Testicular cancer pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gertrude Djouka, M.D.[2], Shanshan Cen, M.D. [3]
Overview
The pathophysiology of testicular cancer depends on the histological cell subtypes and findings. Most testicular cancers derived from the lack of differentiation of primordial germ cell into spermatogonia. On microscopic histopathological analysis of testicular cancer, fried-egg appearance is the characteristic finding of seminoma; marked nuclear atypia is the characteristic finding of embryonal carcinoma; blander cytomorphology, hyaline-type globules, and Schiller-Duval bodies are characteristic findings of yolk sac tumor ; syncytiotrophoblasts and cytotrophoblast cells are the characteristic findings of choriocarcinoma.
Pathogenesis
Normal process
- Primordial germ cell mass leads to gonocytes through cell proliferation
- Gonocytes differentiate into spermatogonia
Germ cells tumors
- Lack of primordial germ cell to differentiate into spermatogonia leads to germ cell neoplasia in Situ[2]
- Germ cell neoplasia in Situ may gain some abnormal chromosome(12), then it leads to seminomas and nonseminomas cancers.
- Seminomas and non seminotous germ cell tumors have similar pathogenesis[3]
- Aneuploid
- Loss of chromosomes 4,5,11,13,18, and Y
- Gain of chromosomes 7,8,12, and X
- More than 90% of all testicular cancers are germ cell tumors. This type of cancer starts in germ cells, which are the cells that develop into sperms.
- About 50% of all germ cell tumors are seminomas, or seminomatous germ cell tumours. They grow slower than non-seminomas.
- Overrepresentation of short arm of chromosomes 12p may be related to invasive growth of seminomas and nonseminomatous testicular cancer.[4]
- Seminomas tumors may have both genetic and immune components due to lymphocytes infiltration in HIV patients.[5]
- Histological of seminomas tumor in HIV patients: tumor infiltrated by lymphocytes which may lead to weak immune system response.[5]
- familial contribution:[6]
- Gene on chromosome Xq27 may be related to testicular germ cell tumors
Germ cell neoplasia in Situ
- Lack of gonocyte to differentiate into spermatogonia
- Hypothesis of gain of short arm of chromosome 12
Gross pathology
Germ cell neoplasia in Situ
- Normal apperance
Seminomas
- Homogeneous in appearance
- Lack of hemorrhage, necrosis
Microscopic Pathology
Germ cell Tumors[7]
- Clonal proliferation of neoplastic germ cells
- Fried-egg appearance
- Non-seminomas
-
- Marked nuclear atypia
-
- Blander cytomorphology
- Hyaline-type globules
- Schiller-Duval bodies
-
- Both syncytiotrophoblasts and cytotrophoblast cells
- Hyperchromatic nuclei
- Prominent nucleoli
- Intact basement menbrane.
Genetics
Genes involved in the pathogenesis of testicular cancer.
- 4q22
- 7q22
- 16q22.3
- 17q22
References
- ↑ Miyai, Kosuke; Ito, Keiichi; Nakanishi, Kuniaki; Tsuda, Hitoshi (2019). "Seminoma component of mixed testicular germ cell tumor shows a higher incidence of loss of heterozygosity than pure-type seminoma". Human Pathology. 84: 71–80. doi:10.1016/j.humpath.2018.09.007. ISSN 0046-8177.
- ↑ 2.0 2.1 Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA (June 2013). "Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis". Endocr. Rev. 34 (3): 339–76. doi:10.1210/er.2012-1045. PMC 3787935. PMID 23575763.
- ↑ Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Møller H (April 2006). "Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries". Cancer Epidemiol. Biomarkers Prev. 15 (4): 652–8. doi:10.1158/1055-9965.EPI-05-0565. PMID 16614105.
- ↑ Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW, Looijenga LH (November 2000). "Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas". Oncogene. 19 (51): 5858–62. PMID 11127816.
- ↑ 5.0 5.1 Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T (May 2003). "Multicenter study of human immunodeficiency virus-related germ cell tumors". J. Clin. Oncol. 21 (10): 1922–7. doi:10.1200/JCO.2003.09.107. PMID 12743144.
- ↑ Rapley, Elizabeth A.; Crockford, Gillian P.; Teare, Dawn; Biggs, Patrick; Seal, Sheila; Barfoot, Rita; Edwards, Sandra; Hamoudi, Rifat; Heimdal, Ketil; Fosså, Sophie D.; Tucker, Kathy; Donald, Jenny; Collins, Felicity; Friedlander, Michael; Hogg, David; Goss, Paul; Heidenreich, Axel; Ormiston, Wilma; Daly, Peter A.; Forman, David; Oliver, Timothy D.; Leahy, Michael; Huddart, Robert; Cooper, Colin S.; Bodmer, Julia G.; Easton, Douglas F.; Stratton, Michael R.; Bishop, D. Timothy (2000). "Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours". Nature Genetics. 24 (2): 197–200. doi:10.1038/72877. ISSN 1061-4036.
- ↑ 7.0 7.1 Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H; et al. (1984). "Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases". Acta Radiol Oncol. 23 (4): 239–47. PMID 6093440.
- ↑ Talerman A, Haije WG, Baggerman L (1980). "Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP". Cancer. 46 (2): 380–5. PMID 6155988.
- ↑ Emerson RE, Cheng L (April 2013). "Premalignancy of the testis and paratestis". Pathology. 45 (3): 264–72. doi:10.1097/PAT.0b013e32835f3e1a. PMID 23478232.
- ↑ Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G (November 2017). "Testicular cancer from diagnosis to epigenetic factors". Oncotarget. 8 (61): 104654–104663. doi:10.18632/oncotarget.20992. PMC 5732834. PMID 29262668.