Uterine cancer Uterine mesenchymal neoplasms Assoc. Prof. Małgorzata Walentowicz-Sadłecka, MD, PhD

Classification of uterine cancers Endometrial carcinoma Pure endometroid carcinoma Serous or clear cell adenocarcinoma Mesenchymal neoplasms Endometrial stromal sarcoma Carcinomasarcoma Uterine leiomyosarcoma Classification of uterine cancers

Endometrial carcinoma

Epidemiology of endometrial carcinoma Endometrial cancer is the most common malignancy of the female genital tract. About 2-3% of women will develop endometrial cancer. Endometrial cancer occurs usually in postmenopausal women (90%). Most cases (approximately 70%) are diagnosed in early stage (FIGO Ia, Ib) Fig. Distribution of the expected cases and deaths for the 5 most common cancers in Europe 2012 in females. IARC 2013.

Two types of endometrial cancer Type 1 – estrogen-dependent Type 2 – estogen-independent 80-90% 10-20% Related to estrogen-exposure risk factors Not related to estrogen-exposure risk factors High differentiated tumors - Endometroid adenocarcinoma, G1, G2 Poorly differentiated tumors: - Clear cell adenocarcinoma - Serous carcinoma - Squamous carcinoma - Undifferentiated carcinoma - Mixed carcinoma Endometrial hyperplasia Endometrial atrophy Favorable prognosis Poor prognosis Precancerous lesion

Endometrial hyperplasia A spectrum of excessive proliferation of the endometrial cells ranging from physiologic states to carcinoma in situ. Type of hyperplasia Risk of cancer Simple without atypia 1% Complex without atypia 2% Simple with atypia 8% Complex with atypia 29% Simple – dialted or cystic glands complex = architecture changes: crwoded glands with less stroma Simple = dilated or cystic glands Complex = architecture changes; crowded glands with less stroma Atypia = large nuclei; variable size and shape

Risk factors Prolonged, estrogen stimulation, in the absence of progestin Higher risk Lower risk Nulliparity Early age of first birth, last pregnancy at a later age Late menopause Late age of menarche Short, irregular ovulatory cycles, unopposed estrogen therapy Longer use of combination oral contraceptives, hormonal intrauterine device Obesity Physical activity Diabetes mellitus Smoking cigarettes Tamoxifen therapy Lynch II syndrome

Symptoms Abnormal uterine bleeding or discharge (90% patients); Cyclical bleeding that continues past the usual age of menopause; Pelvic pressure or discomfort (uterine enlargement); Asymptomatic (<5% patients). Awarness of pathological mass in pelvic/abdominal

Diagnosis (according to ACOG) Transvaginal ultrasonography (TVS) Normal endometrium thickness in postmenopausal women <5mm Normal endometrium thickness in postmenopausal women used estrogen therapy <8mm Hysteroscopy -> dilation and curettage (D&C) to fully evaluate the endometrial lining and exclude a premalignant or benign lesion.

Clinical staging FIGO Stage Characteristic 5-years survival IA Tumor confined to the uterus, no or < ½ myometrial invasion 96% IB  Tumor confined to the uterus, > ½ myometrial invasion 87% II Cervical stromal invasion, but not beyond uterus 80% IIIA Tumor invades serosa or adnexa 48% IIIB Vaginal and/or parametrial involvement 53% IIIC1 Pelvic node involvement 60% IIIC2 Para-aortic involvement IVA   Tumor invasion bladder and/or bowel mucosa 57% IVB Distant metastases including abdominal metastases and/or inguinal lymph nodes 16%

Treatment and prognosis Minimally invasive surgery is preferred for endometrial cancer. Routine lymphadenectomy is not recommended in low-grade cases. High-risk patients (grade 2 or 3, clear cell or serous histology, suspicion of extrauterine disease, family history of disease) benefit from postoperative adjuvant radiotherapy. Endometrial hyperplasia: for women with atypical complex hyperplasia with no longer desire fertility, hysterectomy is reccomended. Other cases may be treated with progestins to try to reverse the lesion. Although women with low-grade, minimally invasive disease do not appear to benefit from routine lymphadenectomy, no definitive pre- or intraoperative predictors exist that can reliably identify them. Consequently, preoperative consultation with a gynecologic oncologist is recommended, especially in the context of preoperative high-risk features or limited intraoperative ability to either assess the extent of uterine disease or adequately stage the patient’s disease. Endometrial cancer is considered high-risk if it is grade 2 or 3 disease, there is evidence of clear cell or papillary serous histology, or any clinical or radiologic suspicion of cervical or extrauterine disease, and when it is diagnosed in a woman with a family history of the disease. Prognosis Overall 5-years survival rate in endometrial cancer is approximately 75%

Uterine sarcoma

Epidemiology of uterine sarcoma Uterine sarcomas constitute 2-6% of uterine malignancies. The development of uterine sarcomas is increased by previous radiation therapy. Carcinosarcomas, leiomyosarcomas, and high- grade endometrial stromal sarcomas are clinically aggressive tumors with local extension by lymphatic or hematogenous pathways.

Symptoms and diagnosis of uterine sarcoma abnormal bleeding, pelvic pain, a polypoid mass or enlarged uterus (50%) Diagnosis: Biopsy of endocervical mass or endometrial curettage

Treatment of uterine sarcomas Reccurences develop in >50% of patients (most common in abdominal or lungs) I and II stage – surgical treatment III stage – combination of surgery, radiation and chemiotherapy IV stage – combinaton of chemiotherapy

Summary Most risk factor of endometrial carcinoma are related to prolonged estrogen stimulation. First step in diagnosis of (obese) postmenopausal women with vaginal bleeding is transvaginal ultrasonography. Most patients with endometrial cancer should undergo surgical treatment. Postoperative, adjuvant radiotherapy is recommended in high- risk cases and high-grade cases. Overall 5-years survival is approximately 75%. Uterine sarcomas are the most malignant uterine tumors.