Oligodendroglioma



Oligodendroglioma


Alexandros D. Polydorides, MD, PhD





Key Facts


Clinical Issues



  • 2-5% of all primary brain tumors, 5-25% of gliomas


  • Most occur in adults, 5-7% arise in infancy/childhood


  • 90% in supratentorial white matter (50-65% frontal)


  • Long symptomatic period (seizures) before diagnosis


  • Slow growing, indolent, but often recur locally


  • Common leptomeningeal or CSF spread


  • Gross total resection, adjuvant chemoradiation



    • 1p/19q deletion: Favorable response, prognosis


  • Resected, well-differentiated lesions: Good prognosis


Image Findings



  • Well circumscribed, heterogeneous, may enhance



    • Hemorrhagic, cystic, calcified


Macroscopic Features



  • Soft, gelatinous, gray-pink, calcified (gritty)


Microscopic Pathology



  • Diffusely infiltrating glioma of cerebral cortex


  • Monomorphic: Round nuclei, small nucleoli


  • Clear perinuclear vacuolization (“halo”)



    • Processing artifact, absent in frozen sections


  • Arborizing microvascular pattern (“chicken wire”)


  • Microcalcifications, microcysts, extracellular mucin


  • Perineuronal satellitosis, subpial aggregates


  • Circumscribed “clones” within tumor


  • Focal “minigemistocytes”: Astrocytic appearing



    • Prominent, eccentric pink cytoplasm


  • Anaplastic oligodendroglioma (WHO grade III)



    • Hypercellularity, atypia, nuclear pleomorphism


    • Increased mitoses, necrosis, vascular proliferation


  • Mixed glioma (oligoastrocytoma)



    • Both astrocytoma, oligodendroglioma components







Axial T2WI MR shows a heterogeneous cortical/subcortical mass image with cystic change image. Despite a circumscribed appearance, oligodendrogliomas have infiltrating margins.






Graphic shows the gross appearance of an oligodendroglioma superficially expanding the cerebral cortex and containing chalky calcifications image and cystic degeneration image.


TERMINOLOGY


Synonyms



  • Malignant = anaplastic oligodendroglioma


Definitions



  • Diffusely infiltrating glioma, mostly in subcortical white matter of cerebral hemispheres, composed of neoplastic cells resembling oligodendrocytes


  • WHO grades: II (well differentiated), III (anaplastic)


  • Chromosome 1p/19q deletion portends better response to chemotherapy and improved prognosis


  • Mixed glioma (oligoastrocytoma): Phenotypic features of both oligodendroglioma and astrocytoma


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • In rats, induced experimentally with nitrosoureas


  • Human cases reported after prior irradiation


  • Viral sequences (SV40, JC, BK) identified in some cases


Histogenesis



  • Morphologic characteristics suggest transformation of oligodendrocytes, but evidence is circumstantial


  • Originating cell may be immature glial precursor



    • Dedifferentiation of putative bipotential stem cell



      • Oligodendrocyte type 2 astrocyte progenitor


    • May explain occasional immunoreactivity for GFAP


    • Possible common precursor in oligoastrocytoma


  • Oligodendrocytes may be related to neurons



    • Some tumors have neurosecretory-like granules


    • Some staining for Hu protein, NMDA receptor 1


    • Ultrastructural findings suggest distinct neoplasm


Genetics



  • Translocation between chromosomes 1 and 19



    • Results in 1p/19q codeletion


    • Incidence varies (40-90%)



      • Not entirely sensitive or specific


      • May be present in some astrocytomas


    • Corresponding gene mutations not yet identified



      • Several gene candidates exist


  • As yet, undetected point mutations may also exist



    • Occasional reports of familial clustering


  • TP53 mutation generally rare in oligodendrogliomas



    • LOH seen in < 10-15% of cases


    • Virtually mutually exclusive with 1p/19q deletions


  • Mixed glioma histogenesis is unclear



    • In 1 study both components had 1p/19q deletion


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 0.2-0.3 per 100, 000 population annually


    • Approximately 2-5% of all primary brain tumors



      • 5-25% of all intracranial gliomas


  • Age



    • Most occur in adults



      • Peak in 4th-6th decade; mean age: 40-45 years


      • Infratentorial lesions tend to occur slightly earlier


    • 5-7% arise in infancy/childhood


  • Gender



    • Variable, slight male preponderance (3:2 to 2:1)


Site



  • Throughout neuraxis, mostly in cerebral hemispheres



    • 90% in supratentorial white matter


    • 50-65% involve frontal lobe


    • Remaining lobes: Temporal > parietal > occipital


    • 50% involve multiple lobes, 20% bilateral


  • Rare lesions in cerebellum, brainstem


  • Unusual spinal/leptomeningeal lesions in children


Presentation



  • Long symptomatic period (1-5 years) before diagnosis


  • Seizures (epileptic), may also be focal/localizing



    • Due to diffuse involvement of cerebral cortex


  • Focal neurologic deficits



  • Increased intracranial pressure, headache



    • Larger posterior fossa lesions (obstruction)


Natural History



  • Most are generally slow growing, indolent


  • Local recurrence is most common cause of death



    • Relapse less likely in lesions with 1p/19q deletion


  • Malignant progression (dedifferentiation) may occur



    • Less commonly than in astrocytomas


  • Leptomeningeal or CSF spread is common (1-14%)


  • Extracranial metastases: Bone, lung, liver



    • More common than in other gliomas



      • Especially in higher grade lesions


  • Oligodendrogliomatosis



    • Diffuse leptomeningeal spread


    • May be component of gliomatosis cerebri


Treatment



  • Surgical approaches



    • Generally thought unresectable (infiltrating glioma)



      • But surgery is mainstay of treatment


      • For diagnosis, reduction of mass effect


    • Attempt at gross total resection



      • At least of radiologic abnormality


  • Adjuvant therapy



    • In unresected or higher grade lesions



      • Radiation &/or chemotherapy (PCV, thiotepa)


      • Favorable response in 1p/19q deleted lesions


    • Not in largely excised well-differentiated lesions



      • Unless neoplasm recurs


Prognosis



  • Well-differentiated lesions carry good prognosis



    • Survival rates: 5-year (˜ 75%), 10-year (˜ 60%)



      • After gross total resection


    • Rates are 1/2 if subtotal resection or higher grade


    • Better than astrocytomas of comparable grade


  • Prognosis still guarded: Recurrence after > decade


  • 1p/19q deletion significantly improves prognosis



    • Median postoperative survival ˜ 10-15 years



      • (vs. ˜ 2-5 years without codeletion)


    • Survival advantage also in anaplastic lesions



      • But may not apply to pediatric lesions


IMAGE FINDINGS


MR Findings



  • Hypointense on T1WI, hyperintense on T2WI


  • Variable mass effect, little peritumoral edema


  • Well-circumscribed margin with brain parenchyma


  • Heterogeneous: Hemorrhage, cystic degeneration


CT Findings



  • Superficially seated, usually large intracortical lesion



    • Rare, deep-seated lesions may cross corpus callosum


  • Hypo- or isodense, well demarcated


  • Absent or minimal contrast enhancement


  • Higher grade (anaplastic) lesions may enhance



    • But lack rim or ring pattern of glioblastoma


  • Calcification common (30-90%) but not diagnostic



    • Usually intracortical and curvilinear, gyriform


MACROSCOPIC FEATURES


General Features



  • Soft, gelatinous, gray-pink



    • May be densely calcified (gritty)


  • Thickened and expanded cerebral cortex



    • But relatively well circumscribed overall


  • Often superficial, may infiltrate leptomeninges



    • May create marked desmoplastic reaction


  • Cystic degeneration, intratumoral hemorrhage


  • Higher grade lesions are more cellular, “fleshy”



    • But lack central necrosis of glioblastoma


Size



  • Mean size at presentation: 3.5 cm


MICROSCOPIC PATHOLOGY


Histologic Features



  • Generally diffusely infiltrating glioma



    • Obscures normal architecture, gray-white junction



      • Despite relatively sharp macroscopic interface


  • Prominent, circumscribed “clones” within tumor




    • Nodules of ↑ cellularity, atypia, mitotic activity


    • MIB-1 labeling index is higher


  • Less common growth patterns



    • Cohesive ribbons, nests, or clusters of cells


    • Parallel palisades of tumor cells with long nuclei


    • Sarcoma-like areas, especially in higher grade lesions


  • “Secondary structures” often form



    • Perineuronal satellitosis



      • Atypical tumor cells orbit large cortical neurons


      • In larger numbers than normal oligodendroglia


    • Perivascular collections, rare focal pseudorosettes


    • Subpial aggregates


  • Microcalcifications very common (90% of tumors)



    • Perivascular or stromal laminated calcospherites


    • In tumor and surrounding cortex


    • Bone may form in highly calcified lesions


    • However, not specific for oligodendrogliomas


  • Characteristic microvascular pattern



    • Interconnected delicate blood vessels


    • Geometric branching: Short arcs, angular segments



      • May arborize, likened to “chicken wire”


    • Separate out lobules of tumor cells


    • Glomeruloid microvascular proliferations absent


  • Extracellular mucin or microcysts are common



    • Protein-rich, amphophilic, PAS(+) fluid


    • Peripheral vacuolization



      • Resembles dysembryoblastic neuroepithelial tumor


    • Not true cysts (not lined by epithelium)


Cytologic Features

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Oligodendroglioma

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