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==[[Germ cell tumor overview|Overview]]==
 
==[[Germ cell tumor overview|Overview]]==
 
A germ-cell tumor (GCT) is a neoplasm derived from germ cells and it can be cancerous or benign. Germ cells can be intragonadal (ovary and testis or extragonadal (may be birth defects resulting from errors during development o
 
A germ-cell tumor (GCT) is a neoplasm derived from germ cells and it can be cancerous or benign. Germ cells can be intragonadal (ovary and testis or extragonadal (may be birth defects resulting from errors during development o
 +
f the embryo). [[Ovarian]] [[germ cell]] [[tumors]] is a [[disease]] in which [[Malignant|malignancy]] originates from the [[germ cells]] of the [[ovary]]. [[Ovarian]] [[germ cell]] [[tumors]] are rare, accounting for 2% to 3% of all ovarian cancers. The median age for [[diagnosis]] differs for each sub-type of germ cell tumor. World health organization (WHO) classified germ cell [[tumors]] into 7 types based on [[histology]]. The most common [[ovarian]] [[germ cell]] [[tumor]] is called [[dysgerminoma]]. Abnormal [[Gonad|gonads]] (due to [[gonadal dysgenesis]] and [[androgen insensitivity syndrome]]) have a high risk of developing a [[dysgerminoma]]. [[Ovarian]] [[germ cell]] [[tumors]] must be differentiated from other [[neoplastic]] [[ovarian]] masses that can present with similar complaints non-neoplastic [[ovarian]] mass, and adnexal mass. Symptoms of [[ovarian]] [[germ cell]] [[tumors]] include [[abdominal distention]], acute/ subacute [[abdominal pain]], [[menstrual irregularities]], and [[precocious puberty]]. The laboratory findings associated with [[ovarian]] [[germ cell]] [[tumors]] include rise in serum [[lactate dehydrogenase]] (LDH), [[human chorionic gonadotropin]] (HCG), [[CA-125]], and [[alpha-fetoprotein]] (AFP). Depending on the extent of the tumor at the time of [[diagnosis]], the [[prognosis]] may vary. [[CT]], [[MRI]], and [[ultrasound]] are used in combination with biopsy not only to distinguish between the subtypes of [[ovarian]] [[germ cell]] [[tumors]] but also for diagnosis confirmation. [[Surgery]] along with [[chemotherapy]] are the mainstay of treatment depending on the staging of the tumor.
 
[[Category:Up-To-Date]]
 
[[Category:Up-To-Date]]
 
[[Category:Oncology]]
 
[[Category:Oncology]]
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[[Category:Gynecology]]
 
[[Category:Gynecology]]
 
[[Category:Surgery]]
 
[[Category:Surgery]]
f the embryo).
 
 
==[[Germ cell tumor classification|Classification]]==
 
==[[Germ cell tumor classification|Classification]]==
 
Germ cell tumors can be classified as follows:  
 
Germ cell tumors can be classified as follows:  

Revision as of 14:45, 23 September 2019


Germ cell tumor
Germ cell tumor.jpg
This thymus was excised from a 5-year-old male and weighed 75 g. "An anterior mediastinal tumor," which proved to be hyperplastic thymus, was detected 2 years 3 months after resection of a testicular germ cell tumor and postoperative chemotherapy. Normal configuration of the thymus is preserved. Note the prominent lobulation on the incisional surface made at the time of sampling.
Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology
ICD-10 C56, C62, D27, D29.2
ICD-9 183, 186, 220, 222.0
ICD-O: 9060-9100

Germ Cell Tumors Microchapters

Patient Information

Overview

Classification

Dysgerminoma
Seminoma
Embryonal carcinoma
Teratoma
Choriocarcinoma
Yolk sac tumor

Causes

Risk Factors

For patient information click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Huda A. Karman, M.D.

Synonyms and Keywords: Polyembryoma; Embryonal carcinoma

Overview

A germ-cell tumor (GCT) is a neoplasm derived from germ cells and it can be cancerous or benign. Germ cells can be intragonadal (ovary and testis or extragonadal (may be birth defects resulting from errors during development o f the embryo). Ovarian germ cell tumors is a disease in which malignancy originates from the germ cells of the ovary. Ovarian germ cell tumors are rare, accounting for 2% to 3% of all ovarian cancers. The median age for diagnosis differs for each sub-type of germ cell tumor. World health organization (WHO) classified germ cell tumors into 7 types based on histology. The most common ovarian germ cell tumor is called dysgerminoma. Abnormal gonads (due to gonadal dysgenesis and androgen insensitivity syndrome) have a high risk of developing a dysgerminoma. Ovarian germ cell tumors must be differentiated from other neoplastic ovarian masses that can present with similar complaints non-neoplastic ovarian mass, and adnexal mass. Symptoms of ovarian germ cell tumors include abdominal distention, acute/ subacute abdominal pain, menstrual irregularities, and precocious puberty. The laboratory findings associated with ovarian germ cell tumors include rise in serum lactate dehydrogenase (LDH), human chorionic gonadotropin (HCG), CA-125, and alpha-fetoprotein (AFP). Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. CT, MRI, and ultrasound are used in combination with biopsy not only to distinguish between the subtypes of ovarian germ cell tumors but also for diagnosis confirmation. Surgery along with chemotherapy are the mainstay of treatment depending on the staging of the tumor.

Classification

Germ cell tumors can be classified as follows:

Histologic-based classification


 
 
 
 
 
 
 
 
 
Germ cell tumors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Germinomatous/Undifferentiated/Immature
 
 
 
 
 
 
 
 
Nongerminomatous/Differentiated/Embryonal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dysgerminoma(Ovary)
 
 
 
Seminoma(Testis)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Embryonal carcinoma
 
 
 
 
 
 
embryonic tissue
 
 
 
 
Extraembryonic tissue
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Teratoma
 
 
Yolk sac tumor
 
Choriocarcinoma
 
 

Location-based classification, regardless to the histologic findings:


 
 
 
 
 
 
 
 
Germ cell tumors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gonadal
 
 
 
 
 
 
 
 
Extragonadal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Located in the gonads
 
 
 
 
 
 
 
 
Located in the midline of the body including:
  • CNS
  • Mediastinum
  • Retroperitoneum
  • Coccyx
  •  
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     


    Types Subtypes Signs and Symptoms Histopathology Lab finding Prognosis
    Germinomatous

    /Undifferentiated

    Seminoma (Testis)

    Gross: pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface
    • Complete blood count and blood chemistry tests.
    • Abnormal serum tumor marker levels (LDH, HCG).
    • CT: Metastases to the para-aortic, inguinal, or iliac lymph nodes. Visceral metastasis may also be seen.
    • Pelvic MRI: may be diagnostic. multinodular tumors of uniform signal intensity
    • Hypo- to isointense on T2-weighted images and inhomogenous enhancement on contrast enhanced T1-weighted images.
    • Other diagnostic studies for seminoma include biopsy, FDG-PET scan, and bone scan.

    Dysgerminoma

    (Ovary)

    • Chemotherapy: except those with stage 1a, stage 1a, 1b dysgerminoma
    • Radiotherapy:

    ** Dysgerminoma is radiosensitive.

    ** Radiotherapy is not anymore the first option of treatment for dysgerminoma considering its association with ovarian failuredevelopment.

    • Surgery: for diagnostic grading and therapy depending on if the patient prefers to preserve the ovary or not.


    Germinomatous/

    Differentiated

    Embryonic

    Teratoma

    • AFP
    • MSAFP
    • CT scans are often used to diagnose teratoma.


    • For malignant teratomas, usually, surgery is followed by chemotherapy.
    • Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.

    Extraembryonic

    Choriocarcinoma(Gestational Trophoblastic Neoplasia)[1][2][3][4][5][6][7][8]

    Early Symptoms:

    Rare Symptoms:

    Late Symptoms

    Gross pathological:

    Microscopic histopathological:


    Human chorionic gonadotropin (HCG or b-HCG) is the most common tumor marker test used to diagnose GTD

    HCG is markedly elevated (usu. >10,000 IU



    Poor prognosis of gestational trophoblastic neoplasia (GTN) can be determined by the following factors:

    Yolk sac tumor

    (Endodermal sinus tumor)

    Symptoms:[9][10]


      • On gross pathology:
      • Encaptulated, firm, smooth, round, globular, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor.
      • On microscopic histopathological analysis:
      • Schiller-Duval bodies (invaginated papillary structures with central vessel) is a characteristic finding of endodermal sinus tumor. The tumors are composed of irregular space lined by flattened to cuboidal cells and recticular stroma
    • An elevated concentration of serum alpha feto-protein is diagnostic of endodermal sinus tumor. [12]
    • AFP is very important for diagnosis, disease monitoring and early metastasis
    • Endodermal sinus tumor may also be diagnosed using biopsy and measurement of GATA-4, a transcription factor[13]


    Causes

    • The cause of germ cell tumor is not understood fully but there are many risk factors that believed to play a role in the development of germ cell tumors.
    The etiology of yolk sac tumors (YSTs) is essentially unknown. It is speculated that hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor that regulates differentiation and function of yolk sac endoderm, may play important roles in the pathogenesis of yolk sac tumors (YSTs)
    Germ cell tumor causes
    General Causes
    Dysgerminoma
    Seminoma Common causes
    • Cryptorchidism
    • Undescended testis
    • Abdominal testis
    • Trauma
    • Mumps
    • Maternal estrogen exposure
    • Genetic Causes
    • Seminoma is caused by a mutation in the KIT gene.
    • 12p11.2-p12.1 chromosomal amplifications and deletions observed in majority of cases.


    Embryonal cell carcinoma
    Choriocarcinoma
    Yolk sac tumor


    Risk Factors

    Germ cell tumor Risk factors
    Ovarian germ cell tumor[19][20][21][22][23][24][25]

    Dysgerminoma:

    Mature teratoma: Common risk factors in the malignant transformation of mature teratoma include:

    • Old age (> 50 years old)
    • Large tumor size (> 10 cm)
    • Presence of a solid portion
    Seminoma[26][27][28][29][30][31][32]

    Common Risk Factors

    Less Common Risk Factors

    Embryonal carcinoma
    Teratoma
    Choriocarcinoma
    • Maternal
    • The risk of choriocarcinoma increases progressively in women older than 25 years
    • The risk increases more rapidly in women older than 39 years
    • The risk is higher for women younger than 20 compared with women aged 20 – 24 years
    • History of Gestational Trophoblastic Disease
    • Reproductive Factors
    Yolk sac tumor




    Risk factors of Ovarian germ cell tumors (Dysgerminoma):

    Mature teratoma

    Dysgerminoma

    Risk factors of Testicular germ cell tumors (Seminoma):

    Common risk factors in testicular seminoma include:[40][41][42][43][44][45][46]

    Common Risk Factors

    Less Common Risk Factors


    Related chapters

    External Links


    References

    1. Signs and symptoms of gestational trophoblastic disease. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/gestational-trophoblastic-disease/signs-and-symptoms/?region=ns Accessed on October 10, 2015
    2. Ober, William B.; Edgcomb, John H.; Price, Edward B. (1971). "THE PATHOLOGY OF CHORIOCARCINOMA". Annals of the New York Academy of Sciences. 172 (10 Physiology a): 299–426. doi:10.1111/j.1749-6632.1971.tb34943.x. ISSN 0077-8923.
    3. Smith, Harriet O.; Kohorn, Ernest; Cole, Laurence A. (2005). "Choriocarcinoma and Gestational Trophoblastic Disease". Obstetrics and Gynecology Clinics of North America. 32 (4): 661–684. doi:10.1016/j.ogc.2005.08.001. ISSN 0889-8545.
    4. Cellular Classification of Gestational Trophoblastic Disease. National Cancer Institute. http://www.cancer.gov/types/gestational-trophoblastic/hp/gtd-treatment-pdq/#section/_5 Accessed on October 8, 2015
    5. Young RH, Scully RE (March 1984). "Placental-site trophoblastic tumor: current status". Clin Obstet Gynecol. 27 (1): 248–58. PMID 6200262.
    6. Allison KH, Love JE, Garcia RL (December 2006). "Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast". Arch. Pathol. Lab. Med. 130 (12): 1875–7. doi:10.1043/1543-2165(2006)130[1875:ETTROA]2.0.CO;2. PMID 17149967.
    7. Diagnosing gestational trophoblastic disease. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/gestational-trophoblastic-disease/diagnosis/?region=ns Accessed on October 13, 2015
    8. Choriocarcinoma. librepathology.org. http://librepathology.org/wiki/index.php/Choriocarcinoma Accessed on October 8, 2015
    9. Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
    10. Gershenson DM, Del Junco G, Herson J, Rutledge FN (1983). "Endodermal sinus tumor of the ovary: the M. D. Anderson experience". Obstet Gynecol. 61 (2): 194–202. PMID 6185892.
    11. Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
    12. 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. doi:10.1002/1097-0142(19800715)46:2<380::aid-cncr2820460228>3.0.co;2-u. PMID 6155988.
    13. Siltanen S, Anttonen M, Heikkilä P, Narita N, Laitinen M, Ritvos O; et al. (1999). "Transcription factor GATA-4 is expressed in pediatric yolk sac tumors". Am J Pathol. 155 (6): 1823–9. doi:10.1016/S0002-9440(10)65500-9. PMC 1866939. PMID 10595911.
    14. 14.0 14.1 Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST (2002). "CT and MR imaging of ovarian tumors with emphasis on differential diagnosis". Radiographics. 22 (6): 1305–25. doi:10.1148/rg.226025033. PMID 12432104.
    15. Hung JH, Shen SH, Hung J, Lai CR (2007). "Ultrasound and magnetic resonance images of endodermal sinus tumor". J Chin Med Assoc. 70 (11): 514–8. doi:10.1016/S1726-4901(08)70052-2. PMID 18063508.
    16. Kato N, Tamura G, Fukase M, Shibuya H, Motoyama T (2003). "Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants". Am J Pathol. 163 (2): 387–91. doi:10.1016/S0002-9440(10)63668-1. PMC 1868235. PMID 12875960.
    17. 17.0 17.1 17.2 "Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute".
    18. Stage Information for Ovarian Germ Cell Tumors. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_8. URL Accessed on November 5, 2015
    19. Pleskacova, J.; Hersmus, R.; Oosterhuis, J.W.; Setyawati, B.A.; Faradz, S.M.; Cools, M.; Wolffenbuttel, K.P.; Lebl, J.; Drop, S.L.; Looijenga, L.H. (2010). "Tumor Risk in Disorders of Sex Development". Sexual Development. 4 (4–5): 259–269. doi:10.1159/000314536. ISSN 1661-5433.
    20. Sharpe, Richard M.; Skakkebaek, Niels E. (2008). "Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects". Fertility and Sterility. 89 (2): e33–e38. doi:10.1016/j.fertnstert.2007.12.026. ISSN 0015-0282.
    21. Skakkebæk, N.E.; Rajpert-De Meyts, E.; Main, K.M. (2001). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 1460-2350.
    22. Walker AH, Ross RK, Haile RW, Henderson BE (April 1988). "Hormonal factors and risk of ovarian germ cell cancer in young women". Br. J. Cancer. 57 (4): 418–22. PMC 2246577. PMID 3390378.
    23. Hackethal A, Brueggmann D, Bohlmann MK, Franke FE, Tinneberg HR, Münstedt K (December 2008). "Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data". Lancet Oncol. 9 (12): 1173–80. doi:10.1016/S1470-2045(08)70306-1. PMID 19038764.
    24. Park, Jeong-Yeol; Kim, Dae-Yeon; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun (2008). "Malignant transformation of mature cystic teratoma of the ovary: Experience at a single institution". European Journal of Obstetrics & Gynecology and Reproductive Biology. 141 (2): 173–178. doi:10.1016/j.ejogrb.2008.07.032. ISSN 0301-2115.
    25. Kliegman, Robert (2011). Nelson textbook of pediatrics. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4377-0755-7.
    26. Risk factors for testicular germ cell tumors. Dr Matt A. Morgan and Dr Andrew Dixon et al. Radiopaedia 2016. Accessed on February 25, 2016
    27. Causes of seminoma. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/001288.htm. Accessed on February 29, 2016
    28. Khan O, Protheroe A (October 2007). "Testis cancer". Postgrad Med J. 83 (984): 624–32. doi:10.1136/pgmj.2007.057992. PMC 2600126. PMID 17916870.
    29. McGlynn KA, Trabert B (April 2012). "Adolescent and adult risk factors for testicular cancer". Nat Rev Urol. 9 (6): 339–49. doi:10.1038/nrurol.2012.61. PMC 4031676. PMID 22508459.
    30. 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.
    31. Ghazarian AA, Kelly SP, Altekruse SF, Rosenberg PS, McGlynn KA (June 2017). "Future of testicular germ cell tumor incidence in the United States: Forecast through 2026". Cancer. 123 (12): 2320–2328. doi:10.1002/cncr.30597. PMC 5629636. PMID 28241106.
    32. Gurney J, Shaw C, Stanley J, Signal V, Sarfati D (November 2015). "Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis". BMC Cancer. 15: 897. doi:10.1186/s12885-015-1905-6. PMC 4642772. PMID 26560314.
    33. Pleskacova, J.; Hersmus, R.; Oosterhuis, J.W.; Setyawati, B.A.; Faradz, S.M.; Cools, M.; Wolffenbuttel, K.P.; Lebl, J.; Drop, S.L.; Looijenga, L.H. (2010). "Tumor Risk in Disorders of Sex Development". Sexual Development. 4 (4–5): 259–269. doi:10.1159/000314536. ISSN 1661-5433.
    34. Sharpe, Richard M.; Skakkebaek, Niels E. (2008). "Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects". Fertility and Sterility. 89 (2): e33–e38. doi:10.1016/j.fertnstert.2007.12.026. ISSN 0015-0282.
    35. Skakkebæk, N.E.; Rajpert-De Meyts, E.; Main, K.M. (2001). "Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: Opinion". Human Reproduction. 16 (5): 972–978. doi:10.1093/humrep/16.5.972. ISSN 1460-2350.
    36. Walker AH, Ross RK, Haile RW, Henderson BE (April 1988). "Hormonal factors and risk of ovarian germ cell cancer in young women". Br. J. Cancer. 57 (4): 418–22. PMC 2246577. PMID 3390378.
    37. Hackethal A, Brueggmann D, Bohlmann MK, Franke FE, Tinneberg HR, Münstedt K (December 2008). "Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data". Lancet Oncol. 9 (12): 1173–80. doi:10.1016/S1470-2045(08)70306-1. PMID 19038764.
    38. Park, Jeong-Yeol; Kim, Dae-Yeon; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Nam, Joo-Hyun (2008). "Malignant transformation of mature cystic teratoma of the ovary: Experience at a single institution". European Journal of Obstetrics & Gynecology and Reproductive Biology. 141 (2): 173–178. doi:10.1016/j.ejogrb.2008.07.032. ISSN 0301-2115.
    39. Kliegman, Robert (2011). Nelson textbook of pediatrics. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4377-0755-7.
    40. Risk factors for testicular germ cell tumors. Dr Matt A. Morgan and Dr Andrew Dixon et al. Radiopaedia 2016. Accessed on February 25, 2016
    41. Causes of seminoma. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/001288.htm. Accessed on February 29, 2016
    42. Khan O, Protheroe A (October 2007). "Testis cancer". Postgrad Med J. 83 (984): 624–32. doi:10.1136/pgmj.2007.057992. PMC 2600126. PMID 17916870.
    43. McGlynn KA, Trabert B (April 2012). "Adolescent and adult risk factors for testicular cancer". Nat Rev Urol. 9 (6): 339–49. doi:10.1038/nrurol.2012.61. PMC 4031676. PMID 22508459.
    44. 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.
    45. Ghazarian AA, Kelly SP, Altekruse SF, Rosenberg PS, McGlynn KA (June 2017). "Future of testicular germ cell tumor incidence in the United States: Forecast through 2026". Cancer. 123 (12): 2320–2328. doi:10.1002/cncr.30597. PMC 5629636. PMID 28241106.
    46. Gurney J, Shaw C, Stanley J, Signal V, Sarfati D (November 2015). "Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis". BMC Cancer. 15: 897. doi:10.1186/s12885-015-1905-6. PMC 4642772. PMID 26560314.

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