Ovarian cancers are now known to be several distinct diseases, which are named after the type of cell they come from: epithelial, germ cell, and stromal. These are the three main cell types that make up the ovary. Each cell type can develop into a different type of tumor, and each type differs in how it spreads, how it’s treated, and its prognosis. In most cases, when we say “ovarian cancer,” we are referring to high-grade serous ovarian cancer (HGSOC), which is the most common type of the disease.
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- Epithelial ovarian cancer, which arises from the surface of the ovary (the epithelium), is the most common ovarian cancer. Fallopian Tube Cancer and Primary Peritoneal Cancer are also included within this designation.
- Germ Cell ovarian cancer arises from the reproductive cells of the ovaries, and is rare.
- Stromal cell ovarian cancer, which arises from connective tissue cells, is very rare.
- Small cell carcinoma (SCCO) of the ovary is an extremely rare ovarian cancer and it is not certain whether the cells in SCCO are from ovarian epithelial cells, sex-cord stromal cells or germ cells.
Not all ovarian tumors are cancer. Some ovarian tumors may be abnormal but not necessarily cancerous. Read more here.
Epithelial ovarian cancer is divided into different types, with High-Grade Serous Ovarian Cancer (HGSOC) being the most common, and all others considered rare forms of the disease:
- Serous Carcinomas (High and Low Grade), including Primary Peritoneal and Fallopian Tube
- Clear Cell Carcinoma (CCC)
Epithelium is one of the four types of tissue in the body (the others are muscle, nervous and connective) and covers the outer surfaces of organs and blood vessels, as well as the inner surfaces of cavities in many internal organs.
Most ovarian cancers—approximately 85-90%—fall into this category. Epithelial ovarian cancer is one of the most common gynecologic malignancies, with 50% of all cases occurring in women older than 65 years. These cancers are diseases in which malignant (cancer) cells form in the tissue covering the ovary, or lining the fallopian tube or peritoneum (the serous membrane lining the cavity of the abdomen and pelvis and covering the abdominal organs) and are called carcinomas.
Serous carcinomas are classified as low-grade and high-grade, with high-grade serous carcinomas the most common type of ovarian cancer—approximately 75% of epithelial ovarian cancer including FTC and PPC fall into this subtype.
Unless otherwise specified, when we say “ovarian cancer,” on this website and in general discussion of the disease, we are referring to high-grade serous ovarian carcinoma.
High-grade serous ovarian carcinoma is the most common type of invasive epithelial ovarian cancer (and includes FTC and PPC), and is diagnosed at advanced stages (defined here as Stage III or Stage IV) 70% of the time. This may be because many of the most common subtypes of high-grade serous cancers may originate in the fallopian tubes, with subsequent cancer in the ovaries a result of the spread from a primary tumor in the fallopian tubes and may explain why these cancers are often detected at an advanced stage. Recent research has found that high-grade serous cancers that begin in the fallopian tubes take on average 6.5 years to progress to the ovaries, and then spread to other areas quickly.
These advanced carcinomas typically spread to the peritoneum first (lining of the organs of the pelvis and abdomen). This may lead to fluid build-up in the peritoneal cavity (ascites) which can result in abdominal bloating. Early stage epithelial, fallopian tube, and peritoneal cancers usually do not cause signs or symptoms. When signs or symptoms do appear, such as abdominal bloating, the cancer is often advanced.
Once symptoms do occur, they often go unrecognized, leading to delays in diagnosis. OCRA and other organizations around the world have made great efforts to enhance physician and patient awareness of the occurrence of these nonspecific symptoms to hasten diagnosis.
Signs and symptoms can include the following:
- Pelvic or abdominal pain
- Difficulty eating or feeling full quickly
- Urinary symptoms (urgency or frequency)
Primary Peritoneal Carcinoma (PPC), Fallopian Tube Cancer (FTC) and epithelial ovarian cancer are often grouped together because they share many similarities, including a similar course of treatment. Both are rare diagnoses. Primary peritoneal carcinoma is an advanced stage cancer, always diagnosed in Stage III-IV, and most often affects people over age 60.
Because the peritoneal lining of the abdomen and surface of the ovary develop from the same embryonic tissue, primary peritoneal carcinoma cells are the same as the most common type of ovarian cancer cells. This means in some cases, patients with primary peritoneal cancer are eligible for clinical trials for advanced ovarian cancer.
- Low-Grade Serous Ovarian Carcinoma (LGSOC)
- Clear Cell Carcinoma (CCC)
- Endometrioid Carcinoma
- Mucinous Carcinoma
- Squamous Cell Carcinoma (SCC)
- Borderline Epithelial Ovarian Tumors
- Borderline Endometrioid Ovarian Tumors
Low-grade serous carcinomas (LGSC) are more similar to serous tumors of low malignant potential and are quite distinct from high-grade serous carcinomas. This research finding has led some researchers to hypothesize that low-grade carcinomas are in fact tumors of low malignant potential that have gone undetected and are therefore more developed. These tumors rarely develop into a high-grade serous carcinoma.
Recent Surveillance, Epidemiology, and End Results (SEER) data revealed that the incidence of ovarian CCC in women living in the United States is 4.8% in whites, 3.1% in blacks, and 11.1% in Asians. In Japan, the prevalence of ovarian CCC is higher, with an estimated incidence of 25% of epithelial ovarian cancers. CCC accounts for approximately 6% of epithelial ovarian cancers. CCC has proven more resistant than other epithelial ovarian cancers to platinum-based front-line chemotherapy, the most commonly used treatment. Recent research has found that CCC showed markedly different drug-based molecular biomarkers from HGSC, which suggests that CCC likely requires a new personalized target therapy in this rare subtype.
Endometriosis is a known risk factor for Clear Cell Carcinoma.
Endometriosis is also a risk factor for Endometrioid tumors. Regardless of disease stage, these tumors seem to respond to treatment slightly better than serous carcinomas
While most epithelial cancers share enough similarities to be addressed in the same way, a diagnosis of primary mucinous carcinoma is distinct, and in some cases can benefit from different treatments. Mucinous tumors are usually large with a median diameter of 18 to 20 cm and tend to remain confined to the ovaries. It can be difficult to distinguish primary mucinous carcinoma tumors from metastatic mucinous tumors from the colon/rectum, appendix, cervix or pancreas, but it is important to do so, in order to allow for most effective treatment. When diagnosed in early stages, prognosis for patients with primary mucinous carcinoma is quite good.
Squamous cell carcinoma is a rare type of ovarian cancer, thought to be of epithelial origin. Generally arising from malignant transformation in a cystic teratoma (ovarian cyst), or from a Brenner’s tumor or endometriosis, SCC accounts for about 2% of ovarian cancer diagnoses. Prognosis can be good when caught in early stages. Treatment becomes more challenging when the disease is caught in later stages, leading to statistically poorer prognosis.
Not all epithelial ovarian tumors are cancer. Ovarian tumors are classified as benign (non-cancerous), borderline or malignant (cancerous). Most epithelial ovarian tumors are benign and do not spread or cause cancer. There are many types of benign ovarian tumor, such as serous cystadenomas, mucinous cystadenomas, and Brenner tumors.
Borderline epithelial ovarian tumors or low malignant potential tumors (LMP) are different from typical ovarian cancers because they do not grow into the supporting tissue of the ovary (stromal)—it is a disease in which abnormal cells form in the tissue covering the ovary. These abnormal cells could become cancer, but usually do not, and usually remain in the ovary. When disease is found in one ovary, the other ovary should also be checked carefully for signs of disease.
These tend to occur in younger women, and are less threatening than most ovarian cancers. These tumors account for 15% of all epithelial ovarian cancers, and nearly 75% are diagnosed at Stage 1. These tumors are recognized as distinct from the malignant invasive carcinomas described below because their prognosis and treatment is markedly different.
Borderline epithelial ovarian cancer may not cause early signs or symptoms. If signs or symptoms do occur, they may include the following:
- Pain or swelling in the abdomen.
- Pain in the pelvis.
- Gastrointestinal problems, such as gas, bloating, or constipation.
The prognosis and treatment options depend on the following:
- The stage of the disease (whether it affects part of the ovary, involves the whole ovary, or has spread to other places in the body);
- What type of cells make up the tumor;
- The size of the tumor;
- The patient’s general health.
Patients diagnosed with ovarian low malignant potential tumors have a good prognosis, especially when the tumor is found early.
The less common endometrioid tumor of low malignant potential is not typically regarded as malignant because it seldom, if ever, metastasizes. Malignant transformation can, however, occur and may be associated with a similar tumor outside of the ovary; such tumors are the result of either a second primary or rupture of the primary endometrial tumor.
Germ cell tumors begin in the reproductive cells (egg or sperm) of the body. In women, this type begins in the cells that form eggs in the ovaries, known as germ cells.
Ovarian germ cell malignant tumors are uncommon, and account for approximately 5 percent of ovarian cancer cases. They can occur in women of any age, but are more often found in young women or adolescent girls. These tumors frequently affect only one ovary, and are generally curable in about 95% of cases, if found and treated early.
Immature teratomas are a type of malignant ovarian germ cell tumors. They typically occur in girls and young women under 18. In cases where tumors have not spread beyond the ovary, they are treated by surgical removal of the ovary. If they have spread beyond the ovary, chemotherapy is typically recommended in addition to surgery.
While ovarian germ cell tumors are rare, this subtype, dysgerminoma, is the most common malignant form and typically affects women in their teens or twenties. These types of tumors do not grow or spread quickly, and are usually treatable. If confined to the ovary, more than 75% of women are cured by the removal of the ovary, and if the cancer has spread, surgery along with radiation and/or chemotherapy can control and/or cure the disease in approximately 90% of patients. New types of treatment are being tested through clinical trials, such as high-dose chemotherapy with bone marrow transplant.Malignant germ cell tumors of the ovary follow the same staging system as epithelial cancers and primary peritoneal cancers.
Yolk sac tumors, also known as endodermal sinus tumors, are a rare type of germ cell tumor, accounting for about 15% of germ cell tumors. Yolk sac tumors are typically diagnosed prior to age 40—median age at diagnosis is 18-19–with about 40% of diagnoses occurring prior to puberty. In pediatric forms, these tumors often present as pure yolk sac tumors, and have a relatively positive prognosis. When diagnosed in older patients, these tumors are more often mixed with other germ cell components, and tend to metastasize quickly, making treatment more challenging.
Most germ cell tumors are benign (non-cancerous). Mature teratomas are the most common type of benign germ cell tumor. These tend to occur in women of reproductive age (teens through forties) and are often called a dermoid cyst. Women with benign germ cell tumors such as mature teratomas are treated by removing the part of the ovary that has the tumor (ovarian cystectomy) or by removing the entire ovary. There may be few symptoms. Abdominal pain or constipation may occur, and when the tumor gets bigger, an abdominal mass may be evident.
- Adult Granulosa Cell Tumor
- Juvenile Granulosa Cell Tumor
- Sertoli-Leydig Cell Tumor
- Granulosa and Sertoli-Leydig Elements (Mixed)
- Granulosa and Sertoli Elements (Mixed)
- Gynandroblastoma (Mixed)
- Malignant Mixed Mullerian Tumor of the Ovary
- Fibromas (most common granulosa stromal tumors)
Malignant ovarian stromal tumors are rare and represent approximately 1.2% of all primary malignant ovarian tumors. In contrast to epithelial and germ cell tumors, however, sex cord-stromal tumors frequently present with signs of hormonal production, such as hirsutism and virilization, menstrual changes, or early puberty as well as signs and symptoms of a pelvic mass, and are often found in adolescents and young adults, with the exception of adult granulosa cell tumors which typically occur later. Ovarian stromal tumors are often found early, and have a 75% survival rate.
Symptoms may include:
- abnormal uterine bleeding (ovarian stromal tumors sometimes produce estrogen);
- in young girls, can cause menstrual periods and breast development prior to puberty;
- less commonly, these tumors can produce testosterone, which can result in cessation of menstrual periods, as well as facial and body hair growth;
- endometrial hyperplasia;
- abdominal distention/bloating;
- sudden, severe abdominal pain can occur if the tumor starts to bleed, or if ovarian torsion occurs.
Several subtypes are associated with genetic predisposition, including those observed in patients with Peutz-Jegher syndrome. Recent studies have revealed the relationship between Sertoli-Leydig cell tumors and DICER1 mutations. Mutations in DICER1, STK11, and FOXL2 influence the development of some of these neoplasms.
Granulosa cell tumors are more often malignant than thecomas or fibromas, which are most often benign. Granulosa cell, theca cell, and mixed tumors are usually hormonally active, in contrast to fibromas, which do not produce hormones.
Malignant Mixed Mullerian Tumors of the Ovary are also known as ovarian carcinosarcomas, malignant mixed mesodermal, or sarcomatoid carcinomas, and make up an estimated 1-4% of ovarian cancer diagnoses, most often affecting post-menopausal women. MMMTs contain both epithelial elements and a stromal component, making it a mixed tumor type. MMMT are considered an aggressive cancer, and have a statistically poor survival rate–though prognosis can depend on stage at diagnosis and biological makeup of the tumor itself.
Currently, individuals with sex cord-stromal tumors receive treatment that is similar to that in individuals with germ cell or epithelial tumors. As translational efforts advance, it is likely that treatment will evolve and that therapies directed at the underlying genetic aberrations may replace more generic treatment. Recurrent disease may be treated with surgery. Radiation therapy may be useful in settings of recurrent disease.
Small cell carcinoma of the ovary (SCCO) is a rare, highly malignant tumor that affects mainly young women, with a median age at diagnosis of 23 years old. It is not certain whether the cells in SCCO are from ovarian epithelial cells, sex-cord stromal cells or germ cells.
The subtypes of SCCO include pulmonary, neuro-endocrine and hypercalcemic. SCCO accounts for 0.1 percent of ovarian cancer cases.
Small cell neuro-endocrine tumors of the ovary are extremely rare, with only 35 known cases reported as of 2011. Median age of diagnosis for those with small cell neuro-endocrine tumors is 23.9. These tumor types are often mixed with other subtypes, and statistically tend to have poor prognosis.
Approximately two-thirds of patients with SCCO have hypercalcemia. The symptoms are the same as other types of ovarian cancer. If you’re interested in viewing a webinar about small cell carcinoma of the ovary, hypercalcemic type, you can watch it here.
For more information and details on research progress surrounding rare ovarian cancers, watch the video Rare Ovarian Cancers, presented by Dr. David Gershenson at OCRA’s virtual National Conference.