Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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February 11, 2021
Meningeal Melanocytosis
- Background:
- Primary melanocytic tumors of the CNS represent a spectrum of rare benign and malignant neoplasms. They arise from melanocytes of the leptomeninges which normally exist and are most concentrated at the base of the brain and ventral cervical spinal cord.
- Diffuse leptomeningeal melanocytosis is characterized by extensive proliferation of histologically benign melanocytes involving the supra- and infratentorial meninges, particularly the cerebellum, pons, medulla, and temporal lobes.
- There are known associations with neurocutaneous melanosis, neurofibromatosis type 1, Sturge-Weber syndrome, and Dandy-Walker syndrome.
- Clinical Presentation:
- May be present at birth or develop later in life
- Clinical features include stillbirth, intracranial hypertension, hydrocephalus, seizure, ataxia, cranial nerve palsies, and neuropsychiatric symptoms.
- Clinical deterioration is usually rapid if malignant transformation occurs (leptomeningeal melanoma or melanomatosis).
- Key Diagnostic Features:
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Radiologic
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MRI is superior to CT for evaluation and shows nonspecific diffuse thickening of the leptomeninges with abnormal enhancement on the postcontrast images.
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On precontrast T1-weighted MR images, the regions of melanocytosis may be isointense or hyperintense from T1 shortening due to the indirect paramagnetic properties of melanin as a metal scavenger.
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FLAIR images show variable leptomeningeal hyperintensity. Disease can be conspicuous on postcontrast FLAIR sequences, which studies have shown have higher sensitivity than postcontrast T1 for leptomeningeal enhancement.
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Degeneration into malignant melanoma is suggested by progressive growth, surrounding vasogenic edema, mass effect, or development of central necrosis.
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Pathologic
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Gross examination shows thickening and darkening overlying the affected brain surfaces.
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Microscopically, atypical polygonal cells with cytoplasmic pigment are seen involving the leptomeninges, often with extension into the perivascular spaces, however, without frank invasion into the CNS parenchyma. A diffuse growth pattern helps to distinguish between other lesions with pigmentation, which are more circumscribed (melanocytoma and metastatic melanoma).
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- Differential Diagnoses:
- The below meningitides (infectious, neoplastic, and granulomatous) overall have a similar imaging appearance with leptomeningeal thickening and enhancement, which is often more nodular or masslike when compared with melanocytosis. Unless complicated by hemorrhage, the below entities do not display intrinsic T1 hyperintensity, which can be seen with melanocytosis. Clinical history is critical in diagnosis.
- Meningeal carcinomatosis: The patient will likely have a known history of primary malignancy, frequently with additional discrete lesions in brain parenchyma, the spine, and/or the skull. Breast cancer, lung cancer, and melanoma are the most common primary tumors that result in leptomeningeal metastases.
- Meningitis (tuberculous/fungal, pyogenic): Typically basal cistern predominance with marked thickening/enhancement and nodular conglomerates formed by tuberculomas. Basal predominance is much less common in the HIV population. Positive CSF cultures are often found by lumbar puncture. Known complications could be evident such as subdural empyema, ventriculitis, or abscess. TB meningitis may also demonstrate parenchymal tuberculomas and is often complicated by ischemia. It is important to look for extracerebral manifestations of TB (cavitary lung lesions).
- Neurosarcoid: Preferentially involves basal cisterns and optic chiasm. Most cases occur with pulmonary/systemic sarcoid (hilar adenopathy, perilymphatic pulmonary nodules, later upper lobe fibrosis). May be associated with a corkscrew appearance of deep medullary veins in about one-third of patients.
- Lymphomatous meningitis: Secondary CNS involvement in the setting of known systemic lymphoma (typically B-cell). May present as single or multiple dural enhancing masses with or without leptomeningeal disease and variable skull involvement. May see cranial nerve enhancement. Primary leptomeningeal lymphoma in the absence of systemic disease is rare.
- Treatment:
- Recent discoveries with respect to molecular characteristics of these neoplasms have sparked subsequent trials of targeted therapeutic options. In children, oncogenic mutations in NRAS (chromosome 1p13) are frequent in both circumscribed and diffuse leptomeningeal melanocytic neoplasms, and somatic mutation in NRAS early during embryogenesis is the underlying pathogenesis of neurocutaneous melanocytosis. Based on these discoveries and knowledge that NRAS activates many downstream pathways, there has been great interest in using a combination of protein inhibitors downstream of the NRAS cascade such as MEK, ERK, and PI3K/mTOR.
- This particular patient had a right frontal craniotomy and open brain/dural biopsy for diagnosis with pericranial flap repair. Following diagnosis, the patient received a ventriculoperitoneal shunt for ventriculomegaly followed by steroids and trametinib (MEK inhibitor).
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