Five Most Common Problems in Surgical Neuropathology
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1 Five Most Common Problems in Surgical Neuropathology If the brain were so simple that we could understand it, we would be so simple that we couldn t Emerson Pugh What is your greatest difficulty in neuropathology? 1. Differentiating glioma from non-neoplastic diseases 2. Metastatic vs. lymphoma vs GBM 3. Pediatric Tumors 4. Grading meningioma 5. I don t deal with neuropathology cases D i f f e r e n t i a t i n g g l i o m a f r.. 63% M e t a s t a t i c v s. l y m p h o m a... 2% P e d i a t r i c T u m o r s 15% G r a d i n g m e n i n g i o m a 6% I d o n t d e a l w i t h n e u r o... 14% CASE 1 FLAIR 49 year-old woman with progressively worsening headaches Physical examination was unremarkable All laboratory analyses within normal limits MRI shows only patchy non-enhancing FLAIR abnormality A brain biopsy was performed. 1
2 CASE 1 40x CASE 1 200x CASE 1 400x 2
3 What is your diagnosis? CASE 1 (continued) 1. Encephalitis, NOS 2. Infiltrating glioma 3. No significant pathology 4. Insufficient biopsy 5. Gliosis 33% 8% 10% 1% E n c e p h a l i t i s, N O S I n f i l t r a t i n g g l i o m a N o s i g n i f i c a n t p a t h o l o g y I n s u f f i c i e n t b i o p s y 48% G l i o s i s In addition to headaches, the patient developed lower extremity weakness and irritability MRI signal abnormalities worsened A second biopsy suggested DDx= Vasculopathy, Encephalitis, Gliomatosis, Toxic/Metabolic Disease, Drug effect? FLAIR DIFFUSION CASE 1 40x 3
4 CASE 1 100x CASE 1 200x First Biopsy 400x Second Biopsy 400x What is your diagnosis now? 1. Chronic Encephalitis 2. Infiltrating glioma 3. Progressive Multifocal Leukoencephalopathy 4. Demyelinating disease 5. Insufficient diagnosis C h r o n i c E n c e p h a l i t i s 1% I n f i l t r a t i n g g l i o m a 55% P r o g r e s s i v e M u l t i f o c a l... 28% D e m y e l i n a t i n g d i s e a s e 7% I n s u f f i c i e n t d i a g n o s i s 9% 4
5 5/27/2011 IDH-1 staining Infiltrating Astrocytoma (Gliomatosis Cerebri) What is helpful Neuroradiology impression Cytology!! IDH-1 (commonly) Ki-67 (MIB-1) P53 protein Neurofilament protein (occasionally) (occasionally) MIB-1 staining Neurofilament protein immunohistochemistry Normal Infiltrating Astrocytoma 5
6 Case 2 62 year old male presented with headaches and left sided weakness. MRI revealed an intra-axial mass lesion consistent with a high grade glioma Smear Smear 6
7 Frozen Paraffin Specimen 7
8 What is your diagnosis? 1. Glioblastoma 2. Metastatic carcinoma 46% 3. Malignant Lymphoma 4. Angiocentric glioma 5. Multiple Sclerosis 22% 14% 19% 0% G l i o b l a s t o m a M e t a s t a t i c c a r c i n o m a M a l i g n a n t L y m p h o m a A n g i o c e n t r i c g l i o m a M u l t i p l e S c l e r o s i s CD20 Malignant Lymphoma (helpful hints) PCNSL can resemble malignant glioma in every aspect; clinically, radiologically and sometimes histologically!! >99% DLBCL, CD20, CD79a, MUM-1 (+) Must exclude systemic DLBCL Association with immunosuppression Other types can be seen (Marginal zone, T-cell, Anaplastic Large Cell, Intravascular, Lymphomatosis) 8
9 Malignant Lymphoma (helpful hints 2) A smear is almost always helpful Frozen section can be helpful if (classic) The angiocentric pattern is recognized Discohesive nature is prominent Endothelial vascular proliferation is present (NOT LYMPHOMA!!!!) Important to ask about prior steroid treatment Case 3 14 year old boy presented with headaches, gait disturbance and nausea. His neurological exam showed a positive Romberg sign. An MRI revealed a solid mass in the posterior fossa Smear T1-contrast FLAIR T1-non contrast 9
10 10
11 What is your diagnosis? Oligodendroglioma-like Lesions 1. Oligodendroglioma 2. Clear Cell Ependymoma 3. Dysembryoplastic Neuroepithelial Tumor 4. Pilocytic Astrocytoma 5. Demyelinating Disease O l i g o d e n d r o g l i o m a 15% C l e a r C e l l E p e n d y m o m a 4% D y s e m b r y o p l a s t i c N e u r o... 5% P i l o c y t i c A s t r o c y t o m a 76% D e m y e l i n a t i n g D i s e a s e 0% Diffuse Astrocytoma (rare subtypes) Clear cell Ependymoma Central Neurocytoma Dysembryoplastic Neuroepithelial Tumor PILOCYTIC ASTROCYTOMA Clear cell Meningioma Macrophage-rich lesion Metastatic clear cell neoplasms (e.g. renal) 11
12 PILOCYTIC ASTROCYTOMA PILOCYTIC ASTROCYTOMA Chronic Disease!!! WHO Grade I Solid tumors occasionally infiltrative at edge Accounts for almost all pediatric oligodendroglioma-like tumors in the posterior fossa Markedly variable histology Rosenthal fibers are helpful but occasionally absent Small biopsies can be difficult BRAF gene duplication appears as a unique genetic aberration, useful in diagnosis in small biopsies. BRAF probe (RED) in Chr 7q PILOCYTIC ASTROCYTOMA Other useful immunostains Neurofilament (lack of infiltrative nature) GFAP (uh-huh??) Olig-2 (maybe? Nuclear stain) Ki-67 /MIB-1 ( low index) Synaptophysin commonly positive (BEWARE) PhosphoERK staining CASE 4 49 year old man presented with headaches and imbalance Physical examination was recorded as unremarkable An MRI revealed an occipito-parietal multilobular mass that avidly enhanced He underwent a gross total resection 12
13 T1-contrast 13
14 What is your diagnosis? 5/27/ H e m a n g i o p e r i c y t o m a S o l i t a r y F i b r o u s T u m o r 1. Meningioma Grade I 2. Atypical Meningioma, Grade II 3. Malignant Meningioma Grade III 4. Hemangiopericytoma 5. Solitary Fibrous Tumor 3% 58% 33% 3% 4% M e n i n g i o m a G r a d e I A t y p i c a l M e n i n g i o m a, G... M a l i g n a n t M e n i n g i o m a...
15 WHO Grade II Meningioma (10%) 4 or more mitoses per 10 HPF, or Brain invasion, or Three of the following Loss of architecture, Increased cellularity, Prominent nucleoli Foci of spontaneous necrosis, Small cell change Chordoid variant Clear-cell variant Grade II or Atypical Meningioma What is helpful This looks weird! Easily recognizable mitotic figures High MIB-1 staining (e.g. 10%) Brain invasion: Identification of meningothelial nests surrounded at least on 3 sides by neuropil Case 5 Presented by Dr. Perry MS Foamy is Cortex Optic thought They're Relapsing Sites neuritis, to of be sharply involvement spinal and autoimmune, demarcated, remitting pathology, seem most demyelinating random periventricular I don't of the know to time, why; disease Marked macrophages Tumefactive Mitotic Axons may myelin figures are be spared involved, MS predominate, loss shouldn't is is challenging, on seen this neurofilament be we on misconstrued, Luxol know plaques diagnostically, now, fast stains, with blue, activity, plaques, Foamy Forming macrophages A chronic debilitating Dawson's plaques but progressive provide disease, Cognitive they looks fingers the determine loss brain gray the Perivascular lymphocyte occurs, fan deficits clue, we and out signs sunken to PAS positive the radially, cuffs, perhaps are let need material spine and you new although affected, most axons clues increase to are surrounding symptoms know therapies, A ring don t enhancing call it mass GBM or often you provokes, might this, the stripping retained too get is naked the that the a how sued tissue crime cellularity we tumor's new myelin eye vascular MS! see biopsy with probably therapies tracks ease not true, 15
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