Benign and malignant ovarian tumors

The objectives

 1.the student must know the the histological types of ovarian tumor.
 2.the student must know the diagnosis of ovarian tumor.
 3.the student must know the risk factors of ovarian tumors.
 the student nice to know the staging & treatment of ovarian tumors

Ovarian Cysts

 Follicular (including atretic follicles)

 Luteal
 Germinal
 Corpora lutea
 Rete ovarii
 Paraovarian cysts

 Germinal Cysts - 20-38%

 Microscopic cystic structures within ovarian cortex and do not impair ovarian function

Other Ovarian Cysts

 Rete Cysts - 9-35%

 Irregular anastomosing tubules with cystic changes in the hilar region of the ovary
 No clinical disease, but replace normal tissue
 Parovarian cysts
 Remnants of the para -/ mesonephric tubules
 Do not impair ovarian function
 Cystic Corpora Lutea - rare

Ovarian Cysts

 Follicular – thin walled, >25 mm

 Follicular Cysts
• Persists for >10 days in the absence of a CL
• No hormone secretion, no response GnRH, PGF2α
 Cystic Follicle
• Regressed or ovulated within 10 days
• Secretes estradiol, luteinizes with GnRH, no response to PGF2α
•
 Follicular Cysts

 Unkown pathogenesis
 Lined with granulosa cells, degenerate cumulus, rarely luteal cells, never oocyte
 Elevated estrogen
 causes - induction of OV or OHS

 Luteal Cysts –
 thick walled, >25mm
 Secretion of progesterone
 Probably luteinization of follicular cysts
 Can be confused with a normal CL containing a fluid filled cavity
 Responds to PGF2α
 Luteal Cysts - 9%
 Luteinized anovulatory follicles
 Insufficient LH for ovulation
 Unknown clinical significance

 Risk Factors
 Heredity, recurrence, repeatability vary
 Increased milk production
 Hypothyriodism
 Drugs
 Estrogen content in feeds

Nutrition

• Ketone concentrations in milk

• Vitamin Deficiencies
 IGF-1
• Positive correlation between IGF-1 and steroidogenic capacity of first
postpartum dominant follicle
• IGF-1 increases the number of LH binding sites in thecal cells and it
changes LH induced production of progesterone and androstenedione.

 Treatment and Outcome

 30-71% may resolve without treatment
 Treatment with GnRH at the first followed by PGF2α 7-10days later should lead
to a resumption of cyclicity within 23 days
OVARIAN TUMOUR

INTRODUCTION

* It is common gynaecological tumour continue to kill more women than all other
gynaecological cancer
* In England the incidents of ovarian cancer 1.4 higher than cervical and endometrial cancer but
lower than breast cancer 7.1%
* Eventually 80 to 85% of women with ovarian cancer die
* Most ovarian cancer as epithelial in origin and incidence increase risk with age.
Germ cell tumour rare and occur mainly in children and young women.
* Survival rater 5 years in 60% of stage I disease ovarian malignancy.

Histopathology and Classification of ovarian mass.

* Ovarian mass Physiological , Neoplastic , Benign , Malignant

* WHO provide international classification that has been universally accepted

Histological classification of ovarian Tumour

Epithelial Tumour
* Serous Tumour
* Mucinous Tumour
* Endometrial Tumour
* Clear Tumour
* Mixed Tumour
* Undifferentiated and Unclassified
Tumour

Sex-Cord Stromal tumours

* Granulosa –stromal cell tumours

* Sertoli – stromal cell tumours
* Gynandroblastoma
* Sex – cord tumour with annular tubules
* Unclassified sex-cord tumoursSteroid cell
tumours
Ovarian germ-cell tumours

* Dysgerminoma
* Teratoma (immature, mature and
monodermal)
* Yolk sac tumour (endodermal sinus
tumour)
* Embryonal carcinoma
* Polyembryoma
* Choriocarcinoma
* Mixed germ-cell tumour

Epithelial Tumour – Arise from surface epithelium of ovary account from 60-65 % of ovarian
tumour and approximately 90% are malignant.

Benign , border line , malignant

Sex cord stromal tumour

- Derived from sex cord & Stroma of ovary

- Account approximately 8% of all ovarian tumour

Germ Cell Tumour

- Arise from germ cells

- Account from 30% of ovarian tumour in the form of mature cyst tertoma (Dermoid Cysts) and
1 – 3 % of ovarian malignancy and represent 60% of ovarian cancer in children and adolescents.

Epithelial ovarian tumour

*common bilateral
*Serous – most common 40 – 50%.
*Mucinous 10% large size associated with pseudomyxoma ovari

* Endometrial ovarian cancer: account for 20% of epithelial tumour. 10% associated with
endometrial cancer.
* Brenner tumour – very small proportion- 99% Benign
* Clear Cell cancer – Account from 5 –10 Worse prognosis
* Mixed epethilium ovarian tumour Borderline ovarian tumour:
* Account approximately 15% of epithelial
ovarian cancer.
* They are low malignant potential.
* Affecting young women and may present
in pregnancy
* Microscopically they show malignant
features but no stromal invasion.
* They have good prognosis.
* They are composed of granuloza, theca
and serotoli cells.
* Granuloza cell tumour produce
oestrogen and serotoli-stromal produce
androgen.
* Most of them are benign and most
clinically malignant are granuloza cell T.
* Meig syndrome - fibroma + ascites and right hydrothorax

Germ Cell Tumour:

* Account approximately 30% of ovarian tumour.
* Commonest in the first two decade of life. 75% present in stage I disease 10-15% Bilateral 5-
10% occur in female with abnormal gonads.

Teratomas:

drived from 2 -3 embroyonic layers

Mature (Dermoid Cysts)

– Commonest ovarian tumour

- Benign
- Unilateral (10-15% Bilateral)
- Leading to torsion.
- Contain teeth and hair in the cyst.
- Malignant transformation 2%

Immature Teratoma:
* 2nd commonest germ cell malignancy.
* Account for 20% ovarian cancer in female under 20 years of age.
* Unilateral
* classified according to differentiation and quantity of immature tissue.

Embryonic Markers:
* Yolk sac tumour AFP - (rare tumor)
* Ovarian choriocarcinoma secret BHCG (rare tumour)
* Normal level does not exclude diagnosis.
* Teratoma & dysgemenoma does not secret this tumor marker.

Secondary ovarian malignancy:

* Account up to 10%.
* Metastases form Colon
Stomach
Breast
Female genital tract

Krukenberg Tumour: Bilateral enlarged ovaries

* Ovarian metastatic tumour from gastric or colon cancer.

* Microscopic assessment – signet ring cells.
* CEA marker increase

Eitology:
* Environmental Factors:
- Unknown
- High fat diet
- Perineal dusting with talcum powder
- Risk of caffeine intake and radiation
unclear.
- Role of certain viral infection (Mumps,
rubella, influenza) inconclusive results.

Reproductive and Hormonal factors:

* Contraceptive pill
* Pregnancy
* Breast feeding
* Tubal ligation and Hysterectomy
- early menarche
- late menopause
- nulliparity

This suggest continous ovulation is

important factor.
* Using of ovulatory stimulants and subsequent development of epithelial ovarian cancer is
currently lacking.
* Heriditary factors not more than 10% of all ovarian cancer.
* BRCAI responsible for 5% of ovarian cancer in young women < 40 years.

Screening of ovarian cancer:

* No role of ovarian screening in
asymptomatic population.
* Women at risk of developing ovarian
cancer based on family history 10%
offered screening.
* Women risk vague pelvic abdominal
symptoms warrant complete history and
examination including vaginal and rectal
examination.

Risk of Malignancy index (RMI)

Serum Ca 125
USS Score (0-3) calculated by:
multilocular cysts
Solid area
Bilateral lesion
Metastasis
Ascites

Menopausal status 1 for premenopausal

3 for post menopausal

This RMI to identify cases for referral to Gynaecology Oncologist

Symptoms:
* Early stage – Pressure symptom
* Late stage – metastatic effect to bowel
mesentery and ascites.
- Vaginal bleeding less
common.

Clinical Signs:

* Supraclavicular, axillary, inguinal lymph

nodes.
* Breast examination
* Chest examination – pleural effusion
* Abdominal examination – liver size
* Pelvic & rectal examination – Irregular
solid mass suggestive of malignancy.

INVESTIGATIONS
- Full blood count
- Urea and electrolyte
- Liver function test
- Tumor marker
- Ca 125
AFP & B-HCG
- CEA
- U/S for pelvis, kidney and liver
- MIR
- CT Scan
- Endometrial biopsy
- Endoscopy
Staging of primary ovarian cancer:

Stage Description 5 –year survival (%)

I Confined to one/both ovaries

Ia Limited to a single ovary, no ascites; 89.9
capsule intact with no surface tumour
Ib Limited to both ovaries, no ascites; 84.7
capsule intact with no surface tumour
Ic One or both ovaries have ruptured 80
 capsule or surface tumour, malignant
ascites or positive peritoneal washings
II Extension to pelvic structures
IIa Extension to uterus or fallopian tubes 69.9
IIb Extension to other pelvic tissues 63.7
IIc As for IIA or IIB but one or both ovaries 66.5
have ruptured capsule or surface tumour;
malignant ascites or positive
peritoneal washings

III As for stage I/II but also with peritoneal

Implants outside pelvis or with positive
retroperitoneal lymph nodes
IIIa Histologically confirmed microscopic 58.5
seeding of abdominal peritoneal surfaces
and negative retroperitoneal lymph nodes
IIIb Histologically confirmed implants of 39.9
abdominal peritoneal surfaces <2cm
and negative retroperitoneal lymph nodes
IIIc Histologically confirmed implants of 28.7
abdominal peritoneal surfaces <2 cm or
positive retroperitoneal lymph nodes
IV Distant metastases (including liver
parenchyma/positive pleural fluid cytology) 16.8

Metastatic ovarian spread:

* Direct – tubes uterus - bladder

* Trascoelmic along peritoneal surface.
* Lymphatic spread – pelvic and para aortic lymph nodes.
* Haematogenous spread - liver
- lung

Technique for Surgical Staging:

* Midline incision – adequate access for surgical staging and full inspections.

1. Sending ascites or peritoneal washing

2. Performing total hystrectomy and bilateral salpingo –ophorectomy.
3. Omentectomy
4. Peritoneal biopsy all suspicious area.
5. Diaphragmatic biopsy or scraping.
6. Sampling of pelvic and a paraaortic lymph nodes.

Surgical Management of Ovarian Cancer:

* Primary surgery in early epithelial ovarian cancer. In young patient – fertility is important:
* Laparotomy is gold, standard for diagnosis and staging
* Frozen section is useful.
* Delaying procedure until histopathology is available regarding further surgical management to
be made in consultation with patient and cancer team. Primary surgery in advanced epithelium
ovarian cancer.
* Primary cytoreductive surgery followed by chemotherapy is current gold standard.
* Cytoreductive surgery – remove all primary cancer and if possible metastatic disease to tumor
load to achieve optimal status.

Chemotherapy:
* Additional therapy in early stage disease with high risk factor.
* Standard adjuvant depending involve IV chemotherapy single agent active in epithelial
ovarian cancer.

Include: Alkalizing agent (cyclophosophomide)

- platinuim compound (cisplatin)
- taxanes (paclitaxel)
- paclitaxel and platinum became new standard of care in advanced ovarian cancer.
- pallative surgery – bowel obstruction involve

– bowel resection and intestinal bypass.

Germ cell tumour:

* Adequate surgical staging.
* Cytoreduction and adjuvant chemotherapy is the standard therapy.
* Usually occur in young patient so conservative of contralateral ovary and uterus is appropriate.
* In dysgeminoma and Immature tertoma stage I ovarian cancer further therapy.

From all after patient 2-3 cycles of combination therapy.

* Tumor marker useful in monitoring
disease and planning management.
Surgery is the gold standard but early stage can be managed by unilateral oophorectomy and
endometrial biopsy when fertility is important.

Treatment of ovarian Cancer

The principle of Treatment

1. Surgical staging – Laparotomy to classify the growth to its extent of spread.

2. Surgical removal of as much malignant tissue as possible( surgical debulking; cyto- reductive
treatment), may involve partial resection of bladder and bowel.
3. Follow up with intensive chemotherapy using various combination of drugs Toxanes with
platinium are first choice of treatment.
4. Second look laparatomy or laparoscopy to determine effectiveness of chemotherapy only
performed for clinical trails.
- Cooperation with general surgeon and experience in field of chemotherapy and
radiotherapy.
- Treatment by radiotherapy only for pallation.
- CA 125 is usually raised in advanced ovarian cancer and used to assess response to
chemotherapy.

Chemotherapy:

- Act by inhibiting cell deviation

* Alkalyting agent preventing replication of DNA
- cyclophosphoamide
- Chloraambucil
*Antimitotic antibiotic – Prevent DNA protein synthesis – actinomycin D Antimetabolites:
Preventing the synthesis of nucleoprotein

Methotrexate:
Other Non Alkylating agent
* Cisplatin
 -Carboplatin
* Taxanes – Paclitaxel

Toxicity:
- Bone marrow depression
- gastrointestinal
- neurotoxic
- nephrotoxic
- alopecia
- candiatoxic
- liver failure
- regular check up for marrow and liver
function

Prognosis for epithelial ovarian cancer

Stage 5 years survival

I 60 – 70%
II 40 - 50%
III 5 - 10%
IV nil

Borderline epithelial Tumour - has excellent prognosis

- 5 years 90 – 95%
- 15 years survival 70-85%- For serous tumour ,5-10% for mucinous
- Chemotherapy is effective in the in frequent germ cell tumour