PATHOLOGY QUICK REVIEW

DR. VILLAROYA
CELLULLAR ADAPTATIONS
• Reversible changes that can be
physiologic or pathologic

• Persistent cellular stress can lead

to cell injury
Cellular Adaptations
Adaptation

Hypertrophy Increase in size of the cells due to increased

structural proteins and organelles
Hyperplasia Increase in number of cells, can be pathologic or
physiologic
Atrophy Reduction in the size of an organ or tissue due to
decrease in cell size and number
Metaplasia Reversible change in which one differentiated cell
type is replaced by another cell type
CELL INJURY
REVERSIBLE IRREVERSIBLE

Cellular Swelling and Fatty Plasma membrane damage

Change
Ribosomal Detachments Pyknosis

Plasma membrane Blebbing Karyolysis

Chromatin Clumping Karyorrhexis

APOPTOSIS
NECROSIS
Type Histology

Coagulative Preserved cellular Organs with end-arterial

architecture supply
Liquefactive Amorphous cellular debris PUS , Brain Infract

Caseous Necrotic Debris with Tuberculosis Infection

granuloma
Fat Fat cells with absence of Pancreatitis
nucleic, saponification

Fibrinoid Eosinophilic Vessel Walls Vasculitis

Gangrenous Coagulative and Liquifactive Limbs

type
Calcification
DYSTROPHIC METASTATIC

In diseased tissues In normal tissues

localized Systemic

normal serum levels of calcium Arises in the setting of

and in the absence of hypercalcemia
derangements in calcium
metabolism
Exudate vs Transudate
Acute Inflammation

• Transient and early response to

injury or infection

• characterized by exudation of fluid

and plasma protein and a
predominantly neutrophilic
leukocyte accumulation
Leukocyte Recruitment
Margination and Rolling:
Selectins

Adhesion: ICAM and

VCAM

Transmigration/Diapedesis
: PECAM

Migration: Chemotactic
Factors
Morphologic Patterns of Acute Inflammation
• Serous inflammation: Outpouring of thin fluid (serous effusion, blisters)

• Fibrinous inflammation: Body cavities; leakage of fibrin; may lead to scar

tissue (adhesions)

• Suppurative (purulent) inflammation: Pus or purulent exudate

(neutrophils, debris, edema fluid); abscess: localized collections of pus

• Ulcers: Local defect of the surface of an organ or tissue produced by the

sloughing (shedding) of inflammatory necrotic tissue
Chronic Inflammation

• Inflammation typified by influx of

lymphocytes and macrophages

• associated with vascular

proliferation and deposition of
connective tissue
Macrophage Activation
Wound Healing - Mediators

FGF Angiogenesis
TGF-β Angiogenesis , Fibrosis
VEGF Angiogenesis
PDGF Vascular remodeling smooth
muscle cell migration and collagen
synthesis
Metalloproteinases Tissue Remodeling
Scar Formation
Hypertrophic Keloid
Type I Collagen Type I and III collagen
Parallel collagen organization Disorganized collagen
Limited to wound border Extends beyond wound border
Associated with excess TGF-β
Neoplasia

Dysplasia Loss of uniformity in cell size and

shapes, loss of orientations,
nuclear changes
Carcinoma in Situ Limited to the basement
membrane
Invasive Carcinoma Beyond the basement membrane
Metastasis Spread to distant sites via
lymphatics or blood
Tumor Nomenclature
BENIGN MALIGNANT
Adenoma Adenocarcinoma
Papilloma Papillary Carcinoma
Hemangioma Angiosarcoma
Leiomyoma Leiomyosarcoma
Rhabdomyoma Rhabdomyosarcoma
Fibroma Fibrosarcoma
Osteoma Osteosarcoma
Lipoma Liposarcoma
Nomenclature
• Teratoma - contains recognizable mature or immature cells
or tissues belonging to more than one germ cell layer

• Hamartomas - disorganized but benign masses composed of

cells indigenous to the involved site

• Choristoma -term applied to a heterotopic rest of cells

• Differentiation - extent to which neoplastic
parenchymal cells resemble the
corresponding normal parenchymal cells,
both morphologically and functionally

• Anaplasia – lack of differentiation

• Grade – degree of cellular differantation

• Stage – degree of localization/spread

Epidemiology
Environmental Factors
• Infectious Agents • Obesity

• Smoking • Reproductive History

• Alcohol Consumption • Environmental Carcinogens

• Diet
Chronic Inflammation and Cancer
Metastases
Site Tumor
Brain Lungs ,Breast , Melanoma,
Colon, Kidney
Liver Colon, Stomach, Pancreas

Bone Prostate, Breast, Kidney,

Thyroid
Oncogenes
GENE Neoplasm
ALK Lung Adenocarcinoma
BCR-ABL CML, ALL
BCL-2 Follicular and DLBCL
BRAF Melanoma, NHL, Papillary Thyroid Carcinoma,
Hairy Cell Leukemia
c-KIT GIST
c-MYC Burkitt Lymphoma
HER2 Breast and Gastric Cancer
n-MYC Neuroblastoma
RET MEN 2a and 2b, Papillary Thyroid Carcinoma
Tumor Suppressor Genes

APC Colon Cancer

BRCA/BRCA2 Breast, Ovarian and Pancreatic Cancer
MEN1 Multiple Endocrine Neoplasia I
NF1 Neurofibromatos is type 1
NF2 Neurofibromatosis type 2
PTEN Breast, prostate, and endometrial
cance
Rb Retinoblastoma, osteosarcoma (bone
cancer)
Oncogenic Microbes

Epstein-Barr Virus/HHV-4 Burkitt Lymphoma, Nasopharyngeal

Carcinoma, Hodgkin Lymphoma
HBV,HCV Hepatocellular carcinoma
HHV-8 Kaposi sarcoma
H pylori Gastric adenocarcinoma and MALT lymphoma
HTLV Adult T-cell leukemia/lymphoma
Clonorchis Sinensis Cholangiocarcinoma
Schistosoma haematobium Squamous cell bladder cancer
HPV Cervical and penile/anal carcinoma, head and
neck cancers
Steps Involved in Chemical Carcinogenesis

• Initiator:
• causes permanent DNA damage
(mutations)
• rapid and irreversible and has
“memory.”

• Promoter:
• induce tumors to arise from
initiated cells, but they are
nontumorigenic by themselves
Carcinogens
Toxin Associated Cancer
Aflatoxins Hepatocellular Carcinoma (HCCA)
Alkylating agents Leukemia/lymphoma
Aromatic amines Transitional cell carcinoma
Arsenic Angiosarcoma, Lung CA, SCCA
Asbestos Bronchogenic CA, Mesothelioma
Cigarette smoke SCCA, Transitional Cell CA, RCCA, Pancreatic CA
Ethanol SCCA, HCCA
Ionizing Radiation Papillary thyroid carcinoma,
leukemias
Nitrosamines Gastric CA
Radon Lung CA
Vinyl Chloride Angiosarcoma
Paraneoplastic Syndromes
Paraneoplastic Syndromes
Hemodynamics

• Edema – fluid collection within tissues

• Effusions – fluid collections within cavities

• Hyperemia: active process in which arteriolar dilation leads

to increased blood flow

• Congestion is a passive process resulting from reduced

outflow of blood from a tissue.
Edema and Effusions
Chronic pulmonary congestion

• caused by congestive heart

failure

• alveoli often contain

numerous hemosiderin-laden
macrophages called heart
failure cells.
Chronic Hepatic Congestion

• Nutmeg liver , centrilobular hemorrhage

Hemostasis
1. Arteriolar vasoconstriction

2. Primary hemostasis: the formation of the platelet plug

3. Secondary hemostasis: deposition of fibrin

4. Clot stabilization and resorption

Primary hemostasis: the formation of the platelet plug

• Disruption of the endothelium

exposes subendothelial von
Willebrand factor (vWF) and
collagen

• Platelet Activation

• Platelet Aggregation – platelet

plug
Secondary hemostasis: deposition of fibrin
• Tissue factor is also exposed at the
site of injury.

• culminates in thrombin generation

• Thrombin cleaves circulating

fibrinogen into insoluble fibrin
Platelet Function
Von Willebrand Factor (vWF):

 Plays a role in primary and secondary

hemostasis.

 vWF has roles in platelet adhesion,

aggregation and in coagulation.

 Secreted by platelets in α-granules

and by endothelial cells in Weibel –
Palade bodies.
Coagulation Cascade
Coagulation Cascade
• The prothrombin time (PT) assay assesses the function
of the proteins in the extrinsic pathway (factors VII, X,
V, II, and fibrinogen)

• The partial thromboplastin time (PTT) assay screens

the function of the proteins in the intrinsic pathway
(factors XII, XI, IX, VIII, X, V, II, and fibrinogen).
 Fibrinolytic system

Plasmin breaks down fibrin and interferes with its polymerization.

Bleeding Disorders

Bernard- Soulier Syndrome Defect in platelet adhesion, ↓ GpIB , large

platelets
Glanzmann Thrombasthenia Defect in platelet aggregation, ↓ GpIIb/IIIa
Immune Thrombocytopenia Anti-GpIIb/IIIa antibodies
Thrombotic Thrombocytopenic Purpura Deficiency of ADAMTS13
Von Willebrand disease ↓ vWF , defective adhesion and aggregation
DIC ↓ fibrinogen, ↑ fibrin split products
Hemophilia A Factor VIII deficiency, X-linked recessive
Hemophilia B Factor IX deficiency, X-linked recessive
Hemophilia C Factor XI deficiency, AR
Arterial Thrombi
• usually begin at sites of
turbulence or endothelial
injury

• Frequently occlusive , consists

of a friable meshwork of
platelets, fibrin, red cells and
degenerating leukocytes
Venous Thrombi
• characteristically occur at sites of
stasis

• almost invariably occlusive, with the

thrombus forming a long luminal cast.

• tend to contain more enmeshed red

cells (and relatively few platelets) and
are therefore known as red, or stasis,
thrombi
 Lines of Zahn

• pale platelet and fibrin deposits

alternating with darker red cell–rich
layers

• signify that a thrombus has formed

in flowing blood their presence can
therefore distinguish antemortem
clots from the bland nonlaminated
clots that occur postmortem
Pulmonary Embolism
• originate from deep venous
thromboses

• most common form of

thromboembolic disease

• originate from DVTs – 95%

Systemic Thromboembolism
• Arises from intracardiac mural thrombi (80%)

• arterial emboli can travel to a wide variety of sites

• most come to rest in the lower extremities (75%) or the brain

(10%)

• outcome is tissue infarction.

 Fat Embolism Syndrome
• When symptomatic, it is termed fat
embolism syndrome

• Pulmonary insufficiency, neurologic

symptoms, anemia and
thrombocytopenia

• Fatal in 5 to 15 % of cases
 Amniotic Fluid Embolism
• fifth most common cause of maternal
mortality worldwide

• results in permanent neurologic deficit in as

many as 85% of survivors.

• ominous complication of labor and the

immediate postpartum period
Infarct
• an area of ischemic necrosis caused by
occlusion of either the arterial supply or
the venous drainage

• arterial thrombosis or arterial embolism

underlies the vast majority of infarctions

• although venous thrombosis can cause

infarction, the more common outcome is
just congestion
 Red Infarct

1. Venous occlusions

2. Loose, spongy tissues

3. Tissues with dual circulations

4. Tissues previously congested

5. Reflow in a site of previous arterial occlusion

 White Infarct
• occur with arterial occlusions in solid organs
with end-arterial circulation

• wedge-shaped, with the occluded vessel at the

apex and the periphery of the organ forming the
base

• infarcts resulting from arterial occlusions in

organs without a dual blood supply typically
become progressively paler and more sharply
defined
 Immunity
Innate immunity
• ready to react to infections even before they occur
• specifically recognize and combat microbes

Adaptive Immunity
• mechanisms that are stimulated by microbes
• capable of recognizing microbial and nonmicrobial
substances
Innate vs Adaptive Immunity
INNATE IMMUNITY ADAPTIVE IMMUNITY

Germline Encoded VDJ recombination in lymphocyte

development
Neutrophils, macrophages, monocytes, T , B Cells and antibodies
dendritic cells, NK cells, complement,
enzymes, physical barriers
No memory response Has memory response

Non-specific Specific
COMPLEMENT SYSTEM
COMPLEMENT SYSTEM
Complement Disorders

C1-C4 recurrent pyogenic sinus and

respiratory tract infections. Increased
risk of SLE.

C5-C9 recurrent Neisseria bacteremia

C1 esterase inhibitor hereditary angioedema
deficiency
Major Histocompatibility Complex

CLASS I MHC CLASS II MHC

HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ, HLA-DR

Binds to CD8 and TCR Binds to CD4 and TCR

Present endogenous antigens (eg, viral Present exogenous antigens (eg,

or bacterial
cytosolic proteins) to CD8+cytotoxic T proteins) to CD4+ helper T cells
cells
Immediate (Type I) Hypersensitivity

Immediate Reaction
• Vasodilation, vascular leakage,
smooth muscle spasms and
glandular secretions

Late-phase reactions
• Infiltration of tissue with
inflammatory cells, tissue
destruction
Antibody-Mediated (Type II) Hypersensitivity

• Antibodies that react with

antigens present on cell
surfaces or in the extracellular
matrix cause disease by
destroying these cells
 Immune Complex–Mediated
(Type III) Hypersensitivity
• Antigen-antibody complexes produce tissue
damage mainly by eliciting inflammation at the
sites of deposition

• antigen combines with antibody in the

circulation, creating immune complexes that
typically deposit in vessel walls

• Immune complex–mediated diseases tend be

systemic
T Cell–Mediated (Type IV) Hypersensitivity
Systemic Lupus Erythematosus (SLE)
• autoimmune disease
involving multiple organs

• Presence of autoantibodies

• Type III Hypersensitivity

Antinuclear antibodies (ANAs)
1. antibodies to DNA

2. antibodies to histones

3. antibodies to nonhistone
proteins bound to RNA

4. antibodies to nucleolar
antigens
Antinuclear antibodies (ANAs)
• Antibodies to double-stranded DNA and the so-
called Smith (Sm) antigen are virtually
diagnostic of SLE
Mechanism of Tissue Injury - SLE
• DNA-anti-DNA complexes can
be detected in the glomeruli
and small blood vessels

• Autoantibodies specific for red

cells, white cells, and platelets
opsonize these cells and
promote their phagocytosis
and lysis
Lupus Nephritis
• Minimal mesangial lupus nephritis (class I)

• Mesangial proliferative lupus nephritis (class II)

• Focal lupus nephritis (class III) - < 50% glomeruli involved

• Diffuse lupus nephritis (class IV) - >50% glomeruli involved, most common and
severe form of lupus nephritis

• Membranous lupus nephritis (class V)

Morphologic Changes – Blood Vessels

Acute necrotizing vasculitis

Drug-Induced Lupus Erythematosus
• Lupus-like syndrome after exposure to
hydralazine, procainamide, isoniazid,
and D-penicillamine

• these drugs are associated with the

development of ANAs

• Antibodies specific for double-stranded

DNA are rare

• there is an extremely high frequency of

antibodies specific for histones
Sjögren Syndrome
• chronic disease characterized by
dry eyes and dry mouth

• antibodies directed against two

ribonucleoprotein antigens SS-A
(Ro) and SS-B (La)
• most commonly in women
between the ages of 50 and 60

• 5% of Sjögren patients develop

lymphoma
Systemic Sclerosis (Scleroderma)
• characterized by excessive fibrosis
throughout the body

• distinctive features are the striking

cutaneous changes, notably skin
thickening

• mild proteinuria occurs in as many as

30% of patients

• Anti-Scl 70 , anti-centromere antibody

Transplant Rejection

MHC presented by donor APC MHC presented by recipient APC

 Antibody-Mediated Reactions
Hyperacute Rejection
• occurs when preformed antidonor antibodies
are present

Acute antibody-mediated rejection

• antidonor antibodies produced after
transplantation

Chronic antibody-mediated rejection

• usually develops insidiously,primarily affects
vascular components
Defects in Leukocyte Function
Inherited defects in phagolysosome
function

Chediak-Higashi syndrome

• autosomal recessive

• defective fusion of phagosomes and

lysosomes
Defects in Leukocyte Function
Inherited defects in microbicidal activity

Chronic granulomatous disease

• defects in the genes encoding components of

phagocyte oxidase

• defects in bacterial killing and render patients

susceptible to recurrent bacterial infection
 Severe Combined Immunodeficiency

• defects in both humoral and cell-

mediated immune responses

• X-linked SCID: mutation in the

common γ-chain subunit of
cytokine receptors

• Autosomal recessive SCID:

adenosine deaminase (ADA)
deficiency
 X-Linked Agammaglobulinemia (Bruton
Agammaglobulinemia

• failure of B-cell precursors (pro-B cells and pre-B

cells) to develop into mature B cells

• mutations in a cytoplasmic tyrosine kinase, called

Bruton tyrosine kinase

• Recurrent Haemophilus influenzae, Streptococcus

pneumoniae, or Staphylococcus aureus infection
DiGeorge Syndrome (Thymic Hypoplasia)

• deficiency that results from failure of

development of the third and fourth pharyngeal
pouches

• variable loss of T cell–mediated immunity,

tetany, congenital heart defects

• variable loss of T cell–mediated immunity

Isolated IgA Deficiency

• extremely low levels of both serum and

secretory IgA

• recurrent sinopulmonary infections and

diarrhea

• Some develop anaphylactic reactions

when transfused with blood containing
IgA
Pathogenesis and Classification of Amyloidosis
Congenital Heart Disease
RIGHT TO LEFT SHUNTS LEFT TO RIGHT SHUNTS
Truncus Arteriosus VENTRICULAR SEPTAL DEFECT
Transposition of Great Vessels ATRIAL SEPTAL DEFECT
Tricuspid Atresia PATENT DUCTUS ARTERIOSUS
Tetralogy of Fallot Eisenmenger Syndrome
Total Anomalous Pulmonary Venous
Return
Ebstein Anomaly
Persistent Truncus Arteriosus

• Failure of aorticopulmonary septum

formation

• Truncus arteriosus fails to divide into

pulmonary trunk and aorta
Transposition of Great vessels
• Aorta arises from Right Ventricle

• Pulmonary Trunk arises from Left Ventricle

• Separation of systemic and pulmonary

circulation

• VSD,PDA, patent FO allows survival for few

months
Tricuspid Atresia

• Absence of tricuspid valve

• Hypoplastic Right Ventricle

Tetralogy of Fallot

• Ventricular Septal Defect

• Obstruction of the right ventricular outflow

tract (subpulmonary stenosis)

• Aorta that overrides the VSD

• Right Ventricular Hypertrophy

Total Anomalous Pulmonary Venous Return

• Pulmonary veins drain into the

right heart circulation

• Associated with ASD and PDA

Ebstein Anomaly
• Displacement of tricuspid valve leaflets
downward to RV

• “atrializing the ventricle”

• Can be caused by lithium exposure in utero

Ventricular Septal Defect

• Most common congenital cardiac

defect

• 90% occur in the region of the

membranous interventricular septum
(membranous VSD)
Atrial Septal Defect

• Secundum defects most

common

• Associated with Down

Syndrome

• May lead to paradoxical

emboli
Patent Ductus Arteriosus

• Machine-like murmur

• Patency is maintained by PGE synthesis

and low O2 tension

• Endomethacin closes PDA

Eisenmenger Syndrome
• Pulmonary Arterial Hypertension from
increased pulmonary blood flow due to
uncorrected left to right shunt

• RVH occurs to compensate, shunt

becomes right to left
Coarctation of the Aorta
• Juxtaductal : narrowing near insertion of
ductus arteriosus

• Brachial-femoral delay: hypertension in

upper extremities, delayed pulse in lower
extremities

• Associated with bicuspid aortic valve, other

heart defects and Turner Syndrome
Congenital Cardiac Defect Associations

Alcohol exposure in utero VSD, PDA, ASD, tetralogy ofFallot

Congenital Rubella PDA, pulmonary artery stenosis, septal defects

Down Syndrome AV septal defect (endocardial cushion defect),

VSD,ASD

Infant of Diabetic Mother Transposition of great vessels, VSD

Prenatal Lithium Exposure Ebstein Anomaly

Turner Syndrome Coarctation of the Aorta, Bicuspid Aortic Valve

Williams Syndrome Supravalvular Aortic Stenosis

22q11 syndromes Truncus Arteriosis, TOF

Marfan Syndrome MVP, thoracic aortic dissection and aneurysm

Arteriosclerosis
1. Arteriolosclerosis
• Hyaline and Hyperplastic Arteriolosclerosis

2. Monckeberg Sclerosis
• Calcification of the internal elastic lamina and
media (no obstruction)

3. Atherosclerosis
• Caused by cholesterol plaques
• Abdominal aorta most common
Hypertension
• Persistent Systolic BP >130mmHg and/or
diastolic BP >80mmHg

• 90% of cases are primary (idiopathic)

• Vascular changes include hyaline and

hyperplastic arteriolosclerosis
Myocardial Infarction
• “ Dominant” : artery that supplies the posterior
third of the septum

• Transmural: obstruction of epicardial vessel, ST

elevation on ECG

• Nontransmural: subendocardial infarcts, ST

depression on ECG

• Coagulative Type of Necrosis

Myocardial Infarction
• ECG is gold standard in the first 6 hours

• Troponin I rises after 4 hrs, peaks at 24 hrs

• CK-MB rises after 6-12 hours, peaks at 24

hrs, normal at 48 hours. USEFUL FOR
DIAGNOSING REINFARCTION
Myocardial Infarction Complications
Anterior Transmural Infarcts Posterior Transmural Infarcts

Free-wall rupture Conduction Blocks

Infarction Expansion Right Ventricular Involvement

Mural Thrombi

Ventricular Aneurysm
Cardiomyopathies
DILATED HYPERTROPHIC RESTRICTIVE

Most common (90%) Ejection Fraction of 50-80% Ejection fraction 45-90%

Ejection Fraction of < 40% Systolic Dysfunction Diastolic Dysfunction

Idiopathic of Familial, 20-50% 100% genetic causes, Amyloidosis, radiation

genetic causes mutations in sarcomeric induced fibrosis, sarcoidosis,
proteins Loffler endocarditis
Alcohol Abuse, Wet Beri-beri,
Coxsackie B, Cocaine, Chagas
disease, Doxurubicin
Diastolic Dysfunction
Bacterial Endocarditis
• Acute:
• S. aureus, large vegetations on previously
normal valves

• Subacute:
• Viridans streptococci, smaller vegetations on
diseased valves

• IV drug users: S. aureus

• Prosthetic valve: S. epidermidis
• Culture negative: HACEK organisms
Rheumatic Fever
• Occurs after infection with group A
streptococcal pharyngitis

• Aschoff bodies – foci of lymphocytes,

plasma cells and Anitschkow cells
(pathognomonic for RF)

• Affects Mitral , aortic and Tricuspid valves

Giant Cell (Temporal)Arteritis
• Large-vessel arteritis

• Elderly females

• Unilateral Headache

• May lead to irreversible blindness

Takayasu Arteritis
• Large-vessel arteritis

• Usually females less than 40 years old

• “pulseless disease” weak upper extremity

pulse

• Granulomatous thickening and narrowing of

aortic arch
Buerger Disease (Thromboangiitis obliterans)
• Medium-vessel vasculitis

• Heavy smokers, male

• Intermittent claudication

• Raynaud phenomenon is often present

Kawasaki Disease
• Medium-vessel vasculitis

• Mucocutaneous lymph node syndrome

• < 4 y.o.

• Conjunctival injection, rash, adenopathy,

strawberry tongue, Hand-foot changes,
fever

• May develop coronary artery aneurysm

Polyarteritis Nodosa
• Medium-vessel vasculitis

• Hepatitis B seropositivity in 30% of patients

• Renal vessels and visceral vessels

Behçet Disease

• Small-vessel vasculitis

• clinical triad of recurrent oral aphthous

ulcers, genital ulcers, and uveitis

• Associated with HLA-B51

Granulomatosis with Polyangiitis
• Wegener granulomatosis

• Small-vessel vasculitis

• Triad of: Necrotizing granulomas of

respiratory tract, necrotizing or
granulomatous vasculitis, focal necrotizing
glomerulonephritis

• PR3-ANCA/c-ANCA
Eosinophilic Granulomatosis w/ Polyangiitis
• Churg-Strauss

• Small-vessel vasculitis

• Asthma, allergic rhinitis, lung infiltrates,

hypereosinophilia, necrotizing
granulomatas

• MPO-ANCA/p-ANCA
Cushing Syndrome
• Exogenous steroids ( decreased ACTH) –
most common cause

• Primary Adrenal Adenoma, Hyperplasia or

Carcinoma

• ACTH-secreting pituitary adenoma (Cushing

disease)
Nelson Syndrome

• Enlargement of existing ACTH-secreting

pituitary adenoma after bilateral
adrenalectomy
Adrenal Insufficiency
PRIMARY SECONDARY TERTIARY
Deficiency of aldosterone and Seen in decreased pituitary Seen in patients with chronic
cortisol due to loss of gland ACTH exogenous steroid use
function
Hypotension, hyperkalemia, No skin hyperpigmentation,
metabolic acidosis, skin no hyperkalemia
hyperpigmentation
Acute – sec to massive
hemorrhage
Chronic – Addison disease (TB
most common in developing
countries)
Waterhous-Friderichsen
Syndrome – N. meningitidis
Hyperaldosteronism
PRIMARY HYPERADLOSTERONISM SECONDARY HYPERALDOSTERONISM

• Adrenal adenoma (Conn syndrome) • Renovascular hypertension

• Bilateral adrenal hyperplasia • Renin-producing tumors

Neuroblastoma
• Most common tumor of the adrenal
medulla in children

• Increased HVA and VMA

• Homer-right rosettes

• N-myc oncogene
Carcinoid Syndrome
• High levels of serotonin (5-HT)

• Common in small intestine and lungs

• Recurrent diarrhea, cutaneous flushing

• 1/3 metastasize
• 1/3 present with 2nd malignancy
• 1/3 are multiple
Pheochromocytoma
• Most common tumor of the adrenal
medulla in adults

• Rule of 10’s

• 10% malignant
• 10% bilateral
• 10% extra-adrenal
Pancreatic Endocrine Neoplasms
INSULINOMA GLUCAGONOMA SOMATOSTATINOMA VIPoma
Tumor of pancreatic Tumor of pancreatic Tumor of pancreatic caused by release of
beta cells alpha cells delta cells vasoactive intestinal
peptide (VIP)
Overproduction of Overproduction of Overproduction of
from the tumor
insulin glucagon somatostatin
Whipple Triad: low Dermatitis, Diabetes, diabetes mellitus, watery diarrhea,
blood glucose, anemia cholelithiasis, hypokalemia,
hypoglycemic steatorrhea, and achlorhydria, or
symptoms, hypochlorhydria WDHA syndrome
resolution of
symptoms after
normalization of
glucose levels
Hashimoto Thyroiditis
• Most common cause of hypothyroidism in iodine
sufficient areas

• Anti-thyroid peroxidase(antimicrosomal) and anti-

thyroglobulin antibodies

• HLA-DR3,HLA-DR5

• Increased risk of non-Hodgkin B – lymphoma

• NONTENDER Thyroid
Subacute granulomatous thyroiditis
• de Quervain thyroiditis

• Self-limited, usually after flu-like illness

• Granulomatous inflammation

• Painful thyroiditis
Riedel Thyroiditis
• Considered as an IgG4 related systemic disease

• Thyroid replaced by fibrous tissue

• Hard/rock-like thyroid

• Painless goiter
Graves Disease
• Most common cause of
hyperthyroidism

• Type II hypersensitivity

• Anti-TSH receptors

• Exophthalmos
Follicular Adenoma

• Most are nonfunctional

• Absence of capsular and vascular

invasion
Papillary Thyroid Carcinoma
• Most common

• Excellent prognosis

• Optically clear nuclei (Orphan-Annie),

Nuclear grooves, Psammomma
bodies

• Lymphatic vessel invasion

• RET/PTC, BRAF mutations

Follicular Carcinoma
• With Capsular and Vascular invasion

• Hematogenous spread

• RAS mutations

• Metastasizes to bone
Medullary Carcinoma
• Tumors of the parafollicular C cells

• Produces Calcitonin

• Neoplastic cells admixed in amyloid

• Associated with MEN2A and 2B

Undifferentiated/Anaplastic Carcinoma
• Seen in old patients

• Rapidly enlarging neck mass

• Poor prognosis

• TP53 mutations
Hyperparathyroidism
PRIMARY SECONDARY TERTIARY
Due to adenoma or Due to decreased Calcium Autonomous
hyperplasia absorption or increased hyperparathyroidism from
phosphate chronic kidney disease
Hypercalcemia, Hypocalcemia,
hypercalciuria, hyperphosphatemia if in CKD
hypophosphatemia
Osteitis fibrosa cystica
Syndrome of Inappropriate Antidiuretic Hormone
• Excessive free water retention

• Euvolemic hyponatremia with continued Na excretion

• Urine Osmolality > Serum Osmolality

• Rapid correction of hyponatremia causes osmotic

demyelination syndrome/central pontine myelinolysis

• Causes: ectopic ADH, CNS disorders

Diabetes Insipidus
• Inability to concentrate urine due to lack of
ADH or failure to response to ADH

• Causes include pituitary tumor, idiopathic, ADH

receptor mutations

• Central Diabetes Insipidus = ↓ ADH

• Nephrogenic Diabetes Insipidus = Normal or ↑
ADH
Diabetes Mellitus
Complications:

• Small vessel disease

• Nodular glomerulosclerosis (Kimmelstiel-
Wilson nodules)
• Coronary artery disease, vascular occlusive
disease
• Neuropathies
Diabetes Mellitus
Multiple Endocrine Neoplasias
MEN1 MEN2A MEN2B
aka Wermer Syndrome aka Sipple Syndrome

Pituitary Tumors , Parathyroid Hyperplasia, Medullary Thyroid

Pancreatic Endocrine Medullary Thyroid Carcinomas,
Tumors and Parathydoid Carcinomas, Pheochromocytomas
Hyperparathyroidism or Pheochromocytomas Neuromas
Adenomas
Mutation of MEN1 Mutation in RET Mutation in RET
(menin)
Salivary Gland Tumors
• Pleomorphic Adenoma
• most common benign tumor

• Mucoepidermoid Carcinoma
• most common malignant
tumor

• Warthin Tumor
• benign tumor
• typically found in smokers
Esophageal Pathologies
Diffuse Esophageal Mallory-Weiss Plummer-Vinson Sclerodermal
Spasm Syndrome Syndrome esophageal
Dysmotility
• “Corkscrew • Longitudinal • Triad of • Smooth muscle
appearance on lacerations of GE Dysphagia, Iron atrophy
barium swallow junction Deficiency
Anemia and • CREST syndrome
• Manometry is • Found in Esophageal
diagnostic alcoholics and Webs
bulimics
Esophageal Pathologies
• Barret Esophagus – intestinal metaplasia,
increased risk for Adenocarcinoma

• SCCA: Common in upper 2/3 of

esophagus

• Adenocarcinoma: Common in lower 1/3

of esophagus
Gastritis
ACUTE GASTRITIS
• NSAIDS – decreases PGE2 ->
decreases mucosal protection
• Burns(Curling ulcer) – mucosal
ischemia from hypovolemia
• Brain Injury (Cushing Ulcer) –
Increased vagal stimulation –>
increased HCL production
CHRONIC GASTRITIS
• Inflammation leads to atrophy and
intestinal metaplasia
• Increased risk for Gastric Cancers
• H.pylori – most common cause ->
MALT lymphoma
• Autoimmune – antibodies to
H/K/ATPase on parietal cells
Gastric Cancer

• Adenocarcinoma is the most

common

• Intestinal type is associated with

H. pylori

• Diffuse signet type not associated

with H. pylori (linitis plastica)
Peptic Ulcer Disease
Gastric Ulcer Duodenal Ulcer

Pain Pain greater with meals Pain decreases with

meals
H pylori infection Present Present
Mechanism ↓ mucosal protection ↓ mucosal protection
against gastric acid against gastric acid or ↑
gastric acid secretion
Other causes NSAIDs Zollinger-Ellison
syndrome
Risk of Malignancy Increased None
Malabsorption syndromes
Celiac Disease Lactose Pancreatic Tropical Sprue Whipple
Intolerance Insufficiency Disease

• Gluten • Lactase • Causes • Associated • Tropheryma

sensitive deficiency malabsorption with whipplei
enteropathy of fat-soluble megaloblastic infection
• Osmotic vitamins anemia due to
• Intolerance to diarrhea folate • PAS +
gliadin deficiency and, macrophages
later, B12 in intestinal
• HLA-DQ2,HLA- deficiency lamina propria
DQ8
Inflammatory Bowel Disease
Diverticula of GI Tract
• True Diverticulum – all gut wall layers

• False Diverticulum – only mucosa and submucosa

• Zenker Diverticulum – false diverticulum , located at pharyngoesophageal area

• Meckel’s Diverticulum – True diverticulum, most common congenital anomaly

of GI tract, 2x likely in males, 2 inches long, 2 feet from ICV, 2% of population,
first 2 years of life
Non-neoplastic Colonic Polyps
• Hamartomatous – solitary lesions,
distorted growths of normal colonic
tissue , associated with Peutz-Jeghers
syndrome

• Hyperplastic – most common polyp

• Inflammatory pseudopolyp – due to

inflammation
Neoplastic Colonic Polyps
• Adenomatous polyps – APC , KRAS
mutations

• Serrated Polyps – CpG island

methylateor phenotype , saw-tooth
pattern of crypts on biopsy
Polyposis Syndrome
1. Familial Adenomatous Polyposis – AD mutation of APC tumor sup. gene,
thousand of polyps may progress to carcinoma (100%)

2. Gardner Syndrome – FAP + osseous and soft tissue tumors

3. Turcot Syndrome – FAP or Lynch syndrome + CNS tumor

(medulloblastoma,glioma)

4. Peutz-Jeghers Syndrome – AD , numerous GI hamartomas, hyperpigmented

macules on mouth, lips, hands and genitals

5. Juvenile polyposis syndrome – AD, <5 years old, hamartomatous GI polyps

Lynch Syndrome
• hereditary nonpolyposis colorectal cancer (HNPCC)

• AD mutation of DNA mismatch repair genes

• microsatellite instability

• 80% progress to colorectal carcinomas

Colorectal Cancer
• Apple core lesion on barium enema

• Iron deficiency anemia

• APC and MSI mutations

• Carcino-embryonic antigen – for monitoring

recurrence

• S.bovis (gallolyticus) bacteremia

Serum Markers of Liver Pathology

AST and ALT ↑ in most liver disease ALT>AST

↑ in alcoholic liver disease AST>ALT

Alkaline Phosphatase ↑ in cholestasis, bone disease

y-glutamyl ↑ in biliary diseases

transpeptidase
Alcoholic Liver Disease
• Hepatic Steatosis
• macrovesicular fatty change

• Alcoholic Hepatitis
• swollen hepatocytes, Mallory bodies,
AST>ALT ratio of 2:1

• Alcoholic Cirrhosis
• end stage, sclerosis, regenerative
nodules with fibrosis
Non-Alcoholic Liver Disease
• due to metabolic syndrome

• may cause cirrhosis and HCC

• ALT>AST
Liver Tumors
• Hepatocellular Carcinoma
• most common primary malignant tumor in adults
• associated with HBV and HCV infection,aflatoxins, ↑ AFP

• Angiosarcoma
• Vinyl Chloride

• Hepatic Adenoma
• oral contraceptive or anabolic steroid use

• Metastases
• most common overall, GI malignancies, breast and lung
Hyperbilirubinemia
Conjugated (Direct) Unconjugated (Indirect)

• Gallstones • Hemolytic Anemia

• Tumors • Physiologic Jaundice
• Primary Sclerosing Cholangitis • Crigler-Najjar and Gilbert Syndrome
• Primary Biliary Cholangitis
• Dubin-Johnson and Rotor Syndrome
Hereditary hyperbilirubinemias
1. Gilbert Syndrome - ↓ UDP-glucuronosyltrsansferase , unconjugated

2. Crigler-Najjar – absent UDP-glucuronosyltrsansferase, unconjugated

3. Dubin-Johnson – defective liver excretion, grossly black liver, conjugated

4. Rotor Syndrome – similar to Dubin-Johnson, no black discoloration,

conjugated
Wilson Disease
• Also known as hepatolenticular degeneration

• Autosomal recessive

• mutations in hepatocyte copper-transporting ATPase

• ↓ copper incorporation to ceruloplasmin

• Kayser-Fleischer Rings
Hemochromatosis
• autosomal recessive

• mutation on HFE gene

• ↑ intestinal absorption of iron

• “bronze diabetes” ( triad of cirrhosis, DM and skin

pigmentation)
Biliary Tract Diseases
Primary sclerosing Primary biliary Secondary biliary
cholangitis cholangitis cholangitis
• “Onion skin” bile duct , • Granulomas and • Extrahepatic biliary
beads of string destruction of bile ducts obstruction
appearance
• Anti-mitochondrial
• Assoicated with antibody
ulcerative colitis

• p-ANCA positive

• ↑ for
cholangiocarcinoma and
gallbladder cancer
Gallbladder
• Cholelithiasis:

• Cholesterol stones – 80%, obesity

• Pigmented stones - hemolysis

• Porcelain Gallbladder:
• calcified gallbladder due to chronic cholecystitis
• ↑ risk of adenocarcinomas
Pancreatitis
Acute Pancreatitis Chronic Pancreatitis

• Autodigestion by pancreatic enzymes • Alcohol abuse

• ↑ serum amylase or lipase (more • Cystic fibrosis

specific) to 3x upper limit

• Complications - pseudocyst
Pancreatic Adenocarcinoma
• poor prognosis

• risk factors: smoking, chronic pancreatitis,

diabetes

• Trousseau syndrome and Courvoisier sign

• CA19-9
Urine Casts
• RBC Casts - Glomerulonephritis, hypertensive emergency

• WBC Casts - Tubulointerstitial inflammation, acute pyelonephritis

• Fatty Casts – Nephrotic syndrome

• Granular Casts – Acute Tubular Necrosis

• Waxy Casts – ESRD, CKD

• Hyaline Casts – Non-specific, can be a normal finding

Glomerular Disorders Nomenclature

Focal < 50% of glomeruli are involved

Diffuse > 50% of glomeruli are involved

Proliferative Hypercellular Glomeruli

Membranous Thickening of GBM

Nephrotic vs Nephritic Syndrome

NEPHROTIC NEPHRITIC
Massive Proteinuria = or > 3.5 gm Hematuria , red cell casts
Hypoalbuminuria, < 3gm/dL Azotemia
Generalized Edema Oliguria
Hyperlipidemia and Lipiduria Mild to Moderate Hypertension

Proteinuria
Acute Proliferative Glomerulonephritis
• Post-infectious: streptococcal

• Enlarged, hypercellular glomeruli

• Granular deposits of IgG and C3, IgM in the

mesangium

• Immune complex deposition on subepithelial

side of GBM “subepithelial humps”
Rapidly Progressive (Crescentic) Glomerulonephritis

• Crescentic glomerulonephritis – fibrin

strands

• Granular immune deposits / linear GBM

fluorescence for Ig and complement

• Rupture in the GBM

Membranous Nephropathy

• Drugs, auto-immune diseases

• PLA2 autoantigen

• uniform, diffuse thickening of the glomerular

capillary wall

• Granular IF deposits of IgG on GBM

• Dense-deposits on the epithelial side of

basement membrane
Minimal – Change Disease

• Most frequent cause of nephrotic syndrome

in children

• Normal glomeruli in light microscopy

• Unremarkable IF findings

• Effacement of foot processes

Focal Segmental Glomerulosclerosis (FSGS)

• Most common cause of nephrotic syndrome

in adults in the US

• Focal and segmental lesions in glomerulus

• IgM and C3 deposition in sclerotic areas and

mesangium

• Effacement of foot processes

Membranoproliferative Glomerulonephritis (MPGN)

• Glomeruli are large and hypercellular,

thickened GBM (double-contour or
tram-track appearance)

• Type I

• granular deposition of IgG and C3

• Subendothelial electron-dense deposits

Membranoproliferative Glomerulonephritis (MPGN)

• Glomeruli are large and hypercellular,

thickened GBM (double-contour or
tram-track appearance)

• Type I

• granular deposition of IgG and C3

• Subendothelial electron-dense deposits

Dense – Deposit Disease MPGN Type II

• Glomeruli are large and hypercellular,

thickened GBM (double-contour or
tram-track appearance)

• Irregular granular or linear C3

deposition, absent IgG

• Intramembranous dense-deposit
Kidney Stones
• Calcium Stones – most common , radiopaque

• Ammonium Magnesium Phosphate – “struvite” ,

staghorn calculi, caused by infection with urease
positive bacteria, radiopaque

• Uric Acid - associated w/ hyperuricemia ,

radiolucent

• Cystine – radiopaque
Renal Cell Carcinoma
• Most common primary renal malignancy

• ↑ incidence with smoking and obesity

• Chromosome 3

• Hematogenous spread – renal vein – lungs,bone

Renal Oncocytoma

• benign tumor arising from collecting

ducts

• large eosinophilic cells (abundant

mitochondria)
Wilms Tumor
• Nephroblastoma

• Most common renal malignancy of childhood

• Stromal , Epithelial and Mesenchymal

Components

• WT1 and WT2 loss of function

• WAGR complex, Denys-Drash Syndrome ,

Beckwith-Wiedemann Syndrome
Urinary Bladder Carcinoma
• Transitional/Urothelial Carcinoma:
• most common tumor of urinary system
• smoking, cyclophosphamide

• Squamous Cell Carcinoma:

• Schistosoma haematobium
Urinary Tract Infections
• Acute Cystitis:
• E.coli – most common
• Staph saprophyticus – sexually active young women
• Proteus mirabilis – ammonia scent urine

• Acute Pyelonephritis:
• neutrophils in the interstitium, spares glomeruli
• E.coli – most common

• Chronic Pyelonephritis:
• Thyroidization of renal tubules
Renal Cyst Disorders
Head and Neck Cancer
• Mostly squamous cell carcinoma

• Risk factors: smoking, alcohol, HPV-16, EBV

• Field Cancerization
Obstructive and Restrictive Lung Diseases

OBSTRUCTIVE RESTRICTIVE

• increased resistance to airflow • reduced expansion of lung

due to airway obstruction parenchyma and decreased
total lung capacity
• FEV1/FVC ratio of less than 0.7
• normal FEV1/FVC ratio
Obstructive and Restrictive Lung Diseases
Obstructive Restrictive
• Chronic Bronchitis • Sarcoidosis
• Emphysema • Inhalation Injury
• Asthma • Pneumoconiosis
• Bronchiectasis • Mesothelioma
Emphysema

• irreversible enlargement of the

airspaces distal to the terminal
bronchiole

• Classified according to its anatomic

distribution within the lobule
Emphysema
Centriacinar/Centriac Panacinar/Panlobular Distal Irregular emphysema
inar Acinar/Paraseptal

• Central and • Respiratory • Distal part of acini • Acini is irregularly

proximal parts are bronchiole to is affected involved
affected terminal alveoli are
affected • Spontaneous • Clinically
• Common in heavy pneumothorax insignificant
smokers • Associated with a1-
antitrypsin
deficiency
Chronic Bronchitis
• persistent cough with sputum
production for at least 3 months in at
least 2 consecutive years, in the absence
of any other identifiable cause

• “Blue bloaters”

• Reid Index: ratio of thickness of

mucosal gland later to thickness of wall
between epithelium and cartilage
Asthma
• chronic disorder of the conducting airways
caused by an immunological reaction

• Cough , wheezing

• Type 1 Hypersensitivity

• Aspirin induced asthma – d/t inhibition of PGE2

• Curschmann Spirals and Charcot-Leyden Crystals

Bronchiectasis
• destruction of smooth muscle and elastic
tissue leads to permanent dilation of
bronchi and bronchioles

• Cystic Fibrosis, Kartagener Syndrome

Pneumoconioses
• Asbestosis

• Silicosis

• Coal workers pneumoconiosis

• Berylliosis
Pneumoconioses
Asbestosis Silicosis Coal Workers Berylliosis
Pneumoconiosis
• Asbestos • Silicon dioxide • Coal dust • Beryllium
exposure exposure exposure exposure

• Asbestos body/ • Most prevalent • Anthracosis • Non-caseating

ferruginous body chronic granuloma
occupational • Carbon-laden
• Bronchogenic CA disease macrophages
and malignant
mesothelioma • Eggshell
calcification
Atelectasis
• Refers either to incomplete expansion of the lung
or to the collapse of a previously inflated lung

• Resorption/Obstructive – mediastinum shifts

towards atelectatic lung

• Compression - mediastinum shifts away from the

affected lung

• Contraction - fibrosis
Pneumonia
Lobar Bronchopneumonia Interstitial/Atypical Cryotpgenic
Organizing
Pneumonia
• S. pneumonia • S. pneumonia • Mycoplasma • Unknown
• S. aureus • Chlamydophilia etiology
• May involve • H. influenza • Legionella
whole lobe • Klebsiella • Viruses • Broncholitis
obliterans
• Congestion – • Patchy • Diffuse patchy
Red Hepatization distribution inflammation
– Gray
Hepatization -
Resolution
Lung Cancer
• No. 1 cause of CA mortality , males and females

• Adenocarcinoma is the most common Lung CA

• Complications include:
• SVC syndrome
• Pancoast Tumor
• Horner Syndrome
• Paraneoplastic Syndromes
• Effusions
Lung Cancer
Small Cell Adenocarcinoma Squamous Cell Large Cell Bronchial
Carcinoma Carcinoma Carcinoma Carcinoid
Tumor
• Central • Peripheral • Central • Peripheral • Central or
Peripheral
• Undifferenti • Most • produces • Poor
ated common PTHrp → prognosis
hypercalcem
• Produces ia
ACTH
Hydatidiform Mole
Invasive Mole

• H. mole that has invaded the

myometrium blood vessels or extra-
uterine sites
Choriocarcinoma
• Can develop during or after a pregnancy

• Malignancy of syncytiotrophoblasts and

cytotrophoblasts

• NO CHORIONIC VILLI present

• ↑ hCG

• Metastasizes to lungs
Vulvar Pathology
• Bartholin Cyst and Abscess
• Blockage of gland duct
• Associated w/ N. gonorrhea infections

• Lichen Sclerosus
• Thinning of the epidermis w/ fibrosis of dermis, slight ↑ risk for SCCA

• Lichen Simplex Chronicus

• Hyperplasia of vulvar squamous epithelium , no risk for SCCA
Vulvar Pathology
• Vulvar Carcinoma
• SCCA

• Extramammary Paget Disease

• Intra-epithelial Adenocarcinoma
• Low risk of underlying carcinoma
Vaginal Pathology
• Squamous Cell Carcinoma
• secondary to cervical SCCA

• Clear Cell Adenocarcinoma

• in-utero exposure to DES

• Sarcoma Botryoides
• embryonal rhabdomyosarcoma
Cervical Pathology
• Dysplasia and Carcinoma in situ
• Disordered epithelial growth
• Limited to basement membrane
• CIN1 , CIN2, CIN3
• Associated with HPV infection
• “koilocytes”

• Invasive Carcinoma:
• SCCA
Ovarian Cysts
• Follicular Cysts:
• From unruptured graafian follicle
• Most common ovarian mass in young women

• Theca-lutein cysts:
• Due to gonadotropin stimulation
• Associated w/ choriocarcinoma and h. mole
Ovarian Tumors
Ovarian Tumors - Surface Epithelial
Serous Cystadenoma Serous Cystadenocarcinoma

• Most common ovarian • Most common malignant

neoplasm ovarian neoplasm

• Lined by fallopian tube-like • Frequently bilateral

epithelium
• Psammoma Bodies
Ovarian Tumors - Surface Epithelial
Mucinous Cystadenoma Mucinous
Cystadenocarcinoma
• Multiloculated • May be metastatic from the GI
tract
• Mucus-secreting epithelium
• Can result in pseudomyxoma
peritonei
Ovarian Tumors - Germ Cell
Mature Cystic Teratoma Immature Teratoma
(Dermoid Cyst)
• Most common ovarian tumor in • Malignant
10 -30 y.o. females
• Contains immature neural like
• From all 3 germ layers tissue

• Struma ovarii – monodermal

• Most common malignant

transformation = SCCA
Ovarian Tumors - Germ Cell
Dysgerminoma Yolk Sac Tumor

• Most common in adolescents • Endodermal sinus tumor

• Equivalent of male SEMINOMA • Schiller – Duval Bodies

• hCG,LDH – tumor markers

Ovarian Tumors - Sex cord stromal
Fibroma Sertoli-Leydig Cell Thecoma

• Spindle-shaped • Produce androgens • Produce estrogen

fibroblasts
• Virilization
• Meigs Syndrome
Ovarian Tumors - Sex cord stromal

Granulosa Cell Tumor

• Most common malignant stromal tumor

• Often produces estrogen and progesterone

• Call- Exner Bodies

Ovarian Tumors
• Brenner Tumors:
• Resembles urinary bladder epithelium
(transitional)
• Coffee-bean nuclei
• Usually benign

• Krukenberg Tumors :
• GI tumor that metastasizes to the ovaries
• Mucin-secreting signet cell adenocarcinoma
Uterine Pathology
Polyp Exophytic masses of variable size
that project into the endometrial cavity
Adenomyosis Presence of endometrial glands in the uterine myometrium
Asherman Syndrome Adhesions , fibrosis in the endometrium
Leiomyoma Most common tumor in females , smooth muscle tumors
Endometrial Increased proliferation of the endometrial glands
Hyperplasia relative to the stroma
Endometrial Carcinoma Most common gynecologic malignancy, Endometrioid type and
Serous Type
Endometritis Inflammation of the endometrium
Endometriosis presence of “ectopic”
endometrial tissue at a site outside of the uterus.
Fibrocystic Changes - Breast
• Most common in premenopausal women

• Cysts, apocrine metaplasia, stromal fibrosis

• Subtypes:

• Sclerosing Adenosis – acini and stromal fibrosis

• Epithelial Hyperplasia – hyperplasia of ductal

and lobular epithelium
Inflammatory Conditions - Breast
• Fat Necrosis
• due to injury of breast tissue

• Lactational Mastitis
• occurs during breastfeeding

• S. aureus most common cause

Benign Tumors – Breast
• Fibroadenoma
• most common in women < 35 y.o.

• Intraductal Papilloma
• most common cause of serous or bloody nipple
discharge

• Phyllodes Tumor
• “leaf-like” lobulations
• can be malignant
Gynecomastia
• breast enlargement in males

• physiologic in newborn, pubertal and elderly

males

• Cirrhosis, hypogonadism, testicular tumors,

drugs
Breast Cancer
• palpable hard mass

• peau d’ orange – dermal lymphatic invasion

• dimpling – retraction of ligaments

• BRCA1 , BRCA2 mutations

Non-invasive Breast Cancer
• Ductal Carcinoma in-situ
• comedocarcinoma

• Paget Disease
• extension of underlying DCIS into the skin

• Lobular carcinoma in-situ

• increase risk of cancer on both breast
Invasive Breast Cancer
• Invasive Ductal Carcinoma
• atypical glandular structures

• Invasive Lobular Carcinoma

• ↓ E-cadherin expression – “single file”, no duct formation

• Medullary Carcinoma
• admixed with lymphocytes and plasma cells

• Inflammatory Carcinoma
• poor prognosis
• invasion of dermal lymphatics
Penile Pathology
• Peyronie Disease • Epispadias
• abnormal curvature of penis • urethral opening on top of penis

• Priapism • Hypospadias
• painful erections • urethral opening on ventral side

• Squamous Cell Carcinoma

• HPV infection
• Bowen disease – in situ SCCA
Testicular Pathology
• Cryptorchidism
• failure of descent of testes
• increased risk for germ cell tumors

• Testicular Torsion
• “bell-clapper deformity”
• orchipexy

• Varicocele
• common on left side
Scrotal Masses
• Hydrocele
• congenital or acquired
• trans-illumination

• Spermatocele
• cyst due to dilated epididymal duct or
rete testis
Testicular Mass – Germ Cell Tumors
Seminoma Yolk Sac Tumor Choriocarcinoma Teratoma Embryonal
Carcinoma

• Most common • endodermal • Trophoblastic • From germ cell • hemorrhagic

testicular sinus tumor tumor layers mass with
tumor necrosis
• Schiller-Duval • ↑ hCG
• Similar to bodies
Dysgerminoma
Testicular Mass – Non- Germ Cell Tumors
Leydig Cell Tumor Sertoli Cell Tumor Testicular
Lymphoma
• contains Reinke • Androblastoma • Common in older
crystals men

• Gynecomastia • B- cell lymphoma

Male GUT Pathology

• Epididymitis and Orchitis

• Chlamydia, N. gonorrhea – young sexually active
men
• E. coli , Pseudomonas – older men

• Prostatitis
• E.coli, Chlamydia, N. gonorrhea
Prostate Pathology
Benign Prostatic Hyperplasia Prostatic Carcinoma

• Hyperplasia of peri-urethral • Increased PSA

lobes
• Osteoblastic metastasis on
• Lower urinary tract symptoms bone

• Gleason grading
Achondroplasia
• most common skeletal dysplasia

• major cause of dwarfism

• gain of function mutation in FGF

receptor 3
Osteopetrosis
• also known as marble bone
disease

• autosomal recessive defects in

the gene for the enzyme carbonic
anhydrase 2 (CA2)
Osteopenia and Osteoporosis

• Osteopenia
• decreased bone mass
• 1 to 2.5 standard deviations below the mean

• Osteoporosis
• severe osteopenia
• at least 2.5 standard deviations below mean
peak bone mass in young adults
Paget Disease (Osteitis Deformans)

• SQSTM1 gene mutation

• Mosaic pattern of lamellar

bone

• Leontiasis ossea, platybasia

Fracture
• Simple – overlying skin is intact
• Compound – bone communicates with the skin surface
• Comminuted – the bone is fragmented
• Displaced - ends of the bone at the fracture site are not
aligned
• Stress - slowly developing fracture that follows a period of
increased physical activity in which the bone is subjected to
repetitive load
• Greenstick - extending only partially through the bone
• Pathologic - involving bone weakened by an underlying
disease process
Osteonecrosis (Avascular Necrosis)
• infarction of bone and marrow

• common site is femoral head

• Most cases of bone necrosis stem

from fractures or corticosteroid
administration
Pyogenic Osteomyelitis
• S. aureus – 80 to 90%

• E. coli, Pseudomonas and Klebsiella –

Genitourinary infections , IV drug abusers

• H. influenza, Group B strep – neonatal

period

• Salmonella – sickle cell disease

Osteomyelitis

• Mycobacterial
• Tuberculous spondylitis – Pott’s
Disease

Skeletal Syphilis
• saber shin deformity
Osteoid Osteoma and Osteoblastoma
Osteoid Osteoma Osteoblastoma

• Less than 2 cm
• Larger than 2 cm
• Younger men in teens and 20’s
• Involves the posterior spine more
• Predilection for the appendicular frequently
skeleton
• Pain NOT relieved by aspirin
• Induces a bony reaction
• Tumor does not induce a bony
• Severe nocturnal pain relieved by reaction
aspirin and NSAID
Osteosarcoma
• osteoid formation by malignant cells

• metaphysis of long bones

• Rb gene mutation

• Codman Triangle
Osteochondroma
• exostosis

• enchondromas – if arising in medullary

cavity

• juxtacortical chondromas – of arising on

bone surface
• Chondromas
• benign tumor of cartilage
• medulla of small bones of hands
and feet

• Chondrosarcomas
• malignant tumor of cartilage
Ewing Sarcoma
• 11:22 translocation

• small round blue cells

• Primitive Neuroectodermal Tumor

• “onion-skin “ appearance on xray

• Homer-Wright rosettes
Fibrous Dysplasia
• also known as metaphyseal fibrous defects

• curvilinear, Chinese character pattern” of

bone trabeculae
Arthritis
Osteoarthritis Rheumatoid Arthritis
• Wear and tear • Auto-immune
• Osteophytes/bonespurs/joint • HLA-DR4
mice • anti-citrullinated peptides
• Heberden and Bouchard node • Pannus formation
• No ankylosis • Swan-neck and Boutonnière
deformity
• With Ankylosis
Seronegative Spondyloarthropathies
• HLA-27 associated

• Ankylosing Spondylitis – bamboo spine

deformity
• Reactive Arthritis - triad of arthritis, non-
gonococcal urethritis or cervicitis, conjunctivitis
• Enteritis Associated
• Psoriatic Arthritis
Gout vs Calcium Pyrophosphate Crystal Deposition

Gout Rheumatoid Arthritis

• monosodium crystals • A.k.a. Pseudogout,
chondrocalcinosis
• NEGATIVELY birefringent
crystals • Calcium pyrophosphate crystals

• POSITIVELY birefringent
crystals
Skin
Skin Disorders

Albinism ↓ melanin , ↓ tyrosinase activity

Melasma Acquired pigmentation, associated with pregnancy

Vitiligo Irregular patches of depigmentation
Atopic Dermatitis IgE, type 1 hypersensitivity
Seborrheic keratosis “stuck on lesions” , horn cysts

Verrucae HPV infection, condyloma acuminatum on anus or

genitalas
Skin Vascular Tumors

Bacillary Angiomatosis Bartonella infections

Cherry Hemangioma Does not regress

Glomus Tumor Painful, from thermoregulatory glomus body
Pyogenic Granuloma Infected hemangioma
Strawberry Hemangioma of infancy, Regresses spontaneously
Hemangioma
Angiosarcoma Vinyl chloride

Kaposi Sarcoma HIV, HHV-8

Pigmented Lesions

Congenital Nevus Present at birth

Blue Nevus Often confused with melanoma clinically

Spitz Nevus Often confused with hemangioma clinically
Halo Nevus Host response against nevus cells
Dysplastic Nevus Precursor to melanoma

Melanoma BRAF V600E mutations , Breslow Thickness

Skin Cancer
• Basal Cell Carcinoma
• most common skin cancer, more
common on upper lip
• waxy, pearly nodules with telangiectasias
• rodent ulcer

• Squamous Cell Carcinoma

• second most common skin cancer
• more common on lower lip
• actinic keratosis is a precursor
Autoimmune Blistering Disorders
Pemphigus Vulgaris Bullous Pemphigoid
• Most common • IgG antibodies against
hemidesmosomes
• IgG antibodies against
desmoglein 1 and 3
Pathologic RBC Forms
Type Conditions
Dacryocytes/ Teardrop Cells Myelofibrosis

Bite Cells G6PD Deficiency

Ringed Sideroblasts Sideroblastic Anemia
Sickle Cells Sickle Cell Anemia
Spherocytes Hereditary Spherocytosis

Target Cells Thalassema, Asplenia

RBC Inclusions
Type Conditions

Basophilic Stippling Lead Poisoning

Heinz Bodies G6PD Deficiency

Howel-Jolly Bodies Asplenia

Pappenheimer Bodies Sideroblastic Anemias

Thalassemia
α - Thalassemia β - Thalassemia
• α – globin gene deletions • point mutations

• 1 deletion = minima • ↓β – chain = minor

• 2 deletion = minor • Absent β chain = major
• 3 deletion = HbH disease
• 4 deletion = Hemoglobin Barts • “Crewcut” skull xray
(hydrops fetalis) • Chipmunk Facies
Megaloblastic Anemia
• Folate Deficiency
• ↑ homocysteine, normal methylmalonic
acid
• NO NEUROLOGIC SYMPTOMS

• B12 Deficiency
• ↑ homocysteine, ↑ methylmalonic acid
• WITH NEUROLOGIC SYMPTOMS (dementia)
Hereditary Spherocytosis

• intrinsic defects in the red cell

membrane skeleton

• vulnerable to splenic sequestration

and destruction

• Ankyrin, band 3, spectrin and band

4.2

• Parvovirus B19 – aplastic crisis

G6PD Deficiency
• ↓ NADPH = ↓ reduced glutathione

• ↑ RBC susceptibility to oxidant stress

• Fava beans – hemolysis

• Heinz Bodies ( denatured Hgb) – bite

cells
Paroxysmal Nocturnal Hemoglobinuria
• Complement-mediated intravascular
RBC lysis

• mutations in the phosphatidylinositol

glycan complementation group A gene
(PIGA)
Sickle Cell Anemia
• β-globin = replacement of a glutamate
residue with a valine residue

• Low O2 tension precipitates sickling

• Howel-Jolly Bodies on RBC

• Salmonella Osteomyelitis
Immunohemolytic Anemias
• caused by antibodies that bind to red cells,
leading to their premature destruction

• Direct Coombs – anti-Ig added to patient’s

RBC

• Indirect Coombs- normal RBC added to

patients serum
 Leukemia Lymphoma
• Lymphoid or Myeloid • Discrete tumor mass from
Neoplasm lymph nodes

• Involves Bone Marrow

• Tumor Cells on Peripheral

Blood
Lymphoma
Hodkgin Lymphoma Non-Hodgkin Lymphoma

• Localized, single group of lymph • Multiple Lymph Nodes Involved

nodes, contiguous spread
• Extranodal Involvement
• Presence of Reed-Sternberg Common
Cells
• Non-contiguous spread
Hodgkin Lymphoma
Subtype
Nodular Sclerosis Most common, , collagen band
deposition, uncommonly associated
with EBV
Mixed Cellularity Numerous eosinophils
Lymphocyte Rich Best prognosis
Lymphocyte Depletion HIV infected individuals
Lymphocyte Predominance “Popcorn Cells”
Non-Hodgkin Lymphoma
Burkitt Lymphoma t(8:14) EBV associated, “starry-sky
appearance”
Diffuse Large B-Cell BCL-2-BCL6 alterations Most common type of NHL in
adults
Follicular Lymphoma t(14:18) BCL2 immunostain positive
Mantle Cell Lymphoma t(11:14), cyclin D1 Aggressive
Marginal Zone Lymphoma t(11:18) Associated with chronic
infections
Primary CNS Lymphoma in immunocompromised
hosts
Adult T-Cell Lymphoma caused by HTLV
Mycosis fungoides, Sezary CD4 cells
Syndrome
Multiple Myeloma
• If solitary = Plasmacytoma

• Lytic Bone lesions

• Ig light chains in urine (Bence Jones

protein)

• M spike is IgG followed by IgA

Waldenström macroglobulinemia

• M spike is IgM
Leukemias
Myeloid Neoplasms Lymphoid Neoplasms

Acute Myelogenous Leukemia Acute Lymphoblastic

Leukemia/Lymphoma

Chronic Myelogenous Leukemia Chronic Lymphocytic Leukemia/Small

Lymphocytic Lymphoma

Hairy Cell Leukemia

Leukemias – Lymphoid Neoplasms

Acute Lymphoblastic most frequently in children, increased lymphoblasts,

Leukemia/Lymphoma t(12:21), may involve CNS and testes

Chronic Lymphocytic most common adult leukemia, Richter Transformation =

Leukemia/Small CLL/SLL transformation to DCBCL
Lymphocytic Lymphoma
Hairy Cell Leukemia mature B-cell tumor, hair-like projections on cytoplasm,
stains tartrate-resistant acid phosphatase
Leukemias – Myeloid Neoplasms

Acute Myelogenous Auer rods in Acute promyelocytic leukemia (t15:17),

Leukemia myeloblasts on blood smear, DIC is common

Chronic Myelogenous Philadelphia Chromosome (t(9:22),BCR-ABL), may transform

Leukemia to AML or ALL in blast crisis.
Epidural Hematoma
• arterial rupture

• “lucid interval” -> rapid deterioration

• Biconvex(lentiform) blood collection

on CT-scan

• Does not cross the suture lines

Subdural Hematoma
• Rupture of bridging veins

• Crescent-shape blood collection

on CT-scan

• Crosses the suture lines

Subarachnoid Hemorrhage

• Bleeding due to trauma, or rupture of

an aneurysm

• “worst headache of my life”

Intraparenchymal Hemorrhage
• Most commonly caused by systemic
hypertension

• Hypertensive hemorrhages (Charcot-

Bouchard microaneurysm) – most
often in putamen of basal ganglia
Cellular Pathology of the CNS

Neurons “Red Neurons”, Axonal Reaction, Neuronal Inclusions

Astrocytes Gliosis

Microglia proliferation, elongation of nuclei (Rod cells), microglial

nodules, neuronophagia
Oligodendrocytes Demyelination
Parkinson Disease
• Hypokinetic movement disorder

• Loss of dopaminergic neurons

• Depigmentation of substantia nigra

• α-synuclein(Lewy Bodies) and Tau inclusions

Alzheimer Disease
• most common cause of dementia in
older adults

• Senile plaques in gray matter – Aβ

• Neurofibrillary tangles - Tau-containing

bundles
Creutzfeldt-Jakob Disease
• most common prion disease

• dementia with myoclonus

• Spongiform transformation of
cerebral cortex

• Aggregation of β-sheet PrPsc

Glioblastoma Multiforme
• Grade IV Astrocytoma

• “Pseudopalisading tumor cells

around a necrotic area”

• Microvascular proliferation
Oligodendroglioma
• “Fried Egg cells”

• “Chicken – wire” capillary pattern

• IDH1/IDH2 – most common

mutations
Meningioma
• arise from the meningothelial cells of the
arachnoid

• most common cytogenetic abnormality is loss

of chromosome 22

• Psammomma bodies
Pituitary Adenoma

• Functioning or non-functioning

• Microadenomas if < 1 cm, Macroadenomas if >

1 cm

• Lactotroph Adenoma – most frequent

hyperfunctioning adenoma
Pilocytic Astrocytoma
• Relatively benign

• Most common primary brain tumor

in childhood

• Rosenthal Fibers are seen

Medulloblastoma
• Most common malignant tumor in
childhood

• Common in cerebeullum

• Homer-Wright rosettes
Ependymoma

• Children - Common in the 4th

ventricle

• Adults – common in the spinal

cord
Mutations in DNA

Silent Nucleotide substitution results in the SAME amino acid

Missense Nucleotide substitution results in DIFFERENT amino acid

Nonsense Nucleotide substitution results in STOP CODON

Frameshift Deletion or insertion of a number of nucleotides not divisible
by 3 → misreading of downstream

Splice Site Mutation at a splice site

Disorders of Imprinting

Prader-Willi Syndrome Paternal allele Maternal genes

– “Hyperphagia” deleted, imprinted

Angelman Syndrome Maternal allele Paternal genes

- “Happy Puppet” deleted imprinted
Modes of Inheritance

Autosomal Both males and female can be affected, 50% chance of

Dominant having disease
Autosomal 25% chance of having disease, 50% carriers, 25%
Recessive unaffected

X-Linked Recessive Sons of heterozygous mothers have a 50%

chance of being affected, No male-male transmission
X-linked Dominant Mothers transmit to 50% of daughters and sons.
Fathers transmit to all daughters but no sons.

Mitochondrial Transmitted only through the mother

Inheritance
Trinucleotide Repeat Expansion

Huntington Disease CAG

Myotonic Dystrophy CTG

Fragile X Syndrome CGG

Friedrich Ataxia GAA