Neurosurgery notes/Tumours/Sellar tumours/Granular cell tumour of the sellar region

Granular cell tumour of the sellar region

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Sellar tumours

General

  • Granular cell tumour of the sellar region is a low-grade neoplasm arising from the pituicytes of the posterior pituitary or infundibulum.
  • A circumscribed tumour that is composed of large epithelioid to spindled cells with distinctively granular, eosinophilic cytoplasm (due to an abundance of intracytoplasmic lysosomes) and that arises from the neurohypophysis or infundibulum
  • Like pituicytomas and spindle cell oncocytomas, granular cell tumours show nuclear expression of TTF1, suggesting that these three tumours may constitute a spectrum of a single nosological entity.

Nomenclature

  • Abrikossoff tumour
  • Choristoma
  • Granular cell myoblastoma
  • Granular cell neuroma

Definition

  • Essential criteria
    • The neoplasm must be composed of polygonal cells with granular cytoplasm.
    • The lesion must be located in the sellar or suprasellar region.
    • There must be evidence of nuclear thyroid transcription factor 1 (TTF1) expression.
    • There must be an absence of pituitary hormone and lineage-specific transcription factor expression.
    • There must be an absence of neuronal and neuroendocrine marker expression.
  • Desirable criteria
    • Interspersed reticulin fibres should be absent.
    • The granules should be PAS-positive and diastase-resistant.
    • The tumour should show CD68 or alpha1-antitrypsin immunoreactivity.

Numbers

  • Rare and typically present in adulthood
    • A meta-analysis identified approximately 270 cases across the entire family of pituicyte-derived tumours.
  • F:M ratio of > 2:1.
  • Peak incidence: 50-60 yrs

Grading

  • Granular cell tumours are considered low-grade neoplasms (benign).
  • No WHO CNS Classification

Cell of origin

  • All share same nosological entity because all have nuclear expression of TTF1, suggesting that these three tumours may constitute a spectrum of a single nosological entity
    • Pituicytomas
    • Spindle cell oncocytomas,
    • Granular cell tumours show
      • Granular cell tumours occasionally occur in the CNS outside the pituitary gland (e.g. in the meninges, cerebral hemispheres, third ventricle, or cranial nerves); these tumours may be derived from glial cells, Schwann cells, or macrophages
  • Pituicyte derivation
    • Pituicyte: any of the glial cells of the posterior pituitary
  • Ultrastructural studies have identified 5 distinct variants of pituicytes in the normal neurohypophysis:
    • Light
      • Most common
    • Dark
      • Small and electron-dense cytoplasm are called "dark"
    • Ependymal
      • Occasional cilia and/or microvilli projection
    • Granular
      • Light pituicytes numerous electron-dense lysosomal bodies, or phago-lysosomes.
      • Granular cell tumours
    • Oncocytic
      • Light pituicytes with numerous mitochondria,
      • Spindle cell oncocytomas

Histopathology

Macroscopy

  • The tumours are usually lobulated and well circumscribed
  • Their texture can vary from firm and vascular to a consistency similar to normal brain tissue.
    • Soft but rubbery consistency firmer than that of pituitary adenoma.
  • Cut surface is grey to yellow.
  • Rare
    • Necrosis
    • Cystic degeneration
    • Haemorrhage are uncommon.
  • These tumours cannot be macroscopically distinguished from pituicytoma or spindle cell oncocytoma.

Microscopy

  • The tumours consist of densely packed polygonal cells with granular eosinophilic cytoplasm.
  • The architecture is typically nodular, though sheets or spindle/fascicular patterns can occur.
  • The cytoplasmic granules are PAS-positive and resistant to diastase digestion.
  • Nuclei are small with even chromatin and inconspicuous nucleoli.
  • Proliferative (Ki-67) activity is usually very low.
Fig. 17.15 Granular cell tumour of the neurohypophysis. A Spindled and whorled cellular architecture. B Characteristic abundant eosinophilic cytoplasm with prominent granularity.
Granular cell tumour of the neurohypophysis.
(A) Spindled and whorled cellular architecture.
(B) Characteristic abundant eosinophilic cytoplasm with prominent granularity.

Immunophenotype

  • +
    • TTF1 (nuclear staining)
    • Due to their lysosomal content, they are positive for
      • CD68 (by KP1 staining)
      • S100 protein
      • Alpha-1-antitrypsin
      • Alpha-1-antichymotrypsin
      • Cathepsin B
  • -
    • NFPs
    • Cytokeratins
    • Desmin
    • SMA
    • Pituitary hormones
    • GFAP
    • Transcription factors (like PIT1 or SF1)
    • Neuroendocrine markers (chromogranin A, synaptophysin)
    • Neurofilaments
 

Pathogenesis

  • They share a common histogenesis with pituicytoma and spindle cell oncocytoma.
  • Some evidence suggests that activation of the MAPK pathway may be involved in their development.

Localisation

  • Along the anatomical distribution of the neurohypophysis, including
    • Posterior pituitary
    • Pituitary stalk / infundibulum (more common)
  • Some examples occupy both the intrasellar and suprasellar compartments, mimicking pituitary macroadenoma

Clinical features

  • Presentation is indistinguishable from other sellar lesions, including headaches, visual field defects, and hypopituitarism.
  • Visual field deficit secondary to compression of the optic chiasm
    • Most common
  • Endocrine
    • Panhypopituitarism
    • Galactorrhoea
    • Amenorrhoea
    • Decreased libido
  • Neuropsychological changes.
  • Rare
    • Diabetes insipidus
  • Develop slowly over a period of years
  • Acute presentation with sudden-onset diplopia, confusion, headache, and vomiting can occur
  • These tumours have occasionally been reported in association with synchronous functional pituitary adenomas, such as those producing growth hormone or ACTH.

Radiology

  • General
    • They are generally indistinguishable from clinically non-functioning pituitary adenomas on neuroimaging.
  • CT
    • Nil calcification
  • MRI
    • On MRI, they appear as masses that are isointense on T1-weighted images.
    • Contrast enhancement after gadolinium administration can be homogeneous or heterogeneous.
    • T2-weighted MRI reveals various signal intensities.
 
A hypoenhancing T1 and T2 intermediate lesion arising from the postero-superior aspect of the pituitary gland. The sellar-suprasellar lesion approximately 10 mm x 6 mm x 7 mm enhances with gadolinium administration. A) Coronal T1 post-gadolinium, B) axial T1 post-gadolinium, C) sagittal T1 post-gadolinium, D) axial T2.
A hypoenhancing T1 and T2 intermediate lesion arising from the postero-superior aspect of the pituitary gland. The sellar-suprasellar lesion approximately 10 mm x 6 mm x 7 mm enhances with gadolinium administration. A) Coronal T1 post-gadolinium, B) axial T1 post-gadolinium, C) sagittal T1 post-gadolinium, D) axial T2.

Management

  • The primary management for granular cell tumours is gross total surgical excision.
    • Firm and vascular nature of pituitary granular cell tumours, sometimes combined with the lack of an obvious dissection plane from the adjacent brain, may hamper gross total resection.

Prognosis

  • These are typically benign, slow-growing tumours.
  • They are generally curable by complete surgical removal.
  • Malignant transformation and distant metastases have not been reported.

Differential diagnosis

  • Craniopharyngiomas
    • Calcification is unusual in granular cell tumours.
  • Regional meningiomas
    • Lack of a dural attachment (dural tail) in granular cell tumours
    • Anatomical location at pituitary stalk in granular cell tumours
  • Pituicytomas
    • Granular cell tumours have only focal spindled areas