Diagnosis of<unk>  is made first by a physical examination,<unk>  biopsy, or dilation and curettage (removal of<unk>  tissue; D&C). This tissue is then examined histologically for characteristics of cancer. If cancer is found, medical imaging may be done to see whether the cancer has spread or invaded tissue. Examination Vaginal ultrasonography with an<unk>  fluid accumulation (darker area) in a postmenopausal uterus,alt=An ultrasound image showing an<unk>  fluid accumulation (darker area) in a postmenopausal uterus, a finding that is highly suspicious for<unk>  Polypoidal<unk>  carcinoma Routine screening of asymptomatic people is not indicated since the disease is highly curable in its early, symptomatic stages. Instead, women, particularly menopausal women, should be aware of the symptoms and risk factors of<unk> . A cervical screening test, such as a Pap smear, is not a useful diagnostic tool for<unk>  because the smear will be normal 50% of the time. A Pap smear can detect disease that has spread to the cervix. Results from a pelvic examination are frequently normal, especially in the early stages of disease. Changes in the size, shape or consistency of the uterus or its surrounding, supporting structures may exist when the disease is more advanced. Cervical stenosis, the narrowing of the cervical opening, is a sign of<unk>  when pus or blood is found collected in the uterus (pyometra or hematometra). Women with Lynch syndrome should begin to have annual biopsy screening at the age of 35. Some women with Lynch syndrome elect to have a prophylactic hysterectomy and salpingo-oophorectomy to greatly reduce the risk of<unk>  and ovarian cancer. Transvaginal ultrasound to examine the<unk>  thickness in women with postmenopausal bleeding is increasingly being used to aid in the diagnosis of<unk>  in the United States. In the United Kingdom, both an<unk>  biopsy and a transvaginal ultrasound used in conjunction are the standard of care for diagnosing<unk> . The homogeneity of the tissue visible on transvaginal ultrasound can help to indicate whether the thickness is cancerous. Ultrasound findings alone are not conclusive in cases of<unk> , so another screening method (for example<unk>  biopsy) must be used in conjunction. Other imaging studies are of limited use. CT scans are used for preoperative imaging of tumors that appear advanced on physical exam or have a high-risk subtype (at high risk of metastasis). They can also be used to investigate extrapelvic disease. An MRI can be of some use in determining if the cancer has spread to the cervix or if it is an endocervical adenocarcinoma. MRI is also useful for examining the nearby lymph nodes. Dilation and curettage or an<unk>  biopsy are used to obtain a tissue sample for histological examination.<unk>  biopsy is the less invasive option, but it may not give conclusive results every time. Hysteroscopy only shows the gross anatomy of the endometrium, which is often not indicative of cancer, and is therefore not used, unless in conjunction with a biopsy. Hysteroscopy can be used to confirm a diagnosis of cancer. New evidence shows that D&C has a higher false negative rate than<unk>  biopsy. Before treatment is begun, several other investigations are recommended. These include a chest x-ray, liver function tests, kidney function tests, and a test for levels of CA-125, a tumor marker that can be elevated in<unk> . Classification<unk> s may be tumors derived from epithelial cells (carcinomas), mixed epithelial and mesenchymal tumors (carcinosarcomas), or mesenchymal tumors. Relative incidences of<unk>  carcinomas by histopathology. Traditional classification of<unk>  carcinomas is based either on clinical and endocrine features (Type I and Type II), or histopathological characteristics (endometrioid, serous, and clear-cell). Some tumors are difficult to classify and have features overlapping more than one category. High grade endometrioid tumors, in particular, tend to have both type I and type II features. Carcinoma The vast majority of<unk> s are carcinomas (usually adenocarcinomas), meaning that they originate from the single layer of epithelial cells that line the endometrium and form the<unk>  glands. There are many microscopic subtypes of<unk>  carcinoma, but they are broadly organized into two categories, Type I and Type II, based on clinical features and pathogenesis. The two subtypes are genetically distinct. Type I<unk>  carcinomas occur most commonly before and around the time of menopause. In the United States, they are more common in white women, particularly those with a history of<unk>  hyperplasia. Type I<unk> s are often low-grade, minimally invasive into the underlying uterine wall (myometrium), estrogen-dependent, and have a good outcome with treatment. Type I carcinomas represent 75–90% of<unk> . Type II<unk>  carcinomas usually occur in older, post-menopausal people, in the United States are more common in black women, and are not associated with increased exposure to estrogen or a history of<unk>  hyperplasia. Type II<unk> s are often high-grade, with deep invasion into the underlying uterine wall (myometrium), are of the serous or clear cell type, and carry a poorer prognosis. They can appear to be epithelial ovarian cancer on evaluation of symptoms. They tend to present later than Type I tumors and are more aggressive, with a greater risk of relapse and/or metastasis. Endometrioid adenocarcinoma In endometrioid adenocarcinoma, the cancer cells grow in patterns reminiscent of normal endometrium, with many new glands formed from columnar epithelium with some abnormal nuclei. Low-grade endometrioid adenocarcinomas have well differentiated cells, have not invaded the myometrium, and are seen alongside<unk>  hyperplasia. The tumor's glands form very close together, without the stromal tissue that normally separates them. Higher-grade endometrioid adenocarcinomas have less well-differentiated cells, have more solid sheets of tumor cells no longer organized into glands, and are associated with an atrophied endometrium. There are several subtypes of endometrioid adenocarcinoma with similar prognoses, including villoglandular, secretory, and ciliated cell variants. There is also a subtype characterized by squamous differentiation. Some endometrioid adenocarcinomas have foci of mucinous carcinoma. The genetic mutations most commonly associated with endometrioid adenocarcinoma are in the genes PTEN, a tumor suppressor; PIK3CA, a kinase; KRAS, a GTPase that functions in signal transduction; and CTNNB1, involved in adhesion and cell signaling. The CTNNB1 (beta-catenin) gene is most commonly mutated in the squamous subtype of endometrioid adenocarcinoma. Serous carcinoma Serous carcinoma is a Type II<unk>  tumor that makes up 5–10% of diagnosed<unk>  and is common in postmenopausal women with atrophied endometrium and black women. Serous<unk>  carcinoma is aggressive and often invades the myometrium and metastasizes within the peritoneum (seen as omental caking) or the lymphatic system. Histologically, it appears with many atypical nuclei, papillary structures, and, in contrast to endometrioid adenocarcinomas, rounded cells instead of columnar cells. Roughly 30% of<unk>  serous carcinomas also have psammoma bodies. Serous carcinomas spread differently than most other<unk> s; they can spread outside the uterus without invading the myometrium. The genetic mutations seen in serous carcinoma are chromosomal instability and mutations in TP53, an important tumor suppressor gene. Clear cell carcinoma Clear cell carcinoma is a Type II<unk>  tumor that makes up less than 5% of diagnosed<unk> . Like serous cell carcinoma, it is usually aggressive and carries a poor prognosis. Histologically, it is characterized by the features common to all clear cells: the eponymous clear cytoplasm when H&E stained and visible, distinct cell membranes. The p53 cell signaling system is not active in<unk>  clear cell carcinoma. This form of<unk>  is more common in postmenopausal women. Mucinous carcinoma Mucinous carcinomas are a rare form of<unk> , making up less than 1–2% of all diagnosed<unk> . Mucinous<unk>  carcinomas are most often stage I and grade I, giving them a good prognosis. They typically have well-differentiated columnar cells organized into glands with the characteristic mucin in the cytoplasm. Mucinous carcinomas must be differentiated from cervical adenocarcinoma. Mixed or undifferentiated carcinoma Mixed carcinomas are those that have both Type I and Type II cells, with one making up at least 10% of the tumor. These include the malignant mixed Müllerian tumor, which derives from<unk>  epithelium and has a poor prognosis. Undifferentiated<unk>  carcinomas make up less than 1–2% of diagnosed<unk> s. They have a worse prognosis than grade III tumors. Histologically, these tumors show sheets of identical epithelial cells with no identifiable pattern. Other carcinomas Non-metastatic squamous cell carcinoma and transitional cell carcinoma are very rare in the endometrium. Squamous cell carcinoma of the endometrium has a poor prognosis. It has been reported fewer than 100 times in the medical literature since its characterization in 1892. For primary squamous cell carcinoma of the endometrium (PSCCE) to be diagnosed, there must be no other primary cancer in the endometrium or cervix and it must not be connected to the cervical epithelium. Because of the rarity of this cancer, there are no guidelines for how it should be treated, nor any typical treatment. The common genetic causes remain uncharacterized. Primary transitional cell carcinomas of the endometrium are even more rare; 16 cases had
Endometrial cancer
Cervical cancer
Uterine cancer
Ovarian cancer
Vaginal cancer
Breast cancer
Intravenous leiomyomatosis
Ovarian disease