Neoplasia 1-2 Flashcards
what is neoplasia?
new growth (a tumor); often refers to cancer, but also includes all other tumors.
5-year cancer survival rate, in general, is about __
2/3
most common types of cancer (and death due to cancer) for males and females
- males: prostate, lung, colorectal.
(Death rates: lung, prostate, colorectal.) - females: breast, lung, colorectal. (Death rate: lung, breast, colorectal.)
Cancer varies globally with __________
incidence and death rate
benign vs malignant tumors
Benign:
- usually not life-threating (depending on where it is)
- relatively slow growth.
- will not disseminate (stays in one area) – much easier to remove surgically.
Malignant: cancer
- often results in death.
- grow rapidly.
- invades and destroys (no delineated boundary)
- often trigger an immune reaction, but not enough to kill them.
gland
adeno-
cartilage
chondro-
RBC
erythro-
blood vessel
hemangio-
liver
hepato-
fat
lipo-
lymphocyte
lympho-
pigment cell
melano-
bone marrow
myelo-
muscle
myo-
bone
osteo-
smooth muscle
leiomyo-
skeletal muscle
rhabdomyo-
nervous tissue
neuro-
benign vs malignant for: squamous cell
- papilloma
- squamous cell carcinoma
benign vs malignant for: glandular cell
- adenoma
- adenocarcinoma
benign vs malignant for: fibroblast
- fibroma
- fibrosarcoma
benign vs malignant for: fat cell
- lipoma
- liposarcoma
tumor of mixed origin
teratoma
differentiated vs undifferentiated cells
differentiated: mimic the structure of their parent organs
- Resemble their cells of origin (e.g. squamous cell in skin)
- Cells have a uniform appearance.
- Cells retain their normal function (e.g. glands have some ability to secrete)
- Cell division normal but rare.
undifferentiated: does not resemble their parent organ.
- Many dividing cells
- Disorganized arrangement – haphazard arrangement of cells.
- Variation in size and shape
- Little evidence of normal function.
- Large, variably shaped nuclei.
- Loss of contact inhibition.
- Increase in growth factor secretion.
- Increase in oncogene expression.
- Loss of tumor suppressor genes
Malignancy: sequential events for glandular cancers.
1.Normal duct
2. Intraductal hyperplasia
3. Intraductal hyperplasia with atypia
a. Don’t look normal, divide more, etc.
4. Intraductal carcinoma in situ
a. Cancer cells but still contained in gland, so if can catch it can get rid of it more easily.
5. Invasive ductal cancer.
how can we achieve early detection of cancer?
- Cervical dysplasia: can detect abnormal architecture and arrangement with biopsy.
- Can look at individual cells: can see larger, darker staining nuclei with irregular shape with cytology.
effect of a benign tumor on the host
- Encapsulated so can remove surgically more easily.
- Compression can occur sometimes if not removed (e.g. meningioma where mass pushes against brain)
- Want to remove since can cause: pain, damage to surrounding tissue, can become malignant, hormones (endocrine tumors), obstruction
how can malignant tumors cause death?
- Tissue destruction – can destroy normal organ, causing vital organ failure.
- Erode blood vessels – causing hemorrhage and anemia.
- Obstruct lumen – blockage in intestine or lung.
- Facilitate infection – local or systemic.
- Metastasis – multiple organ failure
- Cardiac failure – terminal events.
- Systemic effects: can release compounds in circulation: cachexia, immunosuppression, and paraneoplastic syndromes: biochemical, neurological, hematological derangements
what is metastasis
Invasion of the tumor cells across the body using the lymphatic system and blood vessels – unique to malignant tumors.
Sequence of events of metastasis
- Invasion of basement membrane
a. Loosening of intracellular junction.
b. Release various cytokines/enzymes, allowing them to breakdown ECM.
c. Have receptors to latch on and has actin filaments, helping them to move forward.
d. Have laminin, which can bind to collagen, allowing then to migrate. - Migration through surrounding tissue
- Invasion though wall of lymphatic, capillary, or venule
a. Much easier for cells to invade via venules instead of arteries due to thinner walls. - Survival in the circulation
- Extravasation and growth
what basic mechanisms are required for metastasis?
cell adhesion, enzyme release, receptor binding, motility.
ways in which cells can leave the primary tumor
either one cell at a time or in small clusters, the latter being better for their survival.
Patterns of metastasis
- Sometimes spread in a localized area, aka in a lymph node.
- lymph node can contain it for a certain amount of time, where it grows.
- tumor cells enter lymphatics – may first concentrate in a “sentinel” lymph node (the first one in the line)
- go through sequential lymph nodes to the others, but often there are multiple pathways that they use to migrate, like the blood or other lymph nodes.
what is angiogenesis
tumors stimulate growth of blood vessels to increase growth and allow for better spread.
main sites of metastasis
o Bone: occurs very frequently, usually in the proximal sites (legs, arms, spine)
o Brain, liver, lung, and brain.
o Vertebrae: occurs via retrograde venous spread
No valves in the veins of this area, leading to easy spread when it gets in.
explain the genetic instability of tumors
accumulated more abnormalities as it grows and migrates.
Tumor in one place may be vulnerable to therapy but may be resistant in another
which system is used to stage tumors
TNM system:
- Tumor: size of tumor
o T1, T2, T3, T4
- Nodes: how many lymph nodes are involved.
o N0, N1, N2, N3
- Metastasis: whether or not there is metastasis.
o M0 (no metastasis), M1 (metastasis)
Staging is different for different types of cancer.
how are tumors staged?
- TNM system
- Histological grading: looking at the differentiation of cells
- Immunohistochemistry: tell you which receptors are present on surface or inside the tumor, which tells us about the prognosis (predict response to therapy such as chemotherapy).
- Flow cytometry: quantify DNA.
- Tumor markers: different tumors release different chemicals in the blood.
- Image analysis (scans such as x-rays).
how often do paraneoplastic syndromes occur?
15%
what is paraneoplastic syndrome
remote effect of tumor not due to direct effect of primary or metastatic lesion, but instead caused by mediators released from tumor cells (abnormal synthesis or abnormal access), triggering inappropriate physiological or immune response.
what are the effects of paraneoplastic syndrome
- Fever, cachexia, endocrine syndromes, neurological impairment, hematological syndromes, etc.
- includes: release of hormones, cytokines, steroid, antibodies, enzymes, etc.
- neurological symptoms since release factors that alter or cross BBB
what causes cachexia?
- Due to cytokines that are released from tumors that act on hypothalamus, causing the various symptoms.
what is cachexia? what are symptoms and effects?
- Anorexia, weight loss, progressive weakness, nauseous, sarcopenia, pain, etc.
- High risk of death since higher risk of infection and cardiovascular collapse.
- Not the same as starvation, where the body is trying to conserve energy (protein, fat, etc.)
cachexia is most common in which types of cancers?
GI
what is the incidence of lung cancer?
- # 1 cause of cancer death.
- Since smoking rate slowed down, death rate went down.
- Many carcinogens in cigarette smoke – the longer you smoke the more you are exposed to these carcinogens.
tumor growth and progression of lung cancer
- Activation by carcinogens – sequential mutations in cells.
- Squamous metaplasia – DNA adduct formation.
- Mild dysplasia then moderate dysplasia – mutations, epigenetic gene inactivation.
- Severe dysplasia then carcinoma in-situ (anaplasia) – growth suspension evasion, apoptotic resistance, sustained proliferative signaling, angiogenesis.
- Invasion
- Metastasis – start getting symptoms in other organ systems, so is detected.
what are the lung cancer subtypes?
- Small cells (oat cells) – least frequent (15%)
o In large airways (central)
o Origin: neuroendocrine
o Grows very quickly. - Non-small cell subtypes (85%) – grows more slowly
o Squamous cells
In large airways (central)
Origin: basal
o Large cell (undifferentiated)
In small airways (periphery)
o Adenocarcinoma – most common
In small airways (periphery)
Origin: alveolar
what are the local effects of lung cancer?
Obstructive pneumonia, pleural effusion, bronchiectasis, haematosis (coughing up blood)
what are the distal effects of lung cancer? what causes this?
- release of cytokines causes these
Weight loss, cachexia
Increase ADH/ACTH – endocrine effects.
Finger clubbing (swollen fingertips)
If bone metastasis, pain and increase risk of fracture.
Cough, chest pain.
If cerebral metastasis, can cause epilepsy.
Increase infections.
what symptoms can be seen when lung cancer grows within the thoracic cavity?
Tracheal obstruction
Esophageal compression
Hoarseness, laryngeal nerve
Lymphatic obstruction, pleural effusion (excess fluid leaving the lungs)
Obstruction, vena cava (obstruct venous return, which can lead to heart failure)
where does lung cancer usually metastasize to?
Bone (ribs, spine, skull): intractable pain and risk of fracture.
Brain
Adrenal
Liver
how is lung cancer diagnosed?
o Chest x-ray
o Bronchoscopy (especially in central subtypes)
o Cytology of sputum (can diagnose small cell and squamous cell tumors since centrally located can shed)
o PET scan, CT scan, MRI to stage.
o Fine-needle aspiration biopsy of the lung: insert needle in tumor and remove some so pathologist can diagnose properly.
o When tumors are removed, histology can accurately find the type (have different mutations and abnormalities)
what is liquid biopsy and how is this possible?
- instead of getting a physical piece of a tissue, use a liquid (e.g. blood, CSF) – new potential strategy
o Tumors release components into blood and lymph – exosomes, which contain materials that are different that than that of a normal cell.
o Also releases cell-free DNA, which will be different that normal cellular DNA, and tumor-secreted factors.
o Is non-invasive, personalized treatment (mutations in patients differ), and allows for constant monitoring (can keep taking blood samples).
how is lung cancer staged? what is the most common stage of diagnosis?
o Follows the TNM system.
o Half of them is only detected at stage 4 – when there is extensive metastasis and very low survival rate
what is the therapy for lung cancer?
o If possible, will be surgically removed.
Wedge resection: remove a small portion of a lobe – for a small tumor.
Segment resection: remove a larger portion of the lobe.
Lobectomy: remove and entire lobe.
Pneumonectomy: remove an entire lung.
o Small cell carcinoma:
Initially responds to radiotherapy/chemotherapy.
o New strategy: immunotherapy.
Anti-PD-L1 – tumor cell inactivated the T-cell by binding to PD-1 (developed PD-L1 on its surface)
Not all tumors express PD-L1, but if it does, this is an effective treatment – might not heal completely but will increase the quality of life.
what is the prognosis of lung cancer (which types/stage has the worst)?
o Small cell lung cancer has the worst outcome.
o At stage 4 the 3-year survival rate is very low.
what can cause lung cancer?
- smoking
o Asbestos: risk combined with smoking is very high.
Also increases risk of mesothelioma (cancer in pleura).
o Radon: not a frequent cause, but a potential cause.
Decay product of uranium, which slowly rises from soil and come out in water or in basement of home. - Simple solution: add a tube from below basement to the roof.
o Soot/tars/oils, Arsenic, Chromium
what is the incidence of colorectal cancer?
o Incidence and death rate are parallel.
o 2nd cause of cancer death for men and 3rd for women.
what is the progression of colorectal cancer
o Normal colonic cells
o Initiation (a couple cells have accumulated enough mutations to become abnormal).
o Promotion: when in right environment, will spread so that the whole crypt will be made of abnormal cells
o With time, it may pop up into the lumen, forming a benign adenomatous polyp (here it is still detectable)
Three stages: early, intermediate, and late.
o Then, it will progress into a malignant tumor (colorectal carcinoma), burrowing down into the intestinal wall.
what are the sites of metastasis for colroectal cancer?
o Abdominal cavity
o Liver (since blood flow from intestine goes straight to the liver).
o Lung
o Brain
how is colorectal cancer staged? how does it related to prognosis?
o Staging: TNM system
o Prognosis directly related to stage of diagnosis.
o It is not the primary tumor that kills you (since we can remove the entire colon if we want), but the metastases that kill.
symptoms of colorectal cancer vary with what?
location: ½ are in the distal portion (which is good since it is the easiest portion to detect), and ¼ will be in the proximal region.
Pain will be felt in midline.
what is CEA (carcinoembryonic antigen)?
o Present on colon carcinoma – acts as a tumor marker, allows us to see if treatment is working.
o Not good as a marker to diagnose
what is therapy for colorectal cancer?
o Surgery is the main treatment – and if has not spread, will be curative
what are risk factors for colorectal cancer and what lowers the risk?
o ~6% cases are genetic: familial adenomatous polyposis (have 100s of colon polyps, so a matter of time before one turn into cancer)
o Lifestyle:
Diet: high fat, low fiber, high red meat.
Obesity: since there is increased inflammation.
smoking, drinking, inflammatory bowel disease.
o May involve the microbiome.
o What lowers risk:
Exercise, regular NSAID use (e.g. aspirin), hormone replacement therapy.
how can colorectal cancer be detected early?
sigmoidoscopy (only distal region)
colonoscopy
test for occult blood: home test on fecal material for occult blood.
