Pathology Flashcards
apprendre les millions d'affaires de la section pathologie de marde
what are cancer stem cells ?
a parody of a normal stem cell : must be eliminated to cure a cancer, but are resistant to therapy because of low rate of replication and express factor of drug resistance
what are the systemic effects of inflammation ?
- fever
- production of acute-phase proteins
- leukocytosis (production of leukocytes)
- maybe fall in blood pressure (because chemokines induce vasodilatations)
What do cyclins oncogens act ?
they mediate entry into the cell cycle G1-S = super cell proliferation
list and briefly describe the sequence of development of a squamous carcinoma (in the cervix)
- normal mucosa
- dysplasia
- carcinoma-in-situ (all look neoplastic, but no highway for metastase)
- invasive squamous cell carcinoma (neoplastic cells can get to the lymphatic vessels)
compare benign and malignant neoplasm in terms of behavior
B - no matastases (no invasion, slow growth, few systemic effect)
M - potential for metastases (invasion, rapid growth, augmentation of systemic effects)
how does a pathologist do a urgent diagnosis ?
freeze the tissue on a cryostat at -20oC, do a frozen section and stain with H&E
Name the broad overall caracteristics of a disease
- predisposition factors/ history of the disease
- etiology
- pathogenesis
- pathological alterations
- pathophysiology
- clinical manifestations/imaging and laboratory
- diagnosis
- complications
- prognosis and predictives factors
- therapy
what do you call a malignant neoplasm of the breast
phyllodes tumor
What are the 3 most common cancer in men (incidence) ?
- prostate
- lungs & bronchus
- colon and rectum
what do we mean by monoclonal in term of malignant neoplasm transformation ?
neoplastic cells arise from a single transformed cell
general chemicals reactions and specificities of periodic acid Schiff (PAS)
- stains complex carbohydrates
- can digest glycogen if add diastase
what are the Ziehl-Neelsen and Grocott stains useful for ?
microorganisms stains
- ziehl-neelsen = acid-fast bacilli (TB)
- grocott = fungal (aspergillus)
describe the mechanism for invasion and metastases if malignant carcinoma
- carcinoma-in-situ cells
- loosen intercellular junctions between neoplasm cells
- the malignant cell attach and degrade BM
- migrate thru the BM to stroma via cytokines
- go either from lymphatic vessels to lymph nodes, to blood vessels or transcoelomic
List one parasite, one bacterium and 5 viruses that are carcinogenesis by biological agents
- Parasites = clonorchis sinensis
- bacteria = H. pylori
- Virus = RNA, DNA (sarcomas)
Define papilla
(usually microscopic term) = finger-like projection consisting of surface epithelium over core of connective tissue ≈ villus
etiology
CAUSE of the disease
difference between chronic and acute inflammation ?
the predominant neutrophilic infiltration is replaced by infiltration with mononuclear cells (lymphocytes, plasma cells, macrophages)
the definition of pathology : the study of diseases, all the way from molecules to the patient and divided into ?
- general pathology (cell injury, inflammation, immunopathology, neoplasia)
- systemic or “systematic” (organ-based) pathology (heart, lungs, …)
what do you call a malignant neoplasm of the adipocytes ?
liposarcoma
general chemicals reactions and specificities hematoxylin
- dark blue
- is a base
- binds to basophilic substances (acides) like DNA in nuclei
What are the 3 most deadly cancer in women (mortality) ?
- lungs and bronchus
- breast
- colon and rectum
general chemicals reactions and specificities Prussian blue stain for iron
- stains ferric deposits (in liver if a lot of blue, blue is bad)
atrophy (what + mechanism)
- decrease in cell SIZE
- mechanism : lysosomal enzyme pathway, ubiquitin-proteasome pathway, autophagic vacuoles
what do you call a malignant neoplasm of the fibroblast (mesenchymal)
fibrosarcoma
what are the different grades of malignant neoplasm done ?
Grade I : > 75% differentiated
Grade II : 50-75% differentiated
Grade III : 25-50% differentiated
Grade IV : <25% differentiated
carcinomas or sarcomas ? macroscopy variably hard (vs fleshy, firm)
carcinomas
What are the phases of development of malignant neoplasm ?
- transformation
- growth (proliferation of transformed cells)
- diversification/clonal expansion of neoplastic cells
- local invasion
- distant metastases
general chemicals reactions and specificities Masson trichrome
- for collagen + fibrosis
- blue collagen, red muscle
- -> help to see how much fibrosis there’s to know if you need a transplant
what are the different kinds of necrosis and their main caracteristics ?
- COAGULATIVE .- cellular outline maintained, protein degradation
- LIQUEFACTIVE - loss cellular outlines and pus
- CASEOUS - special in mycobacterial infections
- FAT - chalky white areas (fat destroyed through action of lipases)
difference between monocyte and macrophages ?
monocyte change into macrophages after entering the tissue spaces (phagocytosis)
metaplasia (what + mechanism)
- REPLACEMENT of one cell type by another
- mechanism : reprogramming of stem cells or undifferentiated cells
what do you call a benign neoplasm of the salivary glands (mixed tumor)
pleomorphoic adenoma
how PAS-D help make a diagnosis ?
highlight PAS-D positive globules of alpha-1-antitrypsin deficiency (genetic disease predisposing to asthma and cirrhosis)
compare benign and malignant neoplasm in terms of necleus
B- more regular, differentiated
M - anaplastic, large, bizzare, large, abnormal
Intracellular accumulation is produced in response to what ?
Non-lethal persistent cell stress (metabolic alterations/chronic injury)
what’s the only type of cellular adaptive responses that is always PATHOLOGIC
metaplasia
What do we mean by multistep carcinogenesis ?
frequently a multi-step process with sequentially added mutations
Explain the 4 descriptors of carcinogenicity of the IARC/WHO
- Group 1 : carcinogenic to humans (120 agents)
- Group 2 : A- probably (81) and B- possibly carcinogenic to humans (299)
- not classifiable
- probably not carcinogenic to humans (1)
What is immunohistochemistry ?
Using the same principle of Ag-Ab binding to identify specific cellular macromolecules (often proteins).
- Usually purify the Ab and applied to a histologic section along with a brown stain
DIAGNOSTIC MARKERS
Classify the etiologies of human cancer
They’re either exogenous (chemical carcinogens, physical agents, biological agents) or endogenous (heredity, gender and hormones, altered immunity)
what nuclear changes are associated with necrosis ?
- karyolysis (nucleus is starting to break down)
- karyorrhexis (fragmentation of the nucleus)
- pyknosis (rétraction du noyau)
- complete loss of nucleus
3 leading causes of cancer ?
- tabacco
- diet
- sexual behaviour, infections
what do you call a benign neoplasm of the smooth muscle (mesenchymal)
leiomyoma
what do you call a malignant neoplasm of the melanocytes ?
melanoma
Define oncology
1) study of neoplasms, malignancies;
2) medical specialties treating patients with cancer
role of mannose receptor ?
recognition and attachement of the particule to be ingested by the leukocyte (phagocytosis)
carcinomas or sarcomas ? immunohistochemistry vimentin, muscle actin (vs keratins, prostate-specific antigen)
sarcomas
what do you call a benign neoplasm of the hematopoietic cells (bone marrow/lympphoid)
none-existant
2 types of pathologic calcification and differences
- DYTROPHIC : occurs at sites of previous necrosis
- METASTATIC : occurs in setting of hypercalcemia
what do you call a malignant neoplasm of the salivary gland
malignant mixed tumor
name factors that can delay tissue repair
- infections
- protein deficiency
- treatments : glucocorticoids
- poor perfusion
- increased ECM production in keloids (collagens)
what do you call a benign neoplasm of the melanocytes ?
nevus
why should you take care of benign neoplasm ?
- cosmetic
- local symptoms/signs : obstruction, pressure, pain
- distant endocrine effects
- complications : bleeding, necrosis, ulceration, perforation
- some have potential for malignant transformation
Define angiogenesis and distinguish it from vasculogenesis and arteriogenesis
- VASCULOGENESIS : process of blood vessel formation from endothelial progenitor cells (mesenchyme), generally during
embryogenesis, but also in adult - ANGIOGENESIS: process of blood vessel
neoformation from preexisting vasculature - ARTERIOGENESIS: growth and remodeling of preexisting collateral arterioles leading to formation of large well-muscularized conductance arteries and arterioles to compensate for loss of function of occluded arteries
5 cardinals signs of inflammation
- redness
- swelling
- heat
- pain
- loss of function
carcinomas or sarcomas ? Chances increase with age
carcinoma
disadvantages of urgent diagnostic ?
freezing artefacts
Describe 3 radiation-induced cancers and the type of radiation implicated
- ionizing, radioactive elements (x and gamma-rays, alpha et beta particules)
- UV
- electromagnetic fields (low-frequency)
carcinomas or sarcomas ? histochemistry mesenchymal : fat, etc. (vs epithelial: mucin)
sarcomas
compare benign and malignant neoplasm in terms of immunohitochemistry
B - close to normal cell
M - variable loss expression
what are the clinical manifestation of a disease ?
signs and symptoms
carcinomas or sarcomas ? Etiology viral or unknown (versus generally known, environnemental, viral)
sarcomas
what do you call a benign neoplasm of the endothelium (mesenchymal)
hemangioma
what do you call a malignant neoplasm of the tortipotential cells ?
immature teratoma
what is the role of the connective tissue in chronic inflammation ?
- lymphatic spreading of the inflammatory process
- angiogenesis
- scar and fibrosis
what do you call a malignant neoplasm of the endothelium
angiosarcoma
etiology of neoplasm ?
can be wither heritable (genetic mutations) or acquired (carcinogens either physical, biological or chemical)
What is p53?
Tumor supressor gene
compare benign and malignant neoplasm in terms of histology
B - pattern as parent tissue
M - loss of architeture, polarity, stratification
what’s an irreversible cellular injury ?
necrosis
List the different types of cellular adaptive responses that we saw in class
- hypertrophy
- hyperplasia
- atrophy
- metaplasia
what do you call a malignant neoplasm of the hematopoietic cells
leukemia
how is staging done ?
mostly done by examination of a resected surgical specimen
what do you call a malignant of the glandular epithelial ?
adenocarcinoma
Define polyp
any lesion or mass of tissue protruding from normal surface level, usually in lumen of a hollow organ
compare benign and malignant neoplasm in terms of molecular events
B - early
M - advanced
role of phagocytosis in inflammation ?
killing and degradation within neutrophils and macrophages
Cytopathology
branch of anatomic pathology looking at whole cells rather than sections.
- can be divided in gynecologic and non-gynecologic
What can oncogenes be?
- growth factors
- growth factors receptors
- signal transducing proteins
- nuclear transcription factors
- cyclins and CDKs
- p53
- BCL-2 (inhibits apoptosis)
- telomerase
what are the 2 types of apoptosis ?
physiologic and pathologic
why do we say that carcinoma-in-situ in pre-malignant ?
it’s not a benign neoplasm, it’s a carcinoma (has the biological genotype and phenotype of a malignancy, but has not yet invaded through the basement membrane because no lymphatic or blood vessels are above BM (cannot metastasize)
what are the 2 primary mediators of cellular injury ?
HYPOXIA (↓ O2, but blow flow) and ISCHEMIA (↓ O2 by reduction of blood flow)
how is the cell respiration is done in proliferating cancer ?
Mostly anaerobic glycolysis (u can then use glucose hunger to see cancers)
pathophysiology
derangement in function distinguished from structural defects (how is the physiology will be impacted by the disease)
what are the different causes of cell injury
VICTORIAN Vascular Infectious Chemical Trauma and temperature Ospital Radiation Inherited Autoimmune Nutritional
What is anaplasia?
complete dedifferenciation = no ressemblance to the normal parent tissue
what do you call a benign neoplasm of the germ ces
none-existant
are carcinomas more common than sarcomas ?
yes
what do you call a benign neoplasm of the totipotential cells
mature teratoma
What is immunofluorescence (IF) ?
Use for Ag sensitive to loss. Stained with fluorescein-labeled Abs and examined with microscopy microscope
3 types of proliferative capacity tissues
- LABILE tissues: cells are constantly being lost and must be continually replaced by new cells that are derived from tissue stem cells and rapidly proliferating immature progenitors. These tissues can readily regenerate after injury as long as the pool of stem cells is preserved (skin)
- STABLE tissues: made up of cells that are normally in the Go stage of the cell cycle and hence not proliferating, but they are capable of dividing in response to injury or loss of tissue mass (liver)
- PERMANENT tissues: terminally differentiated nonproliferative cells. Injury to these tissues is irreversible and results in a scar, because the cells cannot regenerate. (brain, heart)
granulomatus inflammation is which kind of inflammation ? what is it exactly ?
chronic
- activated macrophages acquiring an epithelioid appearance.
what do you call a malignant neoplasm of the squamous epithelial ?
squamous cell carcinoma
what do you call a malignant neoplasm of the osteocytes
osteosarcoma
What are the two main type if stem cells?
- EMBRYONIC : present in inner cell mass of blastocyst, unlimited potential. THEY GIVE RISE TO ALL TYPE OF CELLS IN THE ORGANISM
- ADULT : less undifferentiated, and differentiate into cells of the particular tissue or organ only. Difficult to find and isolate. ENSURE HOMEOSTASIS OF CELL POPULATIONS IN EACH ORGAN
why the saying blue is bad ?
malignancy have a lot of blue because they have a lot of nuclei
Define nodule
small rounded mass
Name exemples to illustrate intracellular accumulation
- lipofuscin in hepatocytes
- gaucher cells
- cholesterolosis in gallbladder
what do you call a malignant neoplasm of the lymphoid cells ?
lymphoma
what are carcinomas vs sarcomas ?
- CARCINOMAS are malignant EPITHELIAL neoplasm
- SARCOMAS are malignant MESENCHYMAL neoplasm
why the saying red is dead ?
less DNA and RNA, so less blue and proteins denature expose acidic, positively charged group = binds more eosin
what do you call a malignant neoplasm of the germ cells ?
dysgerminoma
What are the 3 most common cancer in women (incidence) ?
- breast
- lungs and bronchus
- colon and rectum
carcinomas or sarcomas ? histology sheets of spindle cells admixed with stroma between cells (vs form island of cells separated by stroma)
sarcomas
pathogenesis
MECHANISM whereby the etiological agent results in the pathological alterations of the disease at different levels
What are the 3 most deadly cancer in men (mortality) ?
- lungs and bronchus
- prostate
- colon and rectum
(same as incidence)
what do you call a benign neoplasm of the glandular epithelial ?
adenoma, papillary adenoma
what do you call a benign neoplasm of the urothelium epithelial ?
urothelial papilloma
hyperplasia (what + mechanism)
- increase in cell NUMBER
- in response to a stimulus
- mechanism : growth factors/hormones, growth receptors, activation of cell cycle regulators, new production from stem cells
what is staging of a malignant neoplasm ?
the determination of the size and extend of spread of a malignant neoplasm
why is electron microscopy useful now in pathology ?
currently diagnostic uses mainly in renal glomerular diseases, also virology
in inflammation, the edema is caused by the exsudates or transudate ?
both
what do you call a benign neoplasm of the lymphoid cells (bone marrow/lympphoid)
none-existant
What is the role of BCL-2?
inhibits apoptosis
name non-neoplastic growth
- malformations
- hyperplasia
- metaplasia
pathological alterations
what we can see (macroscopic, histochemical, molecular, etc.)
what’s the difference between prognostic and predictives factors ?
- prognostic factors : factors influencing the patient outcome, survival (age, gender, $$, specific markers, type of neoplasm)
- predictive factors : predict potential response to a specific therapy (drugs, biological compound, determine responsiveness of a neoplasm to a drug). They determine the chosen therapy
role of TLRs (tool-like receptors)
they are expressed at the surface of leukocytes and are involved in their activation. They RECOGNIZE the pathogen associated signature and INITIATE inflammatory response of the innate immune system
How can cytopathology and surgical pathology be linked ?
if enough tissue can make “cell block” that can be processed as for surgical pathology (in this case amenable to immunohistochemistry, etc.)
what’s the role of selectins and integrins in inflammation ?
adhesion to the endothelium of leukocytes
what do you call a malignant of the urothelium epithelial ?
urothelial carcinoma
name 4 medicinal drugs that are also carcinogenic
- anti-cancer drugs (busulphan)
- hormones/related (estrogens, tamoxifen)
- immunosuppressant (cyclosporine)
2 types of tissue repair
- regeneration
2. scar formation
what do you call a benign neoplasm of the fibroblast (mesenchymal)
fibroma
Outline the steps in the diagnosis of a neoplasm including the role of the pathologist
- Clinical (history, physical exam)
- Radiology/imaging
- Clinical laboratory measurement
- Tumor markers (CEA, AFP, PSA)
- Pathologic or tissue diagnosis: cytopathology, biopsy/histopathology techniques
- Ancillary pathologic diagnostic techniques (immunohistochemistry, molecular analyses)
what do you call a benign neoplasm of the breast (mixed tumor)
fibroadenoma
compare benign and malignant neoplasm in terms of cytoplasm
B - resembles parent
M - variable loss of differentiation
compare benign and malignant neoplasm in terms of macroscopic appearance
B - circumscribed, encapsulated, rare secondary changes
M - irregular shape, not circumscribed, frequent necrosis hemorrhage and ulceration
what’s the difference between macrophages that have been activated by the M1 and M2 activation ?
M1 - phagocytosis and killing of bacteria and fungi, ++ inflammation
M2 - anti-inflammatory effects, wound repair, fibrosis
macrophages are both part of the problem and the solution
compare benign and malignant neoplasm in terms of mitoses
B - few, normal
M - many, +/- abnormal
general chemicals reactions and specificities eosin
- red
- is an acid
- binds to acidophilic substances (bases) in cytoplasm (proteins)
a neoplasm includes the neoplastic _______ and a non-neoplastic _______
a) cells
b) supporting stroma
define grading of a malignant neoplasm
grading = determination of degree of differentiation (aka determination of degree of ressemblance to the normal parent/tissue)
i.e. well differentiated = lot of feature of the normal cell
What’s the probable general mechanism of carcinogenesis of micro-organism?
(Carcinogenecity of chronic infections/cancer)
– Direct via oncogenic protein…(cf. initiators)
– Indirect via inflammation, cell damage and
regeneration with ensuing proliferation (cf.
promoters…) that allow the expression of
new mutations
how does transformation occur ?
Occurs by the accumulation of genetic alterations and epigenetic changes so the cells can escape permanently from normal growth regulatory mechanisms
what do you call a benign neoplasm of the squamous epithelial ?
squamous papilloma
Define tumor
swelling = neoplasm
*Jpas sure pcq dans mes notes j’ai: swelling that does not always mean neoplasm
how is grading of a malignant neoplasm done ?
done by light microscopy based on cytology (nuclear and cytoplasmic changes) and histology (arrangement of cells, glands, …)
what are the staging group ?
- Primary tumor size, characteristics (‘T’)
- Presence or absence of lymph node metastases (‘N’)
- Presence or absence of distant metastases (‘M’)
carcinomas or sarcomas ? metastatic spread hematogenous (vs lymphatic, then hematogenous)
sarcomas
diapedesis
transmigration across the endothelium (during leukocyte migration)
what do you call a malignant neoplasm of the smooth muscle cells
leiomyosarcoma
how is cytopathology and surgical pathology differ ?
Procedures, methods of sampling, fixation, processing if different for both (cyto uses smears, cytocentrifuge, etc.).
what do you call a benign neoplasm of the osteocytes (mesenchymal)
osteoma
what is absolutely needed for tissue regeneration (or only solution is scar formation) ?
an intact ECM matrix because it’s a substrate for cell growth and tissue microenvironment and it’s scaffolding for tissue renewal
Disease associated with granulomatus inflammation
TB (caseous necrosis), sarcoidosis, inflammatory bowel disease.
name a reversible cell injury
cellular accumulations
When someone comes in your office with a mass, how should you think ?
- Is it neoplastic or non-neoplastic ?
- If it’s neoplastic, is it benign or malignant ?
- 1 if it’s benign, is it mesenchymal or epithelial
- 2 if it’s malignant, is it 1o (started there) or 2o (metastasis from somewhere else)
- if it’s 1o, is it mesenchymal, epithelial or mixed ?
there’s 2 main kind of chemical carcinogenesis, what are they and what do they do ?
- INITIATORS : mutagenic and induce potentially heritable DNA damage
- PROMOTORS : not mutagenic, increase proliferation, including of cells with DNA mutations, favoring tumor growth
Define mass
lump = aggregation of quantity of solid tissue
name the steps between biopsy and finished slide for review by pathologist
- macroscopy (small piece = fix directly, larger = sample representative)
- dehydration with graded alcohols
- clearing with an organic solvent which increases translucency
- infiltration by parrafin wax
- embedding - place tissue in correct orientation in cassettes with paraffin and cool it
- cut section on microtime and place on glass slide
- staining with hematoxylin and eosin
- coverslipping
What is cancer?
any malignant neoplasm
what do you call a benign neoplasm of the adipocytes (mesenchymal)
lipoma
Name the differences of necrosis and apoptosis in terms of :
- cell size
- nucleus
- cell membrane
- cell content
- inflammation
- physiologic or pathologic ?
- cell size : N- increased (swelling); A - decreased
- nucleus : N- karyolysis, karyorrhexis, pyknosis; A-fragmentation
- cell membrane: N- disrupted; A- intact with altered structures
- cell content: N- disrupted; A- intact
- inflammation: N-yes; A-No
- physiologic or pathologic ? N- always patho; A- both
List 5 occupational carcinogens
- Arsenic (glass, pesticides)
- asbestos (insulation, textiles)
- benzene (solvent, fuel)
- Cd (pigment, batteries)
- 2-naphthylamine (dyes)
what’s a sequelae ?
after-effects of a disease condition or injury (like fanthom limn after an amputation)
hypertrophy (what + cause + mechanism)
- increase in cell SIZE
- caused by increased functional demand or hormonal stimulation
- mechanism : increased in protein synthesis, re-expression of developmental genes, induction of structural genes
what are the 2 main caracteristics of malignant neoplasm ?
- invasion (the ability to infiltrate and destroy surrounding tissues)
- metastatic potential (secondary foci; the most important caracteristic)
Define lesion
modification of tissue or organ 2o to injury or
disease process, often resulting in impairment of normal function