Definition
- Essential:
- Histopathological features of an embryonal tumour AND
- High proliferative/mitotic activity AND
- Pineal region location
- Desirable:
- Retained nuclear SMARCB1 (IN11) staining DNA methylation profile of pineoblastoma subtype
Numbers
- 35% of all pineal parenchymal tumours
- Age 17.8 yrs
- More in children
- M:F= 0.7:1
Localisation
- Pineal region
- Trilateral retinoblastoma (TRb)
- 5-13%
- is a disease associating unilateral or bilateral retinoblastoma (Rb) with an intracranial midline primitive neuroectodermal tumor (PNET) which usually arises in the pineal gland (PG)
Cell origin
- Same as pineocytoma
CNS WHO grading
- Grade 4
Molecular subtypes
- Through methylation profiling
Pineoblastoma, miRNA processing-altered 1
- Children
- Mutations
- DICER1
- DROSHA
- DGCR8
Pineoblastoma, miRNA processing-altered 2
- Older children
- A relatively good prognosis
- Mutations
- DICER1
- DROSHA
- DGCR8
Pineoblastoma, MYC/ FOXR2-activated
- In infants
- Mutations
- MYC activation
- FOXR2 overexpression
Pineoblastoma, RB1-altered
- Infants
- Causes trilateral retinoblastoma
- 15%
Histopathology
Macroscopy
- Poorly defined, often invading adjacent brain parenchyma
- Cut surface is pink and soft
- Fq areas of necrosis and haemorrhage
Microscopy
- Presence of pattern-less sheets of small immature neuroepithelial cells with
- A high nuclear-to-cytoplasmic ratio (Called ‘small blue cells’ due to dominant nuclear staining over scant cytoplasm),
- Hyperchromatic nuclei, and
- Scant cytoplasm.
- Locally invasive, with poorly defined borders, and have a propensity to disseminate through the CSF.
- Rossettes seen
- No pineocytomatous Rosettes seen in pineocytomas
- Rosettes seen
- Homer Wright rosettes
- Flexner-Wintersteiner rosettes
- Indicating retinoblastic differentiation
- Fq necrosis
- Can get a mixed pineocytoma-pineoblastoma picture
- Ki-67 proliferation index of > 20%
- Pineal anlage tumours
- Extremely rare neoplasms of the pineal region
- A variant of pineoblastoma due to
- Pineal localization
- Primitive neuroectodermal tumour-like component (small blue cells)
- Highly aggressive clinical course
- Consist of two components
- Neuroectoderm component
- Pineoblastoma-like sheets or nests of small blue round cells, neuronal ganglionic/glial differentiation, and/or melanin-containing epithelioid cells.
- Ectomesechymal component
- Rhabdomyoblasts, striated muscle, and/or cartilaginous islands
Immunophenotype
- Positive
- Same as pineocytoma
- SMARCB1: Positive nuclear expression is retained, enabling distinction from atypical teratoid/rhabdoid tumour
- Synaptophysin
- Variable
- Other neuronal markers (e.g. neurone-specific enolase, neurofilament protein and chromogranin-A)
Clinical presentation
- Compression of pineal s(x)
- Cerebral aqueduct:
- Obstruction HCP
- Papilledema
- H/A
- Ataxia
- Impaired vision
- N/V
- Brain stem
- Tectal plate compression: Parinaud syndrome
- Loss of upward gaze
- Cerebellum
- Dizziness
- Tremor
- Endocrine
- Diabetes insipidus
- Present with DI because it infiltrates the floor of 3rd ventricle affecting the pituitary
- Precocious puberty
- Acute clinical presentation can be due to tumour apoplectic
Radiological
General
- Large (>4cm) 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.
- Having a peripherally dispersed or "exploded" calcification (blasted calcification), similar to pineocytomas.
- In contrast, pineal germinomas tend to engulf pineal calcification.
MRI
- T1:
- Isointense to hypointense to adjacent brain
- T2
- Isointense to adjacent brain
- Areas of cyst formation or necrosis may be present
- T1+C (Gd):
- Enhancement is usually present in solid tumour components but can be absent
- DWI/ADC
- Restricted diffusion due to dense cellular packing/hypercellular nature
- ADC values are typically ~400-800 mm2/s
image
Treatment
Surgery
- Extent of resection (EOR) has been shown to influence patient survival, but the data is conflicting
- 5 year OS
- GTR : 84%
- Subtotal resection (STR) 53%
- The addition of radiotherapy to the STR group improved survival (5-year OS 64%),
- But this was still inferior to that achieved with GTR
- Biopsy: 29%,
- Residual disease size less than 1.5 cm3 has been shown to improve survival in PNETs in general
Radiotherapy
- Adjuvant CSI is administered to adults and older children with pineoblastoma (British Neuro-Oncology Society, 2011a). Its use in very young children is subject to debate due to the potential for neurocognitive deficits. Inferior outcomes have been reported in studies employing chemotherapy-only protocols, albeit at normal doses (Duffner et al., 1995; Hinkes et al., 2007).
- Stereotactic radiosurgery: In the absence of good quality data, stereotactic radiosurgery should not be used routinely (Balossier et al., 2015b).
Chemotherapy
- Chemotherapy is associated with improved outcome.
- In a meta-analysis (Tate et al., 2012):
- 5-year OS rates were
- 45% for surgery/radiotherapy
- 52% for surgery/radiotherapy/chemotherapy
- Platinum-based chemotherapy regimens appear to be the most effective and phase II trials employing these in conjunction with conventional radiotherapy have reported 5-year OS rates of 71–83% (Pizer et al., 2006; Hinkes et al., 2007).
- High-dose chemotherapy may be useful in very young children to delay radiotherapy.
- Chemotherapy regimens are poorly tolerated in adults and are not recommended.
Prognosis
- Poor
- CSF seeding is seen in 45% of cases
- Locally invasive
- 5 yr survival of variable 10%-81%
- Poor prognostic factor
- Disseminated disease at the time of diagnosis (as determined by cerebrospinal fluid examination and MRI of the spine)
- Young patient age
- Partial surgical resection
- Good prognosis
- Radiotherapy
- 5-year survival of patients with trilateral retinoblastoma syndrome has significantly increased in the past decade (from 6% to 44%),
- Due to better chemotherapy regimens and earlier detection of pineal disease
Differential diagnosis
- Other pineal parenchymal tumours: pineoblastoma tend to involve adjacent brain structure → this is different than other pineal tumours which are more benign
- 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)
- Embryonal carcinoma
- Choriocarcinoma
- Teratoma: may contain fat
- Pineal cyst
- Thin (<2 mm) wall
- 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
- Astrocytoma of the pineal gland
- Metastasis
- Medulloblastoma
- Imaging is very similar
- Histologically have similar small blue round cells (similar to other primitive neuroectodermal tumours of the CNS)
- Located in the vermis rather than pineal region but can be difficult to distinguish if very high in the vermis and very large
- Embryonal tumour with multi-layered rosettes (ETMR)
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