Chapter 7 Summary

Tumours have 2 x basic components:

1.Parenchyma = determines name + behaviour of tumour

• Made up of the cells that are characteristic of that tissue / organ

o E.g. fat cells in a lipoma or liposarcoma
o E.g. smooth muscle cells in a leioyoma or leiomyosarcoma
• Determines if the tumour is benign or malignant

2.Stroma = the supporting, host-derived, non-neoplastic cells

• Made up of connective tissue, blood vessels, inflammatory cells, etc

• The stroma is important for the growth of the tumour + will determine the
consistency of the tumour
o E.g. hard, rubbery
• Does not play any role in determining whether tumour is benign / malignant
• The Stroma Supports the tumour, determines its Spread + if it is a Scirrhous
(hard)
• A “scirrhous tumour” has more stroma than parenchyma + it feels stony hard

NB!! Marked Dysplastic Change that Involves Entire Thickness of Epithelium

• = carcinoma in situ
• Pre-invasive stage of cancer
o E.g. cigarette smokers: Bronchial epithelium will adapt and change→
metaplasia → dysplasia → carcinoma in situ → invasive cancer
o E.g. bladder cancer that is just in the epithelial layer – i.e. in the lining
of the bladder
o E.g. cancer in the ducts of the female breast – i.e. it is only in the ducts
and hasn’t gone out of the duct into the surrounding tissue

NB!! 3 x Pathways for Metastasis:

1. within body cavities

2. via lymphatics
3. via blood circulation

Seeding Within Body Cavities:

• Cancers can spread by invading the body cavity that it started in

o E.g. cancer on the ovary → spreads inside the abdominal cavity to
cover peritoneal surfaces
o E.g. brain tumour → into ventricles → via CSF → onto meninges in
brain or spinal cord
Lymphatic Spread:

• More typical of carcinomas

• Pattern of node involvement depends on the site of primary neoplasm + the
lymph drainage of area
o Lung (respiratory passage) → regional bronchial lymph nodes →
tracheobronchial + hilar lymph nodes
o Breast → axillary lymph nodes
• Can end up in thoracic duct → into blood vessels

NB!! “Sentinel Lymph Nodes”

• = 1st lymph nodes in regional lymphatic basin that receives lymph flow from
primary tumour
• Found by injection of blue dye / radioactive tracers
• Biopsy of the sentinel lymph node:
o Determine extent of primary tumour
o Plan treatment= do we have to remove the nodes as well as the
tumour? Chemotherapy?

Haematogenous / Blood Spread:

• More typical of sarcomas

• Most feared!!
• Metastases usually happen via veins= why?
• Veins drain the organ / tissue that the cancer is in → takes cancer cells with it
→ cells often stop at 1st capillary bed
o E.g. all portal drainage goes to liver
o E.g. all blood from vena cava goes to lungs
o i.e. lung + liver are most frequent 2nd sites
• BUT: Anatomical location + veins drainage does not always explain metastatic
pathways:
o Prostate → bone
o Bronchogenic → adrenals + brain
o Neuroblastoma→ liver + bones
o Despite skeletal muscle having a great blood supply= tumours rarely
metastasis there

RB Tumour Suppressor Gene

• 1st tumour suppressor gene discovered= first found in retinoblastoma / “RB”

• Found in most cells in the human body
• Controls the G1 checkpoint in mitosis to determine if a cell can:
o Enter cell cycle for mitosis
o Exit cell cycle + differentiate or repair
o Undergo apoptosis
o Once cells go past G1= they have to complete mitosis!!
 • BUT: If the RB gene is damaged / defective damaged cells are allowed to
replicate → stepwise accumulation of DNA changes → cancer
• The RB gene is involved in many cancers= breast, bladder + lung
• DNA viruses= HPV/ HBV/ EBV can suppress the 2 x best-understood tumour
suppressor genes!

p53 Gene= “The Guardian of the Genome”

• Stops neoplastic transformation

• It monitors stress to cell + directs the best response to keep the integrity of the
genetic material in tact
• Many stresses can trigger p53 response
• If p53 senses DNA damage→ assist in DNA repair by:
o Causing G1 arrest
o Induce DNA repair→ if the cell can’t be repaired:
▪ Senescence= it isn’t apoptosed / destroyed, but it isn’t allowed
to replicate anymore
▪ Apoptosis
• p53 is vital in controlling carcinogenesis:
o 70% of human cancer= defect in p53
o Including cancer of the lung, colon, breast

NB!!! Human Papillomavirus (HPV):

• Infect squamous epithelial cells

• Genetically distinct types of HPV have been identified (70+)
• Type 1, 2, 3, 4, 7, 10→ benign squamous papillomas / skin warts

Cervical Cancer:

• High-risk HPVs= type 16 & 18 (31, 33, 35, 51)

o Found in 85% of squamous cell carcinomas of the cervix + precursors
o may cause severe cervical dysplasia + carcinoma in situ
• BUT: Only some women with HPV develop cancer....
o Certain “triggers” set the DNA changes in motion
o e.g. cigarette smoking, co-existing microbial infections, etc
• Vaccine!?!?

Anogenital Warts:

• Low malignant potential

• Type 6 + 11

Warning Signs of Cancer

• Initial signs / symptoms may point to primary site of involvement

o Unusual bleeding / discharge
o Change in bowel / bladder habits
o Change in a wart / mole
 o A sore that doesn’t heal
o Unexplained weight loss
o Anaemia or low Hb
o Persistent fatigue
o Persistent cough or hoarseness without reason
o A solid lump= often painless +/- fixed

Grading of Tumours

• Involves microscopic examination of cancer cells

• Estimate aggressiveness / level of malignancy based on:
o Degree of cytological differentiation of cancer cells
o Number of mitoses in tumour
• Grade I= most differentiated – similar to original cells
• Grade II
• Grade III
• Grade IV= most undifferentiated + anaplastic – highly malignant + likely to
progress quickly
• Criteria differ with each type of tumour

NB: PSA:

• Prostate specific antigen is used to screen for prostatic adenocarcinoma

• Elevated PSA → suspect cancer
o BUT: Also elevated in BPH / prostatitis
• i.e. low specificity + sensitivity for cancer
• BUT: Very useful in managing Rx + monitoring remission
o Successful Rx / resection → levels decrease
o Levels increase → tumour recurrence
• Oncofetal antigens / proteins, e.g. alpha-fetoprotein:
o Usually only produced during foetal period → induced to reappear with
certain benign / malignant neoplasms
o E.g. α-fetoprotein = mainly elevated in hepatocellular cancer (primary
tumour) + germ cell tumours of testes
• CEA= carcinoembryonic AG:
o Produced by embryonic tissues in gut, pancreas + liver
o Increases with colorectal, pancreas, breast, stomach, lung cancer

TREATMENT OF CANCER:

• Surgery
• Chemotherapy
• Radiation therapy
• Hormonal therapy
• Biotherapy
• Other drugs
Surgery

• Localised form of treatment

• Used:
o For staging of tumours
o For removal of tumour
o Small → whole tumour can be removed
o Large → remove part of tumour / may be impossible
o With chemo / radiation
o In control of oncologic emergencies= e.g. GIT haemorrhages
o For palliation
• Type of surgery used is determined by:
o Extent of disease
o Location + structures involved
o Tumour growth rate + invasiveness
o Surgical risk to patient
o Quality of life the patient will have after surgery

Radiation Therapy

• Can be used:
o As primary method of Rx
o As pre- or post-operative Rx
o With chemo
o With chemo + surgery
o As palliative Rx
o To reduce pain associated with bone metastases= may improve
mobility
o To Rx emergencies
• Therapeutic Effects
o Tumour cells (rapidly proliferating and poorly differentiated) = more
likely to be injured by radiation than normal cells
o BUT: Will do some injury to all rapidly proliferating cells!!
▪ E.g. bone marrow, GIT mucosal cells
▪ → infection, bleeding, anaemia
▪ AND: Nausea + vomiting
o Produces lethal and sub-lethal injury
▪ BUT: Cells recover between doses of radiation
▪ i.e. can handle large doses, if split into multiple small doses
▪ Normal tissue recovers faster

Chemotherapy

• One of major systemic treatment modalities

o Drugs can reach the tumour + distant sites
• Can be primary form of treatment or form part of a combined treatment regime
• Chemo is the primary Rx modality for most haematological + some solid
tumours
• Drugs are more toxic to rapidly proliferating cells than non-proliferating cells or
those in G0 of cell cycle
o i.e. more effective against tumours with ↑ growth rate!!
• Most chemo drugs kill a % of tumour cells with every treatment
o Must complete full treatment to prevent re-growth of viable cells!!
• Often referred to in acronyms:
o CHOP = cyclophosphamide + doxorubicin + oncovin + prednisone →
used for Hodgkin disease
o CMF = cyclophosphamide + methotrexate + 5-fluorouracil → used for
breast cancer
• Use maximum dose of drug to ensure killing of cancer cells
o BUT: Affect cancer cells and rapidly proliferating cells of normal tissue
o → ↑↑ side effects
o May be acute (immediately or within a few days) / intermediate (within
a few weeks) / long-term (months to years after chemo)
o Suppress bone marrow function and formation of blood cells:
o Signs of bone marrow suppression
▪ Anaemia
▪ Thrombocytopaenia
▪ Neutropaenia
o Anorexia, nausea, vomiting
o Stomatitis
o Damage to whole GIT mucosal layer
o ↑↑ fatigue
o Hair loss
o Changes in menstrual flow / amenorrhoea
o Oligospermia / azoospermia
o Teratogenic effects
• NB: Chemo drugs are toxic to all cells!!
o Potentially mutagenic, carcinogenic, teratogenic
o Risk of secondary malignancies