Education Resource from the Society for Endocrinology
J Hale
Consultant Paediatric Oncologist, Royal Victoria Infirmary, Newcastle upon Tyne
Summer School 5-8 July 2005
St Aidan’s College, Durham University, Durham, UK
Intracranial germ cell tumours(GCTs) are a heterogeneous and relatively rare group of central nervous system(CNS) tumours that have particular significance for the endocrinologist. The term germ cell tumour encompasses a variety of histological sub-types and the terminology has often been used in a confusing way. The sub-types include mature and immature teratoma and the malignant germinoma, yolk sac tumour, choriocarcinoma and embryonal carcinoma. Within any one tumour several sub-types of GCT may be present. Malignant GCTs are usually divided into germinomatous and non-germinomatous (NGGCT), a distinction which is important for treatment and prognosis.
Intracranial GCTs are tumours of adolescence and early adulthood with 90% occurring under the age of 20. The incidence has slowly increased with time, is higher in the Far East and affects males:females 2:1 overall. About 90% of intracranial GCTs occur in midline sites – 47% pineal, 33% suprasellar, 14% bifocal (pineal + suprasellar).
Clinical presentation depends on the site of the tumour with pineal tumours presenting with raised intracranial pressure, Parinaud’s syndrome and occasionally diabetes insipidus (DI). Suprasellar tumours almost invariably cause DI at diagnosis and may cause growth failure, precocious or delayed puberty and visual field defects. Germinomatous tumours may have a very indolent presentation, particularly if suprasellar, with up to 20-30 months from first symptom to diagnosis.
The hallmark of GCTs is the production of tumour markers by many sub-types. These include alpha fetoprotein (AFP), human chorionic gonadotrophin (HCG) and placental alkaline phosphatase (PLAP) which can be measured in serum and CSF.
Diagnosing GCTs requires early collaboration between oncologist, neurosurgeon and endocrinologist for best outcome. The diagnosis should be considered for any midline intracranial tumour and AFP and HCG should be measured urgently in serum and CSF whilst measures are taken to control raised pressure if needed. If AFP/HCG is elevated this is diagnostic and histological verification is not needed. If markers are negative biopsy, but not resection, is required for diagnosis. In the recent SIOP CNS GCT 96 protocol, of 105 NGGCTs, 43 had open procedures at diagnosis despite elevated markers and 14 sustained significant toxicity including 3 deaths.
Outcome for intracranial GCTs has significantly improved since treatment was conducted within the SIOP CNS GCT 96 protocol in Europe although young adults are still failing to be recruited. Management for germinoma and NGGCTs is different. For germinoma craniospinal radiation, following biopsy, is standard therapy with >90% EFS. Trials are on-going to reduce overall therapy by combining reduced radiotherapy with non-intensive chemotherapy whilst maintaining survival. NGGCTs require chemotherapy (platinum based) followed by radiotherapy to the site of tumour only, unless metastatic. Using this strategy EFS is 75% at 5 years. Administration of chemotherapy with hyper-hydration to patients with DI is challenging and close oncological / endocrinological collaboration is needed.
Long term a large number of patients with CNS GCTs have pituitary dysfunction,
which may evolve with time. As at diagnosis, the best outcome is obtained by
well orchestrated multidisciplinary management.
The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society
Revised:
28-Jul-2005