Organism



Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other | |

|Cushings Disease |Pituitary Hypersecretion of ACTH |↑ Cortisol |Moon Face |55-75% of endogenous cases, more common in women |

| |(usually a microadenoma) |Obesity, Moon Face, Buffalo Hump, Osteoporosis |Buffalo Hump |Diffuse Bilateral Adrenal Hyperplasia w/ thick yellow cortex |

| | |Hirsutism, ↑ Infections, HT, Thin Skin, | |Suppression by High Dose Dexamethasone |

| | |Easy Bruising, Red Stria & Muscle Weakness | |Inferior Petrosal Sinus gradient of 3:1 |

|Cushings Syndrome |Nonpituitary Neoplasm Secretion |↑ Cortisol |Small Cell Carcinoma |Most common in men |

|(Ectopic ACTH or CRH) |(Small Carcinoma, Bronchial & |Obesity, Moon Face, Buffalo Hump, Osteoporosis | |Diffuse Bilateral Adrenal Hyperplasia w/out nodularity |

| |Pancreatic Carcinoids, Thymoma, |Hirsutism, ↑ Infections, HT, Thin Skin, | |½ of Bronchial Carcinoids suppressed by ↑ dose dexamethasone |

| |Pheochromocytoma, Gastrinoma) |Easy Bruising, Red Stria & Muscle Weakness | | |

|Cushings Syndrome |Adrenal Adenoma |↑ Cortisol |↓ CRH & ACTH |↓ CRH & ACTH |

|(Adrenal Hypersecretion) |Adrenal Carcinoma |Obesity, Moon Face, Buffalo Hump, Osteoporosis | |Atrophy of adjacent cortex & contralateral adrenal cortex |

| |Adrenal Nodular Hyperplasia |Hirsutism, ↑ Infections, HT, Thin Skin, | | |

| | |Easy Bruising, Red Stria & Muscle Weakness | | |

|Cushings Syndrome |Exogenous Cortisol Excess |↑ Cortisol |Prednisone |Most common source is Prednisone |

|(Exogenous Cortisol Excess) | |Obesity, Moon Face, Buffalo Hump, Osteoporosis | |↓ Pituitary ACTH & Small Adrenal Glands with thin cortex |

| | |Hirsutism, ↑ Infections, HT, Thin Skin, | |Zona Glomerulosa not affected |

| | |Easy Bruising, Red Stria & Muscle Weakness | | |

|Pseudo-Cushings Syndrome |Depression, Alcoholism, Obesity, Eating|↑ Cortisol | | |

|(Temporary Cortisol Excess) |Disorder, Stress & Illness |Obesity, Moon Face, Buffalo Hump, Osteoporosis | | |

| | |Hirsutism, ↑ Infections, HT, Thin Skin, | | |

| | |Easy Bruising, Red Stria & Muscle Weakness | | |

|Primary Aldosteronism |Aldosterone secreting Adenoma |↑ Aldosterone |↓ Renin & ↑ Aldosterone |Small yellow encapsulated tumor found usually on left & in ♀ |

|(↓ Renin – Conn’s Syndrome) | |HT, ↓ Serum K+, ↑ Extracellular fluid, | |Low Plasma Renin Activity (PRA) |

| | |Alkalosis | |Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test) |

| | |Weakness, Paesthesias, Visual Disturbances | | |

| | |Headaches, Tetany, Cardiac decompensation | | |

|Primary Aldosteronism |Idiopathic |↑ Aldosterone |↓ Renin & ↑ Aldosterone |Bilateral idiopathic hyperplasia = less common than Conn’s |

|(↓ Renin – Adrenal Hyperplasia) | |HT, ↓ Serum K+, ↑ Extracellular fluid, | |Treat w/ spironolactone & something for HT |

| | |Alkalosis | |Low Plasma Renin Activity (PRA) |

| | |Weakness, Paesthesias, Visual Disturbances | |Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test) |

| | |Headaches, Tetany, Cardiac decompensation | | |

|Secondary Aldosteronism |Renal Artery Stenosis |↑ Aldosterone |↑ Renin & ↑ Aldosterone |High Plasma Renin Activity (PRA) |

|(↑ Renin) |Renin producing tunor |HT, ↓ Serum K+, ↑ Extracellular fluid, | | |

| |Chronic edema |Alkalosis | | |

| | |Weakness, Paesthesias, Visual Disturbances | | |

| | |Headaches, Tetany, Cardiac decompensation | | |

|Hyporenemic Hypoaldosteronism |Black Licorice |↓ Aldosterone | | |

| |Chewing Tobacco |Hypertension | | |

|Congenital Adrenal Hyperplasia |21-Hydroxylase Deficiency |↑ ACTH & DHEA → virilization | |Most common cause of CAH & of ambiguous genitalia |

|(21-Hydroxylase Deficiency) |(CYP21A2 Deficiency) |“Classic” = ↓ Aldosterone & Cortisol; ↑ Renin | |Hallmark is increased 17-Hydroxyprogesterone |

| | |“Classic w/out wasting” = nl Ald & ↓ Cortisol | |Treatment = replace aldosterone & cortisol |

| | |“Non-classical” = nl Aldosterone & Cortisol | | |

|Congenital Adrenal Hyperplasia |11β-Hydroxylase Deficiency |↑ ACTH & DHEA → virilization | | |

|(11β-Hydroxylase Deficiency) | |↑ Deoxycortisone | | |

| | |↓ Aldosterone, Renin & Cortisol | | |

|Congenital Adrenal Hyperplasia |17α-Hydroxylase Deficiency |↑ Aldosterone & ACTH | | |

|(17α-Hydroxylase Deficiency) | |↓ Cortisol & Sex Steroids | | |

| | |Hypertension & Hypokalemia | | |

Adrenal Pathology

Adrenal Pathology (contd.)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Cortical Hypofunction |Immediate steroid need | |↑ ACTH |1) Immediate need for steroids – glands unable to respond |

|(Primary Acute Insufficiency) |Rapid steroid withdrawal | | |2) Rapid Withdrawal of steroids |

| |Mass Destruction (DIC,Hemorrhage) | | |3) Massive destruction – hemorrhage, anticoagulants, DIC |

|Waterhouse-Friderichsen Syndrome |Bacteremic Infection |Adrenal Hemorrhage → Cortical Hypofunction |↑ ACTH |More common in children |

|Cortical Hypofunction |Autoimmune (majority) |Destruction of adrenal cortex only |↑ ACTH |Thin cortex w/ lymph infiltrates – unaffected medulla |

|(Primary Chronic Insufficiency) |TB, Histoplasmosis, Carcinoma |Fatigue, muscle weakness, weight loss, GI upset| | |

|(Addison’s Disease) |AIDS, Amyloidosis, Sarcoidosis |Hypoglycemia, Salt craving, Prerenal Azotemia | | |

| |Hemochromatosis |Acidosis, Hypotension & Hyperpigmentation | | |

|Cortical Hypofunction |Autoimmune (majority) |1) Adrenal insufficiency – same as above |↑ ACTH |Thin cortex w/ lymph infiltrates – unaffected medulla |

|(Primary Chronic Insufficiency) |TB, Histoplasmosis, Carcinoma |2) Hypoparathyroidism & Candidiasis | | |

|(Addison’s Disease) |AIDS, Amyloidosis, Sarcoidosis | | | |

|Subtype I |Hemochromatosis | | | |

|Cortical Hypofunction |Autoimmune (majority) |1) Adrenal insufficiency – same as above |↑ ACTH |Thin cortex w/ lymph infiltrates – unaffected medulla |

|(Primary Chronic Insufficiency) |TB, Histoplasmosis, Carcinoma |2) Autoimmune thyroid disease & Type I DM | | |

|(Addison’s Disease) |AIDS, Amyloidosis, Sarcoidosis | | | |

|Subtype II– Schmidt’s Syndrome |Hemochromatosis | | | |

|Cortical Hypofunction |Congenital Adrenal Hyperplasia | |↑ ACTH | |

|(Primary Chronic Insufficiency) |Enzyme Inhibitor (ex. = ketoconazole) | | | |

|(Failure of Cortisol Production) | | | | |

|Cortical Hypofunction |Carcinoma, Infection, Irradiation, |Fatigue, muscle weakness, weight loss, GI upset| |No aldosterone or ACTH deficiency |

|(Chronic 2º/3º Insufficiency) |Infarction |Hypoglycemia, Salt craving, | |Features of panhypopituitarism |

| |Prolonged use of steroids→↓ ACTH | | |Delayed response to prolonged ACTH stimulation test |

|Pheochromocytoma |MEN Type II or III |HT with or without paroxysmal attacks |Adrenomedullary Chromafin cells |Most are solitary & in medulla; pink colored; large = |

| | |Headaches, sweating, fever, GI upset, anxiety | |encapsulated |

| | |Palpitations orthostatic HT, numbness | |Diagnosis = Normetanephrine & metanephrine in plasma |

| | |Cardiac manifestations | |Clonidine useful in exclusion; Paroxysms can be provoked |

| | | | |Rule of 10’s = 10% extrarenal, bilateral, malignant, familial |

|MEN Syndrome Type I | |Parathyroid hyperplasia | | |

|(Wermer Syndrome) | |Pituitary adenomas | | |

| | |Pancreatic islet tumors | | |

|MEN Syndrome Type II | |Pheochromocytoma | |MEN IIA = Parathyroid Adenoma |

|(Sipple Syndrome) | |Medullary Thyroid carcinoma | |MEN IIB = Mucocutaneous ganglioneuromas & Marfanoid habitus |

| | |Parathyroid hyperplasia | | |

|MEN Syndrome Type III | |Pheochromocytoma | | |

| | |Medullary Thyroid carcinoma | | |

| | |Mucosal neuromas/Marfanoid features | | |

Endocrine Pancreas Pathology

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Primary Diabetes Mellitus |Genetic (HLA-DR3 &4) |Blindness (Lens, Retina, Optic Nerve) |HLA-DR3&4 |MI is #1 cause of death; Diabetic ketoacidosis |

|Type I |Autoimmune Antibodies |CV disease (MI, stroke, gangrene) |Diabetic ketoacidosis |Glycosylated collagens →Advanced Glycosylation End Products |

| |Environment (Viral Infection) |Nephropathy & Infections (Mucomycosis) | |Intracellular hyperglycemia→Sorbitol (lens & Schwann Cell) |

| | |Peripheral Neuropathy, Polydipsia & Polyuria | | |

|Primary Diabetes Mellitus |Genetic (not HLA related) |Blindness (Lens, Retina, Optic Nerve) |Hyperosmolar Coma |MI is #1 cause of death; Hyperosmolar Coma |

|Type II |Obesity |CV disease (MI, stroke, gangrene) | |Glycosylated collagens →Advanced Glycosylation End Products |

| |Insulin Deficiency |Nephropathy & Infections (Mucomycosis) | |Intracellular hyperglycemia→Sorbitol (lens & Schwann Cell) |

| |Insulin Resistance (receptor & GLUT) |Peripheral Neuropathy, Polydipsia & Polyuria | | |

|Secondary Diabetes Mellitus |Pancreatitis | | |Destruction of islets after disease |

| |Pancreatic Cancer | | | |

| |Drugs | | | |

Thyroid Pathology

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Diffuse Non-Toxic Goiter |Dietary |Hyperplastic enlargement of thyroid | |Involves whole gland |

|(Endemic) |↓ iodine |↓ T3/T4 | |More common |

| |goitrogens |↑ TSH | | |

|Diffuse Non-Toxic Goiter |Substance interfering with synthesis |Hyperplastic enlargement of thyroid |Young females |Typically young females |

|(Sporadic) |Hereditary enzyme defect |↓ T3/T4 | | |

| | |↑ TSH | | |

|Multinodal Goiter | |Hyperplastic enlargement of thyroid |Nodules/Cysts |Hemorrhage, scarring & calcification |

| | |↓ T3/T4 & ↑ TSH |Irregular | |

| | |Recurrent hyperplasia & involution | | |

| | |Irregular with Nodules & Cysts | | |

|Plummer’s Syndrome |Hyperfunctioning Goiter |↑ T3/T4 | |Toxic multinodal goiter |

| | | | |No skin/eye changes of Grave’s Disease |

|Graves Disease |Autoimmune (LATS/TSI & TGI) |Thyrotoxicosis (with diffuse hyperplasia) | |Typically females |

| |Genetic? (HLA-B8 & DR3) |Ophthalmopathy (Paralysis & exopthalmos) | |Treatment: PTU, methimazole, radioiodine & surgery |

| | |Dermopathy (Pretibial myxedema) | |Eye Muscle Paralysis & Exopthalmos NOT seen in Thyrotoxicosis |

|Thyrotoxicosis |Hyperfunctioning Thyroid |Cardiac: ↑HR,A-fib,Cardiomegaly, CHF |Heat Intolerance |Low TSH (suggestive) & High T4 (confirms) |

| |Leakage from Thyroid |Neuromuscular: Hyperreflexia,tremor,wasting |Lid Lag |Hyperpigmentation over extensor surfaces |

| |Ingestion of iodide or Synthroid |Skin: Heat Intolerance, ↑ Sweat & Pigmentation |↓ Cholesterol |Uncommon causes: Hydatiform mole, Struma ovarii, carcinomas |

| | |↑ Appetite, GI motility, Osteoporosis, Eyes | |Treatment: β Blockers, Propylthiuracil (PTU) , Iodide, Ablation |

|Primary Hypothyroidism |Insufficient Parenchyma |Anemia, ↑ Cholesterol, ↓ Na+, Myxedema |↑ Cholesterol |High TSH (suggestive) & Low Free T4 (confirms) |

| |Hashimoto Thyroiditis (Autoimmune) |Cold Intolerance, Fatigue, Depression, Lethargy|Myxedema |Therapy = T4 replacement (TSH takes 6-8 weeks to normalize) |

| |Developmental, Radiation |Weight ↑, Edema, Constipation, Cardiomyopathy | |Low TSH after Tx → osteoporosis & arrythmias |

| |Ablation |Delayed reflexes (achilles) & Coma (If severe) | | |

|Seondary Hypothyroidism |Pituitary Lesion | | |TSH is unreliable; Use T4 to make diagnosis |

| | | | |TRH stimulation Test = no response |

|Tertiary Hypothyroidism |Hypothalamic Lesion | | |TSH is unreliable; Use T4 to make diagnosis |

| | | | |TRH stimulation Test = delayed response (60 min) |

|Hypothyroidism - Other |↓ Synthesis | | |Use increased dose of T4 during pregnancy |

| |Idiopathic (block of TSH receptors | | | |

| |Heriditary, Hashimoto Thyroiditis | | | |

| |Lithium, Iodides, p-aminosalicylate | | | |

|Cretinism |Infant Hypothyroidism |Mental Retardation |Protruding Tongue | |

| |Early Childhood Hypothyroidism |Short Stature, Coarse Facial Features |Umbilical Hernia | |

| | |Umbilical Hernia | | |

| | |Protruding Tongue | | |

|Fetal Hypothyroidism |Thyroid Agenesis |Delayed Brain Development |Deaf & Mute | |

| |Iodine Deficiency |Deafness & Mutism | | |

| |Congenital Synthetic Defect |Spasticity | | |

| | |Severe Mental Retardation | | |

Thyroid Pathology (contd)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Chronic Autoimmune Thyroiditis |TPO Antibodies (99% sensitive) |Diffusely but painlessly enlarged Thyroid |Early transient Thyrotoxicosis |Female Predominance |

|(Hashimoto Thyroiditis) |Deficiency of Suppressor T Cells |Lymph infiltrates & follicles |Later Hypothyroidism |Early transient Thyrotoxicosis, Later Hypothyroidism |

| |Genetic? (HLA-DR3 &5) |Hurthle Cells (granular cytoplasm) | |Risk for B Cell Lymphomas |

| |TSH antibodies blocking receptor | | |Other antibodies: Thyroglobulin, Thyroid Peroxidase, I |

| | | | |transporter |

|Subacute Thyroiditis |Viral (Mumps, Influenza, Coxsackie) |Painful, diffusely enlarged Thyroid |Painful |Self Limited |

|(DeQuervain’s/Granulomatous) | |Giant Cells & Macrophages (like granuloma) | | |

|Palpation Thyroiditis |Vigorous Palpation |Giant Cells & Macrophages (like granuloma) | | |

| |Disuption of follicles | | | |

|Subacute Lymphocyte Thyroiditis |Idiopathic |Painless Goitrous Enlargement |Post-Partum |Self Limited |

| | | | |Often seen in post-partum women |

|Riedel’s Thyroiditis | |Fibrosing Thyroiditis - Painless | |Causes Laryngeal Nerve Paralysis (SOB & difficulty swallowing) |

| | |Hard gland | |Simulates malignancy |

| | | | |May be associated with fibrosis elsewhere |

|Follicular Adenoma | |Benign, solitary, encapsulated | |Majority of Thyroid neoplasms |

| | |Doesn’t take up iodine | |Not likely to cause thyrotoxicosis |

| | | | |May make more T3 than T4 |

|Papillary Carcinoma |RET gene mutation (MEN II) |Encapsulated or Infiltrating |Radiation |Most common thyroid cancer –↑ incidence in Gardner Syndrome |

| |RAS gene mutation |Complex branching papillae |Little Orphan Annie |Optically clear nuclei in “Little Orphan Annie Cells” |

| |Radiation exposure (most common) |Optically Clear nuclei & Psammoma bodies |Nodal Metastasis |Metastisize to regional nodes; Usually indolent growth |

| | |Intranuclear inclusions, grooves | |Treatment = Thyroidectomy & radioiodine therapy, Survival 98% |

|Follicular Carcinoma |RAS gene mutation |Vascular or Capsular Invasion |Invasion |2nd most common - Survival 92% |

| | | |Blood Metastasis |Hematogenously spread to bone, lungs & brain |

| | | | |Treatment lobectomy or thyroidectomy, radioiodine (if invasive) |

|Hurthle Cell Neoplasm |RAS gene mutation |Abundent granular cytoplasm | |Behave the same as follicular cell carcinoma/adenoma |

|(Adenoma or Carcinoma) | | | | |

|Medullary Carcinoma |RET gene mutation (MEN II) |Parafollicular C Cells (neuroendocrine) |Amyloid Stroma |Rare – most sporadic, 20% as MEN II or familial |

| |RAS gene mutation |Nodule or multifocal |Calcitonin |May be paraneoplastic (CEA, somatostatin, serotonin & VIP) |

| | |Not encapsulated, round or spindle cells |Not encapsulated |Metastasize in blood to lung, liver, bone & nodes |

| | |Amyloid( Calcitonin) tumor stroma | |Treatment = Thyroidectomy |

|Anaplastic Carcinomas |RAS gene mutation |Undifferentiated neoplasms |Elderly |Poor prognosis – uniformly fatal |

| |P53 gene mutation |Large, locally invasive, rapidly growing |Fatal |Loss of I uptake & ↓ Thyroglobulin |

| | | | |Survival less than 1 year from diagnosis |

| | | | |Possibly derived from Papillary Carcinoma |

Leukemia & Lymphoma

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Acute Lymphoblastic Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Rapid Onset, > 20% Blasts |Children |Cells similar to lymphoblastic lymphoma |

|(ALL) |Radiation |Bone Pain, CNS & Testes Involvement |TdT+, |Generally good prognosis (70%) = ↓ WBC, t12:21, < 9yo, diploidy |

| |Alkylating Agents, Benzene |HSmegaly, Anemia & Thrombocytopenia |Scant agranular cytoplasm |Bad = WBC (>10K), T-Type, t9:22, 11q23, organomegaly |

| |Viral |T Type = lymphadenopathy & mediastinal mass | |3 types: Pre B (85%), Pre T (15%), B “like Burkitts” (2%) |

|Acute Myeloid Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Rapid Onset, > 20% Blasts |Auer rods |Fair prognosis (40%), Usually adults |

|(AML) |Radiation |Anemia & Thrombocytopenia |CD13, CD15, CD33 |Frequent infections & mucosal bleeding |

| |Alkylating Agents, Benzene |Monocytic = gum hyperplasia |Granular Cytoplasm |Good = t8:21, t15:17 (treat w/ RA) & Chrom 16 abnormalities |

| |Viral |Promyelocytic (M3) = DIC, ↓WBC | |Bad = t9:22, 11q23, origin from myelodysplasia or treatment |

|Acute Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Myeloid & Lymphoid features | |Poor prognosis |

|of Ambiguous Lineage |Radiation | | | |

| |Alkylating Agents, Benzene | | | |

| |Viral | | | |

|Chronic Myeloid Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Gradual onset, Mature Cells |↓ LAP |Usually adults, Philadelphia Chromosome (t 9:22) |

|(CML) |Radiation |100% cellular Bone Marrow (no fat) |t9:22 or bcr-abl |bcr-abl ↑ Tyrosine Kinase activity ( Treat with Gleevec) |

| |Alkylating Agents, Benzene |Pluripotent Stem Cells→Granulocytes |Pluripotent Stem Cells |↓ Leukocyte Alkaline Phosphatase (LAP) |

| |Viral |Splenomegaly = Draggin Sensation | |Poor Prognosis - Always goes to blast crisis (AML or ALL) |

|Chronic Lymphocytic Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Gradual onset, Mature Cells, Hepatosplenomegaly|Not radiation |Usually adults (most common adult leukemia in west) |

|(CLL) |Alkylating Agents, Benzene |Clonal B Cell Disorder (small lymphocytes) |CD5, CD20, CD23 |Same as CLL; indolent, not affected by therapy |

| |Viral |↑ Infections |Del 13q |Some have large cell transformation (Richter Syndrome) |

| | |Hypogammoglobulinemia |RichterSyndrome |Bad = trisomy 12, CD38 & de1 11q |

|Hairy Cell Leukemia |Trisomy 21, Bloom’s, Fanconi’s |Gradual onset |Adult Men |Usually adult men (2% of leukemias) |

|(HCL) |Alkylating Agents, Benzene |Bacterial & Mycobacterial Infections |Not radiation |Fair prognosis (40%) |

| |Viral |Beefy Red Splenomegaly, ↑ Reticulin in BM |“Fried Egg appearance” |Pancytopenia (70%), Neutropenia & Monocytopenia (90-100%) |

| | |TRAP+ B Cells |TRAP+ |Good Treatment - 2-CDA, pentostatin & interferon |

|Myelodysplastic Syndrome |Idiopathic |BM = Hypercellular, Periphery = Pancytopenia |Ringed Sideroblasts |Many subtypes based on ringed sideroblasts & blast counts |

| |Therapy related (ex. Radiation) |600,000) |Large Platelets |Least common of myeloproliferative disorders |

| | |Large Platelets |No myelofibrosis |Diagnosis by exclusion |

| | |Thrombosis & Hemorrhage | |Good prognosis (>10 year survival) |

|Hodgkin’s Disease |EBV |Predominance of lymphocytes/hystiocytes |No Typical Reed Sternberg Cells |Men more common |

|(Lymphocyte Predominance) | |Typically a cervical node |Lymphohystocytic Cells |Best Prognosis |

| | |Cd20 & CD45 |B Cell Lymphoma |Can turn into Diffuse Large B Cell Lymphoma |

| | | |CD20 & CD45 | |

|Hodgkin’s Disease |EBV |Predominance of lymphocytes/hystiocytes |No Typical Reed Sternberg Cells |Men more common |

|(Lymphocyte Rich) | |CD15 & CD30 |Lymphohystocytic Cells |Can turn into Diffuse Large B Cell Lymphoma |

Leukemia & Lymphoma (Contd.)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Hodgkin’s Disease |EBV |Cervical, Supraclavicular or mediastinal nodes |Lacunar Reed Sternberg Cells |Most common type; affects adolescent or young adult women |

|(Nodular Sclerosis) | |Variable cell composition & necrosis |Collagen Bands |Staging (usually I or II) determines treatment; Good prognosis |

| | |CD15 & CD30 |Women | |

|Hodgkin’s Disease |EBV |Variable cell composition & focal necrosis |Classic Reed Sternberg Cells |2nd most common type; men more common |

|(Mixed Cellularity) | |Disordered fibrosis | |Staging determines treatment; Guarded prognosis |

| | |Eosinophils, Plasma & T Cells | | |

| | |CD15 & CD30 | | |

|Hodgkin’s Disease |EBV |1) Diffuse Fibrosis – RS Cells embedded in |Poor Prognosis |Fairly common – usually in older patients |

|(Lymphocyte Depletion) | |fibrous stroma |Many Reed Sternberg Cells |Often Bone Marrow Involvement (Stage III or IV) |

| | |2) Reticular – RS Cells in sheets |Bone Marrow |Poor prognosis |

| | |↑ #s of Reed Sternberg Cells | |Usually not a true Hodgkin’s Lymphoma? |

|Small Lymphocytic Lymphoma |Trisomy 21, Bloom’s, Fanconi’s |Gradual onset, Mature Cells, Hepatosplenomegaly|Not radiation |Usually adults (most common adult leukemia in west) |

| |Alkylating Agents, Benzene |Clonal B Cell Disorder (small lymphocytes) |CD5, CD20, CD23 |Same as CLL; indolent, not affected by therapy |

| |Viral |↑ Infections |Del 13q |Some have large cell transformation (Richter Syndrome) |

| | |Hypogammoglobulinemia |RichterSyndrome |Bad = trisomy 12, CD38 & de1 11q |

|Follicular Lymphoma | |Nodular Growth Pattern with 2 cell types |CD10,CD20,CD23 |Fairly Common; indolent, not affected by therapy |

| | |1) Centrocytes = cleaved nuclear contours |BCL-2, t14:18 |May transform to diffuse large B cell lymphoma |

| | |2) Centroblasts = clear chromatin & | | |

| | |multinucleate | | |

| | |Bone Marrow frequently involved | | |

|Mantle Cell Lymphoma | |Atrophied germinal center |CD5 & CD20 |Not indolent or treatable |

| | |Small cells with cleaved nuclear contour |BCL-1, t11:14 | |

|Marginal Zone B-Cell Lymphoma |H. Pylori |Large B Cells, some plasma cells |CD20 |Common in GI Tract, Indolent, not dependent on treatment |

|(MALT Type) |Autoimmune (Sjogren, Hashimoto) | | | |

|Diffuse Large B-Cell Lymphoma |EBV |Large cell size, diffuse growth pattern |T14:18, t8:14, t13:14 |Very Common, Very Aggressive |

| |HSV8 | |BCL2,C-Myc,BCL6 |Prognosis depends on treatment, BCL-6 = good prognosis |

| | | | | |

|Burkitt’s Lymphoma |EBV |“Starry Sky picture” |“Starry Sky picture” |One of three bad types in kids |

| | | |CD10,CD19,CD20 |Highest growth fraction of all tumors |

| | | |C-Myc |Most manifest as extra-nodal sites |

| | | | |Responsive to treatment, but poor prognosis |

|Lymphoblastic Lymphoma | |Mediastinal Mass like Hodgkins |CD3, TdT+, TCL-1 (T Type) |One of three bad types in kids |

|(T/B) | | | |Responsive to treatment, but poor prognosis |

|Anaplastic Large T/Null Cell | | |CD3, CD30 |One of three bad types in kids |

|Lymphoma | | |ALK, EMA t2:5 |Uncommon in adults, Common in children |

| | | | |Presents in extra-nodal tissue |

| | | | |Usually T, not B cell |

|Peripheral T-Cell Lymphoma |EBV |Extranodal NK/T Cell Lymphoma |CD3 |Poor Prognosis; Common in Asia, uncommon in US |

| | |Nasal Type – eats face off | | |

Leukemia & Lymphoma (Contd. 2)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Mycosis fungoides | |Cerebriform nuclei |CD4 |Indolent Cutaneous disorder |

| | | |Polyclonal Ig |Extracutaneous spread |

| | | | |(Leukemia = Sezary Syndrome) |

|Multiple Myeloma |Radiation, Chemicals, Asbestos |Painful Bone Destruction, ↓ Humoral Immunity |M Protein |Most common 1º malignant tumor of bone |

| |Black Race |Plasmacytosis with IL-6, Vertebral Fractures |Bence Jones Protein |Complications: Renal failure, Amyloidosis, AML (rarely) |

| |HSV8? |M Protein, Bence Jones proteins, Hypercalcemia |Hypercalcemia |Fair prognosis (3 yr) |

| | |Can spread to nodes, skin, etc |IL-6 | |

|1º Amyloidosis |Radiation, Chemicals, Asbestos |Plasmocytosis with ↑ Light Chain Production |Large Tongue |Usually immunoglobulin light chain |

| |Black Race |Fibrils of β-pleated sheets that stain Congo | | |

| |Multiple Myeloma |Red | | |

| | |Large tongue, Neuropathy, GI | | |

| | |Arrythmias, CHF | | |

|2º Amyloidosis |Chronic Infection or Inflammation |Fibrils of β-pleated sheets that stain Congo |HSmegaly, | |

| | |Red |Proteinuria | |

| | |HSmegaly, | | |

| | |Proteinuria | | |

|Monoclonal Gammopathy of |Aging |M Proteins without other symptoms | |Most common monoclonal gammopathy |

|Undetermined Significance | | | |Diagnosis of exclusion, IgG < 3.5 |

| | | | |May develop into multiple Myeloma |

| | | | |Requires no treatment |

Pituitary Pathology

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Prolactinoma | |↑ Prolactin | |Most common secretory adenoma of anterior lobe |

| | |Amenorrhea, Galactorrhea, Infertility, | |Effects less obvious in postmenopausal women |

| | |Loss of Libido | |Treated with bromocriptine |

|Hyperprolactinemia |Injury to pituitary stalk |↑ Prolactin |Prolactin |Due to decreased dopamine to the anterior lobe |

| |Compression | | |Non-prolactin secreting adenomas may compress stalk |

| |Trauma to Hypothalamus, Infection | | | |

| |Drugs (Phenylthiazines) | | | |

|Somatotroph Adenoma | |↑ Growth Hormone → ↑ Hepatic IGF-1 |IGF-1 |Second most common secretory adenoma of anterior lobe |

| | |Some produce prolactin as well | |Treatment = transsphenoidal resection, bromocriptine & radiation |

| | |Acromegaly (adults) & Gigantism (children) | |Acromegaly = hands, feet, face skin & viscera |

| | |DM, HT, CHF, arthritis, weakness, GI carcinoma | | |

|Corticotroph Adenoma | |↑ ACTH→ ↑ Cortisol (Cushing’s Disease) |ACTH |90% are microadenomas |

| | |Moon facies, central obesity, striae, bruising |Microadenoma |Treatment = transsphenoidal resection |

| | |Osteoporosis, DM & HT | | |

|Gonadotroph Adenoma | |No clinical syndrome | |Secrete hormones inefficiently and variably |

|Thyrotroph Adenoma | | | |Rarest |

|Sheehan’s Syndrome |Pregnancy & Lactotroph Hypertrophy |Hypopituitarism | |Most common cause of anterior lobe ischemic necrosis |

| |Hypotension, DIC | | | |

| |Sickle Cell Anemia, ↑ ICP | | | |

|Empty Sella Syndrome |Maldevelopment of diaphragma sella |Depends on number of residual cells | |Maldevelopment = Arachnoid Herniation via enlarged opening |

| |Pituitary Apoplexy |Hypopituitarism | | |

| |Sheehan’s Syndrome |No syndrome | | |

| |Ablation | | | |

|Diabetes Insipidus |Interruption of DA to Posterior Lobe |Large volume of dilute urine |↓ ADH |Treatment = Administer ADH |

| |Trauma | | | |

| |Tumor | | | |

| |Inflammation | | | |

|Syndrome of Inappropriate ADH |Ectopic ADH (Small Cell Carcinoma) |Water Retention, Hyponatremia |↑ ADH |Treatment = Water Restriction, Slow normalization of Na+ |

|(SIADH) |Lung Disease (TB) |GI Upset, Cerebral Edema | |(Rapid Normalization can cause Central Pontine Myelinolysis) |

| |Intracranial Lesions (↓ Inhibition) | | | |

| |Drugs | | | |

|Hypothalamic Tumors | |Hyperpituitarism, Hypopituitarism | |Glioma & Craniopharyngioma are most common |

| | |Diabetes Insipidus | | |

CNS Pathology

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Concussion |Blunt non-penetrating injury | |Reversible |Reversible Traumatic Paralysis Ocurring Immediately After Injury |

| | | |Paralysis | |

| | | |Immediate | |

|Contusion |Stress on parenchymal vessels |Seizures |Intact pia-glial membrane |Most common sites: Frontal Pole, Temporal Pole, Medial orbital |

| |Coup |Cognitive & Personality Changes | |surface of the temporal lobe |

| |Countercoup |Headaches | |Pia-arachnoid not penetrated |

| | |Dizziness | |Occur at crests of gyri |

|Lacerations |Penetrating Wounds |Subarachnoid bleeding |Meningocerebral cicatrix |Traumatic disruption of pia-arachnoid and brain surface |

| | |Satellite petichial hemorrhages | |Meningocerebral cicatrix (glial scar) = epileptogenic focus |

| | |Edema in tissue | | |

|Epidural Hemorrhage |Fracture |Immediate Loss of Consciousness | |Collection of blood between dura and skull |

| |Most = Arterial (Middle Meningeal) |Lucid Interval | |Lenticular shaped hematoma |

| |Rarely = Dural Sinus, Bridging Veins |Later Loss of Consciousness | | |

|Acute Subdural Hemorrhage |Superficial Cortical Bridging Veins |48 hours-days; appears as clotted blood |Clotted Blood |More Common than epidural hemorrhage |

| |Dural Sinus Laceration |Gradual Loss of Consiousness | |Typically seen in infants, elderly & alcoholics |

| |Depressed Fractures |Hemiparesis → Hemiplegia | |Sheet of blood between dura & arachnoid; forms hyaline sac |

| |Bullet Wounds |Evidence of Herniation (if > 60 cc) | | |

|Subacute Subdural Hemorrhage |Superficial Cortical Bridging Veins |Clotted & Fluid Blood |Clotted & Fluid Blood |More Common than epidural hemorrhage |

| |Dural Sinus Laceration |Gradual Loss of Consiousness | |Typically seen in infants, elderly & alcoholics |

| |Depressed Fractures |Hemiparesis → Hemiplegia | |Sheet of blood between dura & arachnoid; forms hyaline sac |

| |Bullet Wounds |Evidence of Herniation (if > 60 cc) | | |

|Chronic Subdural Hemorrhage |Superficial Cortical Bridging Veins |> 3 weeks & Liquefied Hematoma |Liquefied Hematoma |More Common than epidural hemorrhage |

| |Dural Sinus Laceration |Gradual Loss of Consiousness |Minor Precipitating Event |Typically seen in infants, elderly & alcoholics |

| |Depressed Fractures |Hemiparesis → Hemiplegia | |Sheet of blood between dura & arachnoid; forms hyaline sac |

| |Bullet Wounds |Evidence of Herniation (if > 60 cc) | |Slow Bleeding, No immediate symptoms, Minor precipitating event |

|Subarachnoid Hemorrhage |Trauma |Stiff Neck, Alterations in Consciousness |Stiff Neck |Usually multiple and small |

| |Superficial Cortical Veins |Vasospasm & Hydrocephalus | | |

| |Surface cortical lacerations | | | |

| |Surface cortical contusions | | | |

|Intracerebral Hematoma |Rupture of Intrinsic Cerebral Vessels | | |Not in contact with the cortical surface, usually solitary |

| | | | |Frontal & Temporal Lobes are most common sites |

|Cranial Nerve Damage |Cranial Fractures | | |Damage usually occurs where nerves exit through foramina |

| | | | |Most Common = CNI, CNII, CN V & CN VI |

|Pontomedullary Avulsion |Marked Hyperextension of neck | | |Poor prognosis, Immediately fatal if complete, die later if |

| | | | |incomplete |

|Diffuse Axonal Injury |Diffuse Shearing of axons |Unconscious from moment of impact |Calpain |Results in disconnection of distal axonal segment |

|(1º Axotomy) | |No lucid interval | |Most common sites = Corpus Callosum & S. Cerebellar Peduncles |

| | |Ca2+ influx & swelling | | |

| | |Microtubule depolymerization, Calpain | | |

| | |activation | | |

CNS Pathology (Contd.)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Diffuse Axonal Injury |Small axonal membrane tears that reseal|Unconscious from moment of impact |Axoplasmic Transport |Results in disconnection of distal axonal segment |

|(2º Axotomy) | |No lucid interval | |Most common sites = Corpus Callosum & S. Cerebellar Peduncles |

| | |Ca2+ activated proteases, repair fails | | |

| | |Axoplasmic transport causes swelling | | |

|Hypoxic Brain Injury | | | |Greatest Damage = Hippocampus, Caudate, Putamen, |

| | | | |Cortical Layers 3 & 5, Purkinje Cells of Cerebellum |

| | | | |Diffuse or localized to watershed zone |

|Brain Swelling |Mechanical Damage |White Matter Swelling | |White matter swelling adjacent to contusion |

| |Blood Vessel Impairment |Diffuse Swelling | |Diffuse Swelling of One or Both Hemispheres |

| |Vasodilation | | | |

|Multiple Petechial Hemorrhages |Acceleration/Deceleration? |Frontal & Temporal Lobes (White Matter) | |Usually seen in patients who die soon after head injury |

| | |Thalamus | | |

| | |Brainstem | | |

|Fat Embolism |Fractures of Limbs or Limb Giurdles |3-4 d = white matter petichiae, capillary | |Usually only seen in adults (children have less fat) |

| |(Fat enters veins) |necrosis | | |

| | |4-7d = grey matter alterations, fat in | | |

| | |capillaries | | |

| | |12d-3m = many infarcts in cortex & pons | | |

| | |>3 m = atrophy of white matter | | |

|Early Post Traumatic Epilepsy | |Within first week | |Occurs during first week |

| | | | |More common in children than adults |

| | | | |Associated with: Hematoma, Depressed Fracture, Amnesia |

|Late Post Traumatic Epilepsy |Blunt Head Injury |After first week | |Most common complication of blunt head injury |

| | | | |Occurs later than one week |

| | | | |↑ Risk = Hematoma, Depressed Fracture, Early Epilepsy |

|Multiple Sclerosis |T-Cell Autoimmune against Myelin |Diagnosis = 2 lesions & 2 symptoms |Young Women, CNS |Commonest in young women; Affects CNS myelin, Variable course |

| |Unknown |Visual Impairment, Weakness, Dysarthria |Plaques |Acute Plaque: Sharp Border, Inflammation & Edema, Demyelination |

| |Distance from equator, Environment |Ataxia, Vertigo, Urinary Symptoms |Variability |Inactive Plaque: Sharp Border, No Inflammation Edema or Myelin |

| |Genetic |CSF = ↑ Mono’s & IgG (OCB-not in serum) |Oligoclonal Bands (OCB) |Shadow Plaque: Poor Border, Thin Myelin at Periphery |

|Devic Disease | | |Spinal Cord & CN II Only |Severe necrotic lesions in spinal cord and optic nerve only |

|(Neuromyelitis Optica) | | | |Rapidly progressive |

|Acute Multiple Sclerosis | | | |Fatal in 1-6 months |

|(Marburg Type) | | | |Severe & Rapid with extensive involvement of brain & spinal cord |

|Central Pontine Myelinolysis |Rapid Correction of Hyponatremia |Rapidly evolving quadriplegia |CNS |Symmetric demyelination in the center of the base of the pons |

| |Sever Electrolyte Imbalance Alcoholism,| | |Can affect tegmentum occasionally |

| |Liver Transplant | | |Outcome is variable: Complete Recovery→Fatal |

| |Burns, Malnutrition | | | |

|Guillian-Barre Syndrome |Acute Influenza-like Illness |Inflammation/Demyelination of Nerves & roots |PNS |Treatment: Supportive, Plasmapheresis, IV Immunoglobulin |

| |CMV & Campylobacter jejuni |Cranial & Spinal Motor Roots = Severe |Ascending Paralysis |Outcome: Complete recovery is most common, rarely fatal |

| |Immunization |Ascending Paralysis | |Death due to respiratory paralysis |

| |Autoimmune? | | | |

CNS Pathology (Contd. 2)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Spina Bifida Occulta |Folate Deficiency |Usually assymptomatic |Stigmata (Hypertrichosis) |Variable cord anomaly |

| | |Non-closed vertebral arches without cyst | | |

| | |Stigmata: Hypertrichosis,Dimple,Lipoma,Nevus | | |

| | |Sacral, Anorectal or UG Defect | | |

|Spina Bifida Cystica |Folate Deficiency |Non-closed vertebral arches with cyst |Cyst |Meningocele: Meninges protrude through vertebral defect |

| | |Meningocele or Myelomeningocele | |Myelomeningocele: Meninges & Spinal cord protrude through defect |

| | | | |Most survive > 1 year, but frequently have progressive |

| | | | |deterioration |

| | | | |Disabilities are usual: paraplegia, incontinence, infection, |

| | | | |learning |

|Arnold-Chiari Type II | |Mental Retardation | |1) Myelomeningocele |

| | | | |2) Elongation of Inferior Vermis & Brain Stem with displacement i|

| | | | |into spinal canal |

| | | | |3) Hydrocephalus |

|Annencephaly |Folate Deficiency |Absence of cerebrum & calvarium | |Most common congenital malformation of the brain |

| | | | |Stillborn or die shortly after birth |

|Intraventricular Hemorrhage |Preterm Birth | |Preterm |Most common neonatal intracranial hemorrhage |

|(IVH) |Periventricular Germinal Matrix | |Periventricular Germinal Matrix |PV Germinal Matrix is fragile, fibrinolytic & persists until 34 |

| | | | |weeks |

| | | | |Variable: May be focal & asymptomatic, may spread into ventricles|

|Periventricular Leukomalacia |Infarction of Periventricular White |Initially non-specific |Preterm |Common ischemic lesion of preterm infant |

|(PVL) |Matter |Later: Spastic Motor Dysfunction |Centrum Semiovale |Centrum Ovale = vulnerable boundry zone |

| |(Centrum Semiovale) |Paraplegia/Quadraplegia develops in surviving | |(Ventriculopetal & Ventriculofugal Arteries) |

| | | | |Usually not without permanent sequelae |

|Diffuse Astrocytoma | |Diffusely infiltrate w/o clear margins |Diffusely Infiltrative |20% of gliomas, Rarely Resectable, Progress towards anaplastic |

| | |Found in white matter of cerebrum |No Clear Margins |Graded on: Hypercellularity, endothelial changes & necrosis |

| | | |Cerebrum |Poor Prognosis |

|Brainstem Glioma | |Occur in Pons, infiltrate widely |Children (2nd decade) |Range of grades includes glioblastoma |

|(Atrocytoma Subgroup) | |CN Palsies, Long Tract signs, Gait |Pons |Surgical removal not possible |

| | |abnormalities | | |

| | |Emesis & Cerebellar Signs | | |

|Pilocytic Astrocytom | |Circumscribed, low grade, histology = biphasic |Circumscribed |Young>Old |

| | |Cerebellum, Hypothalamus, Optic Chiasm/Nerve |Midline |Optic Nerve Gliomas associated with Von Recklinghausen’s (NF I) |

| | |Rosenthal Fibers |Rosenthal Fibers | |

| | | |Von Recklinghausen’s (NF I) | |

|Cerebellar Pilocytic Astrocytoma | |60% cystic |Children (2nd decade) |Most common astrocytoma of childhood |

| | |Endothelial proliferation & pleomorphism | |Good Prognosis |

|Subependymal Giant Cell Tumor | |Vascular Intraventricular Mass |Intraventricular |Benign but cause problems due to location & hemorrhaging |

| | |Cells = Large, mix between astrocyte & neuron |Tuberous Sclerosis | |

| | | |Hemorrhage | |

|Glioblastoma Multiforme | |Supratentorial |Common |Most common glioma, Usually in older adults |

| | |Rapid growth, endothelial proliferation, |Adults |Most invasive & aggressive, highly infiltrative |

| | |necrosis |Always Recurs |Tumor always recurs with resection, poor prognosis |

| | |Hemorrhagic Foci, Often zones of mixed tumor |Metastasis |Mix: Oligodendroglioma,Ependymoma,Astrocytoma,Neuroectederm |

| | |May Metastasize (CSF) | | |

CNS Pathology (Contd. 3)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Oligodendroglioma | |Cerebral White Matter, Focal Calcification |Focal Calcification |Unusual in children |

| | |Fried Egg Appearance, Highly vascularized |LOH 1p, LOH 19q |Good = both LOH 1p & 19q |

| | | |CDKN2A |Bad = CDKN2A |

|Ependymoma | |Ventricular System (4th Ventricle is usual) |4th Ventricle |All ages, but more often young>old & children = infratentorial |

| | |Rosette & Pseudorosette Arrangement |NF II |Most common spinal intramedullary glioma, Associated w/ NF II |

| | |Vascularized, differentiated & demarcated |Rosettes & Pseudorosettes |Best to Worst: Spinal Cord, Cerebrum, Posterior Fossa |

| | |May Metastasize |Metastasis | |

|Myxopapillary Ependymoma | |Mucinous Degeneration of Stroma |Cauda Equina |Rare in Children, Usually benign |

| | | |Fila Terminale |Can be locally destructive, Metastatic & can recur |

| | | |Adults | |

| | | |Mucinous Degeneration of Stroma | |

|Subependymoma | |Usually 4th Ventricle |4th Ventricle |Benign, cured by excision |

| | |Extend of caudate or Septum into Lat Ventricle | | |

|Medulloblastoma | |Children = midline, young adults = lateral |Sheets or Rosettes |Young>Old, Accounts for 1/3 of posterior fossa neoplasms |

| | |Grows in sheets or rosettes |CSF Metastasis |Invades leptomeninges & seeds CSF, Good prog except large cell |

| | |May Metastasize into CSF |Myc Amp & LOH 17p |Bad = < 3yo, Mets, Large Cell Variant, Myc Amp, LOH 17p |

| | | |Retinal S, Rhodopsin, TrkC R |Good = Retinal S Antigen, Rhodopsin & TrkC receptor |

|Meningioma | |Grows in sheets w/ poor cytoplasmic borders |Women |Rare in children, More common in adult women |

| | |Whorls & Psammoma Bodies |Attached to Dura |Slight tendency to recur after excision |

| | |Vascular, Attached to dura, Benign |Benign but Compress Brain |Numerous Variants |

| | |Hyperostic Rsponse |Hyperostic Rsponse |Bad = Clear Cell, Rhabdoid, Chordoid & Papillary Subtypes |

|Intracranial Schwannoma | |Encapsulated, Displaces, not Replaces nerves |Encapsulated & Displaces |Spindle = Antoni A (Verocay Bodies); Stellate = Antoni B |

| | |Biphasic (Spindle & Stellate) Growth Pattern |Female |Bilateral Acoustic Schwannomas = von Recklinghausen’s (NF I) |

| | |CN VIII @ Cerebellopontine Angle or IAM |CN VIII |Also common in Neurofibromatosis Type II (NF II) |

| | |CN V (less common) |von Recklinghausen’s | |

|Intraspinal Schwannoma | |Encapsulated, Displaces, not Replaces nerves |Encapsulated & Displaces |Spindle = Antoni A (Verocay Bodies); Stellate = Antoni B |

| | |Biphasic (Spindle & Stellate) Growth Pattern |Cystic |30% of spinal tumors |

| | |All Spinal levels | | |

| | |Cystic | | |

|Peripheral Schwannoma | |Encapsulated, Displaces, not Replaces nerves |Encapsulated & Displaces |Spindle = Antoni A (Verocay Bodies); Stellate = Antoni B |

| | |Biphasic (Spindle & Stellate) Growth Pattern |von Recklinghausen’s |Usually solitary, if multiple = von Recklinghausen’s |

|Neurofibroma | |Arise from small peripheral nerves or trunks |Replaces nerve |Usually multiple, part of von Recklinghausen’s |

| | |Tumor mixed with collagen, reticulin & nerve |Multiple |Plexiform Neurofibroma = von Recklinghausen’s |

| | |Hyperplasia of nerve supporting elements |von Recklinghausen’s | |

|Capillary Hemangioblastoma | |Cerebellum, Retina, Medulla, Cervical Cord |Men, Cerebellum |Adult Male Predominance |

| | |Supratentorial Meninges |Foamy Cytoplasm |Lindau’s: Hemangioblastomas, Cysts, Adrenal/Renal Tumors |

| | |Foamy Cytoplasm |Erythropoietin Substance |Add Retinal Angiomatosis = Von Hippel Lindau Syndrome |

| | |Erythropoietin Substance→Polycythemia |Lindau Syndrome | |

|Primary Sarcoma | |From Fibroblasts | |Rare |

| | |Meninges, Perivascular, Choroid, Tela Choroidea| | |

| | |Attached to meninges | | |

CNS Pathology (Contd. 4)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Primary Lymphoma | |Diffuse Large B Cell |Concentric Laminae |Rare outside of immunosuppressed, Common in AIDS |

|(Reticulum Cell Sarcoma) | |Diffuse Large B Cell Immunoblastic |Reticulin | |

| | |Diffuse Small B Cell Cleaved 9.5 |B Cell | |

| | |Angiocentric growth, laminae, reticulin | | |

|Craniopharyngioma | |Suprasellar (Rathke’s Pouch) |Children |Most Common Supratentorial Tumor in children |

| | |Solid or Cystic, Cords or Sheets (Epithelial) |Hydrocephalus |Often compresses Optic Chiasm or Hypothalamus |

| | |Keratin, Cholesterol Rich Cyst Fluid |Keratin & Cyst Fluid |May bulge into 3rd ventricle & compress CSF flow |

| | |Rosenthal Fiber, Sharp Margins |Rosenthal Fiber |Slow growing, benign (difficult to irradicate due to islands) |

|Germ Cell Neoplasms | |Pineal or 3rd Ventricle |Pineal or 3rd Ventricle |Most common in adult males |

| | |May Metastasize |Males |Most common Germ Cell Tumor of CNS |

| | | |Metastasis |Same as Dysgerminoma/Sminoma, Embryonal Carcinoma, |

| | | | |Chorangiocarcinoma, Teratoma & Endodermal Sinus Tumor |

|Epidermoid Cyst | |Stratified Squamous Lining with Keratin |Skin |Rupture can cause Meningitis→Granuloma |

| | |Partially Calcified |Pons (Cerebello-Pontine Angle) | |

| | |Pons (Cerebello-Pontine Angle) |Keratin | |

| | | |Calcified | |

|Dermoid Cyst | |More Sebacious Glands |Skin |Rupture can cause Meningitis→Granuloma |

| | |Midline of Posterior Fossa |Sebacious “Cheese” | |

| | | |Midline of Posterior Fossa | |

|Meningeal Metastasis | |Rare in Cranium, more common in Spine |Usually Multiple |Most Common = Lung>Breast>Melanoma>Kidney>GI Tract |

|(Metastatic Neoplasms to CNS) | |Hematogenous Seeding, Dissemination via CSF |Spine | |

| | |May enter canal through Dural Root Sleeves | | |

|Parenchymal Metastasis | |More common in Cerebrum than Cerebellum |Usually Multiple |Most Common = Lung>Breast>Melanoma>Kidney>GI Tract |

|(Metastatic Neoplasms to CNS) | |Lodge in grey matter at junction with white |Cerebrum | |

| | |matter |Grey Matter | |

|Transient Ischemic Attack | | | |Deficits occur & disappear completely; Important Predictor of |

|(TIA) | | | |Stroke |

| | | | |(if greater than 30-60 minutes causes infarction) |

| | | | |½ of patients have a diffusion weighted MRI abnormality |

|Cerebral Infarction |Carotid,Vertebral, Basilar |Middle>Posterior>Anterior Cerebral Arteries |Stuttering Onset, at night |Ischemic Necrosis; Most common of all CV Disease |

| |Atherosclerosis |Vasodilation & Immediate Metabolic Change |Older Patients & TIA |1-2d: loss of definition of grey & white, edema; 2-10d: |

| |Age>60, Arteriorsclerosis (DM & HT) |Acidosis; Edema; ↑ Glu; Ca2+ Influx; Free |Atherosclerosis |demarcation |

| |Inflammation, Compression, Spasm |Radical |c-fos, cjun & HSPs |>10d: liquefaction & cyst formation |

| |Polycythemia, Hypotension, ↓ O2 |PMNs; c-fos, cjun & HSPs | |Goal of focal ischemic stroke is to protect penumbra |

|Cerebral Embolus |Heart Arrhythmias & MI |Middle Cerebral Artery |Arrhythmias & MI |Fat emboli cause petichial hemorrhages in white matter of |

| |Aorta & Carotid Plaques |Lesions in cortex & corticomedullary junction |Sudden Onset |cerebrum |

| |Endocarditis | |Multiple Regions |Change of “no flow/reflow” hemorrhage |

| |Surgery & Trauma | |Rapid Improvement (some) | |

|Cerebral Hemorrhage |Hypertension |Charcot-Bouchard Aneurysms |Hypertension |Putamen & Pons = Death;Thalamus & Cerebellum = Recoverable |

| |Amyloid |Disection of parenchyma, rupture into |Waking Hours |Older pts with amyloid can get lobar hemorrhage w/o hypertension |

| | |ventricles |50% Coma |High 30 day mortality |

| | |Hematoma ringed by petichiae |Some stiff neck/headache | |

| | |Large amounts of hemosiderin after recovery | | |

|Subarachnoid Hemorrhage |Head Trauma |Arterial Spasms & Cerebral Infarction |Head Trauma (Saccular Aneurysm) | |

| |Ruptured Aneurysms, Neoplasms |Hydrocephalus |Sudden Onset during Day | |

| |Arteriovenous Malformations, Dyscrasias| |Headache & Stiff Neck in all | |

| |Extension of Hemorrhage | |Younger Patients; Seizures | |

CNS Pathology (Contd. 5)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Lacunar Infarction |Hypertension |Fibrinoid necrosis | |Small (< 1 cm) |

| | |Hyalinization of media & narrowing of lumen | | |

| | |Grey Matter, Internal Capsule, Basis Pontis & | | |

| | |Centra Semiovales | | |

|Mycotic Aneurism |Bacterial Emboli |Distal to bifurcation of Circle of Willis |Cerebral Embolus |Cause Subarachnoid & Intracerebral Hemorrhage |

|Charcot-Bouchard Aneurysms |Hypertension |Found on penetrating intraparenchymal arteries |Cerebral Hemorrhage |Microaneurysms |

| | |Cerebral Hemispheres, Cerebellum & Brainstem | | |

|Saccular Aneurysms |Congenital Defect at Bifurcation |85% in anterior circulation |Subarachnoid Hemorrhage |Berry Aneurysm |

| |Degeneration of IEL |Internal Carotid, Anterior Cerebral | |Multiple in 20% of patients |

| |Atherosclerosis |& Anterior Communicating | | |

| | |Hemorrhage or Compression | | |

|Fusiform Aneurysms | |Vertenral, Basilar or Internal Carotid |Don’t Rupture | |

| | |Segmentally Dilated | | |

| | |Compression | | |

|Capillary Telangiectasis | |Pons or Cerebral White Matter |Pons or Cerebral White Matter |Small Dilated Capillaries separated by neural tissue |

| | |Focal Seizures | | |

| | |Repeated Subarachnoid Hemorrhage | | |

| | |Intracranial Bruits | | |

|Cavernous Malformations | |Focal Seizures | |Dilated Sinusoidal Vessels without neural tissue |

| | |Repeated Subarachnoid Hemorrhage | | |

| | |Intracranial Bruits | | |

|Arteriovenous Malformation | |Found along Middle Cerebral Artery |Middle Cerebral Artery |Composed of arteries & Veins |

| | |Focal Seizures | | |

| | |Repeated Subarachnoid Hemorrhage | | |

| | |Intracranial Bruits | | |

|Venous Malformation | |Found over Subarachnoid Space over Cord |Subarachnoid Space over Cord |Large Numbers of Veins |

| | |Focal Seizures | | |

| | |Repeated Subarachnoid Hemorrhage | | |

| | |Intracranial Bruits | | |

|Venous Occlusive Disease |Infection, Heart Disease, Post-op |Superior Sagital Sinus or Superior Cerebral |Sinus or Veins |Bad = If thrombosis spreads into bridging veins (don’t use TPA) |

| |Trauma |Veins | | |

| |Carcinoma, Fever, Dyscrasias, |Hemorrhage into leptomeninges | | |

| |Dehydration, Cachexia, Hypotension |Hemorrhagic Infarction | | |

| |Puerperium |Hemorrhage in cortex (white matter) | | |

|Acute Pyogenic Meningitis |Neonates: Group B Strep & E. coli |Fever, Headache, Photophobia, Nuchal Rigidity |↓ Glucose (CSF) |A leptomeningitis (leptomeninges & subarachnoid CSF) |

|(Bacterial) |2 y: N. meningitides |↑ CSF Pressure, PMNs, Protein; ↓ Glucose |Medical Emergency |Complications: Hydrocephaly, Infarct, Blindess, Deafness, Ocular |

| |Elderly: S. pneumoniae & Listeria |Hydrocephaly, Infarct, Seizures, CN Palsies | |Palsy, Seizures |

|Aseptic Meningitis |Enterovirus |Effects more mild than Bacterial |Lymphocytes |Usually self-limiting, no long term effects |

|(Viral) |(Echovirus, Coxsackie or Poliovirus) |↑ CSF Pressure, Lymphocytes, Protein | | |

CNS Pathology (Contd. 6)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Chronic Meningitis |Mycobacteria (TB) |Less Fulminating than Bacterial |↑↑ Protein |Meningoencephalitis (Meninges & Brain Parenchyma) |

|(Mycobacterial) | |↑ CSF Pressure, Mono’s or Mixed, Protein |Mononuclear Cell |Very hard to treat, high rate of complications |

| | |Basal Meninges |Basal Meninges |CSF Protein may be very high with TB |

| | |Granulomatous Reaction (not pyogenic) | | |

|Chronic Meningitis |Candida |Less Fulminating than Bacterial |↑↑ Protein |Meningoencephalitis (Meninges & Brain Parenchyma) |

|(Fungal) |Mucor (with Diabetic Ketoacidosis) |↑ CSF Pressure, Mono’s or Mixed, Protein |Mononuclear Cell |Very hard to treat, high rate of complications |

| |Aspergillus |Basal Meninges |AIDS & Diabetes |CSF Protein may be very high with TB |

| |Cryptococcal (with AIDS) |Granulomatous Reaction (not pyogenic) |Basal Meninges |Mucor & Aspergillus tend to invade blood vessels (hemorrhagic) |

|Brain Abscess |Bacteria (Staph & Strep) |Herniation due to mass effect | |Predisposed: Endocarditis; Heart Disease; |

| |Fungi (often immunodeficient) |Rupture into ventricles | |Lung, Sinus & Tooth Infections |

| |Protozoa (Toxoplasma - AIDS) | | | |

|Viral Encephalitis |Eastern Equine-Epidemic |Mononuclear Infiltrate, Microglial Nodules | |Eastern Equine = most virulent, 20-40% mortality |

|(Arbovirus) |West Nile Epidemic |Neuronophagia, Viral Inclusion Bodies | | |

| |Western Equine | | | |

|Viral Encephalitis |HSV-1 |Mononuclear Infiltrate, Microglial Nodules |Inferior Temporal & Frontal Lobes |HSV-1 = Most common cause of sporadic acute encephalitis |

|(Herpes Simplex Type I) | |Neuronophagia, Viral Inclusion Bodies | |Labial Herpes not a significant risk factor |

| | | | |Treatment = Acyclovir |

| | | | |Tropism for Temporal & Frontal Lobes except in neonates (pan) |

|Viral Encephalitis |HSV-2 |Mononuclear Infiltrate, Microglial Nodules | |In immunodeficient pts & neonates; In others = aseptic meningitis|

|(Herpes Simplex Type IIK) | |Neuronophagia, Viral Inclusion Bodies | |High Risk = Babies born to mothers with active genital herpes |

| | | | |Neonates = generalized panencephalitis (no tropism) like above |

|Viral Encephalitis |VZV |Mononuclear Infiltrate, Microglial Nodules |Posterior Ganglionitis |Exemplifies latency |

|(Varicella Zoster Virus) | |Neuronophagia, Viral Inclusion Bodies |Latency | |

| | |Inflammation of a sensory ganglion | | |

|Viral Encephalitis |Rabies |Mononuclear Infiltrate, Microglial Nodules |Hyperexcitability |Peripheral Nervous System as route of entry |

|(Rabies) | |Neuronophagia, Viral Inclusion Bodies |Pharyngospasm |(slowly spreads along peripheral nerves) |

| | |Hyperexcitability | |Slight Touch: Pain,Violent Motor Response, Convulsions |

| | | | |Swallowing: Pharyngospasm (fear of water) |

|Viral Encephalitis |CMV |Mononuclear Infiltrate, Microglial Nodules |Periventricular |Most common opportunistic virus infecting CNS in AIDS |

|(Cytomegalovirus) | |Neuronophagia, Viral Inclusion Bodies | |Succeptability in fetuses & immunodeficient |

| | | | |Periventricular localization |

|Progressive Multifocal |JC Virus |Mononuclear Infiltrate, Microglial Nodules |Oligodendrocytes |Only immunodeficient individuals succeptable |

|Leukoencephalopathy | |Neuronophagia, Viral Inclusion Bodies |Loss of myelin |Tropism for oligodendrocytes |

| | |Widespread loss of myelin | |Poor Prognosis |

|Viral Encephalitis |HIV-1 |Mononuclear Infiltrate, Microglial Nodules |Doesn’t Infect Neurons |Infected: Macrophages, Giant Cells Microglia (NOT neurons) |

|(HIV) | |Neuronophagia, Viral Inclusion Bodies | |Can lead to: Toxo, CMV, Cryptomeningitis, PML |

| | |Dementia, Ataxia, Incontinence, Seizures | |2 most common focal lesions: Toxo Abscess & 1º Lymphoma |

| | |Cerebral Atrophy, Ventriculomegaly | |Infection is rare in congenital AIDS |

|Neurosyphilis |Treponema pallidum | |Absence of Deep Tendon Reflexes |Meningovascular: Meningitis, Meningeal Arteritis |

|(Tertiary Syphilis) | | |Charcot Joints |Paretic: Invastion of parenchyma (dementia & motor instability) |

| | | |“Lightning Pains” |Tabes Dorsalis: Destruction of Dorsal Roots (Ataxia, Skin & Joint|

| | | | |Lesions[Charcot Joints], Dysesthesia, No deep tendon reflexes) |

CNS Pathology (Contd. 7)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Neuroborreliosis |Borrelia burgdorferi |Meningitis | |Major arthropod born disease in US; Evolves through 3 stages |

|(Lyme Disease) | |Encephalopathy | |Nervous System involved in Stage 2 (months) & 3 (years) |

| | |Facial-nerve paralysis | | |

| | |Polyneuropathies | | |

|Transmissible Spongiform |Prion (PrPSc) |Dementia, Ataxia, Insomnia, Paraplegia |PrPSc |Most Common is Sporadic = Creutzfield-Jakob Disease (CJD) |

|Encephalopathy |Sporadic |Paresthesias, Deviant Behavior |No Inflammation |Infection: Corneal Transplants, Electrodes, Dural Grafts & GH |

| |Genetic |No Inflammation; Vacuolization of Tissue | |Course is relentlessly progressive, fatal in a year |

| |Infectious |(Dementia & Startle Myoclonus = CJD) | | |

|Alzheimer’s Disease |Head Trauma, Early Low Linguistic Skill|Progressive decline in memory & cognitive fxn |APP, PS1,PS2 |½ of pts over 85 have AD |

| |Low Educational Achievement |Personality & Behavioral Changes |Tau Tangles |Areas Affected: Basal Nucleus (Ach), Locus Ceruleus (NE) & Dorsal|

| |APO E-4 |Neurofibrillary Tangles (Tau) & Plaques (Aβ) |Aβ Plaques |Tegmentum (5HT); Entorhinal Cortex & Hippocampus |

| |APP(21), PS1, PS2 & Chr 10 Mutations |Loss of CAT & Acetylcholineesterase | |Treatment: Cholinesterase Inhibitors, NMDA Antagonists & Vit. E |

|Frontotemporal Dementia |Inherited |Onset: Personality & Behavioral Changes |Pick Bodies |Pick Bodies = silver positive cytoplasmic inclusions |

|(Pick’s Disease) |Chr 17 & Tau gene mutations |Impaired Judgement, Language & Memory |Chr 17 | |

| | |Frontal & Temporal Lobe Atrophy | | |

| | |Pick Bodies, Balloon Cells | | |

|Parkinson’s Disease |Age, |Tremor, Cogwheel Rigidity, Akinesia |Substantia Nigra |Most Frequent Basal Ganglia Disorder |

| |Mitochondrial Dysfunction |Disturbances of Posture, Equilibrium & |Locus Ceruleus |12 genetic mutations: PARK 1-10, NR4A2, Synphilin-1 |

| |Oxidative Stress |Autonomic Funciton; Dementia |Lewy Bodies | |

| |Excitotoxicity, Toxins (MPTP) |Substantia Nigra & Locus Ceruleus Damaged |Loss of melanin & Dopamine | |

|Dementia with Lewy Bodies | |Dementia, Psychoitc Behavior, Parkinsonism | |Second Most Common Dementia of Elderly |

| | |Lewy Bodies, Senile Plaques, Tangles | | |

|Huntington’s Disease |Genetic (AD) |Choreoathetoid Movement & Dementia |↓ GABA, Glu Decarboxylase, CAT |Genetic Test available for confirmation |

| |HD gene = Chr 4 p16.3 (36-121 CAGs) |GABAergic medium spiny striated neurons | |Patients have a high suicide rate |

| | |Atrophy of Caudate & Putamen | | |

| | |Ventricular Enlargement & Frontal Lobe Atrophy | | |

|Friedreich’s Ataxia |Genetic (AR) |Limb & Trunk Ataxia |Small Spinal Cord |Most Common Inherited Ataxia |

| |Frataxin = 9q13-q21.1 (200-900 GAAs) |Loss of limb proprioception & deep tendon | |Degeneration of posterior spinal cord |

| | |reflex | |Frataxin = unknown function, but disease due to loss of function |

| | |Dysarthria & Extensor Plantar Response | | |

| | |Kyphoscoliosis, Cardiomyopathy & DM | | |

|Spinocerebellar Ataxia Type I |Genetic | | |Second Most Common |

| |Triplet Repeats within gene | | | |

|Dentato-rubro-pallido-luysian |Genetic | | | |

|Atrophy |Triplet Repeats within gene | | | |

|Machado-Joseph Disease |Genetic | | | |

| |Triplet Repeats within gene | | | |

|Amyotrophic Lateral Sclerosis |Excitotoxins, Viral Infection |Upper & Lower Motor Neuron Degeneration |Upper & Lower Motor Neuron |More common in men; rapid progression toward death |

| |Immunological Abnormalities |Lower: Atrophy, Fasiculations, No reflexes |No inflammatory reaction |Familial ALS = Superoxide Dismutase gene on Chr 21 |

| |Trace Elements & Free Radicals |Upper: Hyperreflexia, spasticity | |Difficulty swallowing & chewing; Cell loss most intense in |

| |Genetic (10%) Chr 21 |Demyelination & atrophy of anterior cord | |cervical |

| | | | |No inflammatory reaction |

CNS Pathology (Contd. 8)

|Disease |Cause/Risk Factors |Symptoms |Buzzwords |Other |

|Progressive Bulbar Palsy | |Brainstem Motor Nuclei | |Rapidly Progressive |

|Progressive Spinal Muscular | |Anterior Horn Cells & Nerve Root |Anterior Horn |No change in corticospinal tract |

|Atrophy | | | | |

|Primary Lateral Sclerosis | |Corticospinal Tract |Corticospinal Tract | |

|ALS-Parkinsonism Dementia Complex| | | | |

|of Guam | | | | |

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