Using the Pathologist Flashcards
1
Q
Definition of Neoplasia
A
- sometimes the neoplastic cells originate from a single cell that has undergone multiple mutations rather than just one
2
Q
A
- simple example
- schematically on the left is a tumor that is raising the epidermis of the skin
- on the right: tumor on the end of a cats nose, nasty/aggressive looking tumor –> squamous cell carcinoma - how can we tell?
- Can only really know by looking at the histology, but can take a guess bc this is a white cat and they lack a lot of melanin in the skin and are therefore more predisposed to developing squamous cell carcinomas (particularly on the nasal plane and the ear tips)
- See especially in countries where there is a lot more UV
3
Q
Neoplasia
(benign or malignant)
A
- this classification is key to the prognosis of the animal and the treatment plan you may follow
4
Q
Characteristics of Benign Tumours
A
- grow by expansion rather than infiltration
- we can use these kind of features on gross examination to decide if they are malignant or benign
- freely mobile on palpation - like a lipoma (fatty tissue lump) on a dog –> usually pretty mobile in the skin
- different to such things as a mammary tumor which can be pretty fixed, immobile and rigid in the dermis
- surgical removal can be easy depending on where it arises from - there will be areas where there is very little skin so any growth removal will be hard
- THEY DON’T SPREAD TO DISTANT SITES WITHIN THE BODY
5
Q
A
- cutaneous hemangioma
- black or even dark red nodule within skin
- there in poorly haired skin of dog
- grossly: cutaneous hemangioma
- differential may be a melanoma (black could indicate a pigmented lesion)
6
Q
Microscopic Features of Benign Tumours
A
- ex: work out between melanoma and cutaneous hemangioma differentials
- whatever cell is that is neoplastic, they tend to recapitulate that tissue within the tumor
- well organied in general
- even if benign- the ones of endocrine origin can have quite adverse effects on other parts of body - ex: thyroid adenomas causing throid problems in older cats
- In dogs we adrenocortical tumors which are often functional and then Cushings Disease as a result - benign tumors that may have quite significant functional effects by secreting hormones
- can see surrounding capsule microscopically as well as feel grossly - do not breach capsule
- generally low mitotic rate–> yet there are exceptions to that
7
Q
A
- low power - can see haired skin and tumor below
- tumor has lots of blood filled spaces
- high power shows red (erythrocytes) within these vascular spaces and then lined by a single thin layer of endothelium - same as normal vessels
- but just way too many
- common features of benign tumors
8
Q
A
- slightly higher power
- can see endothelial cells and neoplastic cells
- but they are well defined and forming normal looking vascular structures
- jsut that they are in excess
9
Q
Characteristics of Malignant Tumours
A
- somewhat the entire opposite to benign
- grow by invasion rather than compression of adjacent tissue
- tend not to be encapsulated
- removal can be hard becasue grossly it is hard to tell where the tumor ends or where normal tissue begins
- can recur as they can be hard to completely remove
- can ulcerate on skin or mucosal surface due to rapid growth
- generally depends on tumor type where they go and how frequently they metastasise but one of the characteristics of malignancy is metastasis
- top pic: intramuscular hemangiosarcoma (malignant tumors of BV’s) -can occur anywhere there are BV’s as a primary mass
- bottom: these hemangiosarcomas can metastasise quite early (as seen here in the lungs) and the thoracic cavity is full of blood - these tend to bleed quite easily as they are extremely vascular tumors and they have multiple dark red nodules over surface of the lung
10
Q
Microscopic Features of Malignant Tumours
A
- again somewhat the opposite to benign tumors
- anisocytosis: shape of the cell, cytoplasm in particular
- In malignant cells the size of the nucleus becomes much larger relatively to the cytoplasm than in normal cells or benign neoplastic cells
- ability to divide becomes kind of disrupted and they dont really divide properly - may even result in a binucelated or multinucelated cell
- loss of structure/cohesiveness–> hallmark of invasion
11
Q
A
- what the gross image would look like under microscope
- on left: rather than well differentiated blood vessel structures as seen with benign –> this is much more cellular and the cells that are there are no longer flat endothelial cells, they are much more plump and the cells themselves are larger - vascualr spaces are harder to define
- on right: example of an even more pleomorphic population of neoplastic cells - very prominent nucleoli here and looking at the size and shape of these cells - can appreciate that they are really variable
- marked anisocytosis and anisokaryosis
12
Q
Tumour Nomenclature - Epithelial Origin
(benign/malignant)
A
_*These are all of epithelial origin*_
13
Q
Tumour Nomenclature
(mesenchymal origin)
benign v. malignant
A
- mesenchymal tumors are slightly more complicated
- then depends on the tissue type
- SM, endothelium, skeletal names are a bit less obvious
- granuloma: not a tumor! involves macrophages in an organised manner
14
Q
Tumour Nomenclature - the exceptions
A
- Lymphomas are ALWAYS MALIGNANT (just more of a question of how malignant) ..even though they end in -oma (some will use lymphosarcoma to cover that)
- Melanomas - can be benign or malignant. sometimes more useful to say malignant melanoma to differentiate
- Mast Cell Tumors - tend not to say mastocytoma, mast cell tumors all vary in degree in malignancy.. there really isnt a benign form
- Teratomas- quite primitive tumors arising from the testicle or ovary and there are occassionally malignant variants of these teratomas, but generally benign (90% are)
- Sarcoids: see in the skin of horses and have a viral aetiology. From BPV-1/2
15
Q
Tumour Metastasis
(4)
A
- How do these malignant tumors actually spread?
- vascular referring to BV’s
- Trans-cavity is also called transcoelomic spread
- local spread and infiltration
16
Q
Tumour Metastasis: lymphatic
A
- typical of the epithelial tumors –> carcinomas or adenocarcinomas
- Usually the draining lymph nodes are the first hit and then they would go for example to the lungs (classic 2nd place)
- ex: mammary tumor in the bitch - local lymph nodes would likely be the first place to go from there (inguinal LN or any LN’s along the mammary chain) and from there likely end up in the lungs
- but they have even been seen to metastasise widely in the body and even in rare cases, the brain
- no way of predicting necessarily where they are going to go, but there is a certain probability
- Before undertaking major surgery for a mastectomy, they will take a radiograph of the chest and find out the stage of cancer befre deciding on treatment plan
- Image: in the lymph node - can see that glandular epithelium has invaded the lymph node (should not see this normally in a LN!)
17
Q
Tumour Metastasis: Vascular
A
- sarcomas (the mesenchymal tumors) tend to go via BV’s
- can dgo anywhere where there is a large vascular component
- again ex: THE LUNGS- but go to the lungs via BV’s rather than lymphatics
- other ex’s: to the spleen, the liver
- pic: hemangiosarcoma - renowned for metastasing early, by the time you reach diagnosis they have already metastasized
- tumor of BV’s - those tumor cells can very easily spread among the wider vasculature of the body and may develop secondary tumors elsewhere
- generally quite a poor prognosis
18
Q
Tumour Metastasis: Trans- Cavity
(or Transcoelomic)
A
- tend to arise in a cavity within the body and then spread within that cavity
- ex: mesotheliomas (can occur within thoracic cavities or peritoneal caivty) and then will spread quite easily with tumor cells contacting from one surface to another surface
- or can travel within fluid of that cavity
- also ovarian carcinomas quite frequently in humans and animals alike
- right: example of metastatic ovarian carcinoma in a bitch - wide spread metastasis throughout mesentery, little tumors implanted onto surface of liver, etc. –> quite extensive and quite hard to manage
- It is not that it is really going to spread widely around the body persay, but in humans for example, will spread very quickly throughout lung cavity (linked with asbestos)
- not like a single mass that you can very easily remove
19
Q
Tumour Metastasis: Local
(local spread or local metastasis)
A
- classic in veterinary medicine is fibrosarcomas
- good example is feline vaccine associated
- Injection-site sarcomas - not what is in the picture
- essentially likely driven by the vaccine adjuvant
- but those tumors can be very invasive! - grow and invade the shoulder blades and can grow into bone or muscle (not just the soft tissue of the scruff) - really hard to manage and control
- rarely will metastasise larger than that (i.e. lungs, elsewhere)
- just very infiltrative and aggressive
20
Q
Tumour Metastasis
A
- some of the examples of tumors - lymphoma being the best example- can arise at multiple sites effectively - multicentric tumors (ex: multicentric lymphoma)
- those tend to be viral in aetiology - ex: feline leukaemia virus induced- now less common to multicentric lymphoma in the cat
- FeLV vaccine is aiding this and is very routine now
- osteosarcomas really frequently metastasise
- edit: oral and digital *malignant* melanomas
- mammary carcinomas in DOGS have a much better prognosis than in cats (in cats it is very poor where as in dogs it doesnt necessarily mean poor)
21
Q
Use of Immunohistochemistry in Tumour Diagnosis
A
- what can pathologists do to help reach a diagnosis
- sometimes can get a 99% diagnosis off history/gross appearance, sometimes need histology
- poorly differentiated tumors wil need other tests
- immunohistochemistry: using Ab’s to recognize certain antigens expressed within the tumor cells - intermediate filaments (in the cells themselves/cytoplasm) or cell surface markers (antigens on surfaces of cells)
- really well developed in human oncology! - can have about 40 different Ab’s thrown at that tumor to get info on which proteins it is expressing and which drugs it may be susceptible
- In vet med, a bit behind the curve on this, but definitely improving! -gradually looking in a diagnostic setting at potential drug targets for these situations
- remember the ones listed as they are the more commonly used
- ex: cytokeratin is often expressed in carcinomas
- can apply Ab pair to then stain for cytokeratin and Vimentin separately to distinguish between carcinoma or sarcoma (which it is + for)
- can do similar thing for T-cell and B-cell lymphoma –> important as they have different treatments and prognoses
22
Q
A
- sheet of cells
- really no pattern there, maybe mosaic
- can see individual ccells and some space b/w them
- but no tubules there, no glandular structures
- lymphomas: patternless sheets of cells
- but can’t tell if it is T-cell or B-cell from this
- would need immunohistochemistry
23
Q
A
- use CD3 Ab that stains for T-cells
- brown staining is +
- this is a T-cell lymphoma
24
Q
Tumour Grading
A
- how differentiated is the tumor
- BUT, need to be able to distinguish between grading and staging
- staging is a clinical test, what is the stage of the tumor in its development? has it spread and how far?
- Grading is more how bad is this tumor?
- but you can have a high grade tumor at a low/early stage
- and a low grade at an advanced stage
- so both important but slightly different in how they are worked out!
- prognosis does not always directly correlate to tumor grade - imp to know!
25
Q
Examples of Tumour Grading
A
- immunophenotyping - like what was done with the lymphomas (T or B cells) which has a bearing on the grade
- Ki67 is used most often in vet med for identifying proliferation - how rapidly dividing are the cells, what % of the cells are in active cell division
26
Q
A
- done every day as pathologists
- see high grade vs. lower grade
- on the right: it is a squamous cell carcinoma but generally looks like normal surface epithelium, has a basal layer, and then a layer that looks like the stratum spinosum with a keratinizing layer internally and it is producing keratin which a normal stratified squamous epithelium should be doing. KERATIN PEARLS
- on the left: still a squamous cell carcinoma, but it is much less well differentiated. cells are rarely keratinizing and much more pink cytoplasm are wanting to keratinize but not sure how to do properly, so the differentiation of the tumor is way less. these tumors tend to behave much more aggressively and have poorer prognosis
- rough measure but can be quite useful clinically
27
Q
A
- OR gain expression of the unexpected (often more primitive markers) - ex: renal cell tumors in dogs - poor prognosis –> in the tumor there is a strong expression of a cell cycle regulation 14-3 -3 protein. can actually be targeted by blocking rc’s
- ex: cytokeratin can be a marker of epithelial carcinomas, but sometimes if they are poorly differentiated, they lose this expression or it becomes very weak and it becomes very challenging
- various methods we can use (some at research stage) that can give us more info on grade of tumor
- can give diagnosis but also suggest potential treatments for these cancers
28
Q
A
29
Q
Newer Methods of Tumor Grading
A
- some will run Ki-67 on all mast cell tumors
- can now use grading systems devised that allow us to grade them into low or high grade
- shown that some of those low grade tumors when you use when you use Ki-67 have a very high proliferation rate
- probably should be classified as high rather than low
- for these now tend to use the high/low histological grading and then use Ki-67
30
Q
How the Pathologist can Help the Clinician
A
- can help at least narrow down differential diagnosis list
31
Q
Choosing a Pathologist
A
- often dont have much of a choice
- a lot of larger practices now have contracts with a lab
- some are connected to them by company
- but if you can, may want to pick those with expertise in a certain area
- cost is important
- location is less so now as there are lots of couriers and easy to ship overnight
32
Q
What the biopsy Report should Contain
A
- basically copy directly off submission form for history as somewhat of a double check for right sample and history per animal -make sure it is right!
- SURGICAL MARGINS ARE VERY IMPORTANT- you want to know if you have removed this in its entirety or is there still tumor in the animal
33
Q
A
- example of what is produced at RVC
- macro and microscopic description
- short comments as they are going to the hopsital and they shouldnt need much educating
34
Q
Communication with the Laboratory
A
- If there is something you are not sure about, PHONE THE LAB
- if the diagnosis doesnt fit, discuss with the lab
- or if you are unsure what to submit for a sample
- If you need the results urgently then just say why
- follow up is good!
35
Q
Pathologist’s Requirements
A
- what pathologists need to give a better diagnosis from the clinicians
36
Q
A representative sample
A
- endoscopic: stomach, SI
- wedge: bigger organs - liver, LN’s, spleen
- excisional: whole lump in the skin in its entirety for example
- If you think you have removed the whole thing, say excisional! so they can report back in case you havent in fact removed it all
- include a margin of normal tissue with your sample
- avoid necrotic tissue or cacitated areas (except bone tumors where the middle is where th maximum bone lysis occurs)
- mark margins of interest!! - so many people forget. ex: green was left and red was right (just leaves thin layer to help pathologist orientate)
37
Q
A Correctly Submitted Sample
A
- has to be in a lot of Formalin! (10x amount to that of sample)
- should be no more than 2cm as it will rot before it fixes - if need be cut into it to let the formalin penetrate
*
38
Q
A
- left is well fixed!
- middle is not fixed in the center and that will start to autolyse before it gets fixed - likely was too thick
- tubes: one on left is right amount of formalin ratio, right is not (wil not fix properly)
39
Q
A Correctly Submitted Sample
A
- Correctly label the Sample!
- If you have different sites put them in different pots
- skin biopsies- try to take a bit of normal skin adjacent to or near area for comparison (can give quite useful info on what is normal for that animal)
40
Q
Full Clinical History
A
- remember breed! - disease and tumor dispositions
- any previous lab results need to be included
- current medicines - chemo? immunosuppressants
- if you have a diagnosis you believe it is? can help narrow things down!
- forensic or legal case? put on there
- photographs will help!
41
Q
Horse Kidney with large mass
A
- description of this
- what they need to know
- remember pathologists arent really getting to see what you see in a clinic
- real pictures or schematics can really help! - draw a picture of location!
42
Q
Anisocytosis
A
- variation in size of cells and especially of the red blood cells (as in pernicious anemia)
- Particularly in the cytoplasm of cells
43
Q
Anisokaryosis
A
- A larger than normal variation in the size of the nuclei of cells.
47
Q
Lipoma
A
a benign tumour of fatty tissue
