Daily Radiology Case

Explanation

Neurofibromatosis Type 2 (NF2) is an autosomal dominant tumor suppressor syndrome caused by loss-of-function mutations in the NF2 gene on chromosome 22q12, which encodes merlin (also called schwannomin). Merlin normally suppresses proliferation by mediating contact inhibition; its loss leads to uncontrolled Schwann cell and meningeal cell growth. The hallmark finding is bilateral vestibular schwannomas, which alone satisfy diagnostic criteria and are virtually pathognomonic. Associated tumors include meningiomas (often multiple), spinal ependymomas, and other peripheral schwannomas. Ocular findings include posterior subcapsular cataracts and epiretinal membranes. On MRI, vestibular schwannomas appear as enhancing CPA masses with the "ice cream cone" sign on coronal imaging — the cone representing the tumor in the internal auditory canal and the scoop representing the CPA component. Management options include surgical resection, stereotactic radiosurgery (Gamma Knife), and bevacizumab, which has shown benefit in reducing tumor size and improving hearing in NF2 patients by targeting VEGF-driven tumor vascularity. NF2 is distinguished from NF1 (chromosome 17q11, neurofibromin protein), which presents with café-au-lait spots, axillary freckling, Lisch nodules, optic gliomas, and neurofibromas — but not bilateral vestibular schwannomas. The mnemonic is: NF1 = "one" peripheral finding on the skin; NF2 = "two" ears (bilateral acoustic neuromas).

Source: rID:79097

Hints

• A 24-year-old woman presents to her primary care physician reporting progressive bilateral hearing loss and tinnitus that has developed over the past 18 months, which she initially attributed to frequent headphone use.
• On physical examination, she is found to have bilateral sensorineural hearing loss confirmed on audiometry, along with early posterior subcapsular cataracts noted on ophthalmologic referral.
• MRI of the internal auditory canals with gadolinium reveals bilateral enhancing masses at the cerebellopontine angle, each arising from the vestibulocochlear nerve and displaying the classic "ice cream cone" appearance on coronal sequences.
• Further MRI of the entire neuraxis is obtained and demonstrates additional intradural extramedullary spinal masses at multiple levels as well as a falx meningioma, raising concern for a multifocal tumor syndrome.
• The patient's mother underwent surgery in her 30s for a brain tumor and is now deaf bilaterally, and genetic testing of the patient reveals a pathogenic mutation in the NF2 gene on chromosome 22q12, which encodes the tumor suppressor protein merlin.
• Formal diagnostic criteria are met: the patient has bilateral vestibular schwannomas, which alone are sufficient for diagnosis, and the genetic counselor explains that merlin loss disrupts contact-dependent inhibition of cell proliferation by failing to link the cell membrane cytoskeleton to surface glycoproteins.