QuestionSBA
QuestionChoice
Signet ring cells seen within the ovary are most commonly metastasis from gastrointestinal cancer.
49938
b
Endometrial cancer
QuestionChoice
Signet ring cells seen within the ovary are most commonly metastasis from gastrointestinal cancer.
49941
e
Osteosarcoma
QuestionChoice
Signet ring cells seen within the ovary are most commonly metastasis from gastrointestinal cancer.
49940
d
Lymphoma
QuestionChoice
Krukenberg tumours of the ovary refer to a tumour containing "signet ring" cells. This is typically a gastrointestinal carcinoma, which has metastasised to the ovary.
49937
a
Gastrointestinal cancers
QuestionChoice
Signet ring cells seen within the ovary are most commonly metastasis from gastrointestinal cancer, however can also occur from breast cancers.
49939
c
Breast cancer
Concept
Chapter
# Summary
  
 
Ovarian cancer is a major cause of gynaecological cancer-related mortality in the UK, due primarily to the non-specific nature of symptoms in early stages. The most common type is epithelial ovarian tumours, though germ cell tumours and sex cord stromal tumours also occur. Risk factors include older age, smoking, numerous ovulations, obesity, HRT, and BRCA genes. Parity, breastfeeding, early menopause, and COCP use can be protective. Symptoms typically include abdominal discomfort, bloating, early satiety, and urinary changes, with ascites signifying advanced disease. Differentials include IBS, fibroids, ovarian cysts, and other cancers. Initial investigations include CA-125 and pelvic and abdominal ultrasound. Management depends on disease stage and patient fitness, but can include surgery and chemotherapy.
  
 
# Definition
  
 
Ovarian cancer is a malignancy originating from various cell types found within the ovary. 
  
 
# Aetiology
  
 
The causes of ovarian cancer can be divided into risk factors and protective factors. 
  
 
Risk factors include:
  
 
  - Advanced age
  - Smoking
  - Increased number of ovulations (early menarche, late menopause)
  - Obesity
  - Hormone replacement therapy (HRT)
  - Genetic predisposition (BRCA 1 and 2 genes)

Protective factors include:

  - Childbearing (parity)
  - Breastfeeding
  - Early menopause
  - Use of combined oral contraceptive pill (COCP)


# Classification
  
 
The types of ovarian cancers can be classified according to the cell type from which the cancer originates. The types include:
  
 
**Epithelial ovarian tumours**
  
 
  - Originate from the epithelium which lines the fimbria of the fallopian tubes or the ovaries
  - Epithelial tumours are partially cystic, and the cysts can contain fluid. 
  - The initial metastatic spread typically involves the peritoneal cavity, with seeding particularly affecting the bladder, paracolic gutters and the diaphragm. 
  - Around 90% of ovarian cancers are epithelial ovarian tumours.
  
 
**Germ cell tumours features**
  
 
  - Originate from the germ cells in the embryonic gonad. 
  - These tumours typically grow rapidly and spread predominantly via the lymphatic route
  - Germ cell tumours most commonly arise in young women, which is atypical for most cases of ovarian cancer. 
  - Tumour markers include alpha-fetoprotein and sometimes beta human chorionic gonadotrophin (B-HCG).
  
 
**Sex cord stromal tumours**
  
 
  - Originate from connective tissue. 
  - They are rare, making up less than 5% of all ovarian tumours. They are malignant tumours, but are much less aggressive than epithelial tumours. 
  - Additionally, ovarian cancer can be secondary to another cancer elsewhere, which has metastasised to the ovary. A Krukenberg tumour refers to a "signet ring" sub-type of stromal tumour, typically gastrointestinal in origin, which has metastasised to the ovary. 
  
  
 
# Signs and Symptoms
  
 
The clinical features of ovarian cancer typically present late in the disease progression and include:
  
 
  - Abdominal discomfort
  - Bloating
  - Early satiety
  - Urinary frequency or change in bowel habits
  
 
In later stages, the disease may cause:
  
 
  - Ascites (due to vascular growth factors increasing vessel permeability)
  - Pelvic, back and abdominal pain
  - Palpable abdominal or pelvic mass
  
 
# Differential diagnosis
  
 
Differential diagnoses for ovarian cancer include:
  
 
- Gastrointestinal conditions (e.g., irritable bowel syndrome): characterised by abdominal pain, bloating, and changes in bowel habits. 
2. Fibroids: may cause heavy menstrual bleeding, pelvic pressure or pain, frequent urination, and constipation. 
3. Ovarian cysts: can cause pelvic pain, fullness or heaviness in the abdomen, and bloating.
4. Other cancers (e.g., bladder, endometrial): may present with symptoms such as abnormal bleeding, pelvic pain, and urinary symptoms.
  
 
# Investigations
  
 
Investigations for suspected ovarian cancer include:
  
**Bedside:**
  
  * Abdominal examination: tenderness, abdominal mass
  * Bimanual examination: adnexal mass

  
**Bloods:**
  
* CA-125 levels
       * Measure CA125 in women (especially those aged over 50) with frequent or persistent symptoms of ovarian cancer (i.e. 12 or more times per month)
       * Consider this measurement in women with non-specific symptoms of malignancy, such as unexplained weight loss, fatigue or changes in bowel habit 
* AFP and beta-hCG levels (for younger women who may have germ cell cancers)

  
**Imaging:**

* Pelvic and abdominal ultrasound scan
       * May be helpful to rule out or identify malignancy where CA125 is 35 IU/ml or higher  
* CT chest/abdomen/pelvis (for staging)

**Invasive:**
  
Further investigations may include:
 
* Tissue biopsy 
  
 
**Risk of Malignancy Index** 

These results can be used to calculate the Risk of Malignancy Index (RMI), which stratifies the likelihood of cancer: 
   

**RMI = U x M x CA125**


* U = ultrasound result (between 0-3)
* M = menopausal status (1 = premenopausal, 3 = postmenopausal) 
* Serum CA-125 is measured in IU/ml

- NICE advise referring all women with an RMI I score of 250 or greater to a specialist multidisciplinary team


**2 Week Wait (2WW) Referral Criteria:**

* Physical examination showing ascites and/or a pelvic abdominal mass (that is not due to uterine fibroids) 
* Ultrasound findings suggestive of ovarian malignancy



# Staging
  
 
Stage I (limited to the ovaries):
 
  - Stage IA: limited to one ovary, the capsule is intact
  - Stage IB: limited to both ovaries, capsules intact.
  - Stage IC: tumour limited to one or both ovaries with any of the following: capsule ruptured, tumour on ovarian surface, malignant cells in ascites or peritoneal washings.
  
 
Stage II (involving one or both ovaries with pelvic extension and/or implants):
 
  - Stage IIA: extension and/or implants on the uterus and/or Fallopian tubes. No malignant cells in ascites or peritoneal washings
  - Stage IIB: extension to and/or implants on other pelvic tissues. No malignant cells in ascites or peritoneal washings
  - Stage IIC: pelvic extension and/or implants (Stage IIA or Stage IIB) with malignant cells in ascites or peritoneal washings.
  
 
Stage III (involving one or both ovaries with microscopically confirmed peritoneal implants outside the pelvis):
  
  - Stage IIIA: microscopic peritoneal metastasis beyond pelvis (no macroscopic tumour)
  - Stage IIIB: macroscopic peritoneal metastasis beyond pelvis <2 cm
  - Stage IIIC: peritoneal metastasis beyond pelvis >2 cm and/or regional lymph node metastasis.
  
 
Stage IV: tumour involving one or both ovaries with distant metastasis.
  
 

# Management
  
 
Management depends on the stage of the cancer and the patient's fitness for treatment.

Surgery: 

* If early disease surgery can include removal of the uterus, ovaries, fallopian tubes and omentectomy
* In advanced disease further debulking surgery can be performed.

 
Chemotherapy:

* Adjuvant chemotherapy in combination with surgery
* Intraperitoneal chemotherapy may be performed at the time of operation

Biological therapies are being trialled 
  
 
# Complications

* Bowel obstruction/constipation
* Ascites
* Chemotherapy complications: alopecia, intraperitoneal toxicity, neutropenia, peripheral neuropathy
* Immunotherapy complications: bowel perforation or fistula, hypertension, poor wound healing 
* Surgical complications: thromboembolism, infection, haemorrhage, death
* Death

# Prognosis  

5-year survival:

* 75% for women younger than 50
* > 35% for women over 65
* > 90% for women with localised disease on diagnosis
* 30% for women with distant disease on diagnosis 

# NICE Guidelines
  
 
  [Click here to read NICE CKS on Ovarian cancer](https://cks.nice.org.uk/topics/ovarian-cancer/)
  
  
# References 

[Patient Info](https://patient.info/doctor/ovarian-cancer-pro)
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Ovarian cancer
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Gynaecology
Video
Concept
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Ovarian cancer
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Genetic syndromes and Cancer
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A 53-year-old woman presents to accident and emergency with acute onset right iliac fossa pain. She is taken for an emergency laparoscopy which reveals acute ovarian torsion and a right ovarian mass. She undergoes a right oophorectomy and makes a good recovery postoperatively. Pathology of the ovary reveals a mass containing an invasive proliferation of mucin-producing signet-ring cells.

Which of the following cancers should now be screened for?
a