What types of tumors in the Central Nervous System (CNS) form rosettes?

CNS Tumors That Form Rosettes

The primary CNS tumors that form rosettes include embryonal tumor with multilayered rosettes (ETMR), medulloblastoma, ependymoma, and medulloepithelioma. 1

Embryonal Tumor with Multilayered Rosettes (ETMR)

ETMR is the most distinctive rosette-forming tumor and represents the consolidation of three previously separate entities: ependymoblastoma, medulloepithelioma, and embryonal tumor with abundant neuropil and true rosettes. 1

Key Characteristics:

• Aggressive tumors of infancy that arise throughout the CNS 1
• Feature multilayered ependymoblastic-like rosettes as the defining histologic hallmark 1
• Contain hypercellular sheets of undifferentiated cells, broad zones of neuropil, and scattered perivascular, Homer Wright, and multilayered ependymoblastic-like rosettes 2
• Unified by C19MC microRNA cluster amplification (or uncommonly, fusions) at chromosome 19q13.41 1, 3
• Any CNS embryonal tumor bearing a C19MC alteration should be assigned this diagnosis per WHO 2016 criteria 1

Diagnostic Approach:

• FISH assays readily identify C19MC alterations and should be utilized judiciously when ETMR enters the differential 1
• LIN28A expression by IHC is highly sensitive and specific, being overexpressed in almost all ETMR cases 1, 3
• However, only demonstration of the characteristic C19MC alteration guarantees diagnostic certainty, as LIN28A expression is not entirely specific 1

Clinical Features:

• Predominantly affects girls, unlike other CNS embryonal tumors 4
• Most often arises in cerebral cortex, with cerebellum and brainstem being less frequent sites 4
• Appears as large, demarcated, solid masses with patchy or no contrast enhancement on neuroimaging 4
• Extremely poor prognosis with median survival of 9 months 4

Medulloblastoma

Medulloblastomas can form Homer Wright rosettes, though this is not their most characteristic feature. 2, 4

Rosette Features:

• Homer Wright rosettes (neuroblastic rosettes) may be present 2, 4
• These consist of tumor cells arranged around a central tangle of neuropil without a true lumen 2, 4

Molecular Context:

• Isochromosome 17q is a typical molecular alteration in medulloblastomas 2
• Classified into four molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4 1, 3

Ependymoma

Ependymomas characteristically form perivascular pseudorosettes and true ependymal rosettes. 1

Rosette Types:

• Perivascular pseudorosettes: tumor cells radially arranged around blood vessels with intervening cell-free zones 1
• True ependymal rosettes: tumor cells arranged around a central lumen lined by cells with apical blebs 1

Clinical Features:

• Infratentorial ependymomas arise from the floor of the fourth ventricle 1
• Supratentorial ependymomas can be located in brain parenchyma rather than ventricles 1
• Appear as well-circumscribed mass lesions with heterogeneous appearance on MRI 1

Medulloepithelioma

Medulloepithelioma forms distinctive tubular and papillary structures resembling embryonic neural tube. 1

Classification Update:

• WHO 2016 included medulloepithelioma under ETMR when C19MC alterations are present 1
• Medulloepithelioma, NOS designation retained for lesions lacking demonstrable C19MC abnormalities but with otherwise typical pathology 1

Important Diagnostic Pitfalls

Common Caveats:

• Not all rosette-forming tumors are embryonal tumors—ependymomas can occur at any age and have better prognosis 1
• The presence of rosettes alone does not define ETMR—molecular confirmation of C19MC alteration is required for definitive diagnosis 1
• Chromosome 17 abnormalities (particularly isochromosome 17q) suggest medulloblastoma rather than ETMR 2
• ETMR disproportionately affects female infants, whereas most other embryonal tumors show no strong gender predilection 4

Workup Strategy:

• When rosettes are identified in a pediatric CNS tumor, immediately consider patient age and tumor location 1
• In infants with cerebral cortical masses showing rosettes, prioritize ETMR workup with C19MC FISH and LIN28A IHC 1
• In posterior fossa tumors with rosettes, consider medulloblastoma and ependymoma based on additional histologic features 1, 2
• Reserve fresh-frozen tissue when possible for molecular profiling, though FFPE tissue scrolls are generally adequate 1