Dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease)

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Status

Done

Parent item

Glioneuronal and neuronal tumours

General

• Aka
• Cerebellar granule cell hypertrophy
• Diffuse hypertrophy of the cerebellar cortex
• Gangliomatosis of the cerebellum

Definition

• Essential:
• Gangliocytic lesion enlarging cerebellar folia AND
• Densely packed ganglionic cells of various sizes AND
• Matrix resembling normal neuropil, sometimes more coarsely fibrillar or vacuolated

• Desirable:
• PTEN mutation/deletion or loss of expression
• Abnormal myelination and vacuolization in the outer molecular layer
• Calcification and ectatic vessels

Localisation

• Cerebellum: the enlarged ganglion cells are predominantly located within the internal granule layer and thicken the cerebellar folia.

• Does not really go into the pons/brainstem (LA)

Grading

• Unsure if it is neoplastic or hamartomatous
• If neoplastic it is grade 1
• Features supporting a harmartomatous lesion
• Very low or absent proliferative activity
• Absence of progression
• Features supporting a neoplastic lesion
• Recurrent growth
• Development of dysplastic gangliocytomas in previously normal MRI

Numbers

• Adults > children

• Cowden syndrome
• 1/million
• 32% of cowden syndrome patients have Dysplastic cerebellar gangliocytoma
• PTEN

Clinical presentation

• Dysmetria; other cerebellar signs

• Signs and symptoms of
• Mass effect
• Obstructive hydrocephalus
• Increased intracranial pressure

• Cranial nerve deficits, macrocephaly, and seizures

• Should be monitored for other cancers

Cell origin

• Cerebellar granule neuron
• Aberrant migration
• Hypertrophy

Radiological

CT

• May show a non-specific hypoattenuating cerebellar mass

• Calcification is sometimes seen

MRI

• T1:
• Hypointense

• T2:
• ‘Tiger-striped’ pattern
• Hyperintense with apparently preserved cortical striations
• The MRI features are often so characteristic as to obviate the need for a tissue diagnosis in many cases

• DWI:
• Similar to normal cortex
• May show hyperintensity due to T2 shine through effect

• T1 C+ (Gd)
• Enhancement is rare
• If present usually superficial, possibly due to vascular proliferation

• MR spectroscopy
• Elevated lactate
• Slightly reduced NAA (by about 10%)
• Reduced myo-inositol (by 30-80%)
• Reduced choline (by 20-50%)
• Reduced Cho/Cr ratio

Images

PET/SPECT

• FDG-PET: shows increased uptake

• Tl-201 SPECT: shows increased uptake

Histopathology

Macroscopy

• Cerebellum displays a discrete region of hypertrophy and a coarse gyral pattern that extends into deeper layers.

• Usually confined to one hemisphere

Microscopy

• Diffuse enlargement of the molecular and internal granular layers of the cerebellum, which are filled by ganglionic cells of various size

• Inverted cerebellar cortex
• Relative preservation of the cerebellar architecture
• The folia are enlarged and distorted but not obliterated
• A layer of abnormally myelinated axon bundles in parallel arrays is often observed in the outer molecular layer.
• Scattered cells morphologically consistent with granule neurons are also sometimes found under the pia or in the molecular layer.

Immunophenotype

• Dysplastic neuron cells
• +: synaptophysin.
• -:

• Large atypical ganglion cells
• +: LEU4, PCP2, PCP4, and calbindin

• Both cell groups
• PTEN loss
• Inc. phosphorylation of AKTG and S6

Genetic profile

• PTEN mutation
• Cowden syndrome
• Lhermitte Duclos disease is a major CNS manifestation of Cowden syndrome

Dysplastic cerebellar gangliocytoma vs

• Dysplastic cerebellar gangliocytoma is a feature of Lhermitte Duclos disease, but Lhermitte-Duclos disease have other features like
• Enlarged brain (megalencephaly)
• Hydromyelia
• Extra fingers or toes (polydactyly)
• Partial gigantism, and/or
• Large tongue (macroglossia)

• Patients can have dysplastic cerebellar gangliocytoma without Lhermitte duclos disease
• Definition
• Autosomal dominant disorder
• PTEN germline mutation
• Characterized by multiple hamartomas involving tissues derived from all three germ cell layers
• Classically associated with trichilemmoma (benign cutaneous neoplasm that shows differentiation toward cells of the outer root sheath)
• High risk
• Breast ca
• Life time risk: 85%
• Thyroid ca
• Life time risk: 38%
• Endometrial ca
• Life time risk: 28%
• Mucocutaneous lesions
• Non-malignant thyroid abnormalities
• Fibrocystic disease of the breast
• Gastrointestinal hamartomas
• Early-onset uterine leiomyomas
• Macrocephaly
• Mental retardation
• PTEN mutation identified in all adult diseases → adult and children have very different pathogenetics
• PTEN when mutated will affect downstream pathways eg AKT and MAPK

 

• PIK3CA mutation

Management

Surgery

• Indication
• Enlarging tumours

• Upon exposure of the cerebellum, the large pale broadened gyri should be immediately apparent

• The affected tissue is usually hypovascular and easily removed with ultrasonic aspiration

• Poorly defined borders of the lesion being the major technical issue
• Use preoperative MRI to determine the extent of resection

• Recurrence years after initial resection have been reported so complete resection should be attempted and patients should get periodic follow-up MRI scans

Radiotherapy

• Indication
• Symptomatic stabilization
• Progressive neurological deterioration

Prognosis

• Nil data