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Neoplasia

y Definition and commontermso New growth = neoplasmo Onco = tumoro Cancer: generaltermformalignancy

and can bedividedinto 2 terms

(histogenesis):

Carcinoma: malignantepithelial(squamous and glandular)tumor

Sarcoma: malignantmesenchymaltumor

o An abnormalmassoftissue,the growthofwhichexceeds andisuncoordinated

withthatofnormaltissue andpersists

inthesameexcessivemanner after

cessationofstimuliwhichevokedthe

change

o Neoplasms consistof2 components: Stroma: mesodermalinorigin Parenchyma: usually ectodermalin

origin, butthere areexceptions.

o Metastasisisthrough 2 routes,withsomeexceptions: Mesenchymal

tumorhematogeneous

EpithelialtumorlymphaticsSALISE: to circumvent

Sixfundamentalphysiological changesinthe

neoplastic cell

y Selfsufficiency in growthsignals: producesproductsthatpromote growth

y Ability toinvade andmetastasize:malignant cellproducesenzymesthat

destroy extracellularmatrix.

y Limitlessreplicativepotential: cellcontinuestomultiply

y Insensitivity to growth inhibitory signals:tumorwillevade checkpointsin growth

cyclethatinhibit growth

y Sustained angiogenesis: growthrequiresbloodsupply fornutrition

y Evasionofapoptosis: cellpermits andcontinuestolive

The Language of Pathology

Nomenclatureoftumors

y Definitionofneoplasmo Biologic behavioro Tissueoforigin

Eg, adeno = glandularepithelium Adenoma: benign

Adenocarcinoma: tumorinwhichthe glandular component

ismalignant

Adenosarcoma: Thisdoesexist,butitis a mixedtumor

epithelial component and

malignantstromalcomponent

Eg, Lipo = fromfat (stromal) Lipoma: benignfromfat Liposarcoma: malignant

stromaltumor Eg,osteo = bone (stromal)

Osteoma: benignfrom bone Osteosarcoma: malignant

stromaltumor

Eg, cervixis compromisedof2differentepithelium: non-

keratinizedstratifiedsquamous

epithelium andsimple columnar

epithelium

Therefore,themalignancy can beof2

types: Adenocarcinoma: fromthe

simple columnarepithelium

whichforms glands

Squamous cell carcinoma: fromthenon-keratinizedstratified

squamousepithelium

Eg,mixedtumors ariseifboththeparenchymal andstromal

componentsproliferate andthe

most commontypeisthesalivary

glandtumor. Ifyousay benign

mixedtumor,thestroma and

epithelial componentproliferates.

Also,pleaserecallDr.Navarros

definitionofa mixedtumor: more

than 1 (>1)neoplastic celltype

usually from one germ layer.

Teratoma: insteadof2, 3 germlayersproliferate,usually arises

fromovary. Dermoid cysts are

teratomasthat commonly arise

fromthelateraleyelid. The

immatureteratoma iswhat canbecomemalignant andistermed a

teratocarcinoma. The component

that can becomemalignantisthe

neuroepithelium.

Note: thesuffix oma usually implies a benign

tumor buttheexceptionstothisruleincludethe

following:

Subject: PathologyTopic: Neoplasia 1Lecturer: Dr. CruzDate of Lecture: July 18, 2011Transcriptionist: DominaEditor: GannicusPages: 9

SY

2011-2012

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y Hepatomay Lymphomay Seminomay Melanomay Dysgerminoma

Anaplasia

y Healthy: Notethepolaritynuclei are alllinedup atthe base. (works best atexamining cervicaltissues)Also, cells are,

moreorless,sameshape andsize. All cells

arein alignment.

y Benigntumor: welldemarcated, cells arestillrelatively uniformintheexample below

y Dysplasia: Nuclei arescattered andseemto comprise 4 layers. Cells areofdifferent

size andshape.

y Insitu: hasnotinvadedthe basementmembrane

y Malignant: disoriented;proliferative;differentsizes,shapes, and chromaticity;invasionofstroma

Adenomas

y Acinary Cystic: dilationofthe glandsy Papillary: fingerlikeextensionofthe glandsy Dysplastic: increasedhyperchromaticity,

lossofpolarity, cellsofvarying size and

shape,etc.

Adenocarcinomas 1

In adenomas:proliferation, benign

In adenocarcinoma: isitdysplastic? Invasive? Same

size andshapeofthetumor cells? Ifpapillary, check

themalignant components

y Acinary Cysticy Papillary

y Signet ring: distinctivepatternorappearancefor adenocarcinomas

Adenocarcinomas 2

y Mucinous: very distinctive,stroma ismucousfilledwith glands

y Large-anaplastic: cells arelarge, but aredifferentinsizes andshape

y Cribiform: lotsof holesy Scirrhous: carcinoma cellsevoke

fibroplastic proliferation and are

desmoplastic. Thesetumors areusually

hardinfeel.

Squamous carcinomas

y Keratinpearls arepathognomonicy Cellular bridging

Danger Signals: CAUTIONUS

y Changein bowelor bladderhabitsy A sorethatdoesnothealy Unusual bleeding ordischargey Thickening orlump (breastorelsewhere):

itmay benormaltofindfibrocystic masses

during menstruation, butthey shouldnot

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persistinsize aftermenstruation. Alsoif

thereisdischarge,itshoulddefinitely be

evaluated.

y Indigestionordifficulty swallowingy Obvious changein a moleorwarty Nagging coughorhoarsenessy Unexplained anemiay Suddenunexplainedweightloss: to be

significant,thisshould be >15 - 20% ofbodyweightin 3 4 months.

Below: Leiomyomata

The abovelesions arisefromtheuterinewall

(smoothmuscle). (proliferationofgrowthinskeletal

muscle rhabdomyoma)

Histologically,the cells arespindleshaped. The

nuclei are centrally locatedsothisissmooth

muscle. (inskeletalmuscles,nucleiisperipherally

located)

Below: polyps

Polypsshould beelevated above a mucosalsurface,

eithersessile (attached)orpedunculated (presence

ofstem).

Histologically: pedunculatedpolyp above.

(intestinal)

Based on biologic behavior

y Benigny Malignant

Based on tissue of origin

y Epitheliumy Mesenchymey Mixedy Teratoma

Below: lipoma

Below: liposarcoma

Thisismalignant becauseitishyperchromatic, cells

vary insize andshape, andthenucleusis centrally

located (normalfat cellnucleusshould be

peripherally located) andhascobwebs attached

tothe cytoplasm. Theliposarcoma is composedof

lipoblasts asthey retaintheirembryonic

component.

Below: cervix.

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Hasthesame consistency ofthetipofthenose.

Notethe abnormal growth,thisistheearly stageof

carcinoma.

Histologically: according toDoc theleftsideis

already showing dysplastic features asseen by the

atypicalshapeofthestratum germinativum.

Normally the cellsinthe germinativum areroundor

cuboidal.

Histologically: malignant becauseofcellular

bridging. ThisisindicativeofSCC.

Below: osteoma

Histologically: presenceofosteoidmatrix. Stroma

ismalignant asevident by increasedN:Cratio,etc.

Below: Squamous cell carcinoma oflung

Grossly,thisislung asevident by bronchial

elements. Sincethelesionislocated centrally,

chances areitissquamous cell carcinoma. Ifitis

locatedperipherally,think adenocarcinoma (nows

themost commonmalignanttumorofthelung)

common.Thisis a generality though.

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Histologically: cellular bridging,large cells,

desmosomes,no glandulartissue. Moderately

differentiated.

Below: Malignant breasttumor.

Irregular border,infiltrative.

Histologically: glandularelementsadenocarcinoma

Biologic behavior of tumor depends on:

y Rateofgrowthy Degreeofdifferentiationy Localinvasiony Presenceor absenceof

metastasishallmark of malignancy.

o Forsupraclavicularnodes (aka,sentinel,guard,or Virchowsnode: thinkoftumor arising fromlungsor GI tract

(usually camefromthe chestorthe

abdomen). Ifsquamous cell carcinoma,

think GI tumoroforigin.

Benign vs. Malignant

Benign Malignant

Well-circumscribed Ill-defined

Encapsulated Irregularmargins

Well-differentiated Anaplastic

Pushing margins +invasion/metastasis

(-)metastasis (+)metastasis

Rate of growth

Determined by:

y Doubling timeofthetumor cells(multiplication)

y Fractionoftumor cellsthat areinthereplicativepool*

y Rate atwhich cells areshed andlostinthegrowing lesion

*Growthfraction (it candoubleinhours,months

depending onthetumorex. Breast cell 2 3

months)

Differentiation

y Theextenttowhichparenchymal cellsresemble comparablenormal cells, bothmorphologically andfunctionally.

y Dysplasia:o Disordered growtho Disorderedmaturation

y Anaplasiao Lackofdifferentiation

y Grades:o I: welldifferentiatedo II: moderately differentiatedo III: poorly differentiatedo IV: thisexists butforpurposesofthis

class,the abovewill bediscussed

Characteristics of anaplasia

y Pleomorphism: differentsizes andshapesofcells

y Hyperchromaticity: Innucleus,DNAtakesuphematoxylin. When a cellisheavily

replicating,theDNAwill beincreasedin

amount and appearsdarker.

y Increasednucleo-cytoplasmic ratio: normalis 1:4 to 1:6. Histologically,thenucleus

appearstotakeupmoreroominthe cell.

y Abnormal (atypical)mitotic figures (seearrow atleftin 1

stpicture below and

vertical arrowsin 2nd

picture below)

y Lossofpolarity (lossoforientation)y Presenceofmultipleorenlargednucleoli:

nucleolimeansthatreplicationis

occurring. (normal cellonly has 1 nucleoli)

y Formationoftumor giant cells (see arrow atright): resemblesforeign body giant cell,

thisis becausethe cell (cytoplasm) cannotkeepupwithnucleardivision

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Ploidy

y Testtodetermineifcellishighly divisibleorhave abnormal amountsofchromosomes

y Diploid: normal celly Aneuploid: 3 4 setsofchromosomesy Determined by flow cytometry (seediagram

onlastpage)

y Ifaneuploidy isincreasedin a cell,suspectthatthe cellishighly divisible andmay bedysplastic.

In situ vs. Invasive tumors

y Insituo Malignant cells confinedtoepithelial

lining. Limited by the basement

membrane

Intraepithelial: vulvar area, cervicalarea,prostatic glands

Intramucosal: GI tracty Invasive

o Malignant cells breached basementmembrane and areinthesubepithelial

stroma,lamina propria orsubmucosa

o Microinvasion: has breachedthebasementmembrane butisstillinthe

submucosa.

Intraepithelial neoplasia

Different gradesofneoplasia

y Normal: basaloid cellsy Grade I: 1/3 epithelialinvolvementy Grade II: 2/3 epithelialinvolvementy Grade III: entireepitheliuminvolved.y Insitu: hasnot breachedthe basement

membrane

y Microinvasion: asstated above,hasbreachedthe basementmembrane butis

stillinthesubmucosa.

y Condyloma (genitalwarts): HPV producesgenitalwarts. HPV 8 and 11 arelowrisk.

After 11,most are consideredhighrisk.

Most commonforAsiansisHPV 18.

Below: theepitheliumontherightisdysplastic

becauseitisproliferative andhyperchromatic.

Below: aboveslideinhighermagnification. Notethepresenceofkoilocytes (nucleiin cellsthatwould

normally nothavethem). Thisissometimes

indicativeofHPV infection (or any virus actually).

CIN (cervicalintraepithelialneoplasia) grade II III.

Invasion and Metastasis

y Localinvasiono Invasionthrough basementmembraneo Invasionintolamina propriao Invasionthroughmuscularismucosa

y Metastasiso Contiguousinvasionto adjacentorgan:

eg, cervical carcinoma thathas affected

theendometrialsurface.

o Seeding ofbody cavities/surfaces: eg,fullthickness gastric carcinoma thathas

ruptured andseededtheperitoneum

o Lymphatic spreado Hematogeneousspread

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Sequence of events in invasion and metastasis

y Invasionofintracellularmatrixo Detachmentoftumor cells

E-cahedrinso Attachmenttomatrix components

Laminin,fibronectinso DegradationofECM

Collagenase, cathepsinDo Migrationoftumor cells

y Vasculardissemination/homingo Vascular/lymphatic drainageo Microenvironmento Itisunknownwhy sometumorstarget

certaintissuestometastasize, but

biggesttargets arelungs andliver

becauseoftheneedfor aeration and

detoxification. (most commonly

affected)

Above: TheMetastatic Cascade. Itissomewhat

similartoleukocyte adhesion andtransmigrationin

theinflammatory pathway, butthe cellsproduce

moreenzymes and createmoredestruction.

INVASION

Diapedisis,Trasmigration.Thisisthemechanismfor

metastatic cascade.

Tumor cells attachtothesereceptors.Secrete

moreenzymesforfasterdestructionofthestroma

(throughdissemination)

Asidefromtheenzymesthey have activators.They

producesubstancestopromote angiogenesisto

promotetissuedestruction.They havemore

epithelial growthfactorproduction.

Destructionofstroma

Below: Metastatic breast adenocarcinoma tothe

lung

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Note: thereis glandulartissuewithin a dilated

lymphatic. However,theresidentshavementioned

thatmorehistory will beprobably beprovidedto

distinguishmetastatic breast adenocarcinoma from

adenocarcinoma ofthelung.

B

elow: Glandulartissueinlymphnode(normallyyouhavelymphoidelements,follicles). Definitely

metastasis.

Below: metastasistotheliver.

Cantsay thisenough. Primary carcinomas and

sarcomas areusually solitary. Multiplemasses are

usually metastatic.

Below: SALISEinschematic format.

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Flow cytometry

Howtodetermineifcellishighly divisible? DeterminePloidy.Normaldivisionisdiploid.Aneuploiddivision

becomes 3 subset, 3 subsets. Youdeterminethisthroughflow cytometry.Aneuploidtumorhas badprognonsis.

Itishighly proliferative (numerousmitotic cells,mitotic figures,highnucleoliper cell)

End of transcription

..he cried Lordsaveme. Jesusimmediately reachedoutHishand andtookholdofhimsaying tohim, O youof

littlefaith,why did youdoubt?.Matthew 14:31

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