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In a recent study, about 60% of USCs were found to overexpress the protein HER2/neu—the same one that is overexpressed in some breast cancers. The monoclonal antibody trastuzumab (Herceptin) is currently being tested as a therapy for this subset of USCs.
The antibody trastuzumab (Herceptin), which is used to treat breast cancers that overexpress the HER2/neu protein, has been tried with some success in a phase II trial in women with UPSCs that overexpress HER2/neu.
The primary treatment is surgical. FIGO-cancer staging is done at the time of surgery which consists of peritoneal cytology, total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and omentectomy. The tumor is aggressive and spreads quickly into the myometrium and the lymphatic system. Thus even in presumed early stages, lymphadenectomy and omentectomy should be included in the surgical approach. If the tumor has spread surgery is cytoreductive followed by radiation therapy and/or chemotherapy.
In a study to determine if adjuvant therapy should be used in patients with stage I UPSC who had undergone surgery, no increased survival was seen when radiation therapy was added versus observation, while the postsurgical treatment with chemotherapy may be beneficial but more data are needed.
A study of the usefulness of platinum-based chemotherapy as an adjuvant after surgery of stage I patients showed that patients with stage 1A who had no residual disease in the hysterectomy specimen had no recurrence regardless if chemotherapy was used or not, however, patients with stage 1A disease with residual disease in the hysterectomy specimen had no recurrence with platinum-based therapy, but those who had no such chemotherapy showed recurrence in 43%. Similarly, patients with stage 1B disease with chemotherapy had no recurrence, while those without chemotherapy had a high degree (77%) of recurrence.
There are several experimental therapies for endometrial cancer under research, including immunologic, hormonal, and chemotherapeutic treatments. Trastuzumab (Herceptin), an antibody against the Her2 protein, has been used in cancers known to be positive for the Her2/neu oncogene, but research is still underway. Immunologic therapies are also under investigation, particularly in uterine papillary serous carcinoma.
Cancers can be analyzed using genetic techniques (including DNA sequencing and immunohistochemistry) to determine if certain therapies specific to mutated genes can be used to treat it. PARP inhibitors are used to treat endometrial cancer with PTEN mutations, specifically, mutations that lower the expression of PTEN. The PARP inhibitor shown to be active against endometrial cancer is olaparib. Research is ongoing in this area as of the 2010s.
Research is ongoing on the use of metformin, a diabetes medication, in obese women with endometrial cancer before surgery. Early research has shown it to be effective in slowing the rate of cancer cell proliferation. Preliminary research has shown that preoperative metformin administration can reduce expression of tumor markers. Long-term use of metformin has not been shown to have a preventative effect against developing cancer, but may improve overall survival.
Temsirolimus, an mTOR inhibitor, is under investigation as a potential treatment. Research shows that mTOR inhibitors may be particularly effective for cancers with mutations in PTEN. Ridaforolimus (deforolimus) is also being researched as a treatment for people who have previously had chemotherapy. Preliminary research has been promising, and a stage II trial for ridaforolimus was completed by 2013. There has also been research on combined ridaforolimus/progestin treatments for recurrent endometrial cancer. Bevacizumab and tyrosine kinase inhibitors, which inhibit angiogenesis, are being researched as potential treatments for endometrial cancers with high levels of vascular endothelial growth factor. Ixabepilone is being researched as a possible chemotherapy for advanced or recurrent endometrial cancer. Treatments for rare high-grade undifferentiated endometrial sarcoma are being researched, as there is no established standard of care yet for this disease. Chemotherapies being researched include doxorubicin and ifosfamide.
There is also research in progress on more genes and biomarkers that may be linked to endometrial cancer. The protective effect of combined oral contraceptives and the IUD is being investigated. Preliminary research has shown that the levonorgestrel IUD placed for a year, combined with 6 monthly injections of gonadotropin-releasing hormone, can stop or reverse the progress of endometrial cancer in young women. An experimental drug that combines a hormone with doxorubicin is also under investigation for greater efficacy in cancers with hormone receptors. Hormone therapy that is effective in treating breast cancer, including use of aromatase inhibitors, is also being investigated for use in endometrial cancer. One such drug is anastrozole, which is currently being researched in hormone-positive recurrences after chemotherapy. Research into hormonal treatments for endometrial stromal sarcomas is ongoing as well. It includes trials of drugs like mifepristone, a progestin antagonist, and aminoglutethimide and letrozole, two aromatase inhibitors.
Research continues into the best imaging method for detecting and staging endometrial cancer. In surgery, research has shown that complete pelvic lymphadenectomy along with hysterectomy in stage 1 endometrial cancer does not improve survival and increases the risk of negative side effects, including lymphedema. Other research is exploring the potential of identifying the sentinel lymph nodes for biopsy by injecting the tumor with dye that shines under infrared light. Intensity modulated radiation therapy is currently under investigation, and already used in some centers, for application in endometrial cancer, to reduce side effects from traditional radiotherapy. Its risk of recurrence has not yet been quantified. Research on hyperbaric oxygen therapy to reduce side effects is also ongoing. The results of the PORTEC 3 trial assessing combining adjuvant radiotherapy with chemotherapy were awaited in late 2014.
The average age at time of EIN diagnosis is approximately 52 years, compared to approximately 61 years for carcinoma. The timeframe and likelihood of EIN progression to cancer, however, is not constant amongst all women. Some cases of EIN are first detected as residual premalignant disease in women who already have carcinoma, whereas other EIN lesions disappear entirely and never lead to cancer. For this reason, treatment benefits and risks must be individualized for each patient under the guidance of an experienced physician.
Risk factors for development of EIN and the endometrioid type of endometrial carcinoma include exposure to estrogens without opposing progestins, obesity, diabetes, and rare hereditary conditions such as hereditary nonpolyposis colorectal cancer. Protective factors include use of combined oral contraceptive pills (low dose estrogen and progestin), and prior use of a contraceptive intrauterine device.
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.
Smoking and the use of progestin are both protective against endometrial cancer. Smoking provides protection by altering the metabolism of estrogen and promoting weight loss and early menopause. This protective effect lasts long after smoking is stopped. Progestin is present in the combined oral contraceptive pill and the hormonal intrauterine device (IUD). Combined oral contraceptives reduce risk more the longer they are taken: by 56% after four years, 67% after eight years, and 72% after twelve years. This risk reduction continues for at least fifteen years after contraceptive use has been stopped. Obese women may need higher doses of progestin to be protected. Having had more than five infants (grand multiparity) is also a protective factor, and having at least one child reduces the risk by 35%. Breastfeeding for more than 18 months reduces risk by 23%. Increased physical activity reduces an individual's risk by 38–46%. There is preliminary evidence that consumption of soy is protective.
International Federation of Gynecology and Obstetrics (FIGO) staging is done at the time of surgery:
A malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor, MMMT and carcinosarcoma, is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. It is divided into two types, homologous (in which the sarcomatous component is made of tissues found in the uterus such as endometrial, fibrous and/or smooth muscle tissues) and a heterologous type (made up of tissues not found in the uterus, such as cartilage, skeletal muscle and/or bone). MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in postmenopausal women with an average age of 66 years. Risk factors are similar to those of adenocarcinomas and include obesity, exogenous estrogen therapies, and nulliparity. Less well-understood but potential risk factors include tamoxifen therapy and pelvic irradiation.
Carcinoma "in situ" is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.
Some forms of CIS (e.g., colon polyps and polypoid tumours of the bladder) can be removed using an endoscope, without conventional surgical resection. Dysplasia of the uterine cervix is removed by excision (cutting it out) or by burning with a laser. Bowen's disease of the skin is removed by excision. Other forms require major surgery, the best known being intraductal carcinoma of the breast (also treated with radiotherapy). One of the most dangerous forms of CIS is the "pneumonic form" of BAC of the lung, which can require extensive surgical removal of large parts of the lung. When too large, it often cannot be completely removed, with eventual disease progression and death of the patient.
Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium (modified peritoneum) or from endometrial or Fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment.
There is debate over the naming of MMMT; the term carcinosarcoma was formerly used to describe lesions with homologous tumors, and "malignant mixed Müllerian tumor" or "mixed mesodermal tumor" was used to describe heterologous tumors. While "carcinosarcoma" now considered standard, "malignant mixed Müllerian tumor" has a lengthy history within gynecological literature and is expected to continue to be used. The naming issue to a certain extent reflects histological characteristics and development of the tumors, in which the different types of tissues are believed to either develop separately and join into a single mass (the "collision" theory), that an adenocarcinoma stimulates the stroma to create a tumor (the "composition" theory), or that the tumor is the result of a stem cell that differentiates into different cell types (the "combination" theory). "Collision" tumors are normally easily recognized and not considered true MMMTs; the "combination" theory is most widely held, and is due to evidence that the tumors develop from a single line of cells, developing in a fashion similar to the fundus of the uterus from the Müllerian duct - first from a stem cell into a population of cells, that then differentiates into epithelial and stromal components.
There is evidence that some tumors are better explained by the composition theory, due to the aggressive nature of the epithelial cells involved which tend to metastasize much more readily than the sarcomal component. The behavior of MMMT overall is more related to the type and grade of the epithelium than the sarcoma, which suggests the sarcomal portion is an atypical "bystander" than primary driver of the tumor. Despite this, when purely endometrial tumors are compared to MMMTs, the MMMT tumor tends to have a worse prognosis.
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%.
Ovarian tumors, or ovarian neoplasms, are tumors arising from the ovary. They can be benign or malignant (ovarian cancer).
Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
Benign tumors of the ovary include ovarian cysts, such as borderline tumor cysts.
A urogenital neoplasm is a tumor of the urogenital system.
Types include:
- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)
- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)
- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)
Clear cell ovarian tumors are part of the surface epithelial-stromal tumor group of ovarian cancers, accounting for 6% of these cancers. Clear cell tumors are also associated with the pancreas and salivary glands.
Carcinoma "in situ (CIS), also known as in situ" neoplasm, is a group of abnormal cells. While they are a form of neoplasm there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, breast). Some authors do not classify them as cancer, however, recognizing that they can potentially become cancer. Others classify certain types as a non-invasive form of cancer. The term "pre-cancer" has also been used.
These abnormal cells grow in their normal place, thus ""in situ"" (from Latin for "in its place"). For example, carcinoma "in situ" of the skin, also called Bowen's disease, is the accumulation of dysplastic epidermal cells within the epidermis only, that has failed to penetrate into the deeper dermis. For this reason, CIS will usually not form a tumor. Rather, the lesion is flat (in the skin, cervix, etc.) or follows the existing architecture of the organ (in the breast, lung, etc.). Exceptions include CIS of the colon (polyps), the bladder (preinvasive papillary cancer), or the breast (ductal carcinoma "in situ" or lobular carcinoma "in situ").
Many forms of CIS have a high probability of progression into cancer, and therefore removal may be recommended; however, progression of CIS is known to be highly variable and not all CIS becomes invasive cancer.
In the TNM classification, carcinoma "in situ" is reported as TisN0M0 (stage 0).
Wide, radical, complete surgical excision is the treatment of choice, with free surgical margins to achieve the best outcome and lowest chance of recurrence. Radiation is only used for palliation. In general, there is a good prognosis, although approximately 50% of patients die from disease within 3–10 years of presentation.
The treatment of choice for main-duct IPMNs is resection due to approximately 50% chance of malignancy. Side-branch IPMNs are occasionally monitored with regular CT or MRIs, but most are eventually resected, with a 30% rate of malignancy in these resected tumors. Survival 5 years after resection of an IPMN without malignancy is approximately 80%, 85% with malignancy but no lymph node spread and 0% with malignancy spreading to lymph nodes. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy or robotic surgery. A study using Surveillance, Epidemiology, and End Result Registry (SEER) data suggested that increased lymph node counts harvested during the surgery were associated with better survival in invasive IPMN patients.
Cystadenocarcinoma is a malignant form of a cystadenoma and is a malignant neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. The neoplastic cells manifest varying degrees of anaplasia and invasiveness, and local extension and metastases occur. Cystadenocarcinomas develop frequently in the ovaries, where pseudomucinous and serous types are recognized. Similar tumor histology has also been reported in the pancreas, although it is a considerably rarer entity.
It is the most common malignant ovarian tumor. Contains complex multi-loculated cyst but with exuberant solid areas in places. It usually presents with omental metastases which cause ascites.
Ovarian serous cystadenoma, also (less precisely) known as serous cystadenoma, is the most common ovarian neoplasm, representing 20% of ovarian neoplasms, and is benign.Human Reproduction. University of Utah Medpath http://library.med.utah.edu/kw/human_reprod/seminars/seminar4B2.html.
It has a very superficial resemblance to the most common type of ovarian cancer (serous carcinoma of the ovary) under the microscope; however, (1) it is virtually impossible to mix-up with its malignant counterpart (serous carcinoma), and (2) does not share genetic traits of indeterminate serous tumours, also called "serous borderline tumours", that may transform into serous carcinoma.
Serous cystadenomas (of the ovary) are not related to serous cystadenomas of the pancreas, i.e. the presence of an ovarian "or" pancreatic one does "not" suggest an increased risk for the other one.
A gonadal tissue neoplasm is a tumor having any histology characteristic of cells or tissues giving rise to the gonads. These tissues arise from the sex cord and stromal cells. The tumor may be derived from these tissues, or produce them.
Although the tumor is composed of gonadal tissue, it is not necessarily located in an ovary or testicle.
A gonadal tissue neoplasm should not be confused with a urogenital neoplasm, though the two topics are often studied together. The embryology of the gonads is only indirectly related to the embryology of the external genitals and urinary system.
These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.
Typically, they are cystic neoplasms with polypoid masses that protrude into the cyst. On microscopic pathological examination, they are composed of cells with clear cytoplasm (that contains glycogen) and "hob nail" cells (from which the glycogen has been secreted). The pattern may be glandular, papillary or solid.