Transcript DIAGNOSTICA ECOGRAFICA IN GINECOLOGIA Altomonte …

ENDOMETRIAL CANCER
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Cancer of the uterine endometrial lining
Most common female reproductive cancer
40,000 new cases/year
 7,000 deaths/year
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Most of these malignancies are
adenocarcinoma
Incidence and Prevalence
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Most common gynecologic cancer
4th most common in women (US)
2nd most common in women (UK)
5th most common in women (worldwide)
Western developed > Southeast Asia
Increase in the 1970’s
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Increased use of menopausal estrogen therapy
GYNECOLOGIC CANCER
Endometrium
6% of all cancer in women
2-3% lifetime risk
GYNECOLOGIC CANCER
Endometrium
Age Mean is 61 yrs.
Menopausal 75-80%
Pre-menopausal 20-25%
~5% <40 yrs old.
CARCINOMA DELL’ENDOMETRIO:
EPIDEMIOLOGIA
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In Italia si hanno circa 5.000 nuovi casi ogni
anno.
Generalmente insorge in età postmenopausale,
sebbene circa il 30% dei casi venga diagnosticato
prima della menopausa e il 5% prima dei 40
anni.
Incidence e mortality rates per 100.000
for cancer of the uterus and corpus
80
70
60
50
40
incidence
mortality
30
20
10
0
incidence
mortality
under 50
50 and older
3,6
0,2
78,6
12,8
Corpus Uteri Carcinoma
Histopathologic Types and Grades
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Histopathologic Types
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Histopathologic Grades
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Endometrioid carcinoma (75%-80%)
- Ciliated adenocarcinoma
- Secretory adenocarcinoma
- Papillary or villoglandular
- Adenocarcinoma with squamous
differentiation:
- adenocanthoma
- adenosquamous
Uterine papillary serous (< 10%)
Mucinous (1%)
Clear cell (4%)
Squamous cell (<1%)
Mixed carcinoma (10%)
Undifferentiated
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Gx – Grade cannot be
assessed
G1 – Well differentiated; 5% or
less of a nonsquamous or
nonmorular solid growth
pattern
G2 – Moderately differentiated;
6% to 50% of a nonsquamous
or nonmorular solid growth
pattern
G3 – Poorly or
undifferentiated; more than
50% of a nonsquamous or
nonmorular solid growth
pattern
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FIGO Surgical Staging for Carcinoma of the Corpus Uteri
STAGE DESCRIPTION OF STAGE
IA
IB
IC
Tumor limited to the endometrium
Invasion to less than half of the myometrium
Invasion equal to or more than half of the myometrium
II A
II B
Endocervical glandular involvement only
Cervical stromal invasion
III A
Tumor invades the serosa of the corpus uteri and/or adnexae
and/or positive cytologic findings
Vaginal metastases
Metastases to pelvic and/or paraaortic lymph nodes
III B
III C
IV A
IV B
Tumor invasion of bladder and/or bowel mucosa
Distant metastases, intraabdominal or inguinal lymph
nodes
ENDOMETRIAL CANCER: RISK FACTORS
Increase
Age, obesity, diabetes
and hypertension
Family history
Infertility/low
parity/late
menopause/chronic
anovulation
Estrogen (exogenous,
endogenous)
Tamoxifen
Decrease
Contraceptive pill
RISK FACTORS FOR
ENDOMETRIAL CANCER
Early menarche
(<age 12)
 Late menopause
(>age 52)
 Infertility or nulliparous
 Obesity
 Treatment with tamoxifen for
breast cancer
 Estrogen replacement
therapy (ERT) after
menopause
 Diet high in animal fat
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Diabetes
Age greater than 40
Family history of
endometrial cancer or
hereditary nonpolyposis
colon cancer (HNPCC)
Personal history of breast or
ovarian cancer
Prior radiation therapy for
pelvic cancer
ADENOCARCINOMA DELL’ENDOMETRIO: FATTORI
DI RISCHIO
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TIPO I
Estrogeno correlato
Tende ad essere associato all’iperplasia
Colpisce donne più giovani
Prognosi complessivamente migliore
TIPO II
Non estrogeno correlato
Può insorgere in un endometrio atrofico
Colpisce donne più anziane
Prognosi più severa
RISK FACTORS
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A.
B.
C.
D.
The risk of developing cancer of the
uterine corpus has been related to
reproductive
endocrine
lifestyle
genetic factors
A. REPRODUCTIVE RISK
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Nulliparity has been shown to independently
increase the risk of endometrial cancer
May be related to the higher incidence of
anovulation among nulliparous women
Age at first and last birth were not significant
when results were adjusted for number of
births
There is an age-adjusted decrease in mortality
of 9.2% for each birth.
B. ENDOCRINE RISK
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The major risk factor for endometrial carcinoma is
thought to be endogenous or exogenous estrogen
exposure unopposed by progesterone or synthetic
progestins.
The unopposed estrogen theory suggests that there is a
resultant increase in mitotic activity of endometrials cells,
Dna replications errors and somatic mutations causing
endometrial hyperplasia and malignancy or type I
endometrial carcinoma
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Type II endometrial carcinoma is likely unrelated to
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estrogen exposure and results from atrophic rather
hyperplastic epithelium.
Because the two types differ in histopathologic
appearance and biologic behavior, differences may be
associated with distinct molecular genetic alterations.
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B. ENDOCRINE RISK
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ENDOGENOUS RISK FACTORS that are
known to increase the risk of developing endometrial
cancer include:
1.
Obesity: in postmenopausal women conversion of
androstenedione to estrone in adipose tissue is postulated
as a mechanism for increased risk of endometrial cancer
associated with obesity
2.
Menstruation span: it is theorized that both early
menarche age and older age at menopause increase
uterine exposure to estrogens,thereby increasing risk of
developing endometrial cancer.
Endometrial Cancer
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Strong association with excess
weight
Adipose tissue: Consequences of
Obesity on Cancer Development
Obesity has been implicated in the development of
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Type 2 diabetes
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Heart disease
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Stroke
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Hypertension
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Gallbladder disease
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Osteoarthritis
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Sleep apnea
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Asthma
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Psychological disorders or difficulties
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Some cancers, including ovarian,
and endometrial
Dyslipidemia
Complications of pregnancy
Hirsuitism
Menstrual abnormalities
Stress incontinence
Increased surgical risk
cervical, breast,
Endometrial Cancer and Lifestyle
B. ENDOCRINE RISK
3.
Diabetes: women with diabetes had an
adjusted OR of 1.86 for developing endometrial
carcinoma. The association was influenced and
modified by BMI. When obese (BMI>31.9),diabetic
women had an elevated risk (OR 2.95)
4.
Anovulation and Other
Endocrinopathies
Anovulation can cause infertility and can is responsable of
increased risk for endometrial cancer. PCOS (polycystic
ovary syndrome) is characterized by anovulation,
hyperandrogenism and menstrual dysfunction. Chronic
anovulation associated with PCOS increases risk
for endometrial carcinoma caused by unopposed
estrogen.
B. ENDOCRINE RISK
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1.
EXOGENOUS FACTORS include:
Estrogen replacement therapy (ERT) There is a
parallel increase in the incidence of endometrial cancer
and use of ERT. RR is of 2.3 for women taking estrogen compared
with those not taking estrogen. Among women taking estrogen for 10
years or longer, the RR was 9.5. Progestins appear to
antagonize the effects of estrogen on the endometrium and
prevent or reverse endometrial hyperplasia. Continous
combined estrogen-progestin therapy has been found superior to
estrogen and progestin given sequentially because of bleeding and
other adverse affects associated with sequential therapy.
2.
Oral contraceptive have been shown to reduce the
incidence of endometrial carcinoma as well as epithelial ovarian
cancer
B. ENDOCRINE RISK
3.
Tamoxifen adjuvant therapy
Tamoxifen belongs to a group of drugs known as selective estrogen
receptors modulators that produce varied effects in different body
organs. Tamoxifen increases survival from breast cancer by inhibiting
estrogen-receptor positive cells, but incidence rates for
endometrial cancer are increased somewhat in patients who
take the drug, either because of coincident risk of
developing endometrial carcinoma or direct and indirect
estrogen-like effects on the endometrium.
Tamoxifen benefits in the treatment of breast cancer outweigh the risk of
developing endometrial carcinoma because most tamoxifen-related
endometrial cancers are detected early and are highly curable at early
stage. Raloxifene is under investigation as an alternative to tamoxifen
because it appears to be less likely to cause endometrial stimulation.
C. LIFESTYLE-related RISK
1.
Smoking: cigarette smokers have a reduced risk of
endometrial cancer. Risk reduction was greatest in women
who are obese or who use postmenopausal hormones.
Smoking, however, was associated with advancedstage and higher tumor grade.
2.
Dietary Factors dietary inclusion of complex
carbohydrates such as breads and cereals was
associated with reduced risk,whereas higher levels of
animal fat were associated with higher risk. Reduced
risks were found with phytosterols, vitamin C, folate, alphacarotene, beta-carotene, lycopne and vegetables.
D. GENETIC RISK
Role of alterations in oncogenes and tumor suppressor genes in the
genesis of cancer of the uterine corpus and molecular pathogenesis of
endometrial carcinoma.
1.
2.
3.
4.
Family History
Hereditary Nonpolyposis Colon
Carcinoma
Oncogenes and Tumor Suppressor
Genes
A2 Allele of CYP17
D. GENETIC RISK
1.
Family History: the risk of endometrial cancer was
substantially increased in women who had a first-degree
female relative with endometrial carcinoma.
2.
Hereditary Nonpolyposis Colon Carcinoma:
at least five gene mutations have been identified in families
with HNPCC. Women who inherit HNPCC susceptibility
syndrome have a 60% chance of developing endometrial
cancer as well as an 80% chance of developing colon
cancer.
D. GENETIC RISK
3.Oncogenes and Tumor Suppressor Genes:
Poor survival has been correlated with overexpression of
the HER-2/neu oncogene which occurs in 10% of
endometrial cancer
Mutations in the K-ras oncogene are present in 10% of
American women and in 20% to 30% of Japanese women
with endometrial carcinoma. (26% c.endometrioid; 2%
c.serous)
Overexpression of p53 mutant protein resulting from
mutation of p53 tumor suppressor gene is present in 20% of
women with endometrial adenocarcinomas. (17%
c.endometrioid; 93% serous)
4.
A2 Allele of CYP17:increase the hormones steroid
endogenous
GYNECOLOGIC CANCER
Endometrium—Prevention
Progestin with estrogen
Diet, Exercise and Weight control
If genetic mutation, AND done with
reproduction, offer hysterectomy and BSO
Dietary fiber
Increases estrogen
excretion and decreases
estrogen reuptake: whole
grains, vegetables, fruits,
and seaweeds
SYMPTOMS OF
ENDOMETRIAL CANCER
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Symptoms
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Non-menstrual bleeding or discharge
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Especially post-menopausal bleeding
Heavy bleeding
 Dysuria
 Pain during intercourse
 Pain and/or mass in pelvic area
 Weight loss
 Back pain
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GYNECOLOGIC CANCER
Endometrium
Presentation—Abnormal Bleeding
EVEN ONE DROP OF BLOOD IN A
MENOPAUSAL WOMAN NOT ON HORMONES
DEMANDS WORKUP
10-20% will have endometrial cancer, and probability
increases with age.
ABNORMAL UTERINE BLEEDING(AUB)
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A.
B.
C.
Diagnosis of endometrial carcinoma depends on early
differential assessment of abnormal vaginal bleeding,
present in 90% of women with cancer of the uterine
corpus.
Women of all ages experience unusual vaginal bleeding,
but the significance and likely causes vary with age:
In premenopausal women the causes are: pregnancyrelated disorders,infection,birth control methods and
dysfunctional uterine bleeding (DUB) associated with
anovulation.
In perimenopause an abnormal uterine bleeding is
expected,but heavy abnormal bleeding requires
evaluation.
In postmenopausal women, endometrial carcinoma
should be suspected.
CARCINOMA DELL’ENDOMETRIO:
Sintomatologia
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PAZIENTI
ASINTOMATICHE
(5-10%)
1.
Cellule endometriali al pap
test
Ispessimento endometriale
in pazienti in trattamento
con HRT
o
TAMOXIFENE
Soggetti a rischio di
patologia neoplastica
2.
3.
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PAZIENTI
SINTOMATICH
E
(90-95%)
1.
Perdite ematiche
atipiche
ENDOMETRIAL CANCER
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Diagnosis
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Treatment
Pelvic examination
 Surgery
Pap smear (detect cancer spread to
 Hysterectomy
cervix)
 Salpingo-oophorectomy
Endometrial biopsy
 Pelvic lymph node dissection
Dilation and curettage
 Laparoscopic lymph node
Transvaginal ultrasound
sampling
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Radiation therapy
Chemotherapy
Hormone therapy
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Progesterone
Tamoxifen
CARCINOMA DELL’ENDOMETRIO:
ITER DIAGNOSTICO NELLA PAZIENTE
CON PERDITE EMATICHE ATIPICHE
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ESAME PELVICO
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ECOGRAFIA TRANSVAGINALE
DIAGNOSTICA ECOGRAFICA IN PERI- E
POST-MENOPAUSA
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ENDOMETRIO
1.
Spessore degli echi
Omogeneità
Interfaccia endometriomiometrio
2.
3.
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CAVITA’
UTERINA
1.
Dislocazioni
Neoformazioni
Dilatazioni
Presenza di liquido
2.
3.
4.
DIAGNOSTICA ECOGRAFICA IN
PERI- E POST-MENOPAUSA
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1.
2.
MIOMETRIO
Omogeneità
Neoformazioni
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1.
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1.
ANNESSI
Neoformazioni
SCAVO DEL
DOUGLAS
Occupato da
neoformazioni
solide e/o
versamento
DIAGNOSTICA ECOGRAFICA IN POSTMENOPAUSA
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ECHI ENDOMETRIALI
LINEARI E SOTTILI (<4-5 mm)
CAVITA’ UTERINA
VUOTA
ANNESSI
ATROFICI (ovaie piccole, ellissoidali,
uniformemente ipoecoiche)
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SCAVO DEL DOUGLAS
LIBERO
CARCINOMA DELL’ENDOMETRIO:
DIAGNOSI
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DIAGNOSI DI NATURA
ESAME ISTOLOGICO
DEL CAMPIONE
ENDOMETRIALE
 Biopsia ambulatoriale
 Isteroscopia con biopsia
endometrio
 Raschiamento frazionato
della cavità uterina
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DIAGNOSI DI STADIO
CLINICO
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Isteroscopia
RMN
Dosaggio CA 125
Rx Torace
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CARCINOMA DELL’ENDOMETRIO:
METODI PER LA DIAGNOSI ISTOLOGICA
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Biopsia endometriale ambulatoriale:
PIPELLE o VABRA
Raschiamento frazionato della cavità uterina con
curet (D&C). Richiede ospedalizzazione ed
anestesia generale
Isteroscopia con biopsia diretta alla lesione.
CARCINOMA DELL’ENDOMETRIO:
METODI PER LA DIAGNOSI ISTOLOGICA
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Biopsia endometriale
ambulatoriale:
PIPELLE o
VABRA
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Alta sensibilità (8095%)
Basso costo
Alta compliance
Non richiede
strumentazione costosa
e personale esperto
CARCINOMA DELL’ENDOMETRIO:
DIAGNOSI
RASCHIAMENTO
FRAZIONATO DELLA
CAVITA’ UTERINA
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Si esegue nel 5-10% dei
casi qualora non si riesce
ad eseguire l’isteroscopia
diagnostica ambulatoriale.
Molto costoso
CARCINOMA DELL’ENDOMETRIO:
DIAGNOSI
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ISTEROSCOPIA
AMBULATORIALE
CON BIOPSIA
DIRETTA
Considerata la metodica
ideale
Distingue la patologia
neoplastica maligna da
quella benigna (polipi,
miomi)
Valuta l’interessamento
del canale
QUADRI ISTEROSCOPICI DI CARCINOMA DELL’ENDOMETRIO
QUADRI ISTEROSCOPICI DI CARCINOMA DELL’ENDOMETRIO
QUADRI ISTEROSCOPICI DI CARCINOMA DELL’ENDOMETRIO
CARCINOMA DELL’ENDOMETRIO:
DIAGNOSI DI STADIO CLINICO
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ISTEROSCOPIA: Valutazione
dell’interessamento del canale cervicale
RMN: Valutazione della profondità di
infiltrazione miometriale
DOSAGGIO CA 125: Valutazione della
diffusione extrauterina della malattia