Ovarian tumors are abnormal growths on the ovaries, the female reproductive organs that produce eggs. Ovarian tumors can be noncancerous (benign) or cancerous (malignant). Many things can make you more likely to develop an ovarian tumor.
4. BENIGN OVARIAN TUMORS
Most benign ovarian tumors will be diagnosed following investigation
of women complaining of acute pelvic pain or chronic pelvic pain (CPP),
or noticing the presence of an abdominal mass.
They may also be found incidentally during a gynaecological
examination or pelvic ultrasound scan (USS).
The presentation with the different types of benign ovarian tumors
varies with age.
6. FUNCTIONAL OVARIAN CYSTS
This group of ovarian cysts includes:
follicular
corpus luteal
theca luteal cysts
The risk of developing functional cysts is reduced by the use of the
combined oral contraceptive pill (COCP). diagnosis is made when
the cyst measures more than 3 cm
They appear as simple unilocular cysts on ultrasound
Theca luteal cysts are associated with pregnancy, particularly
multiple pregnancy, and are often diagnosed incidentally at
routine ultrasound. They are often bilateral. Most resolve
spontaneously during pregnancy
Corpus luteal cysts occur following ovulation and may present
with pain due to rupture or haemorrhage, typically late in the
menstrual cycle.
7. MANAGEMENT
Management depends on symptoms:
If asymptomatic, the patient can be reassured and a repeat USS
performed to check resolution or non-enlargement and thereafter
the patient can be discharge.
If symptomatic, she can be booked for laparoscopic cystectomy if
necessary.
Treatment for corpus luteal cyst is expectant, with analgesia.
Occasionally, surgery may be necessary if there has been significant
bleeding to wash out the pelvis and perform an ovarian cystectomy.
8. INFLAMMATORY OVARIAN CYSTS
Inflammatory ovarian cysts are usually associated with pelvic
inflammatory disease (PID)
They are most common in young women.
The inflammatory mass may involve the tube, ovary and bowel and
can be described on imaging as a mass or an abscess.
Occasionally, the tubo ovarian mass can develop from other infective
causes, for example appendicitis or diverticular disease.
Diagnosis is similar to that for PID: inflammatory markers are helpful.
TREATMENT:
Antibiotics
Surgical drainage or excision.
Definitive surgery is usually deferred until after the acute infection has
resolved, due to the risks of perioperative systemic infection and
bleeding from handling acutely inflamed and infected tissue.
9. ENDOMETRIOMA
When endometrial tissue is implanted into the ovary an
endometrioma forms.
This cyst may be large and contains old, altered blood
that has a thick brown appearance, and for this reason is
frequently referred to as a ‘chocolate cyst’
Endometriotic tissue responds to cyclical hormonal
changes and therefore undergoes cyclical bleeding and
local inflammatory reactions.
These regularly repeated episodes of bleeding and
healing lead to fibrosis and adhesion formation between
pelvic organs, causing pain and infertility.
In extreme cases a ‘frozen pelvis’ results, where extensive
adhesions tether the pelvic organs and obliterate normal
pelvic anatomy
TVUSS can detect endometriosis involving the ovaries
(endometriomas or chocolate cysts)
10. GERM CELL TUMORS
These are the most common ovarian tumors in young women aged 20–40 years,
The most common form of benign germ cell tumor is the mature dermoid cyst
(cystic teratoma), which contains fully differentiated tissue types derived from all
three embryonic germ cell layers (mesenchymal, epithelial and stroma).
Hair, teeth, fat, skin, muscle, cartilage, bone and endocrine tissue are frequently
present.
Up to 10% of dermoid cysts are bilateral.
The risk of malignant transformation is rare (<2%), usually occurring in women over
40 years.
Diagnosis is usually confirmed with a pelvic USS and because of the high fat
content present in dermoid cysts, MRI may also be useful where there is
uncertainty.
In general, ovarian cystectomy is indicated because spontaneous resolution is
unlikely.
Surgery is especially indicated if the dermoid cyst is symptomatic and is more than
5 cm in diameter or is enlarging.
Cystectomy will prevent ovarian torsion and provide tissue for histological analysis.
11. EPITHELIAL TUMORS
Benign epithelial tumors increase in frequency with age and are most
common in perimenopausal women.
The most common epithelial tumors are serous cystadenomas,
accounting for 20–30% of benign tumors in women under 40.
Serous cystadenomas are typically unilocular and unilateral
Mucinous cystadenomas are large multiloculated cysts that are
bilateral in 10% of cases.
Brenner tumors are small tumors often found incidentally within the
ovary. They contain urothelial like epithelium and may rarely secrete
estrogen.
12.
13. SEX CORD STROMAL TUMORS
Ovarian fibromas are the most common sex cord
stromal tumors.
They are solid ovarian tumors composed of stromal
cells.
They present in older women, often with torsion due to
the heaviness of the ovary.
Occasionally, patients may present with Meig syndrome
(pleural effusion, ascites and ovarian fibroma).
Following removal of the ovarian fibroma, the pleural
effusion will usually resolve.
Thecomas are benign estrogen-secreting tumors. They
often present after the menopause with manifestations
of excess estrogen production, usually postmenopausal
bleeding.
Although benign, they may induce an endometrial
carcinoma.
14. DIAGNOSIS OF BENIGN OVARIAN TUMORS
History
Details of presenting symptoms
Symptoms may include:
Pelvic discomfort or pressure on the bowel or bladder.
Acute pain may represent torsion of a cyst, rupture or haemorrhage into it.
Full gynecological history
Examination:
General physical examination (hypovolemia, lymphadenopathy, ankle edema)
Abdominal examination
Bimanual examination
Abdominal and bimanual pelvic examination may elicit a pelvic/abdominal mass
that may be tender and will be separate from the uterus.
15. INVESTIGATIONS
The first-line investigation for women with a suspected pelvic mass or pelvic pain
is an USS.
A TVUSS has better resolution for pelvic masses.
A transabdominal ultrasound scan (TAUSS) is indicated in women who have
never been sexually active, or in combinations with a TVUSS where large ovarian
masses extending beyond the pelvis and into the abdomen are present.
The use of color flow doppler may increase the reliability if ultrasound.
Computed tomography (CT) scanning or magnetic resonance imaging (MRI) can
further characterize the nature of ovarian cysts, especially where they are thought
to be potentially malignant.
Serological tumor markers should also be taken to help determine the type of
ovarian cyst and differentiate between a benign and malignant neoplasm
A pregnancy test should be performed to exclude pregnancy.
Inflammatory markers, such as C-reactive protein (CRP) and white cell count
(WCC), are important if the differential diagnosis includes appendicitis or a tubo-
ovarian abscess.
16. Tumor markers used in the investigation and follow-up of ovarian cysts:
18. OVARIAN TORSION
Torsion of an ovary refers to a situation
where there is rotation of the vascular
pedicle supplying the ovary, which
compresses and cuts its blood supply.
Torsion is more likely with enlargement of
the ovary as is seen in the presence of an
ovarian cyst.
Up to 15% of dermoid cysts present acutely
with torsion.
19. Presenting symptoms:
Acute onset of lower abdominal pain associated with nausea and vomiting.
Investigation:
Pelvic USS with Doppler measurement of blood flow may be useful in the diagnosis,
to
confirm the presence of a cyst and comment on blood flow to the ovary.
Torsion of a normal ovary is very unlikely.
Management:
Emergency surgical treatment to untwist the ovary and its attached pedicle is
required to restore blood flow, and the ovarian cyst should then be removed.
However, if this complication is not recognized within a few hours of presentation,
infarction and gangrene may result, necessitating removal of the necrotic ovary.
Decision making to operate should be based on clinical findings, with transvaginal
ultrasound scan (TVUSS) support.
20. MALIGNANT OVARIAN TUMORS
Primary ovarian cancers are:
Epithelial (80%)
Sex cord stromal or germ cell.
The ovary is also a common site for metastatic spread;
Krukenberg tumors are ovarian metastases associated with
primary cancers of the colon, stomach and breast.
22. EPITHELIAL TUMORS
Epithelial tumors of the ovary can be benign, malignant or borderline.
Approximately 10% of epithelial tumours are classified as borderline ovarian tumors
(BOTs).
These tumors are well differentiated, with some features of malignancy (nuclear
pleomorphism, cellular atypia) but do not invade the basement membrane.
BOTs spread to other abdominopelvic structures (peritoneum, omentum) but do not
often recur following initial surgery.
The majority of BOTs are serous tumors.
Mucinous BOTs may actually arise from appendiceal carcinomas of low malignant
potential
High-grade serous carcinomas account for around 75% of all epithelial ovarian
cancers; mucinous and endometrioid tumors are less common, accounting for 10%,
followed by clear cell carcinomas.
High grade serous tumors are characterized histologically by concentric rings of
calcification, known as ‘psammoma bodies’.
Mucinous carcinomas are generally large multiloculated tumors associated with
pseudomyxoma peritoneii.
Endometrioid carcinomas are similar in histological appearance to endometrial
cancer, are associated with endometriosis in approximately 10% of cases and also a
synchronous separate endometrial cancer in 10–15%.
23. ETIOLOGY
HIGH GRADE PELVIC SEROUS CARCINOMAS:
High-grade pelvic serous carcinoma has been coined to
incorporate all high-grade serous tumours arising from
the ovary, Fallopian tube and/or peritoneum.
Data from women with BRCA mutations who have
undergone risk-reducing prophylactic bilateral salpingo-
oophorectomy (BSO) suggest a Fallopian tubal precursor
lesion for high-grade pelvic serous tumours.
These precursors are called serous tubal intraepithelial
carcinoma (STIC) lesions, and they are characterized by
mutations in p53 in secretory cells of the distal Fallopian
tube.
As many as 30% of high-grade pelvic serous cancers have
BRCA mutations, which has implications for the majority of
women who present with apparently sporadic disease.
Endometrioid, mucinous, clear cell,
borderline and low-grade serous
ovarian carcinomas:
• Inclusion cysts of the ovarian surface
epithelium and endometriosis give
rise to neoplasms that are distinctly
ovarian in origin, and can include
mucinous, endometrioid, clear cell,
borderline and low-grade serous
carcinomas.
• Endometriosis-associated ovarian
cancers are usually of endometrioid or
clear cell histological subtype.
• The origin of these tumors involves
driver mutations in KRAS, PTEN, BRAF
and ARID1A rather than TP53.
25. GENETIC FACTORS IN OVARIAN CANCERS
It is estimated that at least 10–15% of women with epithelial ovarian
cancer have a hereditary predisposition.
Women with mutations in BRCA1, BRCA2 and Lynch syndrome have an
increased lifetime risk of epithelial ovarian cancer.
Hereditary cancers usually occur around 10 years before sporadic
cancers and are associated with other cancers (particularly of the breast,
colon and rectum).
The most common hereditary cancer is the breast ovarian cancer
syndrome (BRCA), accounting for 90% of the hereditary cancers.
This syndrome is due to a mutation of tumor suppressor genes BRCA1
(80%) and BRCA2 (15%).
Lynch syndrome is hereditary non-polyposis colorectal cancer (HNPCC)
and is associated with endometrial cancer and a 10% lifetime risk of
ovarian cancer.
Hereditary ovarian cancers tend to be adenocarcinomas, present in later
stages with the exception of Lynch-associated tumors, and recent
evidence supports improved survival, probably due to a better response
26. CLINICAL FEATURES
Most women with ovarian cancer have symptoms; however, these
symptoms are non-specific and often vague.
The difficulty with clinical diagnosis is the main reason that patients
with ovarian cancer present with late stage disease (66% present with
stage 3 disease or greater), and this has a dramatic effect on survival.
The most common symptoms are:
Increased abdominal girth/bloating.
Persistent pelvic and abdominal pain.
Difficulty eating and feeling full quickly.
Other symptoms such as change in bowel habit, urinary symptoms,
back ache, irregular bleeding and
fatigue occur frequently and any women with persistence of these
27. EXAMINATION
Pelvic and abdominal examination may reveal a fixed, hard mass arising
from the pelvis.
The differential diagnosis of a pelvic mass includes:
Non-epithelial ovarian cancer,
Tubo-ovarian abscess,
Endometriomas
Fibroids.
In combination with the presence of ascites, a diagnosis of ovarian cancer is
highly likely.
Early-stage ovarian cancer is difficult to diagnose due to the position of the
ovary, but an adenexal mass may be palpable in a slim woman.
It should be noted that less than 20% of adenexal masses in premenopausal
women are found to be malignant; in postmenopausal women this increases
to around 50%.
Chest examination is important to assess for pleural fluid
28. INVESTIGATIONS
TVUSS is the initial imaging modality of choice
The investigation of any pelvic mass includes the measurement of tumor markers.
CA125 is a non-specific tumor marker that is elevated in over 80% of epithelial ovarian
cancers.
The Risk of Malignancy Index (RMI) is calculated from menopausal status, pelvic
ultrasound features and CA125 level to triage pelvic masses into those at low,
intermediate and high risk of malignancy.
CT and/or MRI scans.
Other investigations required for preoperative work-up include:
chest X-ray,
electrocardiography (ECG)
full blood count
urea and electrolytes
liver function tests.
If the patient presents with gross ascites or pleural effusion, paracentesis or pleural
aspiration may be
required for symptom relief and/or diagnosis
If the diagnosis is uncertain or if primary chemotherapy is being considered (for
advanced disease, or in patients not fit to undergo surgery), a biopsy is needed before
31. MANAGEMENT
Chemotherapy
• Chemotherapy can be given as primary
treatment, as an adjunct following surgery
or for relapse of disease.
• First-line treatment is usually a combination
of a platinum compound with paclitaxel.
• Most regimes are given on an outpatient
basis, 3 weeks apart for six cycles.
• Carboplatin is now the main platinum
compound used as it is less renal toxic and
causes less nausea than cisplatin, but is
equally as effective.
• Following completion of chemotherapy,
patients have a further CT scan to assess
response to treatment.
33. SEX CORD STROMAL TUMORS
They are tumors of low malignant potential
Good long-term prognosis
Some morbidity may arise from the estrogen (granulosa, theca or Sertoli
cell) or androgen production (Sertoli–Leydig or steroid cell) characteristic
of these tumors
Peak incidence is around the age of the menopause
Juvenile granulosa cell tumor usually presents in girls under 10 years of
age, causing precocious puberty.
Granulosa cell tumors are the most common subtype, accounting for over
70% of sex cord stromal tumors.
34. CLINICAL FEATURES
Irregular menstrual bleeding
Postmenopausal bleeding
Precocious puberty in young girls
Unilateral ovarian masses, measuring up to 15 cm in diameter.
Granulosa cell tumors may present as:
A large pelvic mass or with pain due to torsion/haemorrhage.
Sertoli–Leydig cell tumors produce androgens in over 50% of cases.
Patients present with a pelvic mass and signs of virilization.
Common symptoms are:
Amenorrhoea
Deep voice
Hirsutism.
Occasionally, this group of tumors produce estrogen and rarely renin, causing
hypertension.
35. TREATMENT
Treatment is based on the patient’s age and wish to preserve fertility.
If the patient is young:
Unilateral salpingo-oophorectomy
Endometrial sampling
Staging.
In the older group,
full surgical staging is recommended.
Granulosa cell tumors can recur many years after initial presentation
and long term follow-up is required.
Recurrence is usually well defined and surgery is the mainstay of
treatment as there is no effective chemotherapy regime.
36. GERM CELL TUMORS
Malignant germ cell tumors occur mainly in young women
They are derived from primordial germ cells within the ovary and because of this
may contain any cell type.
Dysgerminomas:
50% of all germ cell tumors.
They are bilateral in 20% of cases and occasionally secrete human chorionic
gonadotrophin (hCG).
Endodermal sinus yolk sac tumors:
Second most common germ cell tumors, accounting for 15% of the total.
They are rarely bilateral and secrete α-fetoprotein (AFP).
Spread of endodermal sinus tumours is a late event and is usually to the lungs.
37. Immature teratomas:
15–20% of malignant germ cell tumours and about 1% of all teratomas.
They are classified as mature or immature depending on the grading of neural
tissue present.
About one-third of teratomas secrete AFP.
Occasionally, there can be malignant transformation of a cell type within a
mature teratoma.
The most common cell type to transform is the epithelium, usually squamous
cell carcinoma.
Non-gestational choriocarcinomas:
Very rare,
usually presenting in young girls with irregular bleeding and very high levels of
hCG.
38. CLINICAL FEATURES
The most common presenting symptom is a pelvic mass; 10% present
acutely with torsion or haemorrhage and due to the age incidence,
some present during pregnancy.
Tumour markers are measured preoperatively as this may influence the
need for postoperative chemotherapy.
MRI is helpful to assess morphology, particularly within teratomas.
CT scaning of the abdomen allows assessment of the liver and lymph
nodes.
All patients should have a chest X-ray to exclude pulmonary
metastases.
39. TREATMENT
Surgery is tailored to suit the patient.
As most women presenting with malignant germ cell tumors are of reproductive
age, fertility-sparing treatment may be preferred.
An exploratory laparotomy is performed to remove the tumor and assess
contralateral spread to the other ovary (20% in dysgerminoma).
If there is a cyst present on the other ovary, this should be removed.
Careful inspection of the abdominal cavity is required with peritoneal biopsies and
sampling of any enlarged pelvic or para-aortic nodes performed.
If metastatic disease is found, it should be debulked at surgery.
Intraoperative frozen sections may be required to assess nodal status.
40. Postoperative chemotherapy depends on stage of disease.
Stage 1 dysgerminomas and low-grade teratomas are treated by surgery alone and
the 5-year survival is in excess of 90%.
For the remainder of tumors and for patients with disease outside the ovary,
chemotherapy is given.
The most common regime used is a combination of bleomycin, etoposide and
cisplatin (BEP), given as a course of three to four treatments, 3 weeks apart.
This regime gives long-term cure rates of over 90% and also preserves fertility if
required.
If the patient has recurrent disease, 90% will usually present in the first year
following diagnosis; salvage chemotherapy has very good success rates.