Germ cell tumor classification: Difference between revisions

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Germ cell tumors can be classified as follows:


=== '''Histologic-based classification''' ===
<br />{{familytree/start}}
{{familytree| | | | | | | | | | A01 | | | |A01=Germ cell tumors}}
{{familytree| | | | | |,|-|-|-|-|^|-|-|-|-|-|.| | | }}
{{familytree| | | | | B01 | | | | | | | | | B02 | | B01=Germinomatous/Undifferentiated/Immature|B02=Nongerminomatous/Differentiated/Embryonal}}
{{familytree| | |,|-|-|^|-|-|.| | | | | | | |!| | | |}}
{{familytree| | |!| | | | | |!| | | | | | | |!| | | |}}
{{familytree| | C01 | | | | C02 | | | | | | |!| | | | | C01=[[Dysgerminoma(Ovary)]]|C02=[[Seminoma(Testis)]]}}
{{familytree| | | | | | | | | | | | | | | | |!| | | | | | |}}
{{familytree| | | | |,|-|-|-|-|-|-|-|-|v|-|-|^|-|-|-|.| | |}}
{{familytree| | | | |!| | | | | | | | |!| | | | | | |!| | |}}
{{familytree| | | | D01 | | | | | | | D02 | | | | | D03 | | |D01=[[Embryonal carcinoma]]| D02=[[embryonic tissue]]| D03=[[Extraembryonic tissue]]}}
{{familytree| | | | | | | | | | | | | |!| | | | |,|-|^|-|.| | |}}
{{familytree| | | | | | | | | | | | | E01 | | | E02 | | E03| | |E01=[[Teratoma]]|E02=[[Yolk sac tumor]]|E03=[[Choriocarcinoma]]}}
{{familytree/end}}
=== Location-based classification, regardless to the histologic findings: ===
<br />{{familytree/start}}
{{familytree| | | | | | | | | A01 | | | |A01=Germ cell tumors}}
{{familytree| | | | |,|-|-|-|-|^|-|-|-|-|-|.| | | }}
{{familytree| | | | B01 | | | | | | | | | B02 | | B01=Gonadal|B02=Extragonadal}}
{{familytree| | | | |!| | | | | | | | | | |!| | |}}
{{familytree| | | | C01 | | | | | | | | | C02| | | | |
C01=
Located in the gonads
*Ovary
*[[Testis]]|C02=
Located in the midline of the body including:
*CNS
*Mediastinum
*Retroperitoneum
*Coccyx}}
{{familytree| | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
! rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF| Types}}
! rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Subtypes}}
! colspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Signs and Symptoms}}
! rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF|Histopathology}}
! rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF| Lab finding }}
! rowspan="1" style="background: #4479BA; padding: 5px 5px;" |{{fontcolor|#FFFFFF| Prognosis}}
|-
| rowspan="2;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" |Germinomatous
/Undifferentiated
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
Seminoma (Testis)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Painless [[testicular mass]] with discomfort
*[[Back pain]]
*[[Abdominal discomfort]]
*[[Abdominal mass]].
| style="padding: 5px 5px; background: #F5F5F5;" |Gross: pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface
| style="padding: 5px 5px; background: #F5F5F5;" |
* 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]], [[PET|FDG-PET scan]], and [[bone scan]].
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Prognosis]] of [[seminoma]] is good for all stages with greater than 90% cure rate.
* The International Germ Cell Cancer Consensus Group divides [[seminoma]] into two prognosis groups: good and intermediate.
* Common complications of [[seminoma]] include recurrence, [[lymph node]] [[metastasis]], distant [[metastasis]], and secondary [[malignancies]].
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
Dysgerminoma
(Ovary)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Depend on the type of the [[tumor]] and its potential to produce [[hormonal]]<nowiki/>materials
*[[Abdominal pain]] or distention
*[[Menstrual irregularities]]
* Symptoms of [[virilization]]
* Rapidly growing [[abdominal]]/[[pelvic]] [[mass]]
*[[Acute abdominal pain]] from [[complications]] such as:
*[[Necrosis]]
*[[Capsule|Capsular]] distention
* [[Rupture]] or [[torsion]] and or simply they can be [[asymptomatic]].
| style="padding: 5px 5px; background: #F5F5F5;" |
*The majority of [[ovarian]] [[germ cell]][[tumors]] have a [[solid]] and [[cystic]] appearance with areas of [[hemorrhage]]<nowiki/>and [[necrosis]]
* A uniform “fried egg” appearance ([[dysgerminoma]])
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Beta-hCG]] to rule out [[pregnancy]] in women with abdominopelvic [[symptoms]]
*Cultures for [[gonorrhea]] and [[chlamydia]] and a wet mount in [[reproductive]] and [[sexually active]] women to role out and treat before [[surgery]] if [[positive]].
*[[Lactate dehydrogenase]] ([[LDH]]), [[alpha-fetoprotein]] ([[AFP]]), [[beta-human chorionic gonadotropin]] ([[beta-hCG]]) levels. If any levels are elevated, they may assist in [[diagnosis]] and/ or follow-up of women [[Diagnosis|diagnosed]] with [[malignant]] [[Ovarian germ cell tumor|ovarian GCTs]].
*[[Inhibin A]] and B
*[[CA-125|Cancer antigen 125]] ([[CA-125]]) - For epithelial tumors
*[[Ultrasound]]: [[Dysgerminoma]] often appears as a [[Echogenicity|hypoechoic]] [[mass]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Chemotherapy: except those with stage 1a, stage 1a, 1b [[dysgerminoma]]
* Radiotherapy:
<nowiki>**</nowiki>  [[Dysgerminoma]] is radiosensitive.
[[Radiotherapy|** Radiotherapy]] is not anymore the first option of treatment for [[dysgerminoma]] considering its association with [[ovarian failure]]<nowiki/>development.
* Surgery: for diagnostic grading and therapy depending on if the patient prefers to preserve the ovary or not.
<br />
|-
| rowspan="6;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" | Germinomatous/
Differentiated
| rowspan="1;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" | Embryonic
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
Teratoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Chest pain]]
*[[Cough]]
*[[Shortness of breath]]
*[[Abdominal pain]]
*[[Lump]], Abdominal(ovarian teratoma)
* Abnormal [[bleeding]] from the vagina
*[[Fatigue]], [[weight loss]]
* Limited ability to tolerate exercise
| style="padding: 5px 5px; background: #F5F5F5;" |
* Teratomas belong to a class of tumors known as [[Nonseminoma|nonseminomatous]] [[germ cell tumor]] (NSGCT).
* All tumors of this class are the result of abnormal development of [[pluripotent]] cells: [[Germ cell|germ cells]] and [[Embryo|embryonal cells]].
* Teratomas of embryonal origin are [[Congenital disorder|congenital]]; teratomas of germ cell origin may or may not be congenital (this is not known).
* Embryonal teratomas most commonly occur in the sacrococcygeal region: [[sacrococcygeal teratoma]] is the single most common tumor found in [[Infant|newborn babies]].
| style="padding: 5px 5px; background: #F5F5F5;" |
* AFP
* MSAFP
* CT scans are often used to diagnose teratoma.
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
* 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.
|-
| rowspan="1;" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" |
Extraembryonic
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Choriocarcinoma]]([[Gestational Trophoblastic Neoplasia]])<ref name="xxx2">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</ref><ref name="OberEdgcomb19712">{{cite journal|last1=Ober|first1=William B.|last2=Edgcomb|first2=John H.|last3=Price|first3=Edward B.|title=THE PATHOLOGY OF CHORIOCARCINOMA|journal=Annals of the New York Academy of Sciences|volume=172|issue=10 Physiology a|year=1971|pages=299–426|issn=0077-8923|doi=10.1111/j.1749-6632.1971.tb34943.x}}</ref><ref name="SmithKohorn20052">{{cite journal|last1=Smith|first1=Harriet O.|last2=Kohorn|first2=Ernest|last3=Cole|first3=Laurence A.|title=Choriocarcinoma and Gestational Trophoblastic Disease|journal=Obstetrics and Gynecology Clinics of North America|volume=32|issue=4|year=2005|pages=661–684|issn=08898545|doi=10.1016/j.ogc.2005.08.001}}</ref><ref name="abc3">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</ref><ref name="pmid62002622">{{cite journal |vauthors=Young RH, Scully RE |title=Placental-site trophoblastic tumor: current status |journal=Clin Obstet Gynecol |volume=27 |issue=1 |pages=248–58 |date=March 1984 |pmid=6200262 |doi= |url=}}</ref><ref name="pmid171499672">{{cite journal |vauthors=Allison KH, Love JE, Garcia RL |title=Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=12 |pages=1875–7 |date=December 2006 |pmid=17149967 |doi=10.1043/1543-2165(2006)130[1875:ETTROA]2.0.CO;2 |url=}}</ref><ref name="abc4">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</ref><ref name="aaa">Choriocarcinoma. librepathology.org. http://librepathology.org/wiki/index.php/Choriocarcinoma Accessed on October 8, 2015</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |Early Symptoms:
*[[Vaginal bleeding]]
*[[Nausea]] and [[vomiting]]
*Passing of [[Tissue (biology)|tissue]] resembling a “bunch of grapes” from the [[vagina]]
*Absent [[fetal]] movement during [[pregnancy]]
*[[Abdomen|Abdominal]] distension 
Rare Symptoms:
*[[Headache]]
*[[Edema ]]of the [[Hand|hands]] and feet
*[[Abdomen|Abdominal]] or [[Pelvis|pelvic]] pain
*[[Vaginal discharge]]
*Overactive [[thyroid gland]] ([[hyperthyroidism]]) that causes:
*[[Tachycardia]]
*[[Sweating]]
*Shaking
*Heat intolerance
*[[Fever]]
Late Symptoms
*[[Hemoptysis]]
*Dry [[cough]]
*[[Chest pain]]
*Trouble [[breathing]]
*[[Headache]]
*[[Dizziness]]
*[[Jaundice]]
*[[Paralysis]]
*[[Seizure]]
*[[Dysarthria]] and [[dysphasia]]
*[[Visual system|Vision]] problems
*[[Lump]] in the [[vagina]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Gross pathology|Gross pathological]]:
* Bulky, destructive mass with [[Bleeding|hemorrhage]] and [[necrosis]]
* Can be associated with deep [[Myometrium|myometrial]] invasion
[[Microscopic]] [[Histopathology|histopathological:]]
*Columns and sheets of [[Trophoblast|trophoblastic]] [[Tissue (biology)|tissue]] invading [[Uterus|uterine]] [[muscle]] and [[Blood vessel|blood vessels]]
*[[Syncytiotrophoblast|Syncytiotrophoblasts]] (large [[eosinophilic]] smudgy [[Multinucleate|multinucleated]] [[Cell (biology)|cells]] with large [[Hyperchromicity|hyperchromatic]] [[Cell nucleus|nuclei]]) are intermixed with [[Cytotrophoblast|cytotrophoblasts]] (polygonal [[Cell (biology)|cells]] with distinct borders, and single irregular [[Cell nucleus|nuclei]])
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |[[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
*Human placental lactogen (hPL) is a tumor marker that may be used to follow women with placental site [[trophoblastic]] tumors
* Elevated hPL levels are found in women with some types of GTD
*[[Complete blood count]] can check for [[anemia]] from long-term (chronic) [[vaginal bleeding]]
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
Poor [[prognosis]] of gestational trophoblastic neoplasia (GTN) can be determined by the following factors:
* Age over 35 years ([[P-value|P]] = 0.025)
* Interval since the last [[pregnancy]] of over 2 years ([[P-value|P]] = 0.014)
* Deep [[Myometrium|myometrial]] invasion ([[P-value|P]] = 0.006)
* Stage III or IV ([[P-value|P]] < 0.0005)
* Maximum [[Human chorionic gonadotropin|βhCG]] level > 1000 mIU/ml ([[P-value|P]] = 0.034)
* Extensive [[coagulative necrosis]] ([[P-value|P]] = 0.024)
* High [[Mitosis|mitotic]] rate ([[P-value|P]] = 0.005)
* Presence of [[Cell (biology)|cells]] with clear [[cytoplasm]] ([[P-value|P]] < 0.0005)
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Yolk sac tumor]]
(Endodermal sinus tumor)
| style="padding: 5px 5px; background: #F5F5F5;" |Symptoms:<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/sub acute [[abdominal pain]]
*Signs:<ref name="abc2">{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref>
* Abdomen:
**[[Abdominal distention]]
** Abdominal [[tenderness]]
** Pelvis:
** Adnexal mass  <br />
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
** 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
| style="padding: 5px 5px; background: #F5F5F5;" |
* An elevated concentration of serum alpha feto-protein is 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>
* 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]]<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>
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*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>
*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>
*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>
*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>
* 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>
*[[Ovarian germ cell tumor|Ovarian germ cell tumo]]<nowiki/>r (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>
|-
|}
==References==
{{reflist}}

Latest revision as of 14:23, 23 September 2019