Ovarian Germ Cell Tumors – Flashcards
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What are the 3 main subdivisions of MOGCT?
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WHO classification for MOGCT. 1) Primitive Germ Cell Tumours -Dysgerminoma (32.8%) -Yolk sac tumour (15%) -Polyembryoma -- -Embryonal carcinoma (4.1%) -Non gestational choriocarcinoma (2.1%) Biphasic or Triphasic teratoma -Immature teratoma (35.6%) -Solid mature teratoma (2.6%) -Cystic mature teratoma (dermoid cyst) NA Monodermal teratoma and somatic tumour associated with biphasic or triphasic teratoma (<1%) -Carcinoid -Thyroid group -Sarcoma -Melanocytic -Neuroectodermal tumours Mixed - 5.3%
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In what category of ovarian tumours do dermoid cysts belong and what other tumours are in this category?
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• DYSGERMINOMA • YOLK SAC TUMOR (ENDODERMAL SINUS TUMOR) • EMBRYONAL CARCINOMA • POLYEMBRYOMA • CHORIOCARCINOMA • TERATOMAS - Immature; Mature; Monodermal (struma ovarii, carcinoid) • MIXED GERM CELL TUMOR
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Why is a rapid diagnosis essential in MOGCT?
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MOGCTs that contain yolk sac or trophoblastic elements have a potential doubling time of just a few days. As a consequence symptoms rarely precede presentation by more than a few weeks.
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What are teratomas?
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Contains immature tissue of either ectodermal, mesodermal or endodermal origin with immature neural tissue being the most common Occasional teratomas contain tissues from only two germ layers, and rare teratomas contain tissues from only one germ layer (monodermal teratomas). The most common example of the latter in the ovary is struma ovarii. GRADE - Only germ cell tumour for which histological grade is of prognostic significance Contra-lateral ovary contains mature teratoma in 10-15% of cases
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How common are dermoid cysts and in what age groups do they occur?
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They are the most common ovarian tumor, accounting for approximately 40% of all primary ovarian tumors and for up to 60% of benign forms. They usually occur in children and young adults, but may be encountered throughout reproductive life and may not be discovered until after the menopause.
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What are some rare complications of dermoid cysts?
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(a) TORSION that may lead to one or more of infarction, perforation, hemoperitoneum, and autoamputation; (b) BACTERIAL INFECTION of the cyst; (c) SPONTANEOUS RUPTURE into the peritoneal cavity or a hollow viscus; a sudden rupture may lead to an acute abdomen, whereas a slow leak may lead to a granulomatous peritonitis that can mimic metastatic carcinoma or tuberculosis at operation; (d) HEMOLYTIC ANEMIA that disappears after removal of the tumor.
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What is the risk of malignant transformation of a dermoid cyst?
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RARE, 0.5 - 2% risk of malignant transformation in postmenopausal women. MOST COMMON CA = SCC from squamous lining of the cyst Risk factors for malignant transformation include, a lesion greater than 10 cm, age over 45 and rapid growth. If the cancer has spread beyond the ovary at the time of its removal, the prognosis is poor.
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What are the most common malignant germ cell tumors?
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Dysgerminomas (the ovarian analogue of the testicular seminoma) either pure or mixed are the most frequently occurring MOGCT and compared to nondysgerminomas they are more likely to present as stage I and be bilateral. Accounts for 30-40% of all germ cell ovarian cancers. More rarely they can develop within a gonadoblastoma in female patients with a Y chromosome in patients with gonadal dysgenesis or testicular feminization
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What is the histological features of dysgerminoma?
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Sheets of tumor cells resembling primordial-type germ cells separated by a stroma rich in lymphocytes.
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What is the gross appearance of a dysgerminoma?
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Large lobulated solid mass that is cream or tan coloured.
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Phenotypic females with Y chromosomes - what are the 3 main groups?
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Pure gonadal dysgenesis (46XY, bilateral streak gonads) Mixed gonadal dysgenesis (45X/ 46XY, unilateral streak gonad, contralateral testes) Androgen insensitivity syndrome (46XY/ testicular feminization)
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5% of dysgerminomas are discovered in phenotypical females with abnormal gonads. What is the management?
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In most patients with gonadal dysgenesis, dysgerminomas arise in a gonadoblastoma (benign ovarian tumor composed of germ cells and sex-cord stroma). Need to remove both ovaries.
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What is the consequence of leaving a gonadoblastoma in situ in patients with gonadal dysgenesis?
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More than 50% will develop into malignancies.
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Rate of bilaterality in germ cell tumors
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Dysgerminoma is the only germ cell malignancy with a significant rate of bilaterality (10-15%). The rest are rarely bilateral.
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Most common extraovarian spread of dysgerminomas?
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Lymphatics, esp higher para-aortic nodes.
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What is the role of cytoreductive surgery in germ cell tumors?
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Any surgical resection that is potentially morbid that delays chemotherapy should be resisted. Aim to start chemo 7-10 days after surgery.
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Tumor markers for germ cell tumors - Dysgerminoma
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LDH (most commonly) and HCG. *Lactate dehydrogenase is a nonspecific biochemical marker in the context of MOGCT and can be raised in dysgerminomas. * β-HCG is elevated when trophoblastic elements are present as in choriocarcinoma and occasionally in dysgerminomas when syncytiotrophoblastic giant cells are present.
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Tumor markers for germ cell tumors - Yolk Sac tumor
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AFP (most commonly) / LDH/ HCG/ AFP. Rarely have detectable alpha-1-antitrypsin (AAT) *Elevation of serum AFP in a young woman with an adnexal mass is suggestive of a yolk sac tumor.
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Tumor markers for germ cell tumors - Embryonal
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LDH
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Tumor markers for germ cell tumors - Polyembryoma
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HCG/ AFP
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Tumor markers for germ cell tumors - Choriocarcinoma
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HCG/ LDH/ AFP
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Tumor markers for germ cell tumors - Mixed
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LDH
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Tumor markers for germ cell tumors - Immature teratoma
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AFP/ LDH
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Adjuvant therapy for dysgerminoma?
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Very sensitive to RT - BUT loss of fertility a problem so radiation should rarely be used as first line treatment. Systemic chemotherapy should be treatment of choice. Most frequently used is BEP: 3-4 cycles.
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Management of recurrent dysgerminoma?
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75% recurrence are in the first year. If previous chemotherapy with BEP, then second line of TIP (paclitaxel, ifosfamide, cisplatin can be considered). Consider high dose chemotherapy with peripheral stem cell support.
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Dysgerminoma in a pregnant patient?
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Depends on gestation. Chemotherapy can be used safely in 2nd and 3rd trimester.
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About 10% of ovarian germ cell tumours are "mixed" germ cell tumours. What is a mixed germ cell tumour?
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A germ cell tumor that contains two or more elements from the list of tumors given above. Most common mixed = dysgerminoma (80%). EST (70%), immature teratoma (53%), chorio(20%), embryonal (16%). Most important prognostic feature - size of primary tumor and relative amt of most malignant component. Dermoid cysts therefore need to be examined carefully by the patologist to exclude (a) an associated malignant germ cell tumor (usually in a child or young adult), and (b) a cancer arising from a component of the dermoid cyst, usually squamous cell carcinoma, in an older patient.
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What is the second most common malignant germ cell tumor?
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Endodermal sinus tumor/ yolk sac tumor. They form a fifth of all MOGCT.
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Mean age and pattern of presentation of yolk sac tumor?
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18 years. 1/3 can be pre-menarchal. Characteristically these tumours are aggressive in nature and have the capacity to grow very rapidly and spread extensively by intraperitoneal dissemination.
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Pathological features of yolk sac tumors?
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Unilateral, solid-cystic with areas of h'rr and necrosis. Reticular or tubulocystic pattern with Schiller Duval Bodies characteristic.
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Gross appearance of yolk sac tumor
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Yellowish and more friable than dysgerminomas. Usually necrotic with areas of focal hemorrhage.
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Progression of yolk sac tumor
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Aggressive. Often resulting in rapid growth and extensive intraperitoneal dissemination.
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Presenting symptom of yolk sac tumor?
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Abdominal/ pelvic pain.
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Management of adequately resected yolk sac tumor?
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STILL CHEMO. ALL patients need chemo. Chance of cure with chemo is ~100% with early stage disease and at least 75% for more advanced stage disease.
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When is bleomycin contraindicated in treatment?
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Mainly lung problems: Interstitial Pneumonitis, Lung Fibrosis, Chronic Lung Disease Others: Liver Problems, Kidney Disease, Pregnancy, A Mother who is Producing Milk and Breastfeeding
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VIP (etoposide, ifosphamide and cisplatin) cf to BEP - what is the main disadvantage?
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More myelotoxic, requiring growth factor support.
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Role of POMB-ACE chemotherapy?
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Developed by Charing Cross hospital in London. Superior to BEP for patients with poor prognostic features. Useful for patients with massive metastatic disease. Only moderately myelosuppressive - intervals between each course 9-11 days, minimising time for tumor regrowth.
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Features of embryonal Ca?
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5% of malignant GCTs. One of the most aggressive tumors, distinguished from chorio by absence of syncytiotrophoblastic and cytotrophoblastic tissue.
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How to sort out tumor markers??
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• AFP - Endodermal sinus, mixed germ cell, immature teratomas • LDH - Dysgerminomas • HCG - Dysgerminomas, moles, placental site tumors, choriocarcinomas, embryonal tumors • CEA - Germ cell tumors, epithelial ovarian tumors • Inhibin B - Granulosa cell • Mullerian Inhibiting substance (MIS) - Granulosa cell • Ca125 - Epithelial
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Principle of chemotherapy for germ cell tumors?
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ALL patients should receive post-operative adjuvant therapy EXCEPT those with adequately staged Stage 1a Grade 1 immature teratomas and Stage 1a dysgerminomas.
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How is immature teratoma graded?
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Semiquantification of the amount of neuroepithelium correlates with survival in ovarian immature teratomas and is the basis for grading of the tumors.
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Late Effects of BEP treatment of malignancy germ cell tumors of the ovary?
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Gonadal function, Platinum - significantly increased risk of cardiovascular disease especially hypertension; hearing impairment, nephrotoxicity (renal impairment 30%) and peripheral sensory neuropathy Etoposide exposure- small risk of developing of acute leukemia at a later stage. Bleomycin exposure - permanent lung damage in the form of pulmonary fibrosis.
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Factors affecting gonadal function after BEP chemotherapy ?
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Older age at initiation of chemotherapy, greater cumulative drug dose, longer duration of therapy.
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Risk of secondary malignacies with treatment?
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etoposide associated with risk of treatment related leukemia. Dose related. 2000mg/m2: 5% risk. In 3-4 cycles, cumulative dose is 1500 -2000.
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How to justify use of etoposide since there is a risk of malignancy?
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One case of treatment-induced leukemia expected for every 20 additionally cured patient who received BEP as compared with PVB.
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Principles of surgery for MOGCT?
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In patients with suspected stage 1 disease requires an omentectomy, peritoneal washings,peritoneal biopsies including areas such as the pelvic side walls, diaphragmatic surface, bladder reflection, and bilateral paracolic spaces, and para-aortic and pelvic lymph node sampling. If the patient is going to require chemotherapy for metastatic disease, initial major cytoreductive surgery is contraindicated as they will inevitably require chemotherapy, and the more radical the surgery, the longer it will take before the patient is fit enough to start chemotherapy. Furthermore, any microscopic cancer remaining after surgery can rapidly regrow whilst the patient is recovering from the surgery.
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Advantages of having adjuvant chemotherapy for MOGCT.
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Reduces risk of relapse to <2% Less intensive surveillance required Reduces risk from suboptimal staging It is less important if the patient is lost from follow up Reduced anxiety about relapse
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Disadvantages of having adjuvant chemotherapy for MOGCT.
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Toxicity from chemotherapy Overall survival is not better than those patients who are closely monitored under surveillance Not necessary for >75% of patients Possibility of developing leukemia at a later stage if exposed to etoposide
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Advice regarding pregnancy?
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Patients should be advised not to become pregnant during the first 2 years, the higher-risk period of surveillance since pregnancy causes an increase in AFP and β-HCG which prevents meaningful surveillance of serum tumour markers
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Surveillance following therapy?
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Annual pelvic ultrasound for up to ten years if the patient has a dysgerminoma due the potential for this type of tumour to manifest as a LATE relapse. Patients have a baseline CT chest abdomen and pelvis and this is followed by CT imaging of the abdomen and pelvis only at three months and one year in the absence of lung metastasis.
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Chemotherapy for advanced disease?
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In patients with advanced disease a minimum of 4 cycles of chemotherapy is given, with bleomycin omitted from the fourth course. Chemotherapy should be initiated promptly as MOGCT can be a rapidly growing entity with the propensity for patients to deteriorate quickly. Carboplatin has been substituted for cisplatin to avoid nephrotoxicity and neurotoxicity particularly in the paediatric population. POMB/ACE has been advocated for those with a worse prognosis, associated with higher stage or very high HCG or AFP
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For which germ-cell tumor has second-look laparotomy been found to have some clinical benefit if the primary surgery resulted in incomplete resection?
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There is no evidence for the standard use of second look surgery following chemotherapy in MOGCT as residual disease or relapse can be identified with the aid of radiological imaging and tumour markers. Surgery may be needed later for resection of residual masses following chemotherapy, particularly if there is a suspicion that the masses contain viable cancer or mature teratoma. Mature teratomas can grow and become surgically unresectable causing damage to vital organs as in growing teratoma syndrome.
