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Path 3.doc.doc

  1. 1. Adrenal Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other ↑ Cortisol 55-75% of endogenous cases, more common in women Pituitary Hypersecretion of ACTH Obesity, Moon Face, Buffalo Hump, Osteoporosis Moon Face Diffuse Bilateral Adrenal Hyperplasia w/ thick yellow cortex Cushings Disease (usually a microadenoma) Hirsutism, ↑ Infections, HT, Thin Skin, Buffalo Hump Suppression by High Dose Dexamethasone Easy Bruising, Red Stria & Muscle Weakness Inferior Petrosal Sinus gradient of 3:1 Nonpituitary Neoplasm Secretion ↑ Cortisol Most common in men Cushings Syndrome (Small Carcinoma, Bronchial & Obesity, Moon Face, Buffalo Hump, Osteoporosis Small Cell Carcinoma Diffuse Bilateral Adrenal Hyperplasia w/out nodularity (Ectopic ACTH or CRH) Pancreatic Carcinoids, Thymoma, Hirsutism, ↑ Infections, HT, Thin Skin, ½ of Bronchial Carcinoids suppressed by ↑ dose dexamethasone Pheochromocytoma, Gastrinoma) Easy Bruising, Red Stria & Muscle Weakness ↑ Cortisol Adrenal Adenoma Cushings Syndrome Obesity, Moon Face, Buffalo Hump, Osteoporosis ↓ CRH & ACTH Adrenal Carcinoma ↓ CRH & ACTH (Adrenal Hypersecretion) Hirsutism, ↑ Infections, HT, Thin Skin, Atrophy of adjacent cortex & contralateral adrenal cortex Adrenal Nodular Hyperplasia Easy Bruising, Red Stria & Muscle Weakness ↑ Cortisol Most common source is Prednisone Cushings Syndrome Obesity, Moon Face, Buffalo Hump, Osteoporosis Exogenous Cortisol Excess Prednisone ↓ Pituitary ACTH & Small Adrenal Glands with thin cortex (Exogenous Cortisol Excess) Hirsutism, ↑ Infections, HT, Thin Skin, Zona Glomerulosa not affected Easy Bruising, Red Stria & Muscle Weakness ↑ Cortisol Pseudo-Cushings Syndrome Depression, Alcoholism, Obesity, Obesity, Moon Face, Buffalo Hump, Osteoporosis (Temporary Cortisol Excess) Eating Disorder, Stress & Illness Hirsutism, ↑ Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle Weakness ↑ Aldosterone Small yellow encapsulated tumor found usually on left & in ♀ Primary Aldosteronism HT, ↓ Serum K+, ↑ Extracellular fluid, Alkalosis Aldosterone secreting Adenoma ↓ Renin & ↑ Aldosterone Low Plasma Renin Activity (PRA) (↓ Renin – Conn’s Syndrome) Weakness, Paesthesias, Visual Disturbances Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test) Headaches, Tetany, Cardiac decompensation ↑ Aldosterone Bilateral idiopathic hyperplasia = less common than Conn’s Primary Aldosteronism HT, ↓ Serum K+, ↑ Extracellular fluid, Alkalosis Treat w/ spironolactone & something for HT Idiopathic ↓ Renin & ↑ Aldosterone (↓ Renin – Adrenal Hyperplasia) Weakness, Paesthesias, Visual Disturbances Low Plasma Renin Activity (PRA) Headaches, Tetany, Cardiac decompensation Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test) ↑ Aldosterone Renal Artery Stenosis Secondary Aldosteronism HT, ↓ Serum K+, ↑ Extracellular fluid, Alkalosis Renin producing tunor ↑ Renin & ↑ Aldosterone High Plasma Renin Activity (PRA) (↑ Renin) Weakness, Paesthesias, Visual Disturbances Chronic edema Headaches, Tetany, Cardiac decompensation Black Licorice ↓ Aldosterone Hyporenemic Hypoaldosteronism Chewing Tobacco Hypertension ↑ ACTH & DHEA → virilization Most common cause of CAH & of ambiguous genitalia Congenital Adrenal Hyperplasia 21-Hydroxylase Deficiency “Classic” = ↓ Aldosterone & Cortisol; ↑ Renin Hallmark is increased 17-Hydroxyprogesterone (21-Hydroxylase Deficiency) (CYP21A2 Deficiency) “Classic w/out wasting” = nl Ald & ↓ Cortisol Treatment = replace aldosterone & cortisol “Non-classical” = nl Aldosterone & Cortisol ↑ ACTH & DHEA → virilization Congenital Adrenal Hyperplasia 11β-Hydroxylase Deficiency ↑ Deoxycortisone (11β-Hydroxylase Deficiency) ↓ Aldosterone, Renin & Cortisol ↑ Aldosterone & ACTH Congenital Adrenal Hyperplasia 17α-Hydroxylase Deficiency ↓ Cortisol & Sex Steroids (17α-Hydroxylase Deficiency) Hypertension & Hypokalemia
  2. 2. Adrenal Pathology (contd.) Disease Cause/Risk Factors Symptoms Buzzwords Other Immediate steroid need 1) Immediate need for steroids – glands unable to respond Cortical Hypofunction Rapid steroid withdrawal ↑ ACTH 2) Rapid Withdrawal of steroids (Primary Acute Insufficiency) Mass Destruction (DIC,Hemorrhage) 3) Massive destruction – hemorrhage, anticoagulants, DIC Waterhouse-Friderichsen Bacteremic Infection Adrenal Hemorrhage → Cortical Hypofunction ↑ ACTH More common in children Syndrome Autoimmune (majority) Destruction of adrenal cortex only Cortical Hypofunction TB, Histoplasmosis, Carcinoma Fatigue, muscle weakness, weight loss, GI upset (Primary Chronic Insufficiency) ↑ ACTH Thin cortex w/ lymph infiltrates – unaffected medulla AIDS, Amyloidosis, Sarcoidosis Hypoglycemia, Salt craving, Prerenal Azotemia (Addison’s Disease) Hemochromatosis Acidosis, Hypotension & Hyperpigmentation Cortical Hypofunction Autoimmune (majority) (Primary Chronic Insufficiency) TB, Histoplasmosis, Carcinoma 1) Adrenal insufficiency – same as above ↑ ACTH Thin cortex w/ lymph infiltrates – unaffected medulla (Addison’s Disease) AIDS, Amyloidosis, Sarcoidosis 2) Hypoparathyroidism & Candidiasis Subtype I Hemochromatosis Cortical Hypofunction Autoimmune (majority) (Primary Chronic Insufficiency) TB, Histoplasmosis, Carcinoma 1) Adrenal insufficiency – same as above ↑ ACTH Thin cortex w/ lymph infiltrates – unaffected medulla (Addison’s Disease) AIDS, Amyloidosis, Sarcoidosis 2) Autoimmune thyroid disease & Type I DM Subtype II– Schmidt’s Syndrome Hemochromatosis Cortical Hypofunction Congenital Adrenal Hyperplasia (Primary Chronic Insufficiency) ↑ ACTH Enzyme Inhibitor (ex. = ketoconazole) (Failure of Cortisol Production) Carcinoma, Infection, Irradiation, No aldosterone or ACTH deficiency Cortical Hypofunction Fatigue, muscle weakness, weight loss, GI upset Infarction Features of panhypopituitarism (Chronic 2º/3º Insufficiency) Hypoglycemia, Salt craving, Prolonged use of steroids→↓ ACTH Delayed response to prolonged ACTH stimulation test HT with or without paroxysmal attacks Most are solitary & in medulla; pink colored; large = encapsulated Headaches, sweating, fever, GI upset, anxiety Diagnosis = Normetanephrine & metanephrine in plasma Pheochromocytoma MEN Type II or III Adrenomedullary Chromafin cells Palpitations orthostatic HT, numbness Clonidine useful in exclusion; Paroxysms can be provoked Cardiac manifestations Rule of 10’s = 10% extrarenal, bilateral, malignant, familial Parathyroid hyperplasia MEN Syndrome Type I Pituitary adenomas (Wermer Syndrome) Pancreatic islet tumors Pheochromocytoma MEN Syndrome Type II MEN IIA = Parathyroid Adenoma Medullary Thyroid carcinoma (Sipple Syndrome) MEN IIB = Mucocutaneous ganglioneuromas & Marfanoid habitus Parathyroid hyperplasia Pheochromocytoma MEN Syndrome Type III Medullary Thyroid carcinoma Mucosal neuromas/Marfanoid features
  3. 3. Endocrine Pancreas Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Blindness (Lens, Retina, Optic Nerve) Genetic (HLA-DR3 &4) MI is #1 cause of death; Diabetic ketoacidosis Primary Diabetes Mellitus CV disease (MI, stroke, gangrene) HLA-DR3&4 Autoimmune Antibodies Glycosylated collagens →Advanced Glycosylation End Products Type I Nephropathy & Infections (Mucomycosis) Diabetic ketoacidosis Environment (Viral Infection) Intracellular hyperglycemia→Sorbitol (lens & Schwann Cell) Peripheral Neuropathy, Polydipsia & Polyuria Genetic (not HLA related) Blindness (Lens, Retina, Optic Nerve) MI is #1 cause of death; Hyperosmolar Coma Primary Diabetes Mellitus Obesity CV disease (MI, stroke, gangrene) Hyperosmolar Coma Glycosylated collagens →Advanced Glycosylation End Products Type II Insulin Deficiency Nephropathy & Infections (Mucomycosis) Intracellular hyperglycemia→Sorbitol (lens & Schwann Cell) Insulin Resistance (receptor & GLUT) Peripheral Neuropathy, Polydipsia & Polyuria Pancreatitis Secondary Diabetes Mellitus Pancreatic Cancer Destruction of islets after disease Drugs
  4. 4. Thyroid Pathology Disease Cause/Risk Factors Symptoms Buzzwords Other Dietary Hyperplastic enlargement of thyroid Diffuse Non-Toxic Goiter ↓ iodine Involves whole gland ↓ T3/T4 (Endemic) goitrogens More common ↑ TSH Hyperplastic enlargement of thyroid Diffuse Non-Toxic Goiter Substance interfering with synthesis ↓ T3/T4 Young females Typically young females (Sporadic) Hereditary enzyme defect ↑ TSH Hyperplastic enlargement of thyroid ↓ T3/T4 & ↑ TSH Nodules/Cysts Multinodal Goiter Hemorrhage, scarring & calcification Recurrent hyperplasia & involution Irregular Irregular with Nodules & Cysts Toxic multinodal goiter Plummer’s Syndrome Hyperfunctioning Goiter ↑ T3/T4 No skin/eye changes of Grave’s Disease Thyrotoxicosis (with diffuse hyperplasia) Typically females Autoimmune (LATS/TSI & TGI) Graves Disease Ophthalmopathy (Paralysis & exopthalmos) Treatment: PTU, methimazole, radioiodine & surgery Genetic? (HLA-B8 & DR3) Dermopathy (Pretibial myxedema) Eye Muscle Paralysis & Exopthalmos NOT seen in Thyrotoxicosis Cardiac: ↑HR,A-fib,Cardiomegaly, CHF Low TSH (suggestive) & High T4 (confirms) Hyperfunctioning Thyroid Heat Intolerance Neuromuscular: Hyperreflexia,tremor,wasting Hyperpigmentation over extensor surfaces Thyrotoxicosis Leakage from Thyroid Lid Lag Skin: Heat Intolerance, ↑ Sweat & Pigmentation Uncommon causes: Hydatiform mole, Struma ovarii, carcinomas Ingestion of iodide or Synthroid ↓ Cholesterol ↑ Appetite, GI motility, Osteoporosis, Eyes Treatment: β Blockers, Propylthiuracil (PTU) , Iodide, Ablation Insufficient Parenchyma Anemia, ↑ Cholesterol, ↓ Na+, Myxedema High TSH (suggestive) & Low Free T4 (confirms) Hashimoto Thyroiditis (Autoimmune) Cold Intolerance, Fatigue, Depression, Lethargy ↑ Cholesterol Primary Hypothyroidism Therapy = T4 replacement (TSH takes 6-8 weeks to normalize) Developmental, Radiation Weight ↑, Edema, Constipation, Cardiomyopathy Myxedema Low TSH after Tx → osteoporosis & arrythmias Ablation Delayed reflexes (achilles) & Coma (If severe) TSH is unreliable; Use T4 to make diagnosis Seondary Hypothyroidism Pituitary Lesion TRH stimulation Test = no response TSH is unreliable; Use T4 to make diagnosis Tertiary Hypothyroidism Hypothalamic Lesion TRH stimulation Test = delayed response (60 min) ↓ Synthesis Idiopathic (block of TSH receptors Hypothyroidism - Other Use increased dose of T4 during pregnancy Heriditary, Hashimoto Thyroiditis Lithium, Iodides, p-aminosalicylate Mental Retardation Infant Hypothyroidism Short Stature, Coarse Facial Features Protruding Tongue Cretinism Early Childhood Hypothyroidism Umbilical Hernia Umbilical Hernia Protruding Tongue Delayed Brain Development Thyroid Agenesis Deafness & Mutism Fetal Hypothyroidism Iodine Deficiency Deaf & Mute Spasticity Congenital Synthetic Defect Severe Mental Retardation
  5. 5. Thyroid Pathology (contd) Disease Cause/Risk Factors Symptoms Buzzwords Other TPO Antibodies (99% sensitive) Female Predominance Diffusely but painlessly enlarged Thyroid Chronic Autoimmune Thyroiditis Deficiency of Suppressor T Cells Early transient Thyrotoxicosis Early transient Thyrotoxicosis, Later Hypothyroidism Lymph infiltrates & follicles (Hashimoto Thyroiditis) Genetic? (HLA-DR3 &5) Later Hypothyroidism Risk for B Cell Lymphomas Hurthle Cells (granular cytoplasm) TSH antibodies blocking receptor Other antibodies: Thyroglobulin, Thyroid Peroxidase, I transporter Subacute Thyroiditis Painful, diffusely enlarged Thyroid Viral (Mumps, Influenza, Coxsackie) Painful Self Limited (DeQuervain’s/Granulomatous) Giant Cells & Macrophages (like granuloma) Vigorous Palpation Palpation Thyroiditis Giant Cells & Macrophages (like granuloma) Disuption of follicles Subacute Lymphocyte Self Limited Idiopathic Painless Goitrous Enlargement Post-Partum Thyroiditis Often seen in post-partum women Causes Laryngeal Nerve Paralysis (SOB & difficulty swallowing) Fibrosing Thyroiditis - Painless Riedel’s Thyroiditis Simulates malignancy Hard gland May be associated with fibrosis elsewhere Majority of Thyroid neoplasms Benign, solitary, encapsulated Follicular Adenoma Not likely to cause thyrotoxicosis Doesn’t take up iodine May make more T3 than T4 Encapsulated or Infiltrating Most common thyroid cancer –↑ incidence in Gardner Syndrome RET gene mutation (MEN II) Radiation Complex branching papillae Optically clear nuclei in “Little Orphan Annie Cells” Papillary Carcinoma RAS gene mutation Little Orphan Annie Optically Clear nuclei & Psammoma bodies Metastisize to regional nodes; Usually indolent growth Radiation exposure (most common) Nodal Metastasis Intranuclear inclusions, grooves Treatment = Thyroidectomy & radioiodine therapy, Survival 98% 2nd most common - Survival 92% Invasion Follicular Carcinoma RAS gene mutation Vascular or Capsular Invasion Hematogenously spread to bone, lungs & brain Blood Metastasis 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) Parafollicular C Cells (neuroendocrine) Rare – most sporadic, 20% as MEN II or familial Amyloid Stroma RET gene mutation (MEN II) Nodule or multifocal May be paraneoplastic (CEA, somatostatin, serotonin & VIP) Medullary Carcinoma Calcitonin RAS gene mutation Not encapsulated, round or spindle cells Metastasize in blood to lung, liver, bone & nodes Not encapsulated Amyloid( Calcitonin) tumor stroma Treatment = Thyroidectomy Poor prognosis – uniformly fatal RAS gene mutation Undifferentiated neoplasms Elderly Loss of I uptake & ↓ Thyroglobulin Anaplastic Carcinomas P53 gene mutation Large, locally invasive, rapidly growing Fatal Survival less than 1 year from diagnosis Possibly derived from Papillary Carcinoma
  6. 6. Leukemia & Lymphoma Disease Cause/Risk Factors Symptoms Buzzwords Other Trisomy 21, Bloom’s, Fanconi’s Rapid Onset, > 20% Blasts Cells similar to lymphoblastic lymphoma Children Acute Lymphoblastic Leukemia Radiation Bone Pain, CNS & Testes Involvement Generally good prognosis (70%) = ↓ WBC, t12:21, < 9yo, diploidy TdT+, (ALL) Alkylating Agents, Benzene HSmegaly, Anemia & Thrombocytopenia Bad = WBC (>10K), T-Type, t9:22, 11q23, organomegaly Scant agranular cytoplasm Viral T Type = lymphadenopathy & mediastinal mass 3 types: Pre B (85%), Pre T (15%), B “like Burkitts” (2%) Trisomy 21, Bloom’s, Fanconi’s Rapid Onset, > 20% Blasts Fair prognosis (40%), Usually adults Auer rods Acute Myeloid Leukemia Radiation Anemia & Thrombocytopenia Frequent infections & mucosal bleeding CD13, CD15, CD33 (AML) Alkylating Agents, Benzene Monocytic = gum hyperplasia Good = t8:21, t15:17 (treat w/ RA) & Chrom 16 abnormalities Granular Cytoplasm Viral Promyelocytic (M3) = DIC, ↓WBC Bad = t9:22, 11q23, origin from myelodysplasia or treatment Trisomy 21, Bloom’s, Fanconi’s Acute Leukemia Radiation Myeloid & Lymphoid features Poor prognosis of Ambiguous Lineage Alkylating Agents, Benzene Viral Trisomy 21, Bloom’s, Fanconi’s Gradual onset, Mature Cells Usually adults, Philadelphia Chromosome (t 9:22) ↓ LAP Chronic Myeloid Leukemia Radiation 100% cellular Bone Marrow (no fat) bcr-abl ↑ Tyrosine Kinase activity ( Treat with Gleevec) t9:22 or bcr-abl (CML) Alkylating Agents, Benzene Pluripotent Stem Cells→Granulocytes ↓ Leukocyte Alkaline Phosphatase (LAP) Pluripotent Stem Cells Viral Splenomegaly = Draggin Sensation Poor Prognosis - Always goes to blast crisis (AML or ALL) Gradual onset, Mature Cells, Hepatosplenomegaly Not radiation Usually adults (most common adult leukemia in west) Trisomy 21, Bloom’s, Fanconi’s Chronic Lymphocytic Leukemia Clonal B Cell Disorder (small lymphocytes) CD5, CD20, CD23 Same as CLL; indolent, not affected by therapy Alkylating Agents, Benzene (CLL) ↑ Infections Del 13q Some have large cell transformation (Richter Syndrome) Viral Hypogammoglobulinemia RichterSyndrome Bad = trisomy 12, CD38 & de1 11q Gradual onset Adult Men Usually adult men (2% of leukemias) Trisomy 21, Bloom’s, Fanconi’s Hairy Cell Leukemia Bacterial & Mycobacterial Infections Not radiation Fair prognosis (40%) Alkylating Agents, Benzene (HCL) Beefy Red Splenomegaly, ↑ Reticulin in BM “Fried Egg appearance” Pancytopenia (70%), Neutropenia & Monocytopenia (90-100%) Viral TRAP+ B Cells TRAP+ Good Treatment - 2-CDA, pentostatin & interferon Many subtypes based on ringed sideroblasts & blast counts BM = Hypercellular, Periphery = Pancytopenia Idiopathic Ringed Sideroblasts May progress to AML Myelodysplastic Syndrome <20% blasts in BM, Megaloblastic appearance Therapy related (ex. Radiation) Chromosome 5,7,8 Very poor prognosis Anemia, Infection, Hemorrhage Chromosome 5,7,8 abnormalities ↓ erythropoietin Early organomegaly due to congestion ↑ RBC, Platelets & Granulocytes ↑ Hematocrit Late organomegaly due to extramedullary erythropoiesis Polycythemia Vera Growth Factor Mutations Fibrotic Marrow, Hypertension, Pruritis, Gout Hypertension & Hemorrhage Spent Phase = Fibrotic Marrow DVT, MI, Stroke ↑ Viscosity Fair to good prognosis (depends on treatment-phlebotomy) Early progression to myelofibrosis (spent phase) Dacrocytes (teardrop cells) & enlarged platelets in periphery PDGF & TGF-β Chronic Idiopathic Myelofibrosis Pancytopenia & Etramedullar hematopoiesis “Sensation of fullness” Dacrocytes (Agnogenic Myeloid Metaplasia) Excess collagen from fibroblasts Prognosis is difficult to predict Reticulin Markedly enlarged spleen, Gout Transformation ot AML (20%) Marked Thrombocytosis (>600,000) Least common of myeloproliferative disorders Large Platelets Essential Thrombocythemia Idiopathic Large Platelets Diagnosis by exclusion No myelofibrosis Thrombosis & Hemorrhage Good prognosis (>10 year survival) No Typical Reed Sternberg Cells Predominance of lymphocytes/hystiocytes Men more common Hodgkin’s Disease Lymphohystocytic Cells EBV Typically a cervical node Best Prognosis (Lymphocyte Predominance) B Cell Lymphoma Cd20 & CD45 Can turn into Diffuse Large B Cell Lymphoma CD20 & CD45 Hodgkin’s Disease Predominance of lymphocytes/hystiocytes No Typical Reed Sternberg Cells Men more common EBV (Lymphocyte Rich) CD15 & CD30 Lymphohystocytic Cells Can turn into Diffuse Large B Cell Lymphoma
  7. 7. Leukemia & Lymphoma (Contd.) Disease Cause/Risk Factors Symptoms Buzzwords Other Cervical, Supraclavicular or mediastinal nodes Lacunar Reed Sternberg Cells Hodgkin’s Disease Most common type; affects adolescent or young adult women EBV Variable cell composition & necrosis Collagen Bands (Nodular Sclerosis) Staging (usually I or II) determines treatment; Good prognosis CD15 & CD30 Women Variable cell composition & focal necrosis Hodgkin’s Disease Disordered fibrosis 2nd most common type; men more common EBV Classic Reed Sternberg Cells (Mixed Cellularity) Eosinophils, Plasma & T Cells Staging determines treatment; Guarded prognosis CD15 & CD30 1) Diffuse Fibrosis – RS Cells embedded in Fairly common – usually in older patients Poor Prognosis Hodgkin’s Disease fibrous stroma Often Bone Marrow Involvement (Stage III or IV) EBV Many Reed Sternberg Cells (Lymphocyte Depletion) 2) Reticular – RS Cells in sheets Poor prognosis Bone Marrow ↑ #s of Reed Sternberg Cells Usually not a true Hodgkin’s Lymphoma? Gradual onset, Mature Cells, Hepatosplenomegaly Not radiation Usually adults (most common adult leukemia in west) Trisomy 21, Bloom’s, Fanconi’s Clonal B Cell Disorder (small lymphocytes) CD5, CD20, CD23 Same as CLL; indolent, not affected by therapy Small Lymphocytic Lymphoma Alkylating Agents, Benzene ↑ Infections Del 13q Some have large cell transformation (Richter Syndrome) Viral Hypogammoglobulinemia RichterSyndrome Bad = trisomy 12, CD38 & de1 11q Nodular Growth Pattern with 2 cell types 1) Centrocytes = cleaved nuclear contours CD10,CD20,CD23 Fairly Common; indolent, not affected by therapy Follicular Lymphoma 2) Centroblasts = clear chromatin & multinucleate BCL-2, t14:18 May transform to diffuse large B cell lymphoma Bone Marrow frequently involved Atrophied germinal center CD5 & CD20 Mantle Cell Lymphoma 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) Very Common, Very Aggressive EBV T14:18, t8:14, t13:14 Prognosis depends on treatment, BCL-6 = good prognosis Diffuse Large B-Cell Lymphoma Large cell size, diffuse growth pattern HSV8 BCL2,C-Myc,BCL6 One of three bad types in kids “Starry Sky picture” Highest growth fraction of all tumors Burkitt’s Lymphoma EBV “Starry Sky picture” CD10,CD19,CD20 Most manifest as extra-nodal sites C-Myc Responsive to treatment, but poor prognosis Lymphoblastic Lymphoma One of three bad types in kids Mediastinal Mass like Hodgkins CD3, TdT+, TCL-1 (T Type) (T/B) Responsive to treatment, but poor prognosis One of three bad types in kids Anaplastic Large T/Null Cell CD3, CD30 Uncommon in adults, Common in children Lymphoma ALK, EMA t2:5 Presents in extra-nodal tissue Usually T, not B cell Extranodal NK/T Cell Lymphoma Peripheral T-Cell Lymphoma EBV CD3 Poor Prognosis; Common in Asia, uncommon in US Nasal Type – eats face off
  8. 8. Leukemia & Lymphoma (Contd. 2) Disease Cause/Risk Factors Symptoms Buzzwords Other Indolent Cutaneous disorder CD4 Mycosis fungoides Cerebriform nuclei Extracutaneous spread Polyclonal Ig (Leukemia = Sezary Syndrome) Painful Bone Destruction, ↓ Humoral Immunity M Protein Radiation, Chemicals, Asbestos Most common 1º malignant tumor of bone Plasmacytosis with IL-6, Vertebral Fractures Bence Jones Protein Multiple Myeloma Black Race Complications: Renal failure, Amyloidosis, AML (rarely) M Protein, Bence Jones proteins, Hypercalcemia Hypercalcemia HSV8? Fair prognosis (3 yr) Can spread to nodes, skin, etc IL-6 Plasmocytosis with ↑ Light Chain Production Radiation, Chemicals, Asbestos Fibrils of β-pleated sheets that stain Congo Red 1º Amyloidosis Black Race Large Tongue Usually immunoglobulin light chain Large tongue, Neuropathy, GI Multiple Myeloma Arrythmias, CHF Fibrils of β-pleated sheets that stain Congo Red HSmegaly, 2º Amyloidosis Chronic Infection or Inflammation HSmegaly, Proteinuria Proteinuria Most common monoclonal gammopathy Monoclonal Gammopathy of Diagnosis of exclusion, IgG < 3.5 Aging M Proteins without other symptoms Undetermined Significance May develop into multiple Myeloma Requires no treatment Pituitary Pathology
  9. 9. Disease Cause/Risk Factors Symptoms Buzzwords Other ↑ Prolactin Most common secretory adenoma of anterior lobe Prolactinoma Amenorrhea, Galactorrhea, Infertility, Effects less obvious in postmenopausal women Loss of Libido Treated with bromocriptine Injury to pituitary stalk Compression ↑ Prolactin Due to decreased dopamine to the anterior lobe Hyperprolactinemia Prolactin Trauma to Hypothalamus, Infection Non-prolactin secreting adenomas may compress stalk Drugs (Phenylthiazines) ↑ Growth Hormone → ↑ Hepatic IGF-1 Second most common secretory adenoma of anterior lobe Some produce prolactin as well Somatotroph Adenoma IGF-1 Treatment = transsphenoidal resection, bromocriptine & radiation Acromegaly (adults) & Gigantism (children) Acromegaly = hands, feet, face skin & viscera DM, HT, CHF, arthritis, weakness, GI carcinoma ↑ ACTH→ ↑ Cortisol (Cushing’s Disease) ACTH 90% are microadenomas Corticotroph Adenoma 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 Pregnancy & Lactotroph Hypertrophy Sheehan’s Syndrome Hypotension, DIC Hypopituitarism Most common cause of anterior lobe ischemic necrosis Sickle Cell Anemia, ↑ ICP Maldevelopment of diaphragma sella Depends on number of residual cells Pituitary Apoplexy Empty Sella Syndrome Hypopituitarism Maldevelopment = Arachnoid Herniation via enlarged opening Sheehan’s Syndrome No syndrome Ablation Interruption of DA to Posterior Lobe Trauma Diabetes Insipidus Large volume of dilute urine ↓ ADH Treatment = Administer ADH Tumor Inflammation Ectopic ADH (Small Cell Carcinoma) Syndrome of Inappropriate ADH Water Retention, Hyponatremia Treatment = Water Restriction, Slow normalization of Na+ Lung Disease (TB) ↑ ADH (SIADH) GI Upset, Cerebral Edema (Rapid Normalization can cause Central Pontine Myelinolysis) Intracranial Lesions (↓ Inhibition) Drugs Hyperpituitarism, Hypopituitarism Hypothalamic Tumors Glioma & Craniopharyngioma are most common Diabetes Insipidus CNS Pathology
  10. 10. Disease Cause/Risk Factors Symptoms Buzzwords Other Reversible Concussion Blunt non-penetrating injury Paralysis Reversible Traumatic Paralysis Ocurring Immediately After Injury Immediate Seizures Most common sites: Frontal Pole, Temporal Pole, Medial orbital Stress on parenchymal vessels Cognitive & Personality Changes surface of the temporal lobe Contusion Coup Intact pia-glial membrane Headaches Pia-arachnoid not penetrated Countercoup Dizziness Occur at crests of gyri Subarachnoid bleeding Traumatic disruption of pia-arachnoid and brain surface Lacerations Penetrating Wounds Satellite petichial hemorrhages Meningocerebral cicatrix Meningocerebral cicatrix (glial scar) = epileptogenic focus Edema in tissue Fracture Immediate Loss of Consciousness Collection of blood between dura and skull Epidural Hemorrhage Most = Arterial (Middle Meningeal) Lucid Interval Lenticular shaped hematoma Rarely = Dural Sinus, Bridging Veins Later Loss of Consciousness Superficial Cortical Bridging Veins 48 hours-days; appears as clotted blood More Common than epidural hemorrhage Dural Sinus Laceration Gradual Loss of Consiousness Acute Subdural Hemorrhage Clotted Blood 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) Superficial Cortical Bridging Veins Clotted & Fluid Blood More Common than epidural hemorrhage Dural Sinus Laceration Gradual Loss of Consiousness Subacute Subdural Hemorrhage Clotted & Fluid Blood 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) Superficial Cortical Bridging Veins > 3 weeks & Liquefied Hematoma More Common than epidural hemorrhage Dural Sinus Laceration Gradual Loss of Consiousness Liquefied Hematoma Typically seen in infants, elderly & alcoholics Chronic Subdural Hemorrhage Depressed Fractures Hemiparesis → Hemiplegia Minor Precipitating Event 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 Trauma Superficial Cortical Veins Stiff Neck, Alterations in Consciousness Subarachnoid Hemorrhage Stiff Neck Usually multiple and small Surface cortical lacerations Vasospasm & Hydrocephalus Surface cortical contusions Not in contact with the cortical surface, usually solitary Intracerebral Hematoma Rupture of Intrinsic Cerebral Vessels Frontal & Temporal Lobes are most common sites Damage usually occurs where nerves exit through foramina Cranial Nerve Damage Cranial Fractures Most Common = CNI, CNII, CN V & CN VI Pontomedullary Avulsion Marked Hyperextension of neck Poor prognosis, Immediately fatal if complete, die later if incomplete Unconscious from moment of impact Diffuse Axonal Injury No lucid interval Results in disconnection of distal axonal segment Diffuse Shearing of axons Calpain (1º Axotomy) Ca2+ influx & swelling Most common sites = Corpus Callosum & S. Cerebellar Peduncles Microtubule depolymerization, Calpain activation CNS Pathology (Contd.)
  11. 11. Disease Cause/Risk Factors Symptoms Buzzwords Other Unconscious from moment of impact Diffuse Axonal Injury No lucid interval Results in disconnection of distal axonal segment Small axonal membrane tears that reseal Axoplasmic Transport (2º Axotomy) Ca2+ activated proteases, repair fails Most common sites = Corpus Callosum & S. Cerebellar Peduncles Axoplasmic transport causes swelling Greatest Damage = Hippocampus, Caudate, Putamen, Hypoxic Brain Injury Cortical Layers 3 & 5, Purkinje Cells of Cerebellum Diffuse or localized to watershed zone Mechanical Damage White Matter Swelling White matter swelling adjacent to contusion Brain Swelling Blood Vessel Impairment Diffuse Swelling Diffuse Swelling of One or Both Hemispheres Vasodilation Frontal & Temporal Lobes (White Matter) Multiple Petechial Hemorrhages Acceleration/Deceleration? Thalamus Usually seen in patients who die soon after head injury Brainstem 3-4 d = white matter petichiae, capillary necrosis Fractures of Limbs or Limb Giurdles 4-7d = grey matter alterations, fat in capillaries Fat Embolism Usually only seen in adults (children have less fat) (Fat enters veins) 12d-3m = many infarcts in cortex & pons >3 m = atrophy of white matter Occurs during first week Early Post Traumatic Epilepsy Within first week More common in children than adults Associated with: Hematoma, Depressed Fracture, Amnesia Most common complication of blunt head injury Occurs later than one week Late Post Traumatic Epilepsy Blunt Head Injury After first week ↑ Risk = Hematoma, Depressed Fracture, Early Epilepsy 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 Multiple Sclerosis 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 Severe necrotic lesions in spinal cord and optic nerve only Spinal Cord & CN II Only (Neuromyelitis Optica) Rapidly progressive Acute Multiple Sclerosis Fatal in 1-6 months (Marburg Type) Severe & Rapid with extensive involvement of brain & spinal cord Rapid Correction of Hyponatremia Symmetric demyelination in the center of the base of the pons Sever Electrolyte Imbalance Central Pontine Myelinolysis Rapidly evolving quadriplegia CNS Can affect tegmentum occasionally Alcoholism, Liver Transplant Outcome is variable: Complete Recovery→Fatal Burns, Malnutrition Acute Influenza-like Illness Inflammation/Demyelination of Nerves & roots Treatment: Supportive, Plasmapheresis, IV Immunoglobulin CMV & Campylobacter jejuni PNS Guillian-Barre Syndrome Cranial & Spinal Motor Roots = Severe Outcome: Complete recovery is most common, rarely fatal Immunization Ascending Paralysis Ascending Paralysis Death due to respiratory paralysis Autoimmune? CNS Pathology (Contd. 2)
  12. 12. Disease Cause/Risk Factors Symptoms Buzzwords Other Usually assymptomatic Non-closed vertebral arches without cyst Spina Bifida Occulta Folate Deficiency Stigmata (Hypertrichosis) Variable cord anomaly Stigmata: Hypertrichosis,Dimple,Lipoma,Nevus Sacral, Anorectal or UG Defect Meningocele: Meninges protrude through vertebral defect Non-closed vertebral arches with cyst Myelomeningocele: Meninges & Spinal cord protrude through defect Spina Bifida Cystica Folate Deficiency Cyst Meningocele or Myelomeningocele Most survive > 1 year, but frequently have progressive deterioration Disabilities are usual: paraplegia, incontinence, infection, learning 1) Myelomeningocele 2) Elongation of Inferior Vermis & Brain Stem with displacement i Arnold-Chiari Type II Mental Retardation into spinal canal 3) Hydrocephalus Most common congenital malformation of the brain Annencephaly Folate Deficiency Absence of cerebrum & calvarium Stillborn or die shortly after birth Most common neonatal intracranial hemorrhage Intraventricular Hemorrhage Preterm Birth Preterm PV Germinal Matrix is fragile, fibrinolytic & persists until 34 weeks (IVH) Periventricular Germinal Matrix Periventricular Germinal Matrix Variable: May be focal & asymptomatic, may spread into ventricles Common ischemic lesion of preterm infant Initially non-specific Periventricular Leukomalacia Infarction of Periventricular White Matter Preterm Centrum Ovale = vulnerable boundry zone Later: Spastic Motor Dysfunction (PVL) (Centrum Semiovale) Centrum Semiovale (Ventriculopetal & Ventriculofugal Arteries) Paraplegia/Quadraplegia develops in surviving Usually not without permanent sequelae Diffusely Infiltrative 20% of gliomas, Rarely Resectable, Progress towards anaplastic Diffusely infiltrate w/o clear margins Diffuse Astrocytoma No Clear Margins Graded on: Hypercellularity, endothelial changes & necrosis Found in white matter of cerebrum Cerebrum Poor Prognosis Occur in Pons, infiltrate widely Brainstem Glioma Children (2nd decade) Range of grades includes glioblastoma CN Palsies, Long Tract signs, Gait abnormalities (Atrocytoma Subgroup) Pons Surgical removal not possible Emesis & Cerebellar Signs Circumscribed Circumscribed, low grade, histology = biphasic Midline Young>Old Pilocytic Astrocytom Cerebellum, Hypothalamus, Optic Chiasm/Nerve Rosenthal Fibers Optic Nerve Gliomas associated with Von Recklinghausen’s (NF I) Rosenthal Fibers Von Recklinghausen’s (NF I) 60% cystic Most common astrocytoma of childhood Cerebellar Pilocytic Astrocytoma Children (2nd decade) Endothelial proliferation & pleomorphism Good Prognosis Intraventricular Vascular Intraventricular Mass Subependymal Giant Cell Tumor Tuberous Sclerosis Benign but cause problems due to location & hemorrhaging Cells = Large, mix between astrocyte & neuron Hemorrhage Supratentorial Common Most common glioma, Usually in older adults Rapid growth, endothelial proliferation, necrosis Adults Most invasive & aggressive, highly infiltrative Glioblastoma Multiforme Hemorrhagic Foci, Often zones of mixed tumor Always Recurs Tumor always recurs with resection, poor prognosis May Metastasize (CSF) Metastasis Mix: Oligodendroglioma,Ependymoma,Astrocytoma,Neuroectederm CNS Pathology (Contd. 3)

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