Endometrial Carcinoma
~Introduction
Endometrial carcinoma is the most common malignancy of the female genital tract in developed countries and one of the leading gynecological cancers worldwide. It arises from the endometrium, the inner lining of the uterus, and is predominantly seen in postmenopausal women, although it can also occur in premenopausal women. The disease is often detected at an early stage because of its hallmark symptom—abnormal uterine bleeding—which leads to early medical attention and favorable outcomes in most cases.
With changing lifestyles, increasing obesity, delayed childbearing, and prolonged estrogen exposure, the incidence of endometrial carcinoma has been rising steadily. Understanding its etiology, pathology, clinical presentation, diagnosis, and management is crucial for effective prevention and treatment.
~Epidemiology
Endometrial carcinoma accounts for approximately 5–7% of all cancers in women
Most commonly diagnosed between 50–70 years of age
More prevalent in developed countries
Incidence is higher in:
Obese women
Women with diabetes mellitus
Women with prolonged estrogen exposure
Lower incidence in women who:
Use combined oral contraceptives
Have multiple pregnancies
~Etiology and Risk Factors
Hormonal Factors
The most important etiological factor is unopposed estrogen stimulation of the endometrium without adequate progesterone opposition.
Sources of excess estrogen include:
Obesity (conversion of androgens to estrogen in adipose tissue)
Estrogen-only hormone replacement therapy
Polycystic ovarian syndrome (PCOS)
Estrogen-secreting ovarian tumors
Reproductive Factors
Nulliparity
Early menarche
Late menopause
Infertility
Metabolic Factors
Obesity
Diabetes mellitus
Hypertension (often associated with metabolic syndrome)
Genetic Factors
Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer – HNPCC)
Increased risk due to mismatch repair gene mutations (MLH1, MSH2, MSH6)
Other Risk Factors
Tamoxifen therapy
Prior pelvic radiation
Increasing age
~Pathogenesis
Endometrial carcinoma develops through two main pathogenetic pathways, leading to the classification into Type I and Type II tumors.
Type I (Estrogen-Dependent)
Accounts for 70–80% of cases
Develops from endometrial hyperplasia
Associated with unopposed estrogen
Occurs in younger, perimenopausal women
Usually low-grade and well-differentiated
Better prognosis
Type II (Estrogen-Independent)
Accounts for 20–30% of cases
Arises in atrophic endometrium
Occurs in older, postmenopausal women
High-grade tumors
Aggressive behavior and poor prognosis
~Classification of Endometrial Carcinoma
Histological Types
Endometrioid carcinoma (most common)
Serous carcinoma
Clear cell carcinoma
Mucinous carcinoma
Undifferentiated carcinoma
Carcinosarcoma (malignant mixed Müllerian tumor)
~Pathology
Gross Features
Diffuse or focal thickening of the endometrium
Polypoid or fungating mass projecting into the uterine cavity
Advanced cases may invade the myometrium
Microscopic Features
Endometrioid Carcinoma
Glands resembling normal endometrium
Variable glandular differentiation
Squamous metaplasia may be present
Serous Carcinoma
Papillary architecture
Marked nuclear atypia
High mitotic activity
p53 mutations common
Clear Cell Carcinoma
Clear or hobnail cells
Aggressive behavior
~Grading of Endometrial Carcinoma
Based on the degree of glandular differentiation:
Grade 1: Well-differentiated (>95% glandular)
Grade 2: Moderately differentiated (50–95% glandular)
Grade 3: Poorly differentiated (<50% glandular)
~Staging (FIGO Staging)
Stage I
Tumor confined to the uterus
IA: <50% myometrial invasion
IB: ≥50% myometrial invasion
Stage II
Cervical stromal invasion
Stage III
Local or regional spread
IIIA: Serosa/adnexa involvement
IIIB: Vaginal/parametrial involvement
IIIC: Lymph node metastasis
Stage IV
Invasion of bladder or bowel mucosa
Distant metastasis
~Clinical Features
Common Symptoms
Postmenopausal bleeding (most common)
Menorrhagia or intermenstrual bleeding
Watery or blood-stained vaginal discharge
Pelvic pain (late stages)
Advanced Disease Symptoms
Weight loss
Anemia
Pelvic mass
Urinary or bowel symptoms
~Diagnosis
Clinical Evaluation
Detailed menstrual and reproductive history
Pelvic examination
Investigations
Endometrial Sampling
Endometrial biopsy (gold standard)
Dilatation and curettage (D&C)
Imaging
Transvaginal ultrasound (endometrial thickness >4 mm in postmenopausal women is suspicious)
MRI for local staging
CT scan for metastatic disease
Laboratory Tests
CBC for anemia
Tumor markers (CA-125 may be elevated in advanced disease)
~Differential Diagnosis
Endometrial hyperplasia
Endometrial polyps
Submucosal fibroids
Cervical carcinoma
~Management
Surgical Treatment
Primary treatment is surgery, which includes:
Total abdominal hysterectomy
Bilateral salpingo-oophorectomy
Pelvic and para-aortic lymph node dissection
Radiotherapy
Adjuvant radiotherapy for high-risk patients
Used in advanced stages or inoperable cases
Chemotherapy
Used in advanced or recurrent disease
Common agents: carboplatin, paclitaxel
Hormonal Therapy
Progesterone therapy in:
Young women desiring fertility
Advanced estrogen receptor–positive tumors
~Prognosis
Prognosis depends on:
Stage at diagnosis (most important factor)
Histological type and grade
Depth of myometrial invasion
Lymph node involvement
Survival Rates
Stage I: 80–90%
Stage II: 60–70%
Stage III: 30–50%
Stage IV: <20%
~Prevention
Weight control and healthy lifestyle
Use of combined oral contraceptives
Early treatment of endometrial hyperplasia
Regular screening in high-risk women (Lynch syndrome)
~Recent Advances
Molecular classification (TCGA classification)
Targeted therapies
Immunotherapy for advanced and recurrent disease
Personalized treatment approaches based on genetic profiling
~Conclusion
Endometrial carcinoma is a common and largely preventable gynecological malignancy with a favorable prognosis when detected early. The disease is strongly linked to hormonal imbalance, particularly unopposed estrogen exposure. Early recognition of symptoms such as abnormal uterine bleeding, combined with timely diagnostic evaluation, allows for effective treatment and improved survival rates. Advances in molecular pathology and targeted therapies continue to refine management strategies, offering hope for better outcomes in high-risk and advanced cases.
No comments:
Post a Comment