Magnetic resonance characteristics of adult-onset Lhermitte-Duclos disease: An indicator for active cancer surveillance?

Abstract

Lhermitte-Duclos disease (LDD) is a rare, non-cancerous entity characterized by enlarged, abnormally developed cerebellar folia containing dysplastic cells. Symptomatic LDD is commonly observed in adults (adult-onset LDD, aLDD) as an isolated condition or associated with Cowden's disease (CD). The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and the underlying pathological findings in 7 cases of aLDD, with emphasis on the association with CD and the need for active cancer surveillance once the diagnosis of LDD is confirmed. The MRI findings along with the clinical and histopathological data collected from 7 patients with aLDD were retrospectively reviewed. The diagnosis of CD was based on a range of clinical characteristics, according to the International Cowden Consortium Criteria. A thorough review of the published data was conducted and our results indicated that all 7 cases shared similar MRI characteristics, whether the aLDD was sporadic (2 cases) or associated with CD (5 cases), including a highly typical non-enhancing striated MRI appearance of thickened folia, consisting of alternating bands on T1- and T2-weighted images. On gross examination, the involved cerebellar folia were distorted and enlarged, whereas the histopathological examination revealed that the molecular layer was widened and occupied by abnormal ganglion cells. Moreover, a reduction in the number or absence of the Purkinje cells and hypertrophy of the granular cell layer were observed. Our findings were consistent with the diagnosis of LDD. Variable levels of vacuolization of the white matter and the molecular layer were observed in all the cases. Notably, CD34 immunohistochemical analysis revealed the presence of angiogenesis within the lesions. aLDD associated with CD exhibited no pathological or immunohistochemical characteristics that were distinct from those of isolated aLDD. Of the 7 cases of aLDD, 5 presented with symptoms suggestive of CD, which is a syndrome associated with a high risk of multiple benign and malignant neoplasms. In conclusion, aLDD exhibits characteristic MRI and histopathological findings and displays a strong association with CD. Therefore, we recommend that the MRI diagnosis of aLDD triggers active cancer surveillance and preventive care.

Keywords: Cowden’s disease; Lhermitte-Duclos disease; dysplastic cerebellar gangliocytoma; magnetic resonance imaging; pathology.

Figure 1.

Typical MR images of aLDD in a 23-year-old man. (A) Axial T2- (B) T1- and (C) sagittal T1-weighted MR images of the brain display a highly characteristic non-enhancing striated appearance of aLDD. The fourth ventricle (arrow) is compressed and the vermis is involved. (D) Sagittal contrast-enhanced T1-weighted MR image reveals no enhancement following injection of the contrast agent Gd-DTPA. MR, magnetic resonance; aLDD, adult-onset Lhermitte-Duclos disease.

Figure 2.

MRI of aLDD of the left cerebellar hemisphere in a 36-year-old man shows a characteristic striated pattern. (A) Axial T2-weighted MR image shows a predominantly hyperintense mass with alternating bands of hyper- and isointensity compared to the contralateral normal tissues. A slight mass effect is observed, with no obvious peritumoral edema. (B) On the T1-weighted MR image, the striated appearance presents with an alteration of iso- and hypointense stripes. Moderate hydrocephalus (arrows) and tonsillar herniation (arrow) are observed on (C) coronal T2- and (D) sagittal T1-weighted MR images, respectively. MRI, magnetic resonance imaging; aLDD, adult-onset Lhermitte-Duclos disease.

Figure 3.

Diffusion-weighted imaging shows a mildly increased diffusion of water in a 46-year-old woman with adult-onset Lhermitte-Duclos disease. The lesion shows a mixed signal on axial isotropic diffusion-weighted imaging [(A) b=0 sec/mm²; (B) b=1,000 sec/mm²] and a mildly increased signal intensity compared to that of the normal brain parenchyma on the (C) corresponding apparent diffusion coefficient map, reflecting a mildly increased water diffusivity within the lesion.

Figure 4.

Histopathological examination of the resected aLDD specimens. (A) Photomicrograph [hematoxylin and eosin (H&E) stain, original magnification, ×40] shows widening of the molecular layer, absence of the Purkinje cell layer and hyperplasia of the granular cell layer. (B) Large myelinated fibers are present in the molecular layer. The large and bizarre cells are dysplastic ganglion cells with a prominent nucleus and hyperchromatic nucleoli (arrows) replacing the granular cell layer (H&E, original magnification, ×100). (C) No mitosis or pleomorphism was observed in these cell populations. These characteristics are considered to be diagnostic of LDD. Vacuolization of variable levels and varying size is frequently encountered in the majority of cases and is mainly located in the white matter and in the molecular layer (H&E, original magnification, ×100). aLDD, adult-onset Lhermitte-Duclos disease.

Figure 5.

Immunohistochemical characteristics of adult-onset Lhermitte-Duclos disease. The enlarged cells variably expressed (A) synaptophysin and (B) Neu-N, indicative of a neuronal origin. The staining for the proliferation marker Ki-67 was negative (data not shown). (C) A relatively diffuse immunore-activity of CD34 was observed within the lesions, as evaluated by CD34 immunohistochemistry. (D) Ectatic vessels within the lesion.