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{{Short description|Cancer originating in or on the ovary}}{{Use dmy dates|date=September 2023}}{{cs1 config |name-list-style=vanc |display-authors=6}}









!Gene mutated!Mutation type!Subtype!Prevalence|AKT1|amplification||3%|AKT2|amplification/mutation||6%, 20%|ARID1A|point mutation|endometrioid and clear-cell||BECN1|deletion|||BRCA1|nonsense mutation|high-grade serous|5%|BRCA2|frameshift mutation|high-grade serous|3%|CCND1|amplification||4%|CCND2|upregulation||15%|CCNE1|amplification||20%|CDK12||high-grade serous||CTNNB1||clear-cell||DICER1|missense mutation (somatic)|nonepithelial|29%|DYNLRB1 (km23)| mutation||42%|ERBB2 (Her2/neu)|amplification/overexpression|mucinous and low-grade serous|30%|JAG1|amplification||2%|JAG2|amplification||3%|KRAS|amplification|mucinous and low-grade serous|11%|MAML1|amplification and point mutation||2%|MAML2|amplification and point mutation||4%|MAML3|amplification||2%|MLH1|||1%|NOTCH3|amplification and point mutation||11%|PIK3C3 (PI3K3)|amplification/mutation||12–20%|PIK3CA|amplification|endometrioid and clear-cell|18%|PPP2R1A||endometrioid and clear-cell||RB1|deletion (8%) and point mutation (2%)||10%|TGF-β|mutation/overexpression||12%|TP53|mutation/overexpression|high-grade serous|20–50%|TβRI|mutation||33%|TβRII|mutation||25%|USP36|overexpression||

factoids
name	Ovarian cancer| image = mucinous_lmp_ovarian_tumour_intermed_mag.jpg Micrograph of a mucinous ovarian carcinoma H&E stain>stained by H&E| field = Oncology, gynecology| symptoms = Early: vagueLater: bloating, pelvic pain, constipation, abdominal swelling, loss of appetite| complications = | onset = Usual age of diagnosis 63 years old| duration = | types = * Ovarian origin: sex-cord stromal tumor, germ cell tumor causes		JOURNAL = LANCET	ISSUE = 10053	DATE = OCTOBER 2016	PMC = 5388903, 10.1016/S0140-6736(16)31012-1, | image2 = }}Ovarian cancer is a cancerous tumor of an ovary.BOOK, Female genital tumours: WHO Classification of Tumours,publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/Female-Genital-Tumours-2020, 2020, WHO Classification of Tumours Editorial Board, International Agency for Research on Cancer, Lyon (France), 5th, 4, 978-92-832-4504-9, 1. Tumours of the ovary: introduction, 32–35, It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen.JOURNAL, Žilovič D, ÄŒiurlienÄ— R, SabaliauskaitÄ— R, JarmalaitÄ— S, Future Screening Prospects for Ovarian Cancer, Cancers, 13, 15, 3840, July 2021, 34359740, 8345180, 10.3390/cancers13153840, free, WEB, Basic Information About Ovarian Cancer {{!, CDC |url=https://www.cdc.gov/cancer/ovarian/basic_info/index.htm |website=www.cdc.gov |access-date=9 October 2022 |language=en-us |date=31 August 2022}} The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells.WEB, What is Ovarian Cancer {{!, Ovarian Tumors and Cysts |url=https://www.cancer.org/cancer/ovarian-cancer/about/what-is-ovarian-cancer.html |access-date=2 November 2022 |website=www.cancer.org |language=en}} When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body.WEB, Defining Cancer,www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer, National Cancer Institute, 10 June 2014, live,www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer," title="web.archive.org/web/20140625220940www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer,">web.archive.org/web/20140625220940www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer, 25 June 2014, 17 September 2007, When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses.JOURNAL, Ebell MH, Culp MB, Radke TJ, A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer, American Journal of Preventive Medicine, 50, 3, 384–394, March 2016, 26541098, 10.1016/j.amepre.2015.09.023, These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.BOOK, Ruddon RW, Cancer Biology, 2007, Oxford University Press, 978-0-19-517543-1, 223, 4th,books.google.com/books?id=PymZ1ORk0TcC&pg=PA223, live,web.archive.org/web/20150915231411/https://books.google.com/books?id=PymZ1ORk0TcC&pg=PA223, 15 September 2015, The risk of ovarian cancer increases with age. Most cases of ovarian cancer develop after menopause.WEB, Ovarian Cancer Risk Factors,www.cancer.org/cancer/ovarian-cancer/causes-risks-prevention/risk-factors.html, 2 November 2022, www.cancer.org, en, It is also more common in women who have ovulated more over their lifetime.BOOK, Armstrong DK, Goldman L, Schafer AI, Goldman-Cecil Medicine, 2020, Elsevier, Philadelphia, 978-0-323-55087-1, 1332–1335, 26th, 1,books.google.com/books?id=7pKqDwAAQBAJ&pg=PA1332, en, 189. Gynaecologic cancers: ovarian cancer, This includes those who have never had children, those who began ovulation at a younger age and those who reach menopause at an older age. Other risk factors include hormone therapy after menopause, fertility medication, and obesity.WEB, Ovarian Cancer Prevention,www.cancer.gov/cancertopics/pdq/prevention/ovarian/Patient/page1/AllPages, NCI, 1 July 2014, 6 December 2013, live,www.cancer.gov/cancertopics/pdq/prevention/ovarian/Patient/page1/AllPages," title="web.archive.org/web/20140706002700www.cancer.gov/cancertopics/pdq/prevention/ovarian/Patient/page1/AllPages,">web.archive.org/web/20140706002700www.cancer.gov/cancertopics/pdq/prevention/ovarian/Patient/page1/AllPages, 6 July 2014, WEB, Ovarian Cancer Prevention,www.cancer.gov/cancertopics/pdq/prevention/ovarian/HealthProfessional/page1/AllPages, NCI, 1 July 2014, 20 June 2014, live,www.cancer.gov/cancertopics/pdq/prevention/ovarian/HealthProfessional/page1/AllPages," title="web.archive.org/web/20140706002711www.cancer.gov/cancertopics/pdq/prevention/ovarian/HealthProfessional/page1/AllPages,">web.archive.org/web/20140706002711www.cancer.gov/cancertopics/pdq/prevention/ovarian/HealthProfessional/page1/AllPages, 6 July 2014, Factors that decrease risk include hormonal birth control, tubal ligation, pregnancy, and breast feeding. About 10% of cases are related to inherited genetic risk; women with mutations in the genes BRCA1 or BRCA2 have about a 50% chance of developing the disease. Some family cancer syndromes such as hereditary nonpolyposis colon cancer and Peutz-Jeghers syndrome also increase the risk of developing ovarian cancer. Epithelial ovarian carcinoma is the most common type of ovarian cancer, comprising more than 95% of cases. There are five main subtypes of ovarian carcinoma, of which high-grade serous carcinoma (HGSC) is the most common. Less common types of ovarian cancer include germ cell tumorsJOURNAL, Maoz A, Matsuo K, Ciccone MA, Matsuzaki S, Klar M, Roman LD, Sood AK, Gershenson DM, Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review, Cancers, 12, 6, 1398, May 2020, 32485873, 7353025, 10.3390/cancers12061398, free, and sex cord stromal tumors. A diagnosis of ovarian cancer is confirmed through a biopsy of tissue, usually removed during surgery.Screening is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks.JOURNAL, Grossman DC, Curry SJ, Owens DK, Barry MJ, Davidson KW, Doubeni CA, Epling JW, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW, Screening for Ovarian Cancer: US Preventive Services Task Force Recommendation Statement, JAMA, 319, 6, 588–594, February 2018, 29450531, 10.1001/jama.2017.21926, free, Those at very high risk may have their ovaries removed as a preventive measure. If caught and treated in an early stage, ovarian cancer is often curable. Treatment usually includes some combination of surgery, radiation therapy, and chemotherapy.WEB, Ovarian Epithelial Cancer Treatment,www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/Patient/page1/AllPages, NCI, 1 July 2014, 12 May 2014, live,www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/Patient/page1/AllPages," title="web.archive.org/web/20140705232951www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/Patient/page1/AllPages,">web.archive.org/web/20140705232951www.cancer.gov/cancertopics/pdq/treatment/ovarianepithelial/Patient/page1/AllPages, 5 July 2014, Outcomes depend on the extent of the disease, the subtype of cancer present, and other medical conditions.JOURNAL, Gibson SJ, Fleming GF, Temkin SM, Chase DM, The Application and Outcome of Standard of Care Treatment in Elderly Women with Ovarian Cancer: A Literature Review over the Last 10 Years, Frontiers in Oncology, 6, 63, 2016, 27047797, 4805611, 10.3389/fonc.2016.00063, free, The overall five-year survival rate in the United States is 49%.WEB, SEER Stat Fact Sheets: Ovary Cancer,seer.cancer.gov/statfacts/html/ovary.html, NCI, 18 June 2014, live,seer.cancer.gov/statfacts/html/ovary.html," title="web.archive.org/web/20140706145616seer.cancer.gov/statfacts/html/ovary.html,">web.archive.org/web/20140706145616seer.cancer.gov/statfacts/html/ovary.html, 6 July 2014, Outcomes are worse in the developing world.In 2020, new cases occurred in approximately 313,000 women.WEB, Ovarian cancer statistics {{!, World Cancer Research Fund International |url=https://www.wcrf.org/cancer-trends/ovarian-cancer-statistics/ |access-date=2 November 2022 |website=WCRF International |language=en-US}} In 2019 it resulted in 13,445 deaths in the United States.WEB, USCS Data Visualizations,gis.cdc.gov/grasp/USCS/DataViz.html, 3 November 2022, gis.cdc.gov, en, 25 January 2019,web.archive.org/web/20190125223636/https://gis.cdc.gov/grasp/USCS/DataViz.html, dead, Death from ovarian cancer increased globally between 1990 and 2017 by 84.2%.Zhou Z, Wang X, Ren X, Zhou L, Wang N, Kang H. Disease Burden and Attributable Risk Factors of Ovarian Cancer From 1990 to 2017: Findings From the Global Burden of Disease Study 2017. Front Public Health. 2021 Sep 17;9:619581. doi: 10.3389/fpubh.2021.619581. PMID 34604147; PMCID: PMC8484795. Ovarian cancer is the second-most common gynecologic cancer in the United States. It causes more deaths than any other cancer of the female reproductive system.WEB, 18 May 2022, Ovarian Cancer Statistics {{!, CDC |url=https://www.cdc.gov/cancer/ovarian/statistics/index.htm |access-date=2 November 2022 |website=www.cdc.gov |language=en-us}} Among women it ranks fifth in cancer-related deaths.WEB, Ovarian Cancer Statistics {{!, How Common is Ovarian Cancer |url=https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html |access-date=2 November 2022 |website=www.cancer.org |language=en}} The typical age of diagnosis is 63.WEB, What are the risk factors for ovarian cancer?,www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors, www.cancer.org, 18 May 2016, 4 February 2016, live,www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors," title="web.archive.org/web/20160517173135www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors,">web.archive.org/web/20160517173135www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors, 17 May 2016, Death from ovarian cancer is more common in North America and Europe than in Africa and Asia.BOOK, World Cancer Report 2014, 2014, World Health Organization, 978-92-832-0429-9, Chapter 5.12,publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014, live,publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014," title="web.archive.org/web/20160919073553publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014,">web.archive.org/web/20160919073553publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014, 19 September 2016, In the United States, it is more common in White and Hispanic women than Black or American Indian women. {{TOC limit|3}} Signs and symptoms Early symptoms (File:Site of ovarian cancer.png|thumb|upright=1.3|Site of ovarian cancer)Early signs and symptoms of ovarian cancer may be absent or subtle. In most cases, symptoms exist for several months before being recognized and diagnosed.WEB,www.cdc.gov/cancer/ovarian/pdf/ovarian_facts.pdf, Ovarian Cancer, Inside Knowledge, Get the Facts about Gynecological Cancer, September 2016, Centers for Disease Control and Prevention, 17 June 2017, live,web.archive.org/web/20170616220028/https://www.cdc.gov/cancer/ovarian/pdf/ovarian_facts.pdf, 16 June 2017, {{CDC}} Symptoms can often be misdiagnosed as irritable bowel syndrome.JOURNAL, Jayson GC, Kohn EC, Kitchener HC, Ledermann JA, Ovarian cancer, Lancet, 384, 9951, 1376–1388, October 2014, 24767708, 10.1016/S0140-6736(13)62146-7, 205971030, The early stages of ovarian cancer tend to be painless which makes it difficult to detect it early on. Symptoms can vary based on the subtype. Ovarian borderline tumors, also known as low malignant potential (LMP) ovarian tumors, do not cause an increase in CA125 levels and are not identifiable with an ultrasound. The typical symptoms of an LMP tumor can include abdominal distension or pelvic pain. Particularly large masses tend to be benign or borderline.The most typical symptoms of ovarian cancer include bloating, abdominal or pelvic pain or discomfort, back pain, irregular menstruation or postmenopausal vaginal bleeding, pain or bleeding after or during sexual intercourse, loss of appetite, fatigue, diarrhea, indigestion, heartburn, constipation, nausea, feeling full, and possibly urinary symptoms (including frequent urination and urgent urination). Later symptoms (File:Mature cystic teratoma of ovary.jpg|thumb|Mature cystic teratoma of ovary)Later symptoms of ovarian cancer are due to the growing mass causing pain by pressing on other abdominopelvic organs or from metastases.WEB,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/ovarian-cancer-symptoms, Ovarian cancer symptoms, www.cancerresearchuk.org, 16 May 2015, live,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/ovarian-cancer-symptoms," title="web.archive.org/web/20150512172659www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/ovarian-cancer-symptoms,">web.archive.org/web/20150512172659www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/ovarian-cancer-symptoms, 12 May 2015, WEB, 18 June 2015, Ovarian cancer,www.dynamed.com/topics/dmp~AN~T900705/Ovarian-cancer, subscription, live,www.dynamed.com/topics/dmp~AN~T900705/Ovarian-cancer," title="web.archive.org/web/20150621210904www.dynamed.com/topics/dmp~AN~T900705/Ovarian-cancer,">web.archive.org/web/20150621210904www.dynamed.com/topics/dmp~AN~T900705/Ovarian-cancer, 21 June 2015, DynaMed, Because of the anatomic location of the ovaries deep in the pelvis, most masses are large and advanced at the time of diagnosis.Ebell MH, Culp MB, Radke TJ. A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer. Am J Prev Med. 2016 Mar;50(3):384-394. doi: 10.1016/j.amepre.2015.09.023. Epub 2015 Nov 2. PMID 26541098. The growing mass may cause pain if ovarian torsion develops. If these symptoms start to occur more often or more severely than usual, especially after no significant history of such symptoms, ovarian cancer is considered. Metastases may cause a Sister Mary Joseph nodule. Rarely, teratomas can cause growing teratoma syndrome or peritoneal gliomatosis. Some experience menometrorrhagia and abnormal vaginal bleeding after menopause in most cases. Other common symptoms include hirsutism, abdominal pain, virilization, and an adnexal mass. Children In adolescents or children with ovarian tumors, symptoms can include severe abdominal pain, irritation of the peritoneum, or bleeding. Sex cord stromal tumors produce hormones which can lead to the premature development of secondary sex characteristics. Sex cord-stromal tumors in prepubertal children may be manifested by signs of early puberty; abdominal pain and distension are also common. Adolescents with sex cord-stromal tumors may experience amenorrhea. As the cancer becomes more advanced, it can cause an accumulation of fluid in the abdomen and lead to distension. If the malignancy has not been diagnosed by the time it causes ascites, it is typically diagnosed shortly thereafter. Advanced cancers can also cause abdominal masses, lymph node masses, or pleural effusion. Risk factors There are many known risk factors that may increase a woman’s risk of developing ovarian cancer. The risk of developing ovarian cancer is related to the amount of time a woman spends ovulating. Factors that increase the number of ovulatory cycles a woman undergoes may increase the risk of developing ovarian cancer. During ovulation, cells are stimulated to divide. If this division is abnormally regulated, tumors may form which can be malignant. Early menarche and late menopause increase the number of ovulatory cycles a woman undergoes in her lifetime and so increases the risk of developing ovarian cancer.JOURNAL, Gong TT, Wu QJ, Vogtmann E, Lin B, Wang YL, Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies, International Journal of Cancer, 132, 12, 2894–2900, June 2013, 23175139, 3806278, 10.1002/ijc.27952, Since ovulation is suppressed during pregnancy, not having children also increases the risk of ovarian cancer. Therefore, women who have not borne children are at twice the risk of ovarian cancer than those who have. Both obesity and hormone replacement therapy also raise the risk.The risk of developing ovarian cancer is less for women who have fewer menstrual cycles, no menstrual cycles, breast feeding, take oral contraceptives, have multiple pregnancies, and have a pregnancy at an early age. The risk of developing ovarian cancer is reduced in women who have had tubal ligation (colloquially known as having one’s “tubes tied“), both ovaries removed, or hysterectomy (an operation in which the uterus is removed). Age is also a risk factor. Non-genetic factors such as diabetes mellitus, high body mass index, tobacco, and alcohol use are also risk factors for ovarian cancer. Hormones The use of fertility medication may contribute to ovarian borderline tumor formation, but the link between the two is disputed and difficult to study. Fertility drugs may be associated with a higher risk of borderline tumors. Those who have been treated for infertility but remain nulliparous are at higher risk for epithelial ovarian cancer due to hormonal exposure that may lead to proliferation of cells. However, those who are successfully treated for infertility and subsequently give birth are at no higher risk. This may be due to shedding of precancerous cells during pregnancy, but the cause remains unclear. The risk factor may instead be infertility itself, not the treatment.Hormonal conditions such as polycystic ovary syndrome and endometriosis are associated with ovarian cancer, but the link is not completely confirmed. Postmenopausal hormone replacement therapy (HRT) with estrogen likely increases the risk of ovarian cancer. The association has not been confirmed in a large-scale study,BOOK, Manson JE, Bassuk SS, The Menopause Transition and Postmenopausal Hormone Therapy, Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser SL, Loscalzo J, Harrison’s Principles of Internal Medicine, McGraw-Hill, 2012, 18th, 978-0-07-174889-6, Harrison’s Principles of Internal Medicine, but notable studies including the Million Women Study have supported this link. Postmenopausal HRT with combined estrogen and progesterone may increase contemporaneous risk if used for over 5 years, but this risk returns to normal after cessation of therapy. Estrogen HRT with or without progestins increases the risk of endometrioid and serous tumors but lowers the risk of mucinous tumors. Higher doses of estrogen increase this risk. Endometriosis is another risk factor for ovarian cancer, as is pain with menstruation. Endometriosis is associated with clear-cell and endometrioid subtypes, low-grade serous tumors, stage I and II tumors, grade 1 tumors, and lower mortality.Before menopause, obesity can increase a person’s risk of ovarian cancer, but this risk is not present after menopause. This risk is also relevant in those who are both obese and have never used HRT. A similar association with ovarian cancer appears in taller women. Genetics {{Further|Hereditary breast–ovarian cancer syndrome}}(File:PedigreechartC.png|upright=1.3|thumb|Women with ovarian or breast cancer in a pedigree chart of a family)A family history of ovarian cancer is a risk factor for ovarian cancer. Women with hereditary nonpolyposis colon cancer (Lynch syndrome), and those with BRCA-1 and BRCA-2 genetic abnormalities are at increased risk.The major genetic risk factor for ovarian cancer is a mutation in BRCA1 or BRCA2 genes, or in DNA mismatch repair genes, which is present in 10% of ovarian cancer cases. Only one allele needs to be mutated to place a person at high risk. The gene can be inherited through either the maternal or paternal line, but has variable penetrance. Though mutations in these genes are usually associated with increased risk of breast cancer, they also carry a substantial lifetime risk of ovarian cancer, a risk that peaks in a person’s 40s and 50s. The lowest risk cited is 30% and the highest 60%. Mutations in BRCA1 have a lifetime risk of developing ovarian cancer of 15–45%. Mutations in BRCA2 are less risky than those with BRCA1, with a lifetime risk of 10% (lowest risk cited) to 40% (highest risk cited). On average, BRCA-associated cancers develop 15 years before their sporadic counterparts because people who inherit the mutations on one copy of their gene only need one mutation to start the process of carcinogenesis, whereas people with two normal genes would need to acquire two mutations.In the United States, five of 100 women with a first-degree relative with ovarian cancer will eventually get ovarian cancer themselves, placing those with affected family members at triple the risk of women with unaffected family members. Seven of 100 women with two or more relatives with ovarian cancer will eventually get ovarian cancer.WEB,www.cancer.gov/cancertopics/pdq/prevention/ovarian/healthprofessional, Ovarian Cancer Prevention (PDQ®), National Cancer Institute, 2013, 30 December 2013, live,www.cancer.gov/cancertopics/pdq/prevention/ovarian/healthprofessional," title="web.archive.org/web/20131231100136www.cancer.gov/cancertopics/pdq/prevention/ovarian/healthprofessional,">web.archive.org/web/20131231100136www.cancer.gov/cancertopics/pdq/prevention/ovarian/healthprofessional, 31 December 2013, In general, 5–10% of ovarian cancer cases have a genetic cause. BRCA mutations are associated with high-grade serous nonmucinous epithelial ovarian cancer.(File:BRCA1 and BRCA2 mutations and absolute cancer risk.jpg|thumb|BRCA1 and BRCA2 mutations and absolute cancer risk)A strong family history of endometrial cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (also known as Lynch syndrome), which confers a higher risk for developing a number of cancers, including ovarian cancer. Lynch syndrome is caused by mutations in mismatch repair genes, including MSH2, MLH1, MLH6, PMS1, and PMS2. The risk of ovarian cancer for an individual with Lynch syndrome is between 10 and 12 percent. Women of Icelandic descent, European Jewish descent/Ashkenazi Jewish descent, and Hungarian descent are at higher risk for epithelial ovarian cancer. Estrogen receptor beta gene (ESR2) seems to be a key to pathogenesis and response to therapy.JOURNAL, Kyriakidis I, Papaioannidou P, Estrogen receptor beta and ovarian cancer: a key to pathogenesis and response to therapy, Archives of Gynecology and Obstetrics, 293, 6, 1161–1168, June 2016, 26861465, 10.1007/s00404-016-4027-8, 25627227, Other genes that have been associated with ovarian cancer are BRIP1, MSH6, RAD51C and RAD51D.JOURNAL, Norquist BM, Harrell MI, Brady MF, Walsh T, Lee MK, Gulsuner S, Bernards SS, Casadei S, Yi Q, Burger RA, Chan JK, Davidson SA, Mannel RS, DiSilvestro PA, Lankes HA, Ramirez NC, King MC, Swisher EM, Birrer MJ, Inherited Mutations in Women With Ovarian Carcinoma, JAMA Oncology, 2, 4, 482–490, April 2016, 26720728, 4845939, 10.1001/jamaoncol.2015.5495, CDH1, CHEK2, PALB2 and RAD50 have also been associated with ovarian cancer.JOURNAL, Kuusisto KM, Bebel A, Vihinen M, Schleutker J, Sallinen SL, Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals, Breast Cancer Research, 13, 1, R20, February 2011, 21356067, 3109589, 10.1186/bcr2832, free, Several rare genetic disorders are associated with specific subtypes of ovarian cancer. Peutz–Jeghers syndrome, a rare genetic disorder, also predisposes women to sex cord tumour with annular tubules. Ollier disease and Maffucci syndrome are associated with granulosa cell tumors in children and may also be associated with Sertoli-Leydig tumors. Benign fibromas are associated with nevoid basal cell carcinoma syndrome. Diet Alcohol consumption does not appear to be related to ovarian cancer.JOURNAL, HjartÃ¥ker A, Meo MS, Weiderpass E, Alcohol and gynecological cancers: an overview, European Journal of Cancer Prevention, 19, 1, 1–10, January 2010, 19926999, 10.1097/CEJ.0b013e328333fb3a, 27570587, The American Cancer Society recommends a healthy eating pattern that includes plenty of fruits, vegetables, whole grains, and a diet that avoids or limits red and processed meats and processed sugar.“Ovarian Cancer Risk Factors”. cancer.org. Retrieved 2 January 2021. High consumption of total, saturated and trans-fats increases ovarian cancer risk.JOURNAL, Qiu W, Lu H, Qi Y, Wang X, Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies, Oncotarget, 7, 24, 37390–37406, June 2016, 27119509, 5095084, 10.18632/oncotarget.8940, A 2021 umbrella review found that coffee, egg, and fat intake significantly increases the risk of ovarian cancer.JOURNAL, Tanha K, Mottaghi A, Nojomi M, Moradi M, Rajabzadeh R, Lotfi S, Janani L, Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses, Journal of Ovarian Research, 14, 1, 153, November 2021, 34758846, 8582179, 10.1186/s13048-021-00911-z, free, There is mixed evidence from studies on ovarian cancer risk and consumption of dairy products.JOURNAL, Liao MQ, Gao XP, Yu XX, Zeng YF, Li SN, Naicker N, Joseph T, Cao WT, Liu YH, Zhu S, Chen QS, Yang ZC, Zeng FF, Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies, The British Journal of Nutrition, 124, 10, 1001–1012, November 2020, 32189606, 10.1017/S0007114520001075, 213181277, JOURNAL, Sun H, Gong TT, Xia Y, Wen ZY, Zhao LG, Zhao YH, Wu QJ, Diet and ovarian cancer risk: An umbrella review of systematic reviews and meta-analyses of cohort studies, Clinical Nutrition, 40, 4, 1682–1690, April 2021, 33308841, 10.1016/j.clnu.2020.11.032, 229175041, Environmental factors Industrialized nations, with the exception of Japan, have high rates of epithelial ovarian cancer, which may be due to diet in those countries. White women are at a 30–40% higher risk for ovarian cancer when compared to Black women and Hispanic women, likely due to socioeconomic factors; white women tend to have fewer children and different rates of gynecologic surgeries that affect risk for ovarian cancer.Tentative evidence suggests that talc, pesticides, and herbicides increase the risk of ovarian cancer.JOURNAL, Salehi F, Dunfield L, Phillips KP, Krewski D, Vanderhyden BC, Risk factors for ovarian cancer: an overview with emphasis on hormonal factors, Journal of Toxicology and Environmental Health Part B: Critical Reviews, 11, 3–4, 301–321, March 2008, 18368558, 10.1080/10937400701876095, 2008JTEHB..11..301S, 5589506, The American Cancer Society notes that as of now, no study has been able to accurately link any single chemical in the environment, or in the human diet, directly to mutations that cause ovarian cancer.WEB, Do we know what causes ovarian cancer?,www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes, www.cancer.org, live,www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes," title="web.archive.org/web/20161110052501www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes,">web.archive.org/web/20161110052501www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes, 10 November 2016, Other Other factors that have been investigated, such as smoking, low levels of vitamin D in the blood,JOURNAL, Zhang X, Nicosia SV, Bai W, Vitamin D receptor is a novel drug target for ovarian cancer treatment, Current Cancer Drug Targets, 6, 3, 229–244, May 2006, 16712459, 10.2174/156800906776842939, presence of inclusion ovarian cysts, and infection with human papilloma virus (the cause of some cases of cervical cancer), have been disproven as risk factors for ovarian cancer. The carcinogenicity of perineal talc is controversial, because it can act as an irritant if it travels through the reproductive tract to the ovaries. Case-control studies have shown that use of perineal talc does increase the risk of ovarian cancer, but using talc more often does not create a greater risk. Use of talc elsewhere on the body is unrelated to ovarian cancer. Sitting regularly for prolonged periods is associated with higher mortality from epithelial ovarian cancer. The risk is not negated by regular exercise, though it is lowered.JOURNAL, Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA, Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis, Annals of Internal Medicine, 162, 2, 123–132, January 2015, 25599350, 10.7326/M14-1651, 7256176, Increased age (up to the 70s) is a risk factor for epithelial ovarian cancer because more mutations in cells can accumulate and eventually cause cancer. Those over 80 are at slightly lower risk.Smoking tobacco is associated with a higher risk of mucinous ovarian cancer; after smoking cessation, the risk eventually returns to normal. Higher levels of C-reactive protein are associated with a higher risk of developing ovarian cancer. Protective factors Suppression of ovulation, which would otherwise cause damage to the ovarian epithelium and, consequently, inflammation, is generally protective. This effect can be achieved by having children, taking combined oral contraceptives, and breast feeding, all of which are protective factors. A longer period of breastfeeding correlates with a larger decrease in the risk of ovarian cancer. Each birth decreases risk of ovarian cancer more, and this effect is seen with up to five births. Combined oral contraceptives reduce the risk of ovarian cancer by up to 50%, and the protective effect of combined oral contraceptives can last 25–30 years after they are discontinued. Regular use of aspirin (MALOVA (MALignant OVArian cancer) study)NEWS, Aspirin Lowers Aggressive Form of Ovarian Cancer,www.ibtimes.co.uk/aspirin-lowers-aggressive-form-ovarian-cancer-393165, International Business Times UK, 11 October 2012, en, WEB, Aspirin May Decrease Risk of Aggressive Form of Ovarian Cancer,www.wiley.com/WileyCDA/PressRelease/pressReleaseId-105580.html, www.wiley.com, Wiley, 29 April 2024, or acetaminophen (paracetamol) may be associated with a lower risk of ovarian cancer; other NSAIDs do not seem to have a similar protective effect.Tubal ligation is protective because carcinogens are unable to reach the ovary and fimbriae via the vagina, uterus, and Fallopian tubes. Tubal ligation is also protective in women with the BRCA1 mutation, but not the BRCA2 mutation. Hysterectomy reduces the risk, and removal of both Fallopian tubes and ovaries (bilateral salpingo-oophorectomy) dramatically reduces the risk of not only ovarian cancer but breast cancer as well. This is still a topic of research, as the link between hysterectomy and lower ovarian cancer risk is controversial. The reasons that hysterectomy may be protective have not been elucidated as of 2015.A diet that includes large amounts of carotene, fiber, and vitamins with low amounts of fat—specifically, a diet with non-starchy vegetables (e.g. broccoli and onions) may be protective. Dietary fiber is associated with a significant reduced risk of ovarian cancer.JOURNAL, Zheng B, Shen H, Han H, Han T, Qin Y, Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis, Nutrition Journal, 17, 1, 99, October 2018, 30376840, 6208085, 10.1186/s12937-018-0407-1, free, A 2021 review found that green leafy vegetables, allium vegetables, fiber, flavanoids and green tea intake can significantly reduce ovarian cancer risk.JOURNAL, Khodavandi A, Alizadeh F, Razis AF, Association between dietary intake and risk of ovarian cancer: a systematic review and meta-analysis, European Journal of Nutrition, 60, 4, 1707–1736, June 2021, 32661683, 10.1007/s00394-020-02332-y, 220505663, Pathophysiology {| class“wikitable sortable” align“right” style@width: 50%”
BRAF (gene)>BRAF|point mutation|low-grade serous|0.5%
P16 (gene)>CDKN2A|downregulation (30%) and deletion (2%)||32%
Epidermal growth factor receptor>EGFR|amplification/overexpression||20%
FMS (gene)>FMS|coexpression with CSF-1||50%
Forkhead box L2>FOXL2|point mutation (402 C to G)|adult granulosa cell|~100%
nuclear factor 1>NF1|deletion (8%) and point mutation (4%)|high-grade serous|12%
Neuroblastoma RAS viral oncogene homolog>NRAS||low-grade serous|
PTEN (gene)>PTEN|deletion|endometrioid and clear-cell|7%

Ovarian cancer forms when errors in normal ovarian cell growth occur. Usually, when cells grow old or get damaged, they die, and new cells take their place. Cancer starts when new cells form unneeded, and old or damaged cells do not die as they should. The buildup of extra cells often forms a mass of tissue called an ovarian tumor or growth. These abnormal cancer cells have many genetic abnormalities that cause them to grow excessively.WEB,www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional, Genetics of Breast and Ovarian Cancer (PDQ®), 2 October 2014, 27 October 2014, National Cancer Institute, live,www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional," title="web.archive.org/web/20141022060353www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional,">web.archive.org/web/20141022060353www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional, 22 October 2014, When an ovary releases an egg, the egg follicle bursts open and becomes the corpus luteum. This structure needs to be repaired by dividing cells in the ovary. Continuous ovulation for a long time means more repair of the ovary by dividing cells, which can acquire mutations in each division.Overall, the most common gene mutations in ovarian cancer occur in NF1, BRCA1, BRCA2, and CDK12. Type I ovarian cancers, which tend to be less aggressive, tend to have microsatellite instability in several genes, including both oncogenes (most notably BRAF and KRAS) and tumor suppressors (most notably PTEN). The most common mutations in Type I cancers are KRAS, BRAF, ERBB2, PTEN, PIK3CA, and ARID1A. Type II cancers, the more aggressive type, have different genes mutated, including p53, BRCA1, and BRCA2. Low-grade cancers tend to have mutations in KRAS, whereas cancers of any grade that develop from low malignant potential tumors tend to have mutations in p53. Type I cancers tend to develop from precursor lesions, whereas Type II cancers can develop from a serous tubal intraepithelial carcinoma. Serous cancers that have BRCA mutations also inevitably have p53 mutations, indicating that the removal of both functional genes is important for cancer to develop.In 50% of high-grade serous cancers, homologous recombination DNA repair is dysfunctional, as are the notch and FOXM1 signaling pathways. They also almost always have p53 mutations. Other than this, mutations in high-grade serous carcinoma are hard to characterize beyond their high degree of genomic instability. BRCA1 and BRCA2 are essential for homologous recombination DNA repair, and germline mutations in these genes are found in about 15% of women with ovarian cancer. The most common mutations in BRCA1 and BRCA2 are the frameshift mutations that originated in a small founding population of Ashkenazi Jews.Almost 100% of rare mucinous carcinomas have mutations in KRAS and amplifications of ERBB2 (also known as Her2/neu). Overall, 20% of ovarian cancers have mutations in Her2/neu.Serous carcinomas may develop from serous tubal intraepithelial carcinoma, rather than developing spontaneously from ovarian tissue. Other carcinomas develop from cortical inclusion cysts, which are groups of epithelial ovarian cells inside the stroma.

Diagnosis

Examination

(File:POvarianCA.png|thumb|upright=1.3|A very large ovarian cancer as seen on CT)File:Serous carcinoma cytology.jpg|thumb|Micrograph of serous carcinoma, a type of ovarian cancer, diagnosed in peritoneal fluidperitoneal fluidDiagnosis of ovarian cancer starts with a physical examination (including a pelvic examination), a blood test (for CA-125 and sometimes other markers), and transvaginal ultrasound.WEB, Can Ovarian Cancer Be Found Early?, American Cancer Society,www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/detection.html, Sometimes a rectovaginal examination is used to help plan a surgery. The diagnosis must be confirmed with surgery to inspect the abdominal cavity, take biopsies (tissue samples for microscopic analysis), and look for cancer cells in the abdominal fluid. This helps to determine if an ovarian mass is benign or malignant.Ovarian cancer’s early stages (I/II) are difficult to diagnose because most symptoms are nonspecific and thus of little use in diagnosis; as a result, it is rarely diagnosed until it spreads and advances to later stages (III/IV).JOURNAL, Rossing MA, Wicklund KG, Cushing-Haugen KL, Weiss NS, Predictive value of symptoms for early detection of ovarian cancer, Journal of the National Cancer Institute, 102, 4, 222–229, February 2010, 20110551, 2826180, 10.1093/jnci/djp500, Additionally, symptoms of ovarian cancer may appear similar to irritable bowel syndrome. In women in whom pregnancy is a possibility, BHCG level can be measured during the diagnosis process. Serum alpha-fetoprotein, neuron-specific enolase, and lactate dehydrogenase can be measured in young girls and adolescents with suspected ovarian tumors as younger women with ovarian cancer are more likely to have malignant germ cell tumors.A physical examination, including a pelvic examination, and a pelvic ultrasound (transvaginal or otherwise) are both essential for diagnosis: physical examination may reveal increased abdominal girth and/or ascites (fluid within the abdominal cavity), while pelvic examination may reveal an ovarian or abdominal mass. An adnexal mass is a significant finding that often indicates ovarian cancer, especially if it is fixed, nodular, irregular, solid, and/or bilateral. 13–21% of adnexal masses are caused by malignancy; however, there are other benign causes of adnexal masses, including ovarian follicular cyst, leiomyoma, endometriosis, ectopic pregnancy, hydrosalpinx, tuboovarian abscess, ovarian torsion, dermoid cyst, cystadenoma (serous or mucinous), diverticular or appendiceal abscess, nerve sheath tumor, pelvic kidney, ureteral or bladder diverticulum, benign cystic mesothelioma of the peritoneum, peritoneal tuberculosis, or paraovarian cyst. Ovaries that can be felt are also a sign of ovarian cancer in postmenopausal women. Other parts of a physical examination for suspected ovarian cancer can include a breast examination and a digital rectal exam. Palpation of the supraclavicular, axillary, and inguinal lymph nodes may reveal lymphadenopathy, which can be indicative of metastasis. Another indicator may be the presence of a pleural effusion, which can be noted on auscultation.When an ovarian malignancy is included in a list of diagnostic possibilities, a limited number of laboratory tests are indicated. A complete blood count and serum electrolyte test is usually obtained; when an ovarian cancer is present, these tests often show a high number of platelets (20–25% of patients) and low blood sodium levels due to chemical signals secreted by the tumor. A positive test for inhibin A and inhibin B can indicate a granulosa cell tumor.A blood test for a marker molecule called CA-125 is useful in differential diagnosis and in follow up of the disease, but it by itself has not been shown to be an effective method to screen for early-stage ovarian cancer due to its unacceptable low sensitivity and specificity. CA-125 levels in premenopausal women over 200 U/mL may indicate ovarian cancer, as may any elevation in CA-125 above 35 U/mL in post-menopausal women. CA-125 levels are not accurate in early stage ovarian cancer, as half of stage I ovarian cancer patients have a normal CA-125 level. CA-125 may also be elevated in benign (non-cancerous) conditions, including endometriosis, pregnancy, uterine fibroids, menstruation, ovarian cysts, systemic lupus erythematosus, liver disease, inflammatory bowel disease, pelvic inflammatory disease, and leiomyoma.WEB, Ovarian cancer tests,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/diagnosis/ovarian-cancer-tests, www.cancerresearchuk.org, 16 May 2015, live,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/diagnosis/ovarian-cancer-tests," title="web.archive.org/web/20150518091201www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/diagnosis/ovarian-cancer-tests,">web.archive.org/web/20150518091201www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/diagnosis/ovarian-cancer-tests, 18 May 2015, HE4 is another candidate for ovarian cancer testing, though it has not been extensively tested. Other tumor markers for ovarian cancer include CA19-9, CA72-4, CA15-3, immunosuppressive acidic protein, haptoglobin-alpha, OVX1, mesothelin, lysophosphatidic acid, osteopontin, and fibroblast growth factor 23.Use of blood test panels may help in diagnosis.JOURNAL, Miller RW, Ueland FR, Risk of malignancy in sonographically confirmed ovarian tumors, Clinical Obstetrics and Gynecology, 55, 1, 52–64, March 2012, 22343229, 10.1097/GRF.0b013e31824970cf, The OVA1 panel includes CA-125, beta-2 microglobulin, transferrin, apolipoprotein A1, and transthyretin. OVA1 above 5.0 in premenopausal women and 4.4 in postmenopausal women indicates a high risk for cancer. A different set of laboratory tests is used for detecting sex cord-stromal tumors. High levels of testosterone or dehydroepiandrosterone sulfate, combined with other symptoms and high levels of inhibin A and inhibin B can be indicative of an SCST of any type.Current research is looking at ways to consider tumor marker proteomics in combination with other indicators of disease (i.e. radiology and/or symptoms) to improve diagnostic accuracy. The challenge in such an approach is that the disparate prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results, which in turn may lead to issues such as performing surgical procedures in which cancer is not found intraoperatively.{{citation needed|date=March 2018}} Genomics approaches have not yet been developed for ovarian cancer.CT scanning is preferred to assess the extent of the tumor in the abdominopelvic cavity, though magnetic resonance imaging can also be used. CT scanning can also be useful for finding omental caking or differentiating fluid from solid tumor in the abdomen, especially in low malignant potential tumors. However, it may not detect smaller tumors. Sometimes, a chest x-ray is used to detect metastases in the chest or pleural effusion. Another test for metastatic disease, though it is infrequently used, is a barium enema, which can show if the rectosigmoid colon is involved in the disease. Positron emission tomography, bone scans, and paracentesis are of limited use; in fact, paracentesis can cause metastases to form at the needle insertion site and may not provide useful results. However, paracentesis can be used in cases where there is no pelvic mass and ascites is still present. A physician suspecting ovarian cancer may also perform mammography or an endometrial biopsy (in the case of abnormal bleeding) to assess the possibility of breast malignancies and endometrial malignancy, respectively. Vaginal ultrasonography is often the first-line imaging study performed when an adnexal mass is found. Several characteristics of an adnexal mass indicate ovarian malignancy; they usually are solid, irregular, multilocular, and/or large; and they typically have papillary features, central vessels, and/or irregular internal septations. However, SCST has no definitive characteristics on radiographic study.To definitively diagnose ovarian cancer, a surgical procedure to inspect the abdomen is required. This can be an open procedure (laparotomy, incision through the abdominal wall) or keyhole surgery (laparoscopy). During this procedure, suspicious tissue is removed and sent for microscopic analysis. Usually, this includes a unilateral salpingo-oophorectomy, removal of a single affected ovary and Fallopian tube. Fluid from the abdominal cavity can also be analyzed for cancerous cells. If cancer is found, this procedure can also be used to determine the extent of its spread (which is a form of tumor staging).Pafolacianine is indicated for use in adults with ovarian cancer to help identify cancerous lesions during surgery. It is a diagnostic agent that is administered in the form of an intravenous injection prior to surgery.PRESS RELEASE, FDA Approves New Imaging Drug to Help Identify Ovarian Cancer Lesions, U.S. Food and Drug Administration (FDA), 29 November 2021,www.fda.gov/news-events/press-announcements/fda-approves-new-imaging-drug-help-identify-ovarian-cancer-lesions, 30 November 2021, {{PD-notice}}

Risk scoring

{{anchor | RMI}}A widely recognized method of estimating the risk of malignant ovarian cancer is the risk of malignancy index (RMI), calculated based on an initial workup.WEB,publications.nice.org.uk/ovarian-cancer-cg122/appendix-d-risk-of-malignancy-index-rmi-i, NICE clinical guidelines, April 2011, Guideline CG122. Ovarian cancer: The recognition and initial management of ovarian cancer, Appendix D: Risk of malignancy index (RMI I)., dead,publications.nice.org.uk/ovarian-cancer-cg122/appendix-d-risk-of-malignancy-index-rmi-i," title="web.archive.org/web/20130922075958publications.nice.org.uk/ovarian-cancer-cg122/appendix-d-risk-of-malignancy-index-rmi-i,">web.archive.org/web/20130922075958publications.nice.org.uk/ovarian-cancer-cg122/appendix-d-risk-of-malignancy-index-rmi-i, 22 September 2013, An RMI score of over 200 or 250 is generally felt to indicate high risk for ovarian cancer.The RMI is calculated as: Two methods can be used to determine the ultrasound score and menopausal score, with the resultant scores being referred to as RMI 1 and RMI 2, respectively, depending on what method is used.{| class=“wikitable”! style="width:32%;“| Feature! style="width:34%;“| RMI 1! style="width:34%;“| RMI 2JOURNAL, Geomini P, Kruitwagen R, Bremer GL, Cnossen J, Mol BW, The accuracy of risk scores in predicting ovarian malignancy: a systematic review, Obstetrics and Gynecology, 113, 2 Pt 1, 384–394, February 2009, 19155910, 10.1097/AOG.0b013e318195ad17, 24585101, | Ultrasound abnormalities:

• multilocular cyst
• solid areas
• ascites
• intra-abdominal metastases
• 0 {{={edih} no abnormality
• 1 {{=}} one abnormality
• 3 {{=}} two or more abnormalities }}

• 0 {{={edih} none
• 1 {{=}} one abnormality
• 4 {{=}} two or more abnormalities }}

| Menopausal score

• 1 {{={edih} premenopausal
• 3 {{=}} postmenopausal }}

• 1 {{={edih} premenopausal
• 4 {{=}} postmenopausal }}

| CA-125| Quantity in U/ml| Quantity in U/mlAnother method for quantifying risk of ovarian cancer is the Risk of Ovarian Cancer Algorithm (ROCA), which observes levels over time and determines if they are increasing rapidly enough to warrant transvaginal ultrasound. The Risk of Ovarian Malignancy algorithm uses CA-125 levels and HE4 levels to calculate the risk of ovarian cancer; it may be more effective than RMI. The IOTA models can be used to estimate the probability that an adnexal tumor is malignant.JOURNAL, Kaijser J, Bourne T, De Rijdt S, Van Holsbeke C, Sayasneh A, Valentin L, Van Calster B, Timmerman D, Key findings from the International Ovarian Tumor Analysis (IOTA) study: an approach to the optimal ultrasound based characterisation of adnexal pathology, Australasian Journal of Ultrasound in Medicine, 15, 3, 82–86, August 2012, 28191150, 5025098, 10.1002/j.2205-0140.2012.tb00011.x, They include LR2 risk model, The Simple Rules risk (SRrisk) calculation and Assessment of Different Neoplasias in the Adnexa (ADNEX) model that can be used to assess risk of malignancy in an adnexal mass, based on its characteristics and risk factors. The QCancer (Ovary) algorithm is used to predict likelihood of ovarian cancer from risk factors.

Pathology

(File:Incidence of ovarian cancers by histopathology.png|thumb|upright=1.3|Primary ovarian cancers in women aged 20+, with area representing relative incidence and color representing five-year relative survival rate)Ovarian cancers are classified according to the microscopic appearance of their structures (histology or histopathology). Histology dictates many aspects of clinical treatment, management, and prognosis. The gross pathology of ovarian cancers is very similar regardless of histologic type: ovarian tumors have solid and cystic masses. According to SEER, the types of ovarian cancers in women age 20 and over are:BOOK, Chapter 16: Cancers of the Ovary, Kosary CL, 133–144, National Cancer Institute, SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988–2001, Patient and Tumor Characteristics, Baguio RN, Young JL, Keel GE, Eisner MP, Lin YD, Horner MJ, NIH Pub. No. 07-6215, Bethesda, MD, 2007,seer.cancer.gov/publications/survival/surv_ovary.pdf,seer.cancer.gov/publications/survival/, live,seer.cancer.gov/publications/survival/," title="web.archive.org/web/20131010123756seer.cancer.gov/publications/survival/,">web.archive.org/web/20131010123756seer.cancer.gov/publications/survival/, 10 October 2013, {| class=“wikitable“! Percent of ovarian cancers in women age 20+!Percent of ovarian cancers in women age 20+ by subdivision! Histology! Five-yearRSR| 89.7|| Surface epithelial-stromal tumor (adenocarcinoma)| 54.4||26.4| Papillary serous cystadenocarcinoma| 21.0||15.9| Borderline adenocarcinoma (underestimated - short data collection interval)| 98.2||12.6| Adenocarcinoma, not otherwise specified| 18.3||9.8| Endometrioid tumor| 70.9||5.8| Serous cystadenocarcinoma| 44.2||5.5Papilloma>Papillary| 21.0||4.2| Mucinous cystadenocarcinoma| 77.7||4.0| Ovarian clear-cell carcinoma| 61.5||3.4| Mucinous adenocarcinoma| 49.1||1.3| Cystadenocarcinoma| 50.7| 5.5|| Carcinoma|||4.1| Carcinoma not otherwise specified| 26.8||1.1| Sex cord-stromal tumor| 87.8||0.3| Other carcinomas, specified| 37.3| 1.7|| Müllerian tumor| 29.8| 1.5|| Germ cell tumor| 91.0||0.8| Teratoma| 89.1||0.5| Dysgerminoma| 96.8||0.3| Other, specified| 85.1| 0.6|| Not otherwise specified| 23.0| 0.5|| Ovarian squamous cell carcinoma (Epidermoid)| 51.3| 0.2|| Brenner tumor| 67.9| 0.2|| Other, specified| 71.7Ovarian cancers are histologically and genetically divided into type I or type II. Type I cancers are of low histological grade and include endometrioid, mucinous, and clear-cell carcinomas. Type II cancers are of higher histological grade and include serous carcinoma and carcinosarcoma.

Epithelial carcinoma

(File:Ovarian carcinoma.JPG|thumb|upright=1.3|A pathological specimen of ovarian carcinoma)Epithelial ovarian cancer typically presents at an advanced stage and is derived from the malignant transformation of the epithelium of the ovarian surface, peritoneum, or fallopian tube.JOURNAL, Desai A, Xu J, Aysola K, Qin Y, Okoli C, Hariprasad R, Chinemerem U, Gates C, Reddy A, Danner O, Franklin G, Ngozi A, Cantuaria G, Singh K, Grizzle W, Landen C, Partridge EE, Rice VM, Reddy ES, Rao VN, Epithelial ovarian cancer: An overview, World Journal of Translational Medicine, 3, 1, 1–8, April 2014, 25525571, 4267287, 10.5528/wjtm.v3.i1.1, 19391874, free, It is the most common cause of gynecologic cancer death. There are various types of epithelial ovarian cancer, including serous tumor, endometrioid tumor, clear-cell tumor, mucinous tumor, and undifferentiated or unclassified tumors.WEB, Epithelial ovarian cancer {{!, Cancer Research UK |url=https://www.cancerresearchuk.org/about-cancer/ovarian-cancer/types/epithelial-ovarian-cancers/epithelial |access-date=8 November 2022 |website=www.cancerresearchuk.org}} Annually worldwide, 230,000 women will be diagnosed and 150,000 will die.JOURNAL, Lheureux S, Gourley C, Vergote I, Oza AM, Epithelial ovarian cancer, Lancet, 393, 10177, 1240–1253, March 2019, 30910306, 10.1016/S0140-6736(18)32552-2, 84846601, 20.500.11820/b4f4b3bf-bf1b-4074-8c62-7d30f1c8fb70,www.pure.ed.ac.uk/ws/files/76267579/complete.pdf, free, It has a 46% 5 year survival rate after diagnosis because of the advanced stage of the disease at the time of diagnosis. Typically, around 75% of patients are diagnosed as having an advanced stage of the disease because of the asymptomatic nature of its presentation. There is a genomic predisposition to epithelial ovarian cancer and the BRCA1 and BRCA2 genes have been found to be the causative genes in 65-75% of hereditary epithelial ovarian cancer.

Serous carcinoma

(File:Serous carcinoma (3061775966).jpg|thumb|Serous carcinoma of ovary)Serous ovarian cancer is the most common type of epithelial ovarian cancer and it accounts for about two-thirds of cases of epithelial ovarian cancer. Low-grade serous carcinoma is less aggressive than high-grade serous carcinomas, though it does not typically respond well to chemotherapy or hormonal treatments. Serous carcinomas are thought to begin in the Fallopian tube.WEB, Types of ovarian cancer,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/types-of-ovarian-cancer, live,www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/types-of-ovarian-cancer," title="web.archive.org/web/20150518091024www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/types-of-ovarian-cancer,">web.archive.org/web/20150518091024www.cancerresearchuk.org/about-cancer/type/ovarian-cancer/about/types-of-ovarian-cancer, 18 May 2015, 16 May 2015, www.cancerresearchuk.org, JOURNAL, Velle A, Pesenti C, Grassi T, Beltrame L, Martini P, Jaconi M, Agostinis F, Calura E, Katsaros D, Borella F, Fruscio R, D’Incalci M, Marchini S, Romualdi C, A comprehensive investigation of histotype-specific microRNA and their variants in Stage I epithelial ovarian cancers, International Journal of Cancer, 152, 9, 1989–2001, May 2023, 36541726, 10.1002/ijc.34408, 255034585, free, High grade serous carcinoma accounts for 75% of all epithelial ovarian cancer. About 15–20% of high grade serous carcinoma have germline BRCA1 and BRCA2 mutations. Histologically, the growth pattern of high grade serous carcinoma is heterogenous and has some papillary or solid growth patterns. The tumor cells are atypical with large, irregular nuclei. It has a high proliferation rate. 50% of the time, serous carcinomas are bilateral, and in 85% of cases, they have spread beyond the ovary at the time of diagnosis.Serous Tubal Intraepithelial Carcinoma (STIC) is now recognized to be the precursor lesion of most so-called ovarian high-grade serous carcinomas.BOOK, Gynecologic pathology : a volume in the series Foundations in diagnostic pathology, 978-0-323-35909-2, 946, Second, Nucci MR, 3 February 2020, Elsevier, STIC is characterised by

1. Abnormal p53 staining
2. Ki67 proliferation index in excess of 10%
3. Positive WT1 (to exclude metastases)

Small-cell carcinoma

(File:Small cell carcinoma of the ovary hypercalcemic type - high mag.jpg|thumb|Small cell carcinoma of the ovary, hypercalcemic subtype)Small-cell ovarian carcinoma is rare and aggressive, with two main subtypes: hypercalcemic and pulmonary.JOURNAL, Korivi BR, Javadi S, Faria S, Sagebiel T, Garg N, Patnana M, Prasad SR, Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Clinical and Imaging Review, Current Problems in Diagnostic Radiology, 47, 5, 333–339, September 2018, 28943050, 10.1067/j.cpradiol.2017.08.004, 41153959, This rare malignancy most commonly affects young women under the age of 40 years old with a range between 14 months and 58 years. The mean age of diagnosis of 24 years. Approximately two-thirds of patients will present with paraneoplastic hypercalcemia meaning they have high blood calcium levels for an unknown reason.JOURNAL, Lu B, Shi H, An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings, Journal of Cancer, 10, 1, 223–237, 2019, 30662543, 6329856, 10.7150/jca.26978, The tumor secretes Parathyroid hormone related protein which acts similarly to PTH and binds PTH receptors in the bone and kidney causing hypercalcemia. Recent research has found an inactivating germline and somatic mutation of SMARCA4 gene.JOURNAL, Tischkowitz M, Huang S, Banerjee S, Hague J, Hendricks WP, Huntsman DG, Lang JD, Orlando KA, Oza AM, Pautier P, Ray-Coquard I, Trent JM, Witcher M, Witkowski L, McCluggage WG, Levine DA, Foulkes WD, Weissman BE, Small-Cell Carcinoma of the Ovary, Hypercalcemic Type-Genetics, New Treatment Targets, and Current Management Guidelines, Clinical Cancer Research, 26, 15, 3908–3917, August 2020, 32156746, 7415570, 10.1158/1078-0432.CCR-19-3797, The hypercalcemic subtype is very aggressive and has an overall survival rate of 16% with a recurrence rate of 65% in patients who receive treatment. Patients who have spread of the disease to other parts of the body tend to die 2 years after the diagnosis. Extra-ovarian spread is involved in 50% of cases and lymph node spread is present in 55% of cases. The most common initial presentation is a rapidly growing unilateral pelvic mass with a mean size of 15 cm. Histologically, it is characterized by many sheets of small, round, tightly packed cells with clusters, nests, and cords. Immunohistochemistry is typically positive for vimentin, cytokeratin, CD10, p53, and WT-1.Small cell ovarian carcinoma of the pulmonary subtype presents differently from the hypercalcemic subtype. Typically, pulmonary small cell ovarian cancer usually affects both ovaries of older women and looks like oat-cell carcinoma of the lung. The average age of disease onset is 59 years old and approximately 45% of cases are bilateral for the pulmonary subtype. Additionally, several hormones can be elevated in the pulmonary subtype including serotonin, somatostatin, insulin, gastrin, and calcitonin.

Primary peritoneal carcinoma

Primary peritoneal carcinomas develop from the peritoneum, a membrane that covers the abdominal cavity that has the same embryonic origin as the ovary. They are often discussed and classified with ovarian cancers when they affect the ovary.WEB, Primary peritoneal carcinoma,www.cancerresearchuk.org/about-cancer/type/rare-cancers/rare-cancers-name/primary-peritoneal-carcinoma, www.cancerresearchuk.org, 16 May 2015, live,www.cancerresearchuk.org/about-cancer/type/rare-cancers/rare-cancers-name/primary-peritoneal-carcinoma," title="web.archive.org/web/20150520031318www.cancerresearchuk.org/about-cancer/type/rare-cancers/rare-cancers-name/primary-peritoneal-carcinoma,">web.archive.org/web/20150520031318www.cancerresearchuk.org/about-cancer/type/rare-cancers/rare-cancers-name/primary-peritoneal-carcinoma, 20 May 2015, They can develop even after the ovaries have been removed and may appear similar to mesothelioma.

Clear-cell carcinoma

File:Ovarian clear cell carcinoma - very high mag.jpg|thumb|Ovarian clear-cell carcinomaOvarian clear-cell carcinomaOvarian clear-cell carcinoma is a rare subtype of epithelial ovarian cancer. Those diagnosed with ovarian clear-cell carcinoma are typically younger at the age of diagnosis and diagnosed at earlier stages than other subtypes of epithelial ovarian cancer.JOURNAL, Gadducci A, Multinu F, Cosio S, Carinelli S, Ghioni M, Aletti GD, Clear cell carcinoma of the ovary: Epidemiology, pathological and biological features, treatment options and clinical outcomes, Gynecologic Oncology, 162, 3, 741–750, September 2021, 34247767, 10.1016/j.ygyno.2021.06.033, JOURNAL, Iida Y, Okamoto A, Hollis RL, Gourley C, Herrington CS, Clear cell carcinoma of the ovary: a clinical and molecular perspective, International Journal of Gynecological Cancer, 31, 4, 605–616, April 2021, 32948640, 10.1136/ijgc-2020-001656, 221796329, free, 20.500.11820/0e23c421-d2cf-4858-ac50-021c64de747d, free, The highest incidence of clear-cell carcinoma of the ovary have been observed among young Asian women, especially those of Korean, Taiwanese, and Japanese background. Endometriosis has been linked to being the main risk factor for the development of clear-cell carcinoma of the ovary and has been found to be present in 50% of women diagnosed with clear-cell carcinoma of the ovary. The development of clots in the legs such as deep vein thromboembolism or in the lungs with pulmonary embolism is reported to be 40% higher in patients with clear-cell carcinoma than other epithelial ovarian cancer subtypes. Mutations in molecular pathways such as ARID1A, PIK3, and PIK3CA have been found to be linked to clear-cell carcinoma. They typically present as a large, unilateral mass, with a mean size between 13 and 15 cm. 90% of cases are unilateral. Ovarian clear-cell carcinoma does not typically respond well to chemotherapy due to intrinsic chemoresistance, therefore treatment is typically with aggressive cytoreductive surgery and platinum-based chemotherapy.

Clear-cell adenocarcinoma

(File:Clear cell carcinoma hobnail cells.png|thumb|upright=1.3|Hobnail cells seen in a clear-cell carcinoma sample)Clear-cell adenocarcinomas are histopathologically similar to other clear-cell carcinomas, with clear cells and hobnail cells. They represent approximately 5–10% of epithelial ovarian cancers and are associated with endometriosis in the pelvic cavity. They are typically early-stage and therefore curable by surgery, but advanced clear-cell adenocarcinomas (approximately 20%) have a poor prognosis and are often resistant to platinum chemotherapy.

Endometrioid

Endometrioid adenocarcinomas make up approximately 13-15% of all ovarian cancers. Because they are typically low-grade, endometrioid adenocarcinomas have a good prognosis.JOURNAL, Fadare O, Parkash V, Pathology of Endometrioid and Clear Cell Carcinoma of the Ovary, Surgical Pathology Clinics, 12, 2, 529–564, June 2019, 31097114, 10.1016/j.path.2019.01.009, 157056883, The median age of diagnosis is around 53 years of age. These tumors frequently co-occur with endometriosis or endometrial cancer. Cancer antigen 125 levels are typically elevated and a family history of a first degree relative with endometrioid ovarian cancer is associated with increased risk of developing endometrioid ovarian cancer. The average tumor size is larger than 10 cm.

Malignant mixed müllerian tumor (carcinosarcoma)

Mixed müllerian tumors make up less than 1% of ovarian cancer. They have epithelial and mesenchymal cells visible and tend to have a poor prognosis.

Mucinous

Mucinous tumors include mucinous adenocarcinoma and mucinous cystadenocarcinoma.

Mucinous adenocarcinoma

Mucinous adenocarcinomas make up 5–10% of epithelial ovarian cancers. Histologically, they are similar to intestinal or cervical adenocarcinomas and are often actually metastases of appendiceal or colon cancers. Advanced mucinous adenocarcinomas have a poor prognosis, generally worse than serous tumors, and are often resistant to platinum chemotherapy, though they are rare.

Pseudomyxoma peritonei

(File:Pseudomyxoma.jpg|thumb|Pseudomyxoma peritonei)Pseudomyxoma peritonei refers to a collection of encapsulated mucous or gelatinous material in the abdominopelvic cavity, which is very rarely caused by a primary mucinous ovarian tumor. More commonly, it is associated with ovarian metastases of intestinal cancer.

Undifferentiated epithelial

Undifferentiated cancers - those where the cell type cannot be determined - make up about 10% of epithelial ovarian cancers and have a comparatively poor prognosis. When examined under the microscope, these tumors have very abnormal cells that are arranged in clumps or sheets. Usually there are recognizable clumps of serous cells inside the tumor.

Malignant Brenner tumor

(File:Brenner Tumor of Ovary.jpg|thumb|Brenner Tumor of ovary)Malignant Brenner tumors are rare. Histologically, they have dense fibrous stroma with areas of transitional epithelium and some squamous differentiation. To be classified as a malignant Brenner tumor, it must have Brenner tumor foci and transitional cell carcinoma. The transitional cell carcinoma component is typically poorly differentiated and resembles urinary tract cancer.

Transitional cell carcinoma

Transitional cell carcinomas represent less than 5% of ovarian cancers. Histologically, they appear similar to bladder carcinoma. The prognosis is intermediate - better than most epithelial cancers but worse than malignant Brenner tumors.

Sex cord-stromal tumor

Sex cord-stromal tumor, including estrogen-producing granulosa cell tumor, the benign thecoma, and virilizing Sertoli-Leydig cell tumor or arrhenoblastoma, accounts for 7% of ovarian cancers. They occur most frequently in women between 50 and 69 years of age but can occur in women of any age, including young girls. They are not typically aggressive and are usually unilateral; they are therefore usually treated with surgery alone. Sex cord-stromal tumors are the main hormone-producing ovarian tumors.{{harvnb|Williams Gynecology|2012}}Several different cells from the mesenchyme can give rise to sex-cord or stromal tumors. These include fibroblasts and endocrine cells. The symptoms of a sex-cord or stromal ovarian tumor can differ from other types of ovarian cancer. Common signs and symptoms include ovarian torsion, hemorrhage from or rupture of the tumor, an abdominal mass, and hormonal disruption. In children, isosexual precocious pseudopuberty may occur with granulosa cell tumors since they produce estrogen. These tumors cause abnormalities in menstruation (excessive bleeding, infrequent menstruation, or no menstruation) or postmenopausal bleeding. Because these tumors produce estrogen, they can cause or occur at the same time as endometrial cancer or breast cancer. Other sex-cord/stromal tumors present with distinct symptoms. Sertoli-Leydig cell tumors cause virilization and excessive hair growth due to the production of testosterone and androstenedione, which can also cause Cushing’s syndrome in rare cases. Also, sex-cord stromal tumors occur that do not cause a hormonal imbalance, including benign fibromas, which cause ascites and hydrothorax. With germ cell tumors, sex cord-stromal tumors are the most common ovarian cancer diagnosed in women under 20.

Granulosa cell tumor

Granulosa cell tumors are the most common sex-cord stromal tumors, making up 70% of cases, and are divided into two histologic subtypes: adult granulosa cell tumors, which develop in women over 50, and juvenile granulosa tumors, which develop before puberty or before the age of 30. Both develop in the ovarian follicle from a population of cells that surrounds germinal cells.

Adult granulosa cell tumor

Adult granulosa cell tumors are characterized by later onset (30+ years, 50 on average). These tumors produce high levels of estrogen, which causes its characteristic symptoms: menometrorrhagia; endometrial hyperplasia; tender, enlarged breasts; postmenopausal bleeding; and secondary amenorrhea. The mass of the tumor can cause other symptoms, including abdominal pain and distension, or symptoms similar to an ectopic pregnancy if the tumor bleeds and ruptures.

Juvenile granulosa cell tumor

Sertoli-Leydig cell tumor

Sertoli-Leydig tumors are most common in women before the age of 30, and particularly common before puberty.

Sclerosing stromal tumors

Sclerosing stromal tumors typically occur in girls before puberty or women before the age of 30.

Germ cell tumor

Germ cell tumors of the ovary develop from the ovarian germ cells. Germ cell tumor accounts for about 30% of ovarian tumors, but only 5% of ovarian cancers, because most germ-cell tumors are teratomas and most teratomas are benign. Malignant teratomas tend to occur in older women, when one of the germ layers in the tumor develops into a squamous cell carcinoma. Germ-cell tumors tend to occur in young women (20s–30s) and girls, making up 70% of the ovarian cancer seen in that age group.BOOK, Pediatric and Adolescent Gynecology, Current Diagnosis & Treatment Obstetrics & Gynecology, 978-0-07-163856-2, 11th, 2012, DeCherney A, Nathan L, Goodwin TM, Laufer N, Roman A, McGraw Hill Professional, Germ-cell tumors can include dysgerminomas, teratomas, yolk sac tumors/endodermal sinus tumors, and choriocarcinomas, when they arise in the ovary. Some germ-cell tumors have an isochromosome 12, where one arm of chromosome 12 is deleted and replaced with a duplicate of the other. Most germ-cell cancers have a better prognosis than other subtypes and are more sensitive to chemotherapy. They are more likely to be stage I at diagnosis. Overall, they metastasize more frequently than epithelial ovarian cancers. In addition, the cancer markers used vary with tumor type: choriocarcinomas are monitored with beta-HCG and endodermal sinus tumors with alpha-fetoprotein.Germ-cell tumors are typically discovered when they become large, palpable masses. However, like sex cord tumors, they can cause ovarian torsion or hemorrhage and, in children, isosexual precocious puberty. They frequently metastasize to nearby lymph nodes, especially para-aortic and pelvic lymph nodes. The most common symptom of germ cell tumors is subacute abdominal pain caused by the tumor bleeding, necrotizing, or stretching the ovarian capsule. If the tumor ruptures, causes significant bleeding, or torses the ovary, it can cause acute abdominal pain, which occurs in less than 10% of those with germ-cell tumors. They can also secrete hormones which change the menstrual cycle. In 25% of germ-cell tumors, the cancer is discovered during a routine examination and does not cause symptoms.Diagnosing germ cell tumors may be difficult because the normal menstrual cycle and puberty can cause pain and pelvic symptoms, and a young woman may even believe these symptoms to be those of pregnancy, and not seek treatment due to the stigma of teen pregnancy. Blood tests for alpha-fetoprotein, karyotype, human chorionic gonadotropin, and liver function are used to diagnose germ cell tumor and potential co-occurring gonadal dysgenesis. A germ cell tumor may be initially mistaken for a benign ovarian cyst.

Dysgerminoma

(File:Dysgerminoma surgery.jpg|left|thumb|173x173px|Dysgerminoma)Dysgerminoma accounts for 35% of ovarian cancer in young women and is the most likely germ cell tumor to metastasize to the lymph nodes; nodal metastases occur in 25–30% of cases. These tumors may have mutations in the KIT gene, a mutation known for its role in gastrointestinal stromal tumor. People with an XY karyotype and ovaries (gonadal dysgenesis) or an X,0 karyotype and ovaries (Turner syndrome) who develop a unilateral dysgerminoma are at risk for a gonadoblastoma in the other ovary, and in this case, both ovaries are usually removed when a unilateral dysgerminoma is discovered to avoid the risk of another malignant tumor. Gonadoblastomas in people with Swyer or Turner syndrome become malignant in approximately 40% of cases. However, in general, dysgerminomas are bilateral 10–20% of the time.(File:Dysgerminoma, intermed. mag.1.jpg|thumb|Dysgerminoma histology)They are composed of cells that cannot differentiate further and develop directly from germ cells or from gonadoblastomas. Dysgerminomas contain syncytiotrophoblasts in approximately 5% of cases, and can therefore cause elevated hCG levels. On gross appearance, dysgerminomas are typically pink to tan-colored, have multiple lobes, and are solid. Microscopically, they appear identical to seminomas and very close to embryonic primordial germ cells, having large, polyhedral, rounded clear cells. The nuclei are uniform and round or square with prominent nucleoli and the cytoplasm has high levels of glycogen. Inflammation is another prominent histologic feature of dysgerminomas.

Choriocarcinoma

Choriocarcinoma can occur as a primary ovarian tumor developing from a germ cell, though it is usually a gestational disease that metastasizes to the ovary. Primary ovarian choriocarcinoma has a poor prognosis and can occur without a pregnancy. They produce high levels of hCG and can cause early puberty in children or menometrorrhagia (irregular, heavy menstruation) after menarche.

Immature (solid) teratoma

(File:Mature Cystic Teratoma of the Ovary (5560431170).jpg|thumb|Mature Cystic Teratoma of Ovary)Immature, or solid, teratomas are the most common type of ovarian germ cell tumor, making up 40–50% of cases. Teratomas are characterized by the presence of disorganized tissues arising from all three embryonic germ layers: ectoderm, mesoderm, and endoderm; immature teratomas also have undifferentiated stem cells that make them more malignant than mature teratomas (dermoid cysts). The different tissues are visible on gross pathology and often include bone, cartilage, hair, mucus, or sebum, but these tissues are not visible from the outside, which appears to be a solid mass with lobes and cysts. Histologically, they have large amounts of neuroectoderm organized into sheets and tubules along with glia; the amount of neural tissue determines the histologic grade. Immature teratomas usually only affect one ovary (10% co-occur with dermoid cysts) and usually metastasize throughout the peritoneum. They can also cause mature teratoma implants to grow throughout the abdomen in a disease called growing teratoma syndrome; these are usually benign but will continue to grow during chemotherapy, and often necessitate further surgery. Unlike mature teratomas, immature teratomas form many adhesions, making them less likely to cause ovarian torsion. There is no specific marker for immature teratomas, but carcinoembryonic antigen (CEA), CA-125, CA19-9, or AFP can sometimes indicate an immature teratoma.Stage I teratomas make up the majority (75%) of cases and have the best prognosis, with 98% of patients surviving five years; if a Stage I tumor is also grade 1, it can be treated with unilateral surgery only. Stage II though IV tumors make up the remaining quarter of cases and have a worse prognosis, with 73–88% of patients surviving five years.

Mature teratoma (dermoid cyst)

Mature teratomas, or dermoid cysts, are rare tumors consisting of mostly benign tissue that develop after menopause. The tumors consist of disorganized tissue with nodules of malignant tissue, which can be of various types. The most common malignancy is squamous cell carcinoma, but adenocarcinoma, basal-cell carcinoma, carcinoid tumor, neuroectodermal tumor, malignant melanoma, sarcoma, sebaceous tumor, and struma ovarii can also be part of the dermoid cyst. They are treated with surgery and adjuvant platinum chemotherapy or radiation.

Yolk sac tumor/endodermal sinus tumor

Yolk sac tumors, formerly called endodermal sinus tumors, make up approximately 10–20% of ovarian germ cell malignancies, and have the worst prognosis of all ovarian germ cell tumors. They occur both before menarche (in one-third of cases) and after menarche (the remaining two-thirds of cases). Half of the people with yolk sac tumors are diagnosed in stage I. Typically, they are unilateral until metastasis, which occurs within the peritoneal cavity and via the bloodstream to the lungs. Yolk sac tumors grow quickly and recur easily, and are not easily treatable once they have recurred. Stage I yolk sac tumors are highly treatable, with a 5-year disease-free survival rate of 93%, but stage II-IV tumors are less treatable, with survival rates of 64–91%.Their gross appearance is solid, friable, and yellow, with necrotic and hemorrhagic areas. They also often contain cysts that can degenerate or rupture. Histologically, yolk sac tumors are characterized by the presence of Schiller-Duval bodies (which are pathognomonic for yolk sac tumors) and a reticular pattern. Yolk sac tumors commonly secrete alpha-fetoprotein and can be immunohistochemically stained for its presence; the level of alpha-fetoprotein in the blood is a useful marker of recurrence.

Embryonal carcinoma

Embryonal carcinomas, a rare tumor type usually found in mixed tumors, develop directly from germ cells but are not terminally differentiated; in rare cases, they may develop in dysgenetic gonads. They can develop further into a variety of other neoplasms, including choriocarcinoma, yolk sac tumor, and teratoma. They occur in younger people, with an average age at diagnosis of 14, and secrete both alpha-fetoprotein (in 75% of cases) and hCG.Histologically, embryonal carcinoma appears similar to the embryonic disc, made up of epithelial, anaplastic cells in disorganized sheets, with gland-like spaces and papillary structures.

Polyembryoma

Polyembryomas, the most immature form of teratoma and very rare ovarian tumors, are histologically characterized by having several embryo-like bodies with structures resembling a germ disk, yolk sac, and amniotic sac. Syncytiotrophoblast giant cells also occur in polyembryomas.

Squamous cell carcinoma

Primary ovarian squamous cell carcinomas are rare and have a poor prognosis when advanced. More typically, ovarian squamous cell carcinomas are cervical metastases, areas of differentiation in an endometrioid tumor, or derived from a mature teratoma.

Mixed tumors

Mixed tumors contain elements of more than one of the above classes of tumor histology. To be classed as a mixed tumor, the minor type must make up more than 10% of the tumor. Though mixed carcinomas can have any combination of cell types, mixed ovarian cancers are typically serous/endometrioid or clear-cell/endometrioid. Mixed germ cell tumors make up approximately 25–30% of all germ cell ovarian cancers, with combinations of dysgerminoma, yolk sac tumor, and/or immature teratoma. The prognosis and treatment vary based on the component cell types.

Secondary ovarian cancer

Ovarian cancer can also be a secondary cancer, the result of metastasis from a primary cancer elsewhere in the body. About 5-30% of ovarian cancers are due to metastases, while the rest are primary cancers.JOURNAL, Lee SJ, Bae JH, Lee AW, Tong SY, Park YG, Park JS, Clinical characteristics of metastatic tumors to the ovaries, Journal of Korean Medical Science, 24, 1, 114–119, February 2009, 19270823, 2650975, 10.3346/jkms.2009.24.1.114, Common primary cancers are breast cancer, colon cancer, appendiceal cancer, and stomach cancer (primary gastric cancers that metastasize to the ovary are called Krukenberg tumors). Krukenberg tumors have signet ring cells and mucinous cells. Endometrial cancer and lymphomas can also metastasize to the ovary.BOOK, Premalignant & Malignant Disorders of the Ovaries & Oviducts, Levy G, Purcell K, McGraw-Hill, 2013, CURRENT Diagnosis & Treatment: Obstetrics & Gynecology, 11th, DeCherney AH, Nathan L, Laufer N, Roman AS,accessmedicine.mhmedical.com/content.aspx?bookid=498§ionid=41008645, 978-0-07-163856-2, live,accessmedicine.mhmedical.com/content.aspx?bookid=498§ionid=41008645," title="web.archive.org/web/20170910175639accessmedicine.mhmedical.com/content.aspx?bookid=498§ionid=41008645,">web.archive.org/web/20170910175639accessmedicine.mhmedical.com/content.aspx?bookid=498§ionid=41008645, 10 September 2017,

Borderline tumors

Ovarian borderline tumors, sometimes called low malignant potential (LMP) ovarian tumors, have some benign and some malignant features. LMP tumors make up approximately 10%-15% of all ovarian tumors. They develop earlier than epithelial ovarian cancer, around the age of 40–49. They typically do not have extensive invasion; 10% of LMP tumors have areas of stromal microinvasion (