Precancer, benign and malignant tumors of the

uterus and ovaryEduard Kučera

UTERINE FIBROIDS

RISK FACTORS

● They are many risk factors1 associated with the development of uterine fibroids

1.Flake GP et al, Environmental Health Perspectives 2003; 111(8):1037-54

Mass effectsrelated to the size

and locationof fibroids

Pregnancycomplications

Bleedingcomplaints

These symptoms and consequenceshave been shown to diminish quality of life3

When symptomatic, fibroids can be linkedto at least three major problems3

WHAT ARE THE SYMPTOMS?

● Not all fibroids are symptomatic

● However, for the 50% of women with symptomatic fibroids, the condition is debilitating.1

● Symptoms can include:● Abnormal or heavy

menstrual bleeding1, 2

● Pain,1,2 pressure symptoms1,2 and urinary symptoms2

● Impairment of Quality of Life 2

1. Tropeano G, Amoroso S, Scambia G. Hum. Reprod. Update (2008) 14 (3): 259-274. 2. Downes E, Sikirica V, Gilabert-Estelles J. et al. Eur J Obstet Gynecol Reprod Biol. 2010; 152(1): 96-102.3. Viswanathan M, Hartmann K, McKoy N. et al. Evid Rep Technol Assess (Full Rep). 2007 Jul;(154):1-122. Review.

MECHANISMS FOR FERTILITY IMPACT

• Mechanistic: space; abnormal contractions

• Local inflammation for sperm and embryo

• Inadequate blood supply

DIAGNOSIS - WHEN AND HOW?

● Physical examination may be the first signal that a woman might have uterine fibroids.1

● Imaging methods to evaluatethese benign tumours:1

● Ultrasonography

● Hysteroscopy

● Magnetic resonance imaging(MRI)

1. Evans P, Brunsell S. Am Fam Physician. 2007 May 15;75(10):1503-1508.ian

TREATMENTUterine Fibroids

THERAPEUTIC APPROACH

Currently, therapies are intended to reduce or eliminate uterine fibroid symptoms through one of the following options1

● Reduction of the size of tumours

● Reduction of the amount of bleeding

● Removal of the uterine fibroids or uterus

1. Miller CE, Journal of Minimally Invasive Gynecology 2009; 16:11–21

THERAPEUTIC APPROACH

The choice of therapy is influenced by the patient’s● Symptom severity

● Tumour characteristics (e.g. volume, localisation)

● Age

● Uterine preservation wishes

● Fertility preservation wishes

Endometrial cancer

Endometrial cancer – most common gynecological malignancy

4th most frequent malignancy in women

In Czech Rep. incidence 32/100 000 year

1500 new cases diagnosed per year (e.g. in UK 6,430)

Maximum around 60 - 70 years

Obesity of women – typical phenotype

Etiology

so called „endometrial carcinoma syndrome“: obesity, (DM, hypertension) - peripheral transformation of androgens - insufficiency of ShBG

recently often used so celled.: postmenopausal syndrome age: 6. - 7. decade nulliparity (RR=2,8) Infertility (RR=8) late menopause (RR= 2,4) estrogen producing ovarian cancers high intake of animal proteins and fats exogenous estrogens - unopposed gestagens (RR=2,3) tamoxifen (RR=2,4)

Carcinogenesis in peri- and postmenopausal

women

Carcinogenesis in peri- and postmenopausal

women younger women older women

complex hyperplasia

de novo hyperplasia with atypia

endometrial carcinoma

( Type I usually well diff. ) ( Type II usually poorly diff. ) endometroid carcinoma papillary serous

clear cell carcinoma

younger women older women

complex hyperplasia de novo

hyperplasia with atypia

endometrial carcinoma

( Type I usually well diff. ) ( Type II usually poorly diff. ) endometroid carcinoma papillary serous

clear cell carcinoma

Histological types

Carcinoma (98%) endometroid adenocarcinoma adenocarcinoma with squamous cells clear cell carcinoma papillary serous spinocellular

Sarcoma (2%) leiomyosarcoma endometrial stromal sarcoma mixed mesodermal cancers

Hyperplasia of endometriumHyperplasia of endometrium

Complex atypical hyperplasia = precancerosis of endometrial carcinoma ( especially endometroid type)

- cell polymorphism, mitosis, nucleoplasmic index, hyperchromatosis

- creation is independent on estrogen stimulation in

atrophic endometrium

Motlík,K, Živný,J.:Patologie v ženském lékařství,Grada,2001.

Complex atypical hyperplasia = precancerosis of endometrial carcinoma ( especially endometroid type)

- cell polymorphism, mitosis, nucleoplasmic index, hyperchromatosis

- creation is independent on estrogen stimulation in

atrophic endometrium

Motlík,K, Živný,J.:Patologie v ženském lékařství,Grada,2001.

FIGO staging 2010The 2010 FIGO staging system is as follows: Carcinoma of the EndometriumIA Tumor confined to the uterus, no or < ½ myometrial invasionIB Tumor confined to the uterus, > ½ myometrial invasionII Cervical stromal invasion, but not beyond uterusIIIA Tumor invades serosa or adnexaIIIB Vaginal and/or parametrial involvementIIIC1 Pelvic lymph node involvementIIIC2 Para-aortic lymph node involvement, with or without pelvic node involvementIVA Tumor invasion bladder mucosa and/or bowel mucosaIVB Distant metastases including abdominal metastases and/or inguinal lymph nodes

5 – year survival year

Stage 5 year survival rate

I-A 90%

I-B 88%

I-C 75%

II 69%

III-A 58%

III-B 50%

III-C 47%

IV-A 17%

IV-B 15%

Hysteroscopy and dg. curettageHysteroscopy and dg. curettage

Curettage – frequent false negative results (10-50%) Curettage – in polyps up to 61%Hysteroscopy and targeted biopsy < 2% false negative results (Gimbelson, Loffer 1988, 1989, AJOG) Studies in 1383 histological findings obtained with D&C - 60% inadequate results (Smith, 1985)In 60% patients curetted < 1/2 cavity of the uterus (Stock, Obst.Gyn.,1975)

Curettage – frequent false negative results (10-50%) Curettage – in polyps up to 61%Hysteroscopy and targeted biopsy < 2% false negative results (Gimbelson, Loffer 1988, 1989, AJOG) Studies in 1383 histological findings obtained with D&C - 60% inadequate results (Smith, 1985)In 60% patients curetted < 1/2 cavity of the uterus (Stock, Obst.Gyn.,1975)

Diagnostic hysteroscopy - optionsDiagnostic hysteroscopy - options

Panoramatic view – magnified 1x conventional hysteroscopy allows viewing the whole uterine

cavity and locate pathologies

panoramatic macro-hysteroscopy – 20x magnification in distance < 1 cm

Micro-contact hysteroscopy – 80x magnification allows evaluation of endometrial vascularisation, gland characteristic and their openness

Panoramatic view – magnified 1x conventional hysteroscopy allows viewing the whole uterine

cavity and locate pathologies

panoramatic macro-hysteroscopy – 20x magnification in distance < 1 cm

Micro-contact hysteroscopy – 80x magnification allows evaluation of endometrial vascularisation, gland characteristic and their openness

Tamoxifen a endometriumTamoxifen a endometrium

Nonsteroidal synthetic anti-estrogen

Adjuvant therapy in breast carcinoma

Accumulation of effective substance in basal endometrium

Endometrial proliferative abnormality (up to 40% postmenopausal women) - polyps, hyperplasia as much as endometrial carcinoma (2-3/1000/year)

Higher risk of endometrial carcinoma after using more then 5 (?) years (2-7.5x)

Most safe and effective screening is hysteroscopy in yearly intervals

Nonsteroidal synthetic anti-estrogen

Adjuvant therapy in breast carcinoma

Accumulation of effective substance in basal endometrium

Endometrial proliferative abnormality (up to 40% postmenopausal women) - polyps, hyperplasia as much as endometrial carcinoma (2-3/1000/year)

Higher risk of endometrial carcinoma after using more then 5 (?) years (2-7.5x)

Most safe and effective screening is hysteroscopy in yearly intervals

Tamoxifen – endometrium pathology

Tamoxifen – endometrium pathology

Length of therapy not more then 5 yearsMetrorrhagia always indication to endometrial examinationIn asymptomatic women (cca 70%) HSK vs. UZ part of periodic yearly check upsHigh percentage of false positive results with ultrasound examination– stromal edema (vacuolar degeneration)Tamoxifen - 37 - 71% incidence of polyps – proliferative activity in epithelial and stromal partIncidence of endometrial carcinoma cca in 3%

Length of therapy not more then 5 yearsMetrorrhagia always indication to endometrial examinationIn asymptomatic women (cca 70%) HSK vs. UZ part of periodic yearly check upsHigh percentage of false positive results with ultrasound examination– stromal edema (vacuolar degeneration)Tamoxifen - 37 - 71% incidence of polyps – proliferative activity in epithelial and stromal partIncidence of endometrial carcinoma cca in 3%

Tamoxifen and endometriumTamoxifen and endometrium

International agreement – 1997

Bioptical examination of the endometrium before beginning the therapy

After 3 years of using observation in yearly intervals

Lancet,1698-1711,2000.

International agreement – 1997

Bioptical examination of the endometrium before beginning the therapy

After 3 years of using observation in yearly intervals

Lancet,1698-1711,2000.

Tamoxifen and endometriumTamoxifen and endometrium

Hysteroscopy with biopsy – first choice in patients with Tamoxifen therapy

Symptomatic patients and therapy longer then 3 years

Positive family history

Taponeco,F et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J.Exp.Clin.Cancer,21,2002

Hysteroscopy with biopsy – first choice in patients with Tamoxifen therapy

Symptomatic patients and therapy longer then 3 years

Positive family history

Taponeco,F et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J.Exp.Clin.Cancer,21,2002

Endometrial cancer - therapy

Surgery - radical

Radiotherapy

Hormonal therapy