3. basics of neoplasia

neoplasia

neo= new

plasia= growth 

aka tumor

the process

neoplasm

the product of neoplasia

An abnormal mass of tissue, the growth of which exceeds and is
uncoordinated with that of normal tissue and persists in the same
excessive manner after cessation of the stimuli which evoke the
change

can be benign or malignant

Monoclonal proliferation

All the cells in a cancer are the direct descendants of one single cell gone bad

cancer

malignant neoplasm 

#2 cause of death

oncology 

study of cancer

some prefixes used to naem cancers

naming tumors: epithelial tumors

-Oma = Benign

Carcinoma = Malignant

naming tumors: Connective Tissue Tumors

Oma = Benign

Sarcoma = Malignant

lymphoma + melanoma = malignant (exceptions)

Benign vs Malignant neoplasms: symptoms

Benign: Usually none

malignant: pain, paraesthesia (numbness), systemic symptoms (malaise, wasting etc.)

Benign vs Malignant neoplasms: differentiation

benign: Resembles cell of origin

malignant: Less differentiated, especially with highly malignant tumors

Benign vs Malignant neoplasms: mitotic rate

benign: Few mitoses, all normal Slow growth rate usually

malignant: Many mitoses, some abnormal, May have rapid growth

Benign vs Malignant neoplasms: nuclear features

benign: Relatively normal

malignant: intensely staining (hyperchromatic) nucleus

Relatively large nucleus in relation to cytoplasm (high nuclear/ cytoplasmic ratio)

Benign vs Malignant neoplasms: cellular uniformity

benign: Cells uniform

malignant: Cells and nuclei vary in shape and size (pleomorphism)

Benign vs Malignant neoplasms: prognosis

benign: Usually very good

malignant: Major cause of death

Benign vs Malignant neoplasms: behavior

benign: Grows locally, compressing adjacent tissue usually

malignant: Invades adjacent tissue

Benign vs Malignant neoplasms: suface changes

benign: Stretches overlying tissues

malignant: Overlying epithelium may be ulcerated

Benign vs Malignant neoplasms: margin

benign: Encapsulated often (prevents them from moving to distant tissues) Therefore freely moveable

malignant: regular invasive margins Therefore fixed to adjacent tissues (indurated)

Benign vs Malignant neoplasms: spread

benign: Expands in one area only

malignant:May metastasize through bloodstream or lymphatics
May spread along nerve trunks

Benign vs Malignant Tumor: cause

Both are caused by increased cellular proliferation

i.e. Increased cell cycling

Genotype VS Phenotype of cancer

The genetics of cancer may start long before changes are visible

clinically + microscopically

Dysplastic/ dysplasia

Some mutations
pre cancerous stage

Mild dysplasia

Limited to basal layer

Moderate dysplasia

Basal layer to mid portion of spinous layer

Severe dysplasia

Basal layer to level above midpoint of spinous layer

Ca-in-situ dysplasia

Basal layer to surface ("top-to-bottom")

No invasion

followed by cancer

In situ 

Almost able to invade

Malignant

Invades and can metastasize

actual cancer stage

Induration

a hardening or thickening of tissue

does not ONLY mean malignancy
could also indicate scarring or deep inflammation

cancer spreads by penetrating:

1. basement membrane

2. extracellular matrix

3. blood vessels

cancer spread steps: penetration of BM

1. Tumor cells detach from each other (down regulation of
   cadherins)

2. Laminin - Glue binding the BM constituents to each other & to epithelial cells via receptors

3. increased laminin receptors on cancer cells

4. Penetration of basement membrane

5. Tumor secretes Type IV collagenase & other proteases to break down BM proteins

6. Cleavage products have growth-promoting, angiogenic
   and chemotactic properties

cancer spread steps: penetration of ECM

Overexpression of fibronectin helps cancer to spread

Tumor secretes collagenase and actively moves through the tissues (AMF - autocrine motility factor)

cancer spread steps: penetration of blood vessels

Much like penetrating basement membrane

Tumor cells may clump with platelets forming tumor cell emboli

where can cancer spread?

Local invasion

Lymphatic

Blood-borne (vascular)

Seeding body cavities 

Cancer Families

Cancer is much more likely than in general population
– earlier age
– multiple tumors
– worse prognosis

Rarely, because damaged DNA cannot be repaired

Fanconi’s Anemia, Xeroderma Pigmentosum, Bloom’s syndrome

Gorlin-Goltz Syndrome or Nevoid Basal cell Carcinoma Syndrome

Mutation in tumor suppressor gene patched (PTCH) on chromosome 9

Basal cell carcinoma starting in childhood

Multiple darkly pigmented nevi (mole)

Palmar and plantar pits (palms & soles)

Gorlin - Goltz Syndrome manifestations

Multiple Odontogenic Keratocysts

May be aggressive

Bifid ribs, Scoliosis, Frontal bossing

Hypertelorism, Marfanoid habitus (long + slim face) 

Calcified falx cerebri

Sometimes cleft palate

Gardner Syndrome

Hereditary syndrome - Linked to band 5q21, the adenomatous
polyposis coli locus

Dental team may be first to suspect patient has this disease

Hundreds of colon adenomas that eventually turn into colon cancer

Multiple unerupted and extra teeth

Osteomas

Aggessive fibromatosis (benign desmoid tumors in abdomen)

Cancer & Chromosomes

Cancer may also result from changes in the chromosomes, not just the genes

Numerical + Structural

Structural – Translocation- Examples

Philadelphia Chromosome

Burkitt Lymphoma: Translocation between 8 & 14, Less
commonly 8 & 2 or 8 & 22

Structural - Deletions - Genetic material lost Examples:

Retinoblastoma + Wilms' Tumor

Gene Amplification

Increased expression of oncogene
Example : Neuroblastoma -- N-myc

cancer prevention

Protecting from UV radiation

Avoid Cancer Viruses

Avoid chemical carcinogens

diet

avoid tobacco smoke

Immune Surveillance

Higher rates of cancer in profoundly immunosuppressed patients

Natural selection eliminates clones with lots of antigen

Some may cause immunosuppression, others may result
from it

ex: Organ transplant + HIV / AIDS

cancer detection + diagnosis

biopsy 

pap test

Epidemiology of Cancer

Increases with age

Cancer incidence is different for men and women

Prevalence depends on complex interplay of biology and culture

Example- South-East Asia tobacco chewing is common

Oral cancer is a major health risk

In cultures where women do not smoke, lung cancer is much less common in women

Oral Cancer

In North America, about #6 

80-90% of oral cancer is squamous cell carcinoma

Risk factors for oral SCC

Tobacco
– Cigarettes, Pipe, cigar, chewing
– Reverse smoking

Alcohol

In association with smoking, not by itself

HPV 16, 18, 31, 33

Clinical / Radiographic features of oral SCC: Endophytic

Pebbly, hard

Clinical / Radiographic features of oral SCC: Exophytic

Rolled border

Clinical / Radiographic features of oral SCC: Leukoplakia 

White patch

Clinical / Radiographic features of oral SCC: Erythroplakia 

Red patch

Clinical / Radiographic features of oral SCC: Perineural invasion

Pain, paresthesia

Clinical / Radiographic features of oral SCC: Moth-eaten radiolucency

if spread into bone