Neoplasia refers to abnormal cell growth or tumors. There are two main types of neoplasia - benign and malignant. Benign tumors remain localized and are non-invasive, while malignant tumors can invade surrounding tissues and spread to distant sites through lymphatic vessels or blood vessels in a process called metastasis. The development of cancer is a multistep process that involves genetic mutations that activate oncogenes and inactivate tumor suppressor genes, resulting in uncontrolled cell growth and division. Key hallmarks of cancer include self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and ability to invade and metastasize.

1. NEOPLASIA

2. DEFINITION
• Neo = New ; Plasia= growth
• Abnormal mass of tissue as a result of abnormal growth
or multiplication of cell.
• Growth of neoplastic cell persist in excessive manner
even after the stimulus that evoked the changes stop.

3. CLASSIFICATION OF NEOPLASIA
2 types :
BENIGN MALIGNANT
- Suffix = –oma to cell type which the tumor arise
- Eg: fibrous tissue – fibroma
Bone tissue – Osteoma etc.
- Suffix: –Sarcoma =
Malignant tumor (Cancer) that arises from
transformed cells of mesenchymal origin
Eg: Chondrosarcoma
–Carcinoma= Malignant tumor from epithelial origin
Eg: Adenocarcinoma
- Microscopic and gross characteristic relatively inoncent - Invade and destroyed adjacent structure and spread to distant
site.(metastasize).
- Remain localized • Will invade other neighbouring tissues & m etastasize (Lymph &
BV)
- Amendable to local surgical removal • Lower prognosis than benign tumors

4. DIFFERENCE BETWEEN
MALIGNANT AND BENIGN

5. TYPE BENIGN MALIGNANT
DIFFERENTI
ATION @
ANAPLASIA
- Well differentiated
- Closely resemble their normal
counterpart.
- Mitosis usually rare
- Nuclei remain at basal layer
but usually enlarged.
- Poor differentiate@anaplastic
- Loss of structure and function
- Plemorphism, hyperchromatic,
increase nuclear-cytoplasmic
ration, giant cell.
- Mitosis often numerous.
- Loss of polarity

6. LOCAL
INVASION
- Remain localized at site of
origin
- Does not have the capacity
to infiltrate,invade or
metastasize.
- Encapsulated.
- Grow by progressive
infiltration,invasion,
destraction and penetration of
surrounding tissue.
- Do not develop well of define
capsule.
- Hemmorhage and necrosis.
- Ulceration.

7. METASTASIS - Absent - Metastasize
- Factor increase of metastasis
• Larger of tumor
• Older of tumor
• Poorly differentiated
- Disseminate by 3 pathways
• Seeding body cavity
• Lymphatic spread
• Hematogenous spread

8. METHOD OF
DIAGNOSIS

9. Method Explanation
History and physical
examination
What the health care worker learns from talking to the patient and
through direct examination may give clues to the presence of a
neoplasm. Signs and symptoms such as weight loss, fatigue, and
pain may be present. A mass may be palpable or visible.
Radiographic
technique
The use of plain films (x-rays), computed tomography (CT),
magnetic resonance imaging (MRI), mammography, and
ultrasonography (US) may be very helpful to detect the presence
and location of mass lesions. The findings from these methods
may aid in staging and determination of therapy.
Genetic
Testing
Genetic markers include chromosomal alterations (translocations,
deletions, duplication, etc.); specific gene defects; single
nucleotide polymorphisms, and gene rearrangements. Detection
of specific genes (such as BRCA-1 for breast cancer) may
suggest an increased risk for some malignancies.

10. Cytology Methods that sample cells can be simple and cost-effective and
minimally invasive. A good example is the Pap smear for diagnosis of
cervical dysplasias and neoplasms. Cells exfoliated into body fluids may
also be examined. Fine needle aspiration (FNA) can be used to sample a
variety of mass lesions.
Tissue
biopsy and
surgery
Methods that sample small pieces of tissue (biopsy) from a particular
site, often via endoscopic techniques (such as colonoscopy, upper
endoscopy, or bronchoscopy) can often yield a specific diagnosis of
malignancy. At surgery, portions of an organ or tissue can be sampled, or
the diseased tissue(s) removed and examined in surgical pathology to
determine the stage and grade of the neoplasm.
Autopsy Sometimes neoplasms are not detected or completely diagnosed during
life. The autopsy serves as a means of quality assurance for clinical
diagnostic methods, as a way of confirming diagnoses helpful in
establishing risks for family members, as a means for gathering statistics
for decision making about how to approach diagnosis and treatment of
neoplasms, and to provide material for future research.

11. Laboratory
analyses
General findings such as anemia, enzyme abnormalities (such as an
increased alkaline phosphatase), and hematuria or positive stool
occult blood are helpful to suggest further workup. Tumor markers in
serum such as carcinoembryonic antigen (CEA), alpha-fetoprotein
(AFP), or human chorionic gonadotropin (HCG) can be performed.
Unfortunately, they are not all that specific or sensitive, particularly
when applied as screening tests to a general population. More specific
testing, such as measurement of prostate specific antigen (PSA)
levels, may help to determine the presence of specific neoplasms, but
such tests are not perfect screening tools in a general population.

12. Spread of tumour:
Direct spread Distant spread
-means tumour spreading and involving the
tissues around the tumour.
- As example,if the primary tumours arises
from the bronchus,this tumour can spread
to the lung tissue.
-means the tumour from one site (primary)
is now transferred to a distant site
(secondary).
-This process called metastasis.
-There are three ways on how tumour can
metastasise to distant sites. (refer table in
next slide)

13. Distant spread
By Invasion of
lymphatic
-Lymphatic are channels lined by endothelium-drain lymph from
tissues to lymph nodes (regional lymphnodes)
-Ex : Breast carcinoma-enlarged axillary lymph nodes
-Usually cancers that spread via lymphatic are *CARCINOMAS.

14. Hematogenous
spread
-Spread via blood channels.
-VEINS are more frequently invaded than arteries because:
a-thinner walls
b-lower pressure
c-slower blood flow
-Neoplasm that spread via blood channels usually *SARCOMAS

15. Through body cavity It can either spread via:
1-coelomic cavity
-tumours seeding over surfaces in peritoneal,pleural and
pericardial spaces.
-Ex:Carcinoma in ovary of one side spreading to the other ovary
or to other organs in peritoneum
2-Cerebral spinal fluid
-occurs for cancers in the brain and spinal cord.

17. Grading
(Differentiation)
• Made by Pathologist
• Microscopic appearance
• Assesment depends on :
 Mitotic activity
 Nuclear size &
pleomorphism
 The differentition
• Degree of diff. indicates :
 Prognosis
 Appropiate treatment
Grading of Malignant Neoplasms
Grade Definition
I Well differentiated
II
Moderately
differentiated
III Poorly differentiated
IV Nearly anaplastic
Eg :
Adenocarcinoma

18. Staging
(Spreading)
• Made by Surgeon
• Gross anatomical appearance
Eg : lung carcinoma
Staging of Malignant Neoplasms
Tis In situ, non-invasive
T Refers to Primary tumors
T1
Small, minimally invasive within primary
organ site
T2
Larger, more invasive within the primary
organ site
T3
Larger and/or invasive beyond margins of
primary organ site
T4
Very large and/or very invasive, spread to
adjacent organs
N Refers to Lymph Nodes
N0 No lymph node involvement
N1 Nearby lymph node involvement
N2 Regional lymph node involvement
N3 More distant lymph node involvement
M Refers to anatomical distance metastases
M0 No distant metastases
M1 Distant metastases present

19. Although benign tumours are confined
to their site of origin, they may cause
clinical problems due to:
Pressure on adjacent tissues
(e.g. benign meningeal tumours
causing epilepsy)
Obstruction to the flow of fluid
(e.g. benign epithelial tumour
blocking a duct)
Production of a hormone (e.g.
benign thyroid tumour causing
thyrotoxicosis)
Transformation into a
malignant neoplasm (e.g.
adenormatous polyp progressing
to an adenocarcinoma)
anxiety

21. Morbidity and mortality associated with
malignant tumours:
Pressure on and destruction of
adjacent tissue
Formation of secondary tumours
(metastases)
Blood loss from ulcerated
surfaces
Obstruction of flow (e.g.
malignant tumour of the colon
causing intestinal obstruction)
Production of a hormone (e.g.
ACTH and ADH from some lung
tumours)
Other paraneoplastic effects
causing weight loss and debility

22. Cachexia (wasting syndrome)
• Progressive loss of body fat and lean body mass
accompanied by profound weakness, anorexia, and
anemia.
• The origins of cancer cachexia are obscure.
• Cachexia is not caused by the nutritional demands of the
tumor.
• Results from the action of soluble factors such as
cytokines produced by the tumor or host
• Cachexia- the loss of
1.skeletal muscle,
2.adipose tissue
3.immunological competence.

23. Paraneoplastic Syndrome
• Symptoms complexes in cancer-bearing
patients that cannot be explained by :-
• local or metastatic spread
• elaboration of hormones indigenous to tissue
• May represent early manifestations of tumor
• May represent significant clinical problems
• May even be fatal
• Occurs in about. in 10% of patients with cancer
• They are syndromes involving nonmetastatic
systemic effects that accompany malignant
disease.

24. Paraneoplastic syndromes
Syndrome Mechanism Example
Cushing
Syndrome
Secretion of ACTH-
like substance
Lung small cell anaplastic
(oat cell) carcinoma
Hypercalcemia
Parathyroid hormone-
like substance
Lung (squamous cell)
carcinoma
Hyponatremia
Inappropriate ADH
secretion
Lung small cell anaplastic
(oat cell) carcinoma
Polycythemia
Erythropoietin-like
substance
Renal cell carcinoma
Trousseau
Syndrome
Hypercoagulable state Various carcinomas
Hypoglycemia Insulin-like substance
Various carcinomas and
sarcomas
Carcinoid
Syndrome
5-hydroxy-
indoleacetic acid (5-
HIAA)
Metastatic malignant
carcinoid tumors

25. • From team Omega
It is a process by which normal cells are transformed into cancer cells

26. Malfunction Of MYC Gene

27. Carcinogenesis:Amultiple step process
• Carcinogenesis= A multistep process resulting from the accumulation of
multiple genetic alteration , give rise to transform phenotype .
MUTATION
• Mutation provide cells of precursor lesion with a selective advantage
(Darwinin Selection) . Once initiate, cancer continue undergoes darwinian
selection.
• Over period of time, tumors become more aggressive and acquire greater
malignant potential (Tumor Progression, not represent simply by an
increase in tumor size) .
Non neoplastic
precursor
lesion
Cancer

28. •Some mutation may lethal. Others may spur cell growth by affecting proto-oncogenes or
cancer suppressor genes.

29. Hallmarks of cancer
• Self sufficiency in growth signals
• Insensitivity to growth inhibitory signals
• Evasion (Immortalization) of cell death
• Limitless replicative potential
• Development of sustained angiogenesis
• Ability to invade and metastasize

31. SELF SUFFICIENCY IN GROWTH FACTORS
1.Growth factors:
Normal cells require growth stimulation by growth factors to undergo proliferation.
•Many cancer cells acquire growth self-sufficiency by acquiring ability to synthesize the
same growth factors which they are responsive.
•Another mechanism by which cancer cells acquire growth self-sufficiency is by
interaction with stroma. In some cases, tumor cells send signals to activate normal cells in
the supporting stroma which in turn produce growth factors that promote tumor growth .
2. Growth factor receptors and non-Receptor Tyrosine Kinases
•Mutant receptor proteins deliver continuous mitogenic signals to cells even in the absent
of growth factor in the environment .
•Mutation is overexpression of growth factor to level which growth factor receptor which
render cancer cells hyperresponsive to level of the growth factor that would not normally
trigger proliferation.

32. *** RAS
•Most commonly mutated proto-oncogene in human tumor.
•Normal RAS protein flip back and forth between an excited signal-transmitting state and not active
state.
•Activated RAS stimulates downstream regulators of proliferation by two distinct pathway that
converge on the nucleus and flood it with signal for cell proliferation.
•Mutational activation of these massengers to the nucleus can mimic growth promoting effect of
activation RAS .
•Activating mutation RAS as well as it downstream signaling molecules are very common in wide
variety of tumor .
•Also mutation in RAS mimicked by loss-of—function mutations in the GTPase-activating
proteins with a failure to stimulate GTP hydrolysis and thereby restrain normal RAS protein.

34. INSENSITIVITYTO GROWTH INHIBITORYSIGNALS
• Products of tumor suppresor genes apply brakes to cell proliferation. Disruption of such
genes renders cells refractory to growth inhibition and mimics the growth-promoting
effect on oncogenes .
RB GENES: Governor of the cell cycle
o RB gene product is a DNA-binding protein that expressed in every cell type examined ,
exists in active hypophosphorylated state and an inactive hyperphosphorylated stated.
o RB exerts antiproliferative effect by controlling regulations of G1/S checkpoint (mitosis
cycle) , the portal through which cell must pass before DNA replication commences .

35. o RB in active form, hypophosphorylation bind to E2F transcription factors. This
interaction prevents transcription of genes like cyclin E that are needed for DNA
replication, and so the cell arrested in G1.
o Growth factor signaling leads to cyclin D expression, activation of the cyclin D-CDK4/6
complexes, inactivation of RB by phosphorylation , and thus release E2F .
o Loss of cell cycle control is fundamental to malignant transformation.
o All cancers have disabled G1 checkpoint due to mutation either RB or genes that affect
RB function such as cyclin D, CDK4, and CDKIs

36. TP53 GENE: Guardian of the genome
• The p53-encoding tumor suppressor gene, TP53 , one of the most commonly mutated
genes in human cancers.
• The p53 proteins prevents neoplastic transformation by three interlocking mechanisms :
• Activation of temporary cell cycle arrest (quiescence ) when DNA damage and assist DNA repair
genes.
• Induction of permanent cell cycle arrest (Senescence) when DNA damage genes cannot be
repaired
• Or triggering of programmed death (apoptosis)
• Rb sense external signal, p53 is central monitor of internal stress, directing stress to one
of the three mechanism .
• Example of stresses that trigger the p53 responses pathway including anoxia,
inappropriate oncoprotein activity and damage to integrity of DNA .

39. = The condition or process of deterioration with age.

40. LIMITLESS REPLICATIVE
POTENTIAL:
Telomerase Shortening

42. NORMA
L
TUMOR

43. • Metastatic cascade subdivided into :
Invasion of ECM
Vascular dissemination and homing of tumor
cell
• 2 types of ECM :
 basement membrane both are composed
 Interstitial connective tissue of collagen, glycoprotein
and proteoglycans

45. Loosening of intracellular junctions occurred because
of E-cadherin lost its function (keep cells together &
transmit antigrowth signal) by :
• mutational inactivation of E-cadherin gene
• activation of β-catenin gene
(regulating the coordination of cell–cell adhesion and gene
transcription.)
• inappropriate expression of SNAIL & TWIST
transcription factors (Give Metastatic Ability)
Degradation of basement membrane & interstitial
connective tissue
Tumor cells secrete proteolytic enzymes / induce stromal
cells  elaborate proteases (cathepsin D, urokinase
plasminogen activator, MMPs)  tumor cell invasion
remodel insoluble components of
basement membrane & interstitial
matrix + release ECM-sequestered GF

46. Changes in attachment of tumor cells to ECM
Loss in adhesion in normal cells  apoptosis ; but
tumor cells are resistant to apoptosis, instead caused
matrix modification by cleaving of basement membrane
proteins (collagen IV, laminin) by MMP  generates
novel sites (bind to tumor cells’ receptors)  migration
Migration is directed by tumor cell-derived cytokines
(autocrine motility factors) + cleaved products (collagen &
laminin) + some growth factors + stormal cells (HGF/SCF)

47. • In circulation, tumor cells vulnerable to destruction by host immune cells – it will form emboli & adhere to
the circulating leukocytes = protection
• Site of extravasation & the organ distribution of metastases based on location of primary tumor and its
vascular or lymphatic drainage. This tropism influences by :
i. Expression of adhesion molecules by tumor cells are preferential to the ligand on endothelium of
target organ
ii. Expression of chemokines (participate in chemotaxis of leukocytes) & their receptors – tumor cells use
similar tricks to home in on tissue
iii. When reach the target  colonize the site (tumor cells dependent on a receptive stroma for growth)
• Tumor cells are inefficient in colonizing of distant organs and concept of dormancy refer to prolonged
survival of micrometastases w/o progression

48. Etiology of cancer: carcinogenic events
• Chemical carcinogens
- direct-acting
- Indirect-acting
• Radiation carcinogens
• Viral and microbial oncogenesis

49. CHEMICAL
Direct-acting agents Indirect-acting agents
• Does not require metabolic
conversion to become carcinogenic
• Require metabolic conversion to
become active carcinogenic
• Weak carcinogens • E.g: polycyclic hydrocarbons,
aromatic amines, azo dyes
• E.g: alkylating agents

50. Chemical carcinogens and the tumours
with which they are associated:
Chemical Tumor Comments
Polycyclic hydrocarbon Lung cancer Present on fossil fuels
Aromatic amines Skin cancer
Bladder cancer
Rubber and dye workers
Nitrosamines Gut cancer Proven in animals
Azo dyes Bladder n liver cancer Proven in animals
Alkylating agents
e.g: cyclophosphamide
Leukemia Small risk in human
Other organic chemicals
e.g: vinyl chloride
Liver angiosarcoma PVC manufactures
Arsenic compounds Skin cancer No longer a common
event

51. RADIATION
UV light, x rays, nuclear fission
• Ionizing radiation
- cause chromosome breakage, translocation, less
frequency, point mutation
- Lead to genetic damage n carcinogenesis
- E.g: chronic lymphocytic leukemia , Thyroid carcinoma
(children)
• UV radiation
- Damage DNA by forming pyrimidine dimer
- Cause skin cancer (melanoma, SCC, BCC)
- Risk factor: fair-skinned people

52. •Initiation
- May cause the mutational activation of an oncogen (RAS)
•Promoter
- non-mutagenic, non-tumorigenic
- Induces cell proliferation
- E.g: phorbol esters, hormones, phenols, certain drugs

54. Cancer Progression Due To Constant Irritation

55. Normal

56. Metaplasia

57. Dysplasia

58. Carcinogenesis

59. Xeroderma Pigmentosum
• Autosomal recessive
• Defects in NER genes = (DNA repair mechanism )
• Due to inability to repair DNA damage induced by UV
• 200 X increase risk of skin cancer

60. VIRAL and MICROBIAL
RNA virus:
•Cause by Retrovirus: Human T Cell Lymphotropic Virus-1
(HTLV-1)
•a/w T cell leukemia/lymphoma
•Has tropism for CD4 Tcells  target for neoplastic
transformation
•Transmission: sexual intercourse, blood products or
breastfeedin

61. DNA viruses:
• Human papilloma virus
• Epstein-Barr virus
• Hepatitis B virus
• Kaposi Sarcoma herpes virus