ICL 7.1: Neoplasia Flashcards
what is neoplasia?
the formation or presence of a new, abnormal growth of tissue
it’s a disorder of cell birth that’s triggered by a series of mutations effecting a single cell and its progeny
so tumors are derived from a single cell!
how do you name benign and malignant tumors?
benign: tissue of origin + “oma”
malignant:
epithelial origin = carcinoma
mesenchymal origin = sarcoma
what are the characteristics of a benign tumor?
- well differentiated (closely resemble original tissue they can from)
- structure is usually typical of tissue of origin
- usually slow rate of growth, may come to a standstill or regress - normal mitosis
- usually cohesive, expansile, well demarcates masses that don’t invade or infiltrate surrounding tissues
- no metastasis
what are the characteristics of malignant tumors?
- some lack differentiation = anaplasia
- structure is often atypical/different than tissue or origin
- erratic rate of growth, may be slow to rapid - abnormal mitosis
- locally invasive, infiltrate surrounding tissue
- frequent metastasis
what are the two phases of the metastatic cascade?
- invasion of extracellular matrix (ECM)
2. vascular dissemination, homing of tumor cells and colonization
what are the steps to a tumor becoming invasive?
- loosening of intercellular junctions = cells need to separate
- degradation = cells need to breakdown the components of the basement membrane with enzymes like collagenase
- attachment = cell needs to be able to attach to certain receptors on the ECM
- migration = cell secretes motility factors so it can move around
what happens after a tumor cell has become mobile during the metastasis process?
- intravasation = cell penetrates a blood vessel
tumor cells encounter has defense cells and some tumor cells are destroyed but survival in the circulation is enhanced by platelet-tumor aggregates that protect tumor cells
- extravasation from blood vessel - the cell leaves the blood and establishes a new site
establishment of metastatic tumor relates to anatomic location of primary tumor, natural pathways of lymphatic drainage, and microenvironment of target tissue
what are the steps of tissue invasion?
- loosening of cell-cell contacts
- degradation of ECM
- attachment to novel ECM components
- migration of tumor cells
how are cell-cell contacts lost?
by the inactivation of E-cadherin through a variety of pathways
when a tumor cell is becoming invasive, what is happening during the degradation step?
so first the cell-cell contacts are lost due to e-cadherin enzyme
then proteolytic enzymes secreted by tumor cells and stroll cells degrade the basement membranes and interstitial matrix!
proteolytic enzymes also release growth factors sequestered in the ECM and generate chemotactic and angiogenic fragments from cleavage of ECM glycoproteins
how can you predict the metastatic site of tumors?
they’re easily predicted by the location of the primary tumor and the normal pattern of lymphatic drainage
lots of tumors stop in the first capillary bed they encounter (usually the lung and liver**)
what are the most common locations of metastasis?
lung and liver
what is organ tropism?
it’s when there’s preferential metastasis sites
like for example, lung and prostate cancer cells tend to like to metastasize to bone
probably due to the expression of adhesion or chemokine receptors whose ligands are expressed by endothelial cells of the metastatic site
what are the local effects of tumors on the body?
- impingement on vital tissues impairing their function or causing death of tissues and providing a nidus for infection
- obstruction (like in the GI tract or biliary tract)
- bleeding and secondary infections when tumors ulcerates through natural surfaces
both benign and malignant tumors have these local effects!
how can a tumor cause bleeding?
when the tumor ulcerates through natural surfaces
the bleeding can be from erosive destructive growth or expansile pressure of the tumor
ex. melena (bloody stool) or hematuria (bloody urine)
what are the hormonal effects of tumors?
neoplasms in an endocrine gland can cause clinical problems by producing hormones
non-endocrine tumors may produce hormones or hormone-like products that give rise to paraneoplastic syndromes
both malignant and benign tumors can have hormonal effects!
what types of tumors are more likely to have hormonal effects?
more typical of well-differentiated benign tumors
what is cancer cachexia?
progressive loss of body fat and lean body mass accompanies by profound weakness, anorexia and anemia
we have no idea how this happens but it’s probably due to the interplay between cancer and the immune system - TNFα major suspect
only happens with malignant tumors!!**
what are the characteristics of cancer cachexia?
- equal loss of both fat and lean muscle
- elevated basal metabolic rate
- systemic inflammation = increase in acute phase reactions
what’s the most likely enzyme involved in cancer cachexia?
TNFα
what’s the difference between cancer cachexia and starvation?
in starvation you preferentially have loss of body fat before you lose muscle but with cachexia you lose muscle and fat at the same time
with starvation you have a decrease of BMR while in cancer cachexia you have increase of BMR
what are paraneoplastic syndromes?
symptom complexes in cancer patients that cannot be readily explained by either the local or distant spread of the tumor OR by elaboration of hormones indigenous to the tissue in which the tumor arose
it’s a series of symptoms!
ex. a malignant neoplasm in the pancrease, if it’s producing insulin that’s NOT considered a paraneoplastic syndrome
10% of people with cancer have paraneoplastic syndromes
why are paraneoplastic syndromes important?
- they may be the earliest warning of a neoplasm!!
- they may cause significant clinical problems, even death
- they may mimic metastatic disease and confound treatment
what are the types of paraneoplastic syndromes?
- endocrinopathies (most common)
- neuromyopathic
- dermatologic
- osseus
- vascular & hematologic
