Germ cell tumor
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Germ Cell Tumors Microchapters |
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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;
Overview
A germ-cell tumor (GCT) is a neoplasm derived from germ cells and it can be cancerous or benign. Based on their location, germ cell tumors can be classified into intragonadal (ovary and testis) or extragonadal (mediastinum, brain, retroperitoneum, coccyx). Histologically, Germ cell tumors can be classified as germinomatous/undifferentiated germ cell tumors which include, dysgerminoma and seminoma. and nongermminomatous/differentiated which include embryonic and extra-embryonic germ cell tumors. Embryonic germ cell tumors include teratoma, and extraembryonic germ cell tumors include Choriocarcinoma and Yolk sac tumor. The name of a germ cell tumor came from the word (germinate), which means to begin to grow. During fetus development, germ cells migrate to become the eggs in the ovary or the sperms in the testicles. Germ cell tumors develop due to the abnormal growth of the germ cells in the ovary, testis, brain, mediastinum, coccyx, or pelvis. World health organization (WHO) classified germ cell tumors into 7 types based on histology. The cause of germ cell tumors development is not fully understood but some causes include, genetic mutations, cryptorchidism, undescended testes, trauma, mumps, maternal estrogen exposure. Common risk factors include Caucasian race,Family history or personal history of germ cell tumor, Klinefelter syndrome. Less common risk factors include,Infections such as HIV, orchitis, or history of trauma. Symptoms and signs of germ cell tumors depend on the type and location of the tumor. Symptoms of dysgerminoma can include, abdominal distention, acute/ subacute abdominal pain, menstrual irregularities, and precocious puberty. Symptoms of seminoma include painless testicular mass with discomfort, back pain, abdominal discomfort, or abdominal mass. Common complications of germ cell tumors include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies. Lab findings include abnormal serum tumor marker levels such as LDH, HCG (seminoma), lactate dehydrogenase (LDH), human chorionic gonadotropin (HCG), CA-125, and alpha-fetoprotein (AFP) (ovarian germ cell tumors), alpha fetoprotein (AFP) greater than 100 ng/ml (Endodermal sinus tumor). CT, MRI, and ultrasound are used in combination with biopsy to distinguish between the types and subtypes of germ cell tumors and for diagnosis confirmation. Surgery along with chemotherapy are the mainstay of treatment depending on the staging of the tumor. Depending on the type, location, and the extent of the tumor at the time of diagnosis, the prognosis may vary.
Classification
Germ cell tumors can be classified as follows:
Histologic-based classification
Germ cell tumors | |||||||||||||||||||||||||||||||||||||||||||||||||||
Germinomatous/Undifferentiated/Immature | Nongerminomatous/Differentiated/Mature | ||||||||||||||||||||||||||||||||||||||||||||||||||
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:
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Types | Subtypes | Signs and Symptoms | Histopathology | Lab finding | Prognosis |
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Germinomatous
/Undifferentiated
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Seminoma (Testis) |
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Gross: pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface |
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Dysgerminoma (Ovary) |
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** Dysgerminoma is radiosensitive. ** Radiotherapy is not anymore the first option of treatment for dysgerminoma considering its association with ovarian failuredevelopment.
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Germinomatous/
Differentiated |
Embryonic |
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Teratoma |
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Extraembryonic |
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Choriocarcinoma(Gestational Trophoblastic Neoplasia)[1][2][3][4][5][6][7][8] |
Early Symptoms:
Rare Symptoms:
Late Symptoms
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Gross pathological:
Microscopic histopathological:
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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
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(Endodermal sinus tumor) |
Symptoms:[9][10]
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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.
Germ cell tumor | causes |
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General Causes |
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Dysgerminoma |
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Seminoma | Common causes
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Embryonal cell carcinoma |
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Choriocarcinoma |
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Yolk sac tumor |
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Risk Factors
Germ cell tumor | Risk factors |
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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:
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Seminoma[26][27][28][29][30][31][32] |
Common Risk Factors
Less Common Risk Factors
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Embryonal carcinoma |
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Teratoma |
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Choriocarcinoma |
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Yolk sac tumor |
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Related chapters
External Links
References
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ 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
- ↑ Young RH, Scully RE (March 1984). "Placental-site trophoblastic tumor: current status". Clin Obstet Gynecol. 27 (1): 248–58. PMID 6200262.
- ↑ 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.
- ↑ 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
- ↑ Choriocarcinoma. librepathology.org. http://librepathology.org/wiki/index.php/Choriocarcinoma Accessed on October 8, 2015
- ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
- ↑ 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.
- ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
- ↑ 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.
- ↑ 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.
- ↑ 14.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 17.0 17.1 17.2 "Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute".
- ↑ 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
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Kliegman, Robert (2011). Nelson textbook of pediatrics. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4377-0755-7.
- ↑ Risk factors for testicular germ cell tumors. Dr Matt A. Morgan and Dr Andrew Dixon et al. Radiopaedia 2016. Accessed on February 25, 2016
- ↑ Causes of seminoma. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/001288.htm. Accessed on February 29, 2016
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.