Suprasellar malignant mixed germ cell tumour presenting as craniopharyngioma.
A 15 year old boy presented with diminution in vision of both eyes, diabetes insipidus and hypopituitarism. MRI was suggestive of a large suprasellar and retrosellar craniopharyngioma with stretching of the optic chiasma. Histopathological findings on the first surgical specimen were interpreted as a craniopharyngioma. He was reoperated on account of clinical deterioration and increase in tumour size. Histological examination this time revealed derivatives of all three germ cell lineages along with areas of embryonal carcinoma, and yolk sac tumour besides squamous cysts, establishing the diagnosis of malignant mixed germ cell tumour. Serum and CSF were strongly positive for alpha foetoproteins.
Intracranial germ cell tumours are uncommon, comprising 0.5-11% of all intracranial neoplasms., However, they remain as one of the possibilities in all sellar or suprasellar neoplasms, especially in paediatric patients.,,,,, Germinomas are the most common germ cell tumours in this location but a number of non-germinomatous tumours, including embryonal carcinoma, teratoma, choriocarcinoma, endodermal sinus tumour and a combination of these tumours have also been reported.,, The present communication describes a case of suprasellar malignant mixed germ cell tumour, which was initially misinterpreted as a craniopharyngioma.
A 15 year old boy presented with gradual diminution of vision in left eye, followed by the right, over the past 1½ years. He had generalised headaches for the same duration, which were relieved by analgesics. He also had polyuria and polydypsia for the last 6 months, and was a known marijuana addict. On examination his pulse was 50 per minute. There was no perception of light in left eye. He had perception of hand movements only in the nasal field of right eye. Fundi showed bilateral optic atrophy. Endocrinological investigations revealed T3-0.2 ng/ml (normal 0.5-1.65 ng/ml, T4-2.7 µg/dl (normal 4.5-12.5 µg/dl), TSH-0.28 IU/ml (normal 0.47-5.01 IU/ml, cortisol-38.2 ng/ml (normal 69-223 ng/ml) and prolactin-60.8 ng/ml (normal 2.2 - 18 ng/ml). MRI showed a large suprasellar, rounded, heterogeneous signal intensity, extra-axial mass with intrasellar and retrosellar extension causing obliteration of the suprasellar cistern, without any parasellar or cavernous sinus involvement. There was possible compression of the hypothalamus, midbrain, bilateral oculomotor nerves and the optic chiasma. The appearances were suggestive of a craniopharyngioma [Figure. 1].
He was prepared with l-thyroxine and cortisone, prior to a right pterional craniotomy. Partial removal of a pink, fleshy, moderately vascular tumour, which had a good plane of cleavage from the surrounding structures, was performed. Histopathological examination showed cystic areas and solid masses of stratified squamous epithelium along with occasional glands. There were no areas of calcification. These features were interpreted as suggestive of a craniopharyngioma [Figure. 2].
The patient was readmitted 3 weeks later on account of increasing drowsiness. A repeat MRI showed increase in the size of tumour with areas of haemorrhage and necrosis. The lesion was approached by anterior interhemispheric transcallosal route and a subtotal removal was achieved. It contained areas of tough consistency as well as necrosis and haemorrhage. Histopathological examination revealed additional morphological features, and besides the epithelial elements seen in the first examination, there were embryonal glands, yolk sac elements, primitive neural tissue, and areas of calcification and cartilage formation. These findings were suggestive of a malignant mixed germ cell tumour [Figures. 3]-[Figures. 5].
Subsequent examination of serum and CSF were strongly positive for alphafetoprotein (140 ng/ml- and 175 ng ml-1 respectively), but negative for BETA -HCG. The patient died eight days later.
Intracranial germ cell tumours are relatively uncommon, comprising approximately 0.5-11% of all intracranial tumours., They most commonly arise in the midline, involving the pineal region in 50%, suprasellar region in 40% and both these sites in about 6% of cases. The remaining cases occur in non-midline structures which include basal ganglia, thalamus, cerebral hemisphere and structures in the posterior fossa. However, they remain an important diagnostic possibility in all suprasellar and/or sellar tumours in the paediatric age group.,,,,,,
Suprasellar germ cell tumours present with the classic triad of visual disturbances, diabetes inspidus and varying degree of hypopituitarism in about 20% of patients. They have a significant male predilection (male:female=2.24:1), irrespective of the tumour type, and the majority of patients are diagnosed between 10-21 years of age. Germinomas comprise two-thirds of suprasellar neoplasms, whereas nongerminomatous tumours (teratoma, embryonal carcinoma, endodermal sinus tumour, chorio-carcinoma and various combinations) have rarely been reported in this location.,,, Mixed germ cell tumours (MGCT), which contain areas of embryonal carcinoma, comprise only 5-8% of all intracranial germ cell tumours.,,
Neuroimaging evaluation is useful in distinguishing between germinomas, teratomas and other MGCTs, primarily by evaluation of cystic versus solid lesion (teratoma versus germinoma), contents of the cysts (teratoma versus MGCT), and infiltrative nature of the tumours (seen in MGCT). Presence of haemorrhage and necrosis are indicators of a higher grade of malignancy, e.g. embryonal carcinoma, choriocarcinoma or endodermal sinus tumour.
Elevation of both blood and CSF alphafetoproteins is strongly suggestive of the presence of embryonal carcinoma and endodermal sinus tumour areas, and has been occasionally used independently for management of these patients. However, the significance of histopathological evaluation of the tumour components in determining the modalities of therapeutic interventions as well as prognosis has been repeatedly emphasized in several reviews.,, It has been shown that in non-germinomatous GCTs, the pure malignant GCT has a 27.3% survival for 3 years. On the other hand, 3 year survival varies from 9.3 to 94.1% depending upon the type of germ cell elements as well as the amount of malignant germ cell component represented in the tumour. Sawamura et al reported that the presence of embryonal carcinoma or endodermal sinus tumour lowered the survival in MGCT from 67-69% to 38%. In an autopsy study of six cases, Ikura et al found all tumours to be composed of a non-homogeneous mixture of germinoma and non-germinomatous MGCT, thereby emphasising the need of surgical resection for accurate histological evaluation.
The pathogenesis of the MGCT has been debatable. Germinomas which arise from the most undifferentiated cells have the best prognosis, whereas non-germinomatous MGCTs, such as choriocarcinoma or yolk cell tumour, which arise from the most differentiated cells, have the worst prognosis. It has been suggested that only germinomas arise from the primordial germ cells whereas other tumors arise from misplaced embryonal cells at various stages of embryogenesis, which were wrongly enfolded into the brain at the time of neural tube formation. Their germ cell origin was considered due to their specificity of origin within positive (suprasellar cistern, suprachiasmatic nucleus) and negative (pineal) regulatory control for gonadotropin secretion within the diencephalon. The abrupt rise in the incidence of such tumours in the 10-12 years age group suggests that neuroendocrine events may play an activating influence in the malignant expression of these embryonal tumours.
The present case had a classical clinical presentation of a suprasellar tumour. The rapid clinical deterioration following the first operation and presence of haemorrhage, necrosis and cartilage formation during subsequent surgery was unlike the usual clinical course of a craniopharyngioma. This case highlights the histological difficulties in interpertation of findings if only epithelial elements are represented in such a tumour. Serum and CSF enzyme tumour markers (AFP, ? -HCG) must be done as an adjunct for the diagnosis of mixed germ cell tumours when the histopathological examination sample is small.
The authors gratefully acknowledge the opinion of Dr. A.K. Banerjee,Professor of Neuropathology and Head, Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, on histopathological material of this case.