Sexcord/ stromal ovarian tumors pathophysiology: Difference between revisions
Jump to navigation
Jump to search
| Line 59: | Line 59: | ||
*Other factors that play an important role in the pathogenesis of granulosa cell tuomrs are PI3K/AKT (phosphatidylinositol-3-kinase; serine/threonine kinase), TGF-β (Transforming growth factor beta) signaling pathway, Notch signaling pathway, GATA4 and VEGF (vascular endothelial growth factor) | *Other factors that play an important role in the pathogenesis of granulosa cell tuomrs are PI3K/AKT (phosphatidylinositol-3-kinase; serine/threonine kinase), TGF-β (Transforming growth factor beta) signaling pathway, Notch signaling pathway, GATA4 and VEGF (vascular endothelial growth factor) | ||
[[File:Granulosa cell tumor.jpeg|center|thumb|700px|Schematic representation of the cell signaling pathways in GCT development. PI3K, phosphatidylinositol-3-kinase; AKT, serine/threonine kinase; FOXO 1/3, forkhead box O1/3; AMH, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802052/ Source:Li J, Bao R, Peng S, Zhang C. The molecular mechanism of ovarian granulosa cell tumors. J Ovarian Res. 2018;11(1):13. Published 2018 Feb 6. doi:10.1186/s13048-018-0384-1]]] | [[File:Granulosa cell tumor.jpeg|center|thumb|700px|Schematic representation of the cell signaling pathways in GCT development. PI3K, phosphatidylinositol-3-kinase; AKT, serine/threonine kinase; FOXO 1/3, forkhead box O1/3; AMH, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802052/ Source:Li J, Bao R, Peng S, Zhang C. The molecular mechanism of ovarian granulosa cell tumors. J Ovarian Res. 2018;11(1):13. Published 2018 Feb 6. doi:10.1186/s13048-018-0384-1]]] | ||
'''DICER1''':<ref name="pmid27813081">{{cite journal |vauthors=Fuller PJ, Leung D, Chu S |title=Genetics and genomics of ovarian sex cord-stromal tumors |journal=Clin. Genet. |volume=91 |issue=2 |pages=285–291 |date=February 2017 |pmid=27813081 |doi=10.1111/cge.12917 |url=}}</ref><ref name="pmid26033501">{{cite journal |vauthors=Goulvent T, Ray-Coquard I, Borel S, Haddad V, Devouassoux-Shisheboran M, Vacher-Lavenu MC, Pujade-Laurraine E, Savina A, Maillet D, Gillet G, Treilleux I, Rimokh R |title=DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study |journal=Histopathology |volume=68 |issue=2 |pages=279–85 |date=January 2016 |pmid=26033501 |doi=10.1111/his.12747 |url=}}</ref><ref name="pmid27241106">{{cite journal |vauthors=Stewart CJ, Charles A, Foulkes WD |title=Gynecologic Manifestations of the DICER1 Syndrome |journal=Surg Pathol Clin |volume=9 |issue=2 |pages=227–41 |date=June 2016 |pmid=27241106 |doi=10.1016/j.path.2016.01.002 |url=}}</ref><ref name="pmid29660837">{{cite journal |vauthors=Wang Y, Karnezis AN, Magrill J, Tessier-Cloutier B, Lum A, Senz J, Gilks CB, McCluggage WG, Huntsman DG, Kommoss F |title=DICER1 hot-spot mutations in ovarian gynandroblastoma |journal=Histopathology |volume=73 |issue=2 |pages=306–313 |date=August 2018 |pmid=29660837 |doi=10.1111/his.13630 |url=}}</ref> | '''DICER1''':<ref name="pmid27813081">{{cite journal |vauthors=Fuller PJ, Leung D, Chu S |title=Genetics and genomics of ovarian sex cord-stromal tumors |journal=Clin. Genet. |volume=91 |issue=2 |pages=285–291 |date=February 2017 |pmid=27813081 |doi=10.1111/cge.12917 |url=}}</ref><ref name="pmid26033501">{{cite journal |vauthors=Goulvent T, Ray-Coquard I, Borel S, Haddad V, Devouassoux-Shisheboran M, Vacher-Lavenu MC, Pujade-Laurraine E, Savina A, Maillet D, Gillet G, Treilleux I, Rimokh R |title=DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study |journal=Histopathology |volume=68 |issue=2 |pages=279–85 |date=January 2016 |pmid=26033501 |doi=10.1111/his.12747 |url=}}</ref><ref name="pmid27241106">{{cite journal |vauthors=Stewart CJ, Charles A, Foulkes WD |title=Gynecologic Manifestations of the DICER1 Syndrome |journal=Surg Pathol Clin |volume=9 |issue=2 |pages=227–41 |date=June 2016 |pmid=27241106 |doi=10.1016/j.path.2016.01.002 |url=}}</ref><ref name="pmid29660837">{{cite journal |vauthors=Wang Y, Karnezis AN, Magrill J, Tessier-Cloutier B, Lum A, Senz J, Gilks CB, McCluggage WG, Huntsman DG, Kommoss F |title=DICER1 hot-spot mutations in ovarian gynandroblastoma |journal=Histopathology |volume=73 |issue=2 |pages=306–313 |date=August 2018 |pmid=29660837 |doi=10.1111/his.13630 |url=}}</ref><ref name="LimOliva2018">{{cite journal|last1=Lim|first1=Diana|last2=Oliva|first2=Esther|title=Ovarian sex cord-stromal tumours: an update in recent molecular advances|journal=Pathology|volume=50|issue=2|year=2018|pages=178–189|issn=00313025|doi=10.1016/j.pathol.2017.10.008}}</ref> | ||
*DICER1 mutations are associated with leydig cell tumors and gynandroblastomas | *DICER1 mutations are associated with leydig cell tumors and gynandroblastomas | ||
*Although both germ line and somatic mutations play a role, approximately 60% of sexcord leydig cell tumors have somatic DICER1 mutations | *Although both germ line and somatic mutations play a role, approximately 60% of sexcord leydig cell tumors have somatic DICER1 mutations | ||
Revision as of 15:41, 18 March 2019
|
Sexcord/ stromal ovarian tumors Microchapters |
|
Differentiating Sexcord/ Stromal Ovarian Tumors from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Sexcord/ stromal ovarian tumors pathophysiology On the Web |
|
American Roentgen Ray Society Images of Sexcord/ stromal ovarian tumors pathophysiology |
|
Risk calculators and risk factors for Sexcord/ stromal ovarian tumors pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
The exact pathogenesis of [disease name] is not fully understood.
OR
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Pathophysiology
Physiology
The normal physiology of [name of process] can be understood as follows:
Pathogenesis
- The exact pathogenesis of [disease name] is not completely understood.
OR
- It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
- [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
- Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
- [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
- The progression to [disease name] usually involves the [molecular pathway].
- The pathophysiology of [disease/malignancy] depends on the histological subtype.
Genetics
- The recent advancing analyses have made us understand the pathophysiology of some of these tumor subtypes
- Mutations mainly involving DICER1, STK11, and FOXL2 influence the development of some of these neoplasms
- FOXL2 is a tumor suppressor gene
- It is a member of the forkhead box (FOX) family of evolutionarily conserved transcription factors
- It plays a fundamental and crucial role in ovarian development
- It regulates the ovarian granulosa cell proliferation, follicle development and ovarian hormones synthesis
- Almost all like 97% of adult granulosa cell tumors are characterized by missense somatic point mutations (402 C→G) in FOXL2 gene
- Infact this mutation is a sensitive and specific biomarker for adult granulosa cell tumors making it a pathognomonic feature
- The phosphorylation modification of FOXL2 in particular is responsible to the growth of granulosa cell tumors
- Importantly this mutation alter's antiproliferative pathways and also limit the apoptosis, as a result contributing to the pathogenesis of adult granulosa cell tumors
- Other factors that play an important role in the pathogenesis of granulosa cell tuomrs are PI3K/AKT (phosphatidylinositol-3-kinase; serine/threonine kinase), TGF-β (Transforming growth factor beta) signaling pathway, Notch signaling pathway, GATA4 and VEGF (vascular endothelial growth factor)
- DICER1 mutations are associated with leydig cell tumors and gynandroblastomas
- Although both germ line and somatic mutations play a role, approximately 60% of sexcord leydig cell tumors have somatic DICER1 mutations
- This particular gene DICER1 encodes for a RNA endoribonuclease that helps to cleave precursor miRNA into mature miRNAs
- DICER1 mutations are associated with a lot of tumors of which pleuropulmonary blastoma, is the most common lung tumor of infancy and early childhood
- Others are embryonal rhabdomyosarcoma of the uterine cervix, renal tumors, thyroid nodules and carcinoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, pineoblastoma, and pituitary blastoma
- The above mentioned tumors typically have biallelic DICER1 mutations that are composed of a loss of function in one allele and a missense mutation in the RNase IIIb domain
Associated Conditions
Conditions associated with [disease name] include:
- [Condition 1]
- [Condition 2]
- [Condition 3]
Gross Pathology
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
| Types | Gross pathology | Microscopic pathology | |
|---|---|---|---|
Microscopic Pathology
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
References
- ↑ 1.0 1.1 Lim, Diana; Oliva, Esther (2018). "Ovarian sex cord-stromal tumours: an update in recent molecular advances". Pathology. 50 (2): 178–189. doi:10.1016/j.pathol.2017.10.008. ISSN 0031-3025.
- ↑ 2.0 2.1 Fuller PJ, Leung D, Chu S (February 2017). "Genetics and genomics of ovarian sex cord-stromal tumors". Clin. Genet. 91 (2): 285–291. doi:10.1111/cge.12917. PMID 27813081.
- ↑ Li, Jiaheng; Bao, Riqiang; Peng, Shiwei; Zhang, Chunping (2018). "The molecular mechanism of ovarian granulosa cell tumors". Journal of Ovarian Research. 11 (1). doi:10.1186/s13048-018-0384-1. ISSN 1757-2215.
- ↑ Li J, Bao R, Peng S, Zhang C (February 2018). "The molecular mechanism of ovarian granulosa cell tumors". J Ovarian Res. 11 (1): 13. doi:10.1186/s13048-018-0384-1. PMC 5802052. PMID 29409506.
- ↑ Schultz KA, Harris AK, Schneider DT, Young RH, Brown J, Gershenson DM, Dehner LP, Hill DA, Messinger YH, Frazier AL (October 2016). "Ovarian Sex Cord-Stromal Tumors". J Oncol Pract. 12 (10): 940–946. doi:10.1200/JOP.2016.016261. PMC 5063189. PMID 27858560.
- ↑ Boussios, Stergios; Moschetta, Michele; Zarkavelis, George; Papadaki, Alexandra; Kefas, Aristides; Tatsi, Konstantina (2017). "Ovarian sex-cord stromal tumours and small cell tumours: Pathological, genetic and management aspects". Critical Reviews in Oncology/Hematology. 120: 43–51. doi:10.1016/j.critrevonc.2017.10.007. ISSN 1040-8428.
- ↑ Leung, Dilys T.H.; Fuller, Peter J.; Chu, Simon (2016). "Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors". The International Journal of Biochemistry & Cell Biology. 72: 51–54. doi:10.1016/j.biocel.2016.01.003. ISSN 1357-2725.
- ↑ Goulvent T, Ray-Coquard I, Borel S, Haddad V, Devouassoux-Shisheboran M, Vacher-Lavenu MC, Pujade-Laurraine E, Savina A, Maillet D, Gillet G, Treilleux I, Rimokh R (January 2016). "DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: a GINECO Group study". Histopathology. 68 (2): 279–85. doi:10.1111/his.12747. PMID 26033501.
- ↑ Stewart CJ, Charles A, Foulkes WD (June 2016). "Gynecologic Manifestations of the DICER1 Syndrome". Surg Pathol Clin. 9 (2): 227–41. doi:10.1016/j.path.2016.01.002. PMID 27241106.
- ↑ Wang Y, Karnezis AN, Magrill J, Tessier-Cloutier B, Lum A, Senz J, Gilks CB, McCluggage WG, Huntsman DG, Kommoss F (August 2018). "DICER1 hot-spot mutations in ovarian gynandroblastoma". Histopathology. 73 (2): 306–313. doi:10.1111/his.13630. PMID 29660837.