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{{SK}} Endodermal sinus tumor(EST), yolk sac tumor.
{{SK}} Endodermal sinus tumor(EST), yolk sac tumor.
==Overview==
==Overview==
Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist, in 1971 following publication of a distinctive variety of germ cell tumor. The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor. On gross [[pathology]], 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 is a characteristic finding of endodermal sinus tumor. Endodermal sinus tumor must be differentiated from other [[diseases]] that cause [[ovarian mass]], such as Stein-Leventhal syndrome<ref name="sba">Shaaban AM, Rezvani M, Elsayes KM, et al. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. Radiographics. 2014;34(3):777-801.http://pubs.rsna.org/doi/pdf/10.1148/rg.343130067</ref><ref name="ajk">Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST. CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. Radiographics. 2002;22(6):1305-25.http://www.ncbi.nlm.nih.gov/pubmed/12432104</ref> [[ovary]] teratoma, tubal [[pregnancy]], ovary adenocarcinoma, and tubo-ovarian [[abscess]]. Endodermal sinus tumor have a bimodal distribution more commonly observed among young and adult population. The symptoms of endodermal sinus tumor include the following:<ref name="www">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref>[[abdominal distention]], acute/sub acute [[abdominal pain]]. The mainstay of therapy for endodermal sinus tumor is [[chemotherapy]].
Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist, in 1959. The hypermethylation of the RUNX3 [[gene]] [[promoter]] and [[overexpression]] of GATA-4, a [[transcription factor]] has been associated with the [[development]] of endodermal sinus tumor. Endodermal sinus tumor is a rare type of [[malignant]] [[ovarian tumor]] that occurs in the second decade of life. On [[gross]] [[pathology]], a [[solid]] gray-white with gelatinous, myxoid, or mucoid appearance, [[necrosis]], [[cystic]] changes, and [[hemorrhage]] are characteristic findings of endodermal sinus tumor. On [[microscopic]] [[histopathological]] analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor. Endodermal sinus tumor must be differentiated from other [[diseases]] that cause [[Pelvic|pelvic mass]], such as [[Stein-Leventhal syndrome]], and [[seminoma]]. In 2015, the [[incidence]] of endodermal sinus tumor is estimated to less than 1/100,000 case per year in U.S. Endodermal sinus tumor may be classified according to [[histology]] groups.The [[diagnosis]] of endodermal sinus tumor is made based on the [[imaging]] (U/S and MRI) and [[alpha fetoprotein]] ([[AFP]]) [[tumor marker]] greater than 100 ng/ml. Endodermal sinus tumor have a [[bimodal distribution]] more commonly observed among [[Young adult|young]] and [[adult]] [[population]]. The [[symptoms]] of endodermal sinus tumor include the followings: [[abdominal distention]], acute/sub acute [[abdominal pain]]. Endodermal sinus tumor is treated with [[surgery]] depending on the [[tumor]] [[marker]] and [[imaging]] as well as [[fertility]] desired.The [[medical]] [[therapy]] for endodermal sinus tumor is [[chemotherapy]] such as [[bleomycin]], [[etoposide]], and [[cisplatin]] for 3 to 4 cycles for 21 days.
==Historical Perspective==
==Historical Perspective==
*Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist, in 1971 following publication of a distinctive variety of germ cell tumor.
*Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish [[pathologist]] in 1959.<ref>{{cite book | last = Carmen | first = Marcela | title = Uncommon gynecologic cancers | publisher = Wiley Blackwell | location = Chichester, England | year = 2015 | isbn = 978-1-118-65535-1 }}</ref><ref name="pmid18767035">{{cite journal| author=Shah JP, Kumar S, Bryant CS, Ali-Fehmi R, Malone JM, Deppe G et al.| title=A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females. | journal=Int J Cancer | year= 2008 | volume= 123 | issue= 11 | pages= 2671-5 | pmid=18767035 | doi=10.1002/ijc.23792 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18767035  }}</ref>
 
==Classification==
==Classification==
*Endodermal sinus tumor may be classified according to histology into 10 groups:  
*Endodermal sinus tumor may be classified according to [[histology]] into 10 groups:<ref>{{cite book | last = Weidner | first = Noel | title = Modern surgical pathology | publisher = Saunders/Elsevier | location = Philadelphia, PA | year = 2009 | isbn = 978-1-4160-3966-2 }}</ref>
:*Reticular
 
:*[[Reticular]]
:*Endodermal sinus-like
:*Endodermal sinus-like
:*Microcystic
:*Microcystic
:*Papillary
:*[[Papillary]]
:*Solid
:*[[Solid]]
:*Glandular
:*[[Glandular]]
:*Alveolar
:*[[Alveolar]]
:*Polyvesicular vitelline
:*[[Vesicular|Polyvesicular]] vitelline
:*Enteric  
:*Enteric  
:*Hepatoid
:*Hepatoid
==Pathophysiology==
==Pathophysiology==
*The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor.
*The hypermethylation of the RUNX3 gene promoter and [[overexpression]] of GATA-4, a [[transcription factor]] has been associated with the development of endodermal sinus tumor.<ref name="pmid12875960">{{cite journal| author=Kato N, Tamura G, Fukase M, Shibuya H, Motoyama T| title=Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 2 | pages= 387-91 | pmid=12875960 | doi=10.1016/S0002-9440(10)63668-1 | pmc=1868235 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12875960  }} </ref>
*On gross pathology, solid gray-white with a gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor.
*[[Ovarian]] endodermal sinus tumor may be result of differentiation of primitive [[malignant]] [[germ cell]] components of vitelline structures.<ref>{{cite book | last = Crum | first = Christopher | title = Diagnostic gynecologic and obstetric pathology | publisher = Elsevier, Inc | location = Philadelphia, PA | year = 2018 | isbn = 978-0-323-44732-4 }}</ref>
*On microscopic histopathological analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor.
*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.<ref>{{cite book | last = Carmen | first = Marcela | title = Uncommon gynecologic cancers | publisher = Wiley Blackwell | location = Chichester, England | year = 2015 | isbn = 978-1-118-65535-1 }}</ref>
*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<ref>{{cite book | last = Carmen | first = Marcela | title = Uncommon gynecologic cancers | publisher = Wiley Blackwell | location = Chichester, England | year = 2015 | isbn = 978-1-118-65535-1 }}</ref>.<ref name="pmid63318">{{cite journal| author=Kurman RJ, Norris HJ| title=Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases. | journal=Cancer | year= 1976 | volume= 38 | issue= 6 | pages= 2404-19 | pmid=63318 | doi=10.1002/1097-0142(197612)38:6<2404::aid-cncr2820380629>3.0.co;2-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=63318  }} </ref>
==Causes==
==Causes==
* There are no established causes for endodermal sinus tumor.
* There are no established [[causes]] for endodermal sinus tumor.<ref name="Makris2017">{{cite journal|last1=Makris|first1=Georgios-Marios|title=Giving Birth After Fertility Sparing Treatment for a Yolk Sac Tumour: Case Report|journal=JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH|year=2017|issn=2249782X|doi=10.7860/JCDR/2017/25820.10524}}</ref>
==Differentiating From Endodermal sinus tumor Other Diseases==
 
Endodermal sinus tumor must be differentiated from other diseases that cause ovarian mass, such as:
==Differentiating Endodermal sinus tumor from Other Diseases==
* Stein-Leventhal syndrome<ref name="sba">Shaaban AM, Rezvani M, Elsayes KM, et al. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. Radiographics. 2014;34(3):777-801.http://pubs.rsna.org/doi/pdf/10.1148/rg.343130067</ref><ref name="ajk">Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST. CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. Radiographics. 2002;22(6):1305-25.http://www.ncbi.nlm.nih.gov/pubmed/12432104</ref>
Endodermal sinus tumor must be differentiated from other [[diseases]] that cause [[pelvic mass]], [[abdominal pain]] and [[abdominal distention]] such as:<ref name="sba">Shaaban AM, Rezvani M, Elsayes KM, et al. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. Radiographics. 2014;34(3):777-801.http://pubs.rsna.org/doi/pdf/10.1148/rg.343130067</ref><ref name="ajk">Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST. CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. Radiographics. 2002;22(6):1305-25.http://www.ncbi.nlm.nih.gov/pubmed/12432104</ref>


* [[Ovary]] teratoma
* Stein-Leventhal [[syndrome]]
 
* [[Ovary]] [[teratoma]]


* Tubal [[pregnancy]]
* Tubal [[pregnancy]]


* Ovary adenocarcinoma
*[[Ovary|Ovary adenocarcinoma]]


* Tubo-ovarian [[abscess]]
*[[Tubo-ovarian abscess|Tubo-ovarian]] [[abscess]]
*[[Seminoma]]
* For more information on endodermal sinus tumor differential diagnosis, [[Testicular cancer differential diagnosis|click here]].
* Also, you can find more information by [[Ovarian germ cell tumor differential diagnosis|clicking here]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
*In 2015, the [[incidence]] of endodermal sinus tumor is estimated to less than 1/100,000 case per [[year]] in U.S.<ref name="pmid1111694">{{cite journal| author=Young JL, Miller RW| title=Incidence of malignant tumors in U. S. children. | journal=J Pediatr | year= 1975 | volume= 86 | issue= 2 | pages= 254-8 | pmid=1111694 | doi=10.1016/s0022-3476(75)80484-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1111694  }} </ref>
===Age===
===Age===
*Endodermal sinus tumor have a bimodal distribution more commonly observed among young and adult population.
*Endodermal sinus tumor have a [[bimodal distribution]] more commonly observed among [[Young adult|young]] and [[Adult|adult population]]<ref name="pmid18767035">{{cite journal| author=Shah JP, Kumar S, Bryant CS, Ali-Fehmi R, Malone JM, Deppe G et al.| title=A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females. | journal=Int J Cancer | year= 2008 | volume= 123 | issue= 11 | pages= 2671-5 | pmid=18767035 | doi=10.1002/ijc.23792 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18767035  }} </ref>
* Pure yolk sac tumor (endodermal sinus tumor) affects mostly [[children]] of less 2 years old.<ref name="pmid8127257">{{cite journal| author=Coppes MJ, Rackley R, Kay R| title=Primary testicular and paratesticular tumors of childhood. | journal=Med Pediatr Oncol | year= 1994 | volume= 22 | issue= 5 | pages= 329-40 | pmid=8127257 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8127257  }} </ref>
===Gender===
===Gender===
*Endodermal sinus tumor affects men and women equally.
*Endodermal sinus tumor affects [[men]] and women equally.<ref name="urlEndodermal Sinus Tumor - St. Jude Children’s Research Hospital">{{cite web |url=https://www.stjude.org/disease/endodermal-sinus-tumor.html |title=Endodermal Sinus Tumor - St. Jude Children’s Research Hospital |format= |work= |accessdate=}}</ref>
 
===Race===
*There is no [[racial]] predilection for endodermal sinus tumor.
== Natural History, Complications and Prognosis==
== Natural History, Complications and Prognosis==
*If left untreated, endodermal sinus tumor may progress to develop death.
*Endodermal sinus tumor has a poor [[prognosis]] in [[adult]].<ref name="pmid12432104">{{cite journal| author=Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST| title=CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. | journal=Radiographics | year= 2002 | volume= 22 | issue= 6 | pages= 1305-25 | pmid=12432104 | doi=10.1148/rg.226025033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12432104  }} </ref><ref name="pmid18063508">{{cite journal| author=Hung JH, Shen SH, Hung J, Lai CR| title=Ultrasound and magnetic resonance images of endodermal sinus tumor. | journal=J Chin Med Assoc | year= 2007 | volume= 70 | issue= 11 | pages= 514-8 | pmid=18063508 | doi=10.1016/S1726-4901(08)70052-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18063508  }} </ref>
*Prognosis is generally dependant on the response to treatment.
*Endodermal sinus tumor has a favorable [[prognosis]] in [[children]].<ref name="pmid12875960">{{cite journal| author=Kato N, Tamura G, Fukase M, Shibuya H, Motoyama T| title=Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants. | journal=Am J Pathol | year= 2003 | volume= 163 | issue= 2 | pages= 387-91 | pmid=12875960 | doi=10.1016/S0002-9440(10)63668-1 | pmc=1868235 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12875960  }} </ref>
*Ovarian germ cell tumor (endodermal sinus tumor) is surgically staged using the [[International Federation of Gynecology and Obstetrics|FIGO]] [[cancer staging]] system:<ref name="mmm">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</ref>
*Endodermal sinus tumor is the most common [[malignant germ cell tumor]] in [[children]].<ref name="pmid12432104">{{cite journal| author=Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST| title=CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. | journal=Radiographics | year= 2002 | volume= 22 | issue= 6 | pages= 1305-25 | pmid=12432104 | doi=10.1148/rg.226025033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12432104  }} </ref><ref name="urlDefinition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute">{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/791307 |title=Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute |format= |work= |accessdate=}}</ref>
{| {{table}} cellpadding="4" cellspacing="0" style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;"
*If left untreated, endodermal sinus tumor quickly [[Metastasize|metastasizes]] in other parts of the [[body]] such as the [[brain]].<ref name="urlDefinition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute">{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/791307 |title=Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute |format= |work= |accessdate=}}</ref>
| align="center" style="background:#f0f0f0;" |'''Stage'''
*Endodermal sinus tumor can be found in the [[ovaries]] or [[testicles]] including the [[chest]], [[abdomen]], and the [[brain]].<ref name="urlDefinition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute">{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/791307 |title=Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute |format= |work= |accessdate=}}</ref>
| align="center" style="background:#f0f0f0;" |'''Finding'''
*Ovarian endodermal sinus tumor [[Metastasize|metastasizes]] quiclky into the intraabdominal area compared to [[testicular]] endodermal sinus tumor.<ref>{{cite book | last = Saia | first = Philip | title = Clinical gynecologic oncology | publisher = Elsevier | location = Philadelphia, PA | year = 2018 | isbn = 978-0-323-40067-1 }} </ref>
|-
| I||Growth limited to the ovaries
|-
| Ia||Growth limited to one ovary; no ascites present containing malignant cells. No tumor on the external surface; capsule intact
|-
| Ib||Growth limited to both ovaries; no ascites present containing malignant cells. No tumor on the external surfaces; capsules intact
|-
| Icb||Tumor either stage Ia or Ib, but with tumor on surface of one or both ovaries, or with capsule ruptured, or with ascites present containing malignant cells, or with positive peritoneal washings
|-
| II||Growth involving one or both ovaries with pelvic extension
|-
| IIa||Extension and/or metastases to the uterus and/or tubes
|-
| IIb||Extension to other pelvic tissues
|-
| IIcb||Tumor either stage IIa or IIb, but with tumor on surface of one or both ovaries, or with capsule(s) ruptured, or with ascites present containing malignant cells, or with positive peritoneal washings
|-
| III||Tumor involving one or both ovaries with histologically confirmed peritoneal implants outside the pelvis and/or positive regional lymph nodes. Superficial liver metastases equals stage III. Tumor is limited to the true pelvis, but with histologically proven malignant extension to small bowel or omentum
|-
| IIIa||Tumor grossly limited to the true pelvis, with negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces, or histologic proven extension to small bowel or mesentery
|-
| IIIb||Tumor of one or both ovaries with histologically confirmed implants, peritoneal metastasis of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative
|-
| IIIc||Peritoneal metastasis beyond the pelvis >2 cm in diameter and/or positive regional lymph nodes
|-
| IV||Growth involving one or both ovaries with distant metastases. If pleural effusion is present, there must be positive cytology to allot a case to stage IV. Parenchymal liver metastasis equals stage IV
|}
 
== Diagnosis ==
== Diagnosis ==
=== Diagnostic criteria ===
*The [[diagnosis]] of endodermal sinus tumor is made based on the imaging and [[alpha fetoprotein]] ([[AFP]]) [[tumor]] [[marker]] greater than 100 ng/ml.<ref name="pmid6155988">{{cite journal| author=Talerman A, Haije WG, Baggerman L| title=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. | journal=Cancer | year= 1980 | volume= 46 | issue= 2 | pages= 380-5 | pmid=6155988 | doi=10.1002/1097-0142(19800715)46:2<380::aid-cncr2820460228>3.0.co;2-u | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6155988  }} </ref><ref>{{cite book | last = Saia | first = Philip | title = Clinical gynecologic oncology | publisher = Elsevier | location = Philadelphia, PA | year = 2018 | isbn = 978-0-323-40067-1 }} </ref>
=== Symptoms ===
=== Symptoms ===
The symptoms of endodermal sinus tumor include the following:<ref name="www">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref>  
*Endodermal sinus tumor is usually [[asymptomatic]].<ref name="ChenYip2019">{{cite journal|last1=Chen|first1=Li Hsun|last2=Yip|first2=Kui-Chuen|last3=Wu|first3=Hsing-Ju|last4=Yong|first4=Su-Boon|title=Yolk Sac Tumor in an Eight-Year-Old Girl: A Case Report and Literature Review|journal=Frontiers in Pediatrics|volume=7|year=2019|issn=2296-2360|doi=10.3389/fped.2019.00169}}</ref>
* [[Abdominal distention]]
*Most [[children]] and [[young adults]] with endodermal sinus tumor have stage I.<ref>{{cite book | last = Weidner | first = Noel | title = Modern surgical pathology | publisher = Saunders/Elsevier | location = Philadelphia, PA | year = 2009 | isbn = 978-1-4160-3966-2 }}</ref>
* Acute/sub acute [[abdominal pain]]
*[[Symptoms]] of endodermal sinus tumor may include the following:<ref name="www">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref> <ref name="pmid6185892">{{cite journal| author=Gershenson DM, Del Junco G, Herson J, Rutledge FN| title=Endodermal sinus tumor of the ovary: the M. D. Anderson experience. | journal=Obstet Gynecol | year= 1983 | volume= 61 | issue= 2 | pages= 194-202 | pmid=6185892 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6185892  }} </ref>
 
:*[[Abdominal distention]]
:*[[Acute]]/subacute [[abdominal pain]]
=== Physical Examination ===
=== Physical Examination ===
====Ovarian Germ Cell Tumor Physical Examination====
*[[Patient|Patients]] with endodermal sinus tumor usually appear normal.
=====Abdomen=====
*[[Physical examination]] may be remarkable for:<ref name="abc">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref>
* [[Abdominal distention]] <ref name="abc">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref>
 
* Abdominal [[tenderness]]
:*[[Abdominal distention]]
=====Pelvic exam=====
:*[[Abdominal]] [[tenderness]]
* Adnexal mass
:*[[Adnexal]] [[mass]]
:*[[Testicular mass]]
 
=== Laboratory Findings ===
=== Laboratory Findings ===
*An elevated concentration of serum alpha feto-protein is diagnostic of endodermal sinus tumor.
*An elevated concentration of [[serum]] [[alpha fetoprotein]] is a [[diagnostic]] of endodermal sinus tumor.<ref name="pmid6155988">{{cite journal| author=Talerman A, Haije WG, Baggerman L| title=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. | journal=Cancer | year= 1980 | volume= 46 | issue= 2 | pages= 380-5 | pmid=6155988 | doi=10.1002/1097-0142(19800715)46:2<380::aid-cncr2820460228>3.0.co;2-u | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6155988  }} </ref>
*[[SALL4]] (sal-like [[protein]] 4) is [[positive]] in endodermal sinus tumor.<ref>{{cite book | last = Crum | first = Christopher | title = Diagnostic gynecologic and obstetric pathology | publisher = Elsevier, Inc | location = Philadelphia, PA | year = 2018 | isbn = 978-0-323-44732-4 }} </ref>
*[[Alpha-fetoprotein|AFP]] is very important for [[diagnosis]], [[disease]] monitoring and early [[metastasis]].<ref name="pmid6155988">{{cite journal| author=Talerman A, Haije WG, Baggerman L| title=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. | journal=Cancer | year= 1980 | volume= 46 | issue= 2 | pages= 380-5 | pmid=6155988 | doi=10.1002/1097-0142(19800715)46:2<380::aid-cncr2820460228>3.0.co;2-u | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6155988  }} </ref>
===Imaging Findings===
===Imaging Findings===
*On MRI, endodermal sinus tumor is characterized by areas of [[haemorrhage]].
*On [[MRI]], endodermal sinus tumor is characterized by areas of [[haemorrhage]] and [[necrosis]].<ref name="pmid18063508">{{cite journal| author=Hung JH, Shen SH, Hung J, Lai CR| title=Ultrasound and magnetic resonance images of endodermal sinus tumor. | journal=J Chin Med Assoc | year= 2007 | volume= 70 | issue= 11 | pages= 514-8 | pmid=18063508 | doi=10.1016/S1726-4901(08)70052-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18063508  }} </ref>
*[[Ultrasound]] shows [[solid]] and [[cystic]] [[mass]].<ref name="pmid18063508">{{cite journal| author=Hung JH, Shen SH, Hung J, Lai CR| title=Ultrasound and magnetic resonance images of endodermal sinus tumor. | journal=J Chin Med Assoc | year= 2007 | volume= 70 | issue= 11 | pages= 514-8 | pmid=18063508 | doi=10.1016/S1726-4901(08)70052-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18063508  }} </ref>
 
=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===
*Endodermal sinus tumor may also be diagnosed using biopsy and measurement of  GATA-4, a [[transcription factor]].
*Endodermal sinus tumor may also be [[Diagnosis|diagnosed]] using [[biopsy]] and [[measurement]] of  GATA-4, a [[transcription factor]].<ref name="pmid10595911">{{cite journal| author=Siltanen S, Anttonen M, Heikkilä P, Narita N, Laitinen M, Ritvos O et al.| title=Transcription factor GATA-4 is expressed in pediatric yolk sac tumors. | journal=Am J Pathol | year= 1999 | volume= 155 | issue= 6 | pages= 1823-9 | pmid=10595911 | doi=10.1016/S0002-9440(10)65500-9 | pmc=1866939 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10595911  }} </ref>
== Treatment ==
== Treatment ==
* Endodermal sinus tumor is treated with [[surgery]] depending on the [[tumor]] [[marker]] and [[imaging]] as well as [[fertility]] desired.<ref>"NCCN Clinical Practice Guidelines in Oncology: Endodermal sinus tumor. National comprehensive cancer network, 2017; https://www.nccn.org/patients/guidelines/content/PDF/ovarian.pdf."</ref>
* For positive [[tumor]] [[Marker|markers]] and [[imaging]], [[fertility]] desired
**Treat with [[fertility]]-sapring [[surgery]] and comprehensive [[Staging (pathology)|staging]].
* For [[positive]] [[tumor markers]] and [[imaging]], [[fertility]] not desired
**Treat with completion [[Staging (pathology)|staging]] [[surgery]] with possible [[tumor]] reductive [[surgery]] or [[chemotherapy]]
* For negative [[imaging]] and positive or negative [[tumor markers]]
**Treat with [[chemotherapy]]
=== Medical Therapy ===
=== Medical Therapy ===
* The mainstay of therapy for endodermal sinus tumor is [[chemotherapy]].<ref name="cba">Stage I Ovarian Germ Cell Tumors
* The [[medical]] [[therapy]] for endodermal sinus tumor is [[chemotherapy]] such as [[bleomycin]], [[etoposide]], and [[cisplatin]] for 3 to 4 cycles for 21 days depending on the stage.<ref name="pmid7512129">{{cite journal| author=Williams S, Blessing JA, Liao SY, Ball H, Hanjani P| title=Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group. | journal=J Clin Oncol | year= 1994 | volume= 12 | issue= 4 | pages= 701-6 | pmid=7512129 | doi=10.1200/JCO.1994.12.4.701 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7512129  }} </ref><ref>"NCCN Clinical Practice Guidelines in Oncology: Endodermal sinus tumor. National comprehensive cancer network, 2017; https://www.nccn.org/patients/guidelines/content/PDF/ovarian.pdf."</ref>.
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_33. URL Accessed on Nov 5, 2015</ref><ref name="sss">Stage II Ovarian Germ Cell Tumors
===Surgery===
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_43. URL Accessed on Nov 5, 2015</ref><ref name="www">Stage III Ovarian Germ Cell Tumors
*[[Surgery]] is the mode of treatment for endodermal sinus tumor with [[adjuvant]] [[chemotherapy]]:<ref name="xxx">Stage I Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_54. URL Accessed on Nov 5, 2015</ref><ref name="rrr">Stage IV Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_65. URL Accessed on Nov 5, 2015</ref>
===Stage I endodermal sinus tumor===
:* Unilateral salpingo-oophorectomy with adjuvant [[chemotherapy]]
 
===Stage II endodermal sinus tumor===
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
 
===Stage III endodermal sinus tumor===
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
 
===Stage IV endodermal sinus tumor===
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
 
==Surgery==
[[Surgery]] is the mode of treatment for endodermal sinus tumor when chemotherapy is not effective:<ref name="xxx">Stage I Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_33. URL Accessed on Nov 5, 2015</ref><ref name="abc">Stage II Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_33. URL Accessed on Nov 5, 2015</ref><ref name="abc">Stage II Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_43. URL Accessed on Nov 5, 2015</ref><ref name="aaa">Stage III Ovarian Germ Cell Tumors
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_43. URL Accessed on Nov 5, 2015</ref><ref name="aaa">Stage III Ovarian Germ Cell Tumors
Line 125: Line 111:
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_65. URL Accessed on Nov 5, 2015</ref>
. http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_65. URL Accessed on Nov 5, 2015</ref>
===Stage I endodermal sinus tumor===
===Stage I endodermal sinus tumor===
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy
 
:* Unilateral salpingo-oophorectomy followed by observation
:* Unilateral [[Salpingo-oophorectomy|salpingo-oophorectom]]<nowiki/>y with [[Adjuvant|adjuvan]]<nowiki/>t [[chemotherapy]]<ref name="urlOvarian Germ Cell Tumors Treatment (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK66014/ |title=Ovarian Germ Cell Tumors Treatment (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf |format= |work= |accessdate=}}</ref>
:* Unilateral [[salpingo-oophorectomy]] followed by [[observation]]


===Stage II endodermal sinus tumor===
===Stage II endodermal sinus tumor===
:* Unilateral [[salpingo-oophorectomy]] with [[adjuvant chemotherapy]]
:* Unilateral [[salpingo-oophorectomy]] with [[adjuvant chemotherapy]]
:* Second-look laparotomy
:* Second-look [[laparotomy]]


===Stage III endodermal sinus tumor===
===Stage III endodermal sinus tumor===
:* Total abdominal [[hysterectomy]] and bilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without neoadjuvant chemotherapy
 
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy, with or without [[neoadjuvant chemotherapy]]
:* Total [[abdominal]] [[hysterectomy]] and bilateral [[salpingo-oophorectomy]] with [[adjuvant]] [[chemotherapy]], with or without neoadjuvant [[chemotherapy]]
:* Unilateral [[salpingo-oophorectomy]] with [[adjuvant chemotherapy]], with or without [[neoadjuvant chemotherapy]]
:* Second-look [[laparotomy]]
:* Second-look [[laparotomy]]


===Stage IV endodermal sinus tumor===
===Stage IV endodermal sinus tumor===
:* Total abdominal hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
 
:* Unilateral salpingo-oophorectomy with adjuvant chemotherapy with or without neoadjuvant chemotherapy
:* Total [[abdominal]] [[hysterectomy]] and [[Salpingo-oophorectomy|bilateral salpingo-oophorectomy]] with [[adjuvant chemotherapy]] with or without [[neoadjuvant chemotherapy]]
:* Unilateral [[salpingo-oophorectomy]] with [[adjuvant chemotherapy]] with or without [[neoadjuvant chemotherapy]]
 
===Prevention===
* There are no primary preventive measures available for endodermal sinus tumor.
===Video===
===Video===
{{#ev:youtube|KGKRaTciMK4}}
{{#ev:youtube|KGKRaTciMK4}}

Latest revision as of 15:55, 14 November 2019

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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]; Monalisa Dmello, M.B,B.S., M.D. [3]; Shivali Marketkar, M.B.B.S. [4]; Ammu Susheela, M.D. [5]

For patient information, click here Synonyms and keywords: Endodermal sinus tumor(EST), yolk sac tumor.

Overview

Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist, in 1959. The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor. Endodermal sinus tumor is a rare type of malignant ovarian tumor that occurs in the second decade of life. On gross pathology, a solid gray-white with gelatinous, myxoid, or mucoid appearance, necrosis, cystic changes, and hemorrhage are characteristic findings of endodermal sinus tumor. On microscopic histopathological analysis, Schiller-Duval bodies is a characteristic finding of endodermal sinus tumor. Endodermal sinus tumor must be differentiated from other diseases that cause pelvic mass, such as Stein-Leventhal syndrome, and seminoma. In 2015, the incidence of endodermal sinus tumor is estimated to less than 1/100,000 case per year in U.S. Endodermal sinus tumor may be classified according to histology groups.The diagnosis of endodermal sinus tumor is made based on the imaging (U/S and MRI) and alpha fetoprotein (AFP) tumor marker greater than 100 ng/ml. Endodermal sinus tumor have a bimodal distribution more commonly observed among young and adult population. The symptoms of endodermal sinus tumor include the followings: abdominal distention, acute/sub acute abdominal pain. Endodermal sinus tumor is treated with surgery depending on the tumor marker and imaging as well as fertility desired.The medical therapy for endodermal sinus tumor is chemotherapy such as bleomycin, etoposide, and cisplatin for 3 to 4 cycles for 21 days.

Historical Perspective

  • Endodermal sinus tumor was first discovered by Dr. Gunner Telium, a Danish pathologist in 1959.[1][2]

Classification

  • Endodermal sinus tumor may be classified according to histology into 10 groups:[3]

Pathophysiology

  • The hypermethylation of the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor has been associated with the development of endodermal sinus tumor.[4]
  • Ovarian endodermal sinus tumor may be result of differentiation of primitive malignant germ cell components of vitelline structures.[5]
  • 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.[6]
  • 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[7].[8]

Causes

  • There are no established causes for endodermal sinus tumor.[9]

Differentiating Endodermal sinus tumor from Other Diseases

Endodermal sinus tumor must be differentiated from other diseases that cause pelvic mass, abdominal pain and abdominal distention such as:[10][11]

Epidemiology and Demographics

  • In 2015, the incidence of endodermal sinus tumor is estimated to less than 1/100,000 case per year in U.S.[12]

Age

Gender

  • Endodermal sinus tumor affects men and women equally.[14]

Race

  • There is no racial predilection for endodermal sinus tumor.

Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

Symptoms

Physical Examination

Laboratory Findings

Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Stage I endodermal sinus tumor

Stage II endodermal sinus tumor

Stage III endodermal sinus tumor

Stage IV endodermal sinus tumor

Prevention

  • There are no primary preventive measures available for endodermal sinus tumor.

Video

{{#ev:youtube|KGKRaTciMK4}}

References

  1. ↑ Carmen, Marcela (2015). Uncommon gynecologic cancers. Chichester, England: Wiley Blackwell. ISBN 978-1-118-65535-1.
  2. ↑ 2.0 2.1 Shah JP, Kumar S, Bryant CS, Ali-Fehmi R, Malone JM, Deppe G; et al. (2008). "A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females". Int J Cancer. 123 (11): 2671–5. doi:10.1002/ijc.23792. PMID 18767035.
  3. ↑ Weidner, Noel (2009). Modern surgical pathology. Philadelphia, PA: Saunders/Elsevier. ISBN 978-1-4160-3966-2.
  4. ↑ 4.0 4.1 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.
  5. ↑ Crum, Christopher (2018). Diagnostic gynecologic and obstetric pathology. Philadelphia, PA: Elsevier, Inc. ISBN 978-0-323-44732-4.
  6. ↑ Carmen, Marcela (2015). Uncommon gynecologic cancers. Chichester, England: Wiley Blackwell. ISBN 978-1-118-65535-1.
  7. ↑ Carmen, Marcela (2015). Uncommon gynecologic cancers. Chichester, England: Wiley Blackwell. ISBN 978-1-118-65535-1.
  8. ↑ Kurman RJ, Norris HJ (1976). "Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases". Cancer. 38 (6): 2404–19. doi:10.1002/1097-0142(197612)38:6<2404::aid-cncr2820380629>3.0.co;2-3. PMID 63318.
  9. ↑ Makris, Georgios-Marios (2017). "Giving Birth After Fertility Sparing Treatment for a Yolk Sac Tumour: Case Report". JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. doi:10.7860/JCDR/2017/25820.10524. ISSN 2249-782X.
  10. ↑ Shaaban AM, Rezvani M, Elsayes KM, et al. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. Radiographics. 2014;34(3):777-801.http://pubs.rsna.org/doi/pdf/10.1148/rg.343130067
  11. ↑ Jung SE, Lee JM, Rha SE, Byun JY, Jung JI, Hahn ST. CT and MR imaging of ovarian tumors with emphasis on differential diagnosis. Radiographics. 2002;22(6):1305-25.http://www.ncbi.nlm.nih.gov/pubmed/12432104
  12. ↑ Young JL, Miller RW (1975). "Incidence of malignant tumors in U. S. children". J Pediatr. 86 (2): 254–8. doi:10.1016/s0022-3476(75)80484-7. PMID 1111694.
  13. ↑ Coppes MJ, Rackley R, Kay R (1994). "Primary testicular and paratesticular tumors of childhood". Med Pediatr Oncol. 22 (5): 329–40. PMID 8127257.
  14. ↑ "Endodermal Sinus Tumor - St. Jude Children's Research Hospital".
  15. ↑ 15.0 15.1 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.
  16. ↑ 16.0 16.1 16.2 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.
  17. ↑ 17.0 17.1 17.2 "Definition of endodermal sinus tumor - NCI Dictionary of Cancer Terms - National Cancer Institute".
  18. ↑ Saia, Philip (2018). Clinical gynecologic oncology. Philadelphia, PA: Elsevier. ISBN 978-0-323-40067-1.
  19. ↑ 19.0 19.1 19.2 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.
  20. ↑ Saia, Philip (2018). Clinical gynecologic oncology. Philadelphia, PA: Elsevier. ISBN 978-0-323-40067-1.
  21. ↑ Chen, Li Hsun; Yip, Kui-Chuen; Wu, Hsing-Ju; Yong, Su-Boon (2019). "Yolk Sac Tumor in an Eight-Year-Old Girl: A Case Report and Literature Review". Frontiers in Pediatrics. 7. doi:10.3389/fped.2019.00169. ISSN 2296-2360.
  22. ↑ Weidner, Noel (2009). Modern surgical pathology. Philadelphia, PA: Saunders/Elsevier. ISBN 978-1-4160-3966-2.
  23. ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
  24. ↑ 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.
  25. ↑ 25.0 25.1 Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
  26. ↑ Crum, Christopher (2018). Diagnostic gynecologic and obstetric pathology. Philadelphia, PA: Elsevier, Inc. ISBN 978-0-323-44732-4.
  27. ↑ 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.
  28. ↑ "NCCN Clinical Practice Guidelines in Oncology: Endodermal sinus tumor. National comprehensive cancer network, 2017; https://www.nccn.org/patients/guidelines/content/PDF/ovarian.pdf."
  29. ↑ Williams S, Blessing JA, Liao SY, Ball H, Hanjani P (1994). "Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group". J Clin Oncol. 12 (4): 701–6. doi:10.1200/JCO.1994.12.4.701. PMID 7512129.
  30. ↑ "NCCN Clinical Practice Guidelines in Oncology: Endodermal sinus tumor. National comprehensive cancer network, 2017; https://www.nccn.org/patients/guidelines/content/PDF/ovarian.pdf."
  31. ↑ Stage I Ovarian Germ Cell Tumors . http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_33. URL Accessed on Nov 5, 2015
  32. ↑ Stage III Ovarian Germ Cell Tumors . http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_54. URL Accessed on Nov 5, 2015
  33. ↑ Stage IV Ovarian Germ Cell Tumors . http://www.cancer.gov/types/ovarian/hp/ovarian-germ-cell-treatment-pdq#section/_65. URL Accessed on Nov 5, 2015
  34. ↑ "Ovarian Germ Cell Tumors Treatment (PDQ®) - PDQ Cancer Information Summaries - NCBI Bookshelf".
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