1. Precancer, benign and malignant tumors of the uterus and ovary
Eduard Kučera

2. Uterine fibroids

3. Risk factors
They are many risk factors1 associated with the development of uterine fibroids
Check smoking
1.Flake GP et al, Environmental Health Perspectives 2003; 111(8):

4. 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
Mass effects related to the size and location of fibroids
Pregnancy complications
Bleeding complaints
These symptoms and consequences have been shown to diminish quality of life3
When symptomatic, fibroids can be linked to at least three major problems3
Tropeano G, Amoroso S, Scambia G. Hum. Reprod. Update (2008) 14 (3):
Downes E, Sikirica V, Gilabert-Estelles J. et al. Eur J Obstet Gynecol Reprod Biol. 2010; 152(1):
Viswanathan M, Hartmann K, McKoy N. et al. Evid Rep Technol Assess (Full Rep) Jul;(154): Review.

5. Mechanisms FOR FERTILITY IMPACT
Mechanistic: space; abnormal contractions
Local inflammation for sperm and embryo
Inadequate blood supply

6. DIAGNOSIS - When and how?
Physical examination may be the first signal that a woman might have uterine fibroids.1
Imaging methods to evaluate these benign tumours:1
Ultrasonography
Hysteroscopy
Magnetic resonance imaging (MRI)
Evans P, Brunsell S. Am Fam Physician. 2007 May 15;75(10): ian

7. Uterine Fibroids
TREATMENT

8. 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
Miller CE, Journal of Minimally Invasive Gynecology 2009; 16:11–21

9. 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

10. Endometrial cancer
Endometrial cancer – most common gynecological malignancy
4th most frequent malignancy in women
In Czech Rep. incidence 32/ year
1500 new cases diagnosed per year (e.g. in UK 6,430)
Maximum around years
Obesity of women – typical phenotype

12. Etiology
so called „endometrial carcinoma syndrome“: obesity, (DM, hypertension)
- peripheral transformation of androgens
- insufficiency of ShBG
recently often used so celled.: postmenopausal syndrome
age: 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)

13. 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

14. 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

15. Hyperplasia 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.

16. FIGO staging 2010
The 2010 FIGO staging system is as follows: Carcinoma of the Endometrium
IA Tumor confined to the uterus, no or < ½ myometrial invasion
IB Tumor confined to the uterus, > ½ myometrial invasion
II Cervical stromal invasion, but not beyond uterus
IIIA Tumor invades serosa or adnexa
IIIB Vaginal and/or parametrial involvement
IIIC1 Pelvic lymph node involvement
IIIC2 Para-aortic lymph node involvement, with or without pelvic node involvement
IVA Tumor invasion bladder mucosa and/or bowel mucosa
IVB Distant metastases including abdominal metastases and/or inguinal lymph nodes

17. 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%

18. Hysteroscopy 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)

19. Diagnostic 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

20. Tamoxifen 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

21. Tamoxifen – endometrium pathology
Length of therapy not more then 5 years
Metrorrhagia always indication to endometrial examination
In asymptomatic women (cca 70%) HSK vs. UZ part of periodic yearly check ups
High percentage of false positive results with ultrasound examination– stromal edema (vacuolar degeneration)
Tamoxifen % incidence of polyps – proliferative activity in epithelial and stromal part
Incidence of endometrial carcinoma cca in 3%

22. Tamoxifen and endometrium
International agreement – 1997
Bioptical examination of the endometrium before beginning the therapy
After 3 years of using observation in yearly intervals Lancet, ,2000.

23. Tamoxifen 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

24. Ovarian Neoplasms

25. Ovarian Neoplasms- Introduction
Common neoplasms.
80% are benign – young (20-45)
20% are Malignant - older (>40)
6% of all cancers in women.
50% deaths due to late detection.

26. Ovarian cyst Most ovarian cysts are functional in nature and benign
Functional or non functional
Functional – folicular, corpus luteal, thecal haemorrhagical c.
Non – functional – dermoid, endometriotic, cystadenoma, parovarian etc.

27. Diagnosis - sonography

28. Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary.
Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses
Ovarian cancer is the second most common gynecologic cancer and the deadliest in terms of absolute number.[57] It caused nearly 14,000 deaths in the United States alone in 2010.

29. Risk Factors Null parity Gonadal Dysgenesis Family History
Ovarian cancer genes
BRCA1 (17q12) & BRCA2(13q12)
(Cancer suppressor, Breast & ovary)

30. FIGO staging Stage I — limited to one or both ovaries
IA — involves one ovary; capsule intact; no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings
IB — involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
IC — tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings
Stage II — pelvic extension or implants
IIA — extension or implants onto uterus or fallopian tube; negative washings
IIB — extension or implants onto other pelvic structures; negative washings
IIC — pelvic extension or implants with positive peritoneal washings
Stage III — peritoneal implants outside of the pelvis; or limited to the pelvis with extension to the small bowel or omentum
IIIA — microscopic peritoneal metastases beyond pelvis
IIIB — macroscopic peritoneal metastases beyond pelvis less than 2 cm in size
IIIC — peritoneal metastases beyond pelvis > 2 cm or lymph node metastases
Stage IV — distant metastases to the liver or outside the peritoneal cavity

31. Classification Surface epithelial – 65-70% stromal – 15-20%
Germ cell tumors – 5-10%
Metastatic tumors – 5%

32. 5- year survival rate

33. Surface Epithelial tumors:
Coelomic mesothelium.
Serous(tubal), Mucinous (Cx) & endo
Most common primary neoplasms
90% of malignant tumors of ovary
Morphologically
Cystic – Cystadenomas
Solid/cystic – Cystadenofibromas
Solid - adenofibromas

34. Surface Epithelial tumors
Serous (tubal)
Mucinous (endocx & intestinal)
Endometrioid
Transitional cell - Brenners.
Clear cell

35. Surface Epithelial tumors
all types can be benign, borderline , or malignant, depending upon;
Benign ; - gross: mostly cystic - microscopic; fine papillae, single layer covering (no stratification), no nuclear atypia, no stromal invasion)
Borderline ; - gross; cystic / solid foci - microscopic; papillary complexity, stratification, nuclear atypia, no stromal invasion
Malignant ; - gross; mostly solid & hemorrhage / necrosis
- microscopic; papillary complexity, stratification, nuclear atypia, stromal invasion

36. Serous Tumors: Frequently bilateral (30-66%).
75% benign/bord., 25% malignant.
One unilocular cysts, papillary/less solid- benign/borderline
Tall columnar ciliated epithelium.
Papillary, solid, hemorrhage, necrosis or adhesions – malignancy.
Extension to peritoneum – bad prognosis.

37. Mucinous Tumors: Less common 25%, very large. Rarely malignant - 15%.
Multiloculated, many small cysts.
Rarely bilateral – 5-20%.
Tall columnar, apical mucin.
Pseudomyxoma peritonei.

38. Endometrioid tumors most are unilateral (40% are bilateral)
cells look like endometrium even though they are coming from the coelum of the ovary.
almost all are malignant
about 20% of all ovarian tumors
many are associated with endometrial cancer (30%)
patient may have concurrent endometriosis

39. Clinical course of coelomic surface epithelial tumors
low abdominal pain
abdominal enlargement
GI tract complaints
urinary tract complaints
malignant ones produce ascites
serosal surfaces are seeded with cancer in metastasis
grow slowly and get very large

40. Germ cell Tumors Teratoma – Dysgerminoma
Benign cystic (dermoid cysts)
Solid immature
Monodermal – struma ovarii, carcinoid
Dysgerminoma
Yolk sac tumor (Endodermal sinus tumor )
Choricarcinoma
Mixed germ cell tumor

41. Endodermal sinus tumor (Yolk sac carcinoma)
Tumor is a highly malignant and clinically aggressive neoplasm
Most frequently in children and young females
20% of malignant germ cell tumors.
fatal within 2 years of diagnosis

42. Sex Cord - Stromal Tumors
Granulosa-cell tumor
Thecoma
Fibroma
Sertoli-Leydig cell tumors

43. Granulosa Cell Tumor Hormonally active tumor
The most common estrogenic ovarian neoplasm.
The adult form occurs mainly in postmenopausal women, associated with endometrial hyperplasia and carcinoma
The juvenile type occurs in the first two decades, cause precocious sexual development.

44. Granulosa Cell Tumor
Sheets of granulosa cells containing spaces lined by the cells to give a follicle-like appearance (Call-Exner bodies).

45. Thecoma Functional tumors producing estrogen
It occur in postmenopausal women
Endometrial hyperplasia or carcinoma may develop

46. Sertoli-Leydig cell tumors
1% of ovarian neoplasms
It occur predominantly in young women.
Commonly androgenic, cause defeminization of women manifested as breast atrophy, amenorrhea, and loss of hair and hip fat , to virilization with hirsutism

47. Metastases to ovary
About 3% of malignant tumors in the ovary are metastatic
The most common primary site is the breast followed by the large intestine, stomach, and other genital tract organs.

48. Krukenberg tumor
It is applied to the uniform enlargement of the ovaries (usually bilaterally) due to diffuse infiltration of the ovarian stroma by metastatic signet-ring cell carcinoma .
The commonest primary site is the stomach followed by the colon.

49. Therapy
Surgery
Chemotherapy
Biological therapy