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Histology of wet gangrenous necrosis
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Section 1
(50 cards)
Histology of wet gangrenous necrosis
Liquefactive superimposed on coagulative
dry gangrenous necrosis
Ischemia
Apoptosis
Process of programmed cell death ATP-dependent Activate caspases (cytosolic proteases) -> cellular breakdown including: * cell shrinkage * chromatin condensation * membrane blebbing * formation of apoptotic bodies, which are then phagocytosed
Bcl-2 overexpression
Follicular Lymphoma Decrease caspase activation -> tumorigenesis
Immune cell pathway of extrinsic apoptosis
Cytotoxic T-cell release of perforin and granzyme B
Fat necrosis seen in
Enzymatic: scute pancreatitis (saponification of peripancreatic fat); Nonenzymatic: traumatic (eg, injury to breast tissue)
Fibrinoid necrosis seen in
necrosis of immune reactions (immune vasculitis/endocarditis); preeclampsia; malignant hypertension
Pyknosis is a term used to describe a
small, condensed, dark, fragmented nucleus
extrinsic pathway of apoptosis
Liquefactive necrosis
in brain, bacterial infections (abscesses), or wet gangrene
caseous necrosis
degeneration and death of tissue with a cheese-like appearance; Macrophages wall off the infecting microorganism -> granular debris
Coagulative necrosis histology
Cell outlines preserved but nuclei disappear; increase cytoplasmic binding of eosin dyes
Coagulative necrosis results from?
Sudden cut-off of blood supply to an organ Protein denature, enzymatic degradation
Histology of dry gangrenous necrosis
= coagulative
liquefactive necrosis due to
Neutrophils release lysosomal enzymes that digest the tissue; Enzymatic degradation first, then proteins denature
Pyknosis/karyorrhexis
Bcl-2
prevents cytochrome C release from mitochondria Keeps mtch outer membrane impermeable
Intrinsic pathway factors
Regulated by Bcl-2 family BAX and BAK are proapoptotic, Bcl-2 and Bcl-x are antiapoptotic
liquefactive necrosis histology
Early: cellular debris and macrophages Late: cystic spaces and cavitation (brain); Neutrophils and cell debris seen with bacterial infection
Coagulative necrosis seen in
Ischemia/infarcts in most tissues (except brain)
Fat Necrosis Histology
Outlines of dead cells without peripheral nuclei; Saponification of fat (combined with Ca2+) appears dark blue on H&E stain
Fibrinoid necrosis
Immune complexes combine with fibrin -> vessel wall damage (type III hypersensitivity reaction)
Liquefactive necrosis occurs in the brain because:
It is rich in hydrolytic enzymes and lipids
Necrosis types:
Coagulative Liquefactive Caseous Fat Fibrinoid Gangrenous
Intrinsic mitochondrial pathway
Saponification
When fat dies and fatty acids are released, they combine with Ca to produce chalky white deposits
Apoptosis
Cell injury
cell injury reversible with oxygen
CELL/mitochondrial swelling (low ATP-> lower activity of Na+/K+ and Ca2+ pumps); nuclear chromatin clumping, decreased glycogen, fatty change, ribosomal detachment (decrease protein synthesis) Membrane blebbing
Ischemia
an inadequate blood supply to an organ or part of the body, especially the heart muscles.
Apoptosis histology
Deeply eosinophilic cytoplasm; Basophilic nucleus Pyknosis Karyorhesis Cell membrane typically remains intact (unlike necrosis) DNA laddering (fragment in multiple of 180 bp) is a sensitive indicator
fat necrosis due to
Damaged cells release lipase to break down triglycerides, liberating fatty acids to bind Ca -> saponification
Necrosis
Enzymatic degradation and protein denaturation of cell due to exogenous injury -> intracellular components leak. Inflammatory process (unlike apoptosis)
Karyorrhexis
Fragmentation of nucleus Caused by endonuclease-mediated cleavage
wet gangrenous necrosis
Superinfection
caseous necrosis
Fas-FasL interaction
Last way of killing for CD8+ (apoptosis) "death receptor", finishes up and marks for death Thymic medullary negative selection
coagulative necrosis
Gangrenous necrosis seen in
Distal extremity and GI tract, after chronic ischemia
Necrosis definition
Death of a large group of cells followed by acute inflammation
intrinsic pathway of apoptosis occurs
occurs during embryogenesis, hormone induction, and atrophy Regulating factor is withdrawn from a proliferating cell population (eg, decreased IL-2 after a completed immunologic reaction) Also occurs after exposure to injurious stimuli (radiation, toxins, hypoxia)
caseous necrosis
TB Systemic fungi (eg, Histoplasma capsulatum), Nocardia
Apoptotics pathways
Intrinsic (mitochondrial) Extrinsic (death receptor)
Ligand Receptor Interaction
- Intracellular Receptors - Cell membrane receptors and membrane bound organelles - FasL binding to Fas (CD95) or TNF -a binding to its receptor
liquefactive necrosis
commonly results from ischemic injury to neurons and glial cells in the brain; Bacterial abscesses
Fibrinoid necrosis histology
Vessel walls are thick and pink
Cell injury irreversible
Nucleus: pyknosis, karyorrhexis, karyolysis; Increase mitochondrial permeability; Rupture of lysosomes and autolysis; Plasma membrane damage (degradation of membrane phospholipid) Cell death
Fat necrosis
Disruption of fat, fibrosis, giant cell formation, and inflammation
extrinsic pathway of apoptosis
death-receptor initiated 2 pathways: * ligand receptor interaction * immune cell
defective Fas-FasL interactions →
autoimmune disease (extrinsic apoptotic pathway necessary for T cell negative selection) Autoimmune lymphopriferative syndrome
Section 2
(50 cards)
watershed areas of cerebral circulation
Red infarct
Develops in tissues which have dual blood supplies (infarction) Happens with lung infarction
P-selectin
derived from Weibel-Palade bodies in venular endothelial cells Plateled and endothelial cells. Step 1 leukocyte extravasation
Pale infarct
Occur in solid tissues with a single blood supply
Cellular component of inflammation
Neutrophils extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation, and inflammatory mediator release
pale infarct
Anemic; occur in solid tissues with SINGLE (end-arterial) blood supply like heart, kidney, spleen
Extent of dystrophic calcification
Tends to be localized (eg, calcific aortic stenosis) shows dystrophic calcification and thick fibrosis wall
CD34, glyCAM-1
addressin for L-selectin at lymph nodes
VLA-4
Expressed on activated T cells, guides T cells to site of infection by binding to VCAM-1
ICAM-1
- on APC or endothelium - binds LFA-1 on T cell CD54
Sialyl-Lewis
Adhesion molecules expressed on leukocytes that bind to selectins
Most vulnerable neurons to hypoxic-ischemic insults
Purkinje cells of cerebellum and pyramidal cells of the hypocampus and neocortex
Etiology of dystrophic calcification
2• to injury or necrosis
metastatic calcification associated
Predominantly in interstitial tissues of kidney, lung, gastric mucosa (these tissues lose acid quickly; increase pH favors Ca2+ deposition) Nephrocalcinosis of collecting ducts May lead to nephrogenic diabetes insipidus and renal failure
CREST syndrome
Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, Telangiectasia
PCA
posterior cerebral artery
Dystrophic calcification
MCA
middle cerebral artery
Steps of leukocyte extravasation
Margination and rolling; Tight binding (adhesion₽); Diapedesis; Migration
Step 1 in leukocyte extravasation:
Margination and rolling; E-selectin; P-selection; GlyCAM-1; CD34; Sialyl-LewisX leukocytes; L selectin.
CD11/CD18
markers for integrins
Heart most vulnerable region to hypoxia/ischemia
Subendocardium (LV)
Liver most vulnerable region to hypoxia/ischemia
Area around central vein (zone III)
Chronic inflammation characteristics
Persistent destruction and repair. Associated with blood vessels proliferation, fibrosis. Granulomas. Outcome include scarring, amyloidosis, and neoplastic transformation.
VCAM-1
Expressed on endothelium of blood vessels in inflamed tissue, binds to VLA-4 on T cells CD106
Dystrophic calcification Associate
TB (lung, pericardium) and other granulomatous infection; Liquefactive necrosis of chronic abscesses; Fat necrosis; Infarcts; Thrombi; Schistosomiasis; Congenital CMV; Toxoplasmosis; Rubella; Psamomma bodies; CREST syndrome
Psammoma bodies
Meningiomas, papillary thyroid carc, mesothelioma, papillary serous carcinoma of endometrium/ovary
metastatic calcification
mineral deposits that occur in undamaged tissues due to hypercalcemia; Widespread extent ( metastatic calcification of alveolar walls in acute pneumonia)
watershed areas
areas between terminal branches of major arterial blood supplies where blood supply does not overlap. These areas are susceptible to ischemia from hypoperfusion
Mac-1
Integrin- heterodimer- one chain is CD18-the 2 integrin chain, on monocytes and macrophages
Etiology of metastatic calcification
2• to hypercalcemia (eg, 1• hyperparathyroidism; sarcoidosis; hypervitaminosis D) or high calcium-phosphate product levels (eg, chronic renal failure with 2• hyperparathyroidism, long-term dialysis, calciihylaxis, multiple myeloma)
Dystrophic calcification
calcification of damaged tissue; normal serum calcium;
Vascular component of inflammation
Increased vascular permeability, vasodilation, endothelial injury
Leukocyte extravasation occurs predominately where?
Extravasation predominantly occurs at postcapillary venules.
acute inflammation cells
Neutrophils, eosinophils, atb (pre-existing), mast cell, and basophil mediated.
caseous necrosis histology
Fragmented cells and debris surrounded by lymphocytes and macrophages
E-selectin
Selectin molecule on endothelial cells; Unregulated by TNF and IL-1; Step 1 of leukocyte extravasation.
ACA
anterior cerebral artery
Serum Ca2+ levels in metastatic calcification
Not normocalcemic
Serum Ca2+ levels in patient with dystrophic calcification
Normocalcemic
Subsequent infarction in brain
ACA/MCA/PCA boundary areas
Acute inflammation characteristics
Rapid onset (seconds, minutes) - short duration (minutes, days). Outcome: complete resolution, abscess formation, or progression to chronic inflammation
Granuloma
Nodular collections of epithelioid macrophages (abundant pink cytoplasm) with surrounding multinucleated giant cells and lymphocytes.
VCAM-1 and ICAM-1 aid in the (x) of leukocyte diapedesis
Firm adhesion (x)
LFA-1
molecule expressed by leukocyte that assists in tight-binding stage of leukocyte extravasation
Types of infarcts
Red Pale
Margination and rolling is defective in which disorder(s)?
Leukocyte adhesion deficiency type 2 (decreased Sialyl-Lewis)
red infarct
Hemorrhagic; Occurs in venous occlusion and tissues with multiple blood supplies such as liver, lung, intestine, tested; Reperfusion (after angioplasty) -> injury due to damage by free radicals
Chronic inflammation cells
Mononuclear cell (monocytes/macrophages, lymphocytes, plasma cells) and fibroblast mediated.
Inflammation characterized by....
redness (rubor), heat (calor), swelling (tumor), pain (dolor) and functio laesa (loss of function)
Section 3
(50 cards)
Hypertrophic scar
A raised scar characterized by excess collagen. (III) Parallel organization of collagen Confined to borders of original wound Infrequent No predisposition
Sarcoidosis Dx
Chest Xray, Lesion Biopsy ( Better sample is Lung. Do not take biopsy from erythema Nodosum) Noncaseating granulomas
ERBB1 (EGFR)
Adenocarcinoma of Lung
exudate
cellular (cloudy), protein rich (>2.9 g/dL), high LDH (vs serum). Due to: lymphatic obstruction (chylous), inflammation/infection; malignancy.
Granulomas formation
Th1 cells secrete IFN-y, activating macrophages. TNF-a from macrophages induces and maintains granuloma formation. Associated with hypercalcemia due to calcitriol (1,25 -[OH]2 vitamin D3) production. Caseating necrosis is more common with an infection etiology.
VEGF
stimulates angiogenesis
Congo red stain
Amyloid stains brick red and displays apple green birefringence with polarized light
Autoinflammatory granulomatous disease
Sarcoidosis Crohn disease Primary biliary cirrhosis Subacute (de Quervain/granulomatous) thyroiditis Granulomatosis with polyangiitis (Wegener) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) Giant cell (temporal) arteritis Takayasu arteritis
TGF-b
Angiogenesis, fibrosis, cell cycle arrest
Proliferative phase of healing cells
Fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages.
low ESR
CHF, low plasma protein, polycythemia, sickle cell, microcytosis, hypofibrinogenemia.
Anti-TNF drugs
As a side effect can cause sequestering granulomas to break down, leading to disseminated disease. Always test for Karen TB before starting anti-TNF therapy.
Granulomatous disease from foreign material
Berylliosis Talcosis Hypersensitivity pneumonitis
Diapedesis is the
migration of white blood cells from the blood out to the tissues.
Bacterial granulomatous disease
Mycobacterium; Bartonella henselae (cat scratch disease); Listeria monocytogenes (granulomatous infantiseptica); Treponema pallidum (3• Syphilis)
Light criteria
Dx analysis comparing serum and pleural fluid protein and LDH levels.
Amyloid deposits visualization by polarized light
Apple-green birefringence
effusion
outpouring
Amyloidosis
Abnormal aggregation of proteins (or their fragments) into b-pleated linear sheets -> insoluble fibrils -> cellular damage and apoptosis.
Pleural effusion is exudative if >= 1 of the following criteria is met:
*Pleural effusion protein/serum ratio > 0.5 * Pleural effusion LDH/serum LDH ration > 0.6 * Pleural effusion LDH > 2/3 of the upper limit of normal for serum LDH
PECAM-1
CD31
Oxygen toxicity examples
Retinopathy of premature (abnormal vascularization), bronchopulmonary dysphasia, reperfusion injury after thrombolytic therapy
remodeling phase of healing
Fibroblasts Type III collagen replaced by type I collagen, Increase tensile strength of tissue. Delayed wound healing in zinc deficiency.
free radical injury
damage to cells resulting from reactive oxygen species via: Membrane lipid peroxidation; Protein modification; DNA breakage
CHF (congestive heart failure)
heart is unable to pump its required amount of blood
Keloid scar
Raised and moves beyond edges of wound (genetic and reoccurring) Claw-like projection typically on earlobes, face, upper extremities. Frequent reccurence. Higher incidence in ethnic groups with darker skin, Desorganized types I and III collagen
Granulomas
Hypertrophic scar
Proliferative phase of healing characteristics:
Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, wound contraction (mediated by myofibroblasts). Delayed wound healing in vit C deficiency and cooper deficiency.
Free radicals can be eliminated by
Scavenging enzymes (catalase, superoxide dismitase, glutathione peroxidase); Spontaneous decay; Antioxidants (A,C,E); Certain metal carrier proteins (transferrin, ceruloplasmin).
EGF
epidermal growth factor Stimulate cell growth via tyrosine kinases (eg, EGFR/ErbB1)
PECAM-PECAM binding produces what effect?
Adhesion for transmigration
Metalloproteinases
Tissue remodeling
ROS sources:
Radiation exposure (cancer therapy) Mtb of drugs (phase I) Redox reaction; Nitric oxide (inflammation); Transition metals; WBC (neutrophils, macrophages) oxidative burst.
Transudate
Hypocellular (clear), poor protein (<2.5 g/dL), low LDH (vs serum). Due to: High hydrostatic pressure (eg, HF, Na+ retention) Low oncotic pressure (eg, cirrhosis, nephrotic syndrome)
Migration
4 step of leukocyte extravasation. WBC travels through interstitium to site of injury or infection guided by chemotaxis signals
Erythrocytes sedimentation rate (ESR)
Products of inflammation (eg, fibrinogen) coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube. Often co-tested with CRP levels.
Tissue mediators
PDGF, FGF, EGF, TGF-β, Metalloproteinases, VEGF
C5a, IL8, LTB4, kallikrein, PAF
important neutrophil chemotactic agents
inflammatory phase of healing
Platelets, neutrophils, macrophages; Clot formation, increase vessel permeability and neutrophil migration into tissues; Macrophages cleat debris 2 days later.
Phase of wound healing:
Inflammatory (up to 3 days after wound); Proliferative (day 3-weeks after wound); Remodeling (1 week-6+ months after wound)
ROS drug/chemical toxicity:
Carbon tetrachloride and acetaminophen overdose (hepatotoxicity)
Keloid scar
high ESR
Most anemias; Infection; Inflammation (eg, giant cell [temporal] arteritis, polymyalgia rheumatica); Cancer (eg, metastases, multiple myeloma), Renal Disease (end-stage or nephrotic syndrome); Pregnancy
Parasitic granulomatous disease
Schistosomiasis
Oxygen toxicity symptoms
VENTIAC V ertigo E uphoria N ausea T innitus I mpaired judgement A LOC (Altered LOC) C onvulsions
Fungal granulomatous disease
Endemic mycoses (eg, histoplasmosis)
FGF
Stimulates angiogenesis Fibroblast growth factor
PDGF
Induces vascular remodeling and smooth muscle cell migration; Stimulates fibroblast growth for collagen synthesis; Secreted by activated platelets and macrophages.
Amyloid deposits by H&E
Section 4
(50 cards)
Epithelial benign tumor
Adenine, papilloma
Hypertrophy
Increase in cell size
bone benign tumor
osteoma
Connective tissue benign tumor
Fibroma
Carcinoma
a malignant tumor that occurs in epithelial tissue
ESRD
end-stage renal disease
Heritable amyloidosis
Heterogeneous group of disorders, including familial amyloid polyneuropathies due to transthyretin gene mutation.
Hamartomas
Disorganized overgrowth of tissue in their native location (eg, Peutz-Jeghers polyps)
Neoplastic progression dysplasia
Abnormal proliferation of cell with loss of size, shape, and orientation (eg, koilocytic change)
Tumor Grading
Stage generally has more prognostic value than grade
Colon most vulnerable region to hypoxia/ischemia
Splenic flexure, rectum
AL amyloid (primary)
Deposition of protein from Ig Light chains. Can occur as a plasma cell disorder or associated with multiple myeloma. Often affect multiple organ systems, including renal (nephrotic syndrome), cardiac (restrictive cardiomyopathy, arrhythmia), hematologic (easy bruising, splenomegaly), GI (hepatomegaly), neurologic (neuropathy)
poorly differentiated tumors
recur more rapidly after diagnosis, higher short term mortality Often more aggressive; Look almost nothing like their tissue of origin
blood vessels benign tumor
hemangioma
Hyperplasia
increase in number of cells May be a risk factor for future malignancy (eg, endometrial hyperplasia) but not considered premalignant.
Choristoma
normal tissue aberrant tissue location; pancreatic tissue stomach wall
Tumor stage
Degree of localization/spread based on site and size of 1• lesion, spread to regional lymph nodes, presence of metastases. Based on clinical (c) or pathology (p) findings.
invasive carcinoma
Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases). Cell-cell contacts lost by inactivation of E-cadherin.
Neoplasia
Uncontrolled, clonal proliferation of cells. Can be benign or malignant.
metastasis
spread to distant organs via lymphatics or blood.
Epithelial malignancy
Adenocarcinoma Papillary carcinoma
Atrophy
Decrease in tissue mass due to decrease in size or/and number of cells. Causes include disuse, denervation, loss of blood supply, loss of hormonal stimulation, poor nutrition.
smooth muscle benign tumor
leiomyoma
Seed and soil theory
Seed= tumor embolus Soil = target organ is often the first-encountered capillary bed (liver, lungs, bone, brain, etc)
Dialysis-related amyloidosis
Fibrils composed of b2-microglobulin in patients with ESRD and/or long term dialysis. May present as carpal tunnel syndrome.
organ specific amyloidosis?
Single organ; Alzheimer disease due to deposition of b-amyloid protein cleaved from amyloid precursor protein (APP). IAPP is commonly seen in DM2 and is caused by deposition of amylin in pancreatic islet. Isolated atrial amyloidosis due to atrial natriuretic peptide is common in normal aging and can predispose to increased risk of atrial fibrillation. Amyloid deposition to ventricular endomyocardium in restrictive cardiomyopathy. Calcitonin deposition in tumor cells in medullary carcinoma of the thyroid.
Kidney most vulnerable region to hypoxia/ischemia
Straight segment of proximal tubule (medulla); Thick ascending limb (medulla)
Differentiation
The degree to which a tumor resembles the normal tissue from which it arose
fat benign tumor
lipoma
Malignant tumor
Poor differentiation, erratic growth, local invasion, metastasis, decrease apoptosis. Upregulation of telomerase prevents chromosome shortening and cell death.
Peutz-Jeghers syndrome
GI tract polyposis, mucocutaneous pigmentation -estrogen secreting tumor: precocious puberty
Metaplasia
Replacement of one cell type with another. Usually due to exposure to an irritant, such as gastric acid or cigarette smoke. Reversible if the irritant is removed but may undergo malignant transformation with persistent insult (eg, Barrett esophagus-> esophageal adenocarcinoma)
IAPP
Islet amyloid polypeptide
Koilocytes
Seen in HPV. Dysplastic squamous cervical cells with nuclear enlargement and hyperchromasia
AA amyloid (secondary)
Seen with chronic inflammatory conditions such as RA, IBD, spondylarthropathy, familial Mediterranean fever, protracted infection. Fibrils composed with serum Amyloid A. Often multisystemic.
Sarcoma
Cancer of the supportive tissues (mesenchymal), such as bone, cartilage, and muscle.
Non-neoplastic malformations:
Hamartoma Choristoma
benign tumor
Well differentiated, well demarcated, low mitotic activity, no metastasis, no necrosis.
Anaplasia
Complete lack of differentiation of cells in a malignant neoplasm
Hallmarks of cancer
Eight fundamental changes in cell biology that lead to malignant transformation: Evasion of apoptosis; Growth signal self-sufficiency; Anti-growth Signal insensitivity; Sustained angiogenesis; Limitless replicative potential; Tissue invasion; Metastasis.
Tumor grade
Degree of cellular differentiation and mitotic activity on histology. Range from low grade (well differentiated) to high grade (poorly differentiated, undifferentiated, anaplastic)
Dysplasia
Disordered cell growth, most often referring to proliferation of precancerous cells. Non-neoplastic cell growth. Term used only with epithelial cells. Mild dysplasia is usually reversible, severe dysplasia usually progresses to carcinoma in situ.
Neoplastic progression: normal state, before anything goes wrong
Normal cells w/ basal --< apical differentiation.
carcinoma in situ
noninvasive cancer located in a small area of the epithelial layer. Not invaded the intact basement membrane. Increase nuclear: cytoplasmic ratio and clumped chromatin. Neoplastic cells encompass entire thickness.
Meckel's diverticulum
Gastric tissue in distal ileum
Well-differentiated tumors
(often less aggressive) closely resemble their tissue of origin.
TNM staging system
T = size of T umor / invasiveness N = N ode involvement M = M etastases Each TNM factor has independent prognostic value; N and M are often most important
Lipofuscin
A yellow-brown "wear and tear" pigment associated with normal aging. Formed by oxidation and polymerization of autophagocytosed organellar membranes. Autopsy of elderly person will reveal deposits in heart, colon, liver, kidney, eye, atc.
Striated muscle benign tumor
Rhabdomyoma
Age-related (senile) systemic amyloidosis
Due to deposition of normal ( wild-type) transthyretin (TTR) predominantly in cardiac ventricles. Slower progression of cardiac dysfunction relative to AL amyloidosis.
Section 5
(50 cards)
Cutaneous manifestation of paraneoplastic syndrome
Acanthosis nigricans; Sign of Leser-Trélat
Anti-NMDA receptor encephalitis mechanism
Psychiatric disturbance, memory deficits, seizures, dyskinesias, autonomic instability, language disfunction.
blood vessels malignant tumor
angiosarcoma
bone malignant tumor
osteosarcoma
Endocrine manifestation of paraneoplastic syndrome
Hypercalcemia; Cushing syndrome; Hyponatremia (SIADH)
SIADH
syndrome of inappropriate antidiuretic hormone Hyponatremia Small cell lung cancer
Melanocyte benign tumor
Nevus/mole
The most common cancer
Skin cancer Basal > squamous >> melanoma
Opsoclonus-myoclonus ataxia syndrome
"Dancing eyes, dancing feet" Neuroblastoma (children); Small cell lung cancer (adults)
Paraneoplastic encephalomyelitis
Atb against Hu atg in Neurons. Small cell lung cancer
Anti-NMDA receptor encephalitis seen with what condition?
Ovarian teratoma
Cancer mortality women
lung → breast → colorectal
Cancer mortality men
lung → prostate → colorectal
Paraneoplastic cerebellar dyndrome
Atb again atg in Purkinje cells. Small cell lung cancer (anti-Hu); Gynecologic and breast cancer (anti-Yo), Hodgkin lymphoma (anti-Tr).
Cancer incidence women
breast → lung → colorectal
opsoclonus-myoclonus syndrome
non-rhythmic conjugate eye movement and myoclonus associated with neuroblastoma
Smooth muscle malignant tumor
Leiomyosarcoma
dyskinesia
difficult or painful movement
Neuromuscular manifestation of paraneoplastic syndrome
Anti-NMDA receptor encephalitis; Opsoclonus-myoclonus ataxia syndrome; Paraneoplastic cerebellar degeneration; Paraneoplastic encephalomyelitis; Lambert-Eaton myasthenic Syndrome; Myasthenia gravis.
Pure red cell aplasia associated with
Anemia with low reticulocytes; thymoma, lymphocytic leukemias, parvovirus B19 ifxn.
Blood cells malignancy
Leukemia Lymphoma
Connective tissue malignant tumor
Fibrosarcoma
Sign of Leser-Trelat
Sudden appearance of multiple seborrheic keratoses that may be associated with internal malignancy GI adenocarcinoma and other visceral malignancies
Acanthosis nigricans associated
Gastric adenocarcinoma and other visceral malignancies (but more commonly associated with obesity and insulin resistance)
Lambert-Eaton
Ig against Ca channels -> decrease Ach -> muscle weakness that improves w/ repetition
Trousseau syndrome
migratory spf thrombophlebitis; Thymoma
myasthenia gravis
Antibodies against postsynaptic ACh receptors at NMJ Thymoma
BCR-ABL
Oncogene Tyrosine kinase CML, ALL
Hypercalcemia sign
PTHrP: Squamous cell carcinomas of lung, head, neck; Renal, bladder, breast, ovarian carcinomas. high 1,25-(OH)2 vitamin D3 (calcitriol): Lymphoma
Cancer mortality children
Leukemia > brain and CNS > neuroblastoma
Cancer incidence men
prostate → lung → colorectal
Good syndrome (hypogammaglobulinemia)
Thymoma
Oncogenes
a gene that causes normal cells to change into cancerous tumour cells. Need damage only one allele for disease expression
Cancer incidence children (0-14)
Leukemia > brain and CNS > neuroblastoma
Hematologic manifestation of paraneoplastic syndrome
Polycythemia; Pure red cell aplasia; Good syndrome; Trousseau syndrome; Nombacterial thrombotic (marantic) endocarditis.
Lambert-Eaton myasthenic syndrome
Antibodies against presynaptic (P/Q-type) calcium channels at NMJ Small cell lung cancer
fat malignant tumor
liposarcoma
ALK
Oncogene Receptor tyrosine kinase Lung adenocarcinoma
second leading cause of death in the US
cancer
first leading cause of death in U.S.
heart disease
autonomic instability
NMS, serotonin syndrome
Cushing's syndrome
High cortisol due to excess ACTH. Small cell lung cancer
Striated muscle malignant tumor
Rhabdomyosarcoma
Nonbacterial thrombotic (marantic) endocarditis
Deposition of sterile platelet thrombi on heart valves Adenocarcinomas, especially pancreatic
melanocyte malignant
Melanoma
Acanthosis nigricans
Hyperpigmented velvety plaques in axilla and neck
Polycythemia
High EPO Renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma, pheochromocytoma, leiomyoma.
paraneoplastic syndrome
tumor cells release substances that affect neurological function and may have hormonal effects
NMS
neuroleptic malignant syndrome
myoclonus
the sudden, involuntary jerking of a muscle or group of muscles
Section 6
(50 cards)
TSC1
Hamartin protein Tuberous sclerosis tumor suppressor genes
c-KIT
Cytokine receptor Gastrointestinal stromal tumor (GIST) Oncogene
HTLV-1
Adult T-cell leukemia/lymphoma
aromatic amines (benzidine, 2-naphthylamine)
transitional cell carcinoma Bladder
Vinyl chloride
angiosarcoma of liver
BRCA1/BRCA2
Breast and ovarian cancer, pancreatic cancer DNArepair protein tumor suppressor genes
carbon tetrachloride
centrilobular necrosis, fatty change (liver)
WT1
Tumor Suppressor Gene Associated Disease: Wilms Tumor (Chr. 11) Gene Product: not listed (TF that regulates urogenital development)
JAK2
Tyrosine kinase Chronic myeloproliferative disorders Oncogene
Liver fluke (Clonorchis sinensis)
Cholangiocarcinoma
c-MYC
Transcription factor Burkitt lymphoma Oncogene
TSC2
Tuberin protein Tuberous sclerosis tumor suppressor genes
NF1
tumor supressor: inc risk, need 2 RAS GTPas activating protein (neurofibromin) NF type 1
BCL-2
Oncogene Antiapoptotic molecule (inhibits apoptosis) Follicular and undifferentiated lymphomas
Serum tumor marker
Shouldn't be used as the 1• tool for cancer Dx or screening. Used to monitor tumor reccurence and response to therapy. Definitive Dx via biopsy
Psammoma bodies means
Laminated, concentric spherules with dystrophic calcification.
PTEN
Tumor Suppressor (2 hit) Breast cancer, prostate cancer, endometrial cancer Tyrosine phosphatase of PIP3 (eg, protein kinase B [AKT] activation)
HER2/neu (c-erbB2)
Gene product: Tyrosine kinase receptor Associated tumor(s): Breast, ovarian, & gastric carcinomas Oncogene
KRAS
GTPase Colon cancer, lung cancer, pancreatic cancer Oncogene
tumor suppressor genes
code for proteins that inhibit the cell cycle and promote apoptosis Both alleles must be lost for expression disease
Nitrosamines (smoked foods)
Organ: Stomach Impact: Gastric cancer
EBV associated malignancies? (x3)
Nasopharyngeal carcinoma, Burkitt lymphoma, CNS lymphoma (in ID); Hodgkin lymphoma.
MEN1
AD Tumor Suppressor (2 hit) Menin Parathyroid, pancreatic endocrine, and pituitary tumors
MYCN
Transcription factor Neuroblastoma Oncogene
MYCL1
Transcription factor Lung tumor Oncogene
Aflatoxins (Aspergillus)
Hepatocellular carcinoma
Oncogenic microbes
EBV; HBC,HCV; HHV-8; HPV; H pylori; HTLV-1; Liver fluke (Clonorchis sinensis); Schistosoma haematobium
Alkylating agents
Leukemia/lymphoma this can be a side effect of chemotherapy
PSaMMoma bodies
Papillary carcinoma of thyroid; Serous papillary cystadenocarcinoma of ovary. Meningioma Malignant Mesothelioma
cigarette smoke
Transitional cell carcinoma (Bladder); Cervical carcinoma; Squamous cell carcinoma/ adenocarcinoma (esophagus); Renal cell carcinoma; Squamous cell carcinoma (larynx); Squamous cell carcinoma and small cell carcinoma (lungs); Pancreatic adenocarcinoma.
HBV, HCV
MC risk factors for hepatocellular carcinoma
DCC
Tumor Suppressor (2 hit) Colon cancer DCC—Deleted in Colon Cancer
Li-Fraumeni syndrome SBLA
Sarcoma Breast Leukemia Adrenal gland
NF2
AD Tumor Suppressor (2 hit) NeuroFibromatosis type 2 Merlin (schwannomin) protein
HPV
cervical, penis, and anorectal squamous cancers (16,18) Head and neck cancer
Rb
tumor suppressor gene Inhibits E2F; blocks G1->S phase RetinoBlastoma, osteosarcoma
Asbestos
Bronchogenic carcinoma > mesothelioma
RET
Tyrosine kinase receptor; MEN2A and 2B, medullary thyroid cancer, and Hirschsprung's Oncogene
Arsenic
Angiosarcoma (Liver) lung cancer squamous cell carcinoma (skin)
CDKN2A - cyclin-dependent kinase inhibitor 2A
encodes both P16 and P14 (blocks G1 ->S phase -> plays significant role in development of melanoma as well as SCC, pancreatic cancer tumor suppressor genes
VHL
inhibits hypoxia inducible factor 1a Von Hippel-Lindau disease tumor suppressor genes
APC
Colorectal cancer (associated with FAP) Negative regulator of b-catenin/WNT pathway tumor suppressor genes
Ethanol
Squamous cell carcinoma (esophagus); Hepatocellular carcinoma
ionizing radiation
papillary thyroid carcinoma
BRAF
Produces serine/threonine kinase associated with melanoma, non-Hodgkin lymphoma, papillary thyroid carcinoma Oncogene
Schistosoma haematobium
Bladder cancer (squamous cell)
DPC4/SMAD4
Tumor Suppressor (2 hit) Pancreatic cancer DPC—Deleted in Pancreatic Cancer
TP53
tumor suppressor gene P53, activates p21, blocks G1->S phase Most human cancers, Li-Fraumeni syndrome (multiple malignancies at early age)
HHV-8
Kaposi sarcoma
Radon
Lung cancer (2nd leading cause after cigarette smoke)
Section 7
(22 cards)