5. Cancer Pathology Flashcards
what is a lesion?
any change in tissue or organ from injury or disease that impairs normal function
what is a tumour/mass/lump/nodule/polyp?
swelling caused by abnormal growth of tissue
what is cancer?
malignant neoplasm
what is oncology?
branch of medicine that deals with cancer
difference between polyp and tumour
polyp has a stalk
are all growths neoplasm?
no
what are 5 types of growth that are not neoplasm?
- malformation
- repair from excessive healing
- hypertrophy
- hyperplasia
- metaplasia
3 examples of malformations:
- Choristoma/ectopic tissue/heterotopia –> normal tissue misplaced in abnormal tissue
- Hamartoma –> benign disorganized growth of cells and tissues
- Vascular malformation
hypertrophy
increase in cell size
hyperplasia
increase in cell number
what would you see with pancreatic heterotopia in stomach?
pancreatic tissue in stomach –> ie tissue in wrong location
not neoplastic!
what mediates hyperplasia?
hormones, growth factors
why does hyperplasia differ from neoplasia? (3)
- cells are genotypically and phenotypically normal
- organ involved is usually diffusely enlarged –> not a localized mass
- reversible –> stops when stimulus stops
can hyperplasia become neoplasia?
yes –> hyperplasia can be precursor in some cases
what is metaplasia?
replacement of 1 type of normal adult cell/tissue with another type
what causes metaplasia? (3)
- tissue damage
- tissue repair
- tissue regeneration
what causes metaplasia in epithelial tissue?
inflammation
is metaplasia neoplastic?
no but often becomes malignant
what causes neoplasm?
accumulation of genetic changes
what is neoplasm?
cells grow out of control, independent of physiological growth signals and controls
what are 2 components of neoplasm?
- abnormal neoplastic cells
- non-neoplastic stroma
what is stroma? (3)
- connective tissue
- inflammatory cells
- blood vessels
are all neoplasms the same?
no, there is heterogeneity within and between neoplasms
2 steps when patient has tumour
- neoplasm or not?
- if neoplasm: benign, borderline, or malignant
what is malignant tumour?
tumour is more invasive and destroys surrounding tissue
what is differentiation?
how closely neoplastic cells have similar morphology and function to normal cells
what is anaplasia?
lack of differentiation
what does it mean for cells to be highly differentiated?
cells resemble the tissue they arise from
does a benign tumour have differentiation or lack of differentiation?
benign tumours are differentiated
does a malignant tumour have differentiation or lack of differentiation?
variable differentiation –> well/moderately/poorly/un-differentiated
5 morphological changes of malignant cancer cells
- pleomorphism (varied cell size and shape)
- abnormal nucleus
- increased and atypical mitosis
- loss of polarity, disorganization
- ischemic necrosis
describe difference in colon tissue with benign and malignant tumour:
BENIGN: nuclei at basal layer, cytoplasm outward –> nicely organized
MALIGNANT: lots of cells, poor orientation of cells, big nuclei/nucleoli –> active cells
describe the 7 steps of neoplasia development
- normal cell has genetic change
- abnormal, transformed neoplastic cell
- becomes malignant: dysplasia + neoplasia
- invasion
- overt malignancy
- metastasis
- drug resistance, production of hormones, production of receptors
what is dysplasia?
disordered growth
can dysplasia become malignant?
dysplasia can become malignant if not treated
how can you prevent malignancy from dysplasia?
- change habit
- remove with surgery
what is carcinoma in situ?
severe dysplasia involving the ENTIRE thickness of the epithelium but not yet invaded thru basement membrane –> high probability of progressing to invasive cancer
how can carcinoma in situ become invasive carcinoma?
metastasize by breaking thru basement membrane to access blood and lymph vessels
is benign tumour invasive?
no –> grows slowly, may compress surrounding tissue and stop growth at a point
4 ways for metastases to occur
- direct seeding of body cavities/surfaces
- lymphatic spread
- hematogenous spread (lung, liver)
- other: CSF, implantation
3 types of body cavities/surfaces where metastases can occur
- peritoneum
- pleura
- pericardium
why does metastases occur via body cavities/surfaces?
no barrier to breach, tumour can easily travel
what is the most common type of metastases?
lymphatic spread
is sarcoma or carcinoma most common for hematogenous spread?
sarcoma
overall summary of differentiation of benign vs malignant
benign: well-differentiated, structure typical of normal tissue
malignant: some anaplasia/lack of differentiation, structure atypical
overall summary of growth rate of benign vs malignant
benign: progressive and slow, may stop or regress, normal mitosis
malignant: erratic growth, slow to rapid, abnormal mitosis
overall summary of local invasion of benign vs malignant
benign: cohesive, does not invade
malignant: locally invasive
overall summary of metastasis of benign vs malignant
benign: no metastases
malignant: common, more likely with large undifferentiated primary tumours
how are neoplasms classified? (5)
- organ or precise type
- origin of cell type
- benign vs malignant
- histological type
- additional subtyping
what are 3 ways of additional subtyping?
- immunohistochemistry
- flow cytometry
- molecular and genetic features
what does immunohistochemistry show if malignant tumour?
when cells lose differentiation, use IHC to identify specific proteins that match a cell type to identify the origin
2 types of malignant neoplasm
- carcinoma
- sarcoma
what is carcinoma?
malignant tumour from epithelium
what is sarcoma?
malignant tumour from mesenchymal (cartilage, adipose, bone)
tumours of mesenchymal origin: benign vs malignant suffixes
benign = -OMA
malignant = -SARCOMA
tumours of epithelium origin: malignant suffixes
-CARCINOMA
what are mixed tumours?
more than one neoplastic cell type, derived from 1 germ cell layer
more than one neoplastic cell type derived from MORE THAN 1 germ cell layer =?
teratogenous
what is the paradigm shift in cancer treatments?
we treat patients based on genetic profiling rather than cell origin and morphology
why do we try to treat patients based on genetic profiling now?
different types of cancers in different places can have same mutation
6 clinical aspects of benign neoplasm
- cosmetic
- local symptoms/signs: obstruction, pressure, pain
- distant endocrine effects
- complications: bleeding necrosis, ulceration, perforation
- can cause morbidity
- can cause malignant transformation
2 diseases of malignant neoplasm
- cachexia
- paraneoplastic syndrome
what occurs with cachexia?
HYPERCATABOLIC STATE
when does cachexia occur?
in 50% of cancer patients
6 symptoms of hypercatabolic state
- extreme weight loss
- fatigue
- muscle atrophy
- anemia
- anorexia
- edema
cachexia is responsible for how many cancer deaths? why?
responsible for 30% of cancer deaths due to atrophy of diaphragm and respiratory muscles
even though the cause of cachexia is unknown, what is thought to play an important role?
inflammatory mediators affecting muscles
what is paraneoplastic syndrome?
unexplainable hormone secretion and other unexpected function that leads to clinical symptoms from the tumour
5 results of paraneoplastic syndrome
- endocrinopathies
- neuromyopathic paraneoplastic syndromes
- skin changes
- skeletal and joint abnormalities
- hypercoagulability
what are endocrinopathies?
ACTH, PTH, insulin or similar substances unexpectedly secreted by tumour
what are neuromyopathic paraneoplastic syndromes associated with?
cancer-induced immunologic attack on normal tissues which leads to muscle weakness or neuropathy
2 types of skin changes from paraneoplastic syndromes
- acanthosis nigricans
- multiple seborrheic keratosis
neuromuscular changes in paraneoplastic syndromes?
changes in bone but unknown pathogenesis
how is cancer diagnosed?
integration of clinical and imaging features with pathological assessment by biopsy
what 6 things do we look at in cancer diagnosis?
- clinical history
- physical exam
- radiology/imaging
- lab results
- tumour markers
- assays of circulating tumour cells, RNA/DNA
what are tumour markers?
specific hormone/substances are secreted that we can measure and correlate to tumour presence
are tumour markers good enough to use for diagnosis? why
no –> not specific or sensitive enough bc substance may change in other conditions
how can we use tumour markers?
if level decreases with treatment, you know tumour is responding to treatment
if level goes back up, tumour may have returned
4 macroscopic findings of neoplasms
- mass/swelling/diffuse enlargement
- circumscribed or invasive and metastasizing
- pale, white
- ulceration/bleeding/necrosis
how do we use ink to look at tumour?
marks the margins to know if tumour is fully excised
what type of tumour is necrosis common in?
necrosis common in malignant tumour
once we see the tumour, what diagnostic techniques do we use when looking at cells?
- cytologic methods/cytopathology
- biospy/histopathology
describe cytopathology
examines individual cell changes –> quick and less invasive
3 types of cytopathology
- direct smear
- analysis of fluids
- fine needle aspiration from solid organs
describe biopsy/histopathology methods
examines individual cells and architecture by taking the tissue with surrounding tissue –> very invasive
cytology or biospy first?
cytology first, then if abnormal use biopsy to see invasion
describe quick frozen section and the benefit
tissue is quick frozen in cryostat and prepared for microscopy
benefit: very quick diagnosis during surgery
2 things we learn from quick frozen section
- look at margins of excised tumour
- decide additional studies other than histology
4 ancillary diagnostic techniques
- IHC
- flow cytometry
- circulating tumour cells
- molecular/cytogenetic analyses
3 roles of IHC
- histologic categorization of malignant tumours
- determining site of origin of malignant tumours
- detecting molecules with prognostic or therapeutic significance
1 role of flow cytometry
for immunophenotyping of lymphomas / leukemias
4 examples of molecular/cytogenetic analyses
- FISH
- PCR
- chromosomal analysis
- NGS
molecular/cytogenic analyses tell us: (6)
- diagnosis
- prognosis
- detection of minimal residual disease
- hereditary predisposition
- guiding therapy
- mechanisms of drug resistance
2 parameters to determine how well/poorly a patient with cancer will do
- grading
- staging
what is grading?
degree of differentiation –> how closely does neoplasm resemble original tissue
what does a low grade mean? better or worse prognosis?
well differentiated, closest resemblance to parent tissue
better prognosis
how is grading done?
by light microscopy
what is grading based on? (2)
- cytology (nuclear and cytoplasmic changes)
- histology (architecture, gland formation, mitosis)
is staging or grading more important?
staging!
why are there different grading schemes?
for each carcinoma –> each scheme has different criteria
what is staging?
extent of malignant neoplasm
how is staging done?
examining surgical specimen/pathological staging) and integration of other information
what is the main system for staging? is it the same for all cancers?
TNM system –> varies for specific forms of cancer
what is TNM system?
T = primary Tumour characteristics
N = regional lymph Node involvement
M = distant Metastases
what is the difference in staging for breast cancer and prostate cancer?
in breast cancer can easily see the size of tumour but prostate cancer, can’t measure size so must look at invasion
4 goals of cancer treatment
- cure
- debulking
- adjuvant, neo-adjuvant
- palliative
5 types of cancer treatment
- surgery
- radiation
- chemotherapy
- immunotherapy
- targeted molecular therapy
6 things that affect chances of survival
- histological type of neoplasm
- location
- staging, grading
- biological/molecular properties
- degree of angiogenesis
- state of host
