An aggressive primitive neuroectodermal tumour of the pineal gland which typically arises in children, often presents with symptoms of hydrocephalus and is characterised by an enhancing mass with potential for CSF dissemination.
Description
Pineoblastoma is a rare, highly aggressive, malignant primary brain tumour originating from embryonic precursor cells in the pineal gland. It is most frequently seen in children but can occur at any age. Histologically, pineoblastomas are classified as grade IV neoplasms according to the World Health Organisation (WHO) classification of central nervous system (CNS) tumours, and represent the most aggressive pineal parenchyma tumour.
Pathogenesis
The pathogenesis of pineoblastoma is not well understood due to its rarity. It is thought to derive from primitive neuroectodermal cells of the pineal gland, leading to a small, undifferentiated tumour with a high mitotic rate. No specific genetic alterations have been consistently associated with the formation of pineoblastomas.
Epidemiology, Risk Factors & Associations
- Pineoblastomas constitute around 0.1% of intracranial tumours and 3-8% of pineal region tumours.
- The peak incidence occurs in children, especially under the age of 5 years.
- Associations with familial cancer predisposition syndromes, such as Li-Fraumeni syndrome, and bilateral retinoblastoma have been reported (1-5% of cases, as high as 25% in children). The combination of bilateral retinoblastoma and pineoblastoma is known as trilateral retinoblastoma.
Clinical Features
Common clinical features are related to increased intracranial pressure due to obstructive hydrocephalus from compression of the cerebral aqueduct, which can cause headaches, nausea, vomiting, and lethargy.
Given the tumour’s location, patients may also present with Parinaud’s syndrome (upward gaze palsy, convergence-retraction nystagmus, and light-near dissociation of the pupils), reflecting the compression of the tectal plate.
Complications
Possible complications include obstructive hydrocephalus, due to aqueductal stenosis, and metastasis along the cerebrospinal fluid (CSF) pathways (up to 45% show CSF dissemination).
Pathological Features
Histopathology
- Macroscopic: Poorly defined tumours, often invading adjacent brain parenchyma.
- Microscopic: Pineoblastomas demonstrate small blue round cells with high nuclear-cytoplasmic ratios, frequent mitotic figures, and occasionally rosette or pseudorosette formation.
Immunohistochemistry
There are no characteristic immunohistochemical markers; however, synaptophysin, neuron-specific enolase (NSE), and neural cell adhesion molecule (NCAM) are often positive.
Genetics
Genetic studies are usually non-contributory, with no specific genetic mutations or alterations consistently identified in pineoblastoma.
Radiological Features
General Features
- Large (>4 cm) poorly defined masses which may directly involve adjacent brain structures
- Trilateral retinoblastoma association: May be associated with bilateral intraocular masses representing retinoblastoma.
MRI
- The most sensitive modality for evaluating pineoblastomas.
- These include a pineal gland mass causing mass effect on or invasion of adjacent structures.
- T1: Generally hypo- or isointense to grey matter.
- T2: Hyperintensity may suggest cyst formation and necrosis
- T1 C+: Strong, homogeneous enhancement is a classic feature.
- DWI/ADC: Restricted diffusion due to high cellularity
CT
- The solid components often appear hyperdense due to high cellularity. May demonstrate peripheral calcification
- Demonstrates strong contrast enhancement.
Grading and Staging
Pineoblastomas are classified as grade IV tumours by the WHO due to their high rate of proliferation and aggressive behaviour. No specific staging system is employed for this tumour.
Diagnosis
Diagnosis involves a combination of imaging findings and histopathological examination after biopsy or surgical resection. The presence of small blue round cells, along with rosette or pseudorosette formation, supports the diagnosis. Due to the potential for CSF dissemination, a lumbar puncture is generally performed once the mass effect is controlled.
Differential Diagnosis
- Pineocytomas: These are less aggressive pineal gland tumours, generally presenting in adults. On imaging, they exhibit less intense contrast enhancement.
- Pineal cyst: May also demonstrate central T2 hyperintensity but demonstrates a smooth thin wall.
- Medulloblastoma: These can appear similar histologically but are usually located in the cerebellum. Can be difficult to distinguish if large and located in the vermis.
- Primitive neuroectodermal tumours (PNETs): Histologically similar but location and patient age can help differentiate them.
Management
Imaging of the entire neuraxis pre-operatively. Management generally involves maximal safe surgical resection, followed by adjuvant radiotherapy and chemotherapy due to the aggressive nature of the tumour. Neuro-oncology and neurosurgery are the primary managing specialties. Despite aggressive therapy, the prognosis remains poor due to the tumour’s high-grade nature and the propensity for CSF dissemination.