Endometrial intraepithelial neoplasia
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Synonyms and Keywords: Atypical endometrial hyperplasia; Minimal uterine serous cancer (MUSC); Serous endometrial intraepithelial carcinoma (EIC); MUSC; Minimal uterine serous cancer
Endometrial intraepithelial neoplasia lesions have been discovered beginning in the 1990s which provide a multifaceted characterization of this disease. The endometrial intraepithelial neoplasia diagnostic schema is intended to replace the previous "endometrial hyperplasia" classification as defined by the World Health Organization in 1994, which have been separated into benign (benign endometrial hyperplasia) and premalignant (EIN) classes in accordance with their behavior and clinical management.Endometrial intraepithelial neoplasia may be classified according to WHO94 schema classifies histology based on glandular complexity and nuclear atypia into 4 groups: simple hyperplasia, complex hyperplasia, simple hyperplasia with atypia, and complex hyperplasia with atypia. On microscopic histopathological analysis, individual glands lined by an pseudostratified epithelium one cell layer thick is a characteristic finding of endometrial intraepithelial neoplasia. Hysterectomy is recommended following the diagnosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
- Endometrial intraepithelial neoplasia lesions have been discovered by a combination of molecular, histologic, and clinical outcome studies beginning in the 1990s which provide a multifaceted characterization of this disease. They are a subset of a larger mixed group of lesions previously called "endometrial hyperplasia" The Endometrial intraepithelial neoplasia diagnostic schema is intended to replace the previous "endometrial hyperplasia" classification as defined by the World Health Organization in 1994, which have been separated into benign (benign endometrial hyperplasia) and premalignant (EIN) classes in accordance with their behavior and clinical management.
- Endometrial intraepithelial neoplasia may be classified according to WHO94 schema classifies histology based on glandular complexity and nuclear atypia into 4 groups:
- Simple hyperplasia
- Complex hyperplasia
- Simple hyperplasia with atypia
- Complex hyperplasia with atypia
- 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.
- Endometrial intraepithelial neoplasia lesions demonstrate all of the behaviors and characteristics of a premalignant, or precancerous, lesion.
- Precancer Features of EIN (Table I). The cells of an EIN lesion are genetically different than normal and malignant tissues, and have a distinctive appearance under the light microscope. EIN cells are already neoplastic, demonstrating a monoclonal growth pattern and clonally distributed mutations. Progression of EIN to carcinoma, effectively a conversion from a benign neoplasm to a malignant neoplasm, is accomplished through acquisition of additional mutations and accompanied by a change in behavior characterized by the ability to invade local tissues and metastasize to regional and distant sites.
Table I: Precancer Characteristics of EIN
|Precancer Characteristics||EIN Evidence|
|Precancers differ from normal tissue|
|Precancers share some, but not all, features of cancer|
|Precancers increase risk for carcinoma|
|Precancers can be diagnosed|
|Cancer must arise from cells within the precancer|
- Endometrial intraepithelial carcinoma (EIC) to be the precursor of serous adenocarcinoma.
- The mutation in p53 gene has been associated with the development of endometrial intraepithelial neoplasia.
- On microscopic histopathological analysis, individual glands lined by an pseudostratified epithelium one cell layer thick are characteristic finding of endometrial intraepithelial neoplasia.
- Endometrial intraepithelial neoplasia may be caused by either estrogenic stimulation of the endometrium, unopposed by progestins.
Differentiating Endometrial intraepithelial neoplasia from other Diseases
- Endometrial intraepithelial neoplasia must be differentiated from other diseases that cause endometrial disorders such as:
- Endometrial glandular dysplasia
- Endometrial intraepithelial neoplasia
- Hyperplastic polyp
- Metastatic carcinoma
- The spectrum of disease which must be distinguished from endometrial intraepithelial neoplasia includes benign endometrial hyperplasia and carcinoma:
Epidemiology and Demographics
- The average age at time of endometrial intraepithelial neoplasia diagnosis is approximately 52 years, compared to approximately 61 years for carcinoma.
- Females are affected with endometrial intraepithelial neoplasia.
- 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.
Natural History, Complications and Prognosis
- If left untreated, according to a study, 38% of patients with endometrial intraepithelial neoplasia may progress to develop endometrial cancer.
- Common complications of endometrial intraepithelial neoplasia include endometrial carcinoma, metastases and death.
- Prognosis is generally good with treatment.
- The diagnosis of endometrial intraepithelial neoplasia is made when the following diagnostic criteria are met:
- Area of glands greater than stroma (volume percentage stroma less than 55%)
- Cytology differs between architecturally crowded focus and background
- Maximum linear dimension exceeds 1 mm
- Benign conditions with overlapping criteria (ie, basalis, secretory, polyps, repair)
- Carcinoma if maze-like glands, solid areas, or appreciable cribriforming
|1||Architecture||Gland area exceeds that of stroma, usually in a localized region.|
|Cytology differs between architecturally crowded focus and background.|
|3||Size greater than 1mm||Maximum linear dimension should exceed 1mm. Smaller lesions have unknown natural history.|
|4||Exclude mimics||Basalis, normal secretory, polyps, repair, lower uterine segment, cystic atrophy, tangential sections, menstrual collapse, disruption artifact, etc.|
|5||Exclude Cancer||Carcinoma should be diagnosed if: glands are mazelike and rambling, there are solid areas of epithelial growth, or there are significant bridges or cribriform areas.|
- Symptoms of endometrial intraepithelial neoplasia may include the following:
- Postmenopausal bleeding
- Physical examination may be remarkable for:
- Palpable pelvic masses
- There are no specific laboratory findings associated with endometrial intraepithelial neoplasia.
- Transvaginal ultrasonography is indicated for postmenopausal patient who has bleeding to detect malignancy.
- If transvaginal ultrasonography demonstrate an endometrial thickness greater than 4 mm or an inability to adequately visualize endometrial thickness should warrant further evaluation using sonohysterography, office hysteroscopy, or endometrial biopsy.
Other Diagnostic Studies
- Endometrial intraepithelial neoplasia is mainly diagnosed using endometrial suction curette and hematoxylin and eosin staining.
- The mainstay of medical therapy for endometrial intraepithelial neoplasia is progestin therapy.
- Hysterectomy is recommended following the diagnosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
- Hysterectomy is recommended following the diagnosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
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