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Pathological Processes > Introduction To Pathology > Flashcards

Introduction To Pathology Flashcards

1
Q

What does pathology mean?

A

The study (logos) of suffering (pathos).

Whilst biology is considered the study of life and cellular function, pathology is the study of disease and cellular malfunction.

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2
Q

What do pathologists do?

A

They investigate the changes (structural and functional) in cells, tissues and organs that are seen in disease.

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3
Q

List the main branches of pathology.

A

Medical microbiology - virology

Chemical pathology

Haematology

Immunology

Cellular pathology - neuropathology, forensic pathology, paediatric pathology

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4
Q

What are the roles of each branch of pathology?

A

Medical microbiology and virology - study infectious disease broadly and antibiotics and infection control

Chemical - study problems in metabolic processes

Haematology - Study disorders of the blood

Immunology - study diseases of the immune system

Cellular - macroscopic/microscopic

  • neuro - brain, spinal cord, nerves and muscle
  • forensic - autopsies and crime scenes
  • paediatric - children
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5
Q

What is the difference between histology and cytology?

A

Histology:

  • Core bipsies
  • Often therapeutic as well as diagnostic
  • Can assess architecture as well as cellular atypia
  • Can differentiate invasive from in situ disease
  • Can provide information on completeness of excision and more complete information on grading and staging
  • Better for immunohistochemical and molecular testing

Cytology:

  • fine needle aspirate of breast thyroid lung etc
  • Faster and cheaper
  • Non-invasive or minimally invasive and safe
  • Can be used for cells in fluids
  • Sometimes a preliminary test before other investigations or more tissue taken for histology
  • Higher inadequate and error rates
  • Generally used to confirm/exclude cancer/dysplasia and not to diagnose any other condition with accuracy
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6
Q

What is the importance of a microscopic diagnosis?

A
  • Definitive diagnosis

This is importance before major surgery to remove a lesion

  • It guides the type and extent of surgery
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7
Q

What is the difference between histology and cytology?

A

Histology involves viewing microscopic slides prepared from tissue sections.

Cytology is the study of cells scraped from or sucked out of an organ or lesion or extracted from a body fluid such as urine or a pleural effusion.

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8
Q

What the advantages and disadvantages of a cytology?

A

Cytology is non-invasive or minimally invasive, fast, cheap and generally safe.

However, it has higher inadequate and error rates than histology.

It is sometimes used as a preliminary test or before other investigations are conducted or before histology is taken.

It is generally used to confirm/exclude cancer or dysplasia rather than to diagnose other conditions with accuracy.

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9
Q

What are the disadvantages and advantages of a histology?

A

Histology is used both diagnostically and therapeutically (when a lesion is completely removed).

Advantages over cytology are based on the fact that architecture as well as cellular atypia are assessed.

This allows the differentiation between in situ and invasive malignancy to be made and also allows comment on completeness of excision.

Grading and staging are generally more completely assessed with histology than cytology.

On the whole, histological sections are better for immunohistochemical and molecular testing than cytological preparations.

They can provide further detail of the cancer and lily efficacy of further treatment.

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10
Q

Explain one of the biggest problems with histological interpretations?

A

Sometimes histological interpretation is subjective meaning that pathologists don’t always agree on every diagnosis!

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11
Q

List the 9 processes involved in producing slides for microscopy.

A
  • Fixation
  • Cut-up (trimming)
  • Embedding (processing)
  • Blocking
  • Microtomy
  • Staining
  • Mounting
  • Microscopy
  • Report writing
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12
Q

How does a into pathologist arrive at a diagnosis?

A 
• Pattern recognition 
• They ask:
– Is this normal or not?
– Is this inflammatory or neoplastic?
– Is this benign or malignant?
– Is this a primary tumour or a metastasis?
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13
Q

When its cancer what else can histopathologists tell us?

A
  • Type of cancer
  • Grade of cancer
  • Stage of cancer
  • Completeness of excision and if margins are involved which ones
  • Likely efficacy of further treatments

• All of which influence decisions on further treatment and management

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14
Q

Why does autolysis occur and why is it a problem when preparing tissues for microscopic viewing?

A

Tissue autolysis (self-digestion) begins when the blood supply is cut off.

It destroys cells and tissue architecture
– Everything we need to make a diagnosis

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15
Q

How do you solve autolysis?

A

We can block the biochemical process of autolysis with fixatives

• Fixatives eg. FORMALIN - FORMALDEHYDE IN WATER
– Inactivate tissue enzymes and denature proteins
– Prevent bacterial growth
– Harden tissue, if not it will harden

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16
Q

How do you choose the right bits of tissue for the specimen?

A

It is examined and cut-up (trimming) by a pathologist

Samples are taken and placed into a cassette
– About the size of a stamp so they can be adequately infiltrated by chemicals

– May need to take 30 or more in complicated cases

– Cassettes have holes in

– They are placed in racks in formalin

17
Q

What do you use to get the tissue hard? Why is this important? And how is this done?

A

Paraffin wax

In order to be able to cut very thin sections the tissue has to be surrounded and impregnated
with a hardening agent

With a machine:

Have to remove the water from the tissue first:
– Dehydration using alcohol in a vacuum so that water is drawn out of the cells

– Then replace alcohol with xylene which can mix with wax

– Then replaced xylene with molten paraffin wax, which will even be inside the cells

18
Q

How do you get the tissue into a piece of wax that can be cut?

A

By a process called blocking:

  • Tissue taken out of the cassettes by hand and put into metal blocks
  • These are filled with molten paraffin wax and the body of the cassette is placed on top
  • The wax is allowed to harden and the metal tray is removed
19
Q

What is used to cut the tissues into thin sections?

A

Microtome

Sections must be so thin that we can see through them with a microscope

20
Q

How do you remove the wrinkles in the tissue?

A

The thin wax sections are floated on a warm water-

bath and picked up on a microscope slide

21
Q

How do we colour the tissue so it can be seen under a microscope?

A

• Staining - usually with H&E:

– Haematoxylin stains nuclei purple
• From the bloodwood tree (Greek: haima = blood; xylon = wood)

– Eosin stains cytoplasm and connective tissue pink

– Other stains can be used to demonstrate different substances/structures/micro-organisms

22
Q

How do you preserve and protect the slice of tissue?

A

• Mounting:
– Mounting medium is applied to the slide
– Coverslip is put on top
– Mounting medium dries and hardens, preserving the tissue and attaching the coverslip

23
Q

What happens when the slide containing the tissue has been made?

A

You make a diagnosis

Slides are now ready to be looked at under a microscope by a pathologist

24
Q

What process is used to prove if a substance is in/on cells using specific antibodies?

How does it work?

A

Immunohistochemistry

It looks at the proteins

Usually the antibody is joined to an enzyme (e.g., peroxidase) that catalyses a colour-producing reaction

  • Highlights the substances usually with a brown colour
  • Any substance that is antigenic can be demonstrated:

EXAMPLE - If you wanted to prove that you have smooth muscle of your slide, you’d use Immunohistochemistry against actin and it would come up brown

EXAMPLE - It can tell you if the cancer is positive for hormone receptors and thus if they would respond to tamoxifen

EXAMPLE – Her2 receptor – growth factor receptor, predicts
response of breast cancer to Herceptin

EXAMPLE – Microorganisms, e.g., CMV, HPV, herpes simplex

25
Q

What are the importance of immunohistochemistrys for cytokeratins?

A

Cytokeratins are a family of intracellular fibrous proteins

Present in almost all epithelial cells

So if you want to know if a cancer is epithelial in origin (carcinoma) you can do an immunohistochemistry for theses cytokeratins and it will tell you because only carcinoma will come up

It will also show you where the cancer came from because they are specific for certain parts of the body

26
Q

What is molecular pathology?

A
  • Studies how diseases are caused by alterations in normal cellular molecular biology
  • Can be due to altered DNA, RNA or protein

• In situ molecular tests show how DNA is altered in tissues prepared for microscopy
– E.g., fluorescence in situ hybridisation (FISH) to see if patient will respond to drug herceptin
test for gains of additional copies of Her2 gene in breast cancer

27
Q

How can molecular pathology be used to personalise medical treatment?

A

• Sequencing of DNA purified from tumour tissue can show if a mutation is present in a particular gene
– E.g., if certain mutations in EGFR gene are present in lung cancer then the tumour is likely to respond to anti-EGFR treatments, e.g., erlotinib

• Next generation sequencing enables many genes to be tested simultaneously for mutations

• mRNA expression profiling methods
demonstrate the level of activity of a large number of genes simultaneously - tells you if it has been transcribed

• mRNA signatures

28
Q

When are frozen sections used?

A

Use this when you need an immediate result, eg when a patient is on the operating table and we need to know if their tumour is inflammatory or cancerous.

Urgent histopathology!

  • Method of hardening tissue quickly
  • Not routinely used as morphology not as good as in paraffin sections
  • Intra-operative

• Takes about 10 minutes from receiving specimen in lab to
giving a result

• Aim is to establish presence and nature of a lesion and influence the course of the operation

29
Q

What are the disadvantages of using a frozen section?

A

• Accuracy is in the order of 96%:
– Misinterpretation
– Absence of diagnostic tissue in frozen section (Because the surgeon did not give you the right part of tissue)

30
Q

What is a cryostat used for in frozen section?

A

It rapidly freezes the tissue section in seconds

31
Q

Outline the common layout of a histopathology report

A

1) Clinical History - needs detail, need to know if they’ve had cancer before/treatment so we know how to treat the current problem
2) Macroscopic - what can. Be seen with naked eye
3) Microscopic - what can be seen under microscope
4) Conclusion - it will tell you what was sent and what the tissue is, clinical details are important so they know what they are looking for
5) Reported by

32
Q

What are the names of the two stains?

What are the differences between both stains?

A

Eosin + Haematoxylin

E - stains cytoplasm red/pink
H - stains nucleus blue/purple

Pathological Processes (2 decks)

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