Endometrial Polyps

Endometrial polyps are pedunculated or sessile projections of the endometrium that result from overgrowth of endometrial glands and stroma around a central vascular stalk. Endometrial polyps are a few millimeters to a few centimeters in size, can occur anywhere within the uterine cavity, and, while usually benign, can be malignant, particularly in postmenopausal women. Endometrial polyps present with abnormal uterine or postmenopausal bleeding, although many are asymptomatic and discovered incidentally. Endometrial polyps are best diagnosed with a saline-infusion sonogram, and are usually treated with hysteroscopic resection.

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Overview

Definition

Endometrial polyps result from the usually benign overgrowth of endometrial glands and stroma around a central vascular stalk forming a pedunculated or sessile projection from the endometrium that can develop anywhere in the uterine cavity.

Epidemiology

  • Exact prevalence difficult to establish (many patients are asymptomatic)
  • 10%–24% in women undergoing endometrial biopsy or hysterectomy 
  • Prevalence of malignancy in women with polyps:
    • Postmenopausal women: 4%–5% 
    • Premenopausal women: 1%–2%

Risk factors

  • Unopposed estrogen exposure
  • Tamoxifen use
  • Postmenopausal hormone therapy
  • Advanced age
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome ( hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance)
  • Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome
  • Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome

Classification

  • By shape:
    • Pedunculated: elongated finger-like pedicle (more common)
    • Sessile: large, flat base
  • Endometrial polyps are 1 structural cause of abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding (AUB) in the PALM-COEIN classification.
Causes of aub

Classification of abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding and its causes

Image by Lecturio.

Pathophysiology

The exact mechanisms for pathogenesis are unknown, but estrogen seems to play an important stimulating role.

  • Potential mechanism:
    • Monoclonal endometrial hyperplasia Endometrial Hyperplasia Endometrial hyperplasia (EH) is the abnormal growth of the uterine endometrium. This abnormal growth may be due to estrogen stimulation or genetic mutations leading to uncontrolled proliferation. Endometrial Hyperplasia and Endometrial Cancer
    • Overexpression of endometrial aromatase → ↑ local estrogen production
    • Gene mutations
  • Polyps (such as regular endometrium) are hormonal responsive:
    • Express both estrogen and progesterone receptors:
      • Estrogen: stimulates proliferation
      • Progesterone: anti-proliferative
    • Tamoxifen: 
      • Selective estrogen receptor modulator (SERM) that has estrogenic activity in endometrium
      • Stimulates polyp proliferation (known risk factor)
  • Histopathology:
    • Hyperplastic overgrowth of endometrial glands and stroma occurs, surrounding the vascular core.
    • Smooth muscle may be present.
    • May develop anywhere within uterine cavity
    • Single or multiple lesions
Glandular cystic endometrial polyp

Hematoxylin and eosin (H&E) stain of a glandular cystic endometrial polyp

Image: “Glandular cystic endometrial polyp” by Clinical Hospital ‘Pheophania’ of State Affairs Department, Zabolotny str,, 21, Kyiv 03680, Ukraine. License: CC BY 2.0

Clinical Presentation

Most common presentation of symptomatic polyps involves bleeding:

  • AUB may include:
    • Intermenstrual bleeding (most common)
    • Heavy menstrual bleeding 
  • Postcoital/contact bleeding (if prolapsing through cervix)
  • Postmenopausal bleeding
  • Fertility challenges:
    • Recurrent pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care loss
    • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
  • Abdominal or pelvic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain is less commonly associated.
  • Often asymptomatic

Diagnosis

Imaging

  • Transvaginal ultrasound:
    • 1st-line imaging modality for AUB
    • Finding: thickened endometrial lining
  • Saline infusion sonogram (SIS):
    • Best test for diagnosis of polyps
    • Process:
      • Sonography while uterine cavity is distended with injection of saline 
      • Distension allows visualization of intracavitary pathology.
    • Helpful in distinguishing between: 
      • Polyps
      • Submucosal leiomyomas
      • Septa
      • Synechiae
    • Findings: mass arising from endometrium protruding into uterine cavity
  • Hysteroscopy:
    • Surgical alternative to SIS
    • Allows for simultaneous diagnosis (visually and with biopsies) and treatment of most intrauterine pathology

Tissue sampling

Tissue sampling is required to rule out malignancy within polyps.

  • Hysteroscopic polypectomy:
    • Preferred test 
    • Excisional biopsy with endoscopic guide
    • Diagnostic and therapeutic
  • Dilation and curettage (without hysteroscopy) 
  • Office pipelle endometrial biopsy: 
    • 1st-line test for evaluating AUB or postmenopausal bleeding
    • Low sensitivity for polyps (inadequate for diagnosis)
    • Polyps identified: 
      • Low-risk patients: SIS
      • High-risk patients: hysteroscopic resection
  • Indicated in high-risk patients:
    • All postmenopausal women 
    • Women > 45 years of age with AUB
    • Women < 45 years of age with AUB and other risk factors: 
      • Unopposed estrogen exposure: obesity, ≥ 6 months of ovulatory dysfunction (e.g., polycystic ovarian syndrome Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome)
      • Tamoxifen use
      • Lynch or Cowden syndromes

Management

  • Hysteroscopic polypectomy:
    • Gold standard treatment
    • Preferred treatment in:
      • Postmenopausal women
      • Symptomatic women
      • Asymptomatic patients with risk factors
    • Preferred treatment for polyps that are:
      • > 1.5 cm in size
      • Multiple 
      • Prolapsing through cervix
    • Used in infertility patients undergoing treatment
  • Observation:
    • An option for low-risk patients
    • Spontaneous regression is possible, though uncommon.
  • Options for recurrent polyps:
    • Levonorgestrel-containing intrauterine device (IUD)
    • Endometrial ablation (patients who have completed childbearing)

Differential Diagnosis

  • Leiomyomas: benign tumors arising from smooth muscle cells in uterine myometrium. Similar to polyps, both conditions often present with abnormal bleeding, especially when fibroids are submucosal. Diagnosis is made with pelvic imaging: fibroids are identified as hypoechoic, well-circumscribed, round mass; SIS will help differentiate polyps from submucosal fibroids. Treatment may include surgical resection or medical options to reduce bleeding or bulk.
  • Endometrial hyperplasia or malignancy: abnormal growth of endometrium, which may progress to adenocarcinoma. Caused by excess estrogen unopposed by progesterone, similar to polyps. Typically presents with heavy menstrual and/or intermenstrual bleeding in reproductive years, and postmenopausal bleeding when older. Diagnosis is made on biopsy. Hysterectomy is usually the recommended treatment.
  • Polycystic ovary syndrome ( PCOS PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome): most common endocrine disorder of reproductive-aged women, characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea, and metabolic dysfunction. Bleeding is usually irregular, but when it occurs, may be quite heavy. Diagnosis of exclusion, so other causes of AUB and hirsutism should be ruled out with imaging and lab work. Management includes restoring normal ovulation through weight loss, oral contraceptive pills, and assistance with fertility.

References

  1. Stewart EA. (2021). Endometrial polyps. In A. Chakrabarti, A. (Ed.), UpToDate. Retrieved March 4, 2021, from https://www.uptodate.com/contents/endometrial-polyps
  2. Mansour T. (2020). Endometrial polyp. In Chowdhury, Y. (Ed.), StatPearls. Retrieved March 3, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/21105/ 
  3. American College of Obstetric and Gynecology Committee on Gynecology. (2012). Practice Bulletin No. 128: Diagnosis of abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding in reproductive-aged women. ACOG Vol. 120, No. 1, pp. 197-203.

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