Endometrial cancer

Question 1

General findings

Answer 1

Endometrial cancer is the most common cancer of the female genital tract in the US, with a peak incidence between 60 and 70 years of age. Endometrial cancers can be divided into two types based on histological characteristics; type I cancers account for 75% of all endometrial cancers and are of endometrioid origin, while type II cancers originate from serous or clear cells. Several risk factors are associated with the development of endometrial cancer, of which the most important is long-term exposure to increased estrogen levels, especially in type I cancer. The main symptom is often painless, vaginal bleeding, which presents at an early stage. Later stages may manifest with pelvic pain and a palpable mass, whereby pelvic exams are often normal. The diagnosis is made primarily via an endometrial biopsy, which shows endometrial hyperplasia and atypical cells. Additional imaging studies (e.g., ultrasonography, abdominal CT, X-ray) are usually required for the detection and staging of metastases. Treatment of early-stage endometrial cancer involves hysterectomy with adnexectomy and may also require additional lymph node removal. Radical hysterectomy according to the Wertheim-Meigs method is performed in cases of advanced carcinomas and can be combined with radiotherapy and progestin treatment. The prognosis is usually favorable in cancers diagnosed at an early stage.

Question 2

Type

NB. Il tipo 2 ha è fortemente associato ad una predisposizione genetica

Answer 2

✔Type I endometrial cancer, 75%: endometrioid adenocarcinomas derived from atypical endometrial hyperplasia. Estrogeno dipendente
✔Type II endometrial cancer: tumors of non­endometrioid histology (Histology includes serous, clear, mucinous, squamous, transitional, mesonephric, and undifferentiated cells.)

The development of type I endometrial cancers has been shown to be directly related to long-term exposure to increased estrogen levels. Type II endometrial cancer is mostly estrogen-independent and is strongly associated with a genetic predisposition

Question 3

Risk factors for estrogen-dependent tumors (type I)

Tamoxifene💥
(mentre il Raloxifene non aumenta il rischio di carcinoma endometriale)

Attenzione: mentre per il ‘‘cervical cancer’’ sia la terapia ormonale sostitutiva che la pillola estroprogestinica rappresentano un fattore di rischio, per il carcinoma endometriale la pillola estroprogestinica rappresenta un fattore di protezione!

Answer 3

• Nulliparity
• Early menarche and late menopause
• PCOS (polycystic ovary syndrome) (riduzione progesterone!💥)
• Unopposed estrogen replacement therapy (e.g., for menopausal symptoms) NB
• Breast cancer: history of breast cancer, tamoxifen treatment
• Metabolic syndrome (esp. obesity and diabetes mellitus type 2 )
• Lynch syndrome (hereditary nonpolyposis colorectal cancer) 👓

Question 4

Protective factors

Answer 4

• Low estrogen and high progestin or progesterone levels have a protective effect.
• Multiparity
• Combination oral contraceptive pills 💥
• Tobacco consumption
• Regular physical exercise
• Lifelong soy-rich diet

Question 5

Epidemiology

Postmenopausal women!!! (i polipi endometriali hanno il picco di incidenza ai 50 anni)

Answer 5

The most common cancer of the female genital tract in the US!
Fourth most common cancer in women (after breast, lung, and colorectal cancer)

Age: primarily postmenopausal women affected; peak incidence at 65–74 years
Onset of type I cancer is usually nearer to menopause; type II cancer typically occurs in women who are much older, with the mean age of diagnosis being 67 years.

Question 6

!Vaginal bleeding usually does not occur in type II cancer 🧨

The majority of endometrial cancers are diagnosed at an early stage and have a good prognosis! (situazione diametralmente opposta per il carcinoma ovarico)

Answer 6

!Abnormal uterine bleeding is the main symptom.
1.Postmenopausal: any amount of vaginal bleeding, including spotting or staining

2.Perimenopausal/premenopausal: metrorrhagia, menometrorrhagia

-Later stages may present with pelvic pain, palpable abdominal mass, and/or weight loss.
Pelvic exam is often normal; possible findings include an abnormal cervix, enlarged uterus, or evidence of local metastases

Question 7

Endometrial hyperplasia

Answer 7

Etiology: increased estrogen stimulation leads to excessive proliferation of the endometrium, e.g., in:

1. Follicle persistence
2. PCOS
3. Estrogen-producing ovarian tumors (e.g., granulosa cell tumors, theca cell tumors)
4. Hormone replacement therapy without progestin administration

Classification: based on histology

✔Simple endometrial hyperplasia
Histology: both stromal and glandular cells. Enlarged, dilated mucous membrane glands (Swiss cheese pattern) are located between abundant stromal tissue.
Risk of carcinoma
∼ 1% in simple hyperplasia of the endometrium without atypia
∼ 10% in simple hyperplasia of the endometrium with atypia

✔Complex endometrial hyperplasia (aumenta la componente ghiandolare e diminuisce quella stromale. Ricorda che il carcinoma endometriale type 1 è un adenocarcinoma)
Histology: pronounced proliferation of glandular tissue. The glands are positioned, in part, back-to-back (“dos-à-dos”) with no separating stroma!

∼ 3–10%: complex endometrial hyperplasia without atypia (grades I–II)
∼ 30%: complex endometrial hyperplasia with atypia (grade III)

Clinical features: constant bleeding, intermenstrual bleeding, postmenopausal bleeding

Diagnosis
Ultrasonography: endometrial thickening (> 1 cm in premenopausal women and > 5 mm in postmenopausal women)
Hysteroscopy with fractional curettage (prese bioptiche multiple)
Clinical chemistry: FSH, estradiol, testosterone

Treatment: the choice of treatment primarily depends on the presence of atypia and the age of the patient (vedi sezione iperplasia endometriale)

Question 8

Diagnosi

la stadiazione è chirurgica: significa che prima si opera e poi c’è la stadiazione

Answer 8

L’eco transvaginale integrata dal colordoppler deve essere praticata in tutte le donne che presentino una perdita vaginale anomala! (vale lo stesso per gli uomini con eco pelvi a riguardo di ematuria sopra i 55 anni, sospetto cr vescica fino a prova contraria). Andiamo a valutare lo spessore della parete endometriale: è sospetto sopra i 12 mm nel periodo premenopausale e sopra i 5 mm durante la menopausa. La diagnosi definitiva è istologica

If there is no detectable pathology on biopsy and if no further symptoms occur, endometrial cancer can be ruled out.

✔Imaging

• Transvaginal ultrasonography
• Thickening of the endometrium; regular monitoring required in postmenopausal women with thickening ≥ 5 mm
• Cystic changes, variable echogenicity
• Possibly visible tumor infiltration into neighboring organs
• Abdominal ultrasonography: A complete abdominal ultrasound is indicated to exclude metastasis.
• Chest x-ray, CT, MRI: assessment of metastatic spread (lungs, pelvis)
• Laboratory tests: CBC and coagulation studies to assess anemia and possible other causes of heavy uterine bleeding

There is no routine screening test for endometrial cancer.

Question 9

Treatment

Stadio 1, tumore circoscritto all’utero

1A: invasione miometriale < del 50%
1B:> del 50%

.

1. basso rischio (1A g2,g3).Il trattamento dello stadio 1 prevede isterectomia radicale con annessectomia bilaterale, senza trattamento adiuvante, senza linfadenectomia
2. rischio intermedio: radioterapia adiuvante e linfadenectomia a seguito di isterectomia
3. alto rischio : radioterapia adiuvante e chemioterapia e linfadenectomia a seguito di isterectomia

Stadio 2 : surgery, radio, chemio
Stadio 3/4 : surgery, radio, chemio

G1: < del 5%
G2: 6 < x< 50 %
G3:>50%

Answer 9

!Surgical management
Indication: women with endometrial cancer who are postmenopausal, perimenopausal, or do not intend to become pregnant (SEMPRE isterectomia con annessectomia bilaterale, lavaggioperitoneale, espolarazione cavità addominale, linfoadenectomia pelvica e aortica)

Procedures

• Total hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node removal (in caso di Type 2, bisogna aggiungere una omentectomia con biopsie peritoneali e della cupola diaframmatica)
• Advanced radical hysterectomy and removal of the upper vagina according to Wertheim-Meigs, with progestins.

Radioterapia adiuvante: in aggiunta alla chirurgia di stadiaizone.

1. età oltre i 60 anni
2. invasione vascolare e/o linfonodi positivi
3. tumori maggiori i 20 mm
4. interessamento terzo inferiore utero

!Medical management
Progestins: Indicated for women with early stage endometrial carcinoma (well-differentiated and progesterone and estrogen receptor positive) , who would prefer to avoid TAH-BSO and preserve fertility, or as adjuvant therapy (in questo caso negli stadi avanzati della malattia).
Radiotherapy and/or chemotherapy (adjuvant or palliative)(malattia metastatica)