Case Review
Volume 5, No.1
April 2001
 Mostafa Fadli (1)
 Khalid Mahla (2)
 Rachid Gana (1)
 Fouad Kettani (3)
 Brahim El Mostarchid (1)
 Najia El Abbadi (1)
 Fouad Bellakhdar (1)
 (1) Department of Neurosurgery
   Ibn Sina of the University
 (2) Department of Neurosurgery
   C Lyon Pierre Wetheimer
 Hopital
  (3) Cabinet d'anatomie
    Pathologique
 Rabat Agdal
 Morocco
 Correspondence:
 Dr. Mostafa Fadli
 Service de Neurochirurgie
 Ibn Sina
 BP 8056 Rabat Nations Unies
 Rabat
 Morocco
 Fax: (212) 7 674 758 
Dysplastic gangliocytoma of the cerebellum (Lhermite Duclos disease) - Case report

ABSTRACT


Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) is a rare entity. Authors report a case of 32-year-old male with a 2-month history of elevated intracranial pressure. CT revealed hydrocephalus due to displacement of the fourth ventricle by a large non-enhancing cerebellar mass. Magnetic resonance imaging (MRI) sequences showed a space-occupying lesion within the right cerebellar hemisphere with unusual septations. At operation, the poorly demarcated lesion was excised from the apparently normal cerebellar tissue and the pathological study revealed a dysplastic gangliocytoma. Clinical, radiological and pathological aspects of this entity are discussed.

Keywords: Lhermitte Duclos disease, cerebellar neoplasia and gangliocytoma

INTRODUCTION

Since the original description in 1929 by Lhermitte Duclos of “diffuse ganglioneuroma of the cerebellar cortex”, approximately seventy cases have been reported.7,12,15 Nevertheless, the exact nature of this disease remains controversial. Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease – LDD) is a rare entity, usually presenting as a posterior fossa mass. Dysplastic gangliocytoma is not a true neoplasm but a hard to characterise lesion that may represent an abnormality of cell migration or hacomatosis.18,20 Microscopically, it consists of large, dysplastic granular cells which superficially resemble purkinje neurons, and of thick parallel myelinated fibres.10,21 Until the advent of magnetic resonance imaging (MRI), only pathological examination of surgical specimens (biology) led to the diagnosis.3 We report the first case of LDD in Morocco.
CASE REPORT

A 32-year-old male Moroccan patient presented at the Neurosurgical Division, Ibn Sina University Hospital with a two-month history of gait disturbance, intermittent headaches of increasing intensity and visual disturbance (diplopia and blurring of vision). Neurological examination at admission revealed minor ataxia and mild abducens palsy on the right together with bilateral papilloedema. Motor and sensory functions were normal and the reflexes were symmetrical. There were no cutaneous lesions or significant family history. CT scan showed hydrocephalus and right cerebellar isodense mass without contrast enhance-ment, which compressed the fourth ventricle (Fig. 1). MRI showed a large, septated, non-enhancing space occupying lesion. The mass was hypointense on T1-weighted and hyperintense on T2-weighted (Fig. 2).

The hydrocephalus was treated by ventriculo-peritoneal shunt. Post-operatively, the headaches and abducens palsy improved and CT scan confirmed the successful reduction in ventricular size. A right sub-occipital craniotomy was performed in the sitting position. The dura matter was normal. The cerebellar folia appeared wide, loose and purplish-grey in colour. Large portion of the right cerebellum was removed without tumour identification. After the decompression with frozen section, suggestive of glial tumour or tuberculosis the wound was closed.

The definitive histological study showed a cerebellar cortex characterised by presence of large neurons, which had abundant cytoplasm with peripheral Nissl bodies and large vesicular nuclei with prominent nucleoli. The granular layer was still recognisable. The cells were haphazardly arranged suggesting dysplastic gangliocytoma (Fig. 3a and b).

The post-operative course was uneventful and the patient was discharged on the eighth post-operative day. At one year follow-up the patient was well and resumed work.




Figure 1A


Figure 1B
Figure 1a and b — Pre-operative axial CT scan without (a) and with contrast agent (b) showing the isodense space occupying lesion in the right cerebellar hemisphere, which compressed the fourth ventricle. No enhancement is seen.



Figure 2A


Figure 2B


Figure 2C


Figure 2D
Figure 2a, b, c and d — MRI images of the lesion. a and b) Sagittal T1- and T2-weighted sequences c) coronal T1-weighted with gadolinium infusion d) coronal T2-weighted images showing an hyposignal in T1-weighted sequences, and a hypersignal in T2-weighted sequences with a fine septation inside the tumour. No enhancement of the lesion is identifiable.




Figure 3A


Figure 3B
Figure 1a and b — Histological study showing large cells with ganglionic features including abundant cytoplasm, large nucleoli, and prominent nucleoli evoking Lhermite-Duclos disease.

DISCUSSION

In 1920, Lhermitte & Duclos described an unusual abnormality of the cerebellum, characterised by enlarged cerebellar folia, which contained circum-scribed regions of abnormal ganglion cells.7 This disorder is now commonly classified as a dysplastic gangliocytoma. Its previous classifications included Lhermitte-Duclos disease, granular-cell hypertrophy, diffuse hyperplasia of the cerebellar cortex, gangliomatosis of the cerebellum, haematoma of the cerebellum, ganglioneuroma and purkinjeoma.14 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 generalised thickening of the cerebellar cortex and scarcity or absence of the central white matter.16

Since the initial description there have been speculations whether this disease is part of a congenital malformation or a true neoplasm. Clinical support for a congenital malformation is given by its association with maglencephaly. Other congenital malformations have been leontiasis ossea, partial gigantism and polydactily.14

Recent studies have shown that the abnormal neurons in LDD are not mitotically active and contain no abnormalities of the tumour suppressor gene p53 and the oncogene mdm 2.4,11 Familial occurrences and the association with trisomy 13,15 and 18, and with Cowden’s syndrome suggest a genetically determined developmental abnormality.1,2,5,21 Cowden’s syndrome is a rare autosomal-dominant disorder characterised by multiple haematomas and neoplasms, including skin papules, oral papillomatosis and acral keratosis. Intestinal polyposis, goitre, fibrocystic breast disease, breast cancer and thyroid tumours are the most frequent internal manifestations of the syndrome.5,19

This disease shows prevalence in young adults, during the third or fourth decade. Some paediatric cases, with one in new born have been reported.8,13 There is no significant sex preponderance and the duration of symptoms prior to diagnosis ranges from a few weeks to thirty years.3 Clinically, LDD manifests itself most often by signs of increased intracranial pressure, followed by cerebellar signs and cranial nerve deficits.5,9 Severe orthostatic hypotension and acute subarachnoid haemorrhage are atypical clinical appearances.15,17

The CT scan examination shows a hypodense non-enhancing area in cerebellar hemisphere, sometimes extending to the midline, distorting the fourth ventricle. Peripheral calcifications have been mentioned. Angiography shows an avascular tumour.3,18 MRI on T1-weighted sequences shows a hyposignal area and on T2-weighted images an area of increased signal in a cerebellar hemisphere. The mass is not enhanced by gadolinium. MRI demonstrates a septation corresponding to the thickened cerebellar folia.2,3,6

Macroscopically, cerebellar folia are thickened, reaching up to 3 or 4 mm. They appear yellowish or purplish grey and there is no sharp demarcation from the adjacent tissue. Histological examination reveals thickening and hypermyelination of the molecular layer and large pleomorphic cells that replace the purkinje and granular cell layers.18 Demyelination of the central white matter of the folia is also observed.9,10 The transition between normal and abnormal cerebellar tissue may be gradual.1

The only effective treatment is radical removal of the lesion, but the major difficulty is the lack of sharp delineation of the lesion from the surrounding tissue.2,3 A temporary or permanent CSF shunt is advisable in patients with pre-operative hydrocephalus.3 Recurrence of up to 20 years have been reported after surgical resection.1,8,20 The usefulness of radiation therapy is unknown.

CONCLUSION

Dysplastic gangliocytoma is a rare tumour. It may be one of the manifestations of Cowden’s syndrome. The diagnosis can be made with an MRI which provides valuable information regarding location and extent of the lesion. Surgical removal is the only effective treatment.

REFERENCES

1. Ambler M, Pogacar S, Sidman R: Lhermitte-Duclos disease (granule cell hypertrophy of the cerebellum). Pathological analysis of the first familial cases. J Neuropath Exp Neurol 1969, 28: 622-647
2. Domingo Z, Fisher-Jeffes ND, De Villiers JC: Malignant occipital astrocytoma in patient with Lhermitte-Duclos disease (cerebellar dysplastic gangliocytoma). Br J Neurosurg 1996, 10(1): 99-102
3. Faillot T, Sichex J, Brault J, Capelle L, Kuja M, Brodi L, Boukobza M: Lhermitte-Duclos disease (Dysplastic gangliocytoma of the cerebellum). Report of a case and review of the literature. Acta Neurochir 1990, 22: 44-49
4. Hair LS, Symmans F, Powers JM, et al: Immuno-histochemistry and proliferate activity in Lhermitte-Duclos disease. Acta Neuropath 1992, 84: 570-573
5. Koch R, Scholz M, Nelen MR, Scwechheimer K, Epplen JT, Harders AG: Lhermitte-Duclos disease as a component of Cowden’s syndrome. Case report and review of the literature. J Neurosurg 1999, 90: 776-779
6. Kulkantrakorn K, Awward EE, Levy B, Selhorst JB, Cole HO, Leake D, Gussler JR, Epstein AT, Malik MM: MRI in Lhermitte-Duclos disease. Neurol 1997, 48: 725-731
7. Lhermitte J, Duclos P: Sur un ganlioneurome diffus du cortext du cervelet. Bull Assoc Franc Etude Cancer (Paris) 1920, 9: 99-107
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13. Roessman U, Wongmogkolrit T: Dysplastic gangliocytoma of the cerebellum in newborn: J Neurosurg 1984, 60: 845-847
14. Roski RA, Roessman U, Spetzler RF, Kaufman B, Nulsen FE: Clinical and pathological study of dysplastic gangliocytoma. J Neurosurg 1981, 55: 318-321
15. Schanley DJ, Vassallo CJ: A typical presentation of Lhermitte-Duclos disease: preoperative diagnosis with MRI. Neuroradiol 1992, 34: 103-105
16. Ruchoux MM, Gray F, Guerardi R, Schaeffer A, Comoy J, Poirier J: Orthostatic hypotension from a cerebellar gangliocytoma (Lhermitte-Duclos disease). Case Report. J Neurosurg 1986, 65: 245-248
17. Russell DS, Rubinstein LJ: Pathology of tumours of the nervous system. 5th (Ed.) Williams & Wilkins, Baltimore 1989, p302
18. Vieco PT del Carpio O, Donovan R, Melanson D, Montes J, O’Gorman AM, Meagher-Villemure K: Dysplastic gangliocytoma (Lhermitte-Duclos disease): CT and MR imaging. Paed Radiol 1992, 22:L 366-369
19. Wells GB, Lasner TM, Yousem DM, Zager EL: Lhermitte-Duclos disease and Cowden’s syndrome in an adolescent patient. J Neurosurg 1994, 81: 133-136
20. Williams DW III, Elster AD, Ginsberg LE, Staton C: Recurrent Lhermitte-Duclos disease: report of two cases and association with Cowden’s disease. Am J Neuro-radiol 1992, 13: 287-290
21. Yachnis AT, Rorke LB, Trojanowski JQ: Cerebellar dyplasias in human development and possible relationship to glial and primitive neuroectodermal tumours of the cerebellar vermis. J Neuropathol Exp Neurol 1994, 53: 61-71
 


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