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There is no simple and reliable way to test for ovarian cancer in women who do not have any signs or symptoms. The Pap test does not screen for ovarian cancer.
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.
Ovarian cancer is usually only palpable in advanced stages. Screening is not recommended using CA-125 measurements, HE4 levels, ultrasound, or adnexal palpation in women who are at average risk. Risk of developing ovarian cancer in those with genetic factors can be reduced. Those with a genetic predisposition may benefit from screening. This high risk group has benefited with earlier detection.
Ovarian cancer has low prevalence, even in the high-risk group of women from the ages of 50 to 60 (about one in 2000), and screening of women with average risk is more likely to give ambiguous results than detect a problem which requires treatment. Because ambiguous results are more likely than detection of a treatable problem, and because the usual response to ambiguous results is invasive interventions, in women of average risk, the potential harms of having screening without an indication outweigh the potential benefits. The purpose of screening is to diagnose ovarian cancer at an early stage, when it is more likely to be treated successfully.
Screening with transvaginal ultrasound, pelvic examination, and CA-125 levels can be used instead of preventative surgery in women who have BRCA1 or BRCA2 mutations. This strategy has shown some success.
People with strong genetic risk for ovarian cancer may consider the surgical removal of their ovaries as a preventative measure. This is often done after completion of childbearing years. This reduces the chances of developing both breast cancer (by around 50%) and ovarian cancer (by about 96%) in people at high risk. Women with "BRCA" gene mutations usually also have their Fallopian tubes removed at the same time (salpingo-oophorectomy), since they also have an increased risk of Fallopian tube cancer. However, these statistics may overestimate the risk reduction because of how they have been studied.
People with a significant family history for ovarian cancer are often referred to a genetic counselor to see if they if testing for BRCA mutations would be beneficial. The use of oral contraceptives, the absence of 'periods' during the menstrual cycle, and tubal ligation reduce the risk.
There may an association of developing ovarian cancer and ovarian stimulation during infertility treatments. Endometriosis has been linked to ovarian cancers. Human papillomavirus infection, smoking, and talc have not been identified as increasing the risk for developing ovarian cancer.
After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:
- Stage I: the cancer remains localized to the testis.
- Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).
- Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.
Further information on the detailed staging system is available on the website of the American Cancer Society.
Cases of GTD can be diagnosed through routine tests given during pregnancy, such as blood tests and ultrasound, or through tests done after miscarriage or abortion. Vaginal bleeding, enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis) are the most common symptoms of GTD. But GTD also leads to elevated serum hCG (human chorionic gonadotropin hormone). Since pregnancy is by far the most common cause of elevated serum hCG, clinicians generally first suspect a pregnancy with a complication. However, in GTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinically suspected, serum beta hCG is also measured.
The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see «Treatment» below) in women with hydatidiform mole. However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy is contraindicated, because biopsy may cause life-threatening haemorrhage.
Women with persistent abnormal vaginal bleeding after any pregnancy, and women developing acute respiratory or neurological symptoms after any pregnancy, should also undergo hCG testing, because these may be signs of a hitherto undiagnosed GTD.
Presence of an ovarian tumour plus hormonal disturbances suggests a Leydig cell tumour, granulosa cell tumour or thecoma. However, hormonal disturbances, in Leydig tumours, is present in only 2/3 of cases. Testicular Leydig cell tumours can be detected sonographically, ultrasound examinations may be ordered in the event of a palpable scrotal lump, however incidental identification of these lesions is also possible.
A conclusive diagnosis is made via histology, as part of a pathology report made during or after surgery. Reinke crystals are classically found in these tumours and help confirm the diagnosis, although they are seen in less than half of all Leydig cell tumours. See also Sex cord-stromal tumour. Immunohistochemical markers of Leydig cell tumours include inhibin-alpha, calretinin, and melan-A.
Women with a hydatidiform mole have an excellent prognosis. Women with a malignant form of GTD usually have a very good prognosis.
Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumour and a life-threatening disease, it is very sensitive to chemotherapy. Virtually all women with non-metastatic disease are cured and retain their fertility; the prognosis is also very good for those with metastatic (spreading) cancer, in the early stages, but fertility may be lost. Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. The FIGO staging system is used. The risk can be estimated by scoring systems such as the "Modified WHO Prognostic Scoring System", wherein scores between 1 and 4 from various parameters are summed together:
In this scoring system, women with a score of 7 or greater are considered at high risk.
It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in developing countries.
For surface epithelial-stromal tumors, the most common sites of metastasis are the pleural cavity (33%), the liver (26%), and the lungs (3%).
A widely recognised method of estimating the risk of malignant ovarian cancer based on initial workup is the "risk of malignancy index" (RMI). It is recommended that women with an RMI score over 200 should be referred to a centre with experience in ovarian cancer surgery.
The RMI is calculated as follows:
There are two methods to determine the ultrasound score and menopausal score, with the resultant RMI being called RMI 1 and RMI 2, respectively, depending on what method is used:
An RMI 2 of over 200 has been estimated to have a sensitivity of 74 to 80%, a specificity of 89 to 92% and a positive predictive value of around 80% of ovarian cancer. RMI 2 is regarded as more sensitive than RMI 1.
The main way testicular cancer is diagnosed is via a lump or mass inside a testis. More generally, if a young adult or adolescent has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer.
Other conditions may also have symptoms similar to testicular cancer:
- Epididymitis or epididymoorchitis
- Hematocele
- Varicocele
- Orchitis
- Prostate infections or inflammations (prostatitis), bladder infections or inflammations (cystitis), or kidney (renal) infections (nephritis) or inflammations which have spread to and caused swelling in the vessels of the testicles or scrotum
- Testicular torsion or a hernia
- Infection, inflammation, retro-peritonitis, or other conditions of the lymph nodes or vessels near the scrotum, testicles, pubis, anorectal area, and groin
- Benign tumors or lesions of the testicles
- Metastasis to the testicles from another, primary tumor site(s)
The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases.
The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy - that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.
Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A transscrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy only the retroperitoneal route exists.
Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. Alpha-fetoprotein, human chorionic gonadotropin (the "pregnancy hormone"), and LDH-1 are the typical tumor markers used to spot testicular germ cell tumors.
A pregnancy test may be used to detect high levels of chorionic gonadotropin; however, the first sign of testicular cancer is usually a painless lump. Note that only about 25% of seminomas have elevated chorionic gonadotropin, so a pregnancy test is not very sensitive for making out testicular cancer.
Follow-up imaging in women of reproductive age for incidentally discovered simple cysts on ultrasound is not needed until 5 cm, as these are usually normal ovarian follicles. Simple cysts 5 to 7 cm in premenopausal females should be followed yearly. Simple cysts larger than 7 cm require further imaging with MRI or surgical assessment. Because they are large, they cannot be reliably assessed by ultrasound alone because it may be difficult to see the soft tissue nodularity or thickened septation at their posterior wall due to limited penetrance of the ultrasound beam. For the corpus luteum, a dominant ovulating follicle that typically appears as a cyst with circumferentially thickened walls and crenulated inner margins, follow up is not needed if the cyst is less than 3 cm in diameter. In postmenopausal patients, any simple cyst greater than 1 cm but less than 7 cm needs yearly follow-up, while those greater than 7 cm need MRI or surgical evaluation, similar to reproductive age females.
For incidentally discovered dermoids, diagnosed on ultrasound by their pathognomonic echogenic fat, either surgical removal or yearly follow up is indicated, regardless of patient age. For peritoneal inclusion cysts, which have a crumpled tissue-paper appearance and tend to follow the contour of adjacent organs, follow up is based on clinical history. Hydrosalpinx, or fallopian tube dilation, can be mistaken for an ovarian cyst due to its anechoic appearance. Follow-up for this is also based on clinical presentation.
For multiloculate cysts with thin septation less than 3 mm, surgical evaluation is recommended. The presence of multiloculation suggests a neoplasm, although the thin septation implies that the neoplasm is benign. For any thickened septation, nodularity, or vascular flow on color doppler assessment, surgical removal should be considered due to concern for malignancy.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.
Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers
A pelvic examination may detect an adnexal mass. A CA-125 blood test is a nonspecific test that tends to be elevated in patients with tubal cancer. More specific tests are a gynecologic ultrasound examination, a CT scan, or an MRI of the pelvis.
Occasionally, an early fallopian tube cancer may be detected serendipitously during pelvic surgery.
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rate, even for metastatic gestational choriocarcinoma, is around 90–95%.
At present, treatment with single-agent methotrexate is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclosphosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.
Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding.
Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers.
Fertility subsequent to treatment of surface epithelial-stromal tumors depends mainly on histology and initial
staging to separate it into early borderline (or more benign) versus advanced stages of borderline (or more malignant). Conservative management (without bilateral oophorectomy) of early stage borderline tumors have been estimated to result in chance of over 50% of spontaneous pregnancy with a low risk of lethal recurrence of the tumor (0.5%). On the other hand, in cases of conservative treatment in advanced stage borderline tumors, spontaneous pregnancy rates have been estimated to be 35% and the risk of lethal recurrence 2%.
Surgical exploration and of possible ovarian tissue is required for the definitive diagnosis of ORS, and treatment by excision of the remnant ovarian tissue may be performed during the same procedure. For women who are not candidates for surgery, a clinical diagnosis can be made based on the symptoms and levels (follicle-stimulating hormone and estradiol, after bilateral oophorectomy) and/or findings consistent with the presence of residual ovarian tissue. Laparoscopy and histological assessment can aid in diagnosis.
The risk of ovarian remnant (ORS) is increased by incomplete removal of the ovarian at the time of oophorectomy. Surgical factors that contribute to incomplete removal include those that limit surgical exposure of the ovary, or compromise surgical technique. Factors may include:
- adhesions – these can limit visualization of the ovary and may also cause it to adhere to surrounding tissues. Adhesions are often present due to preexisting conditions and/or prior surgeries. In the majority of cases reported since 2007, endometriosis was the most common indication for the initial oophorectomy in patients who subsequently had ORS. Endometriosis increases the risk for functional ovarian tissue being embedded into adjacent structures, making complete excision of tissue challenging.
- Anatomic variations - unusual location of ovarian tissue, for example
- Intraoperative bleeding
- Poor surgical technique – this may include failure to obtain adequate exposure or restore adequate anatomy, or imprecise choice of incision site
Ovarian remnant (ORS) may first be considered in women who have undergone oophorectomy and have suggestive symptoms, the presence of a mass, or evidence of persistent ovarian function (by symptoms or laboratory testing). A history of oophorectomy is required, by definition, to make the diagnosis. Notes regarding the indication for the procedure and the procedure itself should be reviewed and may include prior abdominal or pelvic surgery, endometriosis, and/or poor surgical visualization. If ORS is possible, pelvic should be performed to evaluate for a pelvic mass.[1]
The usual chemotherapy regimen has limited efficacy in tumours of this type, although Imatinib has shown some promise. There is no current role for radiotherapy.
The usual treatment is surgery. The surgery for females usually is a fertility-sparing unilateral salpingo-oophorectomy. For malignant tumours, the surgery may be radical and usually is followed by adjuvant chemotherapy, sometimes by radiation therapy. In all cases, initial treatment is followed by surveillance. Because in many cases Leydig cell tumour does not produce elevated tumour markers, the focus of surveillance is on repeated physical examination and imaging.
In males, a radical inguinal orchiectomy is typically performed. However, testes-sparing surgery can be used to maintain fertility in children and young adults. This approach involves an inguinal or scrotal incision and ultrasound guidance if the tumour is non-palpable. This can be done because the tumour is typically unifocal, not associated with precancerous lesions, and is unlikely to recur.
The prognosis is generally good as the tumour tends to grow slowly and usually is benign: 10% are malignant. For malignant tumours with undifferentiated histology, prognosis is poor.
The diagnosis is strongly suggested by ultrasound (sonogram), but definitive diagnosis requires histopathological examination. On ultrasound, the mole resembles a bunch of grapes ("cluster of grapes" or "honeycombed uterus" or "snow-storm"). There is increased trophoblast proliferation and enlarging of the chorionic villi. Angiogenesis in the trophoblasts is impaired as well.
Sometimes symptoms of hyperthyroidism are seen, due to the extremely high levels of hCG, which can mimic the normal Thyroid-stimulating hormone (TSH).
Gynecologic ultrasonography is the imaging modality of choice. Use of doppler ultrasound in the diagnosis has been suggested. However, doppler flow is not always absent in torsion – the definitive diagnosis is often made in the operating room.
Lack of ovarian blood flow on doppler sonography seems to be a good predictor of ovarian torsion. Women with pathologically low flow are more likely to have OT (77% vs. 29% in a study). The sensitivity and specificity of abnormal ovarian flow for OT are 44% and 92%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. Specific flow features on Doppler sonography include:
- Little or no intra-ovarian venous flow. This is commonly seen in ovarian torsion.
- Absent arterial flow. This is a less common finding in ovarian torsion
- Absent or reversed diastolic flow
Normal vascularity does not exclude intermittent torsion. There may occasionally be normal Doppler flow because of the ovary's dual blood supply from both the ovarian arteries and uterine arteries.
Other ultrasonographic features include:
- Enlarged hypoechogenic or hyperechogenic ovary
- Peripherally displaced ovarian follicles
- Free pelvic fluid. This may be seen in more than 80% of cases
- "Whirlpool sign" of twisted vascular pedicle
- Underlying ovarian lesion can often be found
- Uterus may be slightly deviated towards the torted ovary.
Prognosis depends to a large degree on the stage of the condition. In 1991 it was reported that about half of the patients with advanced stage disease survived 5 years with a surgical approach followed by cisplatinum-based chemotherapy.
Ovarian torsion is difficult to diagnose accurately, and operation is often performed before certain diagnosis is made. A study at an obstetrics and gynaecology department found that preoperative diagnosis of ovarian torsion was confirmed in only 46% of people.
Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.
Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).
The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.
Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise.
In a series of 12 patients the mean gestation age was 45 days.
Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelberg's criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics:
- The gestational sac is located in the region of the ovary.
- The gestational sac is attached to the uterus by the ovarian ligament.
- Ovarian tissue is histologically proven in the wall of the gestational sac.
- The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).
An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding.
Diagnosis is usually made by ultrasonography showing a solid ovarian lesion, or, on some occasions, mixed tumors with solid and cystic components. Computed tomography and magnetic resonance imaging can also be used to diagnose fibromas.
In a series of 16 patients, 5 (28%) showed elevated levels of CA-125.
Serum follicle-stimulating hormone (FSH) measurement alone can be used to diagnose the disease. Two FSH measurements with one-month interval have been a common practice. The anterior pituitary secretes FSH and LH at high levels due to the dysfunction of the ovaries and consequent low estrogen levels. Typical FSH in POF patients is over 40 mlU/ml (post-menopausal range).