HAEMANGIOBLASTOMA

HAEMANGIOBLASTOMA

• It is a capillary rich neoplasm containing lipidized interstitial or stromal cells

• Cytogenetics

  • Stromal cells are neoplastic component and not the vessels

  • Stromal cells overexpress VEGF resulting in angiogenesis

  • Sporadic hemangioblastoma show

    •  germline mutations  in VHL gene (few cases)

    • Losses on chromosome 3,6,9 and 18

    • Gain on 19

  • VHL – Mutations in the VHL gene

• Clinical features

  • Haemangioblastomas can present in sporadic form or in association with Von Hippel Lindau syndrome

  • Sporadic haemangioblastoma

    • Age – between 30 and 65 years

    • Sex – slight male predomiance

    • Site – common in cerebellum, but can occur in medulla and spinal cord

  • Von Hipple Lindau syndrome

    •  It consists of multiple intracranial or intratspinal hemangioblastomas

      • Retinal hemangioblastoma

      • Cystic lesions of liver, kidney, pancreas and epididymis

      • Benign and malignant renal cell tumor

      • Papillary endolymphatic sac tumor of the ear

    • Age – Younger age

    • Site – Intracranilal,  supratentorial meninges or intraspinal

  • 10% of cases have polycythemia which  results due to production of erythropoietin by tumor cells

• Radiologic findings – Presents as cystic lesion in the cerebellum and spinal canal with contrast enhancing nodule

• Gross finding

  • Highly vascular mass typically abutting the leptomeninges

  • Spinal hemangioblastomas are intramedullary, discrete and are usually in contact with leptomeninges

  • Cut section – Drak red tumor which exudes blood upon compression

  • Depending upon lipid content of the tumor cells it may appear yellow in colour

• Microscopic findings

  •  Tumor has high cellular density areas with alternating pauci cellular areas composed of largely dilated vessels and cyst like spaces

  • Cyst wall and adjacent brain tissue shows dense layer of non-neoplastic piloid gliosis in which Rosenthal fibres are abundant

  • Two variants have been described

    • Reticular variant – in this small islands of cells or individual cells surrounded by reticulin are present. Nuclei is more uniform in this variant.

    • Cellular variant – tumor cells are arranged in large lobules

  • Stromal cells contain lipid which is extracted during tissue processing and cytoplasm appears vacuolated. When non-vacuolated, the cells have smooth border and are epithelioid

  • Cytoplasmic hyaline droplets are present in few cases

  • Nuclei of stromal cells may be round or reniform, but large hyperchromatic nuclei are also scattered through out the lesion

  • mitosis is uncommon and of no prognostic significance

  • Vasculature in hemangioblastoma consists of large feeding to draining vessels as well as iintervening capillaries. Vessels are thin walled and lined by flat endothelial cells (not plump)

  • Mast cells are found and is a common feature of this tumor

  • Occasional foci of extramedullary hematopiesis can occur due to erythropoietin production

• Immunohistochemistry

  • stromal cells are reactive for

    • Inhibin

    • GFAP – positive in few cases like lobular variant

    • Neuron specific enolase

    • S-100

  • They are negative for – CD 31, Keratin, Epithelial membrane antigen, Neurofilament protein, and Synaptophysin

  • These lesions have low MIB-1 labelling index (>3%)

• Differential diagnosis

  • Non representative tissue of cyst wall resemble pilocytic astrocytoma but unlike hemangioblastoma, cerebellar astrocytomas effect primarily the young

  • Renal cell carcinoma metastatic deposit – though the lesion has clear cells but the cells are geometrically arranged or uniformly aligned in relation to the vasculature. Reticulin is usually more abundant in hemangioblastomas in which it surrounds individual tumor cells or small clusters to an extent which is not seen in RCC. RCC are reactive for EMA and CD10 where as hemangioblastomas are negative

  • Foamy macrophages in cerebellar infarct can simulate hemangioblastopma but former lacks reticulin network and are reactive for markers of macrophages

  • Microcystic and angiomatous meningiomas– They differ from hemangioblastoma in having more hyalinized blood vessels and cells are reactive focally for EMA

  • Capillary hemangioma – Unlike hemangioblastoma there are no vacuolated interstitial cells. Vessels in capillary hemangioma are lined by plump endothelial cells, which some times give hobnail appearance where as in hemangioblastomas vessels are lined by flattened endothelial cells

• Treatment and prognosis

  • Treatment – complete resection of tumor

  • Radiotherapy is limited only to the non- resectable tumor of the medullary or high cervical spinal cord