The main clinical problem related to the pineal gland is that of pineal tumours (Box1). They are rare, ten times more common in children than in adults and mainly derive from the three types of cells: neuroglial, parenchymal, and germinal cells. For the first time, the 2016 WHO classification of central nervous system (CNS) tumours uses molecular parameters in addition to histology to define tumour entities, formulating a concept for how CNS tumour diagnoses should be structured in the molecular era.
Box1. Classification of pineal tumours
1. Neuroglial cell tumours (20%) may affect children and adults of any age. Low- grade, pilocytic astrocytomas usually present before the age of 20 years, with no sex predilection, while other types are more frequent in adults (intermediate diffuse and anaplastic astrocytomas or high- grade malignant glioblastomas; Box 1).
2. Parenchymal tumours (15– 30%) secrete melatonin and differ in their degree of malignancy. The 2016 WHO classification grade them from I (pineocytomas, being mostly benign) to IV (pineoblastomas, being highly malignant) (Table 1). However, most parenchymal tumours are either mixed or show intermediate differentiation (WHO grades II and III, Table 1). Histologically, pineocytomas characteristic ally present pineocytomatous rosettes, while pineoblastomas are populated by small, highly undifferentiated cells, often pre sent with haemorrhagic or necrotic components, but rarely calcifications. The major prognostic factor is the extent of surgery. Pineoblastomas are highly malignant, aggressive and of rapid growth (similar to other primitive neuroectodermal tumours like neuroblastomas or medulloblastomas). Papillary tumours of the pineal region (PTPR) were included as a new entity in the 2007 WHO classification. They are very rare neuroepithelial tumours, macroscopically indistinguishable from pineocytomas, combining papillary and solid areas; however, microscopic ally, these tumours are easily distinguished. Recently it has been shown that PTPR have ependymal differentiation and are phenotypically more similar to the circumventricular subcommissural organ of the posterior third ventricle than to the pineal gland. The biological and clinical behaviour of these tumours is variable and may correspond to WHO grades II or III, but definite histological grading criteria remain to be defined. Intermediate grades II and III represent different degrees of differentiation and prognosis (Table 1).
3. Germ cell tumours (30– 50%), histologically and biologically homologous to gonadal germ cell neoplasms, will characteristically present positive markers for alpha fetoprotein (AFP) and beta human chorionic gonadotrophin (β- hCG), with more (teratomas) or less differentiation (germinomas), as well as intermediate degrees (yolk sac tumours).
Table1. Parenchymal pineal tumour classification; the current WHO classification does not provide strict criteria to distinguish grade II and III tumours.
Very rarely, pineal region tumours may derive from meningothelial, mesenchymal, ependymal, choroid plexus elements and peripheral nerves giving rise to gangliogliomas, melanocytic neoplasms, atypical teratoid/ rhabdoid tumours, meningiomas, cavernous angiomas, hemangiopericytomas or neurinomas/ neurofibromas, apart from lymphomas or metastases.
