The distribution of males and females is equal; LDD may present at any age (from neonates to the elderly), but many are diagnosed in the third to fourth decades of life, with very few pediatric cases reported in the literature.

It can occur both sporadically and in familial form. Cowden syndrome is associated with LDD in approximately 40 % of patients.

Patients present with symptoms of a slow-growing cerebellar mass: headaches, nausea, vomiting, ataxia, diplopia, gait disturbances, and cranial nerve dysfunctions. Usually presentation is not acute, with long-standing history of poor localized neurological symptoms. The duration of symptoms ranges from 1 to 3 years. Some patients, in which the cerebellar lesion was not recognized, have been misdiagnosed having chronic tonsillar herniation (Chiari malformation) and syringomyelia and treated with foramen magnum decompression [13]. Occasionally, the patients may even have sudden neurological deterioration due to acute or decompensated chronic hydrocephalus. In children, symptoms or signs such as developmental delay, hemiparesis, and complex ocular movement disturbance have been reported [14]. Orthostatic hypotension and acute subarachnoid hemorrhage have been described among atypical clinical appearances [15].

Macroscopically LDD is characterized by the presence of thickened and distorted folia. Microscopically, histological architecture of the cerebellar cortex is reproduced within the lesion in a disorganized fashion. The normal cerebellar cortex consists of three constant layers: the molecular layer (outermost), the Purkinje layer, and the granular layer (innermost). In dysplastic gangliocytoma, an abnormal population of large neurons is present in the granular layer, and aberrant myelination is seen in the molecular layer. This is associated with a generalized thickening of the cerebellar cortex and scarcity or absence of the central white matter. The granular layer is thickened because of hypertrophy of granule cells; the molecular layer is thickened by hyperplasia and hypertrophy of the myelinated fibers extending from abnormal cells in the granular layer. The Purkinje cells are scarce [15, 16]. The lesion gradually blends into normal cerebellar tissue making the complete surgical removal difficult.

At immunohistochemistry, the dysplastic neurons are positive for neuronal markers (synaptophysin, neurofilaments) and usually show complete or partial loss of PTEN expression accompanied by elevated phosphorylated Akt. No evidence of proliferation is usually shown. This led to the hypothesis that growth of tumor should be produced by increasing size of the abnormal cells rather than multiplication of cells [17]. Malignant transformation of residual or recurrent lesions has never been observed.

Numerous associated abnormalities have been described in patients with LDD. These include megalencephaly, microgyria, spongioblastomas, peritheliomas, hydromyelia, partial gigantism, hemangiomas, polydactyly, macroglossia, and leontiasis ossea [4].

Neuroimaging, showing the presence of enlarged and disorganized cerebellar folia, is so typical that is usually diagnostic for LLD [18]. Magnetic resonance imaging is the imaging modality of choice; however, the lesion can be recognized also on CT scan. It appears on CT scan as a cerebellar mass of mixed density with iso- and hypodense regions, occasionally with scattered or laminar calcification.

This striated or layered appearance (“tiger-striped pattern”) is better appreciable on MRI, especially on T2-weighted images (Fig. 54.2), in which the lesions present with a well-circumscribed high intensity and a striated pattern with isointense bands within these hyperintense areas [19]. Kulkanstrakorn et al. [20] reported that the high signal intensity band corresponded to the inner molecular layer and the granular cell layer. The outer portion of the folia consisting of the outer molecular layer and leptomeninges within effaced sulci created the band isointense to cerebellar grey matter. On T1-weighted images, the striations have been described as hypointense and isointense, respectively, to the cerebellar gray matter. On the short TI inversion recovery (STIR) sequence and the turbo inversion recovery magnitude (TIRM) sequence, the morphologic features of the LDD may be clearly demonstrated [21]. The lesions may demonstrate mass effect on the adjacent cerebellar parenchyma and fourth ventricle with hydrocephalus and tonsillar herniation (Figs. 54.2, 54.3, and 54.4). Lesion usually does not enhance following gadolinium (Fig. 54.2), even if proliferating veins within the lesion, and the surrounding leptomeninges, can do. The disease involves one hemisphere, but it occasionally extends to the vermis or to the contralateral hemisphere (Fig. 54.4).

Perfusion-weighted imaging demonstrates elevated regional cerebral blood volume and regional cerebral blood flow rCBF. On diffusion-weighted images, there may be variable restriction of diffusion depending on contributions from the inner layer and the thick outer molecular layer with large dysplastic neurons, the loss of Purkinje cells, and thinning of medullary white matter. Apparent diffusion coefficient (ADC) mapping may show no disturbance of water diffusion [21]. As compared with the other sequence, the ADC mapping may be helpful in postoperative control, because it delineates tumor from surgical resection margins (Fig. 54.2) [21–23].

Functional imaging (positron emission tomography and magnetic resonance spectroscopy) has also been recently used in diagnosis. F18-fluoro-D-glucose reveals hypermetabolism of the lesion. The reasons for this high uptake, which mimic a malignant tumor, may be increased in overall cell metabolism, increased in cell density, and isolated upregulation in enzyme activity of hexokinase within the lesion [13, 24].

The appearance of LDD on magnetic resonance spectroscopy is also variable. The most frequent findings are elevated level of lactate, near-normal values of Cho/Cr, and decreased ratios in N-acetylaspartate/creatine (NAA/Cr) and NAA/choline (Cho), secondary to a decrease in the concentration of NAA. These can be attributed to a lack of neuronal architecture (a hallmark of hamartoma) and/or the presence of embryonic neural tissue, which fails to express NAA (Fig. 54.3d–e) [25]. The near-normal values of Cho/Cr ratios in LDD indicate a lack of cell turnover or proliferation (increases in Cho levels are associated with enhanced membrane turnover). These results are in favor of “benign” hamartoma rather than a tumor. In other cerebral neoplasia, a decrease in NAA or NAA/Cr ratio is associated with an increase in Cho or Cho/Cr ratio. Lactate, normally undetectable in the brain, accumulates in cysts, necrotic tissue, or within active tumors because of the high rate of glycolysis. Combined with the histopathologic findings of no necrotic areas within the LDD lesion, the elevated lactate levels do not represent cell death, but an abnormal high glucose metabolism [25]. Therefore, LDD has some characteristics of tumors such as decreased NAA and increased lactate, but not increased levels of Cho [26].