Pleomorphic Xanthoastrocytoma

Definition

Clinical Features

• Presentation typically:
  • later childhood
  • early adult life
• Location:
  • predilection for cerebral hemispheres, particularly temporal lobes:1,2
  • also:
    • cerebellar,3 intramedullary4 and retinal5 examples
    • morphologically similar tumors of the pineal region reported as ‘pleomorphic granular cell astrocytoma’6

Pathogenesis

• Appear to be capable of divergent glioneuronal differentiation and may be allied with gangliogliomas because:
  • often harbor cells that:
    • bind antibodies to synaptophysin (among other neuronal antigens)
    • exhibit ultrastructural features of neuronal differentiation, including clear (synaptic-type) and dense core vesicles7
  • xanthoastrocytomatous components are associated with:
    • neuronal malformations (cortical dysplasia)
    • hamartomas
    • neoplasms8,9

Gross Pathology

• Surgical specimens:
  • often mainly occupies leptomeninges and subarachnoid space
  • invariably foci of brain parenchymal invasion in which neoplastic cells permeate Virchow–Robin spaces and neuropil proper

Histopathology

• Histologically alarming
• Named for:
  • potentially bizarre cytologic characteristics
  • tendency of constituent cells to intracytoplasmic lipid accumulation (not uniformly conspicuous)
• Most composed of:
  • spindle-shaped elements in fascicular array admixed with tumor giant cells with:
    • worrisome nuclear abnormalities (Fig. 1
      

      Fig. 1: Pleomorphic xanthoastrocytoma. Spindle and giant cells, including bizarre multinucleated forms, combine to give this relatively indolent neoplasm a most disturbing appearance. Note hyaline, granular, and vacuolar cytoplasmic alterations, the last attesting to lipid accumulation.

      )
    • abundant cytoplasm that:
      • may appear foamy or coarsely vacuolated (advanced lipidization)
      • more commonly assumes ground-glass, finely granular or hyaline quality
  • reactive lymphoid infiltrates, at times extensive
  • aggregated eosinophilic granular bodies
    • representing lysosomes distended by autophagic debris or imbibed proteinaceous material
    • an important clue to diagnosis
    • seen in certain other slowly growing neuroepithelial neoplasms, notably pilocytic astrocytoma and ganglioglioma
    • likely to reflect cellular senescence
• Some ‘composite’ tumors harbor both gangliogliomatous and xanthoastrocytomatous components9
• Rarely cerebral hemispheric astrocytomas of pilocytic type have foci of leptomeningeal spread conforming to histology of the pleomorphic xanthoastrocytoma in unalloyed form
• Additional features in select cases include:
  • cohesive, nesting or alveolar growth pattern10
  • hyalinizing, angiomatoid stromal vascular response11
• Intricate pericellular pattern of reticulin deposition:
  • may render the sarcomatoid histologic presentation even more misleading
  • in violation of principle that such staining in glial (as opposed to mesodermally derived) neoplasms is typically confined to supporting vasculature
  • reflects elaboration by tumor cells of encircling basal lamina material, demonstrable:
    • ultrastructurally
    • by antibodies against type IV collagen or laminin10
  • evidence (together with characteristically superficial location) of derivation from a specialized class of subpial astrocytes having radially oriented cytoplasmic processes normally invested by basement membranes2

Special Stains and Immunohistochemistry

• GFAP expression:
  • mandatory for definitive diagnosis
  • effectively segregates tumor from mesenchymal neoplasms2,7,12
  • typical examples may contain relatively few immunolabeled elements
• S-100 protein:
  • usually diffuse cytoplasmic immunoreactivity
• Tumor cells may be labeled by antisera to:
  • α-1-antitrypsin
  • antichymotrypsin
  • other ‘histiocytic’ markers12
    • decorate a variety of neoplastic (including glial) cell types
    • notoriously little discriminatory value when applied to neurosurgical material

Diagnosis

• Especially suggestive:
  • neuroradiologic demonstration of well-demarcated and partially cystic lesion containing superficially positioned, contrast-enhancing mural components of nodular or plaque-like contour (Fig. 2
    

    Fig. 2: Pleomorphic xanthoastrocytoma. This frontal lobe example is represented by a sharply delimited, intensely and homogenously contrast-enhancing nodule that projects into a large cyst. Pilocytic astrocytomas and gangliogliomas may exhibit identical neuroradiologic profiles and are the major differential diagnostic considerations in this setting.

    )
  • usually unaccompanied by significant mass effect or edema:
    • edema may adhere to dura and can appear at operation to lie largely above the cortical mantle

Differential Diagnosis

Management

• Gross total resection:
  • usually long-term tumor control
  • recurrence-free survivals 72 and 61% at 5 and 10 years, respectively
  • overall survival ≈80 and 70% at 5 and 10 years, respectively1
  • extent of tumor removal critical to risk of regrowth

Prognosis

• Relatively benign
• Scattered mitotic figures do not seem to be an ominous prognostic sign
• Proliferative activity >5 mitoses per 10 high power fields is a predictor of shortened survival1
• A recurring example with histologic evidence of anaplasia, extensive clear cell component and focally papillary growth has been recorded14
• Local failure is the rule, CSF-borne spread is a rarity15