Endometrial intraepithelial neoplasia

Last updated
Histopathology of endometrial intraepithelial neoplasia (EIN), with its typical features: - 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. Histopathology of endometrial intraepithelial neoplasia (EIN).jpg
Histopathology of endometrial intraepithelial neoplasia (EIN), with its typical features:
- 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 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.

Contents

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 hyperplasia". [2] [3] The EIN 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.
EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma ("serous EIC"), which is an early stage of a different tumor type known as papillary serous adenocarcinoma that also occurs in the same location within the uterus.

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 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.

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 CharacteristicsEIN Evidence
Precancers differ from normal tissue
Precancers share some, but not all, features of cancer
Precancers increase risk for carcinoma
  • Elevated concurrent cancer rate (39% in first year after EIN diagnosis) [21]
  • EIN elevates future cancer risk 45-fold. [21]
Precancers can be diagnosed
  • Morphometric reference standard (D-Score) for EIN diagnosis. [4] [22] [23] [24]
  • Subjective EIN diagnosis using criteria (Table 2). [25]
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 PTEN is frequently inactivated in EIN, being abnormally turned off in approximately 2/3 of all EIN lesions. This can be seen with special tissue stains applied to histological sections known as PTEN immunohistochemistry, in which the brown PTEN protein is seen to be absent in the crowded tubular glands that make up an EIN lesion.

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		DiffuseHormone
(estrogen)
Effect		Hormonal therapy
EIN,
Endometrial
Intraepithelial
Neoplasia		Focal
progressing to
diffuse
(clonal)		PrecancerHormonal or
surgical
Endometrial
Adenocarcinoma		Focal
progressing to
diffuse
(clonal)		CancerSurgical
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 CriterionComments
1ArchitectureGland area exceeds that of stroma, usually in a localized region.
2Cytological
Alterations		Cytology differs between architecturally crowded focus and background.
3Size greater than 1mmMinimum linear dimension should exceed 1mm. Smaller lesions have unknown natural history.
4Exclude mimicsBasalis, normal secretory, polyps, repair, lower uterine segment, cystic atrophy, tangential sections, menstrual collapse, disruption artifact, etc.
5Exclude CancerCarcinoma 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

Related Research Articles

<span class="mw-page-title-main">Uterine cancer</span> Medical condition

Uterine cancer, also known as womb cancer, includes two types of cancer that develop from the tissues of the uterus. Endometrial cancer forms from the lining of the uterus, and uterine sarcoma forms from the muscles or support tissue of the uterus. Endometrial cancer accounts for approximately 90% of all uterine cancers in the United States. Symptoms of endometrial cancer include changes in vaginal bleeding or pain in the pelvis. Symptoms of uterine sarcoma include unusual vaginal bleeding or a mass in the vagina.

<span class="mw-page-title-main">Endometrial cancer</span> Uterine cancer that is located in tissues lining the uterus

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

Carcinoma <i>in situ</i> Medical condition

Carcinoma in situ (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question. Some authors do not classify them as cancer, however, recognizing that they can potentially become cancer. Others classify certain types as a non-invasive form of cancer. The term "pre-cancer" has also been used.

<span class="mw-page-title-main">Endometrioid tumor</span> Medical condition

Endometrioid tumors are a class of tumors that arise in the uterus or ovaries that resemble endometrial glands on histology. They account for 80% of endometrial carcinomas and 20% of malignant ovarian tumors.

<span class="mw-page-title-main">Serous tumour</span> Medical condition

A serous tumour is a neoplasm that typically has papillary to solid formations of tumor cells with crowded nuclei, and which typically arises on the modified Müllerian-derived serous membranes that surround the ovaries in females. Such ovarian tumors are part of the surface epithelial-stromal tumour group of ovarian tumors. They are common neoplasms with a strong tendency to occur bilaterally, and they account for approximately a quarter of all ovarian tumors.

<span class="mw-page-title-main">Hyperplasia</span> Increase in the amount of organic tissue that results from cell proliferation

Hyperplasia, or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferation. It may lead to the gross enlargement of an organ, and the term is sometimes confused with benign neoplasia or benign tumor.

<span class="mw-page-title-main">Neoplasm</span> Abnormal mass of tissue as a result of abnormal growth or division of cells

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumour or tumor.

<span class="mw-page-title-main">Benign tumor</span> Mass of cells which cannot spread throughout the body

A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.

<span class="mw-page-title-main">Precancerous condition</span> Medical condition

A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.

<span class="mw-page-title-main">Cowden syndrome</span> Medical condition

Cowden syndrome is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers. It is often underdiagnosed due to variability in disease presentation, but 99% of patients report mucocutaneous symptoms by age 20–29. Despite some considering it a primarily dermatologic condition, Cowden's syndrome is a multi-system disorder that also includes neurodevelopmental disorders such as macrocephaly.

The uterine sarcomas form a group of malignant tumors that arises from the smooth muscle or connective tissue of the uterus.

<span class="mw-page-title-main">Vulvar intraepithelial neoplasia</span> Medical condition

Vulvar intraepithelial neoplasia (VIN) refers to particular changes that can occur in the skin that covers the vulva. VIN is an intraepithelial neoplasia, and can disappear without treatment. VINs are benign but if the changes become more severe, there is a chance of cancer developing after many years, and so it is referred to as a precancerous condition.

<span class="mw-page-title-main">Endometrial hyperplasia</span> Medical condition

Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.

<span class="mw-page-title-main">High-grade prostatic intraepithelial neoplasia</span> Medical condition

High-grade prostatic intraepithelial neoplasia (HGPIN) is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma.

<span class="mw-page-title-main">Uterine serous carcinoma</span> Type of cancer of the uterus

Uterine serous carcinoma is a malignant form of serous tumor that originates in the uterus. It is an uncommon form of endometrial cancer that typically arises in postmenopausal women. It is typically diagnosed on endometrial biopsy, prompted by post-menopausal bleeding.

Uterine clear-cell carcinoma (CC) is a rare form of endometrial cancer with distinct morphological features on pathology; it is aggressive and has high recurrence rate. Like uterine papillary serous carcinoma CC does not develop from endometrial hyperplasia and is not hormone sensitive, rather it arises from an atrophic endometrium. Such lesions belong to the type II endometrial cancers.

The Bethesda system (TBS), officially called The Bethesda System for Reporting Cervical Cytology, is a system for reporting cervical or vaginal cytologic diagnoses, used for reporting Pap smear results. It was introduced in 1988 and revised in 1991, 2001, and 2014. The name comes from the location of the conference, sponsored by the National Institutes of Health, that established the system.

<span class="mw-page-title-main">Bowenoid papulosis</span> Medical condition

Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis. They are associated with human papillomavirus, the causative agent of genital warts. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.

<span class="mw-page-title-main">Villoglandular adenocarcinoma of the cervix</span> Medical condition

Villoglandular adenocarcinoma of the cervix is a rare type of cervical cancer that, in relation to other cervical cancers, is typically found in younger women and has a better prognosis.

Microglandular hyperplasia (MGH) of the cervix is an epithelial benign abnormality (lesion) associated with gland proliferation. It can terminate in mature squamous metaplasia, and it is suspected reserve cells are involved in this process, perhaps in the form of reserve cell hyperplasia with glandular differentiation.

References

  1. ↑ 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   1543-2165.
  2. ↑ 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.
  3. 1 2 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.
  4. 1 2 3 Mutter GL, Baak JP, Crum CP, Richart RM, Ferenczy A, Faquin WC (March 2000). "Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry". J. Pathol. 190 (4): 462–9. doi:10.1002/(SICI)1096-9896(200003)190:4<462::AID-PATH590>3.0.CO;2-D. PMID   10699996. S2CID   30636750.
  5. ↑ Jovanovic AS, Boynton KA, Mutter GL (April 1996). "Uteri of women with endometrial carcinoma contain a histopathological spectrum of monoclonal putative precancers, some with microsatellite instability". Cancer Res. 56 (8): 1917–21. PMID   8620514.
  6. 1 2 Mutter GL, Chaponot ML, Fletcher JA (February 1995). "A polymerase chain reaction assay for non-random X chromosome inactivation identifies monoclonal endometrial cancers and precancers". Am. J. Pathol. 146 (2): 501–8. PMC   1869842 . PMID   7856759.
  7. 1 2 3 Esteller M, García A, Martínez-Palones JM, Xercavins J, Reventós J (January 1997). "Detection of clonality and genetic alterations in endometrial pipelle biopsy and its surgical specimen counterpart". Lab. Invest. 76 (1): 109–16. PMID   9010454.
  8. ↑ Mutter GL, Boynton KA (November 1995). "X chromosome inactivation in the normal female genital tract: implications for identification of neoplasia". Cancer Res. 55 (21): 5080–4. PMID   7585555.
  9. 1 2 3 Esteller M, Catasus L, Matias-Guiu X, et al. (November 1999). "hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis". Am. J. Pathol. 155 (5): 1767–72. doi:10.1016/S0002-9440(10)65492-2. PMC   1866976 . PMID   10550333.
  10. 1 2 3 Pontzer CH, Bazer FW, Johnson HM (October 1991). "Antiproliferative activity of a pregnancy recognition hormone, ovine trophoblast protein-1". Cancer Res. 51 (19): 5304–7. PMID   1913653.
  11. 1 2 3 Mutter GL, Wada H, Faquin WC, Enomoto T (October 1999). "K-ras mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis". Mol. Pathol. 52 (5): 257–62. doi:10.1136/mp.52.5.257. PMC   395707 . PMID   10748874.
  12. 1 2 3 Maxwell GL, Risinger JI, Gumbs C, et al. (June 1998). "Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias". Cancer Res. 58 (12): 2500–3. PMID   9635567.
  13. 1 2 3 Sasaki H, Nishii H, Takahashi H, et al. (April 1993). "Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma". Cancer Res. 53 (8): 1906–10. PMID   8467512.
  14. 1 2 3 Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH (August 1998). "PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma". Cancer Res. 58 (15): 3254–8. PMID   9699651.
  15. 1 2 Mutter GL, Boynton KA, Faquin WC, Ruiz RE, Jovanovic AS (October 1996). "Allelotype mapping of unstable microsatellites establishes direct lineage continuity between endometrial precancers and cancer". Cancer Res. 56 (19): 4483–6. PMID   8813144.
  16. 1 2 Mutter GL, Lin MC, Fitzgerald JT, et al. (June 2000). "Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers". J. Natl. Cancer Inst. 92 (11): 924–30. doi: 10.1093/jnci/92.11.924 . PMID   10841828.
  17. 1 2 Duggan BD, Felix JC, Muderspach LI, Tsao JL, Shibata DK (March 1994). "Early mutational activation of the c-Ki-ras oncogene in endometrial carcinoma". Cancer Res. 54 (6): 1604–7. PMID   8137266.
  18. 1 2 Esteller M, Levine R, Baylin SB, Ellenson LH, Herman JG (November 1998). "MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas". Oncogene. 17 (18): 2413–7. doi: 10.1038/sj.onc.1202178 . PMID   9811473.
  19. ↑ Doherty T, Connell J, Stoerker J, Markham N, Shroyer AL, Shroyer KR (September 1995). "Analysis of clonality by polymerase chain reaction for phosphoglycerate kinase-1. Heteroduplex generator". Diagn. Mol. Pathol. 4 (3): 182–90. doi:10.1097/00019606-199509000-00005. PMID   7493137.
  20. ↑ Shroyer KR, Gudlaugsson EG (March 1994). "Analysis of clonality in archival tissues by polymerase chain reaction amplification of PGK-1". Hum. Pathol. 25 (3): 287–92. doi:10.1016/0046-8177(94)90201-1. PMID   8150459.
  21. 1 2 Baak JP, Mutter GL, Robboy S, et al. (June 2005). "The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system". Cancer. 103 (11): 2304–12. doi:10.1002/cncr.21058. PMC   2600877 . PMID   15856484.
  22. ↑ Mutter GL. Endometrial Precancer Type Collection [On Line]. http://www.endometrium.org 2000.
  23. ↑ Mutter GL (March 2000). "Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group". Gynecol. Oncol. 76 (3): 287–90. doi:10.1006/gyno.1999.5580. PMID   10684697.
  24. ↑ Mutter GL (October 2000). "Histopathology of genetically defined endometrial precancers". Int. J. Gynecol. Pathol. 19 (4): 301–9. doi:10.1097/00004347-200010000-00002. PMID   11109157.
  25. ↑ Hecht JL, Ince TA, Baak JP, Baker HE, Ogden MW, Mutter GL (March 2005). "Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis". Mod. Pathol. 18 (3): 324–30. doi:10.1038/modpathol.3800328. PMC   2573865 . PMID   15529181.

PTEN Gene

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.