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Pathology Flashcards

1
Q 
Eosinophilic cytoplasm
Basophilic nucleus
Pyknosis (nuclear shrinkage)
Karyorrhexis (DNA fragmentation)
No inflammation
A

APOPTOSIS

DNA laddering (180 bp multiples) sensitive sign

occurs when regulating factors like interleukins are withdrawn from proliferating cells

endonucleases cleave DNA at internucleosomal linker regions which are at 180 base pair intervals

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2
Q

Intrinsic (mitochondrial) pathway of apoptosis

Involved in embryogenesis and response to injuring stimuli (e.g. radiation, toxins, hypoxia)

A

p53 activation activates BAX/BAK
BAX/BAK induce cytochrome c release
APAF-1 binds cytochrome c
Induces caspase 9 activation and caspase cascade
Nuclear fragmentation and cytoskeletal dispersion
Formation of cytoplasmic blebs (apoptotic bodies)
Apoptotic bodies phagocytosed by macrophages

Inhibited by Bcl-2 binding of APAF-1

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3
Q

Overexpression of bcl-2 leading to over-inhibition of APAF-1 and thus tumorigenesis.

A

Follicular lymphoma - t[14;18]

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4
Q

Extrinsic (death receptor) pathway

A

FasL (cytotoxic T-cells) binding to Fas (TNF family)
Fas trimerized and binds FADD
Activates initiator caspases (8, 9)
Activates executioner caspases

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5
Q

Defective Fas-FasL interactions.

A

AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME

Interaction necessary in thymic medullary negative selection - results in autoimmune disease

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6
Q

Cell outlines preserved

Cytoplasmic hypereosinophilia

A

COAGULATIVE NECROSIS

Seen in ischemia and infarcts (except brain) - Proteins denature then undergo enzymatic degradation

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7
Q

Early cellular debris and macrophages
Later cystic spaces and cavitation (e.g. brain)
Neutrophils and cell debris seen with bacterial infection

A

LIQUEFACTIVE NECROSIS

Seen in bacterial abscesses and brain infarcts (high fat content)

Neutrophils release lysosomal enzymes that digest tissue - Enzymatic degradation precedes protein denaturing

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8
Q

Fragmented cell and debris surrounded by lymphocytes and macrophages.

A

CASEOUS NECROSIS

Seen in TB, systemic fungi, and Nocardia - Macrophages wall off the infecting organism creating granular debris

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9
Q

Outlines of dead fat cells without peripheral nuclei
Saponification of fat (combined with Ca)
Appears dark blue on H/E stain

A

FAT NECROSIS

Seen in acute pancreatitis or traumatic breast injury - Damaged cells release lipase which breaks down triglycerides in fat cells

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10
Q

Vessel walls are thick and pink on H/E stain

A

FIBRINOID NECROSIS

Seen in vasculitis and malignant HTN - Immune complexes combine with fibrin to cause vessel wall damage

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11
Q

Histology of wet and dry gangrene after chronic ischemia.

A

Dry (ischemia) appears like coagulative necrosis

Wet (superinfection) appears like liquefactive superimposed on coagulative

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12
Q 
Cellular/mitochondrial swelling
Nuclear chromatin clumping
Membrane blebbing
Decreased glycogen
Fatty change
Ribosomal/polysomal detachment
A

REVERSIBLE CELLULAR INJURY

Reversible with O2 - e.g. stable angina

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13
Q

Plasma membrane damage
Nuclear pyknosis (condensation), karyorrhexis (fragmentation), or karyolysis (fading)
Mitochondrial permeability and vacuolization
Mitochondrial phospholipid-containing amorphous densities
Lysosomal rupture

A

Irreversible cellular injury

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14
Q

Regions of the brain most susceptible to hypoxia/ischemia.

A

ACA/MCA/PCA boundaries

Specifically Purkinje cells of cerebellum and pyramidal cells of hippocampus/neocortex

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15
Q

Region of the heart most susceptible to ischemia.

A

Subendocardium

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16
Q

Region of the kidney most susceptible to ischemia.

A

Straight segment of proximal tubule (medulla)

Thick ascending limb (medulla)

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17
Q

Region of the liver most susceptible to ischemia.

A

Zone III - around central vein

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18
Q

Region of the colon most susceptible to ischemia.

A

Splenic flexure

Rectum

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19
Q

Occurs in…
Venous occlusion
Reperfusion
Tissues with multiple blood supplies (liver, lung, intestine, testes)

A

Red (hemorrhagic) infarct

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20
Q

Occurs in solid organs with single end-arterial supply (heart, kidney, spleen)

A

Pale (anemic) infarct

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21
Q

Mediators of acute inflammation - outcome includes complete resolution, abscess formation, or chronic inflammation.

A

Neutrophils
Eosinophils
Antibodies

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22
Q

Mediators of chronic inflammation or persistent destruction and repair associated with blood vessel proliferation and fibrosis - outcome includes scarring and amyloidosis.

A

Monocytes/macrophages (granulomas)
Lymphocytes
Plasma cells
Fibroblasts

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23
Q

Round cellular swelling
Displacement of nucleus to periphery
Dispersion of Nissl (RER) substance throughout cytoplasm

A

CHROMATOLYSIS

Reaction of neuronal cell body to axonal damage - reflects increased protein synthesis

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24
Q

Degeneration of axon distal to site of injury - Macrophages remove debris and myelin.

A

Wallerian degeneration

Cell body undergoes cellular edema - Axonal reaction

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25
Q

Large areas of basophilic staining on H/E
Small bony tissue
Thick fibrotic walls
Patient is normocalcemic

A

DYSTROPHIC CALCIFICATION

Localized Ca deposition in abnormal tissues secondary to injury or necrosis

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26
Q

Ca deposition in interstitial tissues of kidney, lung, and gastric mucosa as these tissues are more basic

Seen in...
Primary hyperparathyroidism
Sarcoidosis
Hypervitaminosis D
CKD with secondary hyperparathyroidism
Long-term dialysis
Calciphylaxis
Warfarin
A

METASTATIC CALCIFICATION

Widespread Ca deposition in normal tissue secondary to hypercalcemia or high calcium-phosphate product levels

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27
Q

Step 1 of leukocyte extravasation

A

MARGINATION AND ROLLING

Margination - Hemoconcentration increases contact with endothelial lining at postcapillary venules

Rolling - Endothelial E/P selectins binds leukocyte Sialyl-Lewis

Note - In lymph nodes GlyCAM-1/CD34 binds leukocyte L-selectins

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28
Q

Leukocyte Adhesion Deficiency type 2

Note - More mild (no delayed umbilical cord separation)

A

Defect in leukocyte adhesion due to decreased Sialyl-Lewis on leukocytes

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29
Q

Step 2 of leukocyte extravasation.

A

TIGHT-BINDING

Endothelial ICAM-1 binds leukocyte CD18 b-2 Integrins (LFA-1, MAC-1)

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30
Q

Leukocyte Adhesion Deficiency type 1

A

Defect in leukocyte tight binding due to defective CD18 integrin subunit

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31
Q

Step 3 of leukocyte extravasation.

A

DIAPEDESIS/TRANSMIGRATION

Leukocyte interaction with PECAM-1 at intercellular junctions

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32
Q

Retinopathy of prematurity

Bronchopulmonary dysplasia

A

Oxygen toxicity

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33
Q 
Very elevated collagen synthesis
Disorganized collagen organization
Possible progressive growth
Frequent recurrence
Increased incidence in darker skin
Extends beyond borders of original wound (claw-like projections)
A

KELOID

Normal variant is hypertrophic scar formation

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34
Q

Secreted by activated platelets and macrophages
Vascular remodeling and smooth muscle cell migration
Fibroblast growth for collagen synthesis

A

PDGF

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35
Q

Mediators (2) stimulating angiogenesis.

A

FGF

VEGF

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36
Q

Requires tyrosine kinases (EGFR/ErbB1)

Cell growth

A

EGF

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37
Q

Mediator for tissue remodeling.

A

Metalloproteinases

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38
Q

Angiogenesis
Fibrosis
Cell cycle arrest

A

TGF-b

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39
Q

Mechanism and effector cells of inflammatory wound healing (< 3 d).

A

Clot formation
Increased vascular permeability
Debris clearing

Platelets
Neutrophils
Macrophages

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40
Q

Mechanism and effector cells of proliferative wound healing (3 d - weeks).

A 
Deposition of granulation tissue and TIII collagen
Angiogenesis
Epithelial proliferation
Clot dissolution
Wound contraction
Fibroblasts
Myofibroblasts
Endothelial cells
Keratinocytes
Macrophages
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41
Q

Mechanism and effector cells of remodeling wound healing (1 week - 6 months)

A

TIII collagen replaced by TI collagen
Increased tensile strength of tissue (70-80% original)

Fibroblasts

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42
Q

Mechanism of granulomatous disease.

A

Th1 cells secrete IFN-y
Macrophages activated
Macrophages release TNF-a
Induces and maintains granuloma

Caseating if infectious
Noncaseating if autoinflammatory

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43
Q

Reason to test for latent TB before starting anti-TNF therapy.

A

Blocking TNF-a causes breakdown of sequestering granulomas, and promotes disseminated disease.

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44
Q

Mechanism of increased ESR in inflammation.

A

Fibrinogen coats RBCs and causes increased aggregation.

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45
Q 
ESR in...
Anemia
Cancer
ESRD
Nephrotic syndrome
Pregnancy
A

Elevated

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46
Q 
ESR in...
SCD
Polycythemia
Microcytosis
HF
Hypofibrinogenemia
A

Decreased

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47
Q

Increased congo-red staining
Increased apple-green birefringence on polarized light
Increased eosinophilic staining within glomerular mesangium and tubular basement membranes on H/E

A

AMYLOIDOSIS

Abnormal aggregation of proteins/fragments form b-pleated sheets - result in damage and apoptosis

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48
Q 
Amyloidosis resulting in...
Nephrotic syndrome
Restrictive cardiomyopathy
Easy bruising
Hepatosplenomegaly
Neuropathy
A

AL (PRIMARY) AMYLOIDOSIS

Deposition of Ig Light chains secondary to plasma cell disorder or MM

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49
Q 
Multisystem amyloidosis seen in...
Rheumatoid arthritis
IBD
Spondyloarthropathy
Familial mediterranean fever
Protracted infection
A

AA (SECONDARY) AMYLOIDOSIS

Deposition of serum Amyloid A fibrils

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50
Q

Amyloidosis seen in ESRD or long-term dialysis - may present as carpal tunnel.

A

DIALYSIS RELATED AMYLOIDOSIS

Deposition of B2-microglobulin fibrils

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51
Q

Inherited polyneuropathy or cardiomyopathy due to transthyretin gene mutation.

A

Heritable/familial amyloidosis

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52
Q

Slow progression of cardiac dysfunction in older patients due to deposition of wild-type transthyretin in ventricles.

A

Age-related (senile) amyloidosis

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53
Q

Deposition of atrial natriuretic peptide - common in normal aging.

A

Isolated atrial amyloidosis

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54
Q

Deposition of amylin in pancreatic islets of a patient with DMT2.

A

Islet amyloid polypeptide (IAPP)

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55
Q

Deposition of B-amyloid cleaved from amyloid precursor protein (APP)

A

Alzheimer disease

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56
Q

Yellow-brown pigment formed by oxidation and polymerization of autophagocytosed organelle membranes - seen in autopsies of older patients.

A

Lipofuscin

57
Q

Abnormal (non-neoplastic) proliferation of cells with loss of size, shape, and orientation - may progress to CIS.

A

Dysplasia

58
Q 
Progression from dysplasia to neoplastic growth
Increased N/C ratio
Clumped chromatin
Encompass entire thickness
Intact basement membrane
A

Carcinoma in situ/preinvasive

59
Q

Loss of cell-cell contacts (inactivation of E-cadherin), and invasion of basement membrane (metalloproteinases including collagenase/hydrolase).

A

Invasive carcinoma

60
Q

Disorganized overgrowth of tissue in their native location (e.g. Peutz-Jeghers).

A

Hamartoma

61
Q

Incidence of skin cancers (greatest to least).

A

Basal
Squamous
Melanoma

62
Q

Top 3 most common cancers (greatest to least).

A

Prostate/Breast
Lung
Colorectal

63
Q

Top 3 cancers with the highest mortality (greatest to least).

A

Lung
Prostate/Breast
Colorectal

64
Q

Cause of paraneoplastic Acanthosis Nigricans.

A

Gastric adenocarcinoma

65
Q

Cause of paraneoplastic sign of Leser-Trelat - sudden onset multiple seborrheic keratoses.

A

GI adenocarcinomas

66
Q

Causes of paraneoplastic hypercalcemia - elevated PTHrP

A 
Squamous cell carcinoma
Renal cell carcinoma
Bladder
Breast
Ovarian
Lymphoma (calcitriol)
67
Q

Cause of paraneoplastic…
Cushing’s (ACTH)
SIADH (ADH)
Cerebellar degeneration (Hu, Yo, Tr antigens in Purkinje)
Encephalitis (Hu antigens in neurons)
Lambert-Eaton (presynaptic P/Q-type NMJ Ca channels)

A

SCLC

68
Q

Causes (5) of paraneoplastic polycythemia - elevated EPO.

A 
Renal cell carcinoma
HCC
Pheochromocytoma
Hemangioblastoma
Leiomyoma
69
Q

Cause of paraneoplastic…
Pure red cell aplasia/anemia with low retics
Good syndrome (hypogammaglobulinemia)
Myasthenia gravis

A

Thymoma

70
Q 
Cause of paraneoplastic...
Trousseau syndrome (migratory superficial thrombophlebitis)
Nonbacterial thrombotic (marantic) endocarditis (deposition of sterile platelet thrombi)
A

Pancreatic adenocarcinoma

71
Q 
Cause of paraneoplastic anti-NMDA receptor encephalitis presenting as...
Psychiatric disturbance
Memory deficits
Seizures
Dyskinesias
Autonomic instability
Language dysfunction
A

Ovarian teratoma

72
Q

Cause of paraneoplastic Opsoclonus-myoclonus ataxia (dancing eyes, dancing feet).

A

Neuroblastoma (children)

SCLC (adults)

73
Q

Cause of paraneoplastic cerebellar degeneration (anti Hu, Yo, Tr antigens in Purkinje cells)

A

SCLC
Hodgkin’s lymphoma
Gynecologic cancers
Breast cancers

74
Q

ALK = receptor tyrosine kinase oncogene

A

Lung adenocarcinoma

75
Q

BCR-ABL = tyrosine kinase oncogene

A

CML

ALL

76
Q

BCL-2 = antiapoptotic oncogene

A

Follicular/diffuse large B cell lymphoma

77
Q

BRAF = serine/threonine kinase oncogene

A

Melanoma

Non-Hodgkin’s lymphoma

78
Q

c-KIT = cytokine receptor oncogene

A

GIST

79
Q

c-MYC = transcription factor oncogene

A

Burkitt lymphoma

Diffuse large B cell lymphoma

80
Q

HER2/neu (c-cerbB2) = tyrosine kinase oncogene

A

Breast carcinoma

Gastric carcinoma

81
Q

JAK2 = tyrosine kinase oncogene

A

Chronic myeloproliferative disorders

82
Q

KRAS = GTPase (RAS/MAP) oncogene

A

Colon cancer
Lung cancer
Pancreatic cancer

83
Q

MYCL1 = transcription factor oncogene

A

Lung tumor

84
Q

MYCN = transcription factor oncogene

A

Neuroblastoma

85
Q

RET = tyrosine kinase oncogene

A

MEN2A/B

Medullary thyroid cancer

86
Q

APC = tumor suppressor gene

A

FAP

87
Q

BRCA1/2 = DNA repair tumor suppressor genes

A

Breast cancer

Ovarian cancer

88
Q

CDKN2A = p16 (blocks G1 to S) tumor suppressor gene

A

Melanoma

Pancreatic cancer

89
Q

DCC = tumor suppressor gene

A

Colon cancer (“Deleted in Colon Cancer”)

90
Q

DPC4/SMAD4 = tumor suppressor gene

A

Pancreatic cancer (“Deleted in Pancreatic Cancer”)

91
Q

MEN1 = Menin tumor suppressor gene

A

MEN1

92
Q

NF1 = Ras inhibiting protein tumor suppressor gene (Neurofibromin)

A

NF1 - Chromosome 17 (“17 letters in Neurofibromatosis”)

93
Q

NF2 = Merlin (schwannomin) protein tumor suppressor gene

A

NF2

94
Q

PTEN = tumor suppressor gene

A

Breast cancer
Prostate cancer
Endometrial cancer

95
Q

Rb = tumor suppressor gene

When hypophosphorylated (active) binds E2F to block G1 to S - Phosphorylated by CDK

A

Retinoblastoma

Osteosarcoma

96
Q

TP53 = tumor suppressor gene activating p21

Note - p21 blocks G1 to S

A

Most human cancers
Li-Fraumeni syndrome (Sarcoma, Breast, Blood, Adrenal)
Aflatoxins

97
Q

TSC1/2 = Hamartin/Tuberin tumor suppressor gene

A

Tuberous sclerosis

98
Q

VHL = tumor suppressor gene inhibiting hypoxia inducible factor 1a

A

Von Hippel-Lindau

99
Q

WT1/2 = tumor suppressor genes

A

Wilms Tumor (nephroblastoma)

100
Q 
Virus associated with...
Burkitt's lymphoma
Hodgkin's lymphoma
Nasopharyngeal carcinoma
Primary CNS lymphoma
A

EBV

101
Q

HPV subtypes associated with cervical, penile, anal, and head/neck cancer.

A

HPV-16/18

102
Q

Bacteria associated with…
Gastric adenocarcinoma
MALT lymphoma

A

H. pylori

103
Q

Retrovirus associated with adult T-cell leukemia/lymphoma.

A

HTLV-1

104
Q

Trematode associated with cholangiocarcinoma.

A

Clonorchis sinensis (liver fluke)

Treat with Praziquantel

105
Q

Trematode associated with squamous cell bladder cancer.

A

Schistosoma haematobium (blood fluke)

Treat with Praziquantel

106
Q

Cancer associated with Aflatoxins from Aspergillus.

A

HCC

107
Q

Cancer associated with alkylating agents (e.g. Cyclophosphamide).

A

Leukemia/Lymphoma

108
Q

Cancer associated with aromatic amines (e.g. Benzidine, Naphthylamine).

A

Transitional cell carcinoma of the bladder

109
Q

Carcinogen associated with..
Angiosarcoma of the liver
Lung cancer
Squamous cell carcinoma

A

Arsenic

110
Q

Cancers associated with asbestos exposure.

A

Bronchogenic carcinoma > Mesothelioma

111
Q

Histological change associated with carbon tetrachloride.

A

Centrilobular necrosis and fatty change of the liver.

112
Q 
Carcinogen associated with...
SCC/adenocarcinoma of the esophagus
SCC of pharynx
Squamous cell lung cancer/SCLC
Pancreatic adenocarcinoma
Renal cell carcinoma
Transitional cell carcinoma of the bladder
Cervical carcinoma
A

Cigarette smoke

113
Q

Carcinogen associated with…
SCC of esophagus
HCC

A

Ethanol

114
Q

Carcinogen associated with ionizing radiation.

A

Papillary thyroid cancer

115
Q

Cancer associated with Nitrosamines (smoked foods).

A

Gastric cancer

116
Q

Cancer associated with Radon exposure.

A

Lung cancer (2nd leading cause)

117
Q

Cancer associated with Vinyl chloride.

A

Angiosarcoma of the liver

118
Q

Cancers associated with Psammoma bodies - laminated, concentric spherules of dystrophic calcification.

(“PSaMMoma”)

A

Papillary carcinoma of thyroid
Serous papillary cystadenocarcinoma of ovary
Meningioma
Mesothelioma

119
Q 
Serum tumor marker for...
Metastases to bone
Metastases to liver
Paget's disease of bone
Seminoma
A

Alkaline Phosphatase

120
Q 
Serum tumor marker for...
HCC
Hepatoblastoma
Yolk sac (endodermal sinus) tumor
Mixed germ cell tumor
Neural tube defects
Abdominal wall defects
A

a-Fetoprotein

121
Q 
Serum tumor marker for...
Hydatidiform moles
Choriocarcinoma (gestational trophoblastic disease)
Testicular cancer
Mixed germ cell tumor
A

b-hCG

Produced by syncytiotrophoblasts of the placenta

122
Q

CA 15-3/CA 27-29 are serum tumor markers for…

A

Breast cancer

123
Q

CA 19-9 is serum tumor marker for…

A

Pancreatic adenocarcinoma

124
Q

CA 125 is serum tumor marker for…

A

Ovarian cancer

125
Q

Calcitonin is serum tumor marker for…

A

Medullary thyroid carcinoma

126
Q 
Serum tumor marker for...
Colorectal cancer
Pancreatic cancer
Gastric cancer
Breast cancer
Medullary thyroid carcinoma
A

CEA (carcinoembryonic antigen)

127
Q

May elevate PSA in absence of prostate cancer.

A

BPH

Prostatitis

128
Q

Classically seen in adrenal cell carcinoma and used to pump out toxins (e.g. chemotherapy) from cancer cells.

A

P-glycoprotein

129
Q

Mediators of cachexia.

A

TNF
IFN-y
IL-1
IL-6

130
Q

Carcinomas (4) which spread hematogenously like sarcomas, rather than via lymphatics.

A

HCC
Choriocarcinoma
Renal cell carcinoma
Follicular thyroid cancer

131
Q

Tumors most commonly metastasizing to the brain (greatest to least).

(“Lots of Bad Stuff Kills Glia”)

A 
Lung
Breast
Skin (Melanoma)
Kidney (RCC)
GI
132
Q

Tumors most commonly metastasizing to the liver (greatest to least).

A

Colon
Stomach
Pancreas

133
Q

Tumors most commonly metastasizing to the bone (greatest to least).

(“Pretty Boys Like To Kiss”)

A

Prostate (blastic) / Breast (mixed)

Lung (mixed) / Thyroid (lytic) / Kidney (lytic)

134
Q

Tumors most commonly metastasizing to the lungs (greatest to least).

(“Bats Can Phly Blind”)

A

Breast
Colon
Prostate
Bladder

135
Q

Multiple nuclei located peripherally in the shape of a horse-shoe

A

LANGERHANS GIANT CELLS

Form in granulomas in response to CD4+ Th1 activation of macrophages

136
Q

Mechanism of T-cell evasion by tumor cells

A

PD-L1 binds PD-1 on T-cells
B7 binds CTLA-4 as co-receptor
Inhibition of CD8 T cells

137
Q

enzyme responsible for activation of inactive procarcinogens

A

cytochrome p450 oxidase system

138
Q

anaplastic tumors have what type of cell

A

giant cells

Step 1 (17 decks)

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