Practices recommendations in the applications of immunohistochemistry and molecular genetics in testicular tumors. Review article.
Authors:
Květoslava Michalová 1
; Michael Michal 1,2; Milan Hora 3; Ondřej Hes 1; Michal Michal 1
Authors place of work:
Šiklův ústav patologie, Univerzita Karlova, Fakultní nemocnice v Plzni
1; Biomedicínské centrum, Univerzita Karlova, Fakultní nemocnice v Plzni
2; Urologická klinika, Univerzita Karlova, Fakultní nemocnice v Plzni
3
Published in the journal:
Čes.-slov. Patol., 56, 2020, No. 3, p. 153-160
Category:
Reviews Article
Summary
The great majority of testicular tumors can be diagnosed on the basis of morphology, while immunohistochemistry and molecular genetics assist in only a small proportion of cases. Similar to other areas of pathology, ancillary diagnostic methods have to be used responsibly and assessed in correlation with morphological, serological and clinical findings. Prior to their effective use, a limited differential diagnosis based on morphology is required.The significance of germ cell tumors is underscored by the fact that they represent the most frequent solid neoplasms occurring in men between 20-30 years and if diagnosed correctly and in early stage, they have excellent prognosis. From the molecular genetic standpoint, germ cell tumors stand apart from the current trend of tumor stratification based on molecular profiles. It is mainly due to the low mutational load, since the main genetic abnormality are chromosomal aneuploidies. Given the frequency of germ cell tumors among testicular neoplasms and since morphology is usually diagnostically most valuable, this review article is focused mainly on germ cell tumors, emphasizing the morphological features. Sertoli cell tumor, NOS is the only sex-cord stromal tumor included in this review as its diagnosis can be challenging. For practical purposes, this reviewis focused on differential diagnosis, including only entities where misdiagnosis would have impact on clinical outcome.
Keywords:
immunohistochemistry – Molecular genetics – testicular tumors – testis
Zdroje
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. EAU guidelines: Testicular cancer. https://uroweb.org/guideline/testicular-cancer/
3. Coffin CM, Ewing S, Dehner LP. Frequency of intratubular germ cell neoplasia with invasive testicular germ cell tumors. Histologic and immunocytochemical features. Arch Pathol Lab Med 1985; 109(6): 555-559.
4. Chieffi P. An up-date on epigenetic and molecular markers in testicular germ cell tumors. Intractable Rare Dis Res 2017; 6(4): 319-321.
5. Miettinen M, Wang Z, McCue PA, Sarlomo-Rikala M, Rys J, et al. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases. Am J Surg Pathol 2014; 38(3): 410-420.
6. Grieco V, Banco B, Giudice C, Mosca F, Finazzi M. Immunohistochemical expression of the KIT protein (CD117) in normal and neoplastic canine testes. J Comp Pathol 2010; 142(2-3): 213-217.
7. Ulbright TM, Tickoo SK, Berney DM, Srigley JR. Best practices recommendations in the application of immunohistochemistry in testicular tumors: report from the International Society of Urological Pathology consensus conference. Am J Surg Pathol 2014; 38(8): e50-59.
8. Cope NJ, McCullagh P, Sarsfield PT. Tumour responding accessory cells in testicular seminoma: an immunohistochemical study. Histopathology 1999; 34(6): 510-516.
9. Wei YQ, Hang ZB, Liu KF. In situ observation of inflammatory cell-tumor cell interaction in human seminomas (germinomas): light, electron microscopic, and immunohistochemical study. Hum Pathol 1992; 23(4): 421-428.
10. Kao CS, Ulbright TM, Young RH, Idrees MT. Testicular embryonal carcinoma: a morphologic study of 180 cases highlighting unusual and unemphasized aspects. Am J Surg Pathol 2014; 38(5): 689-697.
11. Pierce GB, Abell MR. Embryonal carcinoma of the testis. Pathol Annu 1970; 5: 27-60.
12. Grigor KM. Embryonal carcinoma of testis simulating seminoma. J Clin Pathol 1987; 40(11): 1388.
13. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. Am J Surg Pathol 2007; 31(6): 836-845.
14. Cao D, Allan RW, Cheng L, Peng Y, Guo CC, et al. RNA-binding protein LIN28 is a marker for testicular germ cell tumors. Hum Pathol 2011; 42(5): 710-718.
15. Cao D, Li J, Guo CC, Allan RW, Humphrey PA. SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 2009; 33(7): 1065-1077.
16. Rajpert-De Meyts E, Skakkebaek NE. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl 1994; 17(2): 85-92.
17. Izquierdo MA, Van der Valk P, Van Ark-Otte J, Rubio G, Germa-Lluch JR, et al. Differential expression of the c-kit proto-oncogene in germ cell tumours. J Pathol 1995; 177(3): 253-258.
18. Strohmeyer T, Reese D, Press M, Ackermann R, Hartmann M, et al. Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue. J Urol 1995; 153(2): 511-515.
19. Leroy X, Augusto D, Leteurtre E, Gosselin B. CD30 and CD117 (c-kit) used in combination are useful for distinguishing embryonal carcinoma from seminoma. J Histochem Cytochem 2002; 50(2): 283-285.
20. Lau SK, Weiss LM, Chu PG. D2-40 immunohistochemistry in the differential diagnosis of seminoma and embryonal carcinoma: a comparative immunohistochemical study with KIT (CD117) and CD30. Mod Pathol 2007; 20(3): 320-325.
21. Iczkowski KA, Butler SL, Shanks JH, Hossain D, Schall A, et al. Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors. Hum Pathol 2008; 39(2): 275-281.
22. Idrees M, Saxena R, Cheng L, Ulbright TM, Badve S. Podoplanin, a novel marker for seminoma: A comparison study evaluating immunohistochemical expression of podoplanin and OCT3/4. Ann Diagn Pathol 2010; 14(5): 331-336.
23. Kato Y, Sasagawa I, Kaneko M, Osawa M, Fujita N, et al. Aggrus: a diagnostic marker that distinguishes seminoma from embryonal carcinoma in testicular germ cell tumors. Oncogene 2004; 23(52): 8552-8556.
24. Yu H, Pinkus GS, Hornick JL. Diffuse membranous immunoreactivity for podoplanin (D2-40) distinguishes primary and metastatic seminomas from other germ cell tumors and metastatic neoplasms. Am J Clin Pathol 2007; 128(5): 767-775.
25. de Jong J, Stoop H, Gillis AJ, van Gurp RJ, van de Geijn GJ, et al. Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications. J Pathol 2008; 215(1): 21-30.
26. Nonaka D. Differential expression of SOX2 and SOX17 in testicular germ cell tumors. Am J Clin Pathol 2009; 131(5): 731-736.
27. Cheville JC, Rao S, Iczkowski KA, Lohse CM, Pankratz VS. Cytokeratin expression in seminoma of the human testis. Am J Clin Pathol 2000; 113(4): 583-588.
28. Ferreiro JA. Ber-H2 expression in testicular germ cell tumors. Hum Pathol 1994; 25(5): 522-524.
29. Hittmair A, Rogatsch H, Hobisch A, Mikuz G, Feichtinger H. CD30 expression in seminoma. Hum Pathol 1996; 27(11): 1166-1171.
30. Pallesen G, Hamilton-Dutoit SJ. Ki-1 (CD30) antigen is regularly expressed by tumor cells of embryonal carcinoma. Am J Pathol 1988; 133(3): 446-450.
31. Niehans GA, Manivel JC, Copland GT, Scheithauer BW, Wick MR. Immunohistochemistry of germ cell and trophoblastic neoplasms. Cancer 1988; 62(6): 1113-1123.
32. Sung MT, Jones TD, Beck SD, Foster RS, Cheng L. OCT4 is superior to CD30 in the diagnosis of metastatic embryonal carcinomas after chemotherapy. Hum Pathol 2006; 37(6): 662-667.
33. Berney DM, Shamash J, Pieroni K, Oliver RT. Loss of CD30 expression in metastatic embryonal carcinoma: the effects of chemotherapy? Histopathology 2001; 39(4): 382-385.
34. Emerson RE, Ulbright TM. Morphological approach to tumours of the testis and paratestis. J Clin Pathol 2007; 60(8): 866-880.
35. Ye H, Ulbright TM. Difficult differential diagnoses in testicular pathology. Arch Pathol Lab Med 2012; 136(4): 435-446.
36. Kao CS, Idrees MT, Young RH, Ulbright TM. Solid pattern yolk sac tumor: a morphologic and immunohistochemical study of 52 cases. Am J Surg Pathol 2012; 36(3): 360-367.
37. Talerman A. Endodermal sinus (yolk sac) tumor elements in testicular germ-cell tumors in adults: comparison of prospective and retrospective studies. Cancer 1980; 46(5):1213-1217.
38. Milose JC, Filson CP, Weizer AZ, Hafez KS, Montgomery JS. Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance. Open Access J Urol 2011; 4:1-8.
39. Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L. OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol 2004; 28(7): 935-940.
40. Eglen DE, Ulbright TM. The differential diagnosis of yolk sac tumor and seminoma. Usefulness of cytokeratin, alpha-fetoprotein, and alpha-1-antitrypsin immunoperoxidase reactions. Am J Clin Pathol 1987; 88(3): 328-332.
41. Miettinen M, Virtanen I, Talerman A. Intermediate filament proteins in human testis and testicular germ-cell tumors. Am J Pathol 1985; 120(3): 402-410.
42. von Hochstetter AR, Sigg C, Saremaslani P, Hedinger C. The significance of giant cells in human testicular seminomas. A clinico-pathological study. Virchows Arch A Pathol Anat Histopathol 1985; 407(3): 309-322.
43. Mostofi FK, Sesterhenn IA. Pathology of germ cell tumors of testes. Prog Clin Biol Res 1985; 203: 1-34.
44. Looijenga LH, Stoop H, de Leeuw HP, de Gouveia Brazao CA, Gillis AJ, et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res 2003; 63(9): 2244-2250.
45. Hes O, Pivovarcikova K, Stehlik J, Martinek P, Vanecek T, et al. Choriogonadotropin positive seminoma-a clinicopathological and molecular genetic study of 15 cases. Ann Diagn Pathol 2014; 18(2): 89-94.
46. Weissbach L, Bussar-Maatz R, Lohrs U, Schubert GE, Mann K, et al. Prognostic factors in seminomas with special respect to HCG: results of a prospective multicenter study. Seminoma Study Group. Eur Urol 1999; 36(6):601-608.
47. Giannoulatou E, Maher GJ, Ding Z, Gillis AJM, Dorssers LCJ, et al. Whole-genome sequencing of spermatocytic tumors provides insights into the mutational processes operating in the male germline. PLoS One 2017; 12(5): e0178169.
48. Sandberg AA, Meloni AM, Suijkerbuijk RF. Reviews of chromosome studies in urological tumors. III. Cytogenetics and genes in testicular tumors. J Urol 1996; 155(5): 1531-1556.
49. Atkin NB, Baker MC. Specific chromosome change, i(12p), in testicular tumours? Lancet 1982; 2(8311): 1349.
50. Atkin NB, Baker MC. i(12p): specific chromosomal marker in seminoma and malignant teratoma of the testis? Cancer Genet Cytogenet 1983; 10(2): 199-204.
51. Sheikine Y, Genega E, Melamed J, Lee P, Reuter VE, et al. Molecular genetics of testicular germ cell tumors. Am J Cancer Res 2012; 2(2): 153-1567.
52. Litchfield K, Summersgill B, Yost S, Sultana R, Labreche K, et al. Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours. Nat Commun 2015; 6 5973.
53. Brabrand S, Johannessen B, Axcrona U, Kraggerud SM, Berg KG, et al. Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages. Neoplasia 2015; 17(2): 167-174.
54. Cutcutache I, Suzuki Y, Tan IB, Ramgopal S, Zhang S, et al. Exome-wide sequencing shows low mutation rates and identifies novel mutated genes in seminomas. Eur Urol 2015; 68(1): 77-83.
55. Taylor-Weiner A, Zack T, O’Donnell E, Guerriero JL, Bernard B, et al. Genomic evolution and chemoresistance in germ-cell tumours. Nature 2016; 540(7631): 114-118.
56. 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.
57. Oosterhuis JW, Stoop JA, Rijlaarsdam MA, Biermann K, Smit VT, et al. Pediatric germ cell tumors presenting beyond childhood? Andrology 2015; 3(1): 70-77.
58. Muller J, Skakkebaek NE, Ritzen M, Ploen L, Petersen KE. Carcinoma in situ of the testis in children with 45,X/46,XY gonadal dysgenesis. J Pediatr 1985; 106(3): 431-436.
59. Slowikowska-Hilczer J, Romer TE, Kula K. Neoplastic potential of germ cells in relation to disturbances of gonadal organogenesis and changes in karyotype. J Androl 2003; 24(2): 270-278.
60. Trivedi P, Pasricha S, Gupta A. Spermatocytic seminoma associated with undifferentiated sarcoma: a rare case report. Indian J Pathol Microbiol 2011; 54(1): 138-140.
61. Lombardi M, Valli M, Brisigotti M, Rosai J. Spermatocytic seminoma: review of the literature and description of a new case of the anaplastic variant. Int J Surg Pathol 2011; 19(1): 5-10.
62. Mikuz G, Bohm GW, Behrend M, Schafer G, Colecchia M, et al. Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report. Anal Quant Cytopathol Histpathol 2014; 36(3): 177-182.
63. Horn T, Schulz S, Maurer T, Gschwend JE, Kubler HR. Poor efficacy of BEP polychemotherapy in metastatic spermatocytic seminoma. Med Oncol 2011; 28 Suppl 1: S423-425.
64. Steiner H, Gozzi C, Verdorfer I, Mikuz G, Bartsch G, et al. Metastatic spermatocytic seminoma--an extremely rare disease: Part 2. Eur Urol 2006; 49(1): 408-409.
65. 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.
66. Roth LM, Michal M, Michal M, Jr., Cheng L. Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis. Hum Pathol 2018; 82: 68-75.
67. Cummings OW, Ulbright TM, Eble JN, Roth LM. Spermatocytic seminoma: an immunohistochemical study. Hum Pathol 1994; 25(1): 54-59.
68. Jorgensen A, Nielsen JE, Blomberg Jensen M, Graem N, Rajpert-De Meyts E. Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry. Mol Hum Reprod 2012; 18(11): 523-534.
69. Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 2005; 18 Suppl 2: S61-79.
70. Ulbright TM. Gonadal teratomas: a review and speculation. Adv Anat Pathol 2004; 11(1): 10-23.
71. Grady RW, Ross JH, Kay R. Epidemiological features of testicular teratoma in a prepubertal population. J Urol 1997; 158(3 Pt 2): 1191-1192.
72. Visfeldt J, Jorgensen N, Muller J, Moller H, Skakkebaek NE. Testicular germ cell tumours of childhood in Denmark, 1943-1989: incidence and evaluation of histology using immunohistochemical techniques. J Pathol 1994; 174(1): 39-47.
73. Leibovitch I, Foster RS, Ulbright TM, Donohue JP. Adult primary pure teratoma of the testis. The Indiana experience. Cancer 1995; 75(9): 2244-2250.
74. Mostert M, Rosenberg C, Stoop H, Schuyer M, Timmer A, et al. Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis. Lab Invest 2000; 80(7): 1055-1064.
75. Ulbright TM, Young RH. Testicular and paratesticular tumors and tumor-like lesions in the first 2 decades. Semin Diagn Pathol 2014; 31(5): 323-381.
76. Williamson SR, Delahunt B, Magi-Galluzzi C, Algaba F, Egevad L, 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.
77. Perlman EJ, Hu J, Ho D, Cushing B, Lauer S, et al. Genetic analysis of childhood endodermal sinus tumors by comparative genomic hybridization. J Pediatr Hematol Oncol 2000; 22(2): 100-105.
78. Schneider DT, Schuster AE, Fritsch MK, Hu J, Olson T, et al. Multipoint imprinting analysis indicates a common precursor cell for gonadal and nongonadal pediatric germ cell tumors. Cancer Res 2001; 61(19): 7268-7276.
79. Veltman IM, Schepens MT, Looijenga LH, Strong LC, van Kessel AG. Germ cell tumours in neonates and infants: a distinct subgroup? APMIS 2003; 111(1): 152-160; discussion 60.
80. Perrone F, Bertolotti A, Montemurro G, Paolini B, Pierotti MA, et al. Frequent mutation and nuclear localization of beta-catenin in sertoli cell tumors of the testis. Am J Surg Pathol 2014; 38(1): 66-71.
81. Zhang C, Ulbright TM. Nuclear localization of beta-catenin in sertoli cell tumors and other sex cord-stromal tumors of the testis: an immunohistochemical study of 87 cases. Am J Surg Pathol 2015; 39(10): 1390-1394.
82. Colecchia M. Observations on the paper “sclerosing Sertoli cell tumor of the testis: a clinicopathologic study of 20 cases” by Kao et al. Am J Surg Pathol 2014; 38(8): 1160.
83. Verdorfer I, Hollrigl A, Strasser U, Susani M, Hartmann A, et al. Molecular-cytogenetic characterisation of sex cord-stromal tumours: CGH analysis in sertoli cell tumours of the testis. Virchows Arch 2007; 450(4): 425-431.
84. Michal M, Bulimbasic S, Coric M, Sedivcova M, Kazakov DV, et al. Pancreatic analogue solid pseudopapillary neoplasm arising in the paratesticular location. The first case report. Hum Pathol 2016; 56: 52-56.
85. Michalova K, Michal M, Jr., Kazakov DV, Sedivcova M, Hes O, 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.
86. Michalova K, Michal M, Sedivcova M, Kazakov DV, Bacchi C, 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.
87. Notohara K, Hamazaki S, Tsukayama C, Nakamoto S, Kawabata K, et al. Solid-pseudopapillary tumor of the pancreas: immunohistochemical localization of neuroendocrine markers and CD10. Am J Surg Pathol 2000; 24(10): 1361-1371.
88. Serra S, Chetty R. Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas. J Clin Pathol 2008; 61(11): 1153-1159.
89. Tanaka Y, Kato K, Notohara K, Hojo H, Ijiri R, et al. Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm. Cancer Res 2001; 61(23): 8401-8404.
90. Ulbright TM, Young RH. Pseudo-”solid pseudopapillary neoplasms” of the testis: in reality Sertoli cell tumors. Hum Pathol 2019; 83: 228-230.
91. 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.
92. Henley JD, Young RH, Ulbright TM. Malignant Sertoli cell tumors of the testis: a study of 13 examples of a neoplasm frequently misinterpreted as seminoma. Am J Surg Pathol 2002; 26(5): 541-550.
93. Ulbright TM, Young RH. Seminoma with tubular, microcystic, and related patterns: a study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor. Am J Surg Pathol 2005; 29(4): 500-505.
94. Young RH, Finlayson N, Scully RE. Tubular seminoma. Report of a case. Arch Pathol Lab Med 1989; 113(4): 414-416.
95. Zavala-Pompa A, Ro JY, el-Naggar AK, Amin MB, Ordonez NG, et al. Tubular seminoma. An immunohistochemical and DNA flow-cytometric study of four cases. Am J Clin Pathol 1994; 102(4): 397-401.
Štítky
Anatomical pathology Forensic medical examiner ToxicologyČlánok vyšiel v časopise
Czecho-Slovak Pathology
2020 Číslo 3
Najčítanejšie v tomto čísle
- Lymph node metastasis of parotid gland high-grade adenoid-cystic carcinoma
- Immunohistochemistry in hollow urinary tract
- Immunohistochemistry and renal neoplasias
- Immunohistochemistry in prostate pathology