Contributed by Thomas J. Cummings, MD, Robert H. Ebert II, Ph.D., James Provenzale, MD, Roger E. McLendon, MDDIAGNOSIS: DYSPLASTIC GANGLIOCYTOMA OF THE CEREBELLUM (LHERMITTE-DUCLOS DISEASE, LDD)
DISCUSSION:
Lhermitte-Duclos disease was first described in 1920 and is quite rare with fewer than 100 cases having been previously reported (9). This entity has also been described in the literature under the names of Purkinjeoma, granular cell hypertrophy of the cerebellum, hamartoma of the cerebellum, dysplastic gangliocytoma, ganglioneuroma, and gangliomatosis of the cerebellum. Patients tend to be young adults and may present with signs of cerebellar dysfunction or increased intracranial pressure secondary to obstructive hydrocephalus, yet cerebellar signs are minimal or absent in up to one half of those with the lesion (8).
The characteristic MR pattern is a mass lesion within the cerebellar hemisphere exhibiting a striated pattern that is hypointense on T1-weighted images, hyperintense on T2-weighted images, and is non-enhancing with contrast (5,7). Histologically, the hypointense T1 and hyperintense T2 densities correspond to the inner portion of the diseased folia consisting of the deep molecular layer, the internal granular layer, and the white matter (5). The outer molecular layer of the folia remains isointense on MR studies. Although some computed tomographic (CT) scans demonstrate the hypointense-isointense banding pattern, inherent posterior fossa artifact makes MR the imaging modality of choice (5).
Microscopically, the presence of enlarged, circumscribed cerebellar folia containing large ganglion cells in the granular cell layer and prominent myelinated tracts in the outer molecular layer is typical of this disorder (2). Histologically, the severity of the lesion may vary from a recognizable granular cell layer containing occasional large dysplastic neuronal cell bodies, to an unrecognizable granular layer occupied by a population of large nerve cell bodies between the molecular layer and internal white matter (2). The latter, more severe stage of the disease, best describes the current case. Immunohistochemically, the hypertrophic granule cells express neurofilament (NF) protein in a manner similar to Purkinje cells, and it has been postulated that the increased expression of NF proteins by the cerebellar granule cells may account for their hypertrophy and subsequent axonal enlargement leading to myelination within the molecular layer of the cerebellar cortex (13). Although the pathogenesis of this lesion is still unclear, it likely represents a congenital, hamartomatous lesion rather than a true neoplasm. This is supported by the low proliferative index seen here and elsewhere, although recurrent lesions have been reported (3).
LDD is associated with Cowden's syndrome (CS), a rare autosomal dominant familial cancer syndrome with multiple manifestations including trichilemmomas, diverse hamartomas, intestinal polyposis, palmoplantar keratoses, oral papillomatosis, and an increased predisposition to breast cancer and thyroid tumors (1,6). The pathologic criteria for the diagnosis of CS have been compiled from an international consortium (11). In approximately 40% of documented cases of LDD, CS can be diagnosed, and in 60% of cases LDD appears to occur sporadically (9). The gene for CS has been localized to chromosome 10q22-23 (11). In some LDD patients germline missense mutations have been identified in the PTEN candidate tumor suppressor gene at this locus (6,12). However, a definitive relationship between CS, LDD, and PTEN mutations remains to be established (9,10). The patient in the current case warrants close clinical follow-up for stigmata of CS, since most of the mucocutaneous lesions become apparent by 20 years of age (4).
REFERENCES
Contributed by Thomas J. Cummings, MD, Robert H. Ebert II, Ph.D., James Provenzale, MD, Roger E. McLendon, MD
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