Embryonal tumours with multilayered rosettes (ETMR) are rare small round blue cell tumour of the central nervous system. They are one of the most aggressive brain tumours usually encountered in children and are WHO grade 4 tumours.
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Terminology
Previously embryonal tumours with multilayered rosettes (ETMR) were known as embryonal tumour with abundant neuropil and true rosettes (ETANTR). This term was, however, removed from the 2016 update to WHO classification of CNS tumours in favour of embryonal tumours with multilayered rosettes (ETMR) which incorporates not only ETANTR but also ependymoblastoma and primitive neuroectodermal tumour of the central nervous system (CNS PNET), which have also been removed 6.
The terminological changes have resulted from the presence of amplification of the C19MC microRNA cluster on chromosome 19 in both CNS PNET and ETANTR, suggesting that these are the one entity with variable growth pattern 6. Similarly, medulloepithelioma no longer appears as a distinct entity in the 5th Edition (2021) of WHO classification of CNS tumours, and is stated to be "not recommended" terminology 7.
Epidemiology
Embryonal tumour with multilayered rosettes occurs in children aged 4 years and under, mostly in children under 2 years, and is more common in girls, unlike the other CNS embryonal tumours, in which boys are equally or more commonly affected 7.
Clinical presentation
The clinical features are determined by the location and extent of the tumour. Most are supratentorial in location, a few are infratentorial, and they are very rarely encountered in the spinal cord.
Increased intracranial pressure, seizures, hemiparesis, cerebellar signs, cranial nerve palsies, and other neurologic deficits have all been reported.
Pathology
Microscopic appearance
Embryonal tumours with multilayered rosettes demonstrate one of three histological patterns:
embryonal tumour with abundant neuropil and true rosettes
ependymoblastoma
Typically these tumours are characterised by undifferentiated neuroepithelial cells resembling those of classic CNS PNET (historical), abundant well-differentiated neuropil, and ependymoblastic rosettes scattered throughout paucicellular regions of neoplastic neuropil. It has very characteristic ependymoblastic rosettes in both highly cellular as well as acellular areas.
When they have an ependymoblastoma pattern, they lack ganglion cells and a neuropil-like matrix.
Occasionally a distinct histological pattern is encountered that mimics a primitive neural tumour; this is known as a medulloepithelioma pattern.
Genetics
Recently amplification of the C19MC region on chromosome 19 (19q13.42) has been identified as characteristic of these tumours, present in approximately 90% of cases 7.
If C19MC amplification is absent then these tumours are known as ETMR-NOS even if other mutations (e.g. DICER1) are identified 6,7.
Radiographic features
MRI
The tumour appears as a large, demarcated, solid mass featuring patchy or no contrast enhancement, with surrounding oedema, often with significant mass effect. A minority of the reported cases have shown cystic components and microcalcifications.
T1: decreased intensity
T2: increased intensity
T1 C+ (Gd): patchy or no contrast enhancement
MR spectroscopy shows choline peak and a high ratio of choline/aspartate suggesting hypercellularity of the tumour.
Staging
Following maximal surgical resection, patients can be staged according to the extent of spread within and outside of the central nervous system 7,8.
M0: no evidence of subarachnoid or haematogenous metastasis
M1: microscopic tumour cells found in the cerebrospinal fluid
M2: gross nodular seeding demonstrated in the cerebellar/cerebral subarachnoid space or in the third or lateral ventricles
M3: gross nodular seeding in the spinal subarachnoid space
M4: metastasis outside the central nervous system
Treatment and prognosis
Current treatment options for ETMR include surgical resection, systemic chemotherapy and craniospinal radiation (when appropriate).
Unfortunately, the prognosis is dismal, with most recent articles reporting ~75% of cases have died within the median survival of 9 months.
Differential diagnosis
The differential diagnosis varies according to the location of the tumour. The general imaging differential for the brainstem and infratentorial embryonal tumours with multilayered rosettes include:
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