Clark J, van Kessel ADG, Shipley J, van Gurp RJHLM, Gillis AJM, Oosterhuis JW (2003) Role of gain of 12p in germ cell tumour development. APMIS 111:161–173

    Article  PubMed  Google Scholar 

  21. Masson P (1912) Pflügerome. Bull Soc Anat Paris 14:403–404

    Google Scholar 

  22. Masson P (1923) Les tumeurs. Epitheliomas pflugeriens. In: Diagnostics de Laboratoire. Maloine Editions, Paris, pp 477–478

  23. Matoska J, Talerman A (1989) Mixed germ cell–sex cord stroma tumor of the testis. A report with ultrastructural findings. Cancer 64:2146–2153

    Article  PubMed  CAS  Google Scholar 

  24. Matoska J, Talerman A (1990) Spermatocytic seminoma associated with rhabdomyosarcoma. Am J Clin Pathol 94:89–95

    PubMed  CAS  Google Scholar 

  25. Pauls K, Wardelmann E, Franke FE, Heukamp L, Büttner R, Mey U, Zhou H (2005) Primary extragonadal germ cell tumour: unusual localization of a c-kit mutated retroperitoneal seminoma in the gastric wall. Histopathology 47:11–113

    Article  Google Scholar 

  26. Przygodzki RM, Hubbs AE, Zhao FQ, O’Leary TJ (2002) Primary mediastinal seminomas: evidence of single and multiple KIT mutations. Lab Invest 82:1369–1375

    PubMed  CAS  Google Scholar 

  27. Reeves G, Elias E, Sarancone S, Albertengo A (2001) Lesiones mixtas de células germinales, cordones sexuales y estroma del ovaria. Patologia 39:116–126

    Google Scholar 

  28. Rames RA, Richardson M, Swiger F, Kaczmarek A (1995) Mixed germ cell–sex cord stromal tumor of the testis: the incidental finding of a rare testicular neoplasm. J Urol 154:1479

    Article  PubMed  CAS  Google Scholar 

  29. Reuter VE (2005) Origins and molecular biology of testicular germ cell tumors. Mod Pathol 18:S51–S60

    Article  PubMed  CAS  Google Scholar 

  30. Rosai J, Silber I, Khodadoust K (1969) Spermatocytic seminoma. I. Clinicopathologic study of six cases and review of the literature. Cancer 24:92–116

    Article  PubMed  CAS  Google Scholar 

  31. Scully RE (1970) Gonadoblastoma: a review of 74 cases. Cancer 25:1340–1356

    Article  PubMed  CAS  Google Scholar 

  32. Speleman F, Dermaut B, De Potter CR, van Gele M, van Roy N, De Paepe A, Laureys G (1997) Monosomy 22 in a mixed germ cell sex cord–stromal tumor of the ovary. Genes Chromosomes Cancer 19:192–194

    Article  PubMed  CAS  Google Scholar 

  33. Talerman A (1972) A mixed germ cell–sex cord stroma tumor of the ovary in a normal female infant. Obstet Gynecol 40:473–478

    PubMed  CAS  Google Scholar 

  34. Talerman A (1972) A distinctive gonadal neoplasm related to gonadoblastoma. Cancer 30:1219–1294

    Article  PubMed  CAS  Google Scholar 

  35. Talerman A, van der Harten JJ (1977) Mixed germ cell–sex cord stromal tumor of the ovary associated with isosexual precocious puberty in a normal girl. Cancer 40:889–894

    Article  PubMed  CAS  Google Scholar 

  36. Talerman A (1979) Gonadal tumours composed of germ cells and sex cord stroma derivatives. Patol Pol 30:221–228

    PubMed  CAS  Google Scholar 

  37. Talerman A (1980) The pathology of gonadal neoplasms composed of germ cells and sex cord stroma derivatives. Pathol Res Pract 170:24–38

    CAS  PubMed  Google Scholar 

  38. Tavassoli FA (1983) A combined germ cell–gonadal stromal–epithelial tumor of the ovary. Am J Surg Pathol 7:73–84

    PubMed  CAS  Google Scholar 

  39. Tian Q, Frierson HF, Krystal DW, Moskaluk CA (1999) Activating c-kit gene mutations in human germ cell tumors. Am J Pathol 154:1643–1647

    PubMed  CAS  Google Scholar 

  40. Tickoo SK, Hutchinson B, Bacik J, Mazumdar M, Motzer RJ, Bajorin DF, Bosl GJ, Reuter VE (2002) Testicular seminoma: A clinicopathologic and immunohistochemical study of 105 cases with special reference to seminomas with atypical features. Int J Surg Pathol 10:23–32

    Article  PubMed  Google Scholar 

  41. Tokuoka S, Aoki Y, Hayashi Y, Yokoyama T, Ishii T (1985) A mixed germ cell sex cord stromal tumor of the ovary with retiform tubular structure: a case report. Int J Gynecol Pathol 4:161–170

    PubMed  CAS  Google Scholar 

  42. True LD, Otis CN, Delprado W, Scully RE, Rosai J (1988) Spermatocytic seminoma of testis with sarcomatous transformation. A report of five cases. Am J Surg Pathol 12:75–82

    PubMed  CAS  Google Scholar 

  43. Ulbright TM, Srigley JR, Reuter VE, Wojno K, Roth LM, Young RH (2000) Sex cord stromal tumor of the testis with entrapped germ cells. A lesion mimicking unclassified mixed germ cell-sex cord stromal tumor. Am J Surg Pathol 24:535–542

    Article  PubMed  CAS  Google Scholar 

  44. Ulbright TM (2005) Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 18(Suppl 2):S61–S79

    Article  PubMed  Google Scholar 

  45. Young RH, Dickersin GR, Scully RE (1983) A distinctive ovarian sex cord stromal tumor causing sexual precocity in the Peutz Jeghers syndrome. Am J Surg Pathol 7:233–243

    Article  PubMed  CAS  Google Scholar 

  46. 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

    Article  PubMed  Google Scholar 

  47. Zuntova A, Motlik K, Horejsi J, Eckschlager T (1992) Mixed germ cell–sex cord stromal tumor with heterologous structures. Int J Gynecol Pathol 11:227–233

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We would like to thank to Dr. J. Arroyo for allowing us to use a tissue from his case [1] for the study.

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Correspondence to Michal Michal.

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Michal, M., Vanecek, T., Sima, R. et al. Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases. Virchows Arch 448, 612–622 (2006). https://doi.org/10.1007/s00428-006-0155-z

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