Endometrial intraepithelial neoplasia
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- Architectural gland crowding
- Altered cytology relative to background glands
- Minimum size of 1 mm
- Exclusion of adenocarcinoma
- Exclusion of mimics
Mitoses should also preferably be seen. Compare to normal endometrial gland at right.
Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to
History
EIN 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
EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma ("serous EIC"), which is an early stage of a different
Clinical aspects
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
Biology
EIN 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 |
EIN Biomarkers. (Figure 1). There are no single biomarkers which are completely informative in recognition of EIN. The tumour suppressor gene
Diagnosis
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:[3]
Table II: Disease classes that need to be distinguished from EIN.
| Disease Class |
Endometrial Topography |
Functional Category |
Treatment |
|---|---|---|---|
| Benign endometrial hyperplasia |
Diffuse | Hormone (estrogen) Effect |
Hormonal therapy |
| EIN, Endometrial Intraepithelial Neoplasia |
Focal progressing to diffuse (clonal) |
Precancer | Hormonal or surgical |
| Endometrial Adenocarcinoma |
Focal progressing to diffuse (clonal) |
Cancer | Surgical stage-based |
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.
| EIN Criterion | Comments | |
|---|---|---|
| 1 | Architecture | Gland area exceeds that of stroma, usually in a localized region. |
| 2 | Cytological Alterations |
Cytology differs between architecturally crowded focus and background. |
| 3 | Size greater than 1mm | Minimum 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. |
See also
References
- ISSN 1543-2165.
- ^ Mutter GL, Duska L, Crum CP (2005). "Endometrial Intraepithelial Neoplasia". In Crum CP, Lee K (eds.). Diagnostic Gynecologic and Obstetric Pathology. Philadelphia PA: Saunders. pp. 493–518.
- ^ a b Silverberg SG, Mutter GL, Kurman RJ, Kubik-Huch RA, Nogales F, Tavassoli FA (2003). "Tumors of the uterine corpus: epithelial tumors and related lesions". In Tavassoli FA, Stratton MR (eds.). WHO Classification of Tumors: Pathology and Genetics of Tumors of the Breast and Female Genital Organs. Lyon, France: IARC Press. pp. 221–232.
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External links
- American Cancer Society
- OncoLink an educational site from the U. of Pennsylvania
- www.endometrium.org a pathology site focusing on endometrial disease
PTEN Gene
- Cancer Genetics Web PTEN entry
- PTEN and the Endometrium at PubMed
- Entrez Gene PTEN entry