CNS Flashcards
Lobulated brain tumour formed of meningothelial cells with ‘syncytial’ appearance (indistinct cell borders) and whorls of cells streaming in parallel. Cells have eosinophilic cytoplasm and small, oval, regular nuclei with fine powdery chromatin, often with nuclear pseudo inclusions. Psammoma bodies are another classic finding.
Meningothelial meningioma (WHO CNS Grade 1)
Differential diagnoses
Schwannoma
Solitary fibrous tumour
Plan:
Correlate with clinical history/radiology (?dural based)
Examine further blocks (for higher grade features)
IPX to support Dx: SSTR2a, EMA, PR
IPX to rule out DDx: STAT6, S100
Next steps - synoptic report, discuss at MDT
A meningioma in which the vascular component exceeds 50% of the total tumour area
Angiomatous meningioma (WHO CNS Grade 1)
Differential diagnosis:
Haemangioblastoma
Plan:
Correlate with clinical history/radiology (?VHL syndrome ?dural based, haemangioblastoma is intraaxial)
Examine further blocks (for higher grade features)
IPX to support Dx: SSTR2a, EMA, PR
IPX to rule out DDx: Inhibin
Next steps: Synoptic report and discuss at MDT
Brain lesion with prominent perivascular lymphoid infiltrates, numerous macrophages
Multiple sclerosis
Differential diagnosis:
Infarct
Infective process
Other degenerative disorders (e.g ADEM, PML)
Plan:
Correlate with clinical history/radiology (?multiple enhancing white matter lesions, temporal/spacial heterogeneity)
Correlate with concurrent microbiology
Special stains to support Dx: Luxol fast blue (demonstrate demyelination). Also Gram, PAS, GMS, ZN (exclude infective process)
IPX to support Dx: CD68 (confirm macrophage nature of cells)
Diffusely infiltrating, highly cellular brain tumour composed of poorly differentiated tumour cells with nuclear atypia and marked pleomorphism. Mitotic activity is brisk. Necrosis (typically ‘palisaded’) and microvascular proliferation (multilayered endothelia within vessels) is diagnostic.
Glioblastoma multiforme (WHO CNS Grade 4)
Differential diagnosis:
Astrocytoma, IDH mutant, WHO CNS Grade 4
Plan:
Correlate with clinical history/radiology (?sporadic intra-axial enhancing tumour)
IPX to support Dx: GFAP, S100, Olig2
IPX to discount DDx: IDH1 mutant protein
Molecular to support Dx:
ATRX and p53 immunostain
IDH1 gene testing if <65 y/o
Glioma gene panel
Next steps: Synoptic report and discuss at MDT
Brain tumour with round, monotonous nuclei with clear cytoplasm creating a fried egg appearance. The tumour forms a delicate ‘chicken wire’ vasculature. Cells are discohesive, often microcystic, and show satellitosis. Macrocalcifications are a common degenerative change.
Oligodendroglioma (WHO CNS Grade 2)
DDx:
Metastatic clear cell carcinoma
Clear cell meningioma
Demyelinating lesion (macrophages)
Plan:
Correlate with clinical history / radiology
Examine further blocks (for higher grade features)
IPX to support Dx: IDH1 mutant protein, GFAP, Olig2
IPX to disprove DDx: Pancytokeratin, SSTR2a, CD68
Molecular testing: 1p/19q codeletion (must have), glioma gene panel
Next steps: Synoptic report, discuss at MDT
Brain tumour with abrupt interface. Cells have round or oval nuclei with speckled chromatin. Cells form perivascular anucleate zones (pseudorosettes), and in some cases make true rosettes (cells radially arranged around a lumen). Other common features are hyalinization of blood vessels and calcification.
Ependymoma (WHO CNS Grade 2)
Differential diagnosis:
Medulloblastoma (in posterior fossa)
Meningioma
Schwannoma
Plan:
Correlate with clinical history/radiology (?periventricular)
Examine further sections (e.g. for higher grade features)
IPX to support Dx: GFAP, S100, EMA (perinuclear dot like positivity)
IPX to discount DDx: Synaptophysin, SSTR2a
Molecular testing (depending on site)
Supratentorial - YAP1 / ZFTA fusion
Posterior fossa - DNA methylation profile
Spinal - MYCN amplification
Next steps: Synoptic report, discuss at MDT
Paediatric small round blue cell brain tumour with densely packed undifferentiated cells (embryonal cells), frequent mitoses and apoptotic bodies. May have ‘Homer Wright rosettes’
Medulloblastoma (WHO CNS Grade 4)
DDx:
Ependymoma
Atypical teratoid/rhabdoid tumour
Plan:
Correlate with clinical history and radiology (?posterior fossa
IPX to support Dx: Synaptophysin
IPX to discount DDx: GFAP, INI1
Molecular to support Dx:
-GAB1 and YAP1 IHC (for genetic subgroup)
-FISH for MYCN amplification
-DNA methylation profiling
Next steps: Synoptic report, discuss at MDT
Name of rosettes in medulloblastoma
Homer-Wright rosettes
Spinal tumour with glial cells arranged around hyalinized fibrovascular cores which show perivascular accumulation of myxoid material. Myxoid material can also accumulate in microcysts.
Myxopapillary ependymoma (WHO CNS Grade 2)
Plan:
Correlate with clinical history/radiology (?distal spinal cord location)
Next steps: Synoptic report, discuss at MDT
Sellar tumour with cords, lobules, and whorls of squamous cells, which show central ‘stellate reticulum’ (loose, microcystic areas) and prominent peripheral palisading. The tumour produces areas of ghost cells / wet keratin, and there can be cysts, calcification, and granulomatous reaction. Adjacent brain shows piloid gliosis and Rosenthal fibers
Adamantinomatous craniopharyngioma (WHO CNS Grade 1)
Plan:
Correlate with clinical history and radiology
IPX to support Dx: Beta catenin (nuclear positivity)
Next steps: Synoptic report, discuss at MDT
Sellar tumour with non-keratinizing, mature squamous epithelium covering fibrovascular cores. Can have abundant inflammation and the epithelium may show areas of goblet cells and ciliated columnar cells.
Papillary craniopharyngioma (WHO CNS Grade 1)
Plan:
Correlate with clinical history and radiology
IPX to support Dx: BRAFV600E
Next steps: Synoptic report, discuss at MDT
Sellar tumour with monotonous population of cells with finely speckled ‘salt and pepper’ chromatin
Pituitary neuroendocrine tumour (PitNET)
Ddx
Ependymoma
Plan
Correlate with clinical history and radiology (?hormone secreting)
Examine further blocks (eg for tumour invasion, areas of increased mitoses)
Special stains: Reticulin (disrupted network)
IPX to support dx: Synaptophysin, chromogranin (expect positive). Also Ki67, pituitary transcption factors (e.g Pit1, Tpit, SF1 - for subclassification)
IPX to discount Ddx: GFAP
Next steps: Synoptic report, discuss at MDT
Brain with diffusely infiltrating glial cells, without cellular cohesion, generating a loose (often microcystic) fibrillary background. Cellularity is mildly to moderately increased with mild nuclear atypia and mitotic activity should be absent or uncommon.
Diffuse astrocytoma, (WHO CNS Grade 2)
Differential diagnosis:
Oligodendroglioma
Lymphoma
Plan:
Correlate with clinical history / radiology
Examine further sections (for higher grade features)
Stains to support Dx: GFAP, Olig2, IDH1 mutant protein (expect positive)
Stains to discount DDx: CD45, CD20
Molecular testing:
P53 and ATRX immunostains
1p/19q codeletion, CDKN2A/2B, TERT promoter mutation, glioma gene panel
Next steps: Synoptic report, discuss at MDT
Well circumscribed brain tumour of clear/vacuolated lipid containing cells (neoplastic stromal cells) with abundant vascular network. Resembles renal cell carcinoma. Clear cell aggregates can induce extramedullary hematopoiesis
Haemangioblastoma (WHO CNS Grade 1)
Differential diagnosis:
Metastatic clear cell RCC
Clear cell meningioma
Paraganglioma
Plan:
Correlate with clinical history and radiologic features (?cerebellar ?VHL syndrome)
IPX to support Dx: Inhibin-alpha
IPX to discount DDx: AE1/AE3, PR and SSTR2a, synaptophysin and chromogranin
Next steps: Synoptic report, discuss at MDT
Advice to clinician: May be assiociated with VHL syndrome. Clinical correlation required
Circumscribed tumour with biphasic appearance - compact fibrillary portions and loose microcystic areas. Fibrillary areas have cells with bipolar (at both ends of cell) ‘piloid’ (hairlike) processes, and Rosenthal fibers. Looser microcystic areas show cobweb-like cell processes and eosinophilic granular bodies.
Pilocytic astrocytoma
(WHO CNS Grade 1)
Differential diagnosis: Reactive piloid gliosis
Plan:
Correlate with clinical history and radiologic features (?cystic tumour with enhancing mural nodule)
Examine further sections (e.g for anaplastic features)
IPX to support Dx: GFAP, S100, Olig2
Molecular (if available): BRAF fusion
Next steps: Synoptic report, discuss at MDT
Spinal tumor divided into lobules by fibrous septa. Tumour cells are arranged in cords or ribbons set within a myxoid matrix. Tumour cells are large with clear to eosinophilic cytoplasm and vacuolated (bubbly) cytoplasm; these are described as ‘physaliphorous cells’.
Chordoma
Ddx
Chondrosarcoma (if chondroid)
Plan
Correlate with clinical history and radiology (?classic location at clivus / sacrum)
Examine further blocks (e.g for size, relation to margins, areas of de-differentiation)
IPX to support Dx: AE1/AE3, brachyury (chondrosarcoma would be negative)
Next steps: Synoptic report, discuss at MDT
Cerebellar tumour composed of a dense network of thin-walled capillaries separated by large polygonal stromal cells with abundant pale eosinophilic or clear, lipid-rich (vacuolated) cytoplasm and round nuclei. Mast cells are often present.
Haemangioblastoma, WHO CNS Grade 1
Differential diagnosis:
Metastatic clear cell renal cell carcinoma
Meningioma (angiomatous or clear cell type)
Plan:
Correlate with clinical history and radiology (?Von Hippel-Lindau syndrome)
IPX to support Dx: Inhibin-A
IPX to discount DDx: AE1AE3 and PAX8 (renal carcinoma), EMA, PR, SSTR2A (for meningioma)
Next steps: Synoptic report, discuss at neuro-oncology MDT
Advice to clinician: may be assiociated with VHL. Consider VHL screening if appropriate.
Brain tumour with nodular mass of cells with abundant clear cytoplasm, well defined membranes, and large, angular nuclei with coarse chromatin and prominent nucleoli. Packets of cells are separated by delicate branching fibrovascular septa. There is lymphocytic inflammation and often granulomatous inflammation, and there can be areas of fibrosis.
Germinoma
Differential diagnosis:
Embryonal carcinoma
Metastatic carcinoma
CNS DLBCL
Plan:
Correlate with clinical history and radiology (?pineal region ?radiologic evidence of metastases)
Examine further blocks (for other germ cell tumour elements to indicate mixed germ cell tumour)
IPX to support Dx: SALL4, PLAP, cKIT CD117, OCT 3/4
IPX to discount DDx: CD30, AE1/AE3, CD45 and CD20
