A 7-year-old boy presents with headache and vomiting. MRI reveals a midline cerebellar mass with hydrocephalus. Histology shows sheets of small round blue cells with high nuclear-to-cytoplasmic ratio, brisk mitotic activity, and Homer Wright rosettes. Which therapy targets the pathway most commonly dysregulated in this tumor?

• A VEGF inhibitor (bevacizumab)
• B EGFR tyrosine kinase inhibitor
• C Sonic Hedgehog pathway inhibitor (vismodegib) ✓
• D mTOR inhibitor (everolimus)

Explanation

This is medulloblastoma, the most common malignant brain tumor in children, arising in the cerebellar vermis and prone to CSF dissemination. Homer Wright rosettes (tumor cells surrounding a central fibrillary core) are a classic but inconsistent feature. Molecular classification has identified distinct subgroups; the SHH (Sonic Hedgehog) pathway subgroup is the most common and is targeted by smoothened inhibitors like vismodegib. WNT pathway activation characterizes another favorable subgroup.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.