A BROAD OVERVIEW ON MALIGNANT OVARIAN NEOPLASMS
ODEREMI, OLUWAGBEMISOLA MOTUNRAYO
DOKITA Editorial Board Member
Malignant Ovarian Neoplasms are a clinical spectrum that includes all neoplasms derived from abnormal proliferation of ovarian tissue (epithelial cells, stromal cells, and germ cells). It can be subdivided into different histological subtypes.1 Malignant Ovarian Neoplasms have the highest rate of fatality among all types of gynaecological neoplasm. Less than 30% of women with advanced stage ovarian cancer survive long-term. When ovarian cancer is diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. Only 25% of ovarian cancers are detected in stage I due to its nonspecific early symptoms. The most commonly reported symptoms are abdominal or pelvic pain, and abdominal swelling.
The survival rate of cure could be significantly improved if an efficient and effective screening strategy that could detect disease in its earlier stages is found. In the world due to late presentation, diagnosis is usually made at the at the later stages making the prognosis bad.2 Malignant Ovarian neoplasm represents the sixth most commonly diagnosed cancer among women in the world despite the high incidence and fatality rates. Established risk factors for ovarian cancer include age and having a family history of the disease, while protective factors include increasing parity, oral contraceptive use, and oophorectomy.3
Ovarian cancer is the sixth most commonly diagnosed cancer in women, with epithelial ovarian cancer being the most prevalent subtype accounting for 90% of the cases and while nonepithelial (stromal cells and germ cell tumours) account for 10%. The risk of a woman developing ovarian cancer during her lifetime is approximately 1.4%. The risk gradually increases with age until about 70years.4
Ovarian cancer has a wide range difference in incidence by race. The highest incidence rates are seen in the North Americans and Europeans, with rates in these areas more than 0.01 percent, Japan 0.06 percent. South America 0.07 percent, incidence is lower in Asia and Africa. Within the United States, the incidence mimics the observed international differences. Rates are highest among whites 0.14 percent, intermediate for Hispanics 0.11 percent, and lowest among blacks 0.1 percent and Asians 0.09 percent.4
Malignant Ovarian Neoplasms begins with differentiation of the cells overlying the ovary. During ovulation, these cells can be incorporated into the ovary, where they then proliferate. New evidence shows that the majority of these tumours actually originate in the fimbria of the fallopian tube.2
Different peptide growth factors and their receptors are expressed by normal and malignant ovarian cells. Amplification and overexpression of the HER-2/neu and c-myc oncogenes occur in a significant fraction of epithelial ovarian cancers. C-myc amplification is more common in serous cancers. Mutation of hep53 tumour suppressor gene occurs in approximately half of advanced (stage III/IV) ovarian cancers and in 15% of early (stage IA/IB) cases.2
Most recently, preliminary studies have focused on the role of other tumour suppressor genes, cyclins, WAF1, and DNA mismatch repair genes. Approximately 50% of HGSOC are characterised by mutations in genes involved in the homologous recombination pathway of DNA repair, especially BRCA1 and BRCA2.2 Recent studies shows a link between ovarian cancer and endometriosis due to the up regulation of chronic activation of complement pathway in women with endometriosis. 5
RISK FACTORS FOR MALIGNANT OVARIAN NEOPLASM
Long ovulation period
CLASSIFICATION OF MALIGNANT OVARIAN NEOPLASMS
Epithelial Cell Ovarian Carcinoma
About 90% of all ovarian malignancies are of the epithelial cell type. Epithelial Cell Ovarian Carcinoma are derived from mesothelial cells.4 EOC is subdivided into various histological subtypes they fall into two main groups: Type I and Type II tumours. Type I tumours include low-grade serous, mucinous, endometrioid, clear cell carcinomas and tend to grow more slowly, often from an identifiable precursor. In contrast, Type II tumours are characterised by high-grade and rapidly progressive disease. High-grade serous ovarian carcinoma (HGSOC) is the most common Type II tumour, accounting for almost 75% of all EOCs. Unfortunately, it is also one of the most aggressive.
Malignant epithelial serous tumours are the most common malignant epithelial cell tumours. Malignant mucinous epithelial tumours are less common making up approximately one-third of all epithelial tumours, the majority of which are benign or of low malignant potential; only 5% are cancerous. These tumours have a lower rate of bilaterality. They could be associated with widespread peritoneal extension with thick, mucinous ascites, termed pseudomyxomatous peritonei.6
Germ Cell Tumours
Germ cell tumours are derived from primordial germ cells within the ovary. The cells type secretes β hCG (human Chorionic Gonadotropin) or AFP (Alpha Feto Protein) which are used as tumours markers. Germ cell tumours account for less than 10 percent of ovarian tumours and are more common in young women less than 20yrs old. Dysgerminoma and immature teratomas are the most common types. Dysgerminomas are the most common type of germ cell tumours seen in patients with gonadal dysgenesis, they are particularly radiosensitive and chemosensitive. Immature teratomas are the second most common germ cell cancer. They have a good prognosis when treated with chemotherapy.7
Gonadal stromal cell tumour
The gonadal stromal cell tumours are functioning tumours. They are characterised by hormone production of female, male sex steroids, or adrenal steroid hormones.8 The granulosa cell tumour is the most common type characterised by secretion of large amounts of oestrogen. Sertoli–Leydig cell tumours a less common type is rare and is characterised by secretion of testosterone. Other malignant stromal cell tumours include fibrosarcoma and malignant thecoma.9
Malignant mesodermal sarcomas are aggressive and a rare type of ovarian tumour, with a low survival rate. It is usually are diagnosed at late stages. Clinical experience with these tumours is limited.10
An ultrasound scan is taken when a Malignant ovarian neoplasm is suspected. USS characterises the morphology of the neoplasm presence of bilateral tumours and ascites.11 Ca125 levels in the serum are also evaluated. Studies have shown that levels of Ca125 start to rise prior to onset of clinical evidence of disease. Other biomarkers including beta-human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase can also be used.12 A risk of malignancy (RMI) score can be calculated. Surgery is necessary for the diagnosis, staging, and treatment of malignant ovarian neoplasms.13
Primary surgical therapy is indicated in most of the malignant ovarian neoplasm, principles of cytoreductive surgery, or “tumour debulking” are used. Cytoreductive surgery is performed and all tumour sizes are reduced to less than 1 cm in size, causing adjunctive radiation therapy and chemotherapy to be more effective.14
Chemotherapy can be given as primary treatment or as an adjunct following surgery. It is used to prolong clinical remission. First-line treatment is usually a combination of a platinum compound with paclitaxel. Other chemotherapeutic agents, including ifosfamide, hexamethylmelamine, doxorubicin, topotecan, gemcitabine, etoposide, vinorelbine, and tamoxifen may be used on reoccurrence.15 Radiation therapy has only a limited role in the management of ovarian cancer.14
Recent research in the treatment of ovarian cancer focuses on the use of targeted biological therapies. The use of VEGF (vascular endothelial growth factor) pathway has shown the greatest success. Drugs like Bevacizumab, Aflibercept, sorafenib target and inhibit the VEGF pathway. They are used in combination with chemotherapy agents, leads to improvement in symptom control, and a better quality of life.17
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- American College of Obstetricians and Gynecologists. The role of the generalist obstetrician gynecologist in the early detection of ovarian cancer. 2002.
- Risch, H. A., Marrett, L. D., Jain, M., and Howe, G. R. Differences in risk factors for epithelial ovarian cancer by histologic type. Results of a case-control study.1996.
- Berchuck A, Elbendary A, Havrilesky L, Rodriguez GC, Bast RC, Jr. Pathogenesis of ovarian cancers. 2002.
- Hinkula M, Pukkala E, Kyyronen P, Kauppila A. Incidence of ovarian cancer of grand multiparous women–a populationbased study in Finland. 2006.
- Salehi F, Dunfield L, Phillips KP, Krewski D, Vanderhyden BC. Risk factors for ovarian cancer: an overview with emphasis on hormonal factors. J Toxicol Environ Health B Crit Rev. 2008.
- Morch LS, Lokkegaard E, Andreasen AH, Kruger-Kjaer S, Lidegaard O. Hormone therapy and ovarian cancer. JAMA. 2009.
- Eltabbakh, G. H., Natarajan, N., Piver, M. S., and Mettlin, C. J. Epidemiologic differences between women with borderline ovarian tumors and women with epithelial ovarian cancer. 1999.
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- Marchbanks, P. A., Wilson, H., Bastos, E., Cramer, D. W., Schildkraut, J. M., and Peterson, H. B. Cigarette smoking and epithelial ovarian cancer by histologic type. 2000.
- Schwartz PE. Current diagnosis and treatment modalities for ovarian cancer. American Journal of Obstetrics and Gynaecology 2002.
- American Cancer Society. Cancer Facts and Figures 2006. Atlanta: American Cancer Society, 2006.
- D. Luvero, A. Milani, J. A Ledermann. Treatment options in recurrent ovarian cancer. Therapeutic advances in medical oncology. 2014.