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Apoptosis
Programmed cell death.
aka

cell shrinkage, chromatin

condensation, membrane blebbing,
Apoptosis
and
characteristics
formation of apoptotic bodies, which
are then phagocytosed.
- embryogenesis, hormone -induction
(menstruation), -immune cell
Apoptosis mediated death,
when - injurious stimuli (e.g., radiation,
hypoxia),
-atrophy.

Enzymatic degradation of a cell

Necrosis
resulting from exogenous injury.

Characterized by enzymatic digestion

and protein denaturation, with release
Necrosis
of
intracellular components.
 Morphologically occurs as
-coagulative (heart, liver, kidney),
-liquefactive (brain),
Necrosis
different types and there locations -caseous (tuberculosis),
-fat (pancreas),
-fibrinoid, or gangrenous (limbs, GI
tract).

Cell injury
reversible or irreversible Reversible
Cellular swelling?

Cell injury
reversible or irreversible Reversible
Nuclear chromatin clumping?

Cell injury
reversible or irreversible Reversible
Decreased ATP synthesis?

Cell injury
reversible or irreversible Reversible
Ribosomal detachment?

Cell injury
reversible or irreversible Reversible
Glycogen depletion?

Cell injury
reversible or irreversible Irreversible
Plasma membrane damage?
 Cell injury
reversible or irreversible Irreversible
Lysosomal rupture?

Cell injury
reversible or irreversible
Irreversible
Ca2+ influx oxidative
phosphorylation?

Cell injury
reversible or irreversible
Irreversible
Nuclear pyknosis, karyolysis,
karyorrhexis?

Cell injury
reversible or irreversible irreversible
Mitochondrial permeability?

Characterized by
-rubor (redness),
Inflammation -dolor (pain),
5 features -calor (heat),
-tumor (swelling)
-functio lassa (loss of function).

Neutrophil, eosinophil, and antibody

cells in acute Inflammation
mediated

cells in chronic Inflammation Mononuclear cell mediated:

 Fluid exudation
Leukocyte activation
Fibrosis
Phases of Inflammation
Acute
Chronic
Resolution

What happens in different phases of

Increased vascular permeability,
Inflammation?
vasodilation, endothelial injury
Fluid exudation

Emigration (rolling, tight binding,

What happens in different phases of diapedesis)
Inflammation? Chemotaxis (bacterial products,
Leukocyte activation complement, chemokines)
Phagocytosis and killing

What happens in different phases of

Fibroblast emigration and proliferation
Inflammation?
Deposition of ECM
Fibrosis

What happens in different phases of

Neutrophil, eosinophil, and antibody
Inflammation?
mediated
Acute

Mononuclear cell mediated:

What happens in different phases of Characterized by persistent
Inflammation? destruction and repair
Chronic Granulomanodular collections of
macrophages and giant cells
 -Restoration of normal structure

-Granulation tissuehighly
vascularized, fibrotic
What happens in different phases of
-Abscessfibrosis surrounding pus
Inflammation?
Resolution 5 different outcomes
-Fistulaabnormal communication

-Scarringcollagen deposition
resulting in altered structure and
function

Leukocyte
E-selectin on vascular endothelium
extravasation
binding to Sialyl-LewisX
what mediates
on the leukocyte.
Rolling?

Leukocyte
ICAM-1 on vascular endothelium
extravasation
binding to LFA-1 on
what mediates
the leukocyte.
Tight binding?

1. Rolling
Stages of Leukocyte 2. Tight binding
extravasation 3. Diapedesis
4. Migration

Leukocyte
extravasation
chemotactic signals (e.g., cytokines).
what mediates
migration?

leukocyte travels between

What is Diapedisis endothelial cells and exits blood
vessel.
 Initiated via
radiation exposure,
metabolism of drugs (phase I), redox
Free radical injury
reaction,
what initiates it
nitric oxide,
transition metals,
leukocyte oxidative burst.

Free radical injury

reperfusion after thrombolytic therapy.
when is it a big problem

Free radical injury

(vitamins E and A).
what are the antioxidants

Abnormal proliferation of cells with

loss of size, shape, and dysplasia
orientation

Normal cells with basal apical

Normal cells
differentiation

Cells have increased in number hyperplasia

Neoplastic cells have not invaded

basement membrane
High nuclear/cytoplasmic ratio and
In situ carcinoma
clumped chromatin
Neoplastic cells encompass entire
thickness
 Cells have invaded basement
membrane using collagenases and
hydrolases Invasive carcinoma
Can metastasize if they reach a
blood or lymphatic vessel

-plasia definitions
in number of cells (reversible).
Hyperplasia

-plasia definitions 1 adult cell type is replaced by

Metaplasia another (reversible). Often 2

abnormal growth with loss of cellular

orientation, shape, and size in
-plasia definitions
comparison to normal tissue
Dysplasia
maturation; commonly preneoplastic
(reversible).

abnormal cells lacking

differentiation; like primitive cells of
-plasia definitions
same tissue, often
Anaplasia
equated with undifferentiated
malignant neoplasms.

-plasia definitions a clonal proliferation of cells that is

Neoplasia uncontrolled and excessive.

Grade = histo apperance, often based

on the mitoses per high pwer field
Tumor grade vs. stage number
describe
Stage = ammount of spread based on
site and size
 Tumor grade vs. stage
Stage
which is usually more prognostic

T = size of Tumor
TNM staging system: N = Node involvement
M = Metastases

carcinoma
The term ?????? implies epithelial
origin, whereas sarcoma denotes
sarcoma
???????origin. Both terms imply
?????.
malignancy

epithelial
The term carcinoma implies ???????
origin, whereas sarcoma denotes
mesenchymal
??????origin. Both terms imply
?????.
malignancy
Blood cells = There isn't one

Blood vessels = Hemangioma

Tumor nomenclature Smooth muscle = Leiomyoma

Benign tumor of
Mesenchyme Skeletal muscle = Rhabdomyoma

Bone = Osteoma

Fat = Lipoma

Tumor nomenclature Adenoma, papilloma

Benign vs malignant tumor of
Epithelium Adenocarcinoma, papillary carcinoma
 Tumor nomenclature benign = mature teratoma
Benign vs malignant tumor of
> 1 cell type malignint = Immature teratoma

Blood cells = Leukemia, lymphoma

Blood vessels = Angiosarcoma

Smooth muscle =Leiomyosarcoma

Tumor nomenclature
malignant tumor of
Skeletal muscle =
Mesenchyme
Rhabdomyosarcoma

Bone = Osteosarcoma

Fat = Liposarcoma

What is the Neoplasm/s associated ALL (we ALL fall Down),

with Down syndrome? AML

What is the Neoplasm/s associated Melanoma and basal,

with Xeroderma pigmentosum, squamous cell carcinomas
albinism? of skin

What is the Neoplasm/s associated

with Chronic atrophic gastritis,
Gastric adenocarcinoma
pernicious anemia,
postsurgical gastric remnants?

What is the Neoplasm/s associated Astrocytoma and cardiac

with Tuberous sclerosis? rhabdomyoma
 What is the Neoplasm/s associated Squamous cell carcinoma
with Actinic keratosis? of skin

What is the Neoplasm/s associated Esophageal

with Barretts esophagus? adenocarcinoma

What is the Neoplasm/s associated Squamous cell carcinoma

with Plummer-Vinson syndrome? of esophagus

What is the Neoplasm/s associated

with Cirrhosis (alcoholic, hepatitis B or Hepatocellular carcinoma
C)?

What is the Neoplasm/s associated

Colonic adenocarcinoma
with Ulcerative colitis?

What is the Neoplasm/s associated 2 osteosarcoma and

with Pagets disease of bone? fibrosarcoma

What is the Neoplasm/s associated

Malignant lymphomas
with Immunodeficiency states?
 Aggressive malignant
What is the Neoplasm/s associated
lymphomas (non-Hodgkins)
with AIDS?
and Kaposis sarcoma

What is the Neoplasm/s associated Benign and malignant

with Autoimmune diseases? thymomas

Visceral malignancy
What is the Neoplasm/s associated
(stomach, lung, breast,
with Acanthosis nigricans?
uterus)

What is the Neoplasm/s associated

Malignant melanoma
with Dysplastic nevus?

Oncogene or Tumor suppressor

Oncogenes
and what is the associated tumor
CML
abl

Oncogene or Tumor suppressor

Oncogenes
and what is the associated tumor
Burkitts lymphoma
c-myc

Oncogene or Tumor suppressor Oncogenes

and what is the associated tumor
Follicular and undifferentiated
bcl-2 lymphomas (inhibits apoptosis)
Oncogene or Tumor suppressor Oncogenes
and what is the associated tumor
Breast, ovarian, and gastric
erb-B2 carcinomas

Oncogene or Tumor suppressor

Oncogenes
and what is the associated tumor
Colon carcinoma
ras

Oncogene or Tumor suppressor

Oncogenes
and what is the associated tumor
Lung tumor
L-myc

Oncogene or Tumor suppressor

Oncogenes
and what is the associated tumor
Neuroblastoma
N-myc

Oncogene or Tumor suppressor Oncogenes

and what is the associated tumor
Multiple endocrine neoplasia (MEN)
ret types II and III

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Retinoblastoma, osteosarcoma
Rb

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Breast and ovarian cancer
BRCA1 and 2
Oncogene or Tumor suppressor Tumor suppressor
and what is the associated tumor
Most human cancers, Li-Fraumeni
p53 syndrome

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Melanoma
p16

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Colorectal cancer
APC

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Wilms tumor
WT1

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Neurofibromatosis type 1
NF1

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Neurofibromatosis type 2
NF2

Oncogene or Tumor suppressor

Tumor suppressor
and what is the associated tumor
Pancreatic cancer
DPC
Oncogene or Tumor suppressor
Tumor suppressor
and what is the associated tumor
Colon cancer
DCC

Tumor markers
Prostate-specific antigen. Prostatic
carcinoma.
PSA

Tumor markers Very nonspecific but

colorectal and pancreatic
CEA cancers; also others

Tumor markers Hepatocellular carcinomas.

-fetoprotein yolk sac tumor

Tumor markers Hydatidiform moles,

Choriocarcinomas,
-hCG Gestational trophoblastic tumors.

Tumor markers
Ovarian, malignant epithelial tumors.
CA-125

Tumor markers
Melanoma, neural tumors,
astrocytomas.
S-100
 Tumor markers -Metastases to bone,
-obstructive biliary disease, -Pagets
Alkaline phosphatase disease of bone.

Tumor markers
Neuroblastoma, lung and gastric
cancer.
Bombesin

Tumor markers
Hairy cell
leukemiaa B-cell neoplasm.
TRAP

Tumor markers
Pancreatic adenocarcinoma.
CA-19-9

Tartrate-resistant acid phosphatase.

what is TRAP Hairy cell
leukemiaa B-cell neoplasm.

Oncogenic viruses
name the tumor associated with
Adult T-cell leukemia
HTLV-1

Oncogenic viruses
name the tumor associated with
Hepatocellular carcinoma
HBV, HCV
 Oncogenic viruses
name the tumor associated with Burkitts lymphoma, nasopharyngeal
carcinoma
EBV

Oncogenic viruses
Cervical carcinoma (16, 18),
name the tumor associated with
penile/anal
carcinoma
HPV

Oncogenic viruses
Kaposis sarcoma, body cavity fluid B-
name the tumor associated with
cell
lymphoma
HHV-8

Types of HPV that cause CIN 16, 18

Cancer caused by
Liver (hepatocellular carcinoma)
Aflatoxins

Cancer caused by
Liver (angiosarcoma)
Vinyl chloride

Cancer caused by
Liver (centrilobular necrosis, fatty
change)
CCl4
 Cancer caused by
Esophagus, stomach
Nitrosamines

Cancer caused by
Larynx, lung, ...
Cigarette smoke

Cancer caused by
Lung (mesothelioma and
bronchogenic carcinoma)
Asbestos

Cancer caused by
Skin (squamous cell carcinoma)
Arsenic

Cancer caused by
Bladder (transitional cell carcinoma)
Naphthalene (aniline) dyes

Cancer caused by
Blood (leukemia)
Alkylating agents

Paraneoplastic effects of tumors

Small cell lung carcinoma
neoplasm and Mech
ACTH or ACTH-like peptide
Cushings syndrome
 Paraneoplastic effects of tumors Small cell lung carcinoma and
neoplasm and Mech intracranial neoplasms

SIADH ADH

Squamous cell lung carcinoma,

renal cell carcinoma, breast
Paraneoplastic effects of tumors carcinoma, multiple
neoplasm and Mech myeloma, and bone
metastasis (lysed bone)
Hypercalcemia
PTH-related peptide, TGF-, TNF-,
IL-1

Paraneoplastic effects of tumors Renal cell carcinoma,

neoplasm and Mech hemangioblastoma

Polycythemia Erythropoietin

Thymoma, small cell lung

Paraneoplastic effects of tumors
carcinoma
neoplasm and Mech
Antibodies against presynaptic Ca2+
Lambert-Eaton syndrome
channels at neuromuscular junction

Leukemias and lymphomas

Paraneoplastic effects of tumors
neoplasm and Mech
Hyperuricemia due to excess nucleic
acid
Gout, urate nephropathy
turnover (i.e., cytotoxic therapy)
Lots of Bad Stuff Kills Glia.

Lung,
1 tumors that metastasize to brain Breast,
Skin (melanoma),
Kidney (renal cell carcinoma),
GI.
 approximately ??%
50
of brain tumors are from metastases.

??????the most common sites of liver

metastasis after the regional lymph and
nodes. Lungs

mne: Cancer Sometimes Penetrates

Benign Liver.
tumors that metastasize to the liver
Colon > Stomach > Pancreas > Breast
> Lung.

most common Liver cancer Metastasis

P. TT. Barnum Loves Kids.

These 1 tumors metastasize to bone
PROSTATE, Thyroid, Testes,
BREAST, Lung, Kidney.

Lung = Lytic.
Features of 1 tumors that
Prostate = blastic.
metastasize to bone
Breast = Both lytic and blastic.

Most common Bone Tumors Mets from (esp Prostate or Breast)

 Cancer epidemiology Prostate (32%)
Lung (16%)
Most common cancers in Colon and rectum (12%)
Men ..
.. Lung (33%)
deaths in men Prostate (13%)
Cancer epidemiology Breast (32%)
Lung (13%)
Most common cancers in Colon and rectum (13%)
women ...
.. Lung (23%)
deaths in women Breast (18%)

heart disease
1st and 2nd leading killers in the U.S.
cancer

Deaths from lung cancer have

Changes in lung cancer deaths plateaued in males but
continue to in females.

Retinoblastoma, osteosarcoma
Rb
Gene
13q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Breast and ovarian cancer (BRCA)
BRCA1 and 2
Gene
17q, 13q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Most human cancers, Li-Fraumeni p53
syndrome
17p
Gene
Chromosome
and
Oncogene or Tumor suppressor Tumor suppressor
 Melanoma
p16
Gene
9p
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Colorectal cancer
APC
Gene
5q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Wilms tumor
WT1
Gene
11q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Neurobromatosis type 1
NF1
Gene
17q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Neurobromatosis type 2
NF2
Gene
22q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Pancreatic cancer
DPC
Gene
18q
Chromosome
and
Tumor suppressor
Oncogene or Tumor suppressor
Colon cancer
DCC 18q Tumor suppressor
Gene
and
Chromosome
and
ras Oncogenes
Oncogene or Tumor suppressor
 CML
abl
Gene
9:22
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor
Burkitts lymphoma
c-myc
Gene
8:14
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor
Follicular and undifferentiated
lymphomas bcl-2

Gene 14:18
Chromosome
and Oncogenes
Oncogene or Tumor suppressor
Breast, ovarian, and gastric
carcinomas erb-B2

Gene
Chromosome
and Oncogenes
Oncogene or Tumor suppressor
Colon carcinoma
ras
Gene
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor
Lung tumor
L-myc
Gene
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor
 Neuroblastoma
N-myc
Gene
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor
Multiple endocrine neoplasia (MEN)
types II and III ret

Gene
Chromosome
and Oncogenes
Oncogene or Tumor suppressor
Gastrointestinal stromal tumor (GIST)
c-kit
Gene
Chromosome
and
Oncogenes
Oncogene or Tumor suppressor