Lhermitte-Duclos Disease in 3 Children: A Clinical Long-Term Observation

Abstract

We report three boys in whom a diagnosis of Lhermitte-Duclos disease (LDD) was assumed from characteristic neuroimaging findings. LDD was confirmed by an open biopsy in patient 1, while a biopsy in patient 2 was inconclusive. Histologic confirmation in patient 3 was deliberately not attempted. However, a follow-up observation of stable clinical and neuroimaging findings over 2, 5 and 11 years, respectively, support the diagnosis of LDD. Despite extensive expansion of the lesion with brainstem involvement, clinical signs in two boys were minimal, while one patient has cognitive impairment and a complex oculomotor disturbance. So far we found no evidence for an association with Cowden disease (CD). No germline PTEN mutations were detected in these children, but the amount of available biopsy tissue in patients 1 and 2 was insufficient for a complete genetic analysis of tumor tissue. In conclusion, LDD can usually be diagnosed by MRI. In view of the favourable natural history, a conservative “wait and see” strategy is justified, particularly if radical tumor resection is not possible. LDD is often not associated with CD and germline PTEN mutations seem not to be present in isolated LDD.

Key words

Lhermitte-Duclos disease - gangliocytoma - Cowden disease - PTEN mutation - cerebellum - child

References

• 1 Backman S A, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J. et al . Deletion of PTEN in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease.  Nat Genet. 2001;  16 396-403
• 2 Bonneau D, Longy M. Mutation of the human PTEN gene.  Hum Mut. 2000;  16 109-122
• 3 Duerr E M, Rollbrocker B, Hayashi Y, Peters N, Meyer-Puttlitz B, Louis D N. et al . PTEN mutation in gliomas and glioneural tumors.  Oncogene. 1998;  16 2259-2264
• 4 Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria.  J Med Genet. 2000;  37 828
• 5 Iida S, Tanaka Y, Fuji H, Hayashi S, Kimura M, Nagareda T. et al . A heterozygous frameshift mutation for the PTEN/MNAC1 gene in a patient with Lhermitte-Duclos disease - only the mutated allele was expressed in the cerebellar tumor.  Int J Mol Med. 1998;  1 925-929
• 6 Kulkantrakorn K, Awwad E E, Levy B, Selhorst J B, Cole H O, Leake D, Gussler J R. et al . MRI in Lhermitte-Duclos disease.  Neurology. 1997;  48 725-731
• 7 Kwon C H, Zhu X, Zhang J, Knoop L L, Tharp R, Smeyne R J. et al . PTEN regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.  Nat Genet. 2001;  29 404-411
• 8 Levisohn L, Cronin-Golomb A, Schmahmann J D. Neuropsychological consequences of cerebellar tumor resection in children. Cerebellar cognitive affective syndrome in a paediatric population.  Brain. 2000;  123 1041-1050
• 9 Marino S, Krimpenfort P, Leung C, van der Korput H AGM, Trapman J, Camenisch I. et al . PTEN is essential for cell migration but not for fate determination and tumorigenesis in the cerebellum.  Development. 2002;  129 3513-3522
• 10 Meltzer C C, Smirniotopoulos J G, Jones R V. The striated cerebellum: an MR imaging sign in Lhermitte-Duclos disease.  Radiology. 1995;  194 699-703
• 11 Murata J, Tada M, Sawamura Y, Mitsumori K, Abe H, Nagashima K. Dysplastic gangliocytoma associated with Cowden disease: report of a case and review of the literature for the genetic relationship between the two diseases.  J Neuro-Oncol. 1999;  4 129-136
• 12 Nelen M R, Kremer H, Konings I BM, Schoute F, van Essen A J, Koch R. et al . Novel PTEN mutation in patients with Cowden disease: absence of clear genotype-phenotype correlations.  Eur J Hum Genet. 1999;  7 267-273
• 13 Nowak D A, Trost H A. Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma): a malformation, hamartoma or neoplasm?.  Acta Neurol Scand. 2002;  105 137-145
• 14 Ogasawara K, Yasuda S, Beppu T, Kobayashi M, Doi M, Kuroda K. et al . Brain PET and technetium-99 m-ECD SPECT imaging in Lhermitte-Duclos disease.  Neuroradiol. 2000;  43 993-996
• 15 Padberg G W, Schot J DL, Vielvoye G J, Bots G TAM, de Beer F C. Lhermitte-Duclos disease and Cowden disease: a single phakomatosis.  Ann Neurol. 1991;  29 517-523
• 16 Poetsch M, Dittberner T, Woenckhaus C. PTEN/MMAC1 in malignant melanoma and its importance for tumor progression.  Cancer Genet Cytogenet,. 2001;  125 21-26
• 17 Riva D, Giorgi C. The cerebellum contributes to higher functions during development. Evidence from a series of children surgically treated for posterior fossa tumors.  Brain. 2000;  123 1051-1061
• 18 Robinson S, Cohen A R. Cowden disease and Lhermitte-Duclos disease: characterisation of a new phakomatosis.  Neurosurg. 2000;  46 371-382
• 19 Schmahmann J D, Shermann J C. The cerebellar cognitive affective syndrome.  Brain. 1998;  121 561-579
• 20 Steinlin M, Styger M, Boltshauser E. Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia.  Neurology. 1999;  53 966-973
• 21 Sutphen R, Diamond T M, Minton S E, Peacocke M, Tsou H C, Root A W. Severe Lhermitte-Duclos disease with unique germline mutation of PTEN.  Am J Med Genet. 1999;  82 290-293
• 22 Tuli S, Provias J P, Bernstein M. Lhermitte-Duclos disease: literature review and novel treatment strategy.  Can J Neurol Sci. 1997;  24 155-160
• 23 Verdu A, Garde T, Madero S. Lhermitte-Duclos disease in a ten-year old child: clinical follow-up and neuroimaging data from birth.  Rev Neurol. 1998;  158 597-600
• 24 Wells G B, Lasner T M, Yousem D M, Zager E D. Lhermitte-Duclos disease and Cowden's syndrome in an adolescent patient: case report.  J Neurosurg. 1994;  81 133-136
• 25 Wiestler O D, Padberg G W, Steck P A. Cowden disease and dysplastic gangliocytoma of the cerebellum/Lhermitte-Duclos disease. Kleihues P, Cavenee WK Pathology and Genetics: Tumors of the Nervous System. 2nd ed. Lyon; IARC Press 2000: 235-237