Neurosurgery notes/Tumours/Haematolymphoid and histiocytic tumours/Histiocytic tumour/Juvenile xanthogranuloma

Juvenile xanthogranuloma

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Histiocytic tumour
 

General

  • Juvenile xanthogranuloma of the Central Nervous System (CNS) or the meninges, with or without systemic lesions, pathologically corresponds to its cutaneous counterpart.
  • It is a mostly paediatric, non-Langerhans cell histiocytosis characterized by foamy histiocytes, occasional Touton giant cells, and inflammation.

Definition

  • Essential:
    • A histiocytic tumour composed of foamy cells and a mixed inflammatory infiltrate.
  • Desirable:
    • Exclusion of other lines of differentiation (glial, epithelial, melanocytic, lymphocytic, Langerhans cell, meningothelial, etc.).
    • BRAF, ARAF, KRAS, and NRAS mutation status.
    • Evidence of cutaneous manifestations.

Epidemiology

  • CNS juvenile xanthogranuloma typically occurs in children and young adults.
    • 22 months old
  • Neurological involvement is seen in less than 5% of patients with cutaneous juvenile xanthogranuloma.

WHO Grade

  • No grading

Localisation

  • Brain {53%)
  • Intradural extramedullary spine {13%)
  • Nerve roots {15%)
  • Meningeal involvement also being common

Histopathology

Macroscopic

  • Lesions are often received as fragmented, soft, yellow to tan-pink biopsy specimens.

Microscopic

  • The lesion (overlapping with Erdheim-Chester disease) is composed of rounded to spindled variably vacuolated histiocytes, scattered Touton and foreign body-type giant cells, lymphocytes, and occasional eosinophils.
Fig. 14.05 Juvenile xanthogranuloma. Note numerous histiocytic cells and two large multinucleated Touton cells.
Juvenile xanthogranuloma. Note numerous histiocytic cells and two large multinucleated Touton cells.

Immunophenotype

  • +
    • CD11c
    • CD68
    • Factor XII la
    • BRAF p.V600E protein is present in mutant cases.
  • -
    • CD1a
    • Lysozyme
    • S100
  • Variable
    • MAC387

Genetic features

  • The exact frequency of BRAF p.V600E mutations is currently unclear.
  • ARAF mutations occur in 18% of cases.
  • KRAS and NRAS mutations are also frequent (in as many as 20% of cases).
  • Occasional cases can have combined NRAS and ARAF mutations.
  • Mutations of CSF1R and fusions involving an NTRK gene have been reported for peripheral juvenile xanthogranuloma.

Clinical Features

  • Tumour lesions induce location-related neurological symptoms.
    • Commonly seizures, diabetes insipidus, and visual disturbances.
  • The rare neurodegenerative-like lesions induce more diffuse symptoms, including cognitive disturbances.

Radiological Features

  • Tumour lesions appear isointense to hyperintense on T1-weighted images, with homogeneous contrast enhancement.
  • Neurodegenerative-like lesions include non-enhancing hyperintense T2 signals and atrophy.

Management

  • Therapy relies on maximally safe surgery when feasible.
  • Cytotoxic chemotherapies, radiotherapy, and molecular targeted therapies, including MAPK signalling pathway inhibitors, are therapeutic alternatives based on molecular characterization.

Prognosis

  • Drawing prognostic conclusions about juvenile xanthogranuloma of the CNS is difficult because of its rarity.