Dysplastic cerebellar gangliocytoma

Dysplastic cerebellar gangliocytomas perhaps better known as Lhermitte-Duclos disease is a rare tumour of the cerebellum appearing as thickening and increase in T2 signal of the cerebellar folia giving this lesion a characteristic striated appearance. 

Epidemiology

Dysplastic cerebellar gangliocytomas typically present in young adults, although they has been encountered at all ages ^3,6.

Associations

A number of associated conditions have been described ^1,3, including:

• Cowden diseasesyndrome (as part of COLD syndrome, see below)
• disorders of cortical formation
  • megalencephaly
  • grey matter heterotopia
  • polymicrogyria
• polydactyly
• hydromyelia
• macroglossia
• localised gigantism
• leontiasis ossea

Clinical presentation

Small tumours may be asymptomatic or only present with relatively subtle cerebellar signs (e.g. dysmetria). When larger, symptoms are typically related to raised intracranial pressure, obstructive hydrocephalus and to a lesser degree, cerebellar dysfunction ³.

Pathology

Dysplastic cerebellar gangliocytomas are designated as WHO grade 1 tumours and considered one of a number of glioneuronal and neuronal tumours in the current WHO classification of CNS tumours ⁹.

Genetics

Interestingly the genetics of childhood-onset appears different from the more common adult-onset form. In the adult form, PTEN mutations are invariably found, lending additional weight to Lhermitte-Duclos disease being a manifestation of Cowden diseasesyndrome. In such cases, it is termed COLD syndrome (Cowden-Lhermitte-Duclos syndrome) ⁷. In contrast, in children, PTEN mutations are absent ⁶. 

Macroscopic appearance

Dysplastic cerebellar gangliocytomas are usually single and unilateral, presenting as a discrete region of cerebellar hypertrophy ⁶. 

Microscopic appearance

Derangement of the normal laminar cellular organizationorganisation of the cerebellum is present. There is thickening of the outer molecular cell layer, loss of the middle Purkinje cell layer, and infiltration of the inner granular cell layer with dysplastic ganglion cells of various sizes ⁶.

Immunophenotype

• synaptophysin: positive
• loss of PTEN protein expression (Cowden syndrome/COLD syndrome)

Radiographic features

The abnormal tissue involves the cerebellar cortex and is usually confined to one hemisphere, occasionally extending to the vermis but only rarely extending to the contralateral hemisphere ¹.

CT

• may show a non-specific hypoattenuating cerebellar mass
• calcification is sometimes seen ^2,5

MRI

Widened cerebellar folia with a striated/tigroid appearance. Also described as "corduroy/laminated" appearance.⁸

• T1: hypointense ²
• T2: hyperintense with apparently preserved cortical striations ¹
• 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 ⁴
• MR spectroscopy
  • elevated lactate ^1,2
  • slightly reduced NAA (by about 10%) ^1,2
  • reduced myo-inositol (by 30-80%)
  • reduced choline (by 20-50%)
  • reduced Cho/Cr ratio ²

PET/SPECT

• FDG-PET: shows increased uptake
• Tl-²⁰¹ SPECT: shows increased uptake

Treatment and prognosis

The dysplastic mass grows very slowly, and initial treatment revolves around treating hydrocephalus. Surgical resection is often curative, with only a few case reports of recurrence ³. Importantly it is crucial to remember the association with Cowden syndrome, hence, increased risk of other neoplasms such as breast, endometrial and thyroid cancers. Therefore, a recommendation for further imaging or clinical assessment of possible tumours in these locations should be included in the radiologist's report.

History and etymology

It is named after the French neurologist and neuropsychiatrist, Jacques Jean Lhermitte (1877-1959), with his physician colleague P Duclos, who jointly described the condition in 1920 ⁶.

Differential diagnosis

The appearance is very characteristic and usually little differential exists, particularly when appearances are typical.

In the setting of sepsis or acute deterioration, one should consider cerebellitis or subacute cerebellar infarction.

The appearance may be mimicked by extensively nodular medulloblastoma (SHH molecular subgroup).