Journal of the Neurological Sciences 290 (2010) 138–141
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Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
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An unusual cause of posterior fossa mass: Lhermitte-Duclos disease Begül Yağcı-Küpeli a,⁎, Kader K. Oguz b, M. Asım Bilen c, Bilgehan Yalçın a, Nejat Akalan d, Münevver Büyükpamukçu a a
Department of Pediatric Oncology, Hacettepe University Institute of Oncology, 06100 Ankara, Turkey Department of Radiology, Hacettepe University, 06100 Ankara, Turkey Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey d Department of Neurosurgery, Hacettepe University, 06100 Ankara, Turkey b c
a r t i c l e
i n f o
Article history: Received 22 July 2009 Received in revised form 23 October 2009 Accepted 8 December 2009 Available online 8 January 2010 Keywords: Lhermitte-Duclos disease Adolescent Magnetic resonance imaging Posterior fossa
a b s t r a c t Lhermitte-Duclos disease (LDD) (dysplastic cerebellar gangliocytoma) is a rare disorder of unknown pathogenesis, presenting with signs and symptoms resulting from obstruction of cerebrospinal fluid flow and mass effect in the posterior fossa. Magnetic resonance imaging is the diagnostic modality of choice allowing preoperative diagnosis with characteristic findings. Surgery is the choice of treatment. The typical histopathological findings of LDD are characterized by widening of the molecular layer, absence of the Purkinje cell layer and hypertrophy in the granule cell layer. Herein we report an adolescent girl with LDD diagnosed preoperatively by the conventional and advanced MR techniques. © 2010 Elsevier B.V. All rights reserved.
1. Introduction
2. Case report
Lhermitte-Duclos disease (LDD) is a rare clinical entity, defined as dysplastic cerebellar gangliocytoma and categorized as a WHO grade 1 tumor [1,2]. Its pathological features are unique with global hypertrophy of the cerebellum, coarse gyri, and the typical “inverted cortex” pattern [3]. The cases usually present with progressive mass effect in the posterior fossa accompanied with cerebellar dysfunction, non-communicating hydrocephalus and signs of increased intracranial pressure [4]. The disorder is commonly seen in the third or fourth decade. Few pediatric patients are reported in literature. Nevertheless, LDD was reported even in the newborn and elderly in autopsy series [1]. Magnetic resonance (MR) imaging is the appropriate technique allowing preoperative diagnosis with the characteristic striated pattern of exaggerated folia appearance on T2-weighted images [5,6]. The typical histopathologic findings are massive replacement and expansion of the internal granular cell layer by large neurons with vesicular nuclei and prominent nucleoli [7–9]. Although this disease has been known for nearly a century, the pathogenesis is still unclear. Here, we present an adolescent girl with LDD presenting with severe headache and document imaging abnormalities in conventional and advanced MR techniques including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and single-voxel proton (1H) MR spectroscopy study.
A 17-year-old female was referred to our department with severe headache lasting for one week. There were no other neurologic or systemic symptoms. No hamartomatous lesions were found on the other sides of the body. Thorough examination of the skin, thyroid and breasts was normal. An abdominal ultrasound was performed in order to evaluate the intraabdominal organs and found to be normal. The family history was negative for Cowden syndrome. On non-enhanced CT imaging there was a mildly hypodense mass with laminar pattern of calcification (Fig.1A). The mass compressing the fourth ventricle was of T2-hyperintense and T1-hypointense and showed a striated appearance simulating exaggerated folia which is characteristic finding of dysplastic gangliocytoma (Lhermitte-Duclos disease) (Fig.1B). There was a very subtle enhancement along the folia on postcontrast T1-weighted (W) imaging (Fig.1C).The right cerebellar tonsil was herniated caudally into the cervical spine (not shown). The third and lateral ventricles had enlarged with a periventricular interstitial edema (Fig.1D). Advanced imaging techniques applied were DWI, PWI and proton (1H) MR spectroscopy study. On DWI MR imaging, the mass had approximate values of the apparent diffusion coefficient (ADC) (ADClesion 0.73 × 10− 3 mm2/s and ADCnormal left cerebellar parenchyma 0.70 × 10− 3 mm2/s) (Fig.2A). PWI (echo-planar gradient-echo imaging; TR/TE:1980/59, matrix:128 × 128) following bolus administration of intravenous gadolinium (20 cc Meglumin gadolerat [DotaremR 5 cc/sn]), was obtained. Elevated relative cerebral blood volume (rCBV) (Fig.2B) was observed in the lesion with a ratio of rCBV (CBVRight/CBVLeft) = 1762.
⁎ Corresponding author. Tel.: + 90 312 3052990 91; fax: + 90 312 3107018. E-mail address:
[email protected] (B. Yağcı-Küpeli). 0022-510X/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.12.010
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Fig. 1. Non-enhanced axial CT scan (A) shows a right cerebellar mass with laminar pattern of calcification compressing the fourth ventricle. The mass is hyperintense relative to cortices and has a laminated pattern giving the characteristic feature of Lhermitte-Duclos disease on axial T2-weighted (W) imaging (B). There is a very subtle enhancement along the folia on postcontrast axial T1W imaging (C). Due to mass effect on the fourth ventricle, triventricle hydrocephalus with a periventricular edema is seen on axial T2W imaging (D).
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A single-voxel proton ( H) MR spectroscopy (MRS) imaging with an intermediate time-echo (TR:1500 ms,TE:135 ms, number of averages:192) revealed close or mildly elevated N-acetyl-aspartate (NAA)/Creatine (Cr) (1.37), moderately decreased choline (cho)/Cr (0.47) in the lesion compared with the normal left cerebellar parenchyma (NAA/Cr:1, 18, Cho/Cr:0.89) (Fig.2C and D). More than 90% of the mass was resected without ventriculostomy placement, dura was primarily closed and bone flap was replaced in the operation. The histopathological examination revealed thickening of the cerebellar molecular layer, myelinized axons, and dysplastic neurons which showed positive staining for NeuN, synaptophysin, and focal CD-34. After surgery, her headache disappeared dramatically. Postoperative MRI of the cranium showed a residual cerebellar lesion. Postoperative course was uneventful, her neurologic functions were normal and she was discharged at the 4th day after the surgery. She has been under routine follow-up for 2 years and 6 months. On the last control, the physical examination findings, abdominal ultrasound and MRI were normal except for the encephalomalasic changes in the resection cavity.
3. Discussion Lhermitte-Duclos disease is an uncommon hamartomatous benign overgrowth of the cerebellar cortex causing mass effect in posterior fossa. Despite the controversies about its nature, the association of dysplastic cerebellar gangliocytoma with multiple hamartoma-neoplasia complex (Cowden syndrome) favors a hamartomatous rather than a neoplastic origin [4]. Besides, the lesion is classified as a WHO grade 1 tumor [1,2]. It can occur both sporadically and in familial form. In some series, Cowden syndrome was associated with LDD in approximately 40% of patients. Cowden syndrome is an autosomal dominant condition characterized by multiple hamartomas and high risk of thyroid, endometrial and breast malignancies [10]. Due to their hamartomatous nature, LDD and Cowden's syndrome are believed to be a new phakomatosis by some authors [11]. Because of this, periodic breast, thyroid and endometrial examinations for LDD patients are suggested. Lately, the PTEN/MMAC1 (a tumor suppressor gene) mutation was shown in patients with LDD and Cowden's syndrome [12–14]. It is thought
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Fig. 2. There is an approximate or mildly elevated intensity on ADC map (A) in the lesion compared with the normal left cerebellar parenchyma (ADClesion 0.73 × 10− 3 mm2/s and ADCnormal left cerebellar parenchyma 0.70 × 10− 3 mm2/s). On PWI elevated relative cerebral blood volume (rCBV) (B) is observed in the tumor with a ratio of rCBV(CBVRight/CBVLeft) = 1762. A 1 single-voxel H MRS (PRESS, TR/TE:1500/135 ms) study revealed decreased Cho/Cr in the lesion (C) compared with the normal cerebellar parenchyma (D).
that, PTEN mutation can be used for LDD diagnosis in the future. Investigations did not reveal features of Cowden syndrome in our patient. Most cases of LDD are seen in adults, usually diagnosed in the third and fourth decades. However, LDD was reported to be seen in a wide age range from birth to the sixth decade [11]. Nevertheless, the case reports of pediatric patients are rare in literature. There are less than 20 reported cases under the age of 20 [1–3,11,15–18]. In children the disease presentation does not differ from adult patients. Patients usually present with symptoms related to elevated intracranial pressure like diplopia, headache, vomiting and cerebellar signs like ataxia, dysmetria and dysdiadochokinesia. More serious symptoms or signs such as developmental delay, right sided hemiparesis, complex ocular movement disturbance and rotatory nystagmus have also been reported in children [1]. MR imaging is the most important diagnostic tool in the preoperative evaluation. Hydrocephalus due to obstruction of fourth ventricle and a cerebellar mass with a striated pattern of hyperintensity on T2weighted images are typical findings for LDD. Computed tomography provides less specific information showing a non-enhancing mass with or without calcifications [6]. We observed laminar type calcifications in the mass on CT and the diagnosis of LDD was established by the help of conventional MR imaging in the preoperative period.
The new advents in neuroimaging enable some data regarding the microstructural, metabolic and hemodynamic changes by diseases in the cerebral tissue. In this disease Nagaraja et al. [19] reported single1 voxel H MR spectroscopy findings in two adult patients and showed decreased NAA/Cr, similar Cho/Cr ratios when compared with control 1 subjects. Our data derived from the same technique of H MR spectroscopy also revealed reduced Cho/Cr with no remarkable change in NAA/Cr in comparison to the left cerebellar parenchyma. Another report of two adult cases by Klisch et al. [20] showed depressed 1 amplitudes of all major metabolites in LDD on H MR spectroscopy. Together with our MR spectroscopy data, it can be concluded that despite reduced levels of NAA/Cr, lack of elevated Cho/Cr eliminates many other neoplasms in which markedly increased cellular proliferation and membrane turnover occurs. Nagaraja et al. [19] suggested that reduction in NAA/Cr might represent loss of neuronal architecture or persistence of embryonic neural tissue which fails to express NAA. Nearly close ADC values of the mass with the contralateral cerebellar parenchyma, as in a previously published adult case by Klisch et al. [20] go parallel to conventional MR imaging findings where the mass appears very much like hypertrophied/exaggerated folia. On the other hand, the mass showed increased cerebral blood volumes in the lesion with an asymmetry index (R/L) of 1.76 although increased CBV in a mass is usually accepted as a correlate of active tumor component. Although
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usually non-enhancing or enhancing to a mild degree, these tumors show increased values of CBV which can be attributed to dilated thinwalled blood vessels and generalized vessel proliferation. Increased blood volume and flow in these WHO grade 1 tumors have been documented in an adult patient by PWI and in another by Xenon-CT by Klisch et al. [20]. In the same study, hypermetabolism in the LDD as assessed by increased accumulation of 18-FDG on FDG-PET examination was demonstrated [20]. Surgery is the only treatment approach for LDD. However, total resection cannot be possible in masses involving the brainstem. As the lesion is categorized as a WHO grade I tumor, a conservative “wait and see” strategy can be chosen especially in cases without elevated intracranial pressure. Clinical and radiologic follow-ups with MR imaging should be preferred in such cases [1]. The prognosis is excellent in totally resected cases. Rapid improvement in clinical signs and symptoms is observed after the surgery [3]. Before the advent of modern neuroimaging techniques, mortality associated with surgery complications or tumor itself was as high as 30%. [21]. Today, MR imaging provides accurate information for diagnosis and histopathologic as well as hemodynamic properties of these lesions, thus leading appropriate surgical approach. Recurrence in the operation cavity can be seen in case of incomplete resection [5]. Malignant transformation has not been reported until now. In conclusion, LDD is a rare cause of posterior fossa masses in children. Lhermitte-Duclos disease should be included in differential diagnosis in cases with severe headache, increased intracranial pressure symptoms and signs, cerebellar findings and should be 1 scrutinized with MR imaging. In challenging cases, H MR spectroscopy with typical normal or low Cho/Cr, PWI showing elevated CBV despite lack of robust contrast enhancement and ADC map of normal diffusion pattern could establish the diagnosis of LDD. Upon diagnosis of LDD in a child, the physician should search for the signs and symptoms of Cowden syndrome and obtain a detailed family history. Alternatively, brain MR imaging can be used to document LDD in patients with Cowden syndrome. References [1] Capone Mori A, Hoeltzenbein M, Poetsch M, Schneider JF, Brandner S, Boltshauser E. Lhermitte-Duclos disease in 3 children: a clinical long-term observation. Neuropediatrics 2003;34(1):30–5.
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