Embryonal tumours with multilayered rosettes (ETMR) are rare small round blue cell tumour of the central nervous system and are one of the most aggressive brain tumours usually encountered in children.
Previously embryonal tumours with multilayered rosettes (ETMR) where known as embryonal tumour with abundant neuropil and true rosettes (ETANTR). This term has, however, been 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 CNS PNET which have also been removed from the classification) 6. This has resulted due to the presence of amplification of the C19MC region on chromosome 19 in both CNS PNET and ETANTR, suggesting that these are the one entity with variable growth pattern 6.
ETMR occurs in children aged 4 and under, mostly in children under 2, and is more common in girls, unlike the other CNS embryonal tumours, in which boys are equally or more commonly affected.
The clinical features are determined by the location and extent of the tumor, with most located supratentorially, being less commonly seen in the infratentorial region and very rarely in the spinal cord.
Increased intracranial pressure, seizures, hemiparesis, cerebellar signs, cranial nerve palsies, and other neurologic deficits have all been reported.
Embryonal tumors with multilayered rosettes (ETMS) are characterized by undifferentiated neuroepithelial cells resembling those of classic CNS PNET, abundant well-differentiated neuropil, and ependymoblastic rosettes scattered throughout paucicellular regions of neoplastic neuropil. Unlike medulloblastoma, ETMR has no epithelial-like formation. Instead, it has a very characteristic ependymoblastic rosettes in both highly cellular as well as acellular areas.
Recently amplification of the C19MC region on chromosome 19 (19q13.42) has been identified as characteristic of these tumours, along with what historically had been termed CNS PNET. As a result both ETANTR and CNS PNET have been removed from the 2016 update of the WHO classification of CNS tumours and been replaced by the term embryonal tumor with multilayered rosettes (ETMR),
C19MC-altered (or ETMR-NOS if C19MC amplification is absent) 6.
The tumour appears as a large, demarcated, solid mass featuring patchy or no contrast enhancement, with surrounding edema, 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.
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.
The differential diagnosis varies according to the location of the tumour. The general imaging differential for the brain stem and infratentorial ETMR include:
- 1. Ferri Niguez B, Martínez-Lage JF, Almagro MJ et-al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR): a new distinctive variety of pediatric PNET: a case-based update. Childs Nerv Syst. 2010;26 (8): 1003-8. doi:10.1007/s00381-010-1179-x - Pubmed citation
- 2. Gessi M, Giangaspero F, Lauriola L et-al. Embryonal tumors with abundant neuropil and true rosettes: a distinctive CNS primitive neuroectodermal tumor. Am. J. Surg. Pathol. 2009;33 (2): 211-7. doi:10.1097/PAS.0b013e318186235b - Pubmed citation
- 3. Biegel JA, Allen CS, Kawasaki K et-al. Narrowing the critical region for a rhabdoid tumor locus in 22q11. Genes Chromosomes Cancer. 1996;16 (2): 94-105. doi:10.1002/(SICI)1098-2264(199606)16:2<94::AID-GCC3>3.0.CO;2-Y - Pubmed citation
- 4. Adamek D, Sofowora KD, Cwiklinska M et-al. Embryonal tumor with abundant neuropil and true rosettes: an autopsy case-based update and review of the literature. Childs Nerv Syst. 2013;29 (5): 849-54. doi:10.1007/s00381-013-2037-4 - Free text at pubmed - Pubmed citation
- 5. Nowak J, Seidel C, Pietsch T et-al. Ependymoblastoma of the brainstem: MRI findings and differential diagnosis. Pediatr Blood Cancer. 2014;61 (6): 1132-4. doi:10.1002/pbc.24915 - Pubmed citation
- 6. Louis DN, Perry A, Reifenberger G et-al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131 (6): 803-20. doi:10.1007/s00401-016-1545-1 - Pubmed citation