Cerebral Hemispheres: Diagnosis



Cerebral Hemispheres: Diagnosis










Glioblastoma is the most common and most aggressive brain tumor, illustrated here as a large mass with a hemorrhagic and necrotic center and extending across the corpus callosum image, causing midline shift.






Glioblastomas are characterized by markedly pleomorphic tumor cells image with stretchy, densely eosinophilic cytoplasm in a fibrillar background. Mitoses image are present in high-grade tumors.


SURGICAL/CLINICAL CONSIDERATIONS


Goal of Consultation



  • Determine whether a lesion should undergo resection (e.g., glioblastoma [GBM]) or diagnostic sampling only to be followed by treatment with chemo- or radiotherapy (e.g., lymphoma)


  • Allow for proper handling of tissue for ancillary studies (i.e., molecular studies, electron microscopy, microbiologic culture)


Change in Patient Management



  • Tumors requiring resection may have additional tissue excised to obtain tumor-free margins


  • If specimens are not adequate for diagnosis &/or ancillary studies, additional biopsies may be performed


Clinical Setting



  • Patients with neurologic symptoms often require tissue sampling



    • Patients presenting with symptoms and a focal lesion require diagnosis



      • New onset of seizures


      • Localizing signs (e.g., hemiparesis, language difficulty)


      • Signs and symptoms of increased intracranial pressure


    • Patients with known systemic illnesses and suspected brain involvement require diagnosis



      • Metastatic carcinoma


      • Bone marrow transplant or other immunocompromised states


    • Patients with diseases that require tissue sampling for ancillary studies but that do not require intraoperative diagnosis



      • Dementing illness, including Creutzfeldt-Jakob disease: Frozen tissue is saved for molecular analysis, and remaining tissue is treated with formic acid and processed by hand


      • Vasculitis: Levels on paraffin block are more useful for focal lesions


      • Epilepsy resections: Orientation of hippocampal resections may be needed


SPECIMEN EVALUATION


Neuroimaging



  • Imaging findings are very helpful in suggesting most likely diagnosis



    • Neuroanatomic localization


    • Signal characteristics


Gross



  • Usually very few distinctive macroscopic characteristics



    • Gliomas: Soft, gray-translucent, gelatinous texture


    • Metastatic carcinoma: Red or tan, gritty consistency


    • Abscesses: Purulent, sometimes with fibrous wall


  • Distinguish lesional from normal



    • Normal: White, homogeneous, soft consistency


Frozen Section



  • Important not to use entire specimen



    • Additional tissue may not be available for other studies


  • A minute portion of specimen is taken for cytologic preparation


  • Frozen section method



    • Perch tissue to be frozen on small bead of embedding medium, but do not cover with medium


    • Freeze quickly with light touch of metal heat extractor or cryospray to avoid ice crystals in tissue


    • Step section carefully into block to preserve tissue when making slides


  • In some cases, cytologic preparations without frozen sections may be preferable



    • Very small specimens


    • Suspected infectious cases


    • Specimens with calcifications


Cytologic Preparations



  • Smear method



    • Place 1-3 pinhead-sized fragments 1/3 of the way down on glass slide



    • Use 2nd slide to gently smear tissue


    • Place immediately in fixative to avoid drying artifact


  • Touch preparation method



    • Use for firm/calcified/fibrous lesions


    • Gently and rapidly touch tissue (held gently in forceps) once to slide surface



      • If touched multiple times, some of the areas will have air-drying artifact


    • Place immediately in fixative to avoid drying artifact


  • Scan entire slide, as lesions may be heterogeneous


MOST COMMON DIAGNOSES


Pilocytic Astrocytoma (WHO Grade I)



  • Frozen section



    • Dense areas with fibrillary background, containing Rosenthal fibers and eosinophilic granular bodies, alternating with loose, microcystic regions


    • Oval nuclei with variable pleomorphism, rare mitoses


    • Frequent microvascular proliferation, of no prognostic significance


    • Necrosis rare (suggests alternative diagnosis)


    • Smear


    • Clear bipolar cytomorphology


    • Network of fibers in background


    • Rosenthal fibers and eosinophilic granular bodies


    • Knots of microvascular proliferation


Diffuse Astrocytoma (WHO Grade II)



  • Frozen



    • Cellularity slightly > normal brain


    • Cytologic atypia may be mild


    • Elongated nuclei in infiltrating cells in white matter


    • Perineuronal satellitosis in cortex


    • Mitoses very rare


    • No microvascular proliferation or necrosis


  • Smear



    • Fibrillary background clearer than in frozen


    • Individual cytologically atypical nuclei (hyperchromatic, irregularly shaped, enlarged compared to normal glia)


  • Difficulties



    • Findings must correlate with neuroimaging



      • Diffuse astrocytoma is noncontrast enhancing


      • Enhancement implies higher grade


      • Infiltrating edges of high-grade tumors are identical to low grade


    • Distinction from reactive processes, such as encephalitis, may require special studies (i.e., diagnosis deferred to permanents)


Oligodendroglioma (WHO Grade II)



  • Frozen section



    • Uniform, round nuclei


    • Satellitosis around cortical neurons, subpial tumor cell accumulation


    • Branching capillary network (“chicken wire” vasculature)


    • Often, microcalcifications, microcysts


    • May have microvascular proliferation and rare mitoses


    • No brisk mitotic activity or necrosis


  • Smear



    • Fine fibrillary background


    • Uniform, round “naked” nuclei (no cytoplasmic processes, in contrast to astrocytomas)


  • Difficulties



    • Typical perinuclear halos (“fried eggs”) require formalin fixation, so not present on intraoperative preparations



      • Often not distinguishable from diffuse astrocytoma


      • Report as “glioma without anaplastic features”


    • As for diffuse astrocytomas, must correlate with imaging to make sure sample is not from infiltrating edge of higher grade tumor


    • Unlike in astrocytomas, microvascular proliferation does not automatically confer higher grade


Oligoastrocytoma (Mixed Glioma) (WHO Grade II)



  • Features of both diffuse astrocytoma and oligodendroglioma


  • Diagnosis rarely made on intraoperative consultation


  • Report of “glioma without anaplastic features” is sufficient


Ependymoma (WHO Grade II)



  • Frozen section



    • Variably cellular, with perivascular pseudorosettes, ependymal tubules or canals, and small intracytoplasmic vacuoles (lumina)


    • Microvascular proliferation of no prognostic significance


    • Infarct-like necrosis of no prognostic significance


  • Smear



    • Glial tumor cells with uniform oval nuclei, often with small nucleoli


    • Cytoplasmic processes, radially arranged around blood vessels, ± vascular cell proliferation


    • Occasional intracytoplasmic lumina, as well as cilia and terminal bars (blepharoplasts) in tubules


  • Difficulties



    • Though challenging, must distinguish from astrocytoma, as resection is preferred treatment for ependymoma


Anaplastic Astrocytoma (WHO Grade III)



  • Frozen section and smear



    • More cellularity and nuclear pleomorphism than grade II astrocytoma


    • Microvascular proliferation present


    • Mitoses inconspicuous


    • No necrosis


  • Difficulties



    • May be indistinguishable from anaplastic oligodendroglioma or glioblastoma


    • Report of “high-grade glioma” is sufficient


Anaplastic Oligodendroglioma (WHO Grade III)



  • Frozen section and smear



    • More cellularity and nuclear pleomorphism than grade II oligodendroglioma


    • Brisk mitotic activity is usual


    • May have necrosis, microvascular proliferation


  • Difficulties



    • May be indistinguishable from anaplastic astrocytoma or glioblastoma


    • Report of “high-grade glioma” is sufficient



Anaplastic Mixed Oligoastrocytoma (WHO Grade III)



  • Features of both astrocytoma and oligodendroglioma


  • Diagnosis rarely made on intraoperative consultation


  • Report of “high-grade glioma” is sufficient


Anaplastic Ependymoma (WHO Grade III)



  • Frozen section and smear



    • Higher cellularity, pleomorphism, and mitoses than in grade II ependymoma


    • Necrosis prominent


    • Ependymal tubules or perivascular pseudorosettes may be inconspicuous


  • Difficulties



    • Evidence of ependymal differentiation may be scarce, making distinction from anaplastic astrocytoma or glioblastoma challenging


Glioblastoma (GBM) (WHO Grade IV)



  • Frozen section



    • Dense cellularity, pleomorphism, mitotic activity in excess of lower grades


    • Tumor cells may have spindled, epithelioid, gemistocytic, small cell, &/or giant cells



      • GBM variants: Gliosarcoma, small cell GBM, giant cell GBM, granular cell GBM


      • Usually not necessary to distinguish at time of intraoperative consultation


    • Microvascular proliferation with glomeruloid profiles


    • Necrosis with peripheral nuclear palisading


  • Smear



    • Cytologically malignant cells (hyperchromasia, high N:C ratio, irregular nuclear outline, mitoses)


    • Coarse fibrillary background


    • Knotted and blind-ending glomeruloid vessels


    • Necrosis, sometimes with nuclear debris


  • Difficulties



    • Occasionally, epithelioid features mimic carcinoma


    • If only necrotic tissue received, cannot distinguish from necrotic metastasis or lymphoma, infarct, or inflammatory process


Glioneuronal Tumors



  • Ganglioglioma



    • Usually indolent tumor of childhood, arising in temporal lobe


    • Smear and frozen



      • Atypical ganglion cells scattered among variably pleomorphic astrocytoma nuclei, fibrillary or myxoid background


      • Perivascular lymphocytic cuffs


      • Defer grade, unless obvious anaplasia (mitoses, microvascular proliferation, or necrosis)


  • Dysembryoplastic neuroepithelial tumor (DNT)



    • Low-grade, multinodular, cystic tumor of superficial cortex of young patients


    • Smear and frozen



      • Small round neurocytic or oligodendrocyte-like nuclei in single-file or nodular growth pattern


      • Scattered ganglion cells “floating” in microcystic spaces, or myxoid background


      • May have cortical disorganization and abnormal neuronal cytomorphology (cortical dysplasia) at interface with brain


  • Central neurocytoma



    • Low grade, usually arising in ventricles but may be extraventricular


    • Strictly speaking, a neurocytic tumor but with astrocytic features detectable in some cases


    • Smear and frozen



      • Small round neurocytic or oligodendrocyte-like cells, often with perinuclear halos


      • Fine branching capillary network


    • May be impossible to distinguish from oligodendroglioma on frozen


Supratentorial Primitive Neuroectodermal Tumors



  • Smear and frozen: Small blue cells, with high apoptotic and mitotic indices


  • Frozen: Well- or poorly formed tumor cell rosettes with fibrillary centers


  • May be difficult to distinguish from small cell GBM or lymphoma on a limited biopsy


Other Primary Neuroepithelial Tumors



  • Pleomorphic xanthoastrocytoma



    • Superficial cortical lesion, often with cyst, in young adults


    • Frozen and smear



      • Bizarre ganglioid and astrocytic cells, some with foamy cytoplasm


      • Eosinophilic granular bodies in background


    • Definitive diagnosis may require ancillary studies (BRAF analysis, immunohistochemistry)


  • Subependymal giant cell tumor of tuberous sclerosis



    • Bulky, nodular tumor in floor of lateral ventricle


    • Usually, patient has stigmata of tuberous sclerosis (cortical tubers, sebaceous hyperplasia, subungual nodules, Lisch nodules, “ash-leaf” spots)


    • Frozen and smear: Bizarre cytomorphology with large cells having ganglioid and astrocytic features


  • Pilomyxoid astrocytoma



    • Large bifrontal tumor of infants


    • Smear and frozen



      • Bipolar glial cells in myxoid background


      • No Rosenthal fibers or eosinophilic granular bodies


    • Behaves more aggressively than pilocytic astrocytoma


    • If recognized intraoperatively, a more extensive resection might be considered


  • Choroid plexus tumors



    • Papilloma



      • Frozen: Well-formed papillary structures with benign cuboidal or ciliated epithelium


      • Smear: Papillary structures well seen


    • Atypical papilloma



      • Frozen and smear: More complex configurations of epithelial structures, with nuclear atypia


    • Choroid plexus carcinoma



      • Frozen and smear: Very atypical, indistinguishable from metastatic adenocarcinoma


  • Pineal region tumors

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Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Cerebral Hemispheres: Diagnosis

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