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germ cell tumor

{{Infobox medical condition (new)

| name = Germ-cell tumor

| synonyms =

| image = Seminoma high mag.jpg

| caption = Micrograph of a seminoma, a common germ cell tumor.

| pronounce =

| field = Oncology

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A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells.{{Cite book |title=Harrison's principles of internal medicine |date=2022 |publisher=McGraw Hill |isbn=978-1-264-26850-4 |edition=21st |location=New York |pages=690}} Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary{{cite journal | vauthors = Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM | display-authors = 6 | title = Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review | journal = Cancers | volume = 12 | issue = 6 | page = 1398 | date = May 2020 | pmid = 32485873 | pmc = 7353025 | doi = 10.3390/cancers12061398 | doi-access = free }} and testis), but can arise in other areas of the body. Extragonadal GCTs are thought to result from abnormal migration of germ cell precursors during development of the embryo.{{cite journal| author=Glenn, OA and Barkovich AJ | title= Intracranial germ cell tumors: a comprehensive review of proposed embryologic derivation. | journal=Pediatric Neurosurgery | year=1996 | volume=24 | issue= 5 | pages= 242–251 | pmid=8933567 | doi=10.1159/000121046 | url=https://pubmed.ncbi.nlm.nih.gov/8933567/ }}

Classification

File:Relative incidences of testicular tumors.pngs.{{cite journal| author=Gill MS, Shah SH, Soomro IN, Kayani N, Hasan SH| title=Morphological pattern of testicular tumors. | journal=J Pak Med Assoc | year= 2000 | volume= 50 | issue= 4 | pages= 110–3 | pmid=10851829 | doi= | pmc= | url=https://pubmed.ncbi.nlm.nih.gov/10851829 }}]]

GCTs are classified by their histology,{{cite journal | vauthors = Ulbright TM | title = Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues | journal = Modern Pathology | volume = 18 | issue = Suppl 2 | pages = S61–S79 | date = February 2005 | pmid = 15761467 | doi = 10.1038/modpathol.3800310 | doi-access = free }} regardless of location in the body. However, as more information about the genetics of these tumors become available, they may be classified based on specific gene mutations that characterize specific tumors.{{cite journal | vauthors = Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM | display-authors = 6 | title = Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review | journal = Cancers | volume = 12 | issue = 6 | page = 1398 | date = May 2020 | pmid = 32485873 | pmc = 7353025 | doi = 10.3390/cancers12061398 | doi-access = free }} They are broadly divided in two classes:{{EMedicine|med|2246|Germinoma, Central Nervous System}}

  • The germinomatous or seminomatous germ-cell tumors (GGCT, SGCT) include only germinoma and its synonyms dysgerminoma and seminoma.
  • {{anchor|Nonseminoma}}The nongerminomatous or nonseminomatous germ-cell tumors (NGGCT, NSGCT) include all other germ-cell tumors, pure and mixed.

The two classes reflect an important clinical difference. Compared with germinomatous tumors, nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis (around 25 years versus 35 years, in the case of testicular cancers), and have a lower five-year survival rate. The survival rate for germinomatous tumors is higher in part because these tumors are very sensitive to radiation, and they also respond well to chemotherapy. The prognosis for nongerminomatous tumours has improved dramatically, however, due to the use of platinum-based chemotherapy regimens.{{cite book | vauthors = Robbins SL, Kumar V, Cotran RS | title = Robbins Basic Pathology | publisher = Saunders | location = Philadelphia | year = 2003 | page = [https://archive.org/details/robbinsbasicpath0000unse/page/664 664] | isbn = 0-7216-9274-5 | edition = 7th | url-access = registration | url = https://archive.org/details/robbinsbasicpath0000unse/page/664 }}

= Germinomatous =

class="wikitable"
Tumor

! ICD-O

! Peak Age (yr)

! Benign or malignant

! Histology

! Tumor marker

Germinoma (including dysgerminoma and seminoma)

|

| 40–50

| Malignant

| Sheets of uniform polygonal cells with cleared cytoplasm; lymphocytes in the stroma

| About 10% have elevated hCG

Dysgerminoma

| {{ICDO|9060|3}}

|

|

|

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Seminoma

| {{ICDO|9061|3}}

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| Placental alkaline phosphate (PLAP){{cite journal | vauthors = Nielsen OS, Munro AJ, Duncan W, Sturgeon J, Gospodarowicz MK, Jewett MA, Malkin A, Thomas GM | display-authors = 6 | title = Is placental alkaline phosphatase (PLAP) a useful marker for seminoma? | journal = European Journal of Cancer | volume = 26 | issue = 10 | pages = 1049–1054 | year = 1990 | pmid = 2148879 | doi = 10.1016/0277-5379(90)90049-y }}

= Nongerminomatous =

class="wikitable"
Tumor

! ICD-O

! Peak Age (yr)

! Benign or malignant

! Histology

! Tumor marker

Embryonal carcinoma

| 9070/3

| 20–30

| Malignant

| Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation

| secrete hCG, AFP

Endodermal sinus tumor, also known as yolk sac tumor (EST, YST)

| 9071/3

| 3

| Malignant

| Poorly differentiated endothelium-like, cuboidal, or columnar cells

| 100% secrete AFP

Choriocarcinoma

| 9100/3

| 20–30

| Malignant

| Cytotrophoblast and syncytiotrophoblast without villus formation

| 100% secrete hCG

Teratoma including mature teratoma, dermoid cyst, immature teratoma, teratoma with malignant transformation

| 9080/0-9080/3

| 0–3, 15–30

| Mature teratoma, dermoid cyst usually benign (but follow-up required); others usually malignant

| Very variable, but "normal" tissues are common

| Pure tumors do not secrete hCG, AFP

Polyembryoma

| 9072/3

| 15–25

| ?

| ?

| ?

Gonadoblastoma

| 9073/1

| ?

| ?

| ?

| ?

= Mixed =

class="wikitable"
Tumor

! ICD-O

! Peak Age (yr)

! Benign or malignant

! Histology

! Tumor marker

Mixed

|

| 15–30

| Malignant

| Depends on elements present

| Depends on elements present

Mixed germ cell tumors occur in many forms. Among these, a common form is teratoma with endodermal sinus tumor.

Teratocarcinoma refers to a germ cell tumor that is a mixture of teratoma with embryonal carcinoma, or with choriocarcinoma, or with both.{{MeSH name| Teratocarcinoma}} This kind of mixed germ cell tumor may be known simply as a teratoma with elements of embryonal carcinoma or choriocarcinoma, or simply by ignoring the teratoma component and referring only to its malignant component: embryonal carcinoma and/or choriocarcinoma. They can present in the anterior mediastinum.{{cn|date=May 2021}}

Cause

Extragonadal GCTs were thought initially to be isolated metastases from an undetected primary tumor in a gonad, but many germ cell tumors are now known to be congenital and originate outside the gonads. The most notable of these is sacrococcygeal teratoma, the single most common tumor diagnosed in babies at birth.{{cn|date=May 2021}}

Of all anterior mediastinal tumors, 15–20% are GCTs of which about 50% are benign teratomas.{{Cite web |url=http://www.jpmsonline.com/jpms-vol2-issue1-pages11-12-ci.html |title=Clinical Image: Mediastinal Teratoma |access-date=2011-12-22 |archive-url=https://web.archive.org/web/20180804013958/http://www.jpmsonline.com/jpms-vol2-issue1-pages11-12-ci.html |archive-date=2018-08-04 |url-status=dead }} Ovarian teratomas may be associated with anti-NMDA receptor encephalitis.{{cite journal | vauthors = Omata T, Kodama K, Watanabe Y, Iida Y, Furusawa Y, Takashima A, Takahashi Y, Sakuma H, Tanaka K, Fujii K, Shimojo N | display-authors = 6 | title = Ovarian teratoma development after anti-NMDA receptor encephalitis treatment | journal = Brain & Development | volume = 39 | issue = 5 | pages = 448–451 | date = May 2017 | pmid = 28040316 | doi = 10.1016/j.braindev.2016.12.003 | s2cid = 8224022 }}

Location

GCTs most commonly arise in the testis, followed by the ovary and extragonadal sites. Extragonadal GCTs tend to arise in the midline, most commonly at the following sites:{{cite web | url=https://www.cancer.gov/types/extragonadal-germ-cell/patient/extragonadal-treatment-pdq | title=Extragonadal Germ Cell Tumors Treatment - NCI | date=22 November 2004 }}

In females, GCTs account for 20-25% of ovarian tumors, but are predominantly benign mature teratomas. Malignant ovarian GCTs are comparatively rare, and consist of immature teratomas, dysgerminomas, yolk sac tumors, and mixed germ cell tumors.{{cite journal | pmc=10093990 | date=2023 | last1=Cong | first1=L. | last2=Wang | first2=S. | last3=Yeung | first3=S. Y. | last4=Lee | first4=J. H. | last5=Chung | first5=J. P. | last6=Chan | first6=D. Y. | title=Mature Cystic Teratoma: An Integrated Review | journal=International Journal of Molecular Sciences | volume=24 | issue=7 | page=6141 | doi=10.3390/ijms24076141 | doi-access=free | pmid=37047114 }}{{cite web | url=https://www.uptodate.com/contents/ovarian-germ-cell-tumors-pathology-epidemiology-clinical-manifestations-and-diagnosis | title=UpToDate }}

In males, GCTs account of 95% of testicular tumors, and are all considered malignant. Seminoma is the most common diagnosis (50%), followed by mixed-germ cell tumor (40%), and other pure GCTs.{{cite web | url=https://tumourclassification.iarc.who.int/chaptercontent/36/113 | title=BlueBooksOnline }} In neonates, infants, and children younger than 4 years, most are sacrococcygeal teratomas.{{cn|date=May 2021}}

Males with Klinefelter syndrome have a 50 times greater risk of GSTs.{{cite journal | vauthors = Bebb GG, Grannis FW, Paz IB, Slovak ML, Chilcote R | title = Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome | journal = The Annals of Thoracic Surgery | volume = 66 | issue = 2 | pages = 547–548 | date = August 1998 | pmid = 9725401 | doi = 10.1016/S0003-4975(98)00504-9 }} In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.{{Medical citation needed|date=November 2017}}

Treatment

Treatment typically involves a combination of surgery and chemotherapy, depending on the subtype and location of the tumor. Surgery is performed upfront for testicular and ovarian tumors, as biopsies are associated with peritoneal and scrotal tumor seeding.

Benign GCTs such as mature teratomas (dermoid cysts) are cured by simple excision.

Testicular germ cell tumors are treated by orchiectomy, followed by surveillance, lymph node staging, and/or chemotherapy depending on the risk stratification defined by the International Germ Cell Cancer Collaborative Group (IGCCCG).{{cite journal | author = International Germ Cell Cancer Collaborative Group | title = International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group | journal = Journal of Clinical Oncology | volume = 15 | issue = 2 | pages = 594–603 | date = February 1997 | pmid = 9053482 | doi = 10.1200/jco.1997.15.2.594 }}

Treatment for ovarian germ cell tumors typically involves at least ovarian cystectomy. Removal of the ovaries, fallopian tube, uterus, and retroperitoneal lymph nodes may be planned depending on patient age, reproductive status, and extent of disease.{{cite journal | vauthors = Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM | display-authors = 6 | title = Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review | journal = Cancers | volume = 12 | issue = 6 | page = 1398 | date = May 2020 | pmid = 32485873 | pmc = 7353025 | doi = 10.3390/cancers12061398 | doi-access = free }}

Patients with advanced or high-risk GCT may need to be treated with combination chemotherapy.{{cite journal | vauthors = Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM | display-authors = 6 | title = Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review | journal = Cancers | volume = 12 | issue = 6 | page = 1398 | date = May 2020 | pmid = 32485873 | pmc = 7353025 | doi = 10.3390/cancers12061398 | doi-access = free }} The chemotherapy regimen most commonly used in GCTs is called PEB (or BEP), and consists of bleomycin, etoposide, and a platinum-based antineoplastic (cisplatin).{{cite web | url = http://www.cancer.org/Cancer/OvarianCancer/DetailedGuide/ovarian-cancer-treating-germ-cell-tumors | title = Treatment for germ cell tumors of the ovary | work = American Cancer Society | date = 11 January 2012 | access-date = 23 July 2012 | archive-date = 20 December 2016 | archive-url = https://web.archive.org/web/20161220020427/http://www.cancer.org/Cancer/OvarianCancer/DetailedGuide/ovarian-cancer-treating-germ-cell-tumors | url-status = dead }} Targeted treatments, such as immunotherapy, hormonal therapy and kinase inhibitors, are being evaluated for tumors that do not respond to chemotherapy.{{cite journal | vauthors = Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM | display-authors = 6 | title = Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review | journal = Cancers | volume = 12 | issue = 6 | page = 1398 | date = May 2020 | pmid = 32485873 | pmc = 7353025 | doi = 10.3390/cancers12061398 | doi-access = free }}

Prognosis

Germ cell tumors are a heterogeneous group with prognosis specific to their subtype and location, but cure rates exceed 80%. Advanced or metastatic germ cell tumors tend to be relatively responsive to chemotherapy compared to other types of cancer. Even for metastatic non-seminomatous germ cell tumors of the testis, 10-year median overall survival is 70-90%.{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/21482994/ | pmid=21482994 | date=2011 | last1=Olofsson | first1=S. E. | last2=Tandstad | first2=T. | last3=Jerkeman | first3=M. | last4=Dahl | first4=O. | last5=Ståhl | first5=O. | last6=Klepp | first6=O. | last7=Bremnes | first7=R. M. | last8=Cohn-Cedermark | first8=G. | last9=Langberg | first9=C. W. | last10=Laurell | first10=A. | last11=Solberg | first11=A. | last12=Stierner | first12=U. | last13=Wahlqvist | first13=R. | last14=Wijkström | first14=H. | last15=Anderson | first15=H. | last16=Cavallin-Ståhl | first16=E. | title=Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: A report from the Swedish-Norwegian Testicular Cancer Group | journal=Journal of Clinical Oncology | volume=29 | issue=15 | pages=2032–2039 | doi=10.1200/JCO.2010.29.1278 }} In extragonadal GCTs, 5-year median overall survival ranges from 90% for extragonadal seminoma, to 17-70% for non-seminomatous tumors.{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/12176779/ | pmid=12176779 | date=2002 | last1=Hartmann | first1=J. T. | last2=Nichols | first2=C. R. | last3=Droz | first3=J. P. | last4=Horwich | first4=A. | last5=Gerl | first5=A. | last6=Fossa | first6=S. D. | last7=Beyer | first7=J. | last8=Pont | first8=J. | last9=Kanz | first9=L. | last10=Einhorn | first10=L. | last11=Bokemeyer | first11=C. | title=Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors | journal=Annals of Oncology | volume=13 | issue=7 | pages=1017–1028 | doi=10.1093/annonc/mdf176 }}

The 1997 International Germ Cell Consensus Classification{{cite journal | author = International Germ Cell Cancer Collaborative Group | title = International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group | journal = Journal of Clinical Oncology | volume = 15 | issue = 2 | pages = 594–603 | date = February 1997 | pmid = 9053482 | doi = 10.1200/jco.1997.15.2.594 }} is a prognostic tool for estimating the risk of relapse after treatment of germ-cell tumor.

Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with nonseminomatous (nongerminomatous) GCTs diagnosed between 1975 and 1989, five-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, though the unit treated more men with the worst prognosis.{{cite journal | vauthors = Harding MJ, Paul J, Gillis CR, Kaye SB | title = Management of malignant teratoma: does referral to a specialist unit matter? | journal = Lancet | volume = 341 | issue = 8851 | pages = 999–1002 | date = April 1993 | pmid = 8096954 | doi = 10.1016/0140-6736(93)91082-W | s2cid = 29536953 }}

See also

References

{{Reflist}}

External links

{{Medical resources

| ICD10 = {{ICD10|C|56||c|51}}, {{ICD10|C|62||c|60}}, {{ICD10|D|27||d|10}}, {{ICD10|D|29|2|d|10}}

| ICD9 = {{ICD9|183}}, {{ICD9|186}}, {{ICD9|220}}, {{ICD9|222.0}}

| ICDO = 9060–9100

| OMIM =

| OMIM_mult =

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 863

| DiseasesDB =

| MeshID = D009373

}}

  • humpath [http://www.humpath.com/spip.php?page=article&id_article=2658 #2658] {{Webarchive|url=https://web.archive.org/web/20210409232158/http://www.humpath.com/spip.php?page=article&id_article=2658 |date=2021-04-09 }} (Pathology images)
  • [http://www.cancer.gov/cancertopics/pdq/treatment/extracranial-germ-cell/HealthProfessional Childhood Extracranial Germ Cell Tumors]
  • [http://www.cancer.gov/cancertopics/pdq/treatment/extragonadal-germ-cell/healthprofessional Extragonadal Germ Cell Tumors]
  • [http://www.cancer.gov/cancertopics/pdq/treatment/ovarian-germ-cell/HealthProfessional Ovarian Germ Cell Tumors]
  • {{cite journal | vauthors = Packer RJ, Cohen BH, Cooney K, Coney K | title = Intracranial germ cell tumors | journal = The Oncologist | volume = 5 | issue = 4 | pages = 312–320 | year = 2000 | pmid = 10964999 | doi = 10.1634/theoncologist.2000-0312 | doi-access = free }}
  • [http://www.cancer.net/cancer-types/germ-cell-tumor-childhood Cancer.Net: Germ Cell Tumor]

{{Germ cell tumors}}

{{Female genital neoplasia}}

{{Male genital neoplasia}}

{{DEFAULTSORT:Germ Cell Tumor}}

Category:Gynaecological cancer

Category:Colorectal surgery

Category:Male genital neoplasia

Category:Germ cell neoplasia