CNS & pituitary tumors

Gliomas, glioneuronal tumors and neuronal tumors

Neuronal and mixed neuronal-glial tumors

Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)


Editorial Board Member: P.J. Cimino, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Eman Abdelzaher, M.D., Ph.D.

Last author update: 1 July 2024
Last staff update: 1 July 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Dysplastic gangliocytoma of the cerebellum

Eman Abdelzaher, M.D., Ph.D.
Page views in 2024 to date: 891
Cite this page: Abdelzaher E. Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumordysplasticgangliocytoma.html. Accessed July 13th, 2024.
Definition / general
  • Dysplastic cerebellar gangliocytoma, also known as Lhermitte-Duclos disease (LDD), is a cerebellar lesion characterized by thickened cerebellar folia caused by dysplastic ganglion cells that conform to the existing cortical architecture (J Neuropathol Exp Neurol 2005;64:341)
  • CNS WHO grade 1
Essential features
Terminology
  • Not recommended by WHO: cerebellar granule cell hypertrophy; diffuse hypertrophy of the cerebellar cortex; gangliomatosis of the cerebellum
ICD coding
  • ICD-O: 9493/0 - dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)
  • ICD-11: 2A00.21 & XH6K00 - mixed neuronal - glial tumors & dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos)
Epidemiology
Sites
Pathophysiology
Etiology
  • PTEN mutations have been identified in virtually all cases of adult onset LDD but not in childhood onset cases (Am J Hum Genet 2003;73:1191)
  • Adult onset LDD is considered pathognomonic of Cowden syndrome; both are considered a single phakomatosis that now belongs to PTEN hamartoma tumor syndrome (PHTS) (World Neurosurg 2017;104:398, J Neurosci Rural Pract 2023;14:127)
  • Cowden syndrome is an autosomal dominant disorder characterized by multiple hamartomas involving tissues derived from all 3 germ cell layers and increased risk of breast, thyroid, endometrial, renal and colon cancers (Clin Cancer Res 2012;18:400)
  • The majority (85%) of patients with Cowden syndrome have a germline mutation in PTEN; recently, other Cowden syndrome predisposition genes have been identified including the SDH genes, PIK3CA, KLLN and WWP1 (Hum Mol Genet 2020;29:R150, World Neurosurg 2017;104:398, Am J Hum Genet 2008;83:261)
  • Although the associations between LDD, Cowden syndrome and germline PTEN mutations are well documented, the precise relationships among them are less clear, as not all patients with LDD develop the clinical manifestations of Cowden syndrome and some patients with LDD lack germline mutations in PTEN; furthermore, not all patients with germline PTEN mutations manifest Cowden syndrome (J Neuropathol Exp Neurol 2005;64:341)
Diagrams / tables

Images hosted on other servers:
Schematic diagram of Lhermitte-Duclos disease

Histological changes

Pathology of Lhermitte-Duclos disease

Pathology

Clinical features
Diagnosis
  • Neuroimaging is highly suggestive of diagnosis (J Radiol Case Rep 2020;14:1)
  • Biopsy
  • WHO diagnostic criteria
    • WHO essential diagnostic criteria
      • Gangliocytic lesion that enlarges cerebellar folia
      • Densely packed ganglionic cells of various sizes
      • Matrix resembling normal neuropil, sometimes more coarsely fibrillar or vacuolated
    • WHO desirable diagnostic criteria
      • PTEN mutation / deletion or loss of expression
      • Abnormal myelination and vacuolization in the outer molecular layer
      • Calcification and ectatic vessels
Radiology description
Radiology images

Contributed by Eman Abdelzaher, M.D., Ph.D.
MRI, coronal T1 with contrast

MRI, coronal T1 with contrast

MRI, axial T2

MRI, axial T2



Images hosted on other servers:
Tiger stripe sign

Tiger stripe sign

Characteristic alternating iso and hyperintense bands

Characteristic
alternating iso
and hyperintense
bands

T2 hyperintense right cerebellar lesion

T2 hyperintense right cerebellar lesion

FLAIR hyperintense right cerebellar lesion

FLAIR hyperintense right cerebellar lesion

Bilateral cerebellar lesions

Bilateral cerebellar lesions

Prognostic factors
Case reports
Treatment
Clinical images

Images hosted on other servers:
Distorted and enlarged cerebellar hemisphere

Distorted and enlarged cerebellar hemisphere

Gross description
Gross images

Images hosted on other servers:
Enlarged cerebellar folia

Enlarged cerebellar folia

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Eman Abdelzaher, M.D., Ph.D.
Relative preservation of cerebellar architecture Relative preservation of cerebellar architecture

Relative preservation of cerebellar architecture

Replaced internal granular layer Replaced internal granular layer

Replaced internal granular layer

Dysplastic ganglion cells

Dysplastic ganglion cells


Dysplastic ganglion cells

Dysplastic ganglion cells

Variable sized ganglion cells Variable sized ganglion cells

Variable sized ganglion cells

Dysplastic ganglion cells with large nuclei and prominent nucleoli Dysplastic ganglion cells with large nuclei and prominent nucleoli

Dysplastic ganglion cells with large nuclei and prominent nucleoli


Vacuolization of the white matter

Vacuolization of the white matter

Vacuolated neuropil matrix Vacuolated neuropil matrix Vacuolated neuropil matrix

Vacuolated neuropil matrix


Synaptophysin Synaptophysin

Synaptophysin

Synaptophysin Synaptophysin

Synaptophysin

Synaptophysin

Synaptophysin

Cytology description
  • Squash smears show scattered, enlarged cells with vesicular nuclei and prominent nucleoli, thickened axons and many capillary sized vessels against a fibrillary background (J Neurosci Rural Pract 2023;14:127)
Cytology images

Images hosted on other servers:
Enlarged cells with vesicular nuclei and prominent nucleoli

Enlarged cells / thickened axons and capillary sized vessels

Positive stains
Negative stains
Electron microscopy description
  • Ganglion cells with neuronal features, including microtubules, synapses and clear vesicles
Molecular / cytogenetics description
Molecular / cytogenetics images

Images hosted on other servers:
PI3K / PTEN / AKT signaling pathway

PI3K / PTEN / AKT signaling pathway

Pathogenic heterozygous PTEN mutation

Pathogenic heterozygous PTEN mutation

Videos

Lhermitte-Duclos disease

Sample pathology report
  • Right cerebellar hemisphere mass lesion, gross total resection:
    • Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease), CNS WHO grade 1
    • Molecular genetics: PTEN mutation / deletion or loss of expression
Differential diagnosis
  • Ganglioglioma:
    • No preservation of cerebellar architecture
    • Neoplastic ganglion cells do not form broad bands that replace the internal granular cell layer
    • GFAP+ neoplastic glial component
    • Eosinophilic granular bodies
    • Perivascular chronic inflammation
    • BRAF p.V600E mutation in a subset of gangliogliomas (Acta Neuropathol 2013;125:891)
  • Infiltrating glioma with entrapped Purkinje cells:
    • GFAP+ neoplastic glial cells
    • Hypercellularity in both cerebellar cortex and white matter
    • Single cell layer of overrun ganglion cells (Purkinje cell layer)
Board review style question #1

A 35 year old man presented with a headache and ataxia. Magnetic resonance imaging (MRI) showed a left cerebellar hemisphere mass lesion with T2 hyperintensity and a tigroid pattern. A gross total resection of the mass was done and the histopathological features of the lesion are shown in the figure above. Which of the following genetic abnormalities is the hallmark of this tumor?

  1. BRAF mutation
  2. IDH mutation
  3. PRKCA gene fusion
  4. PTEN mutation
Board review style answer #1
D. PTEN mutation. Germline PTEN mutations are detected in most but not all cases of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease). Answers A, B and C are incorrect because BRAF mutations, IDH mutations and PRKCA gene fusion are associated with other neuroepithelial tumors such as gangliogliomas, IDH mutant adult type diffuse gliomas and papillary glioneuronal tumor, respectively.

Comment Here

Reference: Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
Board review style question #2
Lhermitte-Duclos disease (LDD) is closely associated with which of the following syndromes?

  1. Cowden syndrome
  2. Familial adenomatous polyposis
  3. Lynch syndrome
  4. Peutz-Jeghers syndrome
Board review style answer #2
A. Cowden syndrome. Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease) is a component of Cowden syndrome. Answers B, C and D are incorrect because these syndromes are unrelated to LDD.

Comment Here

Reference: Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)
Back to top
Image 01 Image 02