Neuropathology Flashcards
A well circumscribed lesion was found at the conus medullaris of a 65M. Histological appearance below. Dx?
Myxopapillary ependymoma.
Whether obviously perivascular or not, circular profiles filled with myxoid substance are characteristic of MPE. Normally there is mucin surrounding small vascular channels.
Dx?
Genetic mutation?
CNS WHO grade?
IHC?
DDX?
Adamantinomatous craniopharyngioma is a mixed solid and cystic squamous epithelial tumour with stellate reticulum and wet keratin, usually localized to the hypothalamic–pituitary axis and characterized by activating mutations in CTNNB1 (which encodes the b-catenin protein).
Essential criteria: localised to the sellar region, benign squamous non-keratinising epithelium, stellate reticulin or wet keratin. Desireable: Nuclear immunoreactivity for β-catenin, Mutation in CTNNB1, Absence of BRAF p.V600E mutation.
CNS WHO grade 1.
IHC: epithelial cells p63(+), HMWCK (+) (CK5/6, AE1/AE3) and LMWCK (+), PDL1 is expressed in the cyst-lining epithelium of adamantinomatous craniopharyngioma, SOX9 is widely expressed.
DDX: papillary craniopharyngioma, xanthogranuloma, Rathke cleft cyst, epidermoid and dermoid cysts, and pilocytic astrocytoma.
Well circumscribed lesion in the 4th ventricle
dx?
Subependymoma
Glioma characterized by the clustering of uniform to mildly pleomorphic tumour cell nuclei in an abundant fibrillary matrix prone to microcystic change (CNS WHO grade 1).
Tumour cell nuclei cluster in a dense fibrillary matrix.
Below: Tumour cell nuclei are small, uniform, and without mitotic activity.
myxopapillary ependymoma
Essential & diagnostic critera
Common location:
Essential: Glioma with papillary structures and perivascular myxoid change or at least focal myxoid microcysts AND Immunoreactivity for GFAP AND DNA methylation profile aligned with myxopapillary ependymoma (for unresolved lesions)
Desireable: Papillary arrangements of tumour cells around vascularized fibromyxoid cores AND Location in the filum terminale or conus medullaris
Lumbosacral lesion.
dx?
Key dx features
IHC:
Myxopapillary ependymoma
Glioma with papillary structures and perivascular myxoid change or at least focal myxoid microcysts AND Immunoreactivity for GFAP AND (for unresolved cases) DNA methylation profile aligned with myxopapillary ependymoma
Desireable:
Papillary arrangements of tumour cells around vascularized fibromyxoid cores
Location in the filum terminale or conus medullaris
Tumour cells are diffusely and strongly GFAP-immunoreactive.
meningioma
- Subtypes
- Most common subtypes
15 subtypes, see image:
Most common subtypes: meningothelial, fibrous, and transitional meningiomas.
meningioma grading
grading (CNS 2 and 3)
Chordoid and clear cell = WHO grade 2 (Higher likelihood of recurrence) independent of the criteria otherwise applied for CNS WHO grade 2 atypical meningioma;
CNS WHO grade 2:
4 to 19 mitotic figures in 10 consecutive HPF of each 0.16 mm2 (at least 2.5/mm2)
OR
Unequivocal brain invasion (not only perivascular spread or indentation of brain without pial breach)
OR
Specific morphological subtype (chordoid or clear cell; see text)
OR
At least three of the following:
· Increased cellularity
· Small cells with high N:C ratio
· Prominent nucleoli
· Sheeting (uninterrupted patternless or sheet-like growth)
· Foci of spontaneous (non-iatrogenic) necrosis
CNS WHO grade 3
20 or more mitotic figures in 10 consecutive HPF of each 0.16 mm2 (at least 12.5/mm2)
OR
Frank anaplasia (sarcoma-, carcinoma-, or melanoma-like appearance)
OR
TERT promoter mutation
OR
Homozygous deletion of CDKN2A and/or CDKN2B
base of skull/occiptal lesion
dx?
Key features demonstrated in image
Chordoma (conventional type)
Typically involves the clivus, sacrococcygeal bones or vertebrae Chords, sheets and individual cells, including cells with bubbly cytoplasm (physaliphorous cells), arranged in lobules set in a myxoid matrix Positive for cytokeratin, EMA, S100 protein and brachyury Poorly differentiated chordoma demonstrates loss of INI1
Image: cells reside in abundant myxoid stroma
saccrococcygeal lesion
dx
key featurse demonstrated by image
Chordoma
Typically involves the clivus, sacrococcygeal bones or vertebrae Chords, sheets and individual cells, including cells with bubbly cytoplasm (physaliphorous cells), arranged in lobules set in a myxoid matrix Positive for cytokeratin, EMA, S100 protein and brachyury Poorly differentiated chordoma demonstrates loss of INI1 Image: High power view of chordoma demonstrates cells with vesicular chromatin and bubbly to clear cytoplasm.
GB IDH WT (WHO grade 4)
molecular dx criteria sufficient for dx
TERT promoter mutation
EGFR amplification
gain chromosom 7/losso f 10
meningioma subtypes
list subtypes
base of skull lesion
dx
Key features demonstrated
IHC
Meningioma WHO grade 1 (meningothelial)
Lobular growth pattern, syncytium-like appearance due to poorly defined cell borders, and frequent clear nuclear holes, with occasional intranuclear pseudoinclusions.
IHC: EMA/vimentin/SSTR2A (+)
convexity lesion brain
dx
features demonstrated
IHC
Meningioma, CNS WHO grade 1, fibrous subtype
features demonstrated: Fascicular spindle cell tumour with variable collagen deposition.
IHC: EMA (weak +)/SSTR2A (+); S100 (+)
convexity lesion brain
dx
feature demonstrated
meningioma, who grade 1 (transitioanl subtype)
thoracic spine lesion
dx
molecular mutations
meningioma who grade1, psammomatous subtype
45M supratentorial lesion
dx?
Key features
Meningioma, CNS Who grade 2 (chordoid subtype)
Cords of small epithelioid to vacuolated tumour cells embedded in a mucin-rich matrix.
spinal cord lesion
dx
key features
tancytic ependymoma, CNS WHO grade 2 (always)
Most commonly found in s/c
Have both ependymal and astrocytic features. High degree of fibrillar cellular processes resembling astrocytomas and smooth nuclei with rounded borders and salt/peppe chromatin. Pseudorosettes less common. Architecture key diagnostic features: zones with many nuclei and other zones where fibrillar cellular processes predominate.
myxopapillary ependymoma
essential and desireable dx criteria
cervicothoracic spinal cord
dx
IHC
Myxopapillary ependymoma (CNS WHO grade 2)
Prototypical is the radial arrangement of cuboidal to elongated tumour cells around hyalinized fibrovascular cores in papillary fashion, with accumulation of basophilic, myxoid material around blood vessels and in microcysts. Myxoid material, highlighted by PAS and Alcian blue positivity, is useful in the identification of examples manifesting little, if any, papillary structure and composed instead of epithelioid cells in confluent sheets.
Diffuse immunoreactivity for GFAP distinguishes myxopapillary ependymomas from metastatic carcinomas, paragangliomas, schwannomas, chordomas, and myxoid chondrosarcomas. Immunolabelling for S100 is also typical, and reactivity for CD99 and CD56 is frequent { 23455181 }. Tumour cell nuclei are not immunoreactive for OLIG2, and dot-like cytoplasmic EMA labelling is typically absent. Myxopapillary ependymomas are often labelled by the AE1/AE3 pancytokeratin cocktail, but they are generally negative for CAM5.2, CK5/6, CK7, and CK20
15F H/O tuberous sclerosis.
Hydrocephalous. Lateral ventricle lesion
dx?
Key features?
subependymal giant cell astrocytoma ( CNS WHO grade 1). NB: mitoses and pallisading necrosis do not upstage it.
typically arise from the subependymal tissue of the lateral ventricles adjacent to the foramen of Monro.
In this image:
Elongated cytoplasmic profiles and a more ganglioid appearance may be a feature.
Diffuse glioma, IDH-WT
Grading as per WHO
ependymal tumours
Outline the WHO 2021 categories
diagnostic criteria for chordoma
dx criteria for pleomorphic xanthoastrocytoma.
Imaging features
demographic
Usu cystic.
young adults.
Intraventricular tumour, lateral ventricle.
25M
Dx:
Essential and desirable dx features
Central neurocytoma (CNS WHO grade 2)
is an intraventricular neuroepithelial tumour composed of uniform round cells with a neuronal immunophenotype and low proliferation index (CNS WHO grade 2).
Grading of astrocytoma, IDH-mutant:
essential and desirable dx criteria for astrocytoma, IDH-mutant
essential and dx criteria for subependymoma
Image; microcytic change in subependgymoma is common
well circumscribed cerebral lesion.
Dx?
Dx molecular?
Supratentorial ependymoma (WHO grade 2 -3 depending on brisk mitoses or vascular proliferation)
YAP1 or ZFTA fusions; NEC if another alteration is detected and NOS if unable or unfeasible to do molecular.
Molecular can be done by interphase FISH, RT-PCR–based sequencing methods, and next-generation sequencing (including transcriptome sequencing)
cerebellar well circumscribed lesion.
Dx (+ grade):?
DDX:
Dx molecular?
Posterior fossa ependymoma, CNS WHO grade 3
Grade 3 -> microvascular proliferation.
Ddx: Subependymoma
Dx: If feasible, posterior fossa ependymomas should be assigned to a molecular group (PFA, PFB, or subependymoma) { 25965575 }. Absence of immunoreactivity for H3 p.K28me3 (K27me3) in the nuclei of tumour cells is a surrogate marker for PFA ependymoma { 28733933 }, but classification using DNA methylation profiling is considered the standard method, because nuclear expression of H3 p.K28me3 (K27me3) is present in both PFB tumours and subependymomas. If appropriate molecular testing was successfully performed but did not assign a molecular group, a diagnosis of posterior fossa ependymoma can be used with the suffix “NEC” { 29372318 }. An inability to perform the appropriate analysis prompts the addition of “NOS”.
cystic lesion sellar
Dx?
Rathke cleft cyst
intradural cyst.
Dx?
Key features?
Hydatid cyst.
three layers:
Outer acellular laminated membrane.
Germinal membrane ( a transparent nucleated lining)
Protoscolices (attached to the membrane and lining it) (below)
Describe the four molecular groups of medulloblastoma (and their predominant histomorphology)?
WNT-activated, SHH-activated, group 3, and group 4
dx criteria papillary craniopharyngioma?
describe features of a SEGA?
Subependymal giant cell astrocytoma.
a periventricular tumour composed partly of large ganglion-like astrocytes, and strongly associated with tuberous sclerosis (TS) (CNS WHO grade 1).
Imaging: solid, partially calcified masses located in the walls of the lateral ventricles, mostly near the foramen of Monro.
Histo:
Typical appearances range from polygonal cells with abundant, glassy cytoplasm to smaller spindle cells and gemistocyte-like cells arranged in sweeping fascicles, sheets, or nests with intervening fibrillary septa. Giant pyramidal-like cells with a ganglionic-like appearance (without Nissl substance) are common. Considerable nuclear pleomorphism and multinucleated cells are frequent. Clustering of tumour cells and a perivascular rosette-like pattern resembling that of ependymoma are common features. A rich vascular stroma with frequent hyalinized vessels and infiltration by mast cells and lymphocytes, predominantly T lymphocytes, is a constant feature. Parenchymal or vascular calcifications are frequently seen .The presence of mitoses, vascular proliferation, or necrosis does not indicate anaplastic progression.
