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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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