Neoplasia

Basic Course Audit

Revised 2020
Malignant with “benign “ name

´Hepatoma
´Lymphoma
´Seminoma
´Melanoma
´Mesothelioma
Teratoma
´totipotential cell that
differentiate along 3
germ cell layer
´benign (mature)
´malignant(immature)
Harmartoma
´Disorganized
masses
composed of
mature cells
indigenous to the
organ
´pulmonary
chondroid,
hemangioma
Choristoma

´heterotopic rest
of normal tissue
´(endometriosis)
 Anaplasia

PLEOMORPHISM NUCLEAR CHANGES

LOSS OF POLARITY ´increased N:C ratio
TUMOR GIANT CELLS (1:6è1:1)
´hyperchromatic
´ nucleoli
´mitotic figures
 Pathways of Spread

´Seeding of body cavities &

surfaces
´Lymphatics – Carcinoma
´Skip metastasis
´Sentinal nodes
´Hematogenous – Sarcoma
´Lung, Liver
Characteristics BENIGN MALIGNANT
Differentiation Well Well to poorly/
and differentiated undifferentiated/
anaplasia anaplastic
Rate of growth Indolent/slow Rapid, erratic pace
growing
capsule
Local invasion Absent Present-
progressive
infiltration
Metastasis Absent Present
Common Neoplasia of
Infancy and Childhood

´SMALL ROUND BLUE CELL TUMORS

´Neuroblastoma
´Wilms tumor
´Retinoblastoma
´Acute leukemias
´Rhabdomyosarcomas
Autosomal Dominant
Cancer Syndromes
´Li-Fraumeni Syndrome-germ
line mutation in p53 gene
´Multiple Endocrine Neoplasia
(MEN) 1 & 2 mutation in menin
and RET tyrosine kinase
´Hereditary Nonpolyposis colon
cancer (HNPCC)-inactivation
of mismatch repair gene
Molecular Basis of Cancer

´Nonlethal DNA damage

´Monoclonal expansion of single
precursor cell (G6PD isoforms)
´Regulatory genes are the principal
target of genetic damage
´A multistep process, accumulation
of mutations (Tumor progression)
 8 FUNDAMENTAL CHANGES

1. Self sufficiency in 5. Limitless

growth factors replicative
2. Insensitivity to potential
growth inhibitory 6. Sustained
signals
angiogenesis
3. Altered cellular
Metabolism 7. Ability to invade
4. Evasion of and metastasize
apoptosis 8. Ability to evade
the host immune
system
Self Sufficiency of Growth Factors
Oncogenes - Tumors
PDGFB Astrocytoma
ERBBE HER2 neu Breast Ca
RET MEN2AB, Medullary Thyroid
KIT Gastrointestinal stromal
RAS Melanoma, Lymphoma
ABL AML, some ALL
MYC c-Burkitt
N-Neuroblastoma
L-Lung small cell
CYCLIN D Mantle cell lymphoma
CDK4 Melanoma
2. INSENSITIVITY TO GROWTH
INHIBITORY SIGNALS

´TUMOR SUPPRESSORS
´Stop cell proliferation
´RB gene (Retinoblastoma,
Osteo)
´P53 protein (Li Fraumeni)
´APC (Colonic Ca, Gardner Syn.)
´NF1,2 (Neurofibromatosis)
3. Altered Cellular Metabolism
(Warburg Effect)

´Tumors shift to aerobic

glycolysis, high levels of
glucose uptake, increased
conversion of glucose to
lactose
´Oxygen hunger è Glucose
hunger
´Used in PET scanning
 4. EVASION OFAPOPTOSIS

1. Reduced
CD95/Fas
2. Inactivation of
caspase 8
E
3. Protection of tumor X I
cells by BCL2 T N
R T
4. Loss of P53 I R
I
5. Loss of APAF N
N
S
6. Unregulated IAP I S
C I
´Intrinsic more C
frequent
5. LIMITLESS REPLICATIVE
POTENTIAL

´Telomerase-prevents
shortening of telomere
´Active in stem cells

´About 90% of tumors have

telomerase activity
6. SUSTAINED ANGIOGENESIS

´Angiogenic switch
´Loss of inhibitors (angiostatin,
endostatin, vasculostatin)
´Increase in angiogenic
growth factors (VEGF, FGF)
´Dec P53, inc angiogenesis
´Neovascularization and
vasculogenesis
´Vasculature is abnormal
 7. METASTATIC CASCADE

´Two phases
´Invasion of the
extracellular
matrix
´Vascular
dissemination,
homing of tumor
cells and
colonization
 INVASION

1. Detachment of
tumor cells from
one another
´Down regulation of
E cadherins
2. Degradation of
ECM
´Secrete proteolytic
enzymes: MMPs
´Ameboid migration
 INVASION

3. Attachment to
matrix
components
— Intergrins attach
to fibronectin,
laminin
4. Locomotion
— Migration of tumor
cells
VASCULAR DISSEMINATION
tumor cells -clump, form emboli,
adhere to target
Organ trophism
´Adhesion molecules on the
endothelial cells of the target
organ (CD44)
´Chemokine receptors (CXCR4)
´Some tissues are unfavorable
(skeletal muscles, spleen)
Anti Tumor Mechanisms

´Cytotoxic T Lymphocytes
´Natural Killer cells
´Macrophages
´Antibodies
Chromosomal Abnormalities

´Translocation (most common)

MYC of Burkitt Lymphoma

´Hybrid “chimaric” genes

BCR-ABL (Philadelphia chromo.)
CML
´Deletions
Loss of tumor suppressor genes
´RB of retinoblastoma
 CARCINOGENIC CHEMICALS
Aflatoxins HCC Cigarette Pharynx,
Esop, Lung,
Kidney,
Bladder,
Pancreas
Alkylating Leuk./lymph. Nitrosamine Stomach
Alcohol SCC-pharynx, Naphthylamine Urothelial
esophagus, Bladder
HCC
Arsenic SCC-Skin, Lung Vinyl Chloride Angiosarc-
Angiocarc- Liver
Liver
Asbestos Lung Nickle, Silica Lung
Mesothelioma Chromium
RADIATION CARCINOGENS

Ionizing AML, CML. Papillary Thyroid

(radiotherapy)
Non ionizing All types of skin cancer
(UVB)
 VIRAL CARCINOGENS

EBV Nasopharyngeal, Burkitt,

CNS Lymphoma
HHV-8 Kaposi sarcoma
HBV, HCV HCC
HTLV-1 Adult T cell leuk/lymphoma

HPV (16,18, SCC-vulva, vagina, anus,

31,33) cervix
AdenoCa-cervix
Cancer Cachexia

´Progressive loss of body fat & lean

body mass, anemia, anorexia
´Elevated BMR
´Evidence of systemic
inflammation
´Action of soluble factors-
cytokines: TNFa (cachectin), IL-1
Paraneoplastic Syndromes

´Endocrinopathies
´ACTH - Cushing syndrome
´PTHRP - Hypercalcemia (most
common)
´SIADH – Hyponatremia
´Most often from SmCC of lung,
Grading and Staging

´Grading-degree of differentiation,
the number of mitosis within the
tumor
´Staging-size of primary lesion,
spread, regional lymph nodes,

Stage more clinically significant than

grade
 Tumor Markers

´HCG ´CA 125

´choriocarcinom ´ovarian
a ´CA-19-9
´AFP ´colon, pancreas
´HCC ´CA-15-3
´CEA ´Breast
´colon, pancreas ´Calcitonin
´PSA ´Medullary Ca
´prostate thyroid