2. DIFFERENTATIONDIFFERENTATION
Extent to which neoplastic cells resemble comparableExtent to which neoplastic cells resemble comparable
normal cell both morphologically & functionallynormal cell both morphologically & functionally
Well differentiatedWell differentiated cancer evolves from maturation orcancer evolves from maturation or
specialization of undifferentiated cells (stem cell)specialization of undifferentiated cells (stem cell)
UndifferentiatedUndifferentiated malignant tumor derives from proliferationmalignant tumor derives from proliferation
without complete maturation of transformed cells.without complete maturation of transformed cells.
Malignant neoplasms range fromMalignant neoplasms range from
Well Differentiated (more then 75% differentiation)Well Differentiated (more then 75% differentiation)
Moderately differentiated (50-75% differentiation)Moderately differentiated (50-75% differentiation)
Poorly differentiated (25-50% differentiation)Poorly differentiated (25-50% differentiation)
Undifferentiated (less then 25% differentiation)Undifferentiated (less then 25% differentiation)
Well differentiated tumors whether benign or malignant tendWell differentiated tumors whether benign or malignant tend
to retain functional characteristics of their normalto retain functional characteristics of their normal
counterparts e.g hormone production by endocrine cells orcounterparts e.g hormone production by endocrine cells or
keratin production by squamous cellskeratin production by squamous cells
5. AnaplasiaAnaplasia
Lack of differentiation, orLack of differentiation, or anaplasia,anaplasia, a hallmarka hallmark
of malignant transformation.of malignant transformation.
Cytologic features to characterize anaplasia are:Cytologic features to characterize anaplasia are:
I.I. Nuclear and cellular pleomorphismNuclear and cellular pleomorphism
II.II. Hyperchromasia with prominent nucleoliHyperchromasia with prominent nucleoli
III.III. Nuclear cytoplasmic ratio; 1:1Nuclear cytoplasmic ratio; 1:1
IV.IV. Abundant mitosisAbundant mitosis
V.V. Loss of polarityLoss of polarity
VI.VI. Tumor giant cellsTumor giant cells
7. DysplasiaDysplasia
Literally means disordered growthLiterally means disordered growth
Seen in epithelial surfaces or glandular epitheliumSeen in epithelial surfaces or glandular epithelium
Pleomorphism, hyperchromasia, mitosis and lossPleomorphism, hyperchromasia, mitosis and loss
of polarity is seenof polarity is seen
Mild & moderate dysplasia not always progress toMild & moderate dysplasia not always progress to
cancer often reversible if inciting cause removedcancer often reversible if inciting cause removed
Marked dysplasia-full thickness involvement ofMarked dysplasia-full thickness involvement of
epithelium calledepithelium called carcinoma-in-situcarcinoma-in-situ, considered a, considered a
pre-invasive neoplasmpre-invasive neoplasm
Adenocarcinoma-in-situAdenocarcinoma-in-situ
14. Biology of Tumor growthBiology of Tumor growth
Distinction between benign andDistinction between benign and
malignant tumor is based on morphologymalignant tumor is based on morphology
and behavior using four criteria:and behavior using four criteria:
1.1. Malignant change in target cell referredMalignant change in target cell referred
to as transformationto as transformation
2.2. Growth of transformed cellsGrowth of transformed cells
3.3. Local invasionLocal invasion
4.4. Distant metastasesDistant metastases
15. CLONAL EVOLUTIONCLONAL EVOLUTION
Neoplastic cells within tumor arises from singleNeoplastic cells within tumor arises from single
cell that incurred genetic change, tumors arecell that incurred genetic change, tumors are
clonal inclonal in
Some cells undergo further mutations passed onSome cells undergo further mutations passed on
to progeny-called evolution or progression andto progeny-called evolution or progression and
explain morphological variations seen in tumoursexplain morphological variations seen in tumours
Subclones grow more rapidly invade andSubclones grow more rapidly invade and
metastaise more rapidly while others abnormalmetastaise more rapidly while others abnormal
subclones dies outsubclones dies out
16. Tumour GrowthTumour Growth
Tumor progression/growth rate determined by anTumor progression/growth rate determined by an
excess of cell production over cell lossexcess of cell production over cell loss
Fast growing tumors – high cell turnoverFast growing tumors – high cell turnover
Proportion of cells in a tumor actively proliferating –Proportion of cells in a tumor actively proliferating –
growth fractiongrowth fraction, most anticancer drugs act only on cells, most anticancer drugs act only on cells
in cyclein cycle
Malignant tumor grows more rapidly than benign but notMalignant tumor grows more rapidly than benign but not
alwaysalways
Growth rate of tumors correlates-level of differentiationGrowth rate of tumors correlates-level of differentiation
Growth of cancers arising from hormone sensitiveGrowth of cancers arising from hormone sensitive
tissues may be affected by hormonal variationstissues may be affected by hormonal variations
associated by pregnancy and menopause e.g breastassociated by pregnancy and menopause e.g breast
cancercancer
Most cells within cancers remain in Go or G1 phase thusMost cells within cancers remain in Go or G1 phase thus
even in rapidly growing tumors growth fraction is onlyeven in rapidly growing tumors growth fraction is only
about 20% or lessabout 20% or less
Debulking of tumour shift tumour cells into cell cycleDebulking of tumour shift tumour cells into cell cycle
17. Tumor GrowthTumor Growth
Rate of tumour growth determined by threeRate of tumour growth determined by three
main factorsmain factors
1.1.Doubling time of neoplastic cellsDoubling time of neoplastic cells
2.2.Fraction of tumour cells in replicative poolFraction of tumour cells in replicative pool
3.3.Rate of cells death by exfoliation orRate of cells death by exfoliation or
apoptosisapoptosis
18. Clinically Detectable TumourClinically Detectable Tumour
Smallest clinically detectable tumour, 30Smallest clinically detectable tumour, 30
population doublings to produce -10population doublings to produce -1099
cellscells
weighing approximately 1gram. Tenweighing approximately 1gram. Ten
additional doublings cycles required toadditional doublings cycles required to
produce a tumour of 1kg (10produce a tumour of 1kg (101212
cells) whichcells) which
is a maximum size compatible with lifeis a maximum size compatible with life
Latent period for clinically detectableLatent period for clinically detectable
tumour longer than 90 daystumour longer than 90 days
19. Concept of Cancer Stem CellsConcept of Cancer Stem Cells
Cancer stem cells could arise from normal tissueCancer stem cells could arise from normal tissue
stem cells or from more differentiated cells that, asstem cells or from more differentiated cells that, as
the part of the transformation process acquire thethe part of the transformation process acquire the
property of self renewalproperty of self renewal
Tumour Initiating Cells (T-ICs)Tumour Initiating Cells (T-ICs)
Cells that allow a human tumour cell to grow andCells that allow a human tumour cell to grow and
maintain itself indefinitely when transplanted into amaintain itself indefinitely when transplanted into a
immunodeficient miceimmunodeficient mice
They have been indentified in many humanThey have been indentified in many human
tumours like, Breast and Colon cancers, GBM,tumours like, Breast and Colon cancers, GBM,
AML in which they constitute 0.1 to 2% of totalAML in which they constitute 0.1 to 2% of total
cellularitycellularity
21. MetastasisMetastasis
Unequivocally marks a tumour as malignantUnequivocally marks a tumour as malignant
Tumour implants (Secondaries)Tumour implants (Secondaries)
discontinuous with the primary tumourdiscontinuous with the primary tumour
Local extensionLocal extension
RecurrenceRecurrence
All Malignant tumours metastasize exceptAll Malignant tumours metastasize except
BCC, GliomasBCC, Gliomas
22. MetastasisMetastasis
Seeding within body cavitiesSeeding within body cavities
Pseudomyxoma peritoneiPseudomyxoma peritonei
Lymphatic SpreadLymphatic Spread
Sentinel lymph nodeSentinel lymph node
Nodal enlargement in proximity to cancerNodal enlargement in proximity to cancer
may be reactive of metastaticmay be reactive of metastatic
Hematogenous spreadHematogenous spread
All sarcomasAll sarcomas
Some Carcinomas like, HCC,RCC,FCSome Carcinomas like, HCC,RCC,FC
23. Epidemiology of common cancersEpidemiology of common cancers
in Pakistanin Pakistan
Common cancers are;Common cancers are;
In male; Lung , oral cavity, larynx, urinary bladderIn male; Lung , oral cavity, larynx, urinary bladder
lymphomas, prostate, esophagus, stomach,lymphomas, prostate, esophagus, stomach,
colorectal ,livercolorectal ,liver
In females; Breast ,oral cavity, gall bladder, ovary & cervixIn females; Breast ,oral cavity, gall bladder, ovary & cervix
Others; thyroid, bone and soft tissue, germ cell tumors,Others; thyroid, bone and soft tissue, germ cell tumors,
skin, renal, leukemia & CNS tumorsskin, renal, leukemia & CNS tumors
Etiological factors;Etiological factors;
pan and betel chewing, naswar, tobacco, insecticidespan and betel chewing, naswar, tobacco, insecticides
and fertilizers, plastic wares, poultry, food adulteration,and fertilizers, plastic wares, poultry, food adulteration,
genetics, viruses, bacteria, fungus, gall stones, chronicgenetics, viruses, bacteria, fungus, gall stones, chronic
inflammation, U-V rays and radiationsinflammation, U-V rays and radiations
25. Age adjusted cancer death rate inAge adjusted cancer death rate in
selected site in USAselected site in USA
26. Precancerous conditionsPrecancerous conditions
Non-neoplastic disorders
chronic atrophic gastritis of pernicious anemia,
solar keratosis of the skin,
chronic ulcerative colitis,
leukoplakia of the oral cavity, vulva, and penis
Follicular variant of papillary carcinoma arising in in long
standing multinodular goiter
Benign neoplasia
Villous adenoma colon, as it increases in size, develops
cancerous change in up to 50% of cases.
Most benign neoplasms do not become cancerous,
albeit rarely for example, leiomyosarcoma beginning in a
leiomyoma, and carcinoma appearing in longstanding
pleomorphic adenoma of salivary glands.
Carcinoma-in- situ