Endometrial Hyperplasia and Endometrial Cancer

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 carcinoma (EC) is the most common gynecologic malignancy in the developed world, and it has several histologic types. Endometrioid carcinoma (known as type 1 EC) typically develops from atypical endometrial hyperplasia, is hormonally responsive, and carries a favorable prognosis. Other histologic types are known as type 2 EC; they tend to present at more advanced stages, are not hormonally responsive, and carry a far worse prognosis. Women with both EH and EC tend to present with postmenopausal or irregular menstrual bleeding. Diagnosis is histologic. Management most often involves progestin therapy, surgery, and adjuvant radiation therapy (for advanced disease).

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Endometrial hyperplasia (EH) is a state of excessive proliferation of endometrial cells, resulting in an increased gland-to-stroma ratio.

Endometrial carcinoma (EC) refers to excessive proliferation of endometrial cells that are capable of invading surrounding tissues and metastasizing to distant sites.

Epidemiology

  • Endometrial cancer is the most common gynecologic cancer in the developed world ( cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer is most common in developing countries).
  • Incidence:
    • EH: 133 per 100,000 woman-years
    • EC: 25 per 100,000 woman-years
  • Lifetime risk of EC in U.S. women: approximately 2%
  • Both are most common in perimenopausal or early postmenopausal individuals.
  • Peak age at diagnosis:
    • EH: 50–54 years
    • EC: 55–70 years
    • Both are rare at < 40 years.
  • Ethnicity/race discrepancies:
    • Higher risk of developing EC overall: White women
    • Higher risk of developing type 2 EC: Black women
    • Higher risk of mortality from EC: Black women

Classification, Staging, and Grading

Histologic classification of endometrial hyperplasia

There are 2 primary classification systems for endometrial hyperplasia:

  • 2014 World Health Organization (WHO)
  • Endometrial intraepithelial neoplasia (EIN) classification system
Table: Classification of endometrial hyperplasia
WHO system terminology EIN system terminology Characteristics
Normal endometrium Normal endometrium
  • Proliferative phase (prior to ovulation with estrogen alone): no crowding of the glands within the stroma (gland-to-stroma ratio < 2:1)
  • Secretory phase (after ovulation with estrogen + progesterone):
    • Endometrium may display some crowding
    • Glands remain well organized
    • No mitotic activity
Hyperplasia without atypia Benign endometrial hyperplasia
  • Changes seen with prolonged estrogen exposure
  • Diffuse changes throughout the endometrium
  • Gland-to-stroma ratio is increased to > 2:1.
  • Cystic dilation of glands
  • No features of nuclear atypia
  • No mitotic activity
Atypical hyperplasia EIN
  • Changes seen with abnormal monoclonal proliferation as a result of genetic mutations
  • Starts as a focal lesion (progresses to diffuse changes)
  • Premalignant lesions
  • Gland-to-stroma ratio is further increased.
  • Significant glandular crowding
  • Disorganized gland structure
  • Nuclear atypia:
    • Abnormal chromatin
    • Prominent nucleoli
  • Mitotic activity is present.
Endometrial intraepithelial neoplasia/atypical hyperplasia

Histopathology of endometrial intraepithelial neoplasia/atypical hyperplasia:
The image shows closely packed endometrial glands with sparse intervening stroma and stratification of the lining epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
Epithelial cells show cytologic atypia with high nucleocytoplasmic ratio, irregular clumping of nuclear chromatin, and mitotic figures (hematoxylin and eosin stain, ×200)

Image: “Histopathology of complex hyperplasia with atypia” by Shalinee Rao, Sandhya Sundaram, Raghavan Narasimhan. License: CC BY 2.0

Histologic classification of endometrial cancer

Classification of EC is according to its histologic subtype. Low-grade endometrioid adenocarcinoma is known as type 1 and all others are type 2. 

  • Type 1 cancers: 
    • Include only grades 1 and 2 endometrioid adenocarcinoma
    • Make up 80% of ECs 
    • Have generally favorable outcomes
    • Estrogen-dependent cancers typically derived from EIN
  • Type 2 cancers: 
    • Include histologic types:
      • Grade 3 endometrioid adenocarcinoma
      • Serous carcinoma (approximately 10%)
      • Clear cell carcinoma (< 5)
      • Undifferentiated carcinoma
      • Mixed carcinoma
    • Much more aggressive with poor outcomes 
    • Not estrogen dependent
    • Typically exhibit p53 and other genetic mutations
Histology of moderately differentiated grade 2 endometrioid adenocarcinoma

Histology of moderately differentiated grade 2 endometrioid adenocarcinoma:
Note the superficial myometrial invasion of the tumor (arrow). H&E stain x20

Image: “Histology of the primary endometrial cancer and the ileum recurrence” by Frontiers in Oncology. License: CC BY 4.0, cropped by Lecturio.

Grading Grading Cancer is the 2nd leading cause of death in the US after cardiovascular disease. Many malignancies are treatable or curable, but some may recur. Thus, all malignancies must be assigned a grade and stage in order to guide management and determine prognosis. Grading, Staging, and Metastasis endometrial carcinoma

The grade describes the amount of solid glandular growth. Endometrial cancer is classified into 1 of 3 grades.

Table: Endometrial cancer grading
Grade Definition Histology
I Well differentiated ≤ 5% of the tissue exhibits a solid growth pattern
II Moderately differentiated 6%–50% of the tissue exhibits a solid growth pattern
III Poorly differentiated > 50% of the tissue exhibits a solid growth pattern

Staging Staging Cancer is the 2nd leading cause of death in the US after cardiovascular disease. Many malignancies are treatable or curable, but some may recur. Thus, all malignancies must be assigned a grade and stage in order to guide management and determine prognosis. Grading, Staging, and Metastasis endometrial carcinoma

The stage describes the extent of tumor spread. Staging Staging Cancer is the 2nd leading cause of death in the US after cardiovascular disease. Many malignancies are treatable or curable, but some may recur. Thus, all malignancies must be assigned a grade and stage in order to guide management and determine prognosis. Grading, Staging, and Metastasis takes into account the size of the tumor, extent of local invasion, lymph node involvement, and metastasis. There are 4 major stages in EC. Disease is staged based on the “highest” findings. For example, a tumor confined to the cervix but with positive lymph nodes is classified as stage III. Similarly, direct tumor invasion into the bladder mucosa is stage IV regardless of lymph node involvement.

Table: Endometrial cancer staging
Stage Extent of tumor invasion into surrounding tissue Metastasis
I Tumor is confined to the uterine corpus. None
II Tumor invades into cervix stroma, but does not extend beyond the uterus. None
III Tumor invades into adnexa, vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor, or parametrium. Metastasis to regional lymph nodes: pelvic or para-aortic nodes
IV Direct tumor invasion into the mucosa of the bladder or rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal
  • Metastasis to lymph nodes beyond the regional nodes
  • Metastasis to distant structures

Etiology and Pathophysiology

Etiology

  • Benign endometrial hyperplasia: chronic estrogen exposure that is unopposed by progesterone.
  • EIN and EC: 
    • Genetic mutations leading to unrestricted cellular proliferation
    • In many cases, prolonged unopposed estrogen exposure also contributes.

Risk factors

Most of the risk factors for both EH and EC include anything that increases unopposed estrogen exposure.

  • 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: Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue converts androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens to estrogen.
  • 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): a condition of chronic anovulation → ↓ opposing progesterone
  • Nulliparity
  • Early menarche/late menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause: more menstrual cycles = ↑ estrogen exposure
  • Postmenopausal hormone replacement therapy (HRT) without adequate progestins
  • Tamoxifen: estrogen antagonist in breast, but has estrogenic activity in endometrium
  • Estrogen-secreting ovarian tumors (e.g., granulosa cell tumors)
  • 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
    • Also known as hereditary nonpolyposis colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix cancer ( HNPCC HNPCC 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)
    • Carries up to a 60% lifetime risk of EC

Protective factors

The following factors decrease the risk of EH/EC:

  • Use of combination oral contraceptives
  • Cigarette smoking

Pathogenesis of benign endometrial hyperplasia

  • Estrogen naturally stimulates proliferation of endometrial tissue
  • Progesterone (produced by the corpus luteum only after ovulation) counteracts estrogen/has a protective effect on the endometrium
  • Excess estrogenic stimulation → diffuse hyperplasia throughout the cavity
  • Altering the hormonal milieu (e.g., treating with progestins and/or removing estrogenic stimulation) can lead to resolution of hyperplasia.

Pathogenesis of endometrial intraepithelial neoplasia and endometrial carcinoma

  • Genetic mutations lead to:
    • Uncontrolled proliferation starting from a single location
    • Absence of programmed cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death
  • Classic mutations include:
    • PTEN: tumor suppressor (common in type 1 EC)
    • p53: tumor suppressor 
      • Present in > 90% of type 2 ECs
      • Worse outcomes associated with p53 mutations
    • POLE gene: involved in DNA replication DNA replication The entire DNA of a cell is replicated during the S (synthesis) phase of the cell cycle. The principle of replication is based on complementary nucleotide base pairing: adenine forms hydrogen bonds with thymine (or uracil in RNA) and guanine forms hydrogen bonds with cytosine. DNA Replication and repair
    • 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 mutations ( DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure mismatch repair genes)
  • Progression of disease (in order):
    • Uncontrolled endometrial proliferation → EIN → EC 
    • Direct extension into the myometrium and adjacent structures 
    • Invasion into lymphatic capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries 
    • Metastasis to regional lymph nodes:
      • Pelvic lymph nodes
      • Para-aortic lymph nodes
    • Distant metastasis via lymphatic and hematologic spread

Clinical Presentation

About ¾ of women diagnosed with EC are postmenopausal. The classic presentation is a 60-something-year-old obese woman with postmenopausal bleeding. 

  • 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 (most common presenting symptom):
    • Postmenopausal bleeding 
    • Abnormal menstrual cycles in premenopausal individuals
  • Vaginal discharge (clear or white) in postmenopausal women
  • 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/pressure
  • Dyspareunia ( 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 during intercourse)
  • Urinary symptoms:
    • Dysuria
    • Difficulty urinating
  • Unintentional weight loss
  • EH/EC may 1st be noted as an incidental finding:
    • Endometrial cells on a routine screening Papanicolaou (Pap) smear
    • Thickened endometrial lining on pelvic imaging done for other indications in a postmenopausal woman
    • Identified on specimen from a hysterectomy done for other indications (e.g., fibroids)
Endometrioid adenocarcinoma, gross specimen

Endometrioid adenocarcinoma, gross specimen:
Note the tumor primarily in the lower half of the specimen and invading into the surrounding myometrium.

Image: “Endometrioid adenocarcinoma of the uterus FIGO grade III” by Ed Uthman. License: CC BY 2.0

Diagnosis

Biopsy is required for definitive diagnosis of EH and EC. The pelvic exam is usually normal. All women who present with abnormal bleeding (especially postmenopausal bleeding) should be assessed with pelvic ultrasonography and/or biopsy.

Biopsy

  • Gold standard for diagnosing both EH and EC
  • Methods:
    • In-office biopsy with an endometrial pipelle (most reliable when ≥ 50% of the cavity is affected → may miss focal lesions)
    • Surgical biopsy with dilation and curettage (D&C)
  • Histologic findings:
    • Back-to-back glands with no intervening stroma
    • Glands have smooth, luminal contour
    • May see cribriform patterns (gland within a gland)

Imaging

  • Methods:
    • Transvaginal pelvic ultrasound: imaging method of choice
    • Saline-infusion sonography (SIS): 
      • Saline is injected into the uterus while real-time sonography is performed.
      • Distends the cavity to allow assessment of intrauterine pathology
      • Can differentiate diffusely thickened endometrium (a concern for EH/EC) from endometrial polyp
    • Pelvic MRI: may be indicated if ultrasound is unclear or to assess extent of disease.
    • Chest radiography: to look for metastasis
  • Findings worrisome for EH/EC:
    • Endometrial thickness ≥ 5 mm in a postmenopausal woman
    • Heterogeneity of the endometrium
    • Loss of a distinct border between the endometrium and myometrium
    • Cystic lesions in the endometrium
Endometrial cancer seen on sagittal view

Endometrial cancer seen on sagittal view
Left: T2-weighted MRI
Right: contrast-enhanced T1-weighted MRI
T: tumor
M: myometrium

Image: “Use of Myometrium as an Internal Reference for Endometrial and Cervical Cancer on Multiphase Contrast-Enhanced MRI” by Lin CN, Liao YS, Chen WC, Wang YS, Lee LW. License: CC BY 4.0, cropped by Lecturio.

Other assessments

  • Pelvic exam: 
    • Typically normal
    • Findings in more advanced disease:
      • Diffusely enlarged uterus
      • Fixed (nonmobile) pelvic structures
  • Pap smear (should be up to date)
  • CA-125: 
    • Serologic tumor marker sometimes tracked in individuals with type 2 EC
    • Can be used to follow response to treatment and in posttreatment surveillance

Management

Management for benign endometrial hyperplasia (hyperplasia without atypia)

  • Observation (instead of progestin therapy) may be considered in premenopausal women with:
    • Normal weight
    • Known inciting factor removed (e.g., anovulatory woman has now become ovulatory)
  • Medical management: 
    • Candidates:
      • Premenopausal women (1st-line)
      • Can be considered in postmenopausal women
    • Because benign EH is an estrogen-driven process, treatment is typically with progestin therapy (which naturally opposes the effects of estrogens). 
    • Progestin therapy options include:
      • Levonorgestrel intrauterine device (IUD) (1st-line)
      • Oral progestin therapy: megestrol acetate, medroxyprogesterone
      • Combined oral contraceptives pills (for women who also desire contraception)
  • Surgical management:
    • Hysterectomy (definitive treatment)
    • Reasonable in postmenopausal women

Management for endometrial intraepithelial neoplasia (atypical hyperplasia)

  • Hysterectomy: preferred treatment in all individuals
  • Progestin therapy can be an alternative in women who:
    • Desire future fertility
    • Are at high risk for surgical complications

Management for endometrial carcinoma

Management is primarily surgical, with potential for adjuvant radiation therapy. Management of advanced disease is highly individualized.

  • Surgical management:
    • Indicated in women who are able to undergo an operation
    • Procedure: 
      • Hysterectomy with a bilateral salpingo-oophorectomy
      • Possible lymphadenectomy of the pelvic and para-aortic nodes (higher stage/grade)
    • Surgery is often curative in low-risk disease (defined as type 1 EC confined to the endometrium).
    • Individuals with locally advanced or metastatic cancer may have cytoreductive or palliative surgery.
  • Radiation therapy:
    • Often prescribed for individuals with intermediate- or high-risk disease
    • Types:
      • Vaginal brachytherapy (lower toxicity)
      • Pelvic radiation therapy (↑ toxicity, including long-term bladder and bowel complications)
  • Chemotherapy:
    • May be indicated in high-risk disease
    • If used, regimen includes:
      • Carboplatin
      • Paclitaxel
  • Hormone therapy (progestins): may be considered in some cases
  • Long-term surveillance:
    • Regular pelvic exams
    • Can consider following CA-125 levels
    • Imaging for any suspicion of recurrence:
      • PET/CT (preferred)
      • MRI

Prognosis

  • Risk of progression from EH → EC:
    • Benign EH: < 10% progress to EC within 20 years
    • EIN (hyperplasia with atypia): 15%–40% will progress to EC within 20 years 
  • EC prognosis by type:
    • Type 1:
      • Bleeds early in the course of disease → postmenopausal bleeding is an “obvious” symptom → women present and are diagnosed early (often stage 1)
      • Carries a good prognosis
      • Surgery is often curative 
    • Type 2 disease acts more like ovarian cancer Ovarian cancer Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). Ovarian Cancer
      • Generally presents at a higher stage
      • Worse prognosis
      • Higher rates of recurrence
  • 5-year survival rates based on EC stage:
    • Stage I: approximately 80%–90%
    • Stage II: approximately 80%
    • Stage III: approximately 50%–65% 
    • Stave IV: approximately 20%

Differential Diagnosis

  • Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis: very common benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis Adenomyosis Adenomyosis is a benign uterine condition characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Adenomyosis is a common condition, affecting 20%-35% of women, and typically presents with heavy menstrual bleeding and dysmenorrhea. Adenomyosis typically presents with heavy menstrual bleeding and dysmenorrhea. Diagnosis is either clinical or assisted with pelvic imaging, usually transvaginal ultrasonography or, occasionally, MRI. Management is based on the woman’s preference regarding future childbearing and may include hysterectomy, other surgical options, or medical hormonal suppression with progestins.
  • Endometrial atrophy: benign condition in which the endometrial lining becomes thin and atrophic because of prolonged states of low estrogen. With little to no fluid in the cavity, friction may lead to micro-erosions and a subsequent inflammatory reaction that typically presents with postmenopausal light bleeding or spotting. Endometrial atrophy is diagnosed on ultrasonography (which shows a thin endometrial lining) in the setting of a negative endometrial biopsy. No treatment is required.
  • Endometrial or cervical polyps: pedunculated or sessile projections of the endometrium that result from overgrowth of endometrial glands and stroma around a central vascular stalk. Although these polyps are usually benign, they can be malignant, particularly in postmenopausal women. Endometrial or cervical polyps present with abnormal uterine or postmenopausal bleeding, though many are asymptomatic. Endometrial polyps 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 are best diagnosed with saline-infusion sonography (SIS) and are usually treated with hysteroscopic resection. 
  • Leiomyomas (uterine fibroids): common, benign tumors arising from smooth muscle cells in the uterine myometrium. Leiomyomas typically present with abnormal bleeding, 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, and/or bulk symptoms. Fibroids are identified as a hypoechoic, well-circumscribed, round mass on pelvic ultrasonography. Leiomyomas of the vaginal wall are also possible, though extremely rare. 
  • Leiomyosarcoma Leiomyosarcoma Uterine leiomyomas (or uterine fibroids) are benign tumors arising from smooth muscle cells in the uterine myometrium. Leiomyosarcomas, however, are malignant tumors, arising de novo (not from fibroids). Uterine Leiomyoma and Leiomyosarcoma: rare, malignant tumors of uterine smooth muscle that arise de novo (i.e., not from the malignant transformation of fibroids). They present similarly to benign leiomyomas (with abnormal bleeding, 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, and bulk symptoms), making diagnosis difficult. They are usually diagnosed on post-operative hysterectomy specimens done for suspected fibroids. Management involves surgical excision (if not already done) and possibly adjuvant chemotherapy.
  • Cervical cancer: invasive cancer of the cervix (and the most common gynecologic cancer worldwide). There are 2 major histologic types of cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer: SCC and adenocarcinoma, the vast majority of which are caused by high-risk HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomaviridae: HPV infections. Early cervical neoplasia is asymptomatic, though more advanced disease may present with abnormal bleeding (especially bleeding on contact). Diagnosis is made by Pap testing with cytology, HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomaviridae: HPV testing, and biopsy.

References

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  3. Huvila, J., McAlpine, J.S. (2021). Endometrial cancer: pathology and classification. UpToDate. Retrieved September 9, 2021, from https://www.uptodate.com/contents/endometrial-cancer-pathology-and-classification 
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