Ovarian tumour (benign and malignant)

Question 1

What are the different types of ovarian tumours?

Answer 1

Question 2

What is the most common type of ovarian cancer?

Answer 2

Epithelial ovarian cancer (~90% of cases) - develops when there is malignant transformation of the epithelium covering the ovarian capsule and distal fallopian tube

Question 3

When does ovarian cancer usually occur?

Answer 3

Peak age of incidence is 60 years

Question 4

Why does ovarian cancer generally carry a poor prognosis?

Answer 4

Due to late diagnosis.

Question 5

What subtype of ovarian epithelial cancer is most common?

Answer 5

Serous carcinomas

Question 6

Where is the origin of most ‘ovarian’ cancers?

Answer 6

Distal end of the fallopian tube

Question 7

What are the risk factors for ovarian cancer?

Answer 7

FH - mutations in BRCA1 and BRCA2

Many ovulations - early menarche, lane menopause, nulliparity

Question 8

Which medication reduces the risk of ovarian cancer?

Answer 8

COCP -as it reduces the number of ovulations. NB: IVF does not increase risk.

Question 9

What other factors decrease risk of ovarian cancer?

Answer 9

• Multiparity
• Tubal ligation
• Salpingectomy
• Hysterectomy

Question 10

What are the clinical features of ovarian cancer?

Answer 10

• abdominal distension and bloating
• abdominal and pelvic pain
• urinary symptoms e.g. Urgency
• early satiety and difficulty eating
• diarrhoea
• other: change in bowel habit, urinary symptoms, back ache, irregular bleeding, fatigue

Most are vague, non-specific symptoms which may cause them to present in late-stage disease. 66% present with stage 3 or later.

O/E: fixed, hard mass arising from pelvis. Ascites makes ovarian cancer likely. Check for lymphadenopathy in groin and neck.

Question 11

What tumour marker is commonly found in ovarian cancer? When should it be used? What level is significant?

Answer 11

CA125 - should NOT be used in asymptomatic women for screening.

Levels of _>_35 IU/mL mean an urgent scan of the abdomen and pelvis is required

Question 12

What are the non-malignant causes of a raised CA125?

Answer 12

• Endometriosis
• Menstruation
• Benign ovarian cysts

Question 13

What investigations should be done for ovarian cancer?

Answer 13

• CA125 - _>_35IU/mL significant and needs USS. Raised in 80% of epithelilal ovarian cancers.
• USS - characterises the mass in terms of size, consistency, presence of solid elements, bilaterality, ascites, extraovarian disease e.g. peritoneal thickening and omental deposits.
  
  • –> CT/MRI - used for staging and assessing operability
• Laparotomy - usually required for diagnosis
• Paracentesis/pleural aspiration - symptom relief/cytological assessment

Pre-operatively:

• ECG
• CXR
• FBC
• U&E
• LFTs

Question 14

How is the RMI calculated? What is its use?

Answer 14

The Risk of Malignancy Index (RMI) is calculated from:

• menopausal status,
• pelvic ultrasound features
• CA125

Used to triage pelvic masses into those at low, intermediate and high risk of malignancy.

Question 15

How is ovarian cancer staged?

Answer 15

FIGO staging system

• 20% present with stage 1
• 10% present with stage 2
• 50% present with stage 3
• 15% present with stage 4

Question 16

Answer 16

Question 17

Where does metastatic spread occur to in ovarian cancer?

Answer 17

Direct spread –> peritoneum, other organs

Lymphatic spread –> pelvic and para-aortic nodes

Question 18

What is the management of ovarian cancer?

Answer 18

Usually a combination of surgery and platinum-based chemotherapy(with paclitaxel)

Following surgery all patients are discussed at MDT to see whether chemotherapy is necessary.

NB: the surgery and sampling of sites is necessary for diagnosis, staging and treatment.

Question 19

What is a side-effect of paclitaxel containing chemotherapy used in ovarian cancer?

Answer 19

Action: Derived from the bark of the Pacific yew and works by causing microtubular damage to the cell. This prevents replication and cell division.

SE: peripheral neuropathy, neutropenia and myalgia are common and dose dependent. Paclitaxol causes total loss of all body hair, irrespective of dose.

Question 20

How can you monitor for ovarian cancer recurrence?

Answer 20

Measure CA125 - levels start to rise prior to onset of clinical evidence of disease recurrence but treating the rising CA125 alone does not improve survival.

Question 21

Question 22

What is the prognosis with ovarian cancers? What are the 4 most important prognostic factors in ovarian cancer?

Answer 22

Overall 5-year survival is 46%

Most important prognostic factors:

1. Age at presentation
2. Stage of disease
3. Histological type and grade
4. Volume of residual disease post-surgery

Question 23

What is a Krukenberg tumour?

Answer 23

Ovarian metastases associated with primary cancers of the colon, stomach and breast.

Question 24

How are epithelial tumours classified based on risk of malignancy?

Answer 24

• Benign
• Malignant
• Borderline - make up 10% and called borderline epithelial tumours (BOTs).

Question 25

What are the histological features of borderline epithelial tumours? Where do they spread?

Answer 25

* Well differentiated * Some features of malignancy (nuclear pleomorphism, cellular atypia) * Do not invade the basement membare * Most are **serous** tumours Spread to omentum and peritoneum but do not recur after initial surgery.

Question 26

What are the subtypes of epithelial ovarian cancers, from most to least common?

Answer 26

* High-grade serous carcinomas * Micinous and endometrioid tumours * Clear cell carcinomas

Question 27

What is a characteristic histological feature of high-grade serous tumours of the ovary?

Answer 27

'Psammoma bodies' - concentric rings of calcification

Question 28

Which epithalial ovarian tumour can cause pseudomyxoma peritoneii? Describe their appearance.

Answer 28

Mucinous carcinoma- they are large multiloculated tumours

Question 29

Describe the appearance of endometrioid ovarian carcinomas.

Answer 29

Similar in histological appearance to endometriosis Tend to be well differentiated and are associated with a better survival than high-grade serous carcinomas

Question 30

Which epithelial ovarian cancer other than endometrioid, can also arise from endometriosis?

Answer 30

Clear cell carcinoma - characterised by presence of clear cells

Question 31

What are fallopian tubal precursor lesions for high grade serous pelvic carcinomas called? What mutations do these have?

Answer 31

serous tubal intraepithelial carcinoma (STIC) **p53** and as many as 30% of high-grade pelvic serous cancers have **BRCA** mutations

Question 32

What mutations do endometriosis associated cancers usually contain?

Answer 32

Driver mutations in KRAS, PTEN, BRAF and ARID1A (rather than TP53)

Question 33

Why is 'incessant ovulation' hypothesised to increase risk of ovarian cancer?

Answer 33

The ‘incessant ovulation’ theory holds that the repeated damage to the ovarian surface epithelium that occurs at ovulation increases the risk of mutations that drive ovarian carcinogenesis. Excess gonadotrophin secretion is also thought to drive tumorigenesis through oestrogen-stimulated epithelial proliferation and subsequent malignant transformation

Question 34

Which genetic conditions increase risk of ovarian cancer? When do cancer usually occur in these conditions?

Answer 34

10-15% have a genetic predisposition which may include: * Breast ovarian cancer syndrome (BRCA) - BRCA1 and BRCA2 mutations. Account for 90% of hereditary cancers. * Lynch syndrome (HNPCC) - also associated with endometrial cancer and 10% lifetime risk of ovarian cancer. * Risk of ovarian cancer increases from background 1.4% to 5% in the presence of these mutations.* * Occurs **10 years before s**poradic cancers.*

Question 35

IS BRCA1 or BRCA2 more common in breast ovarian cancer syndrome? Which tends to cause cancer earlier?

Answer 35

BRCA1(80%) - mid 30s BRCA2 (15%) - mid 40s *These are tumour suppressor genes*

Question 36

Which type of ovarian cancer do hereditary conditions tend to be associated with?

Answer 36

Adenocarcinomas (with the exception of Lynch-associated tumours)

Question 37

What measures are taken to prevent ovarian cancer in BRCA mutation carriers?

Answer 37

1. Prophylactic BSO- once completed family. Reduces ovarian cancer risk by 90% and breast by 50%. 2. Chemoprevention - using COCP reduces ovarian cancer risk by up to 50% NB: TVUSS and CA125 measurement has not been shown to improve survival in those with FH of ovarian cancer.

Question 38

What is a primary peritoneal carcinoma?

Answer 38

High grade pelvic serous carcinoma - histologically indistinct from tumours arising from the Fallopian tube or ovary but there are differences based on findings at laparotomy: 1. Normal sized ovaries 2. More extraovarian disease than ovarian disease 3. Low volume peritoneal disease

Question 39

How do sex-cord stromal ovarian tumours present? What are the types?

Answer 39

Account for 10% of ovarian tumours, but 90% of functional ovarian tumours. Oestrogen producing types: * Granulosa - most common (70%) * Theca * Sertoli Androgen producing types: * Sertoli-Leydig * Steroid cell Complications: * Precocious puberty - juvenile granulosa cell tumours (\<10 years) * Abnormal menstrual bleeding * Androgen --\> virilisation, amenorrhoea, deep voice, hirsutism, HTN * Increased risk of endometrial cancer * Peak incidence around menopause

Question 40

How do ovarian germ cell tumours present?

Answer 40

Derived from primordial germ cells within ovary - contain any cell type. Pelvic mass or acutely with torsion (10%) or haemorrhage . Often in girls/young women. MRI useful for diagnosis. CXR should be done to exclude pulmonary metastases. 1. **Dysgerminomas** (50%) - may secrete hCG 2. **Endodermal sinus yok sac tumours** (15%) - may secrete AFP, spread to lungs 3. **Immature teratomas** (15-20% of all malignant germ cell tumours and 1% of all teratomas) - mature or immature based on presence of neural tissue, may secrete AFP (33%), can undergo mailgnant transformation to epithelial carcinoma (SCC). 4. **Non-gestational choriocarcinoma** - young girls with irregular bleeding and very high hCG