Oncology Pathophysiology Notes – the different neoplasms Prostate Carcinoma - peak

incidence in 65-75 years of age - hormonal influence – androgens may play a part
in the development since growth of the tumor can be inhibited by ORX or treatmen
t with estrogens such as diethylstilbestrol o not as well known hormonal influen
ce for the nodular hyperplasia of the prostate - Genetic factors – increased incid
ence of first degree relatives of patients with prostate cancer – chromosome 1 and
10 with the PTEN gene o Occurs earlier and more commonly in African Americans (
increased CAG repeats on Androgen receptor gene) o Frequency of incidental prost
ate cancer is comparable across all ages Means that race plays a role in the pro
gression of established lesions, but not in initial development of the lesions o
Genetic differences may play a role in the action of androgens on the prostate
- Environmental factors – increased incidence in certain industrial settings and s
ignificant geographic differences o Particularly common in the Scandinavian coun
tries, uncommon in Japan and other Asian countries o Males emerging from low ris
k moving to high risk areas maintain their low risk, but subsequent generations
have an intermediate risk o High animal fat diet is suggestive - Morphology of P
rostatic Carcinoma o 70-80% arise from the outer portion of the gland and can be
palpable with the finger on rectal exam – therefore, prostatic carcinoma is less
likely to present with urethral obstruction in the early stages o early lesions
usually lie near the capsule of the prostate, locally advanced lesions usually i
nfiltrate the seminal vesicles and periurethral zones of the prostate and may in
vade adjacent soft tissue and the wall of the urinary bladder o Denonvillier’s fas
cia covering the lower GU tract from the rectum prevents the posterior growth of
the tumor so rectal involvement is less common - Microscopic evaluation o Prost
ate carcinoma is an adenocarcinoma o Neoplatic glands are lined by single layer
of cuboidal cells and basal cell layer is absent. Usually, 2 layers of identical
cells (basal and cuboidal cell layers) are seen in normal and hyperplastic pros
tates o Gleason index is indicative of the anatomic stage of the carcinoma histo
logically and the prognosis – it is measured from a scale of 2-10, and 2 Gleason s
cores are given per evaluation and the sum of which makes the final Gleason Scor
e. BPH does not get assigned a Gleason Score o Staging is based on the level of
local and/or systemic involvement o Metastatic spread is via direct extension (a
s in to the seminal vesicle), lymphatic (as in to the retroperitoneal nodes, or
local nodes to the para-aortic nodes) or hematogenous (to bone – causing anemia – nu
cleated RBCs seen, left shift in WBC) - Clinical features o Often are clinically
silent, especially during early stages o Up to 20% is discovered unexpectedly,
60% incidence in males over 80 o more extensive disease can present as a BPH unt
il needle biopsy is performed to find out o can have ↓ in urinary stream, trouble
starting urination, dribbling, cystitis due to incomplete voiding 1
-
-
-
o some initially present with metastases m- especially bone – Batson’s plexus – to the
axial skeleton causing osteoblastic lesions (usually carcinoma metastases cause
s osteolytic lesions) osteoblastic lesions are a sign of advanced prostatic carc
inoma Diagnosing o Serum PSA levels – correlates with tumor mass o PSA is a serine
protease which functions in maintaining fluid semen to allow for easy sperm mot
ility and also has systemic effects in regulating IGF levels by functioning in c
leaving IGF-1 binding proteins o Any condition that disrupts the normal architec
ture such as adenocarcinoma, hyperplasia or prostates can cause ↑ PSA Carcinoma pa
tients usually have higher levels, but there is overlap in the range between BPH
and carcinoma Rate of change of PSA levels, ratio of PSA levels vs. prostate si
ze and measurement of free vs. bound PSA is used also for more sensitivity o If
used alone its not as good as in using it with a rectal exam, needle biopsy or t
ransrectal sonography o 4 ng/ml is the upper limit of normal Anatomic staging (T
MN system) o Depends on presence of local invasion o Border between T2 and T3 is
where there is the start of local invasion o N staging gives the extent of Lymp
h Node involvement o M staging gives the extent of metastases Tx o Depends on st
aging and Gleason index Surgery – used for cases that are localized to the gland,
complications are incontinence and impotence (due to nerve damage) Radiotherapy –
also for localized cases – can result in impotence over time or can also cause rad
iation induced prostatis Hormonal Therapy – can not help metastatic cases, but can
be good for shrinking size of tumor – usually use GnRH analog or ORX (both which
decrease serum androgen levels) or use of androgen blocking drugs such as flutam
ide (intracellular receptor blocker) Chemotherapy – not shown to prolong survival –
used more for palliative care
Testicular Carcinoma - most important cause of firm, painless enlargement of the
testis - occurs in 2 of 100,000 males – peak incidence in males 15-34 - 95% arise
from germ cells (which are malignant), not from Sertoli or Leydig cells (which
are benign) - non-germ cell tumors present with endocrine abnormalities - increa
sed risk in those with testicular dysgenesis (as in testicular feminization, Kli
nefelter’s Syndrome), cryptorchidism (associated with a 4 fold increase in undesce
nded as well as increased risk in the contralateral descended testis), also incr
eased risk in those with chromosomal aberration of short arm of 12, increased ri
sk in siblings, but no consistent hereditary basis - more common in whites than
blacks, if > 50, most common testicular tumor is a malignant lymphoma - in infan
ts and pre-pubertal boys, 50% of the germ cell tumors are teratomas, and the oth
er 50% are endodermal sinus (yolk sac) tumors - Germ cell tumors o one histologi
c pattern Seminoma – accounts for 60% of germ cell neoplasms • Large, soft, well-dem
arcated homogeneous, gray-white tumors • Usually confined to the testis by an inta
ct tunica albuginea • Large tumors can contain necrosis, but usually there is no h
emorrhage 2
-
Microscopically the tumors are composed of large cells with distinct cell border
s, clear, glycogen rich cytoplasm, and round nuclei with conspicuous nucleoli – ce
lls can be arranged in lobules with intervening fibrous septa with a lymphocytic
infiltrate which is usually present and may overshadow cancerous cells, and gra
nulomas can also be noted (the 7-24% with syncytiotrophoblastic giant cells here
secrete hCG which is why sometimes these patients have elevated hCG levels) • Cla
ssical, anaplastic, spermatocytic (occurs in older men, and metastases is very r
are) are other types Embryonal carcinoma – 20-25% • Ill-defineed, invasive masses co
ntaining foci of hemorrhage and necrosis • Microscopically you see large, anaplast
ic, pleiomorphi c cells with hyperchromatic nuclei and basophilic cytoplasm – thes
e cells can form glandular, tubular, alveolar or undifferentiated patterns Chori
ocarcinomas – most malignant of the germ line tumors • Small, non-palpable, hemorrha
gic masses that are small even if they have metastasized – microscopically you see
small cuboidal cells irregularly intermingled with or capped by large, eosinoph
ilic, syncytial cells containing multiple dark, pleiomorphic nuclei which form a
primitive placenta like structure (these cells are larger with distinct borders
) • hCG can be stained in the syncytiothrophoblastic cells Teratomas – composed of c
ell types from multiple germ cell layers • Firm masses that contain cysts and reco
gnizable areas of cartilage • 3 variants of teratomas – Mature – exceedingly rare with
fully differentiated cells from different cell lines, Immature – with some primit
ive elements like those in fetal development and Malignant teratoma – containing m
alignant non-germ cell elements in the form os squamous cell carcinoma or adenoc
arcinoma o Non-germ cell line tumors (such as Leydig cell, Sertoli or gonadoblas
tomas) Leydig cell can occur at any age an results in excess androgens causing p
recocious puberty in children, gynecomastia in adults – the utmor is bright yellow
in color due to lipid content and histologically shows large, polygonal cella w
ith cytoplasm that may be pink and granular or clear. Crystalloids of Reinke may
be seen o Adenomatoid tumors – derived from mesothelial cells of the tunica which
can also occur in paratesticular locations Clinical features – painless enlargeme
nt of the testis or sometimes, non-seminomatous germ-cell carcinomas can presnt
with widespread metastases with the absence of a palpable lesion o 40% of cases
have elevated hCG or α-fetoprotein levels hCG levels correl te with the # of tumor
cells in body. 10% of seminom s h ve elev ted levels – hCG c n sitmul te estrogen
production from the testis which c n result in gynecom sti α-fetoprotein indic t
ed non-seminom tous lesion (but lso elev ted in liver c ncer) elev tions of b
oth t the s me time re indic tive of mixed cell neopl sm o Seminom s usu lly
rem in confined to the testis – but while hem togenous met st ses is r re, met st
ses c n occur in lymph tics nd is most common in the ili c nd p r - ortic lym
ph nodes (upper lumb r region), inguin l node met st ses is uncommon unless tr
nscrot l biopsy w s performed ( procedure which llows the c ncer cells to ent
er the derm l lymph tics in the scrot l skin which ultim tely p sses to the ingu
in l region) o Non-seminom tous lesions met st size e rlier by both lymph tic n
d hem togenous routes nd re most common to the liver or lung
•
3
o Germ cell neopl sms re cl ssified with St ges – St ge I (confined to testis), S
t ge II (met st ses confined to retroperitone l lymph nodes, sub-di phr gm tic),
St ge III (met st ses beyond the RP lymph nodes with supr -di phr gm tic involv
ement) Tx o Surgery (remov l – ORX – vi inguin l ORX to void cont min ting the ing
uin l nodes by cont min ting the skin lymph tics, RP lymph node met st ses c n b
e resected o R diother py – c n be cur tive for seminom s o Chemother py – cispl tin
, belomycin, vinbl stine nd etoposide show good cure r tes even with met st ses
in non-seminom tous tumors – cure r te ↑ with less tumor cell # Bl dder c ncer - in
cre sed frequency in smokers, m les nd those exposed to niline dyes o smokers –
h ve incre se c rcinogens in urine o niline dye is lso secreted in urine, so i
t c n h ve c rcinogenic effects on bl dder - pe k incidence in 50-70 ye rs of g
e - multiple bl dder c ncer etiology – field effect (multiple cells exposed to c r
cinogen) or spre d due to m lign nt cells which re shed nd then spre d to othe
r sites in the bl dder mucos - genetic f ctors h ve mut tions in p53, Rb gene
nd k-r s, chromosome 9 bnorm lity, loss of p16 - Types o Tr nsition l cell (90%
) – prognosis is good Most re p pill ry nd non-inv sive, but c n lso be sessile
or inv sive C rcinom in-situ refers to non-p pill ry, non-inv sive lesions, Gr
de I, while Gr de IV would be severely n pl stic o Squ mous cell c rcinom (5%
) – b d prognosis Results form chronic irrit tion such s with schistosomi sis inf
ections, bl dder stones, recurrent c ther teriz tion o Adenoc rcinom (5%) – pure
denoc rcinom is r re From ur ch l remn nt or origin ting from the trigone Also
b d prognosis - Clinic l fe tures o Most st rt from mucos l l yer nd then gr
ows in polyploidy f shion into the bl dder o Loc l tumor re necrosis c n le
d to hem turi nd clot form tion in the bl dder P ss ge of the clots c n c use
p in, nd enough bleeding c n result in nemi o Depth of inv sion of the tumor
determines clinic l signific nce – if the tumor h s penetr ted deep, then, 5 ye r
surviv l is < 20% Most reoccur except for the benign p pillom s Most de th from
bl dder c ncer is result of obstruction of the ureters r ther th n metz o Tumo
r growth into the segments of the colon c n form vesico-colonic fistul o Spre
d in the RP c n c use ureter obstruction o In fem les growth c n c use vesico
-v gin l fistul o LN spre d to the p r - ortic nodes c n result in leg edem o
Hem togenous spre d c n occur to liver, lungs nd bone - Tx o Surgery – tr nsureth
r l resection or cystectomy (for more deep inv ding tumor) o R diother py – only f
or those who c n not st nd surgery, nd s p lli tive c re for bone metz o Chemo
ther py – used for p tients who h ve h d resections but re t high risk for devel
oping further tumors BCG in the bl dder to stimul te cytotoxic immunity Drugs su
ch s thiotep ( lkyl ting gent) nd doxorubicin directly into bl dder Combin t
ion ther py with cispl tin, doxorubicin nd gemcit bine
4
Lung C ncer - The most common c use of c ncer de ths in the US - Cure r te is ve
ry low (10% survive p st 5 ye rs) – most common c use of c ncer de th in m + f - 9
5% of prim ry lung c ncers re bronchogenic c rcinom s - most common benign lesi
on re spheric l, sm ll 3-4 cm “coin like lesion” h m rtom s – which consist m inly of
c rtil ge, but re often dmixed with f t, fibrous tissue nd blood vessels in
v rying proportions - Etiology – exposure to c rcinogenic gents including o cig r
ette smoke (90%) – risk is dependent on dose of cig rettes – gre test incre se in >2
p cks/d y, quitting for 15 ye rs brings risk b ck down close to norm l – results
of epidemiologic nd experiment l evidence – stepwise progression from b s l cell
hyperpl si squ mous neopl si squ mous dyspl si c rcinom in situ note the squ
mous nd sm ll cell re most rel ted to smoking o Asbestos - c uses pulmon ry
sbestosis, mesotheliom of the pleur (25-40 ye r l tency – rising in the p riet
l or viscer l pleur – results in thick, white firm pleur l tumor) nd peritoneum
nd bronchogenic lung c ncer, risk is lso c rried in those who h ve lose dose e
xposure – i.e., wives of the industry workers who did their l undry – risk is multip
lied by smoking – synergistic rel tionship o Ionizing r di tion – ur nium mining,
r don in b sements – multiplied risk if concurrent smoker o Chemic ls – such s chlo
romethy-methyl ether, benzpyrene ( by-product of steel smelting) o Molecul r b
sis tumor suppressor gene on 3p is gone e rly on, nd then p53 nd k-r s occur l
ter. Seems to demonstr te field effect from c rcinogens - The Bronchogenic c
rcinom the #1 c use of c ncer rel ted de ths o R tes re rising in fem les, but
leveling off in m les due to their smoking h bits o M:F is 2:1, pe k incidence
in 55-65 ye rs of ge o At time of di gnosis, 50% lre dy h ve met st ses o Ther
e re 4 types Adenoc rcinom nd bronchio lveol r c rcinom – k-r s oncogene mut t
ion, p16, CDKN2A – most common prim ry lung tumor – especi lly common in non-smoking
women younger th n 45 • Gener lly more peripher lly loc ted, grows slower th n ot
her lung c ncers but h s tendency to met st size widely e rly on • Atypic l den
om tous hyperpl si (often sites of prior sc rring) is the offici l precursor to
n denoc rcinom • M ny re monoclon l – cells show inv sive properties • Bronchio l
veol r c rcinom is n denoc rcinom th t grows with the rchitecture of the lu
ng p renchym without inv sion nd so they preserve the pre-existing lveol r r
chitecture Squ mous cell c rcinom (p16/CDKN2A) • More common in men • Arises s c
entr l lesion (in m in bonchi) th t spre ds to loc l hil r lymph nodes • L rge les
ions c n undergo centr l necrosis giving rise to c vit tion, • Usu lly preceded fo
r ye rs by squ mous cell met pl si nd dyspl si in the bronchi l epithelium,
nd then c n progress to c rcinom in situ which c n rem in for m ny ye rs sinc
e it is symptom tic nd undetect ble on r diogr phs. • Symptoms form from the les
ion growing into the lumen of the bronchus nd obstructing irflow which c n pro
duce dist l telect sis nd infection (progression to bronchiest sis) nd lso i
nv sion loc lly into the p renchym • Histologic lly the lesions show intercellul
r bridges, poorly differenti ted cells nd ker tin 5
C n result in some p r neopl stic syndromes such s hyperc lcemi (due to PTHrP
rele se) L rge cell c rcinom (p16/CDKN2A) • Too undifferenti ted to c tegorize,
n pl stic cells with l rge vesicul r nuclei with prominent nuclei, some re gi n
t cells th t re multinucle ted, while some c n be spindle sh ped cells • H s ve
ry poor prognosis due to tendency to spre d to dist nt sites e rly on Sm ll cell
c rcinom (p53 nd Rb gene mut tions) • Centr lly loc ted p le gr y m sses with ex
tension into the lung p renchym nd e rly involvement of the hil r nd medi sti
n l lymph nodes • Cells h ve sc nt cytopl sm, finely gr nul r chrom tin nd mitoti
c figures re frequently seen, necrosis is present in the lesions s well, cells
how crushed ppe r nce on biopsy specimens due to its fr gility • Cells re der
ived from neuroendocrine cells of the lung (kulchitsky cells) nd c n lso resul
t in p r neopl stic syndromes (SIADH, Cushings), cerebell r trophy, E ton L mbe
rt Syndrome (imp ired tr nsmission t motor end pl tes) Note th t the gener l cl
ssific tion is into sm ll cell nd non-sm ll cell – this is bec use lmost ll sm
ll cell c rcinom s h ve met st sized by the time of di gnosis nd so is not tre
ted with surgery but with chemo nd r di tion. Non sm ll cells usu lly respond
poorly to chemo nd is tre ted with surgery, nd they h ve better prognosis th
n sm ll cells Bronchi l C rcinoid – thought to rise from kulchitsky cells – neuroe
ndocrine origin • Pe k incidence t 40 ye rs of ge • Rel ted to sm ll cell c rcinom
, but is respect ble nd cur ble • Origin te in m instem bronchi nd then grows i
n 1 of 2 p tterns o 1 – onstucting polyploidy, spheric l intr lumin l m ss or o 2 –
mucos l pl que penetr ting the bronchi l w ll nd f nning out to peribronchi l t
issue • 5-15% h ve met st sized to hil r nodes t present tion • s lt nd pepper chr
om tin, bsent or r re mitosis nd little pleiomorphism o Clinic l fe tures Tumo
r grow c n n rrow the irw ys resulting in ltered irflow loc lized wheezing (
s opposed to sthm which h s gener lized whole lung wheezing) irrit tion of n
erve endings due to tumor growth c n result in coughing, erosion of the irw y w
ith v scul r disruption le ding to hemoptysis progressive obstruction c n le d t
o dist l mucus st sis nd infection (post-obstructive pneumoni ) p r neopl stic
syndromes, clubbing of finger nd toes, neuromuscul r syndromes, DIC, NB endoc r
iditis telect sis with dyspne if l rge portions of lung re involved Met st ti
c spre d • Direction extension – inv ding dj cent structures o Symp thetic trunk – Ho
rner’s o Br chi l Plexus – P in in shoulder nd rm o Recurrent L rynge l Nerve – Ho r
seness of voice o Inv sion of peric rdium – t mpon de, effusion o Inv sion of pleu
r – effusion o Inv sion of chest w ll – p in, inv sion of esoph gus – difficulty sw l
lowing • Lymph tic spre d – esp to hil r, medi stin l, nd supr cl vicul r lymph nod
es 6
•
o C n result in SVC syndrome – imp ir venous return from the he d nd neck nd upp
er extremities, resulting in enl rgement of proxim l veins nd edem of those r
e s • Hem togenous spre d – commonly to the br in, bone, liver nd dren ls o Tx str
tegy depends on the histologic l type, extent of spre d, st ging nd over ll me
dic l condition of the p tient Surgery – for non-sm ll cell c rcinom s nd for tum
ors th t re gener lly loc lized R diother phy – lso for loc lized tumors Chemoth
er py – etoposide nd cispl tin nd other multi drug regimens especi lly for those
with sm ll cell c rcinom s • Dist nt br in metz c n be tre ted with r diother py
P ncre tic C rcinom - presents in the l te sixties, pe k is between 60-80 ye rs
of ge - incidence h s not ch nged – 5th most frequent c use of c ncer - risk is
incre sed in smokers nd p tients with chronic p ncre titis (40X incre sed risk)
- 5-8% of c ncers re of f mili l f ctors - very b d prognosis with <5% with
5 ye r surviv l - 90% of c ses re noted with k-r s nd p16 genes, 50% of c ses
h ve tp53 mut tion, nd 50% lso h ve DPC4, BRCA mut tions re lso noted - P
thology o Sometimes, neopl stic tissue m int ins exocrine function, so you c n g
et c rcinom of the β cells and get hyperinsulinemic and hypoglycemic as a result
o Morphologically a tumor arising from the exocrine portion of the gland – an aden
ocarcinoma, very rare to get it from the
Islets of Langerhans 60-70% arise from
the head portion, 5-10% arise from the ody, 10-15% from the tail and 20% diffus
ely involves the entire gland usually an adenocarcinoma with some having desmopl
astic characterisitic

locally

invading adjacent tissues neoplasms of the

head po
rtion results in o structed ile flow (can result in distention of the iliary t
ree) and ulceration

of the tumor into the duodenal mucosa may also
occur carcino
mas of the

ody and tail remain silent
for a longer period of time ecause

they
do not o struct anything so they can e quite large and disseminated y the time
they are discovered – they extend into the retroperitoneal spaces,

infiltrate adj
acent nerves, occasionally invades the spleen, adrenals, verte ral columns, tran
sverse colon and stomach. Peri pancreatic, gastric,
mesenteric, omental and port
ohepatic nodes are frequently involved, and liver, one and lungs are frequent s
ites of metastases perineural invasion is common and invasion of the splanchnic
nerves can result in pain and impaired gastric motility histologically, tumors o
f the head or other
parts

look the same - Clinical features o Pain is usually th
e first
symptom, ut y the time that occurs, the tumor has progressed significa
ntly o O structive
jaundice
can occur in cases where the head portion is involve
d o Migratory throm
ophel itis is also common especially if the carcinoma
involv
es portions

of the

ody and tail - Tx o Surgery – only curative method, ut rarely
occurs ecause y the time the patient
presents, it has already spread o Radiot
herapy

– mostly
used for palliation for one mets o Chemotherapy – not that effectiv
e, ut gemcita ine is used for palliative therpy 7



Gastric Carcinoma - incidence has ↓ since 1900’s which may e attri uted to ↓ use to c
hemical preservatives in good and increased consumption of
fresh fruit and veggi
es - highest rates are in Japan and other areas of Asian, ut those who move to
the US acquire US incidence rates, which means there is
heavy environmental fact
ors for etiology - etiology exactly is not known – may e H. Pylori (organism that
causes peptic ulcers in the

stomach and duodenum) since there
is higher rate of
cancer in those who have een infected with H. pylori, or may e due to the cytot
oxic response of the immune system to H. pylori which results in damage to the g
astric epithelial DNA o environmental influences – diet (nitrite rich foods), smok
ed foods, pickled veggies, excess salt intake, ↓ fruit and veggie intake - Carcino
ma of the stomach is the most common malignancy in the stomach (90-95%), then MA
LTomas which are lymphomas (4%) and carcinoids (3%) and mesencyhmal spindle cell
tumors (2%) - 5 year survival is <20% - 2 morphological types o intestinal vari
ant – arises from gastric mucosal cells that have undergone intestinal metaplasia
in the setting of chronic gastritis this is the more common type in high risk po
pulations (diminishing in US) occurs after 50, with 2:1 favoring males forms mal
ignant cells of colonic adenocarcinoma o diffuse variant – arises de novo

from gas
tric mucous cells, not associated with chronic gastritis and tends to e poorly
differentiated
this variant has not changed in incidence
over the past 60 years
and makes up a out 50% of the gastric carcinoma cases may e due to autosomal dom
inant E-cadherin
mutation? occurs earlier in life, with no sex preference does n
ot form glands,

ut rather permeates the mucosa and has am ore invasive type gro
wth pattern o oth tumors can metz to lymph nodes, usually first to the supracla

vicular nodes resulting in Virchow’s node, and
in females, sometimes, you get ila
teral ovary involvement which result in Kruken erg tumor Morphology o 50-60% of
cases

are in the pylorus or antrum o 25% in cardia, and remainder in the fundus
or ody o 40% of the time, the lesser curvature is involved and the greater curv
ature 12% of the time most common sight is lesser curvature at the antrum/pyloru


s region o ulcerative

lesions of the greater curvature are less frequent, ut mo
re likely to e malignant o depth of invasion is crucial for
classifying the tum
or early gastric
tumor lesions are confined to mucosa and su mucosa, regardless
of presence

or a sence of perigastric LN metastases, advanced lesions have invad
ed the su mucosa into the muscular wall

gastric dysplasia is the precursor lesio
n o macroscopically the lesions can e exophytic (protruding, not within the pla
ne of the epithelium

– may contain portions of an adenoma), flat or depressed or e
xcavated (shallow, ut erosive crater – may mimic ulcers)
- Clinical Features o Is
usually asymptomatic in the
early stages and can also e in the later stages La
ter stages can present with a dominal discomfort or weight loss o Stage of
tumor
at surgical resection is indicative of prognosis o Hematemesis,

Chronic
lood l
oss can cause iron deficiency anemia o Some can result in o structive pro lems,
causing vomiting and nausea 8
-
TX
o Metastatic spread can go tot eh transverse colon and result in a gastrocolic f
istula, some tumor cells can extend within the wall of the stomach to cause a ri

gid stomach with ↓ peristaltic motion o Hematolgoic spread is most often to the o
nes, lungs, and CNS o Surgery – resection is the only curative therapy o Radiother
apy – not curative, more for palliation o Chemotherapy – usually used post surgery t
o ↓ risk of developing recurrence 5-FU and Leucovorin are used
Colon Cancer
- common in the US, people > 50 - high incidence in US, Canada, wes
tern Europe ut low in Japan, Japanese immigrants to the US have the same risk a
s US people – indicates environmental influence - risk factors o high fat diet, an
d
grilling of meats (due to ↑ heterocyclic amines) is known to ↑ risk o parents or
s
i lings of a patient will ↑ risk o patients with Crohn’s Disease or inflammatory ow
el disease (ulcerative colitis) o patients with hereditary conditions – familial a
denomatous

polyposis, hereditary non-polyposis cancer syndrome o high alcohol -
high fi er, Ca, Vit D, Folic acid reduces the risks - genetic causes o chromosom
al deletions are common in 5, 17, 18 o familial adenomatous polyposis have a mut
ation of the APC tumor suppressor gene on 5q during polyp development, wild type
gene is deleted, no the functional copy of APC is gone non-hereditary colon can
cer also has this mutation (APC) APC regulates β-catenin

which

effects the express
ion of myc oncogene P53 is on 17p, and it too is a sent
on oth alleles in non-h
ereditary colon cancer cases • P53 protects the genome ecause
it prevents progres
sion of the cell cycle if there is damaged DNA • If damage is eyond repair, p53 m
akes sure they enter apoptosis 50% of patients have a k-ras mutation and 10% hav
e a BRAF mutation o hereditary non-polyposis syndrome altered genes in the misma
tch repair family of genes hMSH2 and hMLH1

• these genes repair mutations due to p
olymerase errors or mutagen covalently onding to DNA • as a result of the loss of
the repair genes, mutations accumulate and occur in genes such as β-catenin, BRAF
, TGF-β II receptor…etc, and then cancer develops o Colonic adenocarcinoma

Right sid
ed • Right colon has thin wall and
larger diameter so is more

distensi

le and sinc
e the stool is more liquid there, o struction or changes in owel
ha its are not

likely • Grossly a polyploidy mass with patient presenting with leeding (occult
lood
in stool) and iron deficiency anemia • Cecum and ascending colon cancers ten
d to e polyploidy and
grow into the lumen Left sided • Left side is thicker walle
d, and narrower, so o struction symptomatology is more likely 9


Usually a circumferential growth producing a “napkin ring” like formation and arium
studies show an apple core lesion, growth is
more likely
to infiltrate the musc
ular layer • Patients

present with change in owel ha
its constipation or diarrhea


, reduced cali er of stools (pencil

thin
stool) and o struction • If there is loo
d in the stool, patient sees right red lood in the toiler and on the paper Met
astatic spread • Direct extension through the muscularis and serosal layers to inf
iltrate the peritoneum and then grow into adjacent structures and the organs
inv
olved depends were the tumor invaded (i.e. rectosigmoid tumor can
infect the la
dder, cecal tumor can invade adjacent soft tissue and can even e palpated if la
rge enough, pain can result from intraneural invasion) • Lympathic spread first to
lymphatics in the mesentery, then to the cisternae chylli and then spread to th
e
thoracic duct to go everywhere (Virchow’s node) • Hematogenous spread to liver and
ones Tx – depends on stage of cancer • surgery – for primary colon cancer localized

to the colon or as palliation for
severe cases where patients have intestinal

o
struction or sever, persistent leeding • radiotherapy – used in com ination with ch
emotherapy and surgery in patients, more important role in palliation
• chemothera
py – adjuvant given post op for patients with Duke’s

B or C – a 5-FU ased regiment
wi
th irinotecan o Duke’s Staging A – confined to owel wall B – extended
through the ow
el walls C – LN metastases D – distant Metastasis such as to liver or one Epidemiol
ogy • Peaks incidence in 60-70, with < 20% occurring in patients <50 • In young pers
ons, pre-existing ulcerative colitis or polyposis syndrome is suspected • Step-wis
e progression of the tumor o 2 pathways 80% of the time APC/Β-Catenin pathway – loss
of APC (APC degrades β-catenin so that it can not go intot he nucleus to turn on
myc and cyclin D1) then loss of k-ras (trapped in active state and deliver mitot
ic signals and prevent apoptosis 18q21 deletion (DCC gene – gene involved in expre
ssion nectrin-1 which is involved in axonal guidance and also a
loss of the DPC/
SMAD genes result in TGF-β signaling loss – which normally inhi its cell cycle progr
ession) loss of p53 15% of the time DNA mismatch repair genes loss of MLH1, hMSH
2 resulting in formation

of microsatellites in non-coding regions of the
genome
(which are unsta le during replication) resulting in microsatellite insta  ility
(MSI) mutation

due to microsatellite forming in TGF-β II receptor and AX genes so
, no inhi ition and no apoptosis 10
•
Ovarian Cancer - causes death more than cervical or uterine carcinoma together -
silent growth makes them dangerous - > 50 yo – most cases - nulliparous
women (lo
w # pregnancies or history of infertility have an increased
risk - irth control
pills may reduce risk - 5-10% occur in familial setting ( reast-ovarian cancer
syndrome, Lynch Syndrome type
II – increased risk of colon cancer) - diverse cell
types seen in ovarian cancer ecause 3 cell types make up the ovary – the coelomic
covering epithelium, totipotent germ cell, and multipotent stromal cells o epit
helium cancers are the most common (90%) - Pathogenesis o Increased risk with in
creased

# of menstrual cycles suggest that disruption of the ovarian
cortex with
su sequent cellular proliferation and repair increases the

possi ility of mutat
ion that can lead to cancer formation o Familial cases pro a ly have to do in pa
rt with
 inherited mutation in the tumor suppressor
gene or DNA mismatch repair g
enes RCA1 gene, located on chromosome 17q • A out 20-40% of women with this mutat
ion will develop ovarian cancer • With RCA 2 mutation, the risk is 10-20% Mutatio
n in the DNA mismatch repair genes can lead to Lynch II Syndrome which has a 10%
increased risk - Classification according to their cell of origin o Epithelial
tumors – thought to arise from mullerian duct (para-mesonephric ducts),

formed as
an outpouching

of the celomic epithelium into the UG mesenchyme, can e
enign,
malignant or orderline
(low malignant potential)

Serous tumors – occur etween 30
-40 years of age • Can e solid

or cystic, ut is mostly cystic – cystadenomas or cy


stadenocarcinomas

• 60% are enign (covering

is glistening and smooth – 25% of the
enign forms are ilateral), 15% are orderline and 25% are malignant (malignant
forms show nodular

irregularity which represents penetration of the tumor throug
h the serosa) • orderline and malignant are the most common malignant
tumors (60%
of malignant tumors) • small cystic tumor can reveal
a single cavity, ut larger
lesions are multiloculated
with sections separated
y septa – cystic spaces are fi
lled with fluid, considera le amount of mucus can e present
• papillary masses pr
oject into the lumen of the cystic spaces • histologically – enign tumors have sing
le tall columnar epithelium that lines the cyst,
some cells are dome shaped secr
etory cells and other are ciliated o Psammoma odies (concentrically laminated c
oncretions) are common in the tips of the papillae o With malignancy,
 you see in
vasion of the stroma and more

anaplasia of the lining cells o orderline cells c
an seed to the peritoneum, ut rarely invade – prognosis depends on
if there is in
vasion o Malignancy and spread to regional lymph nodes is common, ut distant ly
mphatic and hematogenous metastases is uncommon o
Malignant tumors confined to t
he ovary – 70% 5 year survival, 100% if it was a orderline tumor, those cancers
w
hich have penetrated the capsule, 13% for 10 year survival, 80% if it was order
line and penetrated capsule 11


Mucinous tumors – similar to serious tumors, ut the epithelium here consists of m
ucinsecreting

cells similar to those
of the endocervical mucosa, overall
less li
kely to e malignant tumors • 5% are enign and 20% are malignant ilateral tumors
, overall lower incidence than serous • larger and more multiloculated
than serous
tumors and less likely to have papillary formations, no psammoma odies on the
tips of papillae, however, if the tumor is malignant, it will have prominent pap
illation, serosal penetration and solidified areas • histologically separated into
mucinous cell types – those of endocervical, intestinal type epithelium and mulle
rian mucinous cystadenoma (associated with endometric cysts) • mucinous
tumor rupt
ure can result in deposits in the peritoneum (pseudomyxoma peritonei) – ut majori
ty of pseudomyxoma cases, ovarian cancer is a result of GI metastases Endometroi
d tumors – mass projecting from the
endometriotic cyst filled with chocolate color
ed fluid, microscopically you see
tu ular glands
within the linings ofcystic sp
aces • Usually malignant although enign and orderline forms exist • ilateral in 3
0% of cases, and 15-30%

of patients with this have a concomitant endometrial car
cinoma Cystadenofi roma –
a variant of serous cystadenoma which has more pronounce
d proliferation of the fri rous stroma  that underlies the columnar epithelium – tr
ansformation into malignancy is rare renner Tumor – uncommon, unilateral, ovarian
tumor o Germ cell tumors – occur  mainly in children or young women Teratomas – comp
rise 15-20% of ovarian tumors • enign (mature) Cystic Teratoma (90%)
o Mature ect
odermally differentiated cells o Onfetn
form cysts filled with se aceous secreti
on and matted

hair that reveal a hair- earing

epidermal lining o Occasionally yo
u’ll see ones, teeth, cartilage, GI or ronchial epithelium in them o 1% transfor
m into a malignant squamous cell carcinoma • Immature Malignant Teratoma
o Mean ag
e 18 years o More malignant, seeing a more solid, hard cyst than the enign coun
terpart – neuroepithelial differentiation is also noted o Stromal sex co rd tumors
– ovarian mesenchyme origin, some of these tumors produce hormones Granulosa-thec
a cell tumors – mostly occurring in postmenopausal women, unilaterally
• Varies in s
ize, with cystic spaces present – composed of a mixture of cu oidal granulose cell
s in cords, sheets, or strands and spindled or plump lipid laden theca
cells – the
granulose

cells may recapitulate ovarian follicle called Call Exner odies • May
ela orate large amounts

of estrogen from theca cell components and so may promot
e endometrial

or reast carcinoma. Post menopausal may regain menstrual cycles T
hecoma-fi roma – any age, unilaterally • 40% produce ascities and hydrothorax (Meig’s
Syndrome)
Sertoli-Leydig Cells – all ages, unilateral • Recaps development of testis
with
tu ules or cords and plump, pink Sertoli cells • May masculinize or defemini
ze, ut uncommonly malignant 12
-
-
-


o Metastatic

carcinoma – older ages,

occurs mostly ilaterally Primary metastases
from reast, lung, and GI (Kruken erg tumors) May see signet-ring mucin secretin

tumor Non-neoplastic syndromes of the ovaries o Follicle and Luteal Cysts May
g
e found on physical exam
– usually regress spontaneously and only clinically sign
ificant

if they cause o struction from their growth o Endometriosis – cysts lined
y endometrial glands and stroma can cause discomfort during menstruation, infer
tility, or as a mass can affect other organs o Polycystic ovaries (Stein-Levinth
al Syndrome)

Clinical approach to Ovarian Carcinomas o CA 125 levels – a glycoprot


ein made
y ovarian cancer cells that is released

into circulation and can e me
asured y monoclonal

assay system and allows a ility
to monitor the course of th
e illness, ut, the test is not specific enough to e used
as a screening method
for making a diagnosis o Growth can invade the rectum, ladder, and other pelvi
c structures o Lymphatic drainage goes to the para-aortic lymph nodes and other
lymphatics
lead to the external iliac and
inguinal nodes o Hematogenous spread i
s uncommon ut can occur to the lungs, ones, or liver o Most common metastases
is via trans-coelomic spread – shedding of tumor cells into the peritoneum, often
you can see metastases all over the peritoneum If it spreads into the lymphatics
, they can end up in the lungs, reaching the pleura and then anterior mediastina
l lymph nodes Disruption of normal fluid drainage and changes I the peritoneal s
urface results in formation
of ascites Therapy o Surgery – effective if completely
limited to the ovaries, ut this is uncommon Frequent use with chemotherapy Cyt
oreductive

surgery involves an attempt to remove all of the
tumorous nodules vis
i le during the surgery, the more complete a resection, the etter the patient’s p
rognosis o Radiotherapy – radiation treatment useful in palliation
due to a locali
zed tumor o Chemotherapy – systemic
chemotherapy is a valua le tool for patients w
ith ovarian cancer that can not e completely
removed, or to reduce the risk of
recurrence following a complete resection Car oplatin and taxol are most effecti
ve Interperitoneal chemotherapy is useful only in cases where there is a small v
olume of cancer

– in theory, it tries

to deliver higher doses of chemo tot eh tumo
r nodules, ut there is stilla pro lem of delivery since diffusion into the tumo
r nodules limits this approach
Cervical Cancer - higher incidence in women who have had many sexual partners an
d those who had 1st sexually intercourse at a young age - HPV 16 and 18 infectio
n increases risk greatly, types

6 and 11 are lower risk o HPV causes activation


of E6 and E7 proteins which u iquinates the p53 protein leading

to its

reakdown
and results in lower p53 levels in cells, E7 results in inding to R gene and
increase in DNA synthesizing enzymes, overall E6 and E7 enhance the cell’s prolife
rative capacity - Smoking increases the risk (carcinogens in cigarette smoke dep
osit in the cervical epithelium), lower socioeconomic status - Starts froma prec
ursor lesion called CIN with peak incidence around 30 years, and which can turn
into an invasive carcinoma with peak incidence at 45 years of age 13
-
Pathology o Cervical Cancer precursors
CIN (cervical intraepithelial neoplasia) •
This precursor can precede the cancer y 20
years, and only some progress to an
invasive carcinoma CIN I – mild dysplasia (a out 1/3 of cells dysplastic) CIN II – m
oderate dysplasia CIN III – severe dysplasia

and carcinoma in situ Higher grade ca
ncer has a higher chance to progress, ut many instances also exist where the le
sions do not progress to cancer HPV is detected in 90% of CIN and invasive carci
nomas, condylomas are associated with low risk HPV types Morphology
• CIN I – koiloc
ytosis – nuclear angulation with perinuclear vacuolization produced y the
virus (
HPV) • CIN II – involves these changes to more layers of the epithelium,

ut superfi
cial layer of cells is still well differentiated

• CIN III – marked y even greater
variation in cells and disorientation

and a normal mitosis affecting all layers
of epithelium All of the a ove develops in the T – zone of the cervix – key features
are koilocytic atypia, increased mitotic activity,
loss of maturation, nuclear
enlargement, hyperchromasia and irregularity and a normal mitotic figures o 70%
of women with carcinoma in situ will go on to develop invasive carcinoma o Invas
ive Cervical Carcinoma 75-90% are squamous cell carcinomas, 10-25% are adenocarc

inomas, adenosquamous or undifferentiated carcinomas may present with vaginal l
eeding especially

after intercourse due to tumor enlargement and
ulceration if
m
etz to the ladder you can get hematuria, or it can result in o struction of ot
h ureters, which can result in renal failure, encephalopathy, hyperkalemia and t
hen eventual cardiac arrhythmia and death, intraneural

involvement causes intens
e pain lymphatic mets can go to the iliac, o turator, deep, hypogastric and sacr
al nodes, ultimately leading to the para-aortic nodes, and enlarged nodes can le
ad to impair drainage from legs causing leg edema, or compression of adjacent ve
ins can
also result in leg swelling hematogenous spread
can go to the lungs, liv
er, and ones Therapy • Surgery – extensive resection, ut can result
in poor qualit
y of life • Radiotherapy – can result in cystitis, or proctitis, ut is generally

us
ed for cnacer that is localized to the pelvic area and for palliation of one me
ts o Sometimes, chemotherapy is given concomitantly to make the radiotherapy mor
e effective (i.e.

cisplatin) • Chemotherapy – can result in decreased tumor size pos
t treatment, ut usually this lasts only for a short time
14
Lymphomas - Malignant Lymphomas o Hematopoietic neoplasms resulting from clonal
expansion of lymphoid cells, accumulation
in lymph nodes causing lymphadenopathy
, if the cells spill over into the lood it starts a leukemic phase where it can
infiltrate tissues and impair function o Usually derived from a single transfor
med cell and is therefore a monoclonal proliferation (as opposed to a reactive l
ymphoid hyperplasia
 which is polyclonal) o Most of the Lymphomas seen in the wes
tern world are cell derived
and these cells express surface or cytoplasmic Igs
and Light chain analysis can e used to assess monoclonality o Cell markers are
used to distinguish the cell lineage cells – CD 19, 20, 22, 79a T cells – CD 2, 3
, 4, 5, 7, 8 NK
cells – CD 2, 56 Cells tend to go to areas where they normally go,
they are capa le of
re-circulating and seeding other lymphoid or non-lymphoid o
rgans throughout the ody - Malignant Lymphomas are
separated into 2 major group
s – Hodgkin and Non-Hodgkin which are distinguished ased on histological appearan
ce with staining,
immunophenotyping and genetic analysis. In
addition, the prese
nce of Reed-Stern erg Cells are indicative
of Hodgkin - Some asic info of Lymph
ocytes o Precursor T cells made in the one marrow go to Thymus  to finish develo
pment and then enter peripheral
circulation later o Precursor cells undergo de
velopment and maturation in the one marrow and then circulate
to secondary lymp
hoid tissues where they may come into
contact with antigen to ecome active and
to terminally differentiate into A producing  plasma cells - Lymphocyte prolifer


ation and Differentiation o In lymph nodes Cells are in the follicles, su caps
ular region of the cortex and medullary cords, T cells are in the paracortical z
ones o In spleen T cells are in
the Periarteriolar sheaths - Classification
of L
ymphomas o WHO
 classification – ased on the REAL classification – is ased on the c
ell lineage cell
neoplasms T cell

and NK cell neoplasms Hodgkin Lymphoma Hodgk
in Lymphomas - imodal
age distri ution – once in early 20s and second in 50s  - un
common with only a out 7000 incidence yearly - unknown etiology – although
E V is
involved in 50% of cases - Pathology o Histological Presence of Reed Stern erg C

ell – central to diagnosis, in the lymph node These cells can come mononuclear, i
or multinucleated variants ackground has reactive inflammatory cells including
small

lymphocytes, histiocytes, granulocytes and plasma cells - Classifications
ased on WHO o Nodular Lymphocyte PredominanceHodgkin Lymphoma (6% of cases) P
opcorn cells Neoplastic cells are CD20+, CD45+
cells derived from the germinal
center o Classical Hodgkin
 Lymphoma Reed-Stern erg Cells – large cells with large
eosinophilic nuclei cell lineage Cells – are CD30+ and CD15+ and CD4515
-
-


Classical Hodgkin is divided into • Nodular Sclerosing – nodular pattern,
collagen
ands seen and lacunar cells • Mixed Cellularity – frequent

Reed Stern erg cells • Lymp
hocyte rich • Lymphocyte deplete – numerous Reed Stern erg cells
and few lymphocytes
Clinical features o Enlarged Lymph Nodes – can sometimes cause o struction of adj
acent structures, depending on location (i.e. adenopathy in the
mediastinum may
result in occlusion of the SVC, nodes in retroperitoneum can o struct the ureter
s) – use CT scan to assess extent of nodal

involvement o Infiltration to Organs – in
advances stages, can go to the liver, one marrow and lungs and can result in l
ife-threatening organ dysfunction o Systemic Effects – often see
fever without

evi
dence of infection, night sweats and weight loss (all known to e mediated y cy
tokines)

o Staging system I – single group of lymph nodes II – groups of lymph
nodes
, ut all on the same side of the diaphragm III – Groups of lymph nodes on oth si
des of
the diaphragm (mediastinal and retroperitoneal) IV – visceral organ infiltr
ation ( one marrow and liver, etc) If there are no systemic symptoms,
 then A is
added to the
end, if they have a systemic symptom, then you add Tx – spread is i
n a predicta le, node to node manner to adjacent chains so treatment is dependen
t on staging, however, surgery is usually not a mode of
therapy for Hodgkin o Ra
diotherapy

– used

for localized lymphoma, provides valua le palliation and can als
o e used
as com ination therapy with

chemotherapy

o Chemotherapy – anthracyclines
(doxoru icin), vinca alkaloids (vin lastine),

elomycin and DTIC
are used and t
herapeutic goals are for a cure and can e given as an outpatient ased regimen
Non-Hodgkin Lymphoma (NHL) - often presents in extranodal phase or leukemic phas
e of the disease - increasing incidence in US, with 60,000 newly diagnosed annua
lly - increased risk in people
 with impaired immunity such as AIDS or immuno-sup
pressed post transplant - urkitt’s Lymphoma is highest in east Africa and is asso
ciated with E V infection, also seen in the US associated



with HIV infection - T
cell leukemia for people in southern Japan

and Cari ean asin associated with
HTLV-1 infection - Etiology – unknown, ut associated factors are o HTLV-1 infecti
on – small fraction of infected patients who are
infected develop this o Follicula
r Lymphoma t(14;18) – gene on chromosome 18 is cl-2 (an anti-apoptosis

gene), whi
ch gets transposed onto Ig heavy chain gene to cause it to ecome activated, all
ows cells to avoid normal
 apoptotic pathway and to have a decreased responsivene
ss to chemotherapy o urkitt’s Lymphoma t(8;14) – or also, 2;8, 8;22 – chromosome 8 ge
ne codes for c-myc and the translocation turns on the expression of 14, 2, or 22
constitutively (this heavy chain and 2 ligth chain variants) o Mantle cell Lymp
homa t(11;14) – fuses the cyclin D gene to Ig heavy chain gene on 14 - Classificat
ion and Histopathology o Check for immunological markers (CDs) o Cytogenic analy
sis – for identified translocations o Gene rearrangement studies – clonal rearrangem
ent of Ig genes - Clinical features – vary greatly depending on the specific type
of lymphoma 16
-
o Enlarged lymph nodes – Non-Hodgkin has a discontinuous Lymph node involvement an
d tends to involve nodes out of the central group, and again, enlargement can ca
use compression of adjacent

structures o Infiltration of Organs – in non-Hodgkin,
lymphoma cells enter the loodstream earlier on
o Systemic Effects – fever, night
sweats, weight loss Tx – has
a very unpredicta

le course o Radiotherapy – effective
against localized disease, ut can not e a cure since more cases have dissemina
ted
disease o Chemotherapy – alkylating agents, anthracyclines, and vinca alkaloid
s A against CD20 antigen on cells given IV can result in remission


reast Cancer - most

common cancer in women next to skin cancer, ut lung cancer
is still
the num er one killer due to cancer - mortality has decreased in recen
t years, ut incidence

as increased - 2/3 of cases occur in women >50 – increased
risk with age, ut plateaus after menopause - risk is increase with women who ha
ve has early onset of periods (early menarche),

late menopause, are nulliparous
or have had a late first pregnancy or reast feeding for more than 16 months – all
suggestive of a role for exposure to estrogen o oral contraceptives

and hormone
replacement therapy has minimal increased incidence - reast is sensitive to th
e carcinogenic effect of ionizing radiation – so you see increased risk in women f
rom Japan (WW II), those who have received radio therapy to the mediastinal area
for Hodgkin’s therapy - incidence is increased in women with first degree relativ
e, may have a role
in common environmental exposures and/or heredity (5-10% of c
asesare known to e of hereditary origin) o hereditary conditions have
 mutation
in RCA1 on chromosome
17q, or on RCA2 on chromosome
13q. RCA1 and RCA2 muta
tions have to do with a out 50% of hereditary cases of reast cancer  o men with
the mutations
have increased risk
 of prostate
 cancer, those with RCA2 have incr
eased risk of reast cancer o RCA1 and RCA2 mutations are also associated
with
Ovarian cancer o Li-Fraumeni Syndrome – p53 mutation on 17p seen in some reast c
ancer cases - Alcohol increases risk -
Environmental factors play
a crucial role
, diet may play a role - Pathology o Fi roadenoma – most common enign tumor, peak
incidence

in 3rd decade of life Clinically presents as solitary, discrete and m
ovea le masses which can enlarge late in pregnancy or during
the menstrual cycle
and can regress

and calcify


post-menopausally Almost never ecomes malignant
We
ll circumscri ed, tan, ru
ery mass Microscopically
you see proliferation of en
ign stroma, ducts and lo ules o Phyllodes tumor Fi
roadenoma variant that involv
es older patients >50 that arises from the intralo ular stroma Microscopically – i
ncrease cellularity, stromal overgrowth

and irregular margins, may locally recur
or rarely metastasize (only a out 15% of the time) o Intraductal

Papilloma Neop
lastic growth within a duct,

and present clinically with a loody nipple dischar
ge, presence of a small su areolar tumor
a few millimeters

in diameter and rarel


y nipple retraction Solitary ones remain enign, ut the multiple lesions can e
come malignant 17



Considered enign if
oth epithelial and myoepithelial cells are present
in the
papillary neoplasm, ut if the myoepithelial portion is missing, it can e a pap
illary carcinoma o Malignant Carcinoma Prognostic factors for consideration • invo
lvement of axillary lymph nodes – greater spread, poorer prognosis • size of tumors
determine

likelihood of metastasis • expression of receptors for progesterone or e
strogen y tumor cells –
determined with immunohistochemistry


o presence of recept
ors
is associated with a etter prognosis ecause it will e responsive to hormo
ne ased therapy
o over expression

of the her2/neu receptor which is an EGF-rece
ptor occurs in a out 25% of reast cancer
cases and is associated with a poorer
outcome • presence of enzymes which reak down the stroma (i.e. cathepsin D) is as
sociated with a poorer prognosis • increase in # of microscopic

vessels,

increase
serum levels of VEG-F are negative prognostic factors – pro a ly ecause
metastase
s is facilitated with

higher vascularity Most often
involves the left reast mor
e, 4% of cases are ilateral or 2 lesions in same reast 50% are in upper outer
quadrant, 20% are central portion, 10% in each of the other quadrants
classifica


tion is divided in those that have invaded or not invaded the asement mem rane
Non-invasive Carcinomas • Ductal Carcinoma In Situ (DCIS;
intraductal
carcinoma)

o
Composed

of cells of
ductal epithelium that are confined y the asement

mem ra
ne, may e identified y its association with microcalcifications visi le on mam
mograms o Has increased

incidence with more mammography (due to the fact that th
e calcifications can e picked up) o Primarily
an ipsilateral risk in developing
invasive carcinoma (8-10X higher risk) • Lo ular carcinoma
in situ (LCIS) o Invol
ves cells in the terminal ducts and acini, typically ilateral and multifocal wi
th a 6-9X increased risk of developing invasive cancer o Has
a more uniform appe
arance

than DCIS o A marker for the development

of invasive reast cancer o Expa
nds, ut does not alter the underlying lo ular architecture Invasive Carcinomas •
Invasive ductal

carcinoma not otherwise specified o Most common type – associated
with
DCIS, ut rarely LCIS o Produces
a desmoplastic response which replaces nor
mal reast fat forming a hard, palpa le mass – heterogeneous appearance of cells w
ith irregular margins forming ducts within the desmoplastic stroma o Advanced le
sions can cause dimpling of
the skin, retraction of the nupple or fixation to th
e chest

wall • Invasive
lo ular carcinoma – an invasive carcinoma with cells that re
sem le the lining of lo ules – the cells are small
with scant cytoplasm can grow i
n a classic Indian file pattern or target
like ulls eye pattern – 5-10% are this
type and it has a higher incidence of ilaterality – 20% 18
•
•
•
• o Therapy Local disease • Masectomy or lumpectomy – if lumpectomy, you need radiatio
n therapy afterwards, either method has same survival • Axillary dissection Metast
ases • Tamoxifen (anti-androgen drug) • Chemotherapy

– sensitive to alkylating gents (
cyclophosphamide),


anthracyclines (doxoru icin) taxanes and vinca alkaloids – tras
tuzami inds to the her2/neu receptor on the cell surface and may improve progn
osis Radiation therapy

– improves the outcome if used as an adjuvant • Useful also a
s palliation for one metz Hormonal

therapy – good if the tumor expresses estrogen
receptors • Use tamoxifen –
locks estrogen’s actions o
Primarily used as adjuvant to
prevent reoccurrence • Possi le to use drugs which inhi it aromatase action so th
at no estrogen is made o Other malignancies
Piaget’s disease of the nipple – indicat
ed there is a cancer somewhere in the reast • Ulceration, oozing, crusting and fi
ssuring of the nipple and areola o Microscopically see intraepidermal spread of
tumor cells (Paget cells), with tumor cells occurring singly or in groups, often
have a clear halo surrounding the nucleus o Commonly associated with an underly
ing invasive or in situ ductal carcinoma


Good
prognosis su types o Medullary carcinoma (associated with RCA1)
– 2%
of case
s of reast cancer – sheets of large anaplastic cells, well circumscri ed orders
Has a lymphocytic

infiltrate o Colloid carcinoma – microscopically

see clusters of
small, land tumor
cells floating in pools of mucin o Tu ular carcinoma – rarely
presents as palpa

le masses – accounts for 10% of invasive carcinomas – composed of
well formed tu ules with lowgrade nuclei, LN mets are rare Poorer prognosis – Infl
ammatory carcinoma o Red, warm erthyematous
skin (due to clogged lymphatics not
actual inflammation), thickened skin
resem ling
 an orange peel with dimples, ext
ensive dermal lymphatic invasion y the tumor iopsy is necessary to confirm lym
ph node spread – patients with

> 10 axillary
nodes involved have poor prognosis Sy
stemic mestastases is possi le to the lungs, ones, CNS
19