Uterine corpus

benign diseases: - endometritis - endometriosis and adenomyosis - endometrial polyps precursor lesions of endometrial carcinoma endometrial carcinoma mesenchymal tumors of the uterus

Endometritis Pregnancy-related after a vaginal delivery 2-3% after Cesarean delivery % - enterococcus - streptococcus - chlamydia … puerperal sepsis Unrelated to pregnancy usually ascending infection IUD acute - neutrophils within endometrial glands - Neisseria gonorrhoeae - Chlamydia trachomatis chronic - plasma cells - pelvic inflammatory disease

Puerperal sepsis bacterial infection contracted during childbirth or abortion usually treatable with antibiotics can be fatal! between 1991 and 2001: 137 women died up to 42 day after the delivery (12,5 / deliveries) - in the Czech Republic only 5 of them (4,3%) died because of infection common condition – historically during the 18th century it took on epidemic proportions particularly when home delivery practice changed to delivery lying-in hospital - at those times, there still was a total ignorance of asepsis

Endometriosis presence of endometrial tissue outside the endometrium and myometrium pathogenesis (two theories): 1) metastatic theory: implantation of endometrial tissue to its ectopic location 2) metaplastic theory: development of the endometrial tissue at the ectopic site

Endometriosis true prevalence is unknown as many patients are asymptomatic estimated prevalence in women of reproductive age is 10-15% >80% of patients are in reproductive age group sites of endometriosis: - peritoneum - urinary bladder - ovaries - uterine ligaments - large bowel, skin -lungs, bone, stomach

Adenomyosis presence of endometrial glands and stroma within the myometrium common condition, detected in 15-30% of hysterectomy specimen clinical features: - pre- or perimenopausal women - abnormal bleeding and dysmenorrhea - uterus is enlarged

Endometrial polyps common 2-23% of patients undergoing endometrial biopsy because of abnormal uterine bleeding probably related to hyperestrogenism may be single or multiple increased frequency of polyps in patients taking tamoxifen

Precursor lesions

Endometrial hyperplasia hyperplasia without atypia atypical hyperplasia

Natural history of hyperplasia hyperplasia without atypia fewer than 2% progress to carcinoma atypical hyperplasia 23% progress to carcinoma

Endometrial intraepithelial carcinoma precursor lesion of invasive endometrial serous carcinoma formerly also had been referred to as „carcinoma in situ“ can be associated with metastatic disease histological features: - numerous mitotic figures - high-grade nuclear atypias - enlarged nuclei - prominent nucleoli - can be papillary arrangement

Tumors of the uterine corpus

Epithelial Carcinoma: endometrioid mucinous serous clear cell Mixed epithelial and mesenchymal carcinosarcoma Mesenchymal Benign leiomyoma endometrial stromal nodule Malignant leiomyosarcoma endometrial stromal sarcoma

Endometrial carcinoma dualistic model of carcinogenesis

Type I low-grade carcinomas associated with estrogenic stimulation indolent behaviour histologic subtypes: - low grade endometrioid - mucinous precursor lesion: - atypical hyperplasia

Type II high-grade carcinoma not related to estrogenic stimulation aggresive behaviour histologic subtypes: - high-grade endometrioid - serous - clear cell precursor lesion: - endometrial intraepithelial carcinoma

FeatureType IType II Frequency 80-85%10-15% Histologic subtypes Endometrioid (low grade) Mucinous Serous Clear cell Endometrioid (high grade) Tumor grade lowhigh Precursor lesion atypical hyperplasia- endometrial glandular dysplasia - endometrial intraepithelial carcinoma Unopposed estrogen presentabsent Menopausal status pre- and perimenopausalpostmenopausal Prognosis goodpoor Genetic alterations PTEN MSI k-ras p53 Her2/neu E-cadherin

Etiology (type I) Risk factors hormonal stimulation - unopossed estrogen stimulation (after 2 years – 2-3fold increase in the risk of EC) constitutional factors - obesity - diabetes mellitus increased total caloric intake high-fat diet genetic alterations - mutation of PTEN - microstallite instability (HNPCC – lynch syndrome) Protective factors increased physical exercise addition of progestin to HRT smoking diet rich in vegetables parity

Clinical features initial manifestation: - abnormal vaginal bleeding - rarely asymptomatic most women postmenopausal in young women – generally low grade, minimally invasive, excelent prognosis

Gross findings almost uniformly exophytic focal or diffuse myometrial invasion may result in enlargement of the uterus involvement of the cervix – approximately 20% cases

Tumors of the uterine corpus Epithelial Carcinoma: endometrioid mucinous serous clear cell Mixed epithelial and mesenchymal carcinosarcoma Mesenchymal Benign leiomyoma endometrial stromal nodule Malignant leiomyosarcoma endometrial stromal sarcoma

Prognosis Uterine factors histologic type grade hormone receptor status depth of myometrial invasion cervical involvement vascular invasion Extrauterine factors adnexal involvement intraperitoneal metastasis lymph node metastasis

Prognosis Uterine factors histologic type grade hormone receptor status depth of myometrial invasion cervical involvement vascular invasion Extrauterine factors adnexal involvement intraperitoneal metastasis lymph node metastasis stage

3

Tumors of the uterine corpus Epithelial Carcinoma: endometrioid mucinous serous clear cell Mixed epithelial and mesenchymal carcinosarcoma Mesenchymal Benign leiomyoma endometrial stromal nodule Malignant leiomyosarcoma endometrial stromal sarcoma

Leiomyoma the most common uterine tumors noted clinically in 20-30% of women over 30 years of age when systematically searched – 75% of women

Gross findings location: - submucosal (rare pedunculated) - intramural (most common) - subserosal (can be pedunculated) multiple tumors in 2/3 of women spherical, firm sharply demarcated cut surface: - white to tan - whorled trabecular pattern

Clinical features most asymptomatic, only a minority requires treatment therapy is indicated if: - tumors are symptomatic (metrorrhagia, abdominal pain, urination problems) - interfere with fertility - rapidly enlarge - pose a diagnostic problem

Leiomyosarcoma about 1.3% of uterine malignancies more than 50% of uterine sarcomas most intramural averages 6-9 cm in diameter soft, fleshy, poorly defined margins cut surface: gray-yellow or pink, often with areas of necrosis and hemorrhage poor prognosis: 5 year survival rate 15-25%

Carcinosarcoma (malignant mixed Müllerian tumor) composed of malignant epithelial and mesenchymal components frequently polypoid poor prognosis