Endometrial intraepithelial neoplasia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]
Synonyms and keywords: Atypical endometrial hyperplasia; Minimal uterine serous cancer (MUSC); Serous endometrial intraepithelial carcinoma (EIC); MUSC; Minimal uterine serous cancer
Overview
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, indiidual glands lined by an pseudostratified epithelium one cell layer thick is a characteristic finding of endometrial intraepithelial neoplasia. Hysterectomy is recommended following the diagnvosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
Historaical Perspective
- Endometrial intraepithelial neoplasia was first 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.[1][2]
Classification
- Endometrial hyperplasia may be classified according to new World Health Organization (WHO2014) into two groups:[3]
- Hyperplasia without atypia (non-neoplastic)
- Atypical hyperplasia (endometrial intraepithelial neoplasm)
- Endometrial hyperplasia may be classified according to new World Health Organization (WHO1994) into 4 groups:[4]
- Simple hyperplasia without atypia
- Complex hyperplasia without atypia
- Simple atypical hyperplasia
- Complex atypical hyperplasia
Pathophysiology
- 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.
- 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.
Causes
- Endometrial intraepithelial neoplasia may be caused by either estrogenic stimulation of the endometrium, unopposed by progestins.[5]
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
Age
- The average age at time of endometrial intraepithelial neoplasia diagnosis is approximately 52 years, compared to approximately 61 years for carcinoma.
Gender
- Females are affected with endometrial intraepithelial neoplasia.
Risk Factors
- The most potent risk factor in the development of endometrial intraepithelial neoplasia (EIN) is exposure to endogenous (exogenous estrogen without opposing by a progestin).[6]
- Other risk factors include:[7][8][9][10][11]
- Aging
- Early menarche
- Late menopause (after age 55)
- Obesity
- Diabetes
- Tamoxifen therapy
- Polycystic ovary syndrome (chronic anovulation)
- Nulliparity
- Cowden syndrome
- Lynch syndrome (hereditary conditions such as hereditary nonpolyposis colorectal cancer)
- Family history (endometrial, ovarian, breast, colon cancer)
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.
Diagnosis
Diagnostic Criteria
- 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
| 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 | 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
- The hallmark of endometrial intraepithelial neoplasia is postmenopausal bleeding.
- Postmenopausal bleeding
Physical Examination
- Physical examination may be remarkable for:
- Palpable pelvic masses
Laboratory Findings
- There are no specific laboratory findings associated with endometrial intraepithelial neoplasia.
Imaging Findings
- 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.
Treatment
Medical Therapy
- The mainstay of medical therapy for endometrial intraepithelial neoplasia is progestin therapy.
Surgery
- Hysterectomy is recommended following the diagnosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
Prevention
- Hysterectomy is recommended following the diagnosis of endometrial intraepithelial neoplasia to prevent endometrial carcinoma.
References
- ↑ Mutter GL, Duska L, Crum CP (2005). "Endometrial Intraepithelial Neoplasia". In Crum CP, Lee K. Diagnostic Gynecologic and Obstetric Pathology. Philadelphia PA: Saunders. pp. 493–518.
- ↑ 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. WHO Classification of Tumors: Pathology and Genetics of Tumors of the Breast and Female Genital Organs. Lyon, France: IARC Press. pp. 221–232.
- ↑ Emons G, Beckmann MW, Schmidt D, Mallmann P (February 2015). "New WHO Classification of Endometrial Hyperplasias". Geburtshilfe Frauenheilkd. 75 (2): 135–136. doi:10.1055/s-0034-1396256. PMC 4361167. PMID 25797956.
- ↑ Wang, Steven; Wang, Zhenglong; Mittal, Khushbakhat (2015). "Concurrent endometrial intraepithelial carcinoma (EIC) and endometrial hyperplasia". Human Pathology: Case Reports. 2 (1): 1–4. doi:10.1016/j.ehpc.2014.07.003. ISSN 2214-3300.
- ↑ Owings, Richard A.; Quick, Charles M. (2014). "Endometrial Intraepithelial Neoplasia". Archives of Pathology & Laboratory Medicine. 138 (4): 484–491. doi:10.5858/arpa.2012-0709-RA. ISSN 0003-9985.
- ↑ Chandra V, Kim JJ, Benbrook DM, Dwivedi A, Rai R (January 2016). "Therapeutic options for management of endometrial hyperplasia". J Gynecol Oncol. 27 (1): e8. doi:10.3802/jgo.2016.27.e8. PMC 4695458. PMID 26463434.
- ↑ Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, van den Brandt PA, van de Vijver K, Thompson PJ, Strom BL, Spurdle AB, Soslow RA, Shu XO, Schairer C, Sacerdote C, Rohan TE, Robien K, Risch HA, Ricceri F, Rebbeck TR, Rastogi R, Prescott J, Polidoro S, Park Y, Olson SH, Moysich KB, Miller AB, McCullough ML, Matsuno RK, Magliocco AM, Lurie G, Lu L, Lissowska J, Liang X, Lacey JV, Kolonel LN, Henderson BE, Hankinson SE, Håkansson N, Goodman MT, Gaudet MM, Garcia-Closas M, Friedenreich CM, Freudenheim JL, Doherty J, De Vivo I, Courneya KS, Cook LS, Chen C, Cerhan JR, Cai H, Brinton LA, Bernstein L, Anderson KE, Anton-Culver H, Schouten LJ, Horn-Ross PL (July 2013). "Type I and II endometrial cancers: have they different risk factors?". J. Clin. Oncol. 31 (20): 2607–18. doi:10.1200/JCO.2012.48.2596. PMC 3699726. PMID 23733771.
- ↑ Smith RA, von Eschenbach AC, Wender R, Levin B, Byers T, Rothenberger D, Brooks D, Creasman W, Cohen C, Runowicz C, Saslow D, Cokkinides V, Eyre H (2001). "American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001--testing for early lung cancer detection". CA Cancer J Clin. 51 (1): 38–75, quiz 77–80. PMID 11577479.
- ↑ Elwood, J. Mark; Cole, Philip; Rothman, Kenneth J.; Kaplan, Samuel D. (1977). "Epidemiology of Endometrial Cancer
2". JNCI: Journal of the National Cancer Institute. 59 (4): 1055–1060. doi:10.1093/jnci/59.4.1055. ISSN 1460-2105. line feed character in
|title=at position 35 (help) - ↑ La Vecchia C, Franceschi S, Decarli A, Gallus G, Tognoni G (September 1984). "Risk factors for endometrial cancer at different ages". J. Natl. Cancer Inst. 73 (3): 667–71. PMID 6590913.
- ↑ Kalin A, Merideth MA, Regier DS, Blumenthal GM, Dennis PA, Stratton P (February 2013). "Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer". Obstet Gynecol. 121 (2 Pt 2 Suppl 1): 461–4. doi:http://10 1097/AOG.0b013e318270444f Check
|doi=value (help). PMC 3799979. PMID 23344409.