Germ Cell Tumours

CASE PRESENTATION Dr. Lynda Ayade

BIODATA Miss K.W. is a 20 year old student who hails from Okrika in Rivers State and is a Christian of the pentecostal denomination.

PRESENTATION Histology report of Yolk Sac Tumour following an exploratory laparotomy at a private clinic (25/09/03). Had presented at the Gynaecology clinic a month earlier (25/08/03) with USS report of pedunculated uterine leiomyoma. She was given a 2 week appointment to prepare for myomectomy Developed acute abdomen that necessitated the emergency exploratory laparotomy at the private clinic.

• Admitted to Gynaecology ward. • Was commenced on adjuvant

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chemotherapy using the BEP regimen; 3 cycles were given every 21 days. Received a total of 8 units of blood for the period of chemotherapy. Developed facial nerve palsy, proptosis, and vomiting- symptoms of secondary metastasis to the CNS. Consult sent to Neurosurgical team to review patient. However, she absconded before they could review.

SUMMARY Miss K.W., a 20 year old student who presented with a histological diagnosis of Yolk Sac Tumour following an exploratory laparatomy in a private clinic. Had 3 courses of chemotherapy. She developed symptoms of CNS metastasis but absconded before a neurosurgical review.

GERM CELL TUMOURS

Dr. James E. Omietimi Department of Obstetrics and Gynaecology, UPTH.

INTRODUCTION Tumours of the ovaries are common forms of neoplasm in women. They are the 3rd commonest gynaecological tumours. However, because they present very late, death from ovarian tumours supercedes death from cervical & endometrial tumours combined. Fortunately, 80%-90% of ovarian tumours are benign (20-45years) while 10%-20% are malignant (40-65years). Malignant Germ Cell Tumours account for about 5% of ovarian cancers

ASSOCIATED RISK FACTORS FOR OVARIAN TUMOURS

Risk factors are much less clear than for other gynaecological tumours. Accepted risk factors: NULLIPARITY & FAMILY HX. Nulliparity & low parity are associated with carcinoma of the ovaries. Gonadal dysgenesis in children is associated with a higher risk of ovarian cancer. Genetic mutation Tumour suppressor genes; p53 -50% of ovarian carcinoma BRCA-1 & BRCA-2 :Serous cystadenocarcinomas HER2/neu oncogene -30% adenocarcinoma (correlates with a poor prognosis) CA-125 –80% of Serous & endometrioid CA`s

CLASSIFICATION OF OVARIAN TUMOURS

Ovarian tumours are classified according to their cell of origin: SURFACE EPITHELIAL CELLS Serous tumour Mucinous tumour Endometroid tumour Clear cell tumour

 SEX CORD STROMAL TUMOURS  Granulosa–Stromal cell tumour  Sertoli-Stromal cell tumour  Sertoli-Leydig cell tumour

GERM CELL TUMOURS  Teratoma: • Mature(adult) – Solid – Cystic e.g Dermoid cyst

• Immature • Monodermal (e.g Struma ovarii, carcinoid)  Dysgerminoma  Yolk sac tumour (Endodermal Sinus tumour)  Mixed germ cell tumours  Choriocarcinoma  METASTATIC (NON-OVARIAN) TUMOURS  From Uterus, Fallopian tubes, Contralateral Ovary, Breast & GIT e.g. Krukenberg tumour

Germ Cell Tumours 15-20% of all ovarian tumours Most are benign cystic teratomas like Dermoid Cysts. Malignant Germ Cell Tumours are very uncommon accounting for only 5% of ovarian cancers They are found mainly in children (teenagers) and young adults in their twenties They arise from germ cell differentiation. Endodermal Sinus (Yolk Sac) Tumour accounts for 20% of malignant germ cell tumours

Teratomas Mature (Benign) teratomas: Most are dermoid cysts Benign and derived from ectodermal differentiation of totipotential cells. Found in young women during active reproductive years. Originate from a meiotic germ cell with a karyotype of 46,XX. Morphology: Bilateral in 10-15% of cases Unilocular cysts containing hair and cheesy sebaceous material. Thin wall lined by an opaque, gray-white, wrinkled apparent epidermis. Within the wall, it is common to find tooth structures and areas of calcification.

Histology: Cyst wall is composed of stratified squamous epithelium with underlying sebaceous glands, hair shafts, and other skin structures. Structures from other germ layers can be identified, e.g., bone, cartilage, thyroid tissue. About 1% of dermoids undergo malignant transformation of any one of its components e.g., thyroid carcinoma, melanoma but most commonly squamous cell carcinoma. Rarely, a teratoma is solid but is composed of benign-looking heterogenous structures derived from all three germ layers.

Immature (Malignant) teratomas Rare tumours. Its component tissue resembles that in the embryo or foetus. Found in prepubertal adolescents and young adults. Mean age 18 years. Morphology: Bulky and have a smooth external surface. Have a predorminantly solid structure. Hair, grumous material, cartilage, bone and calcification may be present. Microscopy: Varying amounts of immature tissue differentiating toward cartilage, bone, glands, muscle and others. They grow rapidly and frequently penetrate the capsule with spread or metastases. Stage 1 tumours have an excellent prognosis.

Monodermal or Specialized teratomas Rare , always unilateral. Most common are Struma ovarii and carcinoid. Struma ovarii is composed entirely of thyroid tissue which may hyperfunction producing hyperthyriodism. Ovarian carcinoid arises from intestinal epithelium in a teratoma and may be functioning, producing 5hydroxytryptamine and the carcinoid syndrome. Rarely there is a combination of both in the same ovary – strumal carcinoid. Primary carcinoids are uncommonly (< 2%) malignant.

Dysgerminoma Uncommon tumours. 2% of all ovarian cancers yet 50% of all malignant germ cell tumours. 75% occur in the 2nd and 3rd decades. Composed of large vesicular cells having clear cytoplasm, well defined boundaries and centrally placed regular nuclei. Morphology: Usually unilateral, frequently solid tumours. Yellow-white to gray-pink cut surface and are often soft and fleshy. Histology: Cells are dispersed in sheets or cords separated by scant fibrous stroma. Fibrous stroma is infiltrated with mature lymphocytes and occasional granulomas. All dysgerminomas are malignant. Only about one third are aggressive. A unilateral tumour that has not spread has an excellent prognosis. They are extremely radiosensitive. Overall survival exceeds 80%.

Endodermal Sinus (Yolk Sac) Tumour Rare but the 2nd most common malignant germ cell tumour (20%). Generally, Germ Cell Tumours are unilateral & slow growing but Endodermal Sinus (Yolk Sac) Tumours grow rapidly and aggressively.  Mostly seen in children or young women with abdominal pain and rapidly developing pelvic mass.  Characteristic histological feature is a glomerulus-like structure composed of a central blood vessel enveloped by germ cells within a space lined by germ cells (Schiller-Duval body)  Intracellular and extracellular hyaline droplets are present in all tumours.  Prognosis is improved with combination chemotherapy.

Choriocarcinoma Most exist in combination with other germ cell tumours Pure choriocarcinomas are extremely rare. Histologically identical to the more common placental lesions. Ugly tumours that generally have metastasized widely through the blood stream to the lungs, liver, bone, and other viscera by the time of diagnosis. They elaborate high levels of chorionic gonadotropins- B-hCG. They are generally unresponsive to chemotherapy and are highly fatal.

Other Germ Cell Tumours Embryonal carcinoma: Highly malignant tumour of primitive embryonal elements. Polyembryoma: A malignant tumour containing so-called embryoid bodies. Mixed germ cell tumours: Containing various combinations of dysgerminoma, teratoma, endodermal sinus tumour, and choriocarcinoma.

Clinical Presentation Symptomatology is vague; May be assymptomatic & incidental Symptoms may include; weight loss GIT upset -vomiting, constipation or diarrhoea Urinary frequency, urgency or dysuria Abdominal mass Abdominal pain; haemorrhage, rupture or torsion Abnormal vaginal bleeding

DIAGNOSIS; clinical, radiological, biochemical & surgical Clinical; May be cachetic, lymphadenopathy, pale & ascites An abdomino-pelvic mass; Smooth & Cystic Hard & Irregular Bimanual exam; mass separate from uterus Radiological; Abd. USS for large masses Colour flow Doppler Trans-vaginal USS for small pelvic masses CT Scan

DIAGNOSIS contd. Biochemical; CA 125 –protein produced by most ovarian cancers Also produced in pregnancy & other benign conditions; endometriosis, fibroids, diverticulitis Alpha- FP & Alpha-1 anti-trypsin are specific for York Sac Tumours B-hCG is a useful tumour marker for Choriocarcinoma & other GCTs Tumor markers are also useful for post operative & chemotherapy phase of mgt. Rate of decline following Rx. is prognostic.

DIAGNOSIS Contd. Surgical; Definitive diagnosis is histopathological after surgery; laparotomy or laproscopy Staging is also done at laparotomy Frozen section at surgery or histopathology thereafter – Our patient had laparotomy & histopathology revealed York Sac Tumor

FIGO staging for Ovarian Cancers

I Growth limited to the ovaries Ia Tumor in one ovary; capsule intact, no tumor on surface, no ascites Ib As in Ia but tumor in both ovaries Ic As in Ia or Ib, but ascites with cancer cells, or capsule ruptured or tumor on surface, or positive peritoneal washings II Growth on one or both ovaries with peritoneal implants within the pelvis IIa Extension or metastases to fallopian tubes or uterus IIb Extension to other pelvic organs IIc As in IIa or IIb, but ascites with cancer cells, or capsule ruptured or tumor on surface, or positive peritoneal washings

Staging of Ovarian Cancers Contd. III Tumor in one or both ovaries with peritoneal implants outside the pelvis, or retroperitoneal node metastases IIIa Tumor grossly limited to the true pelvis, microscopic implants on abdominal peritoneal surfaces; no nodal involvement IIIb As in IIIa, but abdominal implants are <2cm in diameter IIIc As in IIIa, but abdominal implants are >2cm in diameter +_ retroperitoneal lymph node metastases IV Tumor involving one or both ovaries with distant metastases, e.g. parenchymal liver metastases, malignant pleural fluid

MANAGEMENT OF GERM CELL TUMOURS

DR. B.O. ALTRAIDE DEPT. OF OBSTETRICS AND GYNAECOLOGY UPTH

History Physical Examination Investigations Treatment Prognosis Conclusion

INVESTIGATIONS A) GENERAL -FBC plus ESR -Serum E/U/Cr - Coagulation Studies (when indicated) - LFT (when indicated) - Urinalysis/ Urine MCS

B) SPECIFIC - Ultrasonography - Colour Flow Doppler Studies - Computed Tomography - Magnetic Resonance Imaging - Chest X-ray - Barium Enema - Mammography - Intravenous Urography - Serum Tumour Markers - Radio Immunoscintigraphy

TREATMENT - Surgical - Adjunct Combination Chemotherapy - Radiotherapy SURGICAL TREATMENT - Aims at conserving future fertility -Normally appearing contralateral adnexa and uterus preserved. - Biopsy of contralateral ovary not recommended because of risk of peritubal and periovarian adhesions.

COMBINATION CHEMOTHERAPHY -Can be curative -Much more effective than single agent regimens -Tumour cells resistance is reduced. -Cumulative toxic effects of each drug reduced -Act at different cell sites to give synergistic effect - Usually Vinblastine, Bleomycin and Cisplatin or Bleomycin, Etoposide and Cisplatin are used. -Doses are;-Bleomycin 0.25-0.5 U/kg I.V.,I.M. or S.C. wkly -Etoposide 50-100mg/m² per day for 5 days -Cisplatin 15-20mg/m² I.V. daily for 5 days -Cisplatin & Etoposide are repeated every 3-4 wks - May be associated with a variety of potentially life threatening side effects. - FBC with differentials, LFT and Serum E/U/Cr are used to monitor between cycles of therapy.

RADIOTHERAPY - Especially useful in the treatment of dysgerminoma. - Otherwise germ cell tumours are generally not responsive to radiotherapy. PROGNOSIS - Significantly improved when the disease is detected while still confined to the ovary. -Amongst the malignant Ovarian Tumours, Germ Cell Tumours are associated with a better prognosis. - Overall 5 year survival rate for Ovarian Tumours is about %.