Pineoblastoma

Pineoblastomas are tumours that are best thought of small round blue cell tumours located in the pineal region and thus, they closely resemble (both on imaging and on histology) medulloblastomas and retinoblastomas. They are the most aggressive and highest grade tumour among pineal parenchymal tumours, and considered WHO grade IV tumours.

On imaging, they usually present as large lobulated and enhancing tumours (more than 3 cm), hyperattenuating on CT (highly cellular), with heterogeneous signal intensities on MRI, sometimes with evident necrotic and haemorrhage regions. Restricted diffusion is commonly evident and, in almost all cases, obstructive hydrocephalus is observed at the presentation.

Epidemiology

Pineoblastomas are the most aggressive pineal parenchymal tumour and account for a substantial proportion of such tumours (24-50%) ⁷. They are typically found in young children, with only a slight female predilection (M:F 0.7:1; similar to other pineal parenchymal tumours), which is in contrast to the male predominance seen in pineal germinomas) ¹².

There is a well-established association with hereditary retinoblastomas. Patients with hereditary (bilateral) retinoblastoma no more than 5% develop midline (suprasellar or pineal) neuroblastic tumours ^6,10. Such cases are sometimes referred to as trilateral retinoblastoma.

Patients with DICER1 syndrome have an increased risk for developing pineoblastomas¹³.

Clinical presentation

Pineoblastomas are typically large and almost always associated with obstructive hydrocephalus, due to compression of the cerebral aqueduct. Compression of the tectal plate may also result in the Parinaud syndrome.

They are highly malignant tumours prone to CSF seeding, which is present in 15% of patients at the time of diagnosis.

Pathology

Pineoblastomas originate from pinealocytes and/or their precursors ¹¹. They are the least differentiated pineal cell tumours, with pineocytomas and pineal parenchymal tumour with intermediate differentiation representing better-differentiated tumours along the same spectrum. Pineoblastomas are considered WHO grade IV tumours ¹².

Macroscopic appearance

These tumours are poorly defined, often invading adjacent brain parenchyma. Their cut surface is pink and soft, with areas of necrosis and haemorrhage not infrequently seen ¹².

Microscopic appearance

Pineoblastomas are composed of tightly packed small round blue cells (high nuclear to cytoplasmic ratio) which in turn determines their imaging appearances (see below) ⁷. The growth pattern is largely featureless with the pineocytomatous rossettes seen in pineocytomas not present ¹². In contrast, Homer Wright rosettes and Flexner-Wintersteiner rosettes are occasionally seen ¹².

Areas of necrosis are frequently encountered ¹². Mitotic rate is usually high.

Immunophenotype

Immunophenotype is similar to other pineal parenchymal tumours ¹².

• synaptophysin: positive
• SMARCB1: positive
• other neuronal markers (e.g. neuron-specific enolase, neurofilament protein and chromogranin-A): variable

Radiographic features

Pineoblastomas tend to be large poorly defined masses, with frequent CSF seeding at presentation. They have a tendency to involve directly adjacent brain structures, which helps distinguish them from other pineal tumours that tend to be better circumscribed.

CT

The solid component tends to be slightly hyperdense compared to the adjacent brain due to high cellularity. This is a characteristic shared by other small round blue cell tumours such as PNET and medulloblastoma.

Classically, they are described as having peripherally dispersed or "exploded" calcification (mnemonic: blasted calcification), similar to pineocytomas. In contrast, pineal germinomas tend to engulf pineal calcification.

MRI

Pineoblastomas tend to appear as sizable (>4 cm) irregular masses often with evidence of invasion into adjacent brain ^6,9. Typical signal characteristics include ⁹:

• T1: isointense to hypointense to adjacent brain
• T2
  • isointense to adjacent brain
  • areas of cyst formation or necrosis may be present
• T1 C+ (Gd): vivid heterogeneous enhancement
• DWI/ADC
  • restricted diffusion due to dense cellular packing
  • ADC values are typically ~400-800 mm²/s ⁷

Central necrosis is sometimes present which can make the mass appear centrally cystic and thus can roughly mimic a pineal cyst, although the latter should have a smooth, thin wall ⁶.

Screening of the whole neural axis is necessary as CSF seeding is seen in 45% of cases ⁷.

Treatment and prognosis

Treatment is usually a combination of surgery, chemotherapy and radiation ⁷. Despite treatment, the prognosis has historically been poor, with a 5-year survival as low as 10%. More recently 5-year survival of 58-81% have been reported ^8,12 with median overall survival times of 4-8 years ¹².

The most important factors predicting a favourable outcome are early detection and treatment with at least chemotherapy, preferably a high dose regime with stem cell rescue ¹¹.

Differential diagnosis

General imaging differential considerations include:

• other pineal parenchymal tumours
  • pineocytoma: mature well-differentiated tumour: smaller and better circumscribed
  • pineal parenchymal tumour with intermediate differentiation
  • papillary tumour of the pineal region
• germ cell tumours
  • germinoma
    • marked male predominance
    • engulfed calcification
    • ADC values are typically much higher (~1000-2000 mm²/s ⁷)
  • embryonal carcinoma
  • choriocarcinoma
  • teratoma: may contain fat
• pineal cyst
  • thin (<2 mm) wall
• astrocytoma of the pineal gland
• metastasis
• medulloblastoma
  • imaging is very similar
  • located in the vermis rather than pineal region but can be difficult to distinguish if very high in the vermis and very large