CNS DISEASES
CNS DISEASES
Key Diagnostic /
Disease / Condition Pathology Gross & Micro Findings Remarks
Molecular Features
Autoimmune Gray plaques (gross), periventricular; Oligoclonal IgG bands in Relapsing-remitting, optic
Multiple Sclerosis
demyelination active plaques show foamy macrophages CSF, Th1/Th17 mediated neuritis common
Autoimmune vs Bilateral optic neuritis + spinal
Neuromyelitis Optica Necrosis, Ig & complement, eosinophils Anti-AQP4 antibodies
aquaporin-4 cord involvement
Diffuse demyelination (ADE), more Monophasic, similar-stage
ADE & ANHE Post-viral/infectious ANHE = Weston Hurst disease
severe necrosis (ANHE) lesions
Central Pontine Osmotic Myelin loss in central pons; axons Post-hyponatremia
Locked-in syndrome
Myelinolysis demyelination preserved correction
Diffuse Astrocytoma IDH mutation = better
Infiltrative glioma Diffuse, poorly defined mass May progress to GBM
(WHO II) prognosis
Anaplastic Astrocytoma Malignant
↑ Cellular, mitotic activity Often IDH mutated Precursor to GBM
(WHO III) astrocytoma
Glioblastoma (WHO IV) High-grade Necrosis + palisading, microvascular IDH-WT = primary (poor), Common in cerebral
Key Diagnostic /
Disease / Condition Pathology Gross & Micro Findings Remarks
Molecular Features
astrocytoma prolif. IDH-mut = secondary hemispheres
Pilocytic Astrocytoma
Benign astrocytoma Cystic + mural nodule; Rosenthal fibers BRAF-KIAA1549 fusion Kids; cerebellum/optic path
(WHO I)
IDH-mut + 1p/19q co-
Oligodendroglioma Infiltrating glioma “Fried egg” cells, chicken-wire vessels Best prognosis among gliomas
deletion
NF2 mutation in spinal
Ependymoma Ventricular tumor Perivascular pseudorosettes Posterior fossa in kids
type
Choroid Plexus Benign papillary Lateral ventricle (kids), 4th
Papillary + fibrovascular core None specific
Papilloma tumor (adults)
Choroid Plexus Malignant
Atypical cells, aggressive Rare Common in children
Carcinoma counterpart
Neuron-glial mixed
Ganglioglioma Large dysplastic neurons BRAF V600E mutation Epilepsy-related
tumor
Cortical Mucin-rich nodules, columnar
DNET None specific Benign, intractable epilepsy
glioneuronal tumor arrangement
Embryonal Small round blue cells, Homer-Wright SHH or WNT subtype, Ki- Radiosensitive; CSF drop mets
Medulloblastoma
cerebellar tumor rosettes 67 ↑ common
CD20+, PDL1+, EBV+
Primary CNS Lymphoma DLBCL, extranodal Diffuse infiltration of large lymphocytes Immunocompromised >60 y/o
(AIDS)
NF2 deletion (22q12),
Meningioma Dural-based tumor Whorls, psammoma bodies Progesterone-sensitive
TERT, CDKN2A
Secondary Lung, breast, kidney,
Metastatic Tumors Circumscribed, multiple lesions Site-specific histology
malignancies choriocarcinoma
Paraneoplastic CNS PCA-1 (Purkinje), anti-Hu, Limbic encephalitis, cerebellar
Immune-mediated Perivascular lymphocytes, gliosis
Syndrome VGCC Abs degeneration
NF1 Tumor syndrome Gliomas, Lisch nodules NF1 (17q11) Café-au-lait, neurofibromas
Bilat. vestibular schwannomas, Meningiomas, spinal cord
NF2 Tumor syndrome NF2 (22q12)
ependymomas lesions
Key Diagnostic /
Disease / Condition Pathology Gross & Micro Findings Remarks
Molecular Features
mTOR pathway TSC1 (9q34) / TSC2
Tuberous Sclerosis Cortical tubers, SEGA Seizures, autism
disorder (16p13)
Vascular tumor VHL gene (3p25.3) → RCC, pheochromocytoma co-
Von Hippel-Lindau Hemangioblastoma with clear cells
syndrome ↑VEGF occur
Microscopic / Histo
Disease / Condition Pathology Gross Findings Etiology / Risk Diagnostic Clues
Features
Senile plaques (β-
Cortical Cortical atrophy, amyloid), neurofibrillary ApoE4, age, Down Gradual dementia,
Alzheimer’s Disease
neurodegeneration widened sulci tangles (tau), Hirano syndrome memory loss
bodies
Lewy bodies (α-synuclein,
Basal ganglia SNCA mutation, MPTP Triad: bradykinesia,
Parkinson’s Disease Pale substantia nigra haloed), loss of pigmented
degeneration toxin rigidity, tremor
neurons
Caudate Caudate atrophy, Neuronal loss, gliosis in HTT gene (CAG repeats, Chorea, dementia, 15-
Huntington’s Disease
degeneration enlarged ventricles striatum AD) year course
Motor neuron
Thin anterior spinal degeneration, Bunina Muscle weakness,
ALS UMN + LMN loss Sporadic or familial
roots bodies, protein aggregates atrophy, fasciculations
(e.g., SOD1, C9orf72)
CJD (Spongiform) Prion-induced Atrophic brain Spongiform vacuoles, Prion ingestion, Rapid dementia,
encephalopathy neuronal loss, PrPSc sporadic, iatrogenic myoclonus, EEG:
aggregates periodic sharp waves
Mitochondrial Oxidative Variable Ragged red fibers mtDNA (maternal Leigh, MELAS
Microscopic / Histo
Disease / Condition Pathology Gross Findings Etiology / Risk Diagnostic Clues
Features
phosphorylation (muscle), necrosis, gliosis
Encephalomyopathy inheritance) syndromes
defect in CNS
GM2 ganglioside Lysosomal ballooning, Infants, seizures, no
Tay-Sachs Disease Macrocephaly HEXA mutation (AR)
accumulation cherry red spot hepatomegaly
Sphingomyelin Foamy Zebra bodies, lipid-laden SMPD1 or NPC1 Cherry red spot +
Niemann-Pick Disease
storage hepatosplenomegaly macrophages mutation organomegaly
Globoid cells (macrophage
Galactocerebrosidase Stiffness, rapid death
Krabbe Disease Myelin degradation White matter loss aggregates),
def. (AR) <2 yrs
oligodendrocyte loss
Metachromatic
Metachromatic Sulfatide Gray-white
macrophages (toluidine Arylsulfatase A def. (AR) Pediatric demyelination
Leukodystrophy accumulation demarcation loss
blue+), gliosis
Demyelination,
Symmetric white Boys: behavior change,
Adrenoleukodystrophy VLCFA accumulation lymphocytic infiltration, ABCD1 gene (X-linked)
matter loss adrenal insufficiency
adrenal atrophy
Wernicke-Korsakoff (B1 Mamillary body Necrosis, gliosis in 3rd/4th Alcoholism, Ophthalmoplegia,
Thiamine deficiency
Deficiency) hemorrhage ventricle walls malnutrition ataxia, confabulation
Myelin vacuolation,
Subacute spinal Ataxia, paresthesia,
Vitamin B12 Deficiency None specific axonal loss in posterior & Pernicious anemia, diet
degeneration spastic paresis
lateral columns
Pseudolaminar necrosis, Reversible if early;
Hypoglycemia Energy depletion Cortical necrosis Insulin OD, starvation
Sommer sector loss resembles hypoxia
Hyperglycemia Osmotic brain injury Pallidal necrosis Minimal; may see edema DKA or HHS in diabetes Confusion → coma
Hepatic Encephalopathy Ammonia toxicity Minimal Alzheimer type II Liver failure Flapping tremor, coma
astrocytes (large pale
nuclei)
Pallidal necrosis, Hypoxia symptoms +
CO Poisoning Hypoxia from HbCO Cherry red skin (acute) CO exposure
demyelination CNS necrosis
Microscopic / Histo
Disease / Condition Pathology Gross Findings Etiology / Risk Diagnostic Clues
Features
Direct + nutritional Purkinje cell loss, Alcoholism, Gait disturbance, ataxia
Ethanol Toxicity Cerebellar atrophy
injury Bergmann gliosis malnutrition even sober
Radiation Therapy-induced Coagulative necrosis Delayed: papilledema,
White matter necrosis >10 Gy radiation
Encephalopathy necrosis (unusual in brain) confusion
EYES
Disease Information (from the file only) Disease Information (from the file only)
- Axial proptosis- Accumulation of extracellular Pleomorphic
- Lacrimal gland tumor- Encapsulated
Graves Disease matrix, fat, inflammatory cells- Involves rectus Adenoma
muscles Dermoid Cyst - Benign orbital lesion
- Lacrimal gland enlargement- Granulomas- Neurilemmoma - Orbital tumor
Sarcoidosis (Orbital) “Mutton-fat” keratic precipitates in uveitis- Non-Hodgkin - May involve entire orbit or specific
Candle wax drippings in retina Lymphoma compartments (e.g., lacrimal gland)
- IgG4-related- Lacrimal gland, muscles, Tenon - Obstructed sebaceous gland drainage-
Idiopathic Orbital Blepharitis
capsule involvement- Chronic inflammation, Superficial eyelid inflammation
Inflammation
fibrosis, eosinophils - Blocked Meibomian gland- Lipogranuloma-
Granulomatosis with - Vasculitis, necrosis, collagen degeneration in Chalazion
Deeper eyelid inflammation
Polyangiitis orbit - Most common eyelid neoplasm- Palisading
Capillary - Infancy/childhood- Unencapsulated vascular Basal Cell Carcinoma cells, stromal clefts- Lower lid and medial
Hemangioma tumor canthus predilection
Lymphangioma - Unencapsulated orbital lesion Sebaceous Carcinoma - Spread via lacrimal drainage and
Cavernous nasopharynx- May mimic chalazion,
- Encapsulated- Found in adults
Hemangioma blepharitis- Multivacuolated cells, pagetoid
Disease Information (from the file only) Disease Information (from the file only)
spread- Metastasis to parotid and Keratitis hygiene
submandibular nodes Calcific Band - Calcium in Bowman’s layer- Seen in chronic
- AIDS-related- Purple eyelid lesion, red in Keratopathy uveitis
Kaposi Sarcoma
conjunctiva Actinic Band - UV-induced- Yellow/golden spherules under
Trachoma (Chlamydia Keratopathy epithelium
- Conjunctival scarring- “Boiled sago” follicles
trachomatis) - Bilateral- Associated with Marfan, Down
Ocular Cicatricial - Conjunctival scarring- Dry eye from goblet Keratoconus syndrome- Corneal thinning, conical shape-
Pemphigoid cell loss Histology: breaks in Bowman layer
- Submucosal elevation near limbus- Does not - Inherited- Loss of endothelial cells- Stromal
Pinguecula Fuchs Endothelial
cross cornea edema, bullous keratopathy- Guttata:
Dystrophy
- Submucosal fibrovascular tissue- Crosses excrescences on Descemet membrane
Pterygium limbus onto cornea- May cause mild - Lens opacity- Causes: age, DM, galactosemia,
astigmatism Cataract Wilson disease, steroids- Nuclear sclerosis:
Squamous Neoplasm - At limbus- Range from papilloma to brown lens, blue color distortion
(Conjunctiva) carcinoma- HPV 16, 18 associated - Impaired outflow despite open meshwork-
Open-Angle
Melanocytic - Nevus: benign with cysts- Melanoma: Chronic, idiopathic- Risk: age, family history,
Glaucoma
Neoplasm spreads to parotid/submandibular nodes- thin cornea, DM, HPN
(Conjunctiva) BRAF mutation in ~40% Angle-Closure - Hyperopia-associated- Pupillary block → iris
Scleritis - Blue sclera- Inflammation-related thinning Glaucoma (Primary) bombé- IOP rises rapidly
- High IOP- Blue sclera due to uveal tissue Angle-Closure - Neovascular membranes (e.g., diabetic
Staphyloma
lining ectatic area Glaucoma retinopathy)- VEGF-induced- Membranes
Osteogenesis (Secondary) contract → close angle
- Blue sclera due to defective collagen
Imperfecta - Intraocular inflammation- Keratic
Congenital Melanosis - Pigmented uvea- Blue sclera- Skin Endophthalmitis precipitates- Adhesions: anterior (glaucoma),
Oculi / Nevus of Ota pigmentation posterior (subcapsular cataract)
- Caused by bacteria, fungi, viruses, protozoa- Panophthalmitis - Involves retina, choroid, sclera, and orbit
Keratitis Corneal ulceration, hypopyon- Activation of Granulomatous - Mutton-fat keratic precipitates- Candle wax
collagenases Uveitis (Sarcoidosis) retinal appearance
Acanthamoeba - Associated with contact lens use- Poor Retinal Toxoplasmosis - Uveitis and scleritis- Common in AIDS
Disease Information (from the file only) Disease Information (from the file only)
- Bilateral granulomatous panuveitis- - Choroidal neovascularization- Leaks →
Sympathetic Wet AMD
Autoimmune after injury- Delayed-type scarring- Treat with anti-VEGF
Ophthalmia
hypersensitivity to retinal antigen - Inherited- Rod/cone loss- Night blindness,
Retinitis Pigmentosa
- Most common primary adult intraocular tunnel vision
Uveal Melanoma tumor- GNAQ, GNA11 (early), BAP1 (late)- - Retinal abscesses- Seen in IV drug use or
Candida Retinitis
Spreads to liver systemic infection
Rhegmatogenous - Retinal break- Fluid enters subretinal space- CMV Retinitis - In AIDS- Retinal necrosis
Retinal Detachment Medical emergency - Most common intraocular tumor in children-
Non- Retinoblastoma RB gene mutation- Leukocoria- Flexner-
- No break- Fluid from inflammation, tumors,
Rhegmatogenous Wintersteiner rosettes
HTN
Retinal Detachment - Older adults- Involves neurosensory retina
Retinal Lymphoma
- AV nicking, copper/silver wiring- Phases: and RPE- DLBCL type- Spreads via optic nerve
Hypertensive
vasoconstrictive, sclerotic, exudative- Cotton- Anterior Ischemic - Like optic nerve stroke- May be segmental or
Retinopathy
wool spots Optic Neuropathy complete infarction- Cause: vasculitis (e.g.,
Diabetic Retinopathy (AION) temporal arteritis)
- Microaneurysms- Macular edema- Exudates
(Non-Proliferative) - Bilateral optic disc swelling- Due to ↑ICP or
Diabetic Retinopathy - Retinal neovascularization- Risk of Papilledema local compression- Visual function initially
(Proliferative) hemorrhage preserved
- Premature infants on O₂- Ischemia → VEGF Glaucomatous Optic - Cupping and atrophy- Infant: buphthalmos,
Retinopathy of
→ neovascularization- Fibrosis → Nerve Damage megalocornea- Adult: staphyloma
Prematurity
macular/retinal displacement Leber Hereditary - Mitochondrial mutation- Young males-
Central Retinal Artery - Atherosclerosis, emboli- Pale retina- Cherry Optic Neuropathy Sudden vision loss
Occlusion red fovea - Demyelination- Often first MS symptom- May
Optic Neuritis
Central Retinal Vein - Ischemic: neovascular glaucoma- Non- recover
Occlusion ischemic: hemorrhages, exudates - End-stage eye- Small, disorganized, low IOP-
- Drusen on Bruch membrane- RPE atrophy- Phthisis Bulbi Causes: trauma, inflammation, chronic
Dry AMD
Central vision loss detachment