“SOME BODIES IN THE BRAIN” Noon Diagnostic Conference 11-20-2003 Ronald L. Hamilton, M.D. Associate Professor of Neuropathology, University of Pittsburgh

Some Bodies in the Brain Identify these “bodies” that populate neuropathology

Psammoma bodies

Verocay body

Eosinophilic Granular Bodies (EGB)

Negri bodies

Cortical Lewy Body

Round basophilic inclusion #1 (Pick body vs. mnd inclusion body)

Round basophilic inclusion #2 (Pick body vs. mnd inclusion body)

Bunina bodies

Corpora amylacea

PAS stain Lafora body (polyglucosan body)

Hirano body

Granulovacuolar degeneration (Simchowicz bodies)

Marinesco body

Herring bodies

Buscaino bodies (mucocytes)

Zebra bodies

Fingerprint bodies

Psammoma bodies Psammoma bodies: meningioma

Psammoma bodies Derived from meningothelial whorls Psammomatous meningioma spinal cord (females)

Psammoma bodies melanotic Schwannomas - 50% are psammomatous half of melanotic psammomatous Schwannomas have Carney complex Auto dominant mutation in Protein kinase A holoenzyme lentiginous facial pigmentation cardiac myxoma, calcifying Sertoli cell tumors endocrine overactivity Cushing syndrome multinodular adrenal hyperplasia acromegaly - pituitary adenoma

Verocay bodies Schwannoma Antoni A areas Infrequent in acuostic and cellular Schwannomas

Verocay bodies Bilateral acoustic schwannomas = NF II autosomal dominant 22q12 - merlin (schwannomin) similar to cytoskeletal proteins moesin, ezrin, radixin (MER) +meningiomas, spinal ependymomas, posterior lens opacities, meningioangiomatosis

Eosinophilic Granular Bodies (EGB) Gangliogliomas, Pilocytic Astrocytomas, Pleomorphic Xanthoastrocytoma Degenerating tumor astrocytes PAS-positive

Eosinophilic Granular Bodies (EGB)

Eosinophilic Granular Bodies (EGB)

Negri bodies Rabies encephalitis Purkinje cells, CA-1 hippocampus >10,000 human deaths per year

Negri bodies

Lewy bodies Parkinson’s Disease DLB, LBVAD, MSA, age

Lewy bodies May be multiple

Lewy bodies Cortical Lewy bodies Entorhinal cortex, cingulate gyrus, insular cortex, other neocortex

Lewy bodies Cortical LB can be difficult to detect on H&E Strongly ubiquitin-positive (vs. globose NFT)

Lewy bodies Alpha-synuclein positive, specific and sensitive

Lewy bodies Hyaline bodies are abnormal aggregates of AS May be precursor to LB

Pick bodies Pick’s disease Fronto-temporal dementia Severe neuronal loss and gliosis (“knife-edge” atrophy) Neocortex, dentate gyrus

Pick bodies Tau Strongly argyrophilic (silver stains - Bielschowsky, Bodian) ++tau, +ubiquitin +/- Pick cells (balloon cells) EM-straight filaments Pick cell

MND-inclusion bodies Motor Neuron Disease (MND) inclusion body ALS, ALS with dementia or aphasia FTD (mnd-inclusion body dementia), Primary progressive aphasia Superficial neocortex, dentate gyrus NOT IN MOTOR NEURONS

MND-inclusion bodies ubiquitin ubiquitin Negative silver stain Ubiquitin positive Negative for tau and alpha-synucelin Composition unknown

Pick bodies vs. mnd-inclusion bodies Tau I MND-inclusion ubiquitin Bielschowsky

Bunina bodies Lower motor neurons ALS Unknown composition

ALS - other LMN inclusions Hyaline bodies Ubiquitin skeins

Corpora amylacea Subpial and perivascular most common location

Corpora amylacea Increased with age, Neurodegeneration. Olfactory bulb, base of brain, spinal cord Astrocytic inclusion

Corpora amylacea Ubiq PAS PAS-positive and ubiquitin-positive

Lafora Bodies Lofora Body Disease Polyglucosan Body Disease Myoclonic epilepsy Autosomal recessive Intraneuronal inclusions Liver biopsy

Hirano bodies Hippocampus CA-1, subiculum Neuronal cytoplasmic inclusion Actin and actin-related proteins Non-specific Increased with age esp. with AD

Hirano bodies

Hirano Body (x165,000)

Granulovacuolar bodies of Simchowicz Non-specific, increased in aged and esp. AD Hippocampus CA-1, subiculum, more rarely other

Granulovacuolar bodies of Simchowicz Often multiple Tau-positive Unknown composition

Marinesco bodies Non-specific Substantia Nigra, LC Aged, Parkinson’s PAS-neg, pink on Masson’s trichrome

Herring Bodies Posterior pituitary, swollen axons, incidental

Herring bodies I

Buscaino Bodies Artifact of formalin fixation ?<10%, ?not buffered Do not mistake for edema or storage disorder

Buscaino Bodies “mucocytes” PAS-positive

Zebra bodies Lysosomal storage disorder Mucopolysaccharidoses (MPS I, II and III) Hunter-Hurler, Sanfillipo Cranial nerve nuceli, liver, skin PAS-positive, LFB-positive Water soluble Rare in metachromatic leukodystrophy

Fingerprint bodies Neuronal ceroid lipofuscinosis (NCL, types 1-7) Batten’s Disease, et al. Autosomal recessive PAS-positive LFB, Sudan Black, Oil-red O Lipid stains remain in paraffin Autofluorescent EM - Skin biopsy, lymphocytes (buffy coat prep)

Fingerprint bodies EM 60,000-80,000

NCL Curvilinear bodies Skin biopsy Lymphocytes (buffy coat prep)

Fingerprint bodies Infantile NCL - granular osmiphilic deposits (GRODs) Late-infantile NCL - curvilinear bodies Juvenile NCL - FINGERPRINT BODIES Onset age 4-9 years old pigmentary retinopathy seizures, dementia, blindness spastic paraplegia death age 20-30

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