Premalignant lesions

PATHOLOGYPATHOLOGY OFOF
PREMALIGNANTPREMALIGNANT LESIONSLESIONS
Dr. Nitin ChikhaleDr. Nitin Chikhale

IntroductionIntroduction
Lesion that isLesion that is not itself malignantnot itself malignant, but has, but has greatergreater
probability of becoming soprobability of becoming so than normal tissue.than normal tissue.
Cancinogenesis – a multistep process,Cancinogenesis – a multistep process,
Cancer evolve through a series ofCancer evolve through a series of intermediate lesionsintermediate lesions
whichwhich have greater premalignant potentialhave greater premalignant potential than onethan one
that preceded it,that preceded it,
At risk cell population can be sampled for detection ofAt risk cell population can be sampled for detection of
early abnormality e.g. cervix by pap smear,early abnormality e.g. cervix by pap smear,
Difficult in some organs like pancreasDifficult in some organs like pancreas

Chronic persistent stimulusChronic persistent stimulus
Tissue damageTissue damage
RegenerationRegeneration ProliferationProliferation
Hyperplasia / MetaplasiaHyperplasia / Metaplasia
DysplasiaDysplasia
Ca. in situCa. in situ
Invasive CarcinomaInvasive Carcinoma
HormonesHormones
Chr. irritationChr. irritation

HyperplasiaHyperplasia
↑↑ iin no. of cells in an organ or tissue,n no. of cells in an organ or tissue,
Occur if, cellular populOccur if, cellular populnn
is capable synthesizingis capable synthesizing
DNA & undergoing mitosis,DNA & undergoing mitosis,
Process can beProcess can be PhysiologicalPhysiological oror PathologicalPathological,,
MechanismMechanism ––
 ↑↑ production ofproduction of growth factorsgrowth factors (GF),(GF),
 ↑↑ GF receptorsGF receptors on responding cells,on responding cells,
 ActivActivnn
of particularof particular intracellular signaling pathwayintracellular signaling pathway,,

Compensatory hyperplasiaCompensatory hyperplasia
–– not only by proliferation of remaining cells, butnot only by proliferation of remaining cells, but
also by, development of new cells byalso by, development of new cells by Stem cells,Stem cells,
Pathological HyperplasiaPathological Hyperplasia :-:-
 Excess stimulExcess stimulnn
byby hormonehormone oror GF,GF,
e.g. – Endometrial hyperplasia by estrogen,e.g. – Endometrial hyperplasia by estrogen,
–– BPH by androgens,BPH by androgens,
 Regress, if , stimulus is removed,Regress, if , stimulus is removed,
 Fertile soil for cancer developmentFertile soil for cancer development
HyperplasiaHyperplasia

MetaplasiaMetaplasia
Reversible change with replacement of one adultReversible change with replacement of one adult
cell type (epi / mesen.) by another adult cell type,cell type (epi / mesen.) by another adult cell type,
Adaptive response of sensitive cells to stress,Adaptive response of sensitive cells to stress,
Columnar to squamous –Columnar to squamous – MC epi. metaplasiaMC epi. metaplasia
 e.g. in respiratory tract in chronic smokers,e.g. in respiratory tract in chronic smokers,
 ↓↓ levels of vit. A induce sq. metaplasia,levels of vit. A induce sq. metaplasia,
Squamous to columnar – e.g. Barrette’s esophagus,Squamous to columnar – e.g. Barrette’s esophagus,
Connective tissue (mesenchymal) metaplasia mayConnective tissue (mesenchymal) metaplasia may
occur e.g. Myositis ossificans,occur e.g. Myositis ossificans,

MechanismMechanism ––
 No change in phenotype of differentiated cells,No change in phenotype of differentiated cells,
 Reprogramming of stem cellsReprogramming of stem cells,,
 Differentiation to particular lineage caused byDifferentiation to particular lineage caused by
cytokines & GFscytokines & GFs,,
 Involve tissue specific differentiation genes,Involve tissue specific differentiation genes,
e.g. Bone Morphogenetic Proteine.g. Bone Morphogenetic Protein
Epithelial metaplasia – double edged sword,Epithelial metaplasia – double edged sword,
Influences, if persist, may produce malignantInfluences, if persist, may produce malignant
transformation of metaplastic epi.transformation of metaplastic epi.
MetaplasiaMetaplasia

DysplasiaDysplasia
Disordered growth,Disordered growth,
Loss of uniformity of individual cells and theirLoss of uniformity of individual cells and their
architectural orientation,architectural orientation,
Example of extreme adaptive response,Example of extreme adaptive response,
Characterized by –Characterized by –
 Pleomorphism,Pleomorphism,
 Hyperchromatic nuclei,Hyperchromatic nuclei,
 ↑↑ no. of mitoses (N / Abn.),no. of mitoses (N / Abn.),
Marked dysplasia not invading BM –Marked dysplasia not invading BM – Ca. in situCa. in situ,,
Does not necessarily progress to carcinoma,Does not necessarily progress to carcinoma,

FEMALE GENITAL TRACTFEMALE GENITAL TRACT

Ca. cervix was leading cause of death,Ca. cervix was leading cause of death,
↓↓ bby 2/3y 2/3rdrd
due todue to ↑ detection rate of precancerous↑ detection rate of precancerous
lesions,lesions,
Papanicolaou cyto. test & improved colposcopyPapanicolaou cyto. test & improved colposcopy
& biopsy techniques,& biopsy techniques,

Precancerous lesionsPrecancerous lesions
of Cervixof Cervix
Majority of Ca. Cx preceded by precancerous lesMajority of Ca. Cx preceded by precancerous lesn,n,
LesLesnn
exists for as long as 20 yrs. shedding abnormalexists for as long as 20 yrs. shedding abnormal
cells,cells,
Do not invariably progress to invasive ca., but, riskDo not invariably progress to invasive ca., but, risk ↑↑
with severity ofwith severity of leslesnn
(CIN III),(CIN III),
High gradeHigh grade leslesnn
associated with high risk HPV,associated with high risk HPV,

Pathogenesis of cervical neoplasiaPathogenesis of cervical neoplasia

ClassificationsClassifications
Dysplasia (Oldest) :-Dysplasia (Oldest) :-
- Mild - Moderate - Severe (Ca. in situ),- Mild - Moderate - Severe (Ca. in situ),
Cervical Intraepithelial Neoplasia (CIN) :-Cervical Intraepithelial Neoplasia (CIN) :-
- CIN I - CIN II - CIN III (Ca. in situ),- CIN I - CIN II - CIN III (Ca. in situ),
Low gradeLow grade andand High gradeHigh grade Intraepithelial LesIntraepithelial Lesnn
..

Cervical Intraepithelial Neoplasia (CIN)Cervical Intraepithelial Neoplasia (CIN)
Term related to squamous epithelium,Term related to squamous epithelium,
In majority of cases, affect areas of sq. epi. at TZ,In majority of cases, affect areas of sq. epi. at TZ,
Extension to cervical canal – common,Extension to cervical canal – common,
May extend along upper vagina and endometrial cavityMay extend along upper vagina and endometrial cavity
((up to Fallopian tubesup to Fallopian tubes))

Basal cell layerBasal cell layer
Regular arrangement andRegular arrangement and
maturationmaturation
Enlarged, hyperchromatic nucleiEnlarged, hyperchromatic nuclei
(Viral cytopathic effect)(Viral cytopathic effect)
Cytoplasmic halosCytoplasmic halos
(koilocytotic atypia)(koilocytotic atypia)

Hyperchromatic nuclei,Hyperchromatic nuclei, ↑↑ mitotic fig.mitotic fig.
Atypical cells withAtypical cells with ↑↑ N:C ratioN:C ratio
& nuclear pleomorphism& nuclear pleomorphism
Persistent differentiationPersistent differentiation
Complete loss of diff. withComplete loss of diff. with
atypical cells in all layers ofatypical cells in all layers of
epitheliumepithelium

Cervical IntraepithelialCervical Intraepithelial
Neoplasia (CIN)Neoplasia (CIN)
Cervical cytologyCervical cytology
((Pap smearPap smear) :-) :-
 Progressive loss ofProgressive loss of
cellular diff. on surfacecellular diff. on surface
 Increase N:C ratio withIncrease N:C ratio with
reduction in cytoplasmreduction in cytoplasm
with increasing grade ofwith increasing grade of
lesionlesion
 NormalNormal
 CIN ICIN I
 CIN IICIN II
 CIN IIICIN III

Not all lesions start as CIN I,Not all lesions start as CIN I,
D/Ds:-D/Ds:- i) Florid squamous metaplasia,i) Florid squamous metaplasia,
ii) Transitional metaplasia,ii) Transitional metaplasia,
Iodine test (Iodine test (used to delineate dis. extent before conizationused to delineate dis. extent before conization))
may cause (may cause (esp. in abnormal cells)esp. in abnormal cells) :-:-
 Cell shrinkage,Cell shrinkage,
 Cytoplasmic eosinophilia & vacuolation,Cytoplasmic eosinophilia & vacuolation,
 Pyknosis of nucleiPyknosis of nuclei

In situ Adenocarcinoma of CxIn situ Adenocarcinoma of Cx
Cervical Intraepithelial GlandularCervical Intraepithelial Glandular
NeoplasiaNeoplasia :-:-
 Controversial concept,Controversial concept,
 Cytological atypia,Cytological atypia,
 Majority positive for CEA.Majority positive for CEA.
 Decreased hormone receptors.Decreased hormone receptors.
 Imp D/Ds – Tubal hyperplasia,Imp D/Ds – Tubal hyperplasia,
 Strong association with HPV inf.Strong association with HPV inf.
(strong positivity for p16)(strong positivity for p16)

EndometriumEndometrium
Cystic hyperplasia,Cystic hyperplasia,
Atypical proliferative hyperplasia,Atypical proliferative hyperplasia,
Atypical secretory hyperplasia,Atypical secretory hyperplasia,
Carcinoma in situ,Carcinoma in situ,
Polyp, with dysplastic change.Polyp, with dysplastic change.

Proliferating endometrium featuring glandularProliferating endometrium featuring glandular
architectural abnormality,architectural abnormality,
Commonly presents as abnormal uterineCommonly presents as abnormal uterine
bleeding,bleeding,
Proliferating glands –Proliferating glands –
 Glandular crowding,Glandular crowding,
 Cystic dilatation or glandular budding,Cystic dilatation or glandular budding,
 Stratification / Pseudostratification,Stratification / Pseudostratification,
 Varying degrees of nuclear atypia,Varying degrees of nuclear atypia,
(Nuclear enlargement, prominent nucleoli)(Nuclear enlargement, prominent nucleoli)
Endometrial HyperplasiaEndometrial Hyperplasia

WHO classificationWHO classification (1994) :-(1994) :-
 Architectural feature -Architectural feature -
 Simple,Simple,
 Complex (Adenomatous),Complex (Adenomatous),
 Cytological features –Cytological features –
 Without atypia,Without atypia,
 With atypia,With atypia,

Simple TypicalSimple Typical
Complex AtypicalComplex Atypical

Types of HyperplasiaTypes of Hyperplasia Progression to CaProgression to Ca. (%). (%)
Simple typicalSimple typical 11
Complex typicalComplex typical 33
Simple atypicalSimple atypical 88
Complex atypicalComplex atypical 2929

Endometrial Intraepithelial Neoplasia (EIN) :-Endometrial Intraepithelial Neoplasia (EIN) :-
 Recently proposed byRecently proposed by Mutter et alMutter et al (2000),(2000),
 Glands with neoplastic change without stromal invasion,Glands with neoplastic change without stromal invasion,
 Term ‘Term ‘stage 0 castage 0 ca.’ is used.’ is used
Endometrial hyperplasiaEndometrial hyperplasia EIN / CISEIN / CIS Invasive Ca.Invasive Ca.
Criteria :-Criteria :-
 Architectural – gland area > stroma (in localized region),Architectural – gland area > stroma (in localized region),
 Cytological – different cytology between crowded &Cytological – different cytology between crowded &
normal glandsnormal glands

Female BreastFemale Breast
Epithelial proliferative changes –Epithelial proliferative changes – ↑↑ risk of Ca.risk of Ca.
 Mild (3 – 4 epithelial cell layers),Mild (3 – 4 epithelial cell layers),
 Moderate to Florid (> 4 layers),Moderate to Florid (> 4 layers),
 Atypical (ADH & ALH),Atypical (ADH & ALH),
Categories on basis of risk of invasive ca. :–Categories on basis of risk of invasive ca. :–
CategoriesCategories Type of HyperplasiaType of Hyperplasia RiskRisk
II No / Mild hyperplasiaNo / Mild hyperplasia nono ↑ risk↑ risk
IIII moderate / floridmoderate / florid 1.5 – 2 times1.5 – 2 times
IIIIII ADH / ALHADH / ALH 5 times5 times
IVIV CISCIS 8 – 10 times8 – 10 times

DCISDCIS :-:-
 Intratubular lumina –Intratubular lumina –
regular, rounded spacesregular, rounded spaces
 Long axis of nuclei – atLong axis of nuclei – at
right angle to axis ofright angle to axis of
bridge ‘Roman arches’bridge ‘Roman arches’
 No streaming pattern,No streaming pattern,
 Monotonous epi. Cells,Monotonous epi. Cells,
 Cytoplasm pale,Cytoplasm pale,
homogenoushomogenous
 MyoepitheliumMyoepithelium
incomplete,incomplete,
 ↑↑ (abn) m(abn) mitotic activity,itotic activity,
 Necrosis / Hemorrhage +,Necrosis / Hemorrhage +,
SolidSolid CribriformCribriform
MicropapillaryMicropapillaryComedo Ca.Comedo Ca.

ADH :-ADH :-
 Lesion with cytologic and archietectural featuresLesion with cytologic and archietectural features
indistinguishable from low grade DCIS but,indistinguishable from low grade DCIS but,
 intimately admixed with usual ductal hyperplasia,intimately admixed with usual ductal hyperplasia,
 showing only partial inv. of TDLU,showing only partial inv. of TDLU,
 +nce of features of DCIS in+nce of features of DCIS in ≤≤ 2 glandular spaces2 glandular spaces
(Page & Rodgers)(Page & Rodgers),,
 DCIS involvingDCIS involving ≤ 2 mm area≤ 2 mm area (Tavassoli & Norris)(Tavassoli & Norris)

LCISLCIS :-:-
 Monomorphic, small, roundMonomorphic, small, round
cells withcells with ↑↑ N:C ratio,N:C ratio,
 Uncohesive, regularly spacedUncohesive, regularly spaced
 Fill lumen completely,Fill lumen completely,
 Moderate (> 50 % acini)Moderate (> 50 % acini)
lobular distension,lobular distension,
 Pagetoid spread seenPagetoid spread seen
ALHALH :-:-
 Similar cells with –Similar cells with –
 Slightly distendingSlightly distending
lobule,lobule,
 Central lumina +,Central lumina +,
 < 50 % of acini affected,< 50 % of acini affected,
 Other cells like spindleOther cells like spindle
cells & leucocytes +,cells & leucocytes +,

Radial scarRadial scar 1.8 times1.8 times ↑↑
Sclerosing adenosisSclerosing adenosis
1.7 times1.7 times ↑,↑,
6.7 (SA + ADH)6.7 (SA + ADH)
FibroadenomaFibroadenoma
3.1 times3.1 times ↑↑
3.7 (family history +)3.7 (family history +)
Atypical apocrine adenosisAtypical apocrine adenosis 5.5 times5.5 times ↑↑
Other Premalignant LesionsOther Premalignant Lesions

GASTROINTESTINALGASTROINTESTINAL
TRACTTRACT

Barrett’s EsophagusBarrett’s Esophagus
Distal squamous epithelium replaced by metaplasticDistal squamous epithelium replaced by metaplastic
columnar epithelium,columnar epithelium,
Complication of long standing GERD (10 % pts.),Complication of long standing GERD (10 % pts.),
White males / 40 – 60 yrs,White males / 40 – 60 yrs,
Two types :- a) Long seg. (> 3cm from GEJ),Two types :- a) Long seg. (> 3cm from GEJ),
b) Short seg. (< 3cm from GEJ),b) Short seg. (< 3cm from GEJ),
Two criterion for diagnosis :-Two criterion for diagnosis :-
 Endoscopic evidence of columnar lining above GEJ,Endoscopic evidence of columnar lining above GEJ,
 Histologic evidence of intestinal metaplasia in biopsy.Histologic evidence of intestinal metaplasia in biopsy.
Single most imp. risk factor for carcinoma.Single most imp. risk factor for carcinoma.

 GrossGross :-:-
• Red velvety mucosa between, pale pinkRed velvety mucosa between, pale pink
squamous & light brown gastric mucosa,squamous & light brown gastric mucosa,
 MicroscopyMicroscopy :-:-
• squamous epi. replaced by columnar,squamous epi. replaced by columnar,
• +nce of goblet cells = definitive diagnosis+nce of goblet cells = definitive diagnosis

Carcinoma nearly always preceded by dysplasia,Carcinoma nearly always preceded by dysplasia,
Dysplasia nearly always arise in incomplete intestinalDysplasia nearly always arise in incomplete intestinal
metaplasia,metaplasia,
Dysplasia should be distinguish from reactive hyperplasiaDysplasia should be distinguish from reactive hyperplasia
30 – 40 fold30 – 40 fold ↑↑ risk of adenocarcinoma for long seg. Barrett’srisk of adenocarcinoma for long seg. Barrett’s

LGDLGD
HGDHGD
Diagnostic categories :-Diagnostic categories :-
 Negative for dysplasia,Negative for dysplasia,
 Indefinite for dysplasia (IND),Indefinite for dysplasia (IND),
 Low grade dysplasia (LGD),Low grade dysplasia (LGD),
 High grade dysplasia (HGD),High grade dysplasia (HGD),
 Intramucosal carcinoma,Intramucosal carcinoma,

Molecular alterations :-Molecular alterations :-
 Mutation & overexpression of p53,Mutation & overexpression of p53,
 myc amplification,myc amplification,
 Mutations ofMutations of ββ--catenin & cadherin/catenincatenin & cadherin/catenin
membrane complex,membrane complex,
 Microsatellite instabilityMicrosatellite instability
Other malignant tumours arising in BE :-Other malignant tumours arising in BE :-
 Adenosquamous Ca.,Adenosquamous Ca.,
 Squamous cell Ca.,Squamous cell Ca.,
 Sarcomatoid Ca.Sarcomatoid Ca.
 Neuroendocrine Ca.Neuroendocrine Ca.
 Choriocarcinoma.Choriocarcinoma.

STOMACHSTOMACH
Chronic GastritisChronic Gastritis
Chronic mucosal inflammatory change leading toChronic mucosal inflammatory change leading to
mucosal atrophymucosal atrophy andand intestinal metaplasiaintestinal metaplasia,,
May becomeMay become dysplasticdysplastic & forms fertile soil for Ca.& forms fertile soil for Ca.
Common risk factor :-Common risk factor :-
 Chronic infection byChronic infection by H. pyloriH. pylori,,
 Autoimmune gastritis,Autoimmune gastritis,
 Toxins – Alcohol & Smoking,Toxins – Alcohol & Smoking,
Chronic gastritisChronic gastritis → Multifocal atrophy → ↓ acid→ Multifocal atrophy → ↓ acid
secretion (Hypochlorhydria) →secretion (Hypochlorhydria) → Intestinal metaplasiaIntestinal metaplasia
→→ DysplasiaDysplasia → Ca.→ Ca.

Chronic GastritisChronic Gastritis
 GrossGross :-:-
• Reddened mucosa with coarser texture,Reddened mucosa with coarser texture,
• Thickened rugal folds,Thickened rugal folds,
• Long standing cases – thin & flat mucosaLong standing cases – thin & flat mucosa
 MicroscopyMicroscopy :-:-
 infiltration of lymphocytes (follicles withinfiltration of lymphocytes (follicles with
germinal center) &germinal center) & plasma cellsplasma cells,,
 +nce of neutrophils = active inflam.+nce of neutrophils = active inflam.
 Regenerative changeRegenerative change :- constant feature,:- constant feature,
 MetaplasiaMetaplasia :- 2 types:- 2 types
1) Pyloric metaplasia of fundic mucosa,1) Pyloric metaplasia of fundic mucosa,
2) Intestinal metaplasia,2) Intestinal metaplasia,
 AtrophyAtrophy :-:- ↓↓ parietal cellsparietal cells
- G-cell hyperplasia (carcinoid)- G-cell hyperplasia (carcinoid)
 DysplasiaDysplasia :- long standing chr. cases:- long standing chr. cases
Normal epitheliumNormal epithelium
Metaplastic columnarMetaplastic columnar
epitheliumepithelium

H. pylori GastritisH. pylori Gastritis
Two types :-Two types :-
 Predominantly Antral type ( high acid production),Predominantly Antral type ( high acid production),
 Pangastritis ( Multifocal Atrophic Gastritis),Pangastritis ( Multifocal Atrophic Gastritis),
IL 1IL 1ββ » powerful gastric acid inhibitor,» powerful gastric acid inhibitor,
» ↑ levels in pangastritis» ↑ levels in pangastritis
↑↑ risk of Gastric ca. & Lymphoma (more in Pangastritis)risk of Gastric ca. & Lymphoma (more in Pangastritis)
Diseases ass. with H. pylori infectionDiseases ass. with H. pylori infection
DiseasesDiseases AssociationAssociation
 Chronic GastritisChronic Gastritis StrongStrong
 Peptic ulcer dis.Peptic ulcer dis. StrongStrong
 Gastric Ca.Gastric Ca. StrongStrong
 MALT LymphomaMALT Lymphoma Definitive etiologic roleDefinitive etiologic role

Gastric Carcinoma :-Gastric Carcinoma :-
 Adenocarcinoma of Intestinal type,Adenocarcinoma of Intestinal type,
 Arises in intestinal metaplastic epi.Arises in intestinal metaplastic epi.
Lymphoma (MALToma) :-Lymphoma (MALToma) :-
 Relation strong with lymphoma ,Relation strong with lymphoma ,
 ↓↓ H. pylori = regression of lymphoma (initially),H. pylori = regression of lymphoma (initially),
 Arise in MALT (B cells of marginal zone),Arise in MALT (B cells of marginal zone),
 Chr. InfectionChr. Infection → ↑ Lymphocytic infiltration → B cell→ ↑ Lymphocytic infiltration → B cell
proliferation → genetic abn. t (11,18) → MALTomaproliferation → genetic abn. t (11,18) → MALToma
H. pylori GastritisH. pylori Gastritis

Peptic UlcerPeptic Ulcer
Benign Peptic UlcerBenign Peptic Ulcer Malignant Peptic UlcerMalignant Peptic Ulcer
AgeAge YoungerYounger OldOld
LocationLocation
Lesser curvature &Lesser curvature &
antrumantrum
Greater curvature &Greater curvature &
antrumantrum
Size &Size &
EdgesEdges
< 2cm,< 2cm,
Punched outPunched out
> 4 cm,> 4 cm,
SlopingSloping
MarginsMargins
At same level of surr.At same level of surr.
mucosa & convergingmucosa & converging
rugae.rugae.
Rolled, everted &Rolled, everted &
indurated.indurated.
Medical t/tMedical t/t RespondingResponding Non respondingNon responding

INTESTINAL POLYPSINTESTINAL POLYPS
Neoplastic epithelial lesions :-Neoplastic epithelial lesions :-
 AdenomasAdenomas
Benign polyps :-Benign polyps :-
 Hamartomatous polyps,Hamartomatous polyps,
 Juvenile polyposis syndrome,Juvenile polyposis syndrome,

Colon > Small intestineColon > Small intestine
Small intestine – Duodenum & jejunum > IleumSmall intestine – Duodenum & jejunum > Ileum
Single / Multiple, Pedunculated / Sessile,Single / Multiple, Pedunculated / Sessile,
Microscopically :-Microscopically :-
 TubularTubular
 VillousVillous
 Tubulo-villousTubulo-villous
Risk of malignancy correlated withRisk of malignancy correlated with ––
 Polyp size (>4 cm),Polyp size (>4 cm),
 Histologic architecture (sessile villous lesions),Histologic architecture (sessile villous lesions),
 Severity of epithelial dysplasia (Low / HighSeverity of epithelial dysplasia (Low / High
grade)grade)
AdenomasAdenomas

Villous adenoma :-Villous adenoma :-
 Commom in old age,Commom in old age,
 Rectum & recto-sigmoid,Rectum & recto-sigmoid,
 GROSS :-GROSS :-
 Large, sessile (upto 10 cm)Large, sessile (upto 10 cm)
 Cauliflower like masses,Cauliflower like masses,
 MICRO :-MICRO :-
 Frondlike, villiformFrondlike, villiform
mucosal extensions,mucosal extensions,
 Covered by dysplasticCovered by dysplastic
columnar epi.,columnar epi.,
 > 4 cm> 4 cm,, sessilesessile – 40 % risk– 40 % risk
of malignancyof malignancy
AdenomasAdenomas

Adenoma-Carcinoma sequenceAdenoma-Carcinoma sequence
 Described by Fearon and Vogelstein,Described by Fearon and Vogelstein,
 Sequential malignant transformation of polyps,Sequential malignant transformation of polyps,

Hamartomatous PolypHamartomatous Polyp
 MicroMicro :-:-
• Glands supported by broad bandsGlands supported by broad bands
of smooth muscle fibres,of smooth muscle fibres,
• Bands thick in centre & thinner atBands thick in centre & thinner at
periphery,periphery,
• Intermingling of glandsIntermingling of glands
 Most common childrens < 5 yrs,Most common childrens < 5 yrs,
 Juvenile polyposis synd :–Juvenile polyposis synd :–
- 50 – 100 polyps,- 50 – 100 polyps,
- Risk of adenoca.- Risk of adenoca.
 In adult – ‘In adult – ‘Retention polyps’Retention polyps’
-- Occur singly,Occur singly,
- No malignant potential- No malignant potential

LARGE INTESTINELARGE INTESTINE
Ulcerative ColitisUlcerative Colitis
20 -25 yrs, F > M,20 -25 yrs, F > M,
Ulcero-inflammatory dis. limited to colon &Ulcero-inflammatory dis. limited to colon &
affecting onlyaffecting only mucosa & submucosamucosa & submucosa,,
Continuous inv.Continuous inv. without skip leswithout skip lesnn
& well& well
formed granulomas,formed granulomas,
Ass. with –Ass. with – polyarthritis, sacroiliitis, ankylosingpolyarthritis, sacroiliitis, ankylosing
spondylitis, uveitis & primary sclerosingspondylitis, uveitis & primary sclerosing
cholangitis,cholangitis,

Gross :-Gross :-
 Continuous disease with NContinuous disease with N
serosa,serosa,
 Reddened, granular & friableReddened, granular & friable
mucosa,mucosa,
 Bulging islands of regen.Bulging islands of regen.
Mucosa – ‘Mucosa – ‘PseudopolypsPseudopolyps’’
Micro :-Micro :-
 Diffuse MN infiltrate in LP,Diffuse MN infiltrate in LP,
 Collection of neutrophils inCollection of neutrophils in
crypt lumina – ‘crypt lumina – ‘crypt abscesscrypt abscess’’
 Frequent areas of dysplasia.Frequent areas of dysplasia.

Risk of malignancy =Risk of malignancy = 5 – 10 %,5 – 10 %,
Higher risk, when –Higher risk, when –
 Disease involve entire colon,Disease involve entire colon,
 Continuous, unremitting dis.,Continuous, unremitting dis.,
 Long standing dis. ( for > 10 yrs.),Long standing dis. ( for > 10 yrs.),
Almost always preceded byAlmost always preceded by dysplasia,dysplasia,
 Occurs inOccurs in flat mucosaflat mucosa,,
 Should be disting. fromShould be disting. from regenerative atypiaregenerative atypia
(away from areas of active inflam(away from areas of active inflamnn
),),
 Can beCan be Low gradeLow grade oror High gradeHigh grade..

IHC :-IHC :-
 ↑↑ sialomucin production,sialomucin production,
 ↑↑ reactivity for CEA,reactivity for CEA,
 Cytoplasmic stainingCytoplasmic staining forfor sucrase-isomaltasesucrase-isomaltase,,
( only( only membranous stainingmembranous staining in inflam / regen. mucosa ),in inflam / regen. mucosa ),
Molecular studies :-Molecular studies :-
 p53 mutation,p53 mutation,
 KRAS mutation,KRAS mutation,
 Microsatellite instabilityMicrosatellite instability,,

22ndnd
– 3– 3rdrd
decade,decade,
F > M,F > M,
Regional enteritis (Skip lesions),Regional enteritis (Skip lesions),
Gross :-Gross :-
 Rubbery & thick int. wall,Rubbery & thick int. wall,
 ‘‘cobblestone app.’ d/t skip lescobblestone app.’ d/t skip lesnn
,,
 Initially, focal mucosal ulcersInitially, focal mucosal ulcers
resembling aphthous ulcers,resembling aphthous ulcers,
 Later, ulcer coalesce into long,Later, ulcer coalesce into long,
serpentine linear ulcers alongserpentine linear ulcers along
axis of bowel,axis of bowel,
Small IntestineSmall Intestine
Crohn’s DiseaseCrohn’s Disease

Small IntestineSmall Intestine
Crohn’s DiseaseCrohn’s Disease
Micro :-Micro :-
 Mucosal inflammMucosal inflammnn
,,
 Chronic mucosal damage,Chronic mucosal damage,
 Ulceration,Ulceration,
 Transmural inflammTransmural inflammnn
,,
 Non-caseating granulomas,Non-caseating granulomas,
5 – 6 fold increased risk of5 – 6 fold increased risk of
malignancymalignancy

Oral CavityOral Cavity
Oral cancers common worldwide with high mortality,Oral cancers common worldwide with high mortality,
Screening and early detection in high risk populScreening and early detection in high risk populnn
possible, but,possible, but,
Visual detection of definitive premalignant lesVisual detection of definitive premalignant lesnn
isis
difficult -difficult -
 Early cancer fails to demonstrate charact. of advancedEarly cancer fails to demonstrate charact. of advanced
carcinoma,carcinoma,
 Clinical presentation is highly heterogenousClinical presentation is highly heterogenous,,
LeukoplakiaLeukoplakia andand ErythroplakiaErythroplakia

LeukoplakiaLeukoplakia :-:-
 WHO defWHO defnn
‘‘white patch or plaque that can’t bewhite patch or plaque that can’t be
scraped off and not characterized clinically &scraped off and not characterized clinically &
pathologically as any other lesionpathologically as any other lesion.’.’
 Equivalent to ‘Equivalent to ‘keratosis’keratosis’ of other sites,of other sites,
 Worldwide prevalence 3 %,Worldwide prevalence 3 %,
 5 – 25 % premalignant,5 – 25 % premalignant,
 All leukoplakias must be considered premalignant,All leukoplakias must be considered premalignant,
unless proved otherwiseunless proved otherwise

LeukoplakiaLeukoplakia
Thin with well demarkated bordersThin with well demarkated borders Diffuse and thickDiffuse and thick
Irregular with granular surfaceIrregular with granular surface Diffuse and corrugatedDiffuse and corrugated

MicroscopyMicroscopy :-:-
 Spectrum of epi. changes fromSpectrum of epi. changes from,,
 Hyperkeratosis overlying acanthotic mucosa, to,Hyperkeratosis overlying acanthotic mucosa, to,
 Markedly dysplastic epitheliumMarkedly dysplastic epithelium,,
 More dysplasia = more subjacent inflam.More dysplasia = more subjacent inflam.
infiltrateinfiltrate (lymphocytes & Macrophages)(lymphocytes & Macrophages)
LeukoplakiaLeukoplakia

ErythroplakiaErythroplakia :-:-
 Similar lesion with red color,Similar lesion with red color,
 Less common, but, more ominous,Less common, but, more ominous,
 Epithelium markedly dysplastic,Epithelium markedly dysplastic,
 Higher risk of malignant transformHigher risk of malignant transformnn,,
Histologically –Histologically –
 Majority with superficial erosion &Majority with superficial erosion &
dysplasia,dysplasia,
 Intense subepithelial inflam. reactIntense subepithelial inflam. reactnn
,,
 Vascular dilatation (Red color)Vascular dilatation (Red color)

Hepato-biliary systemHepato-biliary system

Viral hepatitis,Viral hepatitis,
Liver cirrhosis,Liver cirrhosis,
Liver cell dysplasia,Liver cell dysplasia,
Adenomatous hyperplasia,Adenomatous hyperplasia,

 Complication of both, HBV & HCV,Complication of both, HBV & HCV,
 Not only through cirrhosis but also in noncirrhoticNot only through cirrhosis but also in noncirrhotic
livers,livers,
 Now regarded as a leading cause of HCC,Now regarded as a leading cause of HCC,
 Development of HCC after 15 yrs,Development of HCC after 15 yrs,
 27 % in Hepatitis B,27 % in Hepatitis B,
 75 % in Hepatitis C,75 % in Hepatitis C,
 HBV / HCV surface Ag found in > 90 % of HCC,HBV / HCV surface Ag found in > 90 % of HCC,
 X Ag of HBV – stimulates viral gene expressionX Ag of HBV – stimulates viral gene expression
and replicationand replication
Viral HepatitisViral Hepatitis

Risk markers for HCC -Risk markers for HCC -
 ↑↑ proliferative indices,proliferative indices,
 ↑↑ levels of AFP,levels of AFP,
Viral HepatitisViral Hepatitis

CirrhosisCirrhosis
60 – 80 %60 – 80 % of ca. developed in cirrhotic livers,of ca. developed in cirrhotic livers,
More inMore in MacronodularMacronodular cirrhosis, clinically apparentcirrhosis, clinically apparent
or silent,or silent,
Incidence of HCC in cirrhotic liver =Incidence of HCC in cirrhotic liver = 3 %,3 %,
Also ass. withAlso ass. with Biliary cirrhosisBiliary cirrhosis,,
Ca. have tendency for widespread inv.,Ca. have tendency for widespread inv.,

Liver cell dysplasiaLiver cell dysplasia
 Large cell DysplasiaLarge cell Dysplasia ––
 Cellular enlargement,Cellular enlargement,
 Nuclear pleomorphism & multinucleation,Nuclear pleomorphism & multinucleation,
 Normal N:C ratio,Normal N:C ratio,
Conditions of liverConditions of liver
Incidence of large cellIncidence of large cell
dysplasiadysplasia
Normal liverNormal liver 1 %1 %
HCC in normal liverHCC in normal liver 6.9 %6.9 %
CirrhosisCirrhosis 20.3 %20.3 %
HCC with cirrhosisHCC with cirrhosis 64.5 %64.5 %
Anthony et alAnthony et al

Large cell DysplasiaLarge cell Dysplasia :-:-
 Strong relationship with +nce of HBV surface Ag,Strong relationship with +nce of HBV surface Ag,
 Also seen in other forms of hepatitis,Also seen in other forms of hepatitis, αα11 antitrypsin def.antitrypsin def.
 Aneuploidy – common,Aneuploidy – common,
Small cell DysplasiaSmall cell Dysplasia :-:-
 ↓↓ hepatocytic cytoplasm & ↑ N:C ratio,hepatocytic cytoplasm & ↑ N:C ratio,
 ↑↑ chromatin density,chromatin density,
 Less chances of malignancy than LCD,Less chances of malignancy than LCD,
Liver cell dysplasiaLiver cell dysplasia

Adenomatous hyperplasiaAdenomatous hyperplasia
Atypical nodular lesions in cirrhosis not fulfillingAtypical nodular lesions in cirrhosis not fulfilling
criteria for HCCcriteria for HCC,,
 Macroregenerative nodule (ordinaryMacroregenerative nodule (ordinary
adenomatous hyper.)adenomatous hyper.) – No premalignant– No premalignant
potential,potential,
 Borderline nodule (Atypical adeno. hyper.)Borderline nodule (Atypical adeno. hyper.) ––
 Foci ofFoci of ↓ reticulum staining,↓ reticulum staining,
 Small cell dysplasia,Small cell dysplasia,
 Isolated glandular structure – ‘Pseudoglands’,Isolated glandular structure – ‘Pseudoglands’,
 Three cell thick liver plates,Three cell thick liver plates,

PancreasPancreas
Pancreatic Intraepithelial Neoplasia (PanIN)Pancreatic Intraepithelial Neoplasia (PanIN) :-:-
 Used for entire spectrum of noninvasive proliferativeUsed for entire spectrum of noninvasive proliferative
ductal lesions,ductal lesions,

Actinic (Solar) KeratosisActinic (Solar) Keratosis :-:-
 Changes in epidermis exposed to sunlightChanges in epidermis exposed to sunlight (UV spectrum),(UV spectrum),
 Atrophic, hyperplastic & eventually dysplastic changes,Atrophic, hyperplastic & eventually dysplastic changes,
 Frequent in renal transplant recipients (lip region),Frequent in renal transplant recipients (lip region),
 p53 mutation in 3/4p53 mutation in 3/4thth
casescases
SkinSkin

SkinSkin
Bowen’s DiseaseBowen’s Disease :-:-
 Indolent, scaly, erythematousIndolent, scaly, erythematous
plaquesplaques
 Pred. on skin unexposed to sun,Pred. on skin unexposed to sun,
 HistologicallyHistologically –– Atypical changes likeAtypical changes like,,
 Cytoplasmic vacuolization,Cytoplasmic vacuolization,
 Nuclear hyperchromasia,Nuclear hyperchromasia,
 Multinucleated keratinocytes withMultinucleated keratinocytes with
individual cell dyskeratosisindividual cell dyskeratosis
 ↑↑ no. of (abn.) mitosesno. of (abn.) mitoses
Regarded as ca. in situ of skin /Regarded as ca. in situ of skin /
sq. intraepidermal neoplasiasq. intraepidermal neoplasia

SkinSkin
Dysplastic NeviDysplastic Nevi :-:-
 Precursor ofPrecursor of Malignant MelanomaMalignant Melanoma
 Larger than other types (> 5 mm),Larger than other types (> 5 mm),
multiple,multiple,
 Flat macule / slightly raised plaqueFlat macule / slightly raised plaque
 ‘‘Target-like lesTarget-like lesnn
’ with irregular flat’ with irregular flat
periphery,periphery,
 Occur on sun exposed / non-exposedOccur on sun exposed / non-exposed
areas,areas,
Micro :-Micro :-
 Lentiginous hyperplasiaLentiginous hyperplasia,,
 Cytologic atypia,Cytologic atypia,
 Loss of melanin,Loss of melanin,
 Linear fibrosisLinear fibrosis in dermis,in dermis,

SKELETAL SYSTEMSKELETAL SYSTEM

Paget’s Disease,Paget’s Disease,
Bone infarcts,Bone infarcts,
Fibrous dysplasia,Fibrous dysplasia,
Enchondroma,Enchondroma,
OsteochondromatosisOsteochondromatosis

Paget’s DiseasePaget’s Disease
Above 50 yrs of age, M > F (4:3),Above 50 yrs of age, M > F (4:3),
MC sites – Lumbosacral spine, pelvis & skull,MC sites – Lumbosacral spine, pelvis & skull,
Usually polyostotic withUsually polyostotic with ↑ ALP levels,↑ ALP levels,
Monostotic common in long bones with normalMonostotic common in long bones with normal
ALP levelsALP levels
Ribs rarely inv.,Ribs rarely inv.,
PainPain MC presentation,MC presentation,
Slow viral infSlow viral infnn
byby paramyxovirusparamyxovirus ((Measles / RSVMeasles / RSV),),
Hyperresponsive osteoclasts to Vit. D & RANKL,Hyperresponsive osteoclasts to Vit. D & RANKL,

‘‘Mosaic patternMosaic pattern’’ of lamellar bone,of lamellar bone,
Abnormal largeAbnormal large osteoclastsosteoclasts withwith
>100 nuclei,>100 nuclei,
Newly formedNewly formed woven or lamellarwoven or lamellar
bonebone

Complications :-Complications :- 1) Fractures, 2) Tumour development,1) Fractures, 2) Tumour development,
Most dreaded compl. –Most dreaded compl. – development of Sarcomadevelopment of Sarcoma,,
MC –MC – OsteosarcomaOsteosarcoma,,
 Monostotic = 0.7 – 0.9 %,Monostotic = 0.7 – 0.9 %,
 Polyostotic = 5 – 10 %,Polyostotic = 5 – 10 %,
OthersOthers –– ChondrosarcomaChondrosarcoma,, MFHMFH,,
Benign tumoursBenign tumours –– GCT, Giant cell reparative granulomaGCT, Giant cell reparative granuloma

Bone infarctsBone infarcts
Result of large no. of etiological factors,Result of large no. of etiological factors,
Radiographic findings – depends on age of lesRadiographic findings – depends on age of lesnn
,,&&
–– degree of repair,degree of repair,
↑↑ incidence of primary malignancy with large infarctincidence of primary malignancy with large infarct
of long bones,of long bones,
MC – medulla of femur or tibia of male adults,MC – medulla of femur or tibia of male adults,
Primary malignancies developing are –Primary malignancies developing are –
 MFH,MFH,
 Osteosarcoma,Osteosarcoma,
 Fibrosarcoma,Fibrosarcoma,
 angiosarcomaangiosarcoma

Fibrous dysplasiaFibrous dysplasia
Benign tumour with localized developmental arrestBenign tumour with localized developmental arrest,,
Two formsTwo forms :-:-
 Monostotic,Monostotic, (more common, young adults, ribs/femur/tibia),(more common, young adults, ribs/femur/tibia),
 Polyostotic,Polyostotic, (less common, unilateral inv., syndrome assoc(less common, unilateral inv., syndrome assocnn
),),
GROSSGROSS –– gritty, tan-white to grey-yellow, thin cortexgritty, tan-white to grey-yellow, thin cortex,,
MICROMICRO –– narrow, curved bony trabeculae without osteoblasticnarrow, curved bony trabeculae without osteoblastic
rimming, fibrous tissue of variable cellularityrimming, fibrous tissue of variable cellularity

Complication – development of bone tumour,Complication – development of bone tumour,
Risk more with polyostotic inv.,Risk more with polyostotic inv.,
MC –MC – Osteosarcoma,Osteosarcoma,
Others –Others – ChondrosarcomaChondrosarcoma andand MFH,MFH,
↑↑ risk with irradiated lesionrisk with irradiated lesion
Fibrous dysplasiaFibrous dysplasia
Osteofibrous dysplasiaOsteofibrous dysplasia
Cortical lesion on radiography,Cortical lesion on radiography,
Micro :- Osteoblastic rimming of trabeculae,Micro :- Osteoblastic rimming of trabeculae,
- +nce of lamellar bone- +nce of lamellar bone

EnchondromaEnchondroma
Begin in spongiosa of diaphysis,Begin in spongiosa of diaphysis,
Common in small bones of hands & feetCommon in small bones of hands & feet (Proximal phalanges),(Proximal phalanges),
30 % multiple,30 % multiple,
Risk significantlyRisk significantly ↑ in –↑ in –
 Ollier’s disOllier’s dis. – multiple unilateral enchondromas,. – multiple unilateral enchondromas,
 Maffucci’s syndMaffucci’s synd. – multiple enchondromas with soft tissue. – multiple enchondromas with soft tissue
hemangiomas,hemangiomas,
Transform intoTransform into ChondrosarcomaChondrosarcoma,,
Mature lobules of hyalineMature lobules of hyaline
cartilagecartilage

OsteochondromatosisOsteochondromatosis
Multiple cartilagenous exostosis, Ehrenfried’s hereditaryMultiple cartilagenous exostosis, Ehrenfried’s hereditary
deforming chondrodysplasia, Diaphyseal aclasis,deforming chondrodysplasia, Diaphyseal aclasis,
Risk of developingRisk of developing Chondrosarcoma,Chondrosarcoma,
10 % risk,10 % risk,
Upregulation ofUpregulation of PTHrPPTHrP && bcl-2bcl-2,,

Male Reproductive SystemMale Reproductive System

ProstateProstate
Prostatic Intraepithelial Neoplasia (PIN)Prostatic Intraepithelial Neoplasia (PIN) :-:-
 Intra-acinar prolifIntra-acinar prolifnn
of cells with nuclear atypia in benignof cells with nuclear atypia in benign
glands,glands,
 May be Low grade or High grade ,May be Low grade or High grade ,
 Main disting. features are nuclear & nucleolar characters,Main disting. features are nuclear & nucleolar characters,
Low Grade PINLow Grade PIN :-:-
 Less nuclear atypia with benignLess nuclear atypia with benign
architecture,architecture,
 Common finding in young male pt.Common finding in young male pt.
 Majority have N diploid DNA,Majority have N diploid DNA,

 High grade PIN (HGPIN)High grade PIN (HGPIN) ––
 Widely separated, larger branchingWidely separated, larger branching
glands,glands,
 Papillary infolding,Papillary infolding,
 Glands surrounded by patchy layerGlands surrounded by patchy layer
of basal cells,of basal cells,
 Intact basement membrane,Intact basement membrane,
Evidence in support of precursor natureEvidence in support of precursor nature ––
Both HGPIN & Ca. pred. in peripheral zone,Both HGPIN & Ca. pred. in peripheral zone,
Prostate having ca. have high frequency of HGPIN,Prostate having ca. have high frequency of HGPIN,
ProstateProstate

Atypical Adenomatous hyperplasia (Adenosis)Atypical Adenomatous hyperplasia (Adenosis) :-:-
ProstateProstate
LP view similar to wellLP view similar to well
diff. adenocarcinoma,diff. adenocarcinoma,
Architectural distortionArchitectural distortion
without nuclear changes,without nuclear changes,
Complex & disorderlyComplex & disorderly
cluster of glands,cluster of glands,
Acidic mucin often +nt inAcidic mucin often +nt in
lumen,lumen,
Risk of transformation toRisk of transformation to
adenoca. not clearly known,adenoca. not clearly known,

Male Reproductive SystemMale Reproductive System
TestisTestis
Intratubular Germ Cell Neoplasia (IGCN)Intratubular Germ Cell Neoplasia (IGCN) :-:-
 Encountered in high frequency in (Encountered in high frequency in ( ↑ing risk ) :-↑ing risk ) :-
 Cryptorchidism,Cryptorchidism,
 Prior germ cell tumours,Prior germ cell tumours,
 Strong family history of GCT,Strong family history of GCT,
 Androgen insensitivity syndrome,Androgen insensitivity syndrome,
 Gonadal dysgenesis syndrome,Gonadal dysgenesis syndrome,
 Progression to invasive ca. – 50 % over 5 yrs,Progression to invasive ca. – 50 % over 5 yrs,
 If diagnosed, can be t/t by destroying germ cells withIf diagnosed, can be t/t by destroying germ cells with
radiotherapy, preserving andro. secretionradiotherapy, preserving andro. secretion

Intratubular Germ CellIntratubular Germ Cell
Neoplasia (IGCN)Neoplasia (IGCN)
Classification :-Classification :-
 Unclassified,Unclassified,
 With extratubular extension,With extratubular extension,
 Intratubular seminoma,Intratubular seminoma,
 Intratubular embryonal ca.,Intratubular embryonal ca.,
 Other formsOther forms like Intratubularlike Intratubular
yolk sac or chorioca.yolk sac or chorioca.
H & EH & E
PASPAS

PenisPenis
Two lesions with CIS featuresTwo lesions with CIS features
Bowen disease :-Bowen disease :-
 Involves skin of shaft of penis & scrotum.Involves skin of shaft of penis & scrotum.
 Gross – Solitary, thickened, g/w, opaque plaque with shallowGross – Solitary, thickened, g/w, opaque plaque with shallow
ulceration & crusting.ulceration & crusting.
 Shiny red, velvety plaques on glans & prepuce k/a ‘Shiny red, velvety plaques on glans & prepuce k/a ‘ErythroplasiaErythroplasia
of Queyrat’of Queyrat’
 Microscopy – Epidermis – proliferation with numerous mitoses.Microscopy – Epidermis – proliferation with numerous mitoses.
Cells are dysplastic with sharp delineation of dermoepidermalCells are dysplastic with sharp delineation of dermoepidermal
junct.junct.
 10 % cases – Invasive squamous cell ca.10 % cases – Invasive squamous cell ca.
Bowenoid papulosis :-Bowenoid papulosis :-
 Young malesYoung males
 No malignant potential.No malignant potential.

KidneysKidneys
Acquired cystic disease –Acquired cystic disease –
 Complication of long term dialysis (80-90 % in 10 yrs)Complication of long term dialysis (80-90 % in 10 yrs)
 Also seen in uremic non dialised patients.Also seen in uremic non dialised patients.
 cysts-cysts-
 usually bilateral, both in cortex & medulla.usually bilateral, both in cortex & medulla.
 Range from 0.5 to 3 cm,Range from 0.5 to 3 cm,
 Most lined by flattened epith, some by hyperplasticMost lined by flattened epith, some by hyperplastic
cuboidal to columnar epith. with papillary projections.cuboidal to columnar epith. with papillary projections.
 MC tumor – Papillary adenoma,MC tumor – Papillary adenoma,
 RCC - in 6 % , predominantly papillary.RCC - in 6 % , predominantly papillary.

Urinary BladderUrinary Bladder
Two precursor lesions –Two precursor lesions –
 Non invasive papillary tumours -Non invasive papillary tumours -
 More common,More common,
 Arise from papillary urothelial hyperplasia,Arise from papillary urothelial hyperplasia,
 Can be of varying grades,Can be of varying grades,
 Gross – Small, delicate structures attached to mucosaGross – Small, delicate structures attached to mucosa
 Micro – finger like papillae with central core of looseMicro – finger like papillae with central core of loose
fibrovascular tissue lined by transitional epi. cells.fibrovascular tissue lined by transitional epi. cells.
 In high grade tumor – discohesive cells shedding intoIn high grade tumor – discohesive cells shedding into
urine.urine.

Urinary BladderUrinary Bladder
Dysplasia / CISDysplasia / CIS
Flat urothelial ca. (CIS) – always high grade,Flat urothelial ca. (CIS) – always high grade,
Gross –Thickened, granular, reddened mucosa,Gross –Thickened, granular, reddened mucosa,
- Usually multifocal- Usually multifocal
Predilection for trigone & lateral wall.Predilection for trigone & lateral wall.
Microscopy – same as CIS for other locations.Microscopy – same as CIS for other locations.
Progression to invasive ca. in 50 – 75 % cases.Progression to invasive ca. in 50 – 75 % cases.

Three types of precursor lesions :-Three types of precursor lesions :-
 Squamous dysplasia / CIS,Squamous dysplasia / CIS,
 Atypical adenomatous hyperplasia,Atypical adenomatous hyperplasia,
 Diffuse idiopathic pulmonary NE cell hyperplasia,Diffuse idiopathic pulmonary NE cell hyperplasia,
LUNGSLUNGS

LUNGSLUNGS
Carcinoma in situ (CIS) :-Carcinoma in situ (CIS) :-
 Similar diagnostic criteria used elsewhere,Similar diagnostic criteria used elsewhere,
 In most cases – unifocal in segmental bronchus,In most cases – unifocal in segmental bronchus,
 ‘‘Early invasive’Early invasive’ or ‘or ‘Intramucosal’ ca -Intramucosal’ ca -
 Superficial stromal invasion not extending toSuperficial stromal invasion not extending to
bronchial cartilage,bronchial cartilage,
 Aberrant expression of p53 & EGF receptors,Aberrant expression of p53 & EGF receptors,

SummarySummary
““PREVENTION IS BETTER THAN CURE”PREVENTION IS BETTER THAN CURE”
Premalignant conditions are the spectrum of diseases thatPremalignant conditions are the spectrum of diseases that
act as BRIDGE between Benign & Malignant lesions.act as BRIDGE between Benign & Malignant lesions.
Usually these lesions lasts for long duration & can beUsually these lesions lasts for long duration & can be
detected in earlier stages by various screeningdetected in earlier stages by various screening
techniques.techniques.
Thus identification & early treatment of these lesionsThus identification & early treatment of these lesions
helps in decreasing incidence of carcinomas.helps in decreasing incidence of carcinomas.

Peutz-Jegher SyndromePeutz-Jegher Syndrome
Prone to develop Adenoca. of GI tract,Prone to develop Adenoca. of GI tract,
Poor prognosis because of lateness of diagnosis,Poor prognosis because of lateness of diagnosis,
Prone for other malignancies likeProne for other malignancies like
 Ovarian sex cord tumour with annular tubulesOvarian sex cord tumour with annular tubules
(Adenoma malignum of uterine cervix)(Adenoma malignum of uterine cervix)
 Ovarian mucinous tumour,Ovarian mucinous tumour,
 Breast carcinomaBreast carcinoma

Premalignant lesions

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