Germ cell tumours Flashcards
Classification of GCT
- GCT classification can be best understood by returning to the basics of early embryonic development. Oocytes are totipotent (i.e. can become any tissue within the embryo) and hence GCTs, even as an abnormal growth, develop along embryological cell lines:
Trophoblast (syncytiotrophoblast and cytotrophoblast)
Yolk sac (endodermal cells)
Embryo (epiblast)
GCT
- Undifferentiated (Dysgerminoma: 45 %)
- Differentiated
- Teratoma 20 % (mature/immature)
- Yolk sac tumor (yolk sac tumor 20 %)
- Whole blastocyst (embryonal carcinoma <5 %)
- Trophoblast (Choriocarcinoma < 1 %)
Match the germ cell tumour type to its originating cell line.
1 - Dysgerminoma
Yolk sac
Undifferentiated tumour
Trophoblast
Embryological derivation
2 - Choricarcinoma
Yolk sac
Undifferentiated tumour
Trophoblast
Embryological derivation
3 - Yolk sac tumour (also called endodermal sinus tumour)
Yolk sac
Undifferentiated tumour
Trophoblast
Embryological derivation
4 - Teratoma
Yolk sac
Undifferentiated tumour
Trophoblast
Embryological derivation
1 - The answer is undifferentiated tumour.
2 - The answer is trophoblast.
3 - The answer is yolk sac.
4 - The answer is embryological derivation.
Hormones produced by different tumours
Tumour α-FP hCG LDH
Dysgerminoma (-) ± ±
Immature teratoma ± – ±
Yolk sac tumour
(endodermal sinus tumour)+ – ±
Choriocarcinoma – + –
Key points of tumor marker
Women of childbearing age with an ovarian mass should have hCG, α-FP, LDH and CA125 measured.
Knowledge of tumour marker half-lives is important (hCG: 16-48 hours; α-FP: 5–7 days) when evaluating risk of residual disease following surgical removal of suspected stage IA disease.
diagnosis of GCT
Diagnosis
History: as above
Examination:
distended abdomen
pelvic mass
ascites.
Features of advanced disease:
pleural effusions
palpable lymph nodes
hepatomegaly.
Imaging:
doppler ultrasound and contrast-enhanced MRI of pelvis to look for adnexal masses and assess ease of operability
contrast-enhanced CT/MRI to evaluate abdomen/solid organs
contrast-enhanced CT chest
MRI brain with contrast should be done in any woman with disease spread above the diaphragm or if otherwise clinically indicated.
Blood tests:
Full blood profile
Biochemistry to include urea and electrolytes/liver function tests/bone
Tumour markers: α-FP, hCG, LDH and CA125.
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Presentation OF GCT
The clinical presentation of MOGCTs tends to be quite different and distinct from that of the more common epithelial ovarian cancer. Typical presenting symptoms of epithelial ovarian cancer usually relate to upper abdominal dissemination and include bloating, early satiety, loss of appetite, abdominal distension and vague chronic abdominal pain. On the other hand, ovarian GCTs often present more acutely and at an earlier stage. Typical presentations would be with a rapidly enlarging abdominal/pelvic mass, acute severe lower abdominal pain due to tumour rupture, haemorrhage or torsion. Ovarian GCTs may present with urinary symptoms, such as dysuria and urinary frequency or rectal symptoms or menstrual irregularities in post-menarche patients. Occasionally, patients may present with symptoms due to tumour related β-hCG production, such as a positive pregnancy test. Very rarely, women can present with isosexual precocious puberty (although this is more common in males) or with ectopic hyperthyroidism due to cross-reactivity of β-hCG (at extremely high concentrations) with the TSH receptor.
In contrast to epithelial cancers, where bilateral ovarian involvement is not unusual, unilaterality is typical for ovarian GCTs (CAVE:~10–20% of dysgerminomas are bilateral).
Prognostic factors for malignant germ cell tumours include tumour size (>10cm), histological type (endodermal sinus, choriocarcinoma) and grade (high grade for immature teratomas).
Answer whether the following symptoms relate to germ cell tumours, epithelial ovarian tumours, neither or both!
Pelvic mass
Epithelial ovarian tumour Germ cell tumour Both Neither Ascites
Epithelial ovarian tumour Germ cell tumour Both Neither GI symptoms
Epithelial ovarian tumour Germ cell tumour Both Neither A 6-month delay in presentation
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
1 - The answer is both.
2 - The answer is epithelial ovarian tumour.
3 - The answer is epithelial ovarian tumour.
4 - The answer is epithelial ovarian tumour.
Answer whether the following management options relate to germ cell tumours, epithelial ovarian tumours, neither or both!
1 - Surgery – total abdominal hysterectomy and bilateral salpingo-oophorectomy omentectomy
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
2 - Surgery – oophorectomy
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
3 - Surgery – biopsy only
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
4 - Chemotherapy – includes platinum
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
1 - The answer is epithelial ovarian tumour.
2 - The answer is germ cell tumour.
3 - The answer is neither.
4 - The answer is both.
Answer whether the following prognosis relates to either a germ cell tumour, an epithelial ovarian tumour, neither or both!
1 - 88% survival
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
2 - 50% survival
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
3 - 30% survival
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
1 - The answer is germ cell tumour.
2 - The answer is neither.
3 - The answer is epithelial ovarian tumour.
Answer whether the following relate to a germ cell tumour, a epithelial ovarian tumour, neither or both!
1 - Age at presentation is 16–20 years
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
2 - Age at presentation is 60–75 years
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
3 - Stage at presentation is stage I
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
4 - Stage at presentation is stage III
Epithelial ovarian tumour
Germ cell tumour
Both
Neither
1 - The answer is germ cell tumour.
2 - The answer is epithelial ovarian tumour.
3 - The answer is germ cell tumour.
4 - The answer is epithelial ovarian tumour.
Key points of GCT presentation
Typical symptoms include rapidly enlarging abdominal/pelvic mass, acute severe lower abdominal pain due to tumour rupture, haemorrhage or torsion.
Other symptoms may include dysuria, urinary frequency, rectal symptoms, menstrual irregularities, positive pregnancy test (rarely: precocious puberty, hyperthyroidism).
Ovarian GCTs are commonly unilateral (CAVE: ~10–20% of dysgerminomas bilateral).
Prognostic factors for malignant GCTs include tumour size (>10 cm), histological type (endodermal sinus, choriocarcinoma) and grade (high grade for immature teratomas).
A nulliparous 18-year-old woman presents to A&E with a 2-week history of worsening abdominal pain, nausea and vomiting. She is not septic or dehydrated, but is in pain. Examination demonstrates a tender, distended abdomen, but no rebound or guarding. Urinalysis is normal and she is apyrexial, normotensive and not tachycardic.
What could be the differential diagnosis?
What investigations are needed at the outset?
The common causes of abdominal and pelvic pain in a young woman are:
appendicitis ectopic pregnancy ovarian cyst accident mesenteric adenitis pelvic inflammatory disease constipation Infective causes (PID, appendicitis, mesenteric adenitis) would be unlikely without a tachycardia or temperature, but would be worth excluding.
Investigations that would be helpful initially would be:
Abdominal examination Any signs of an acute abdomen? Any peritonism? Bowel sounds
Vaginal examination Cervical excitation? Pelvic mass or tenderness? Purulent/bloody cervical discharge
Rectal examination Any right iliac fossa pain or mass associated with appendicitis (low lying)?
Full blood count Looking for anaemia and neutrophilia
β-hCG To exclude ectopic pregnancy
Pelvic ultrasound (transvaginal if possible) To investigate for adnexal masses
Case study – results of the investigations
Abdomen Soft. No rebound or guarding. Some tenderness in the right iliac fossa
VE/PR Normal-sized anteverted uterus. Smooth, firm and mobile right adnexal mass. Empty rectum
Full blood count Haemoglobin: 10.9
White cell count: 8.4
Platelets: 280
β-hCG Negative
Midstream urine No growth
Ultrasound scan Normal uterus and left ovary. Thin endometrium. 10 × 13 cm right adnexal mass with cystic and solid components. No free fluid.
A germ cell is suspected. Complete the assessment on the following page about what investigations are required.
A germ cell tumour is suspected. Which of the following investigations are required preoperatively?
A germ cell tumour is suspected. Which of the following investigations are required preoperatively?
α-fetoprotein
True
False
Chest x-ray
True
False
hCG
True
False
LDH
True
False
1 - The answer is true. This is a marker for teratomas and yolk sac tumours.
2 - The answer is true. Lung metastases are possible particularly with choriocarcinomas.
3 - The answer is true. Ovarian choriocarcinomas are rare but are a form of germ cell tumour.
4 - The answer is true. LDH is a marker for dysgerminomas.
A germ cell tumour is suspected. Which of the following investigations are required preoperatively?
A germ cell tumour is suspected. Which of the following investigations are required preoperatively?
Group and save
True
False
CA125
True
False
ECG
True
False
CA19-9
True
False
1 - The answer is true. This is appropriate for any laparotomy.
2 - The answer is true. This is appropriate for any large pelvic mass.
3 - The answer is false. ECGs are only required preoperatively in patients with a known cardiac history or who are aged >50 years.
4 - The answer is false. This is a marker to look for upper gastrointertinal tumours.
The following should be removed via surgery from a young woman you suspect of having a GCT.
The following should be removed via surgery from a young woman you suspect of having a GCT.
Uterus
True
False
Ovarian mass
True
False
Contralateral ovary
True
False
1 - The answer is false. The standard surgery for an epithelial ovarian tumour would be a total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. However, this would be inappropriate in a young woman with a chemosensitive tumour.
2 - The answer is true. Removal is clearly needed both for histology and, if required, symptom resolution.
3 - The answer is false. The standard surgery for an epithelial ovarian tumour would be a total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy. However, this would be inappropriate in a young woman with a chemosensitive tumour.
The following should be removed via surgery from a young woman you suspect of having a GCT.
The following should be removed via surgery from a young woman you suspect of having a GCT.
Enlarged pelvic and para-aortic lymph nodes
True
False
Omentum
True
False
1 - The answer is true. A systematic pelvic lymphadenectomy is not appropriate in a chemosensitive tumour. However, a careful clinical assessment and removal of any enlarged nodes is advisable. This is for staging only, not for treatment.
2 - The answer is true. Ovarian tumours of all types commonly spread transcoelomically. Hence an omental biopsy for staging to plan future chemotherapy is appropriate. An omentectomy is also appropriate – the choice is really dependent upon the surgeon, the access and the route of surgery (laparoscopic or open).
Key points of surgery of GCT
- Fertility-preserving surgery via mid-line incision (unilateral salpingo-ophorectomy and surgical staging) is accepted standard of care in early-stage disease.
- Biopsy of a contralateral normal ovary is not recommended (might impair fertility).
- In advanced stage, chemotherapy is recommended as primary treatment followed by completion surgery to resect residual masses.
- In recurrence, surgical removal is recommended, followed by chemotherapy if adverse features were found in the histological specimen.
Standard recommendations of treatment of GCT
Tumour Stage Treatment
Dysgerminoma:
- Stage IA/IB
Surgery + surveillance
- Stage IC
Surgery + postoperative chemotherapy
Non-dysgerminoma
- Stage IA, IB of any type or Stage IC immature GCT grade 1/2
Surgery + postoperative surveillance
- Stage IC, grade 3 immature
Surgery + surveillance
Or
Surgery + postoperative adjuvant chemotherapy
- Stage IC or unsuspected stage II
Surgery + chemotherapy - Stage II or greater
Neoadjuvant chemotherapy followed by surgery
Side effects of chemotherapy
While effective, there are toxicities associated with chemotherapy; common side effects from BEP/POMB-ACE chemotherapy include:
1 - nausea and vomiting (manageable with 5-hydroxytryptamine 3 receptor antagonists/ dexamethasone and neurokinin-1 antagonists)
2 - fatigue
3 - sore mouth
4 - high-tone hearing loss/tinnitus (ototoxicity; due to cisplatin)
5 - peripheral neuritis
6 - nephrotoxicity (exacerbated by dehydration)
7 - myelosuppression with risk of infection (neutropenic sepsis)/bleeding (thrombocytopenia) and anaemia
8 - pulmonary toxicity (bleomycin). Any new-onset cough/shortness of breath should be investigated urgently to exclude pneumonitis or fibrosis.
Chemotherapy
Stage IC yolk sac tumours are treated with surgery alone.
True
False
Germ cell tumours are usually hereditary.
True
False
All dysgerminomas require chemotherapy
True
False
Surgery for a germ cell tumour is total abdominal hysterectomy and bilateral salpingo-oophorectomy and omentectomy.
True
False
Bleomycin toxicity is dose-related
True
False
1 - The answer is false.
2 - The answer is false. They are rarely hereditary.
3 - The answer is false.
4 - The answer is true.
Chemotherapy
The long-term side effects of etoposide include an increased incidence of leukaemia
True
False
The complete remission rate following chemotherapy is approximately 90%
True
False
Pregnancy is uncommon following chemotherapy for germ cell tumours
True
False
There is an increased incidence of congenital abnormalities in babies born following chemotherapy for germ cell tumours
True
False
1 - The answer is true.
2 - The answer is true.
3 - The answer is false.
4 - The answer is false.
Key points, Chemotherapy of GCT
- Chemotherapy is standard of care for all MOGCTs.
- Decision to treat is based on the type of GCT, the grade of differentiation and disease stage.
- Stage IA tumours are managed safely without immediate adjuvant chemotherapy (reserved for relapse), but an intensive surveillance protocol must be in place (e.g. tumour markers, chest x-ray and abdomino-pelvic MRI).
- The woman should be counselled to avoid pregnancy for first 2 years following treatment.
- Adjuvant chemotherapy is the accepted standard for most cases with greater than stage IA disease.
- Commonly used regimen include BEP or for high-risk patients POMB/ACE.
There are several strategies available for breaking bad news but all, in essence, follow a similar pattern:
elicit what is known so far
a ‘warning shot’
allow pauses for thought and questions; don’t rush
explanation if requested
empathy
plan of management
offer of future help, support and meetings.
Look up the published success rates for chemotherapy for an ovarian GCT, consider the side effects, and then plan how you would talk to a young woman and her family about a diagnosis of a stage IC dysgerminoma following surgery.
Things to remember when planning a discussion of a cancer diagnosis:
breaking bad news – how to do it (to help the patient and yourself)
little of what is said is taken in – be concise
what does the patient want to know – everything, a little or nothing?
it is likely that important questions will come up – survival, side effects and questions about future fertility.
