Intracranial germ cell tumours (ICGCT) are rare tumours that primarily affect children and adolescents, with a male predominance, accounting for 3.6% of brain tumours in Western Europe and reaching a higher incidence of 15.4% in Japan ^[1][2][3][1,2,3]. A comparative study between Japanese and American populations regarding ICGCT revealed a different distribution of the tumours. More cases of basal ganglia involvement were present in the Japanese, whereas more bifocal (synchronous pineal and suprasellar) locations in western society, suggesting the presence of genetic or environmental factors, thus, contributing to the phenotypic diversity [4]. According to the WHO classification of the central nervous system (CNS) tumours, the germ cell tumours group, composed of germinoma, represents the most common histological type (60%), followed by mixed germ cell tumours (17.4%), teratoma (15.7%), yolk sac tumour (4.2%), choriocarcinoma (1.6%), and embryonal carcinoma (1.1%) [5]. According to Matsutani et al., pure germinoma and mature teratoma have a good prognosis, but other histological types may result in unfavourable prognosis. Intermediate prognosis corresponds to germinoma with syncytiotrophoblastic giant cell [STGC], immature teratoma, teratoma with malignant transformation and mixed tumours composed mainly of germinoma or teratoma, whereas poor prognosis is found in choriocarcinoma, yolk sac tumour, embryonal carcinoma, as well as in mixed tumours composed mainly of choriocarcinoma, yolk sac tumour, or embryonal carcinoma ^[6][7][6,7].

Germinomas usually develop in the midline areas of the brain, most often in the pineal gland (50% of the pineal tumours are germinomas) and the suprasellar region [8]. In approximately 5–10% of the cases, the tumour is ectopically situated (in other areas than neurohypophysial or pineal sites), including the basal ganglia, thalamus, corpus callosum, cerebellum, septum pellucidum, temporal lobe, and the spinal cord ^{[9][10][11][12][13]}[9,10,11,12,13]. Suprasellar germinomas are associated with female patients (<15 years old), while pineal germinomas with male patients (>15 years) [14]. In rare cases, germinomas have been described to occur later in life. Several reports mention the diagnosis in the sixth or seventh decade of life, outlining the fact that germinoma should be included as a differential diagnosis even in the elderly ^{[15][16][17][18][19]}[15,16,17,18,19]. Germinomas can also be present as synchronous lesions in the pineal region and hypothalamo-neurohypophyseal axis, also referred to as “bifocal germinomas”, with an incidence ranging from to 6% to 26% and even as high as 41% in some studies ^{[20][21][22][23][24]}[20,21,22,23,24]. Metastatic germinomas caused by the dissemination of tumour cells through the cerebrospinal fluid are reported in approximately 4.5% of the cases, usually after a mean period of 6–7 years after the initial tumour diagnosis ^[25][26][25,26]. According to the literature, the most common type of metastasis is spinal “drop metastasis” (32.5%), followed by ventricular dissemination (30%), and to a lesser extent, the suprasellar region, corpus callosum, subarachnoid space ^[26][27][28][26,27,28]. Concomitant metastases to the ventriculoperitoneal shunt can appear in 20% of the cases [26].

Tumours of the pineal gland obstruct the posterior wall of the third ventricle and of the aqueduct of Sylvius, resulting in acute hydrocephalus with headaches, nausea, projectile vomiting, papilledema, and lethargy. Generally, a 2 cm pineal tumour can cause obstructive hydrocephalus [29]. When the tumour grows, it has a compressive effect on the nerve pathway connecting the cortex to the oculomotor nuclei and the superior colliculi, resulting in Parinaud’s syndrome: upward gaze palsy, pupillary reflex dysfunction, and convergence-retraction nystagmus [30]. In comparison with other types of pineal tumours, upward gaze palsy seems to be more frequently encountered in pure germinomas (90%), as a consequence to the mesencephalic dysfunction caused by the germinoma’s progression pattern [31]. In cases of pituitary germinoma, visual disturbances can result from optic chiasma compression or perioptic meningeal seeding [32].

Germinomas developed in the suprasellar region or anterior third ventricle may be presented with endocrinopathy at the diagnosis (diabetes insipidus, delayed growth or gonadal function, precocious puberty, menstrual irregularities, visual field/acuity deficits). Neurohypophyseal axis dysfunction may also appear as an adverse effect of the radiotherapy treatment ^{[21][30][33][34][35]}[21,30,33,34,35]. Diabetes insipidus (DI) is the most common symptom associated with germinomas occurring in the hypothalamic-neurohypophysial region, followed by visual deficits, hypopituitarism, and increased intracranial pressure [36]. Diabetes insipidus seems to be a reliable predictor of tumoral invasion of the hypothalamus and third ventricle even in the absence of MRI evidence of suprasellar and third ventricle disease ^[37][38][39][37,38,39]. GH (growth hormone) deficiency and hypogonadism are the most frequent endocrine insufficiencies (89–95% of cases), followed by hypothyroidism and hypocortisolaemia, in approximately 50% of patients [40]. Boys with intracerebral germ tumours can develop precocious puberty (isosexual pseudoprecocity) because of beta-human chorionic gonadotropin (β-hCG) secretion of the syncytiotrophoblasts component of the tumour, which stimulates Leydig cells, with subsequent production of testosterone ^[41][42][41,42].

Patients with basal ganglia/thalamus germinoma often develop hemiparesis, headache, ataxia, cognitive impairment, and mental status alterations, though the severity of clinical picture does not seem to correlate with the tumour size ^[43][44][43,44]. Cases of optic nerve germinoma, although rare, present with progressive visual deficits, followed by endocrine dysfunction (most often DI), symptoms that may be inconsistent with the MRI findings, causing a delay in diagnosis [45].

A retrospective study on 49 children diagnosed with pure germinomas reported visual impairments as the most common symptom (47.9%), followed by motor dysfunctions (40.8%), frequently including focal or general weakness, hemiparesis, facial palsy. Patients presenting endocrinological symptoms had a significant delay in diagnosis [39]. Approximately one-third of the patients have prolonged symptomatology (>6 months) before the diagnosis, these cases being associated with a higher risk of metastatic disease [46]. A summary of the clinical presentation is shown in Table 1.