Neoplasia- continuous cell proliferation can be benign or malignant. Increase mitotic rate.

Even
benign can be reversed
Endometrial hyperplasia- bleeding cervical os , post menopause, reversible
HPV- CIn1 ,2 ,3(high grade dysplasia) , from hyperplasia to dysplasia
Tumor- can be benign or malignant (note malignant does not mean metastasis)
Cancer- malignant, most cancer of an organ is a metastis from a primary

Adeno- glandular (breast, GIT, note baretts esophagus persistent gerd can cause
adenocarcinoma,
Sarcoma-mostly hematogenous
Melanoma- fastest growing cancer
Lymhoma-Non Hodkins lympha (large B-celll lymphoma, follicular lymphoma, burkit
lymphoma,hairy cell)

Benign—usually small size, capsulated or demarcated, e.g tubular adenoma can be find using
full endoscopy DON’T USE SIGMOIDOSCY. Tubular adenoma also called peduncular adenoma-
Most common leiomyomas- Is benign and common in uterus, don’t turn into sarcoma but
multiple firbomas, African young female, most common cause of dysmonnerhea.
tetraoma-common in midle, mediastinum, pineal gland, between center of ovaries and testes, if
young patient think about sacrococcygeal, in xray has calcification, female more benign male more
malignant tetrotoma common hypothyroid in CT scan- whitish area

Malignant - darkened T-increase mitotic rate malignant has lots of M phase, metaphase
pleophorphic adenoma- most common site in salivary gland-parotid which is benign but its
benign malignant- increase nuclear activity, lots of mitosis, increase nucleus size,hyperchromasia.
Plenomorphism can bening or malignant as salivary adenoma in the parotid

prognostc indicator of breast cancer- axillary lymp node thru invasion grading is differentiation
squamoius cell- with pearls has well differntiated, tongue, crvix, larynx, skin poorly dfifenriated-
anaplastic, adenoma-lower esophagus , gastric, colorectoal, pancreatic ,
lymphoma- mostly bcell cd1 cd5 is tcell is in skin
19 20- bcel originl lymp node or GI tract
osteosarcmona- mos common in knee, near tibia metaphysis part of the bone.

Cytokeratin- epithelial carcinoma

Rhamdomysocarma- desmin
Sarcoma and mesenchymal s- vimentin
PSA- BPH(frequency and inability to void) prostate cancer not central or peri-urethral so prostate
cancer wont give BPH symptoms
Lower CD-T-cell (1,5), Higher CD-Bcell 19 20
S100 is for melanoma but not specific but BRAF

Malignant Neoplasma
-starts with increasing PROLIFERARTING creating in-situ , note in-situ is malignant
BURSTING then metastasis , THEY Bust BASEmemebrane thru type 4 collagenase.
Colorecttal cancer spread to liver via portal vein . Movemement is from basement membrane to
instersitium and tumor cells within the instersitium interacts with fibronectin.
Carcinoma- role of thumb prefers lymphatic EXCEPT colorectal cancer where
hemategouns via portail vein same as renal cancer via renal vein. COLOREACTAL 3RD
LEADING CAUSE OF DEATH BOTH GENDER
- If carcinoma enters the lymp node they eventually enter the blood hemetagenous

Seeding – csf, ovarian and pleura. Surface.

- OVARIAN cancer most common is thru surface called serous
cystadenomcarcimoma most common malignant ovarian cancer thru seeding in
peritoneum.
- Only cause of mesolthelium in US a roofer is asbestos.
- Most common cancer in the brain in dults is glioblastoma multiforme which seeds
into csf
Bone metastasis- 72yr old, digital exam , gritty prostate, increase alkaline phosphate, increase
PSA called prostate cancer,. Usually in the peripheral sde. If its metastize in the verbtebrae
csf bone metastasis-most common site is the vertebrae. thru batso paravertebral plexus increase
alkalin phosphatase- osteblastic, deposition of bone,more opaque, “hot bone”,
osteolytic- bullets , punced out lesion, hypercalcemia(multiple myeloma), decreae opacity prstat cx-
rigid, periphery. Multiple myeloma not mestatsis

bone fractures with decrease opacity- bone metastasis

Epidemilogy of Cancer
Ovarian cancer- aged 42-45, post menopausal bleeding, but diagnosed at aged 61, 21 yrs
causing increase ovarian.

cervical- papsmear , cervical os bleeding or post-renal failure thru lateral invasion cervical cance-
HPV 16, 18, 31 33 vqaccine-gardasil cervic

Proto-oncogene- we required for normal growth, when mutated it becomes oncogene.

Receptor communicates to the signal transducer in the cytoplasm then to the nucleus
In the nucleus you need transcription factors, dna repair,

8:14 translocation-Burkitts lymphoma ( 8 upon 14)

igH- Heavy chain of chromosome 14
myc oncogene is on the chromosome 8
when you have a oncogene in an immunoglobulin, increase immunoglobulin. 2 types of burkits,
endemic is Africa, non endemic will be nirth africa

Light chain immunoglobulin- multiple myeloma,IgG,IgA. Note bence-jones proteins for multiple
myeloma. Note normal chromosome no translocation

Gene Amplication- N-myc

- Instruct a DNa to never stop replicating
- N-myc neuroblastoma
Growth Factors- stimulate receptors in excess, increase signal transduction down to the
nucleus thus increase growth

FGF- associated with HST1 LEADs stomach cancer

FGF- INt
PDGF- astrocymoma (gliomas). 2 types of astrocytoma: glioblastoma multiforme and palisdic
type of neuroglioma

Growth receptors

ERB1- squamous cell lung cancer

ERB2- breast, ovary carcinoma
RET- medullary cancer in thyroid, mEn 2a and 2b

Chromosal translocation
9:22 bcr abl fusion protein
chronic myellgenic leukoma aged 40
ALL is in a child
Both assoc with Non RTK

RAS-mostly in pancrease and colon

Assoc with GTP, N-ras (neuro problem)

n-myc gene gets amplified in its location on the chromosome giving rise to a
homogenous staining region (HSR) because the same gene is present in too many
copies in tandem

CDK
Within the cell, mantle cell lymphoma 11:14

E2f and Rb regulators for g1 and sphase.

When rb is phsophyrlated it promotes to sphase
CDK4 and cyclin D is the active kinase for phosrolyting RB
Cyclin D-part of mantle cell lymphoma, upregulated Cyclin D increasing CDK4 then
Increase growth factor, myc, ras increases Cyclin D
P53
- Cell stress, dna damage it induces repaired genes
- If cant be repaired, so it wont go to the cell cycle(apoptosis)
- P53 will arrest cell, it inhibits cdk4,cyclin d thru p21
- pINk4
- p16 is a tumor suppressor
 - MDm2 and p53 is a feed back regulation

Active e2f- g1 to sphase

- G0 QUITE CELLS (hepatocytes)

Transcription of Cyclin E/CDK2-progression to sphase

P27- inhibits cyclin e/cdk2

RAS
-associated with G-protein
-activated GTP, and need to be inacted by GTPase
-GDP is inactive
- cancer RAS is always active, RAS always active GTP, GTPASE not working
-GTPase augmenting protein is inhibited in cancer
-RAS bound to Gprotein in the cytoplasm in the membrane active MAP, MYC
- GFactor bound to the receptor , GTP bound to RAS , RA. After RAS is completed, GAP will be
there
-in cancer, downreguated GTPASE and GAP. Thus increase RAS activity.
-fernasyl protein anchors ras to the membrane

Tumor Suppressor Genes

- P53 –
- RB BOUND TO E2F , CDK4/Cyclin D
- FIRST HIT: germline or inherited(familial). Two hit hypothesis 2 alleles
- 2nd hit- sporadic or acquired
- Inherited/familial: familial retinoblaslatoma – fundocoscopy shws leuocorrhoea, in the
retina has color white in its in chromosome 13
- LI-fraumena syndrome- coughing blood, early satiety, infertility, weight gain , increase
left supraclavicalr lymp node, e-cadherina negative thus spread to left supraclailar node
called virchows node(gastric adenocarcinoma), hemompotysis and early satiety Is gastric
adenocarcinoma. Chest Xray shows primry one nodule in mediastinum. IF infertility, non
hemorrhagic seminoma in male. 2 primary cancer in gastric, seminoma

Paraneoplastic syndrome
Acanthosis nigricans- thickening of the keratinocyte giving dark color in the armpit or back
of neck think about pancreatic or gastric adenomcarcinoma
Doc tired, at night feeling great like 5pm , gets stronger – eaton lambert opposite with
myasthnai—small cell carcinoma assoc with cancer
- They attack calcium channels (voltage gated) autoautoanitbodies attack the calcium,
no rcepot problem,
Hypethropic osteoropathy- bone underneath the nail, fingers clubbed but is actually
hypetrophy of bone underneath the nails- bronchogenic carcinoma
NBTE(non bacterior- mucu secreting cancer such aspancreatic and colorectal cancer. None
bacterial sterile
Sorrheic keratosis- adenoma carcium, ecadherin negative,
Superfiil migratory migratory thrombophlebitis- trousseau syndrome
Troessua sign- tapping of the cn7 chovstek, carpopedal spasm with brachial cuff and hp

Retinoblastoma
- Two hits needed (inherited and acquired)
- p53- associated with 50% of all cancer while ras is 25-40%
- many cancers note its li-fraumeni
- caspase 9 is for apoptosis
- Enterocytes- APC mutation causes polyp increasing the risk of colorectal cancer
- If APC is present b-catenin is dissolved or broken
- Pepmigus vulgaris a type 2 hypersenstive reaction when u scrape ur skin and shedding
off, IgG is attacking desmosome. E-cadherin is a desmosome derivate attaching
enterocytes
- If APC mutated at chromosome 5, endless b-catenin transcrptionj,
- Increase WNT increases polyps coz taget APC
- Negative Edcahderin primary gastric adenomcarcinoma goes to the left suprclaviular
lymp hones then goes to the skin called lesser trelet sign and if hematgenous goes to
the ovary then called krukenbberg
- - negative breast cancer primary lobular spreading to axillary lymph none
- mutated apc familial adempatosis polyposis
Tumor suppressor genes
-VHL Normally controls hypoxic inducible factor 1 alph (HIF-1a) CONTROLLING VEGF
- so if you lose VHL thus increase VEGF causing renal cell carcinoma(childhp00d(,
hemangiolblasmtima in the cerebellum and retina.
WT-1- wilms tumor, renal cell carcinoma of the adult, hematuria, weight loss , and flank pain.
WAGI- wilms tumor, anirida, genital abnormalities and intellectual disability.
WT2- wide body half body, renal cell carcnmoma I child with becwithman
NF2- cn8 between cerebellu and pontine, the angle there causing acoustic neuroma or
schwannoma
BRCA 1 and 2
Colorectal cancer- can also rectpro kinas siltxumiba, DCC positive, CEa positive, p53 knocked
out, Ras knocked out

Evasion of Apoptosis
-bcl2- prevents apoptosis, don’t confuse with bcr-abl with tyrosine kinase 9-22
-but bcl2 overexpressed in follicular lymphoma 14:!8, lymphoma you wont find reed-steenberg
cell thus non-hodking cell.

Most cancer is mono-clonal (one isoenzyme)

-