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Diagnosis of EIN lesions is of clinical importance because of the increased risk of coexisting (39% of women with EIN will be diagnosed with carcinoma within one year) or future (the long term endometrial cancer risk is 45 times greater for a woman with EIN compared to one with only a benign endometrial histology) endometrial cancer. Diagnostic terminology is that used by pathologists, physicians who diagnose human disease by examination of histologic preparations of excised tissues. Critical distinctions in EIN diagnosis are separation from benign conditions such as benign endometrial hyperplasia (a field effect in endometrial tissue caused by excessive stimulation by the hormone estrogen), and cancer.
The spectrum of disease which must be distinguished from EIN (Table II) includes benign endometrial hyperplasia and carcinoma:
Table II: Disease classes that need to be distinguished from EIN.
EIN may be diagnosed by a trained pathologist by examination of tissue sections of the endometrium. All of the following diagnostic criteria must be met in a single area of one tissue fragment to make the diagnosis (Table III).
Table III: EIN diagnosis.
For surface epithelial-stromal tumors, the most common sites of metastasis are the pleural cavity (33%), the liver (26%), and the lungs (3%).
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.
It is important to exclude a tumor which is directly extending into the ear canal from the parotid salivary gland, especially when dealing with an adenoid cystic or mucoepidermoid carcinoma. This can be eliminated by clinical or imaging studies. Otherwise, the histologic differential diagnosis includes a ceruminous adenoma (a benign ceruminous gland tumor) or a neuroendocrine adenoma of the middle ear (middle ear adenoma).
Investigations by the physician include imaging (ultrasound, CAT scan, MRI) and, if possible, obtaining a tissue diagnosis by biopsy, hysteroscopy, or D&C.
Ultimately the diagnosis is established by the histologic examination of the specimen. Typically malignant lesions have >10 mitosis per high power field. In contrast a uterine leiomyoma as a benign lesion would have < 5 mitosis per high power field.
For more general information, see ovarian cancer.
For advanced cancer of this histology, the US National Cancer Institute recommends a method of chemotherapy that combines intravenous (IV) and intraperitoneal (IP) administration. Preferred chemotherapeutic agents include a platinum drug with a taxane.
Prognosis of the UPSC is affected by age, stage, and histology as well as treatment.
There are many diagnostic methods that can be used to determine the type of salivary gland tumour and if it is benign or malignant. Examples of diagnostic methods include:
Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.
MRI
Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer, and has been shown to produce accurate results when differentiating between benign and malignant tumours.
Radiographs: An OPG (orthopantomogram) can be taken to rule out mandibular involvement. A chest radiograph may also be taken to rule out any secondary tumours.
Ultrasound: Ultrasound can be used to initially assess a tumour that is located superficially in either the submandibular or parotid gland. It can distinguish an intrinsic from an extrinsic neoplasm. Ultrasonic images of malignant tumours include ill defined margins.
Intraductal papillary mucinous neoplasms can come to clinical attention in a variety of different ways. The most common symptoms include abdominal pain, nausea and vomiting. The most common signs patients have when they come to medical attention include jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), weight loss, and acute pancreatitis. These signs and symptoms are not specific for an intraductal papillary mucinous neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.
Once a doctor has reason to believe that a patient may have an intraductal papillary mucinous neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal dilatation of the pancreatic duct or one of the branches of the pancreatic duct. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.
IPMN forms cysts (small cavities or spaces) in the pancreas. These cysts are visible in CT scans (X-ray computed tomography). However, many pancreatic cysts are benign (see Pancreatic disease).
A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (i.e. undergoing an ultrasound, CT or MRI scan) for another reason. Up to 6% of patients undergoing pancreatic resection did so for treatment of incidental IPMNs.
In 2011, scientists at Johns Hopkins reported that they have developed a gene-based test that can be used to distinguish harmless from precancerous pancreatic cysts. The test may eventually help patients with harmless cysts avoid needless surgery. Bert Vogelstein and his colleagues discovered that almost all of the precancerous cysts (intraductal papillary mucinous neoplasms) of the pancreas have mutations in the KRAS and/or the GNAS gene. The researchers then tested a total of 132 intraductal papillary mucinous neoplasms for mutations in KRAS and GNAS. Nearly all (127) had mutations in GNAS, KRAS or both. Next, the investigators tested harmless cysts such as serous cystadenomas, and the harmless cysts did not have GNAS or KRAS mutations. Larger numbers of patients must be studied before the gene-based test can be widely offered.
99% of cervical polyps will remain benign and 1% will at some point show neoplastic change. Cervical polyps are unlikely to regrow.
The diagnosis of salivary gland tumors utilize both tissue sampling and radiographic studies. Tissue sampling procedures include fine needle aspiration (FNA) and core needle biopsy (bigger needle comparing to FNA). Both of these procedures can be done in an outpatient setting. Diagnostic imaging techniques for salivary gland tumors include ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI).
Fine needle aspiration biopsy (FNA), operated in experienced hands, can determine whether the tumor is malignant in nature with sensitivity around 90%. FNA can also distinguish primary salivary tumor from metastatic disease.
Core needle biopsy can also be done in outpatient setting. It is more invasive but is more accurate compared to FNA with diagnostic accuracy greater than 97%. Furthermore, core needle biopsy allows more accurate histological typing of the tumor.
In terms of imaging studies, ultrasound can determine and characterize superficial parotid tumors. Certain types of salivary gland tumors have certain sonographic characteristics on ultrasound. Ultrasound is also frequently used to guide FNA or core needle biopsy.
CT allows direct, bilateral visualization of the salivary gland tumor and provides information about overall dimension and tissue invasion. CT is excellent for demonstrating bony invasion. MRI provides superior soft tissue delineation such as perineural invasion when compared to CT only.
The lesion is found in patients who present typically with abnormal or postmenopausal bleeding. Such bleeding is followed by further evaluation leading to a tissue diagnosis, usually done by a dilatation and curettage (D&C). A work-up to follow would look for metastasis using imaging technology including sonography and MRI. The median age at diagnosis in a study of 138 women was 67 years, of these 54 had stage I, 20 stage II, 41 stage III, and 23 stage IV disease.
Histopathologically, uterine serous carcinomas is typically characterized by (1) nipple-shaped structures (papillae) with fibrovascular cores (2) marked nuclear atypia (irregularies in the nuclear membrane, enlarged nuclear size), (3) psammoma bodies and (4) cilia.
Unusual or postmenopausal bleeding may be a sign of a malignancy including uterine sarcoma and needs to be investigated. Other signs include pelvic pain, pressure, and unusual discharge. A nonpregnant uterus that enlarges quickly is suspicious. However, none of the signs are specific. Specific screening test have not been developed; a Pap smear is a screening test for cervical cancer and not designed to detect uterine sarcoma.
The definitive diagnosis is by histologic analysis, i.e. and examination under the microscope.
Under the microscope, OKCs vaguely resemble keratinized squamous epithelium; however, they lack rete ridges and often have an artifactual separation from their basement membrane.
On a CT scan, The radiodensity of a keratocystic odontogenic tumour is about 30 Hounsfield units, which is about the same as ameloblastomas. Yet, ameloblastomas show more bone expansion and seldom show high density areas.
Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.
Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.
A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.
Radiologically
- Odontogenic Myxoma
- Ameloblastoma
- Central Giant Cell Granuloma
- Adenomatoid odontogenic tumor
Histologically
- Orthokeratocyst
- Radicular cyst (particularly if the OKC is very inflamed)
- Unicystic ameloblastoma
Patients are usually managed by a multidisciplinary team including surgeons, gynecologists, and dermatologists because of the complex nature of this disorder. Follow-up for the increased risk of breast cancer risk includes monthly breast self-examination, annual breast examination, and mammography at age 30 or five years earlier than the youngest age of breast cancer in the family. The magnitude of the risk of breast cancer justifies routine screening with breast MRI as per published guidelines.
Cervical polyps can be removed using ring forceps. They can also be removed by tying surgical string around the polyp and cutting it off. The remaining base of the polyp can then be removed using a laser or by cauterisation. If the polyp is infected, an antibiotic may be prescribed.
Diagnosis of endometrial hyperplasia can be made by endometrial biopsy, which is done in the office setting or through curettage of the uterine cavity to obtain endometrial tissue for histopathologic analysis. A workup for endometrial disease may be prompted by abnormal uterine bleeding, or the presence of atypical glandular cells on a pap smear.
Endometrial polyps are usually benign although some may be precancerous or cancerous. About 0.5% of endometrial polyps contain adenocarcinoma cells. Polyps can increase the risk of miscarriage in women undergoing IVF treatment. If they develop near the fallopian tubes, they may lead to difficulty in becoming pregnant. Although treatments such as hysteroscopy usually cure the polyp concerned, recurrence of endometrial polyps is frequent. Untreated, small polyps may regress on their own.
The treatment is simple excision and exclusion of a malignant neoplasm.
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 endometrial cancer. A cervical screening test, such as a Pap smear, is not a useful diagnostic tool for endometrial cancer 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 and/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 endometrial cancer 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 endometrial and ovarian cancer.
Transvaginal ultrasound to examine the endometrial thickness in women with postmenopausal bleeding is increasingly being used to aid in the diagnosis of endometrial cancer in the United States. In the United Kingdom, both an endometrial biopsy and a transvaginal ultrasound used in conjunction are the standard of care for diagnosing endometrial cancer. 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 endometrial cancer, so another screening method (for example endometrial 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 endometrial biopsy are used to obtain a tissue sample for histological examination. Endometrial 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 endometrial 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 endometrial cancer.
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.
Endometrial polyps can be detected by vaginal ultrasound (sonohysterography), hysteroscopy and dilation and curettage. Detection by ultrasonography can be difficult, particularly when there is endometrial hyperplasia (excessive thickening of the endometrium). Larger polyps may be missed by curettage.
Endometrial polyps can be solitary or occur with others. They are round or oval and measure between a few millimeters and several centimeters in diameter. They are usually the same red/brown color of the surrounding endometrium although large ones can appear to be a darker red. The polyps consist of dense, fibrous tissue (stroma), blood vessels and glandlike spaces lined with endometrial epithelium. If they are pedunculated, they are attached by a thin stalk (pedicle). If they are sessile, they are connected by a flat base to the uterine wall. Pedunculated polyps are more common than sessile ones.
Prognosis of the CC is affected by age, stage, and histology as well as treatment
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.
The five years survival was reported to be 68%.