Key changes in WHO classification 2022 of testicular tumors

Czech version

Authors: Květoslava Michalová ^1,2; Ondřej Hes ^1,2; Michal Michal ^1,2
Authors‘ workplace: Šiklův ústav patologie, Lékařská fakulta Univerzity Karlovy v Plzni a Fakultní nemocnice Plzeň, Česká republika ¹; Bioptická laboratoř s. r. o., Plzeň, Česká Republika ²
Published in: Čes.-slov. Patol., 58, 2022, No. 4, p. 198-204
Category: Reviews Article

Overview

Compared to the WHO classification of the male genital tumors in 2016, minimal changes were introduced in the current WHO 2022. Classification of germ cell tumors remains the same as in the previous edition, dividing germ cell tumors into those derived from germ cell neoplasia in situ (GCNIS) and those independent of GCNIS. The group of GCNIS derived germ cell tumors is essentially unchanged. Most remarkable change was made to the chapter teratoma with somatic malignancy. Primitive neuroectodermal tumor (PNET), a particular type of somatic malignancy arising in the setting of teratoma, is currently termed embryonic-type neuroectodermal tumor (ENET). Diagnostic criteria for teratoma with somatic type malignancy have been mildly modified. Seminoma now belongs to the group of germinomas. There is one novel entity in the category of germ cell tumors independent of GCNIS, namely testicular neuroendocrine tumor, prepubertal type. Similar to other organ systems, the term carcinoid is no longer used.

Two new entities were introduced in the category of sex cord stromal tumors: myoid gonadal stromal tumor and signet ring stromal tumor. Diagnostic criteria for malignant sex cord stromal tumors were moderately changed. Mitotic activity is now assessed according to mm2 instead of historical assessment according to the number of mitoses per high power fields.

There is a new separate chapter named Genetic tumor syndromes. Intratubular large cell hyalinizing Sertoli cell neoplasia which arises exclusively in patients with Peutz-Jeghers syndrome, now belongs here. Large cell calcifying Sertoli cell tumor occurs as a hereditary tumor in patients with Carney complex as well as sporadically. Therefore, it is enlisted both in the chapter on sex cord tumors and as well as in genetic tumor syndromes. Well differentiated papillary mesothelial tumor was added as a new entity to the section of testicular adnexal tumors. Sertoliform cystadenoma, a tumor previously belonging to testicular adnexal tumors, is currently recognized as a subtype of Sertoli cell tumor.

Keywords:

testicular tumors – WHO classification 2022 – tumors of the testis

Sources

1. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016; 70(1): 93- 105.

2. WHO Classification of Tumours Editorial Board. Urinary and male genital tumours (5th ed). Lyon: International Agency for Research on Cancer; 2022.

3. Berney DM, Cree I, Rao V, et al. An Introduction to the WHO 5(th) Edition 2022 Classification of Testicular tumours. Histopathology In press 2022.

4. Hes O, Pivovarcikova K, Stehlik J, et al. Choriogonadotropin positive seminoma-a clinicopathological and molecular genetic study of 15 cases. Ann Diagn Pathol 2014; 18(2): 89- 94.

5. 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(9): 1824- 1833.

6. Ganjoo KN, Foster RS, Michael H, Donohue JP, Einhorn LH. Germ cell tumor associated primitive neuroectodermal tumors. J Urol 2001; 165(5): 1514-1516.

7. Kato K, Ijiri R, Tanaka Y, et al. Testicular immature teratoma with primitive neuroectodermal tumor in early childhood. J Urol 2000; 164(6): 2068-2069.

8. Michael H, Hull MT, Ulbright TM, Foster RS, Miller KD. Primitive neuroectodermal tumors arising in testicular germ cell neoplasms. Am J Surg Pathol 1997; 21(8): 896-904.

9. 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. Am J Surg Pathol 2021; 45(10): 1299-1302.

10. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, eds. World Health Organization classification of tumours of the central nervous system (revised 4th ed). Lyon, IARC; 2016.

11. WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. (5th ed). Lyon: International Agency for Research on Cancer; 2021.

12. Ulbright TM, Hattab EM, Zhang S, et al. Primitive neuroectodermal tumors in patients with testicular germ cell tumors usually resemble pediatric-type central nervous system embryonal neoplasms and lack chromosome 22 rearrangements. Mod Pathol 2010; 23(7): 972-980.

13. Heikaus S, Schaefer KL, Eucker J, et al. Primary peripheral primitive neuroectodermal tumor/Ewing’s tumor of the testis in a 46-year-old man-differential diagnosis and review of the literature. Hum Pathol 2009; 40(6): 893-897.

14. Grimsby GM, Harrison CB. Ewing sarcoma of the scrotum. Urology 2014; 83(6): 1407-1408.

15. Magers MJ, Kao CS, 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(10): 1396-1409.

16. Colecchia M, Necchi A, Paolini B, Nicolai N, Salvioni R. Teratoma with somatic-type malignant components in germ cell tumors of the testis: a clinicopathologic analysis of 40 cases with outcome correlation. Int J Surg Pathol 2011; 19(3): 321-327.

17. Ahmed T, Bosl GJ, Hajdu SI. Teratoma with malignant transformation in germ cell tumors in men. Cancer 1985; 56(4): 860-863.

18. Motzer RJ, Amsterdam A, Prieto V, et al. Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol 1998; 159(1): 133-138.

19. Hwang MJ, Hamza A, Zhang M, et al. Somatic- type malignancies in testicular germ cell tumors: A clinicopathologic study of 63 cases. Am J Surg Pathol 2021; 46(1): 11-17.

20. Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol 2003; 21(23): 4285-4291.

21. Wagner T, Scandura G, Roe A, et al. Prospective molecular and morphological assessment of testicular prepubertal-type teratomas in postpubertal men. Mod Pathol 2020; 33(4):713-721.

22. Zhang C, Berney DM, Hirsch MS, Cheng L, Ulbright TM. Evidence supporting the existence of benign teratomas of the postpubertal testis: a clinical, histopathologic, and molecular genetic analysis of 25 cases. Am J Surg Pathol 2013; 37(6): 827-835.

23. Williamson SR, Delahunt B, Magi-Galluzzi C, et al. The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel. Histopathology 2017; 70(4): 335- 346.

24. Ulbright TM. Gonadal teratomas: a review and speculation. Adv Anat Pathol 2004; 11(1): 10-23.

25. Wang WP, Guo C, Berney DM, et al. Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases. Am J Surg Pathol 2010; 34(4): 519-524.

26. Fujita K, Wada R, Sakurai T, Sashide K, Fujime M. Primary carcinoid tumor of the testis with teratoma metastatic to the para-aortic lymph node. Int J Urol 2005; 12(3): 328-331.

27. Matoska J, Ondrus D, Hornak M. Metastatic spermatocytic seminoma. A case report with light microscopic, ultrastructural, and immunohistochemical findings. Cancer 1988; 62(6): 1197-1201.

28. Steiner H, Gozzi C, Verdorfer I, et al. Metastatic spermatocytic seminoma--an extremely rare disease. Eur Urol 2006; 49(1): 183-186.

29. Horn T, Schulz S, Maurer T, Gschwend JE, Kübler HR. Poor efficacy of BEP polychemotherapy in metastatic spermatocytic seminoma. Med Oncol 2011; 28 Suppl 1: S423-425.

30. Mikuz G, Böhm GW, Behrend M, et al. Therapy- resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report. Anal Quant Cytopathol Histpathol 2014; 36(3): 177-182.

31. Wagner T, Grantham M, Berney D. Metastatic spermatocytic tumour with hybrid genetics: breaking the rules in germ cell tumours. Pathology 2018; 50(5): 562-565.

32. Weidner N. Myoid gonadal stromal tumor with epithelial differentiation (? testicular myoepithelioma). Ultrastruct Pathol 1991; 15(4-5): 409-416.

33. Du S, Powell J, Hii A, Weidner N. Myoid gonadal stromal tumor: a distinct testicular tumor with peritubular myoid cell differentiation. Hum Pathol 2012; 43(1): 144-149.

34. Kao CS, Ulbright TM. Myoid gonadal stromal tumor: a clinicopathologic study of three cases of a distinctive testicular tumor. Am J Clin Pathol 2014; 142(5): 675-682.

35. Greco MA, Feiner HD, Theil KS, Mufarrij AA. Testicular stromal tumor with myofilaments: ultrastructural comparison with normal gonadal stroma. Hum Pathol 1984; 15(3): 238- 243.

36. Evans HL. Unusual gonadal stromal tumor of the testis. Case report with ultrastructural observations. Arch Pathol Lab Med 1977; 101(6): 317-320.

37. Renshaw AA, Gordon M, Corless CL. Immunohistochemistry of unclassified sex cord-stromal tumors of the testis with a predominance of spindle cells. Mod Pathol 1997; 10(7): 693-700.

38. Renne SL, Valeri M, Tosoni A, et al. Myoid gonadal tumor. Case series, systematic review, and Bayesian analysis. Virchows Arch 2021; 478(4): 727-734.

39. Nistal M, Puras A, Perna C, Guarch R, Paniagua R. Fusocellular gonadal stromal tumour of the testis with epithelial and myoid differentiation. Histopathology 1996; 29(3): 259- 264.

40. Allen PR, King AR, Sage MD, Sorrell VF. A benign gonadal stromal tumor of the testis of spindle fibroblastic type. Pathology 1990; 22(4): 227-229.

41. Cornejo KM, Young RH. Sex cord-stromal tumors of the testis. Diagnostic Histopathology 2019; 25(10): 398-407.

42. Lau HD, Kao CS, Williamson SR, et al. Immunohistochemical characterization of 120 testicular sex cord-stromal tumors with an emphasis on the diagnostic utility of SOX9, FOXL2, and SF-1. Am J Surg Pathol 2021; 45(10): 1303-1313.

43. WHO Classification of Tumours Editorial Board. Female genital tumours (5th ed). Lyon: International Agency for Research on Cancer; 2020.

44. Deshpande V, Oliva E, Young RH. Solid pseudopapillary neoplasm of the ovary: a report of 3 primary ovarian tumors resembling those of the pancreas. Am J Surg Pathol. 2010; 34(10): 1514-1520.

45. He S, Yang X, Zhou P, Cheng Y, Sun Q. Solid pseudopapillary tumor: an invasive case report of primary ovarian origin and review of the literature. Int J Clin Exp Pathol 2015; 8(7): 8645-8649.

46. Kominami A, Fujino M, Murakami H, Ito M. beta-catenin mutation in ovarian solid pseudopapillary neoplasm. Pathol Int 2014; 64(9): 460-464.

47. Cheuk W, Beavon I, Chui DT, Chan JK. Extrapancreatic solid pseudopapillary neoplasm: report of a case of primary ovarian origin and review of the literature. Int J Gynecol Pathol 2011; 30(6): 539-543.

48. Michalova K, Michal M, Sedivcova M, et al. Solid pseudopapillary neoplasm (SPN) of the testis: Comprehensive mutational analysis of 6 testicular and 8 pancreatic SPNs. Ann Diagn Pathol 2018; 35: 42-47.

49. Michal M, Bulimbasic S, Coric M, et al. Pancreatic analogue solid pseudopapillary neoplasm arising in the paratesticular location. The first case report. Hum Pathol 2016; 56: 52- 56.

50. Mengoli MC, Bonetti LR, Intersimone D, Fedeli F, Rossi G. Solid pseudopapillary tumor: a new tumor entity in the testis? Hum Pathol 2017; 62: 242-243.

51. Michalova K, Michal M, Jr., Kazakov DV, et al. Primary signet ring stromal tumor of the testis: a study of 13 cases indicating their phenotypic and genotypic analogy to pancreatic solid pseudopapillary neoplasm. Hum Pathol 2017; 67: 85-93.

52. Butnor KJ, Pavlisko EN, Sporn TA, Roggli VL. Mesothelioma of the tunica vaginalis testis. Hum Pathol 2019; 92: 48-58.

53. Stevers M, Rabban JT, Garg K, et al. Well-differentiated papillary mesothelioma of the peritoneum is genetically defined by mutually exclusive mutations in TRAF7 and CDC42. Mod Pathol 2019; 32(1): 88-99.

54. Churg A, Allen T, Borczuk AC, et al. Well-differentiated papillary mesothelioma with invasive foci. Am J Surg Pathol 2014; 38(1): 990- 998.

55. Brimo F, Illei PB, Epstein JI. Mesothelioma of the tunica vaginalis: a series of eight cases with uncertain malignant potential. Mod Pathol 2010; 23(8): 1165-1172.

56. Trpkov K, Barr R, Kulaga A, Yilmaz A. Mesothelioma of tunica vaginalis of “uncertain malignant potential” - an evolving concept: case report and review of the literature. Diagn Pathol 2011; 6: 78.

57. Tan WK, Tan MY, Tan WS, et al. Well-Differentiated Papillary Mesothelioma of the Tunica Vaginalis: Case Report and Systematic Review of Literature. Clin Genitourin Cancer 2016; 14(4): e435-439.