Lhermitte-Duclos Disease: Circumscribed Cerebellar Cortical Overgrowth With Granule Cell Hypertrophy and Altered PTEN/mTOR Signaling

摘要

A case of recurrent Lhermitte-Duclos disease is presented. Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) is a rare disorder of localized brain overgrowth that most often presents in middle-aged adults as a tumor-like cerebellar cortical mass. Symptoms are typically due to posterior fossa compressive effects and fourth ventricular obstruction. Neuroimaging features can be distinctive, with an alternating isointense and hyperintense lamination pattern ("tiger striping") of grossly enlarged cerebellar folia by magnetic resonance imaging. The lesion is characterized histologically by marked hypertrophy of the cell bodies and axons of granule neurons, which send axons into the molecular layer as "parallel fibers." Secondary myelination of parallel fibers (normally unmyelinated) adds to the mass effect of the lesion. Lhermitte-Duclos disease is strongly associated with the familial hamartoma-neoplasia syndrome (Cowden disease), and both conditions are linked to alterations of the PTEN/AKT/mTOR pathway. Current therapy for this essentially benign process is gross total excision, although the lesion may recur. Patients with Lhermitte-Duclos disease should be evaluated for Cowden disease because of the increased risk of some systemic malignancies (breast, endometrium, thyroid, kidney). Targeting the PTEN/ AKT/mTOR pathway may provide novel therapies in the future.