Endometrial hyperplasia
Authors:Aarti Sharma, M.D., Ricardo R. Lastra, M.D.
Editorial Board Member:Jennifer A. Bennett, M.D.
Editor-in-Chief:Debra L. Zynger, M.D.
Last author update: 20 February 2020
Last staff update: 6 October 2022 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Endometrial hyperplasia[TI] review[ptyp]
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Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Treatment | Gross description | Gross images | Frozen section description | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Immunohistochemistry & special stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Sharma A, Lastra RR. Endometrial hyperplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/uterusendometrialhyperplasiageneral.html. Accessed January 28th, 2023.
Definition / general
- Proliferation of endometrial glands with a resulting increase in gland to stroma ratio
- Current system of classification (Kurman: WHO Classification of Tumours of the Female Reproductive Organs, 4th Edition, 2014):
- Hyperplasia without atypia
- Atypical hyperplasia / endometrioid intraepithelial neoplasia (AH / EIN)
- Prior terminologies (simple and complex) are no longer included
- AH / EIN is considered a premalignant condition
- Increased risk of both progression to and simultaneous endometrial endometrioid adenocarcinoma
Essential features
- Estrogen driven precursor lesion to endometrial endometrioid adenocarcinoma
- Increase in gland to stroma ratio (> 3:1 glandular to stromal elements)
- Divided into 2 groups: with or without atypia
- Definitive treatment for AH / EIN is hysterectomy; progestin therapy for fertility preservation
Terminology
- Obsolete terms:
- Cystic hyperplasia
- Adenomatous hyperplasia
- Simple and complex hyperplasia
ICD coding
- ICD-10: N85.00 - endometrial hyperplasia, unspecified
- ICD-O: 8380/2 - endometrioid intraepithelial neoplasia
Epidemiology
- Similar to that of endometrial endometrioid adenocarcinoma
- Age: fourth to sixth decades (peak fifth)
- Increased circulating estrogen:
- Body mass index (BMI): dose response relationship of BMI ≥25 and risk of hyperplasia (Am J Obstet Gynecol 2016;214:689.e1)
- Nulliparous females (Cancer 1985;56:403, Am J Epidemiol 2008;168:563)
- No race predilection
Sites
- Uterus: endometrium, endometrial polyps or adenomyosis
- Any tissue involved by endometriosis
- Ectopic endometrial glands / stroma are responsive to estrogen stimulation and can also develop an endometrial-like hyperplasia and subsequently carcinoma (Gynecol Oncol 2002;84:280, Gynecol Oncol 1996;60:238, Int J Gynecol Pathol 1996;15:1)
Pathophysiology
- Increased endogenous or exogenous estrogen, unopposed by progesterone (Semin Oncol Nurs 2019;35:157):
- Initially, estrogen has mitogenic effect on both endometrial glands and stroma
- Chronic estrogenic stimulation without progesterone affects glands to a greater extent → glandular overgrowth (hyperplasia)
Etiology
- Premenopausal
- Polycystic ovarian syndrome (PCOS): increased circulating androgens peripherally converted into estrogen
- Chronic anovulation / infertility: dysregulated estrogen without opposing progesterone secretion → simultaneous proliferation and breakdown
- Peri and postmenopausal
- Exogenous estrogen:
- Estrogen supplementation: systemic therapy to alleviate symptoms of menopause → endometrial proliferation
- Tamoxifen: hormonal treatment for breast cancer acts as estrogen receptor antagonist in breast but agonist in endometrium
- Exogenous estrogen:
- Any age
- Obesity: aromatase (enzyme converting circulating androgens to estrogen) is found in adipose tissue → peripheral hyperestrogenism (Mod Pathol 2000;13:295, Am J Obstet Gynecol 2016;214:689.e1)
- Ovarian pathology:
- Stromal hyperplasia and hyperthecosis: stromal luteinization → hyperandrogenism → hyperestrogenism (BJOG 2003;110:690)
- Hormone secreting stromal tumors: granulosa cell tumor, thecoma
Clinical features
- Abnormal or dysfunctional uterine bleeding (Obstet Gynecol Surv 2004;59:368)
- Rare cases asymptomatic
Diagnosis
- Pelvic / transvaginal ultrasound
- Endometrial biopsy
- Hysteroscopy with endometrial curettage (Eur J Gynaecol Oncol 2007;28:400)
Laboratory
- No validated biomarker for endometrial hyperplasia
Radiology description
- Thickened endometrial stripe on pelvic / transvaginal ultrasound (Obstet Gynecol Sci 2016;59:192)
- Generally no discrete mass
Prognostic factors
- Endometrial hyperplasia
- Presence / absence of atypia is most important feature
- AH / EIN associated with:
- Progression to endometrial endometrioid adenocarcinoma in up to 28% of cases without hysterectomy after 20 year followup (J Clin Oncol 2010;28:788)
- Concurrent endometrial carcinoma in up to 43% of cases (Cancer 2006;106:812)
- Majority are low grade (FIGO grade 1) and low stage (FIGO stage IA or IB) (J Obstet Gynaecol Can 2008;30:896)
- Hyperplasia without atypia: progression to endometrial endometrioid adenocarcinoma in up to 4.6% of cases after 20 year followup (J Clin Oncol 2010;28:788)
Treatment
- Endometrial hyperplasia without atypia:
- Hysterectomy too aggressive; risk of progression to or simultaneous endometrial endometrioid adenocarcinoma is low (refer to Prognostic factors)
- Treatments outlined below for AH / EIN acceptable within appropriate clinical context
- Endometrial hyperplasia without atypia arising in endometrial polyp: polypectomy curative if completely excised under hysteroscopic guidance
- Endometrial ablation can be used (not adequate alternate therapy for AH / EIN or refractory endometrial hyperplasia without atypia) (Am J Obstet Gynecol 1998;179:569)
- AH / EIN:
- Hysterectomy with or without bilateral salpingo-oophorectomy is definitive treatment
- If patient desires fertility or is not a surgical candidate:
- AH / EIN arising in endometrial polyp
- Polypectomy curative if completely excised under operative hysteroscopy
- Hysterectomy occasionally warranted in appropriate clinical context
- Progestin therapy: oral or intrauterine device (Am J Obstet Gynecol 2014;210:255.e1, Hum Reprod 2013;28:1231, Obstet Gynecol 2013;121:1165)
- Latter considered superior for efficacy, compliance and prevention of recurrence
- Can even be trialed for fertility preservation in cases up to nonmyoinvasive FIGO grade 1 endometrioid adenocarcinoma
- Metformin controversial (Cochrane Database Syst Rev 2017;10:CD012214)
- AH / EIN arising in endometrial polyp
Gross description
- Usually not grossly appreciable
- Florid to pseudopolypoid endometrium (similar to that of secretory phase)
Gross images
Images hosted on other servers:
Tag: What Is Endometrial Intraepithelial Neoplasia
Endometrial hyperplasia
Frozen section description
- Not appropriate for diagnosing hyperplasia or atypia
- Intraoperative consultation may be utilized for diagnosing adenocarcinoma in a patient with preoperative diagnosis of AH / EIN but this is not considered standard of care
- Concurrent carcinoma may be missed intraoperatively due to endometrial undersampling for lack of gross lesion (Am J Obstet Gynecol 2007;196:e40, Asian Pac J Cancer Prev 2012;13:1953)
Microscopic (histologic) description
- Endometrial hyperplasia without atypia
- Architecture:
- Closely packed glands such that gland to stroma ratio is > 3:1 but stroma is still present between glandular basement membranes (however minimal)
- Variation in gland size with cystic dilatation or irregular luminal contours (budding, angulation, invagination, outpouching, papillary projections)
- Associated with stromal breakdown
- Increased volume of endometrial tissue on biopsy / curetting is typical but NOT required for diagnosis
- Cytologic features:
- Reminiscent of normal proliferative endometrium with pseudostratified, mitotically active, elongated columnar cells
- Can show mild cellular enlargement but retain smooth nuclear contours without distinct nucleoli
- Metaplastic changes common (eosinophilic, papillary syncytial, squamous morular, mucinous, ciliated)
- Architecture:
- AH / EIN
- Architecture:
- Similar to the spectrum described above for hyperplasia without atypia
- Cytologic features:
- Enlarged, rounded and irregular nuclear contours
- Prominent, enlarged nucleoli with coarse and vesicular chromatin
- Occasionally, cytoplasmic eosinophilia imparts a distinct low power appearance
- Stratified cells demonstrating loss of polarity with respect to basement membrane
- Metaplastic changes can be seen
- Architecture:
Microscopic (histologic) images
Contributed by Aarti Sharma, M.D.
Hyperplasia without atypia
AH / EIN
AH / EIN bordering on FIGO grade I endometrial endometrioid adenocarcinoma
Virtual slides
Images hosted on other servers:
AH / EIN
Immunohistochemistry & special stains
- Not typically useful in differential diagnosis between normal endometrium and benign / malignant endometrial proliferations
- Loss of PTEN or PAX2 (Int J Gynecol Pathol 2015;34:40, Cancer Res 2010;70:6225)
- Most frequently mutated genes in endometrioid endometrial carcinoma and its precursors (tumor suppressor and transcription factor inactivation, respectively)
- Helpful but neither sensitive nor specific for AH / EIN
Molecular / cytogenetics description
- No reproducible genomic alterations
- AH / EIN is variably associated with mutations in PTEN, PIK3CA, KRAS, CTNNB1 (Jpn J Cancer Res 1998;89:985, Cancer Res 1998;58:3254, Med Klin 1975;70:812)
- Similar to endometrial endometrioid adenocarcinoma
- Loss of mismatch repair proteins resulting in progressive accumulation of microsatellite unstable loci (Mod Pathol 2019;32:1508)
Sample pathology report
- Endometrium, curettage:
- Disordered proliferative endometrium with focus of hyperplasia without atypia
- Endometrium, biopsy:
- AH / EIN focally bordering on endometrial endometrioid adenocarcinoma (FIGO grade I) (see comment)
- Comment: There are rare minute foci suspicious for a FIGO grade 1 endometrioid endometrial adenocarcinoma. Recommend additional sampling with endometrial curettage for a more definitive diagnosis.
Differential diagnosis
Benign:
- Compression artifact:
- Telescoping and pseudocompression of glands due to procedure / processing artifact may create appearance of packed and back to back glands
- Absence of peripheral stromal elements to lesion in question is a clue to artificial density
- Cystic atrophy:
- Can have similar low power appearance to hyperplastic endometrium with closely apposed and cystically dilated glands but these do not have the irregular contours of hyperplasia
- Glandular lining is low cuboidal to flattened without mitotic activity, in contrast to proliferative endometrium
- Stroma is dense and resembles that of endometrium basalis
- Endometrial polyp:
- Similar low power appearance in biopsies (by definition - altered, disorganized or irregular glands)
- Distinct densely fibrotic stroma
- Thick walled blood vessels
- Endometrial polyps can contain foci of AH / EIN
- Disordered proliferative endometrium:
- No well delineated criteria
- Histologically considered as degree below hyperplasia without atypia on a shared morphologic spectrum and distinction is often not reproducible
- Both have similar treatment (exogenous progestin)
- Metaplastic changes:
- Squamous and morular metaplasia
- When involving nonhyperplastic glands, can create false appearance of solid crowding
- As in endometrial endometrioid adenocarcinoma, squamous component should be subtracted in assessment of glandular architecture
- Surface syncytial and eosinophilic metaplasia
- Similar low power appearance due to cytoplasmic eosinophilia and epithelial proliferation
- Metaplasia is usually cytologically bland
- Squamous and morular metaplasia
- Endometrial stromal / glandular breakdown:
- Menstrual endometrium may demonstrate altered cytology, such as loss of polarity due to nuclear piling and coarsening of chromatin
- Collapse of glands creates artificial crowding without stromal scaffolding
- Presence of glandular aggregation amidst necrotic predecidua can deceptively mimic carcinoma
Malignant:
- Endometrioid adenocarcinoma, FIGO grade 1:
- Degree of atypia between the two is usually similar
- AH / EIN should NOT have:
- Cribriforming, confluent glands
- Labyrinthine intraluminal connections
- Areas of purely solid epithelium
- Stromal alteration suggesting invasion - desmoplasia (myofibroblasts, edema, inflammation) or necrosis (intervening endometrial stroma replaced by pools of neutrophilic debris)
Additional references
- Mod Pathol 2000;13:309, Semin Diagn Pathol 2010;27:199
Board review style question #1
The uterine lesion in the image above is commonly associated with which of the following?
- Anovulatory menstrual cycles
- Brown-red and firm, infiltrative gross appearance
- Intrauterine device is considered definitive therapy
- No increased risk of endometrial carcinoma
- Weak staining for WT1 and GATA3
Board review style answer #1
A. Anovulatory menstrual cycles. The photomicrograph shows an image of endometrioid intraepithelial neoplasia.
Comment Here
Reference: Endometrial hyperplasia / endometrioid intraepithelial neoplasia (EIN)
Board review style question #2
Which of the following features is required for a diagnosis of endometrial hyperplasia?
- Crowded glands with minimal residual intervening stroma
- Diffuse nuclear staining for p53
- Documentation of a PTEN mutation or loss of PTEN by IHC
- Glands with cribriforming architecture and cytologic alterations distinct from surrounding glands
- Loss of mismatch repair proteins
Board review style answer #2
A. Crowded glands with minimal residual intervening stroma
Comment Here
Reference: Endometrial hyperplasia / endometrioid intraepithelial neoplasia (EIN)
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FAQs
How serious is endometrial hyperplasia? ›
Untreated atypical endometrial hyperplasia can become cancerous. Endometrial or uterine cancer develops in about 8% of women with untreated simple atypical endometrial hyperplasia. Close to 30% of women with complex atypical endometrial hyperplasia who don't get treatment develop cancer.
What is the treatment for endometrial hyperplasia? ›In many cases, endometrial hyperplasia can be treated with progestin. Progestin is given orally, in a shot, in an intrauterine device (IUD), or as a vaginal cream. How much and how long you take it depends on your age and the type of hyperplasia. Treatment with progestin may cause vaginal bleeding like a period.
Does endometrial hyperplasia lead to cancer? ›Endometrial hyperplasia is an increased growth of the endometrium. Mild or simple hyperplasia, the most common type, has a very small risk of becoming cancer. It may go away on its own or after treatment with hormone therapy. If the hyperplasia is called “atypical,” it has a higher chance of becoming a cancer.
Should I have a hysterectomy for endometrial hyperplasia? ›Women with atypical hyperplasia should undergo a total hysterectomy because of the risk of underlying malignancy or progression to cancer. A laparoscopic approach to total hysterectomy is preferable to an abdominal approach as it is associated with a shorter hospital stay, less postoperative pain and quicker recovery.
Will a hysterectomy cure endometrial hyperplasia? ›Atypical hyperplasia can turn into cancer of the womb. However, hysterectomy is a complete cure if carried out before the cancer develops. After a hysterectomy for endometrial hyperplasia, the condition cannot return, as there is no endometrium left to grow.
What happens if endometrial hyperplasia is left untreated? ›Endometrial hyperplasia can progress to endometrial cancer if left untreated. Hormonal therapies such as the levonorgestrel-releasing intrauterine system (LNG-IUS) and oral progestogens have a role in preventing disease progression.
What is the most common age to get endometrial hyperplasia? ›Results. Endometrial hyperplasia peak incidence was: simple-142/100,000 woman-years, complex-213/100,000 woman-years, both in the early 50s; and atypical-56/100,000 woman-years in the early 60s.
What are the side effects of endometrial hyperplasia? ›- Heavy menstrual bleeding.
- Bleeding that happens after menopause.
- Menstrual cycles that are shorter than 21 days.
Endometriosis is an estrogen-dependent disease, which means that its symptoms may worsen when estrogen levels are higher. However, there is no evidence that this can cause weight gain.
Does endometrial hyperplasia show up on Pap smear? ›Pap tests are not used to screen for endometrial cancer; however, Pap test results sometimes show signs of an abnormal endometrium (lining of the uterus). Follow-up tests may detect endometrial cancer.
Can losing weight help endometrial hyperplasia? ›
This study found that weight loss improves response rates in women with obesity and atypical hyperplasia or low-risk endometrial cancer undergoing conservative management with intrauterine progestin.
How long does hyperplasia turn into cancer? ›At 5 years after diagnosis, about 7% of women with atypical hyperplasia may develop breast cancer. Put another way, for every 100 women diagnosed with atypical hyperplasia, 7 can be expected to develop breast cancer five years after diagnosis.
Can endometrial cancer be seen on ultrasound? ›Images from the TVUS can be used to see if the uterus contains a mass (tumor), or if the endometrium is thicker than usual, which can be a sign of endometrial cancer. It may also help see if cancer is growing into the muscle layer of the uterus (myometrium).
How do you reverse endometrial hyperplasia? ›Three approaches to medical reversal can be considered: (1) simply stopping estrogen, (2) stopping estrogen and giving progestin, and (3) continuing estrogen with addition of progestin. It is unclear whether hyperplasia can reverse with only stopping estrogen.
Should I be worried about endometrial hyperplasia? ›In women with endometrial hyperplasia, cells that amass in the uterine lining are abnormal and may, over time, become cancerous. For this reason, women with heavy periods and other symptoms of endometrial hyperplasia should not wait to seek diagnosis and treatment.
Does endometrial hyperplasia cause fatigue? ›When endometrial-like tissue grows outside of the uterus, the body launches an immune response to try to remove the tissue. This can cause extreme pain but also chronic fatigue.
Does exercise help endometrial hyperplasia? ›Exercise Training Prevents Endometrial Hyperplasia and Biomarkers for Endometrial Cancer in Rat Model of Type 1 Diabetes - PMC. The .
What type of hysterectomy is done for endometrial hyperplasia? ›A postmenopausal patient needing surgery for benign endometrial hyperplasia/hyperplasia without atypia can be offered total hysterectomy with bilateral salpingo-oophorectomy.
When should I worry about endometrial thickness? ›If an endometrial thickness of ≥ 8 mm is considered abnormal, 0.9% of women without cancer and without bleeding and 12% of women without cancer and with bleeding will have endometrial measurements above this threshold, and 95% of women with cancer will have endometrial measurements above this threshold.
What happens after a positive endometrial biopsy? ›After an endometrial biopsy, some women experience light bleeding, so you may want to wear a sanitary pad for a few days. Keep in mind, however, that you shouldn't use tampons during this time. With regard to pain, mild cramping is fairly common, so you may want to take an over-the-counter pain reliever.
Can you reverse endometrial hyperplasia? ›
Results: Based on four large series, more than 90% of endometrial hyperplasia caused by ERT can be reversed by medical treatment.
Does hyperplasia get worse? ›Hyperplasia without atypia can eventually develop atypical cells. The main complication is the risk that it will progress to uterine cancer. Atypia is considered precancerous. Various studies have estimated the risk of progression from atypical hyperplasia to cancer as high as 52 percent.
What are the 4 types of endometrial hyperplasia? ›- simple hyperplasia without atypia,
- complex hyperplasia without atypia,
- simple atypical hyperplasia,
- complex atypical hyperplasia 1, 2.
The endometrial hyperplasia has a cystic lace-like appearance on ultrasound. Endometrial polyps manifest as focal areas of endometrial thickening, and the stalk of the polyp may be seen if sufficient fluid is present in the endometrial cavity.
How can I reduce endometrial thickness naturally? ›- Increase your intake of omega-3 fats. ...
- Reduce your intake of trans fats. ...
- Increase your intake of antioxidants. ...
- Try an anti-inflammatory diet. ...
- Avoid sugar and processed foods.
A buildup of endometrial-like tissue can cause inflammation in the abdomen, resulting in swelling, water retention, and bloating. The endometrial-like tissue can cover or grow into the ovaries. Trapped blood can form cysts when this happens, which may cause bloating.
Who is at risk of endometrial hyperplasia? ›Endometrial hyperplasia is more likely to occur in women with the following risk factors: Age over 35 years. Never having been pregnant. Older age at menopause (over 55 years old).
Does hyperplasia mean precancerous? ›Breast anatomy
Atypical hyperplasia is a precancerous condition that affects cells in the breast. Atypical hyperplasia describes an accumulation of abnormal cells in the milk ducts and lobules of the breast. Atypical hyperplasia isn't cancer, but it increases the risk of breast cancer.
Atypical hyperplasia is generally treated with surgery to remove the abnormal cells and to make sure no in situ or invasive cancer also is present in the area. Doctors often recommend more-intensive screening for breast cancer and medications to reduce your breast cancer risk.
Is hyperplasia a biopsy finding? ›Diagnosis of hyperplasia
Hyperplasia doesn't usually cause a lump that can be felt, but it can sometimes cause changes that can be seen on a mammogram. It's diagnosed by doing a biopsy, during which a hollow needle or surgery is used to take out some of the abnormal breast tissue for testing.
What happens if you have endometrial hyperplasia? ›
Endometrial hyperplasia is a condition in which the lining of your womb becomes too thick. In some women, this can lead to cancer of the uterus. Endometrial hyperplasia is rare. It affects about 133 out of 100,000 women.
Does hyperplasia go away after menopause? ›Simple Hyperplasia can go away on its own or with hormonal treatment. Endometrial Hyperplasia is caused by either too much estrogen or not enough progesterone.