Newly Recognized Genetic Tumor Syndromes of the CNS in the 5th WHO Classification: Imaging Overview with Genetic Updates

ELP1-related medulloblastomas in siblings. A 6-year-old boy (sibling A) with MR imaging revealing a heterogeneously T2 hyperintense (A, axial T2 TSE) mass with cystic changes and heterogeneous enhancement (B, coronal postcontrast). Histopathology with immunohistochemistry revealed a large-cell anaplastic-pattern WHO grade 4, SHH-activated (TP53 wild-type) medulloblastoma. The patient’s older brother, an 18-year-old boy (sibling B), was diagnosed with a similar tumor 7 years later. MR imaging revealed a right lateral cerebellar T2 hyperintense mass (C, axial T2 TSE) with solid contrast enhancement (D, coronal postcontrast). Pathology revealed an SHH-activated (TP53 wild-type) medulloblastoma with desmoplastic/nodular morphology. A neuro-oncology genetic panel (utilizing NGS technique) in both siblings showed biallelic inactivation of ELP1 due to somatic loss of chromosome arm 9q along with homozygous deletion of the tumor-suppressor gene PTCH1, confirming an ELP1 germline mutation. Both siblings remain disease-free (9 years postsurgery for sibling A, and 1 year for sibling B) (Online Supplemental Data).

Rhabdoid intracranial and spinal meningiomas with loss of BAP1 expression. Left lateral cerebellomedullary cistern enhancing mass (A, axial postcontrast T1, white arrow) in a 36-year-old man, extending into the hypoglossal canal, revealing atypical meningioma (CNS WHO grade 2) on histology, with rhabdoid features (B) and loss of BAP1 expression on immunohistochemistry (Online Supplemental Data). Coronal (C) and axial (D) contrast-enhanced MR images in a different patient depict an extramedullary cervical mass extending along the left neural foramen (arrows). Histopathology (not shown) revealed rhabdoid meningioma with loss of BAP1 expression.

DICER1-mutant intracranial sarcoma. Sagittal T2 (A) and postcontrast (B) MR images in a 16-year-old adolescent girl reveal a dural-based left parasagittal T2-hyperintense enhancing mass, presumed to be a meningioma on imaging. Histopathology, however, revealed spindle and pleomorphic cells (C), and immunohistochemistry tests were negative for GFAP, OLIG2, SSTR2 (D), STAT6, S-100, and SOX10, arguing against glial, meningothelial, or melanocytic tumors. A Somatic Disease/Germline Comparator Exome sequencing panel revealed a pathogenic germline DICER1 mutation. Overall, the histomorphologic and immunophenotypic findings supported a sarcomatoid neoplasm. The additional presence of pathogenic DICER1 mutations was diagnostic of primary intracranial sarcoma, DICER1-mutant. Because the prognosis for patients with DICER1-mutant primary intracranial sarcoma remains unknown due to limited clinical data, a CNS WHO grade designation was not rendered, according to the 2021 WHO Classification of Tumors of the Central Nervous System.

MMNST in a 26-year-old woman with CNC. Coronal MR images (A and B) reveal a mass along the left S1–S2 neural foramen with intrinsic T1-hyperintense content (A, T1-weighted, non-fat-saturated, arrow) with peripheral enhancement and a central nonenhancing component (B, postcontrast with fat saturation, arrow). Note marked expansion of the neural foramen and erosive osseous changes along the inferior edge on coronal CT (C, arrow). Histopathology reveals a spindle cell (D, white arrow) neoplasm with psammomatous bodies (D, black arrow). Immunohistochemistry was positive for SOX10, S-100, and MelanA, confirming the diagnosis of MMNST. Neoplastic cells showed complete loss of PRKAR1A, confirming an association with CNC (Online Supplemental Data).

HNPGs in 2 different patients, one with SDH mutation (patient A) and the other with normal SDH expression (patient B). Patient A has familial paraganglioma syndrome with multiple HNPGs and a left adrenal phaeochromocytoma (A, arrowheads) on a ⁶⁸Ga-DOTATATE PET scan, with complete loss of SDH expression on immunohistochemistry (C). A solitary HNPG along the right carotid artery is noted on a ⁶⁸Ga-DOTATATE PET scan in patient B (B, arrow) with normal SDH expression on pathology (D).