General features of Malignancy vs Benign Flashcards
What is neoplasia?
Uncontrolled and excessive cell growth and proliferation. Growth continues even if stimuli is removed
What features enable neoplasm’s to continue growing?
I.e. hallmarks of cancer
Replicative immortality, immune evasion, induce angiogensis, invasion, resist cell death, sustain proliferative signalling, evade growth suppression
Emerging hallmarks = deregulation of cellular energetics (as require a lot of energy), promotion of inflammation and genome instability & mutation
What is the general definition of a benign lesion?
Proliferation but that is not excessive and rarely causes disease, unless compresses on other structures
Still uncontrolled growth, arising from single cell mutation
What are the main features of a benign lesion (macro- & microscopic)?
Well circumscribed often encapsulated (fibrous capsule) Do not invade/contained locally Well differentiated cells - less cell atypia Generally slow growing
What are the main features of a metastatic lesion (macro- & microscopic)?
Often poorly circumscribed
Invasive (locally + metastasis)
Poorly/variable differentiated cells - cytological atypia
Often areas of necrosis (out grow blood supply)
Induce desmoplasia of surrounding stroma (secrete TGF-beta induction of fibroblasts to produce more ECM)
What is the most common cancer in both sexes and the most common for each sex?
Both = bowel Female = breast Male = prostate`
What are three methods of metastasis?
Lymphatic - i.e. lung tumur cells enter lymphatics and spread to local LNs, filtered and grow there (enlarged LNs)
Haematogenous - usually enter venous system after lymphatic drainage
Transcoelomic - spread into the body cavities (pleural, peritoneal, colelonic cavities)
Where do malignancies often metastasise too?
Liver, brain, lungs and bone
What bones do bony mets commonly form?
Spine, pelvis, ribs & proximal limbs
What cancers commonly result in bony mets?
Prostate, lung, kidney and breast
What are some symptoms of bony mets?
Hypercalcemia (mainly from bone destruction), pathological fracture, bone pain, bone marrow failure + anaemia (if significant mets disrupting haemopoietic tissue)
How many lesion foci are typically present in primary vs metastatic cancers?
Primary usually single lesion and usually multiple in metastatic
Particularly mets to brain - often many small lesions
Transcoelimic spread to body cavities can result in what?
Fluid accumulation in the cavity
I.e. ascities in the peritoneal cavity and pleural effusion in the pleural cavity
What are the features of cell atypia?
Pleomorphic nuclei (various size and shape)
Larger nuclei
Prominent nucleoli
Abnormal mitotic figures
Coarse, hyperchromatic chromatin (dark staining nuclei)
What are HISTOLOGICAL features of malignant lesions?
More cell atypia as cells are less well differentiated
Desmoplastic stroma - tumor makes its own stroma
Architectural disorganisation
+/- Necrosis
What are the features of desmoplastic stroma?
Tumor secretes cytokines that allow production of its own stroma
More cellular with darker staining nuclei- i.e. more fibroblasts
Increased ECM and it is more dense
Has own blood vessels in stroma
What are the 2 main types of epithelial neoplasms?
What are benign and malignant of each called?
Glandular or squamous epithelial
Benign = glandular (adenoma), squamous (papilloma)
Malignant = glandular (adenomcarcinoma), squamous (carcinoma)
Main histological features of ‘adeno’ lesions (glandular)?
Cells try to form a glandular lumen
Signet ring cell formation
Formation of mucin
Main histological features of squamous lesions?
Keratin pearl formation
Intercellular bridges
What does the grade of a lesion refer to?
The level of differentiation
Can be well, moderately, poorly or anaplastic (no differentiation, can’t tell cell origin)
What 3 histological features relate to the level of differentiation?
Level of architectural disorganisation
Degree of cell atypia
How closely they resemble mature cells
Why is the tumor stroma important for its growth?
Contains immune cells, endothelial cells, fibroblasts, ECM, cytokines
There is communication between stromal & tumour cells
Influences the development of cells and to some extent its ability for growth
Some treatments may influence the stroma to suppress tumor growth
How do neoplasms arise?
Arise from a single cell
Genetic alteration in that cell to allow unregulated cell growth
Usually a multistep process
i.e. Damage to DNA, failure of repair, mutation, alteration in gene function leading to unregulated growth & decreased apoptosis, clonal expansion, acquires additional mutations allowing development of other features (i.e. immune evasion, angiogenesis)
How does DNA damage initially arise?
Radiation (i.e. UV)
Chemical (i.e. cigarette smoke)
Carcinogens
Some microbes i.e. EBV, HPV, helicobacter
Inherited mutations
Normal mistakes in DNA replication that are not repaired
sustained cell proliferation from any cause increasing risk of mutation
What are pre-malignant epithelial lesions?
Non-invasive precursors of malignancy that show DYSPLASIA (failure of normal maturation)
Referred to as intraepithelial neoplasia or dysplasia
What are the grades for pre-malignant lesions and give a few cancer specific examples of the grading
Mild, moderate or severe
Severe = carcinoma in situ = cells show marked atypia (dysplasia) but have not yet invaded the basement membrane or whatever barrier defines invasion in that organ (i.e. Muscularis mucosae in colorectal cancer)
Cervical cancer use CIN rating for premalignant lesion
Breast and prostate also have important premalignant lesion signs
Why can’t severely dysplastic or in situ lesions metastasise?
Can this change?
Do not have blood vessels in the epithelium to allow metastasis but there is a high risk of developing angiogenesis and becoming malignant and invasive
Severe dysplasia still considered benign as can’t invade but they have a high chance of becoming malignant
