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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