Classification of Endometrial Tumors

Endometrial cancers are classified into two main types depending on their histological subtype:

Type 1 Tumors

• Endometrioid adenocarcinomas

• Estrogen-driven

• Arise from a background of endometrial hyperplasia

• Account for 75–80% of all endometrial tumors

• Generally low-grade and have a good prognosis

Type 2 Tumors

• Include high-grade serous and clear cell histological subtypes

• Arise from an atrophic endometrium

• More aggressive and associated with a worse prognosis

Sarcomas of the Uterus

Uterine sarcomas are derived from the stromal cells and may be endometrial or myometrial in origin.
These are rare tumors, accounting for approximately 5% of all uterine cancers.
The most common types are:

• Leiomyosarcomas

• Carcinosarcomas

Classification

1. Pure sarcomas

2. Mixed epithelial sarcomas

3. Heterologous sarcomas

Pure Sarcomas

This group includes:

• Endometrial stromal sarcomas

• Leiomyosarcomas

Endometrial stromal sarcomas occur mainly in perimenopausal women, presenting with irregular bleeding and a soft, enlarged uterus.
The majority of these tumors are low grade.

Leiomyosarcomas are rare tumors of the myometrium.
They are rarely (0.75%) associated with malignant transformation of benign fibroids and often present with:

• Rapidly growing pelvic mass

• Pelvic pain

Other symptoms include:

• Postmenopausal bleeding

• Vaginal discharge

• Pelvic pain or pressure symptoms

Preoperative diagnosis is difficult but may be aided by MRI, which can delineate areas of necrosis within a fibroid suggestive of malignant transformation.

Treatment:

• Surgery is the mainstay.

• Adjuvant therapy may be considered if the mitotic count is high (>10 mitoses per high-powered field).

Metastatic spread is usually vascular, involving distant sites such as the lungs and brain.

Mixed Epithelial Sarcomas (Carcinosarcomas)

This group, formerly known as malignant mixed Müllerian tumors, contains both carcinomatous and sarcomatous elements.

• The carcinomatous component is usually glandular.

• The sarcomatous component can be:

  • Homologous: composed of tissues normally found in the uterus (endometrial, stromal, and/or smooth muscle).

  • Heterologous: composed of tissues not normally found in the uterus (bone, cartilage, skeletal muscle).

Presentation of Mixed Epithelial Sarcomas

• Most cases occur after menopause.

• Sometimes associated with previous pelvic irradiation.

• Typical presentation includes:

  • Postmenopausal bleeding (PMB)

  • A fleshy mass protruding from the cervix

  • An enlarged, soft uterus

Treatment

• Surgery is the main treatment.

• Followed by postoperative radiotherapy.

Prognosis:

• 5-year survival: 73% if confined to uterus

• 5-year survival: 25% if tumor spreads beyond the uterus

Heterologous Sarcomas

These rare tumors consist of sarcomatous tissue not normally found in the uterus, such as:

• Striated muscle

• Bone

• Cartilage

The most common is rhabdomyosarcoma, which may occur in children, presenting as:

• A grape-like mass protruding from the cervix

• Watery vaginal discharge

Histology: reveals primitive rhabdomyoblasts.
Recurrence rates are high with frequent distant metastases.

Risk Factors for Endometrial Cancer

• Obesity

• Diabetes mellitus

• Nulliparity

• Late menopause (>52 years)

• Unopposed estrogen therapy

• Tamoxifen therapy

• Family history of colorectal or endometrial cancer

Presentation of Endometrial Cancer

• Most commonly occurs in postmenopausal women.

• Usually presents early, often following postmenopausal bleeding (PMB).

• Approximately 5–10% of women with PMB have an underlying gynecological malignancy.
  → This is a “red flag” symptom and should always be investigated.

In premenopausal women, it presents with:

• Abnormal uterine bleeding (heavy, irregular, or intermenstrual bleeding).

Advanced disease may present with:

• Abdominal pain

• Urinary dysfunction

• Bowel disturbances

• Respiratory symptoms

Signs and Symptoms of Endometrial Cancer

• Bleeding from the cervical os during speculum examination

• Bulky uterus on bimanual pelvic examination

• In many women, pelvic examination may be normal

• Pain may indicate metastatic spread

• Discharge may be present, often associated with pyometra

Diagnosis

Postmenopausal bleeding (PMB) is a critical symptom that must always be investigated.

Steps in assessment:

1. Inspection of external genitalia

2. Speculum examination – to exclude vulval, vaginal, and cervical cancers as potential causes.

Investigations

• Transvaginal Ultrasound Scan (TVUSS)

• Hysteroscopy

• Endometrial biopsy

FIGO Staging of Carcinoma of the Uterus

Management of Endometrial Cancer

Surgery

Surgery is the mainstay of treatment.
The extent of surgery depends on:

• Tumor grade and stage

• Patient’s comorbidities

Standard surgery:

• Total hysterectomy with bilateral salpingo-oophorectomy (BSO) — removal of uterus, both fallopian tubes, and ovaries.

Can be performed:

• Abdominally

• Laparoscopically (total, vaginally assisted, or robotically)

If MRI suggests cervical involvement, a modified radical hysterectomy is performed, which includes:

• Removal of a cuff of vagina

• Paracervical and parametrial tissues

• Ensures adequate excision margins

Advanced or High-Grade Disease

If the tumor is:

• High grade (Grade 3) or

• Type 2 histology,

many centers perform pelvic and para-aortic lymph node dissection, since nodal disease (pelvic or para-aortic) occurs in about one-third of patients.

However, the role of nodal dissection is contentious.
The ASTEC trial (large UK study) found no survival benefit from pelvic node dissection in endometrial cancer.

Adjuvant Treatment

Radiotherapy

• Postoperative radiotherapy reduces local recurrence but does not improve overall survival.

• Strategies:

  • Brachytherapy (localized vaginal vault radiotherapy) for early/local disease

  • External beam radiotherapy + brachytherapy for stage III or locally advanced disease

Chemotherapy

• Used for advanced or metastatic disease.

• Evidence supporting its efficacy remains limited.

Hormonal Therapy

• High-dose progestins (oral or intrauterine) are effective in some women with:

  • Complex atypical hyperplasia

  • Low-grade stage IA endometrial carcinoma

• However, relapse rates are high after hormonal treatment.

Differential Diagnosis for Pelvic Masses

From the Uterus

• Fibroids (leiomyomas)

• Uterine malformations

• Blood accumulation (hematometra)

• Pyometra

• Uterine body neoplasms

From the Ovaries

• Endometriosis

• Functional or organic ovarian cysts

• Benign and malignant ovarian tumors

From the Fallopian Tubes

• Tubo-ovarian abscess

• Pelvic inflammatory disease

• Hydrosalpinx

• Para-ovarian cysts

• Ectopic pregnancy

• Fallopian tube neoplasms