Malignant uterine neoplasms (Endometrial cancer (Risk factors ( high…
Malignant uterine neoplasms
high social and economic status,
high education status,
in a population of black women endometrial cancer is rare but more agressive, poor prognosis
religion – no dependence was found.
age: 75% - 80% patients – postmenopausal age (10 - 15 years later then cervical cancer),
two peaks of the incidence: 50 - 54 years and 70 - 74 years
under 45 years old - 5% - 10% of patients,
early menarche, late menopause
menstrual disturbances (amenorrhoea primaria, amenorrhoea secundaria, oligomenorrhoea), anovulating cycles, irregular menstrual periods
meal and fat diet, alcohol drinking,
primary radiotherapy due to cervical cancer
obesity, diabetes mellitus, hypertension,
hormonal disturbances, tumours with hormonal activity, Polycystic Ovarian Syndrome (Stein-Loeventhal Syndrome), gonadal dysgenesia (Turner Syndrome)
hormonal replecement therapy and oral contraception
diseases of hepar and gallbladder – more often
hypothyreosis, Cushing syndrome,
rheumatoid disease, clotting disturbances (thrombophlebitis).
Routes of spread
myometrial spread => uterine wall, parametrium, peritoneal cavity (pelvis / abdomen), regional organs,
cervical invasion (4-20%) and oviductal invasion (3-10%), ovarian and peritoneal implants (via abdominal opening of the oviducts)
blood vessels pathway => hepar, lungs, bones, skin, kidneys, brain, vagina,
lymph nodes pathway:
localisation in the uterine fundus => oviductal lymph nodes => ovarian lymph nodes => paraaortic lymph nodes => mediastinal lymph nodes => supraclavicular lymph nodes
localisation in the lateral sides of the uterus and uterine isthmus => iliac and obtural lymph nodes => vagina, urethra
via teres ligament => inquinal lymph nodes
simple hyperplasia (hyperplasia endometrii simplex)
complex hyperplasia (hyperplasia endometrii complex)
simple hyperplasia / complex hyperplasia with nuclear atypia (hyperplasia endometrii simplex / complex cum atypia nucleorum) – precancerous status
Endometrioid adenocarcinoma - Adenocarcinoma endometrioides endometrii: villous type, secretory type, ciliac-cells type, type with squamous differentiation (metaplasia).
Papillary serous adenocarcinoma - Adenocarcinoma serosum
Clear cell adenocarcinoma - Adenocarcinoma clarocellulare (mesonephroides).
Mucinous adenocarcinoma - Adenocarcinoma mucinosum.
Squamous carcinoma - Carcinoma planoepitheliale.
Mixed types of endometrial cancer.
Non-differential carcinoma (solid) - Carcinoma nondifferentiatum (solidum).
G 1 – high – differentiated adenocarcinoma ≤ 5% solid (non - squamous) cells
G 2 – medium – differentiated adenocarcinoma 6 - 50%
G 3 – low – differentiated adenocarcinoma ≥ 50%
Papillary serous carcinoma of the endometrium
primary endometrial neoplasm, morphological equivalent of the most frequent type of ovarian cancer. It is created the most often by papillary, oval / round cells about different degree of atypia, the presence of psammomas cells was affirmed sometimes.
Histological and clinical course of adenocarcinoma serosum (also adenocarcinoma clarocellulare) can be approximate to clinical view of analogous histologic types of ovarian cancer.
They are endometrial neoplasms independent from estrogens, with deep myometrial invasion, invasion of lymph nodes and lymph vessels, quick dissemination and the bad prognosis
Serous type of endometrial cancer appears about 10 years later than endometrial cancer: the age of diagnosis has hesitated since 40 till 86 years, from average 66 years.
It is not connected with diabetes mellitus, obesity, hypertension or previous estrogenotherapy.
Serous type of endometrial cancer is rare – about 5% of all cases of endometrial cancer.
The neoplasm has the tendency to deep invasion of the wall of uterus and the spreading beyond uterus as well as the creating of embolisms in blood vessels and lymph vessels
In despite of correct macroscopic view, in microscopic investigation affirms the invasion of muscular membrane of the uterus and spreading beyond uterus. Lymph nodes metastases were affirmed in 72% cases.
5–year survival in I and II clinical stage of serous adenocarcinoma of the endometrium is 36% - 68%, III and IV stage – is very rare
Type I – estrogenous - dependent:
G-1 or G-2 endometrioid adenocarcinoma
limited growth, exophytic tumour, coexisted endometrial hyperplasia,
Type II – estrogenous – non - dependent:
G-3 endometrioid adenocarcinoma, papillary serous adenocarcinoma, clear cell carcinoma
deep myometrial infiltration, coexisted endometrial atrophy
bleeding (the most common – postmenopausal)
discharge - fetid, bloody, purulent
pain – pelvis region, abdomen, vertebral column
systemic symptoms – weight loss, secondary anaemia, constipation, lower extremities oedema
anamnesis – case history – symptoms, risk factors,
dilatation and curretage of the uterus + histologic study: sensitivity - 90-92%
hysteroscopy: sensitivity - ±100%
endometrial biopsy: sensitivity - ±50%
ultrasound detection (abdominal, transvaginal, Doppler detection), TK, magnetic resonance detection (MRI), urography, X-ray chest examination, scyntygraphy (bone metastases)
cytologic smear (25%) remains negative – malignant endometrial cells do not reach the vaginal pool
Familiar incidence of endometrial cancer
Lynch II syndrome - Hereditary Nonpolyposis Colorectal Cancer
often, familiar incidence of colorectal cancer, ovarian cancer and endometrial cancer
endometrial cancer – secondary with frequency, 1% - 3% patients with Lynch II syndrome
4 genes mutation – autosomal dominant inherited
surgical treatment – abdominal or vaginal hysterectomy with/without bilateral salpingooophorectomy, pelvic and paraaortic lymphadenectomy
radiotherapy – primary, secondary
coexisting with other neoplasms
10% - 22,7% patients with endometrial cancer Develop second primary malignant neoplasm
higher risk of breast cancer and/or colorectal cancer,
coexistence endometrial cancer, ovarian cancer and oviductal cancer as systemic cancer process - 13% - 15%.
uterine fibromas (leiomyomas) - 25% - 35%,
endometrial polyps, cervical polyps,
into uterine corpus are rare.
breast & gastrointestinal tract by blood vessels
ovary by lymphatic vessels
uterine cervix, uterine tube, bladder, rectum by infiltration
five-year cure rate
Stage I 72,3% - 95%
Stage II 56,4% - 73%
Stage III 31,5% - 52%
Stage IV 10,6% - 27%
Recurrence and metastases
Most relapses - first 2- 3 years after surgical treatment.
Local recurrence :
after surgical treatment - vagina, parametrium
after primary radiotherapy - uterus, adnexa
Distant metastases :
via lymphatic vessels – pelvic and paraaortic lymph nodes, pelvic organs
via blood vessels - lungs, bones, kidneys, adrenal glands, brain, skin, hepar, pancreas
Histologic type + morphologic differentiation (grading)
Clinical staging – myometrial invasion – lymph nodes metastases
Peritoneal cytology. Invasion of the vessel space
Age of the patient
Genetic factors (DNA ploidy, nuclear atypia, expression of some genes). Hormonal receptors
The type of treatment
rare –1% – 3% of all uterine neoplasms, 15% cases of death due to female genital tract neoplasms (the highest mortality due to female genital tract malignant neoplasms).
pathology and histology
Primary tissues of the uterine sarcomas
connecting tissue, myometrium, muscular tissue of uterine fibroma, tissues of blood vessels walls, stroma of endometrium.
The neoplasm is built with diverse masses of round cells or the spindle - shaped, at children – the presence of striped muscles, at older persons – presence of cancer tissues and the tissues of mesodermal origin, for example chondrus.
limited type – pedunculated, often similar to cervical polyp,
disseminated type (invasive) – filling all uterine cavity with myometrial invasion,
type arising from uterine fibroma (rare) – yellowish, fleshy tumor with necrotic focuses.
age of patients
The age of patients be comprises from period of infancy till 8 decade of life (average 55,7 years).
In younger patients more often leiomyosarcoma occurs (average age – about 45 years), older patients – more often mixed mesodermal sarcoma and stromal sarcoma (average age – about 55 years).
similar to endometrial cancer
coexisted obesity (18%), hypertension (11%) and diabetes mellitus (8%)
nulliparas and unmarried women
unbalanced estrogenous therapy and tamoxifen treatment
primary radiotherapy due to cervical cancer or urine bladder cancer – the risk arises 6x (the exidence of uterine sarcoma can take place 5 to 20 years after radiotherapy)
massive uterine bleeding (postmenopausal bleeding, before menopause – hypermenorrhea / intermenstrual bleeding), abdominal pain, purulent vaginal discharge
Gynaecologic examination – pathologic tumor in the pelvis – unlarged, tumorous changed uterus (sometimes in cervical ostium – brittle tissues); younger women and children – tumor arising from vagina or uterine cervix (rare)
Differetiation– microscopic (histologic) examination of the probe of sarcomatic tissue.
Endometrial Stromal Sarcoma - ESS
about 15 – 20% of all uterine sarcomas, the most often women before menopause
hormonal – depended neoplasm, low malignancy
the best prognosis, the most often diagnosis in early clinical stages, 5-year survival is 60 – 80%
trongly expression of estrogen and progesterone receptor (almost 100% of cells)
surgical treatment – hysterectomy with adnexectomy (ovarian synthesis of estrogens can stimulate the recurrence of the disease); hysterectomy without ovaries can be performed in young women under 35 years old with tumours less then 3cm (the patient should be informed about the risk of relapse of the disease)
pelvic lymphadenectomy performed in advanced clinical stages (the risk of metastases to lymph nodes in advanced clinical stages is 33 – 45%); in early clinical stages pelvic lymphadenectomy is not recommended
possibility of adjuvant hormonotherapy and chemotherapy based on adriamycin and ifosfamide
about 40% of all uterine sarcomas, about 60% cases concerns tumours limited to the uterus (in these cases the percentage of curing carries out 20 – 60%)
it characterised with special susceptibility to early creating in lungs metastases, however the occupation of lymphatic glands is rare (3 – 7%); the risk of metastases to adnexa, particularly in low – grade tumours does not cross 3%
5–year survival is 12 – 40%
preoperative diagnostic methods permit on recognition this tumour seldom, because it develops in muscular layer of the uterus.
adjuvant treatment – chemotherapy: adriamycin, ifosfamid, docetaxel with gemcytabine or trabektydyne
hormonotherapy can be an option of treatment of the recurrence of low–grade tumours, due to expression of hormonal receptors in sarcomatic tissue
in the case of recurrence of leiomyosarcoma surgical resection of single neoplasmatic tumours can be connected with patient benefit (but relapse more then 6 months after first line of treatment).
the most often, especially in young women, excision of the uterine tumour is performed first, estimated by operator as uterine myoma
in the case of leiomyosarcoma, after conservative operation, next step is hysterectomy
in premenopausal women adnexectomy is not recommended, lymphadenectomy is not connected wit better prognosis, too.
Undifferentiated Sarcoma – UES
previously classificated as high – grade stromal sarcoma; account 5 – 10% of stromal sarcomas
rare neoplasm, different and poor – known biology and process of carcinogenesis
extremely agressive and rapid neoplasmatic process, quick and early local recurrences and distatant metastases (in 25% of patients, in the moment of diagnosis, sacromatis process spreads out of the uterus, metastases to lymph nodes 7 – 25%)
5-years survival – about 10% of patients
surgical treatment – hysterectomy with adnexectomy and all macroscopic lesions, the role of lymphadenectomy is of uncertain value
adjuvant chemotherapy (adriamycin, ifosfamide) – because of relative rarity of these tumours – no standard chemotherapy; no verify the role of radiotherapy
in the case of relapse – sometimes possibility of surgical treatment.
mixed neoplasm consists of benign epithelial component and mesenchymal component (the most often low–grade endometrial stromal sarcoma hormonal – dependend)
treatment – hysterectomy with adnexectomy with adjuvant hormonotherapy
in young women conservative surgical treatment is possible (sparing uterus and/or ovaries)
when mesenchymal component is undifferentiated sarcoma (poor prognosis) radical hysterectomy with bilateral adnexectomy, cytoreduction and adjuvant chemotherapy is recommended.
Endometrial Stromal Sarcoma and Leiomyosarcoma can be classificated with regard on degree of differentiation of tissue elements as low-grade and high-grade.
very agressive type of sarcoma, malignant charcter of both components (epithelial and mesenchymal)
may occur in women in every age – the most often postmenopausal (median age is 65 years – higher then in case of leiomyosarcoma)
5 – years survival is about 5 – 35%
clinical behaviour, biology, carcinogenesis and way of spread – similar to ovarian cancer or serous endometrial cancer high – grade adenocarcinoma (G-3)
metastases to lymph nodes – 16 – 60%
in 30% of tumour cells estrogens and progesterone receptors are found
clinical classification by FIGO – the same like endometrial cancer.
surgical treatment – hysterectomy with bilateral adnexectomy and pelvic and paraaortic lymphedenectomy, in the case of invasion of parametrium – radical hysterectomy; cytoreduction in advanced cases
given the adjuvant radiotherapy show the reduction of local relapse, without the influence to 5-years survival; limited role of hormonotherapy
adjuvant chemotherapy based on paclitaxel and carboplatin.