Classification, Grading and Staging Flashcards

1
Q

Causes of Enlargement

A
Inflammatory
Hyperplastic
Non-neoplastic Cyst
Neoplastic
= specimen from Mass
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2
Q

Microscopic diagnosis of malignancy

A
Cells relationship
Invasion
Nucleus:
- increased nuclear staining due to increased DNA present
- nucleus size variation
- mitotic activity
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3
Q

Tumour diagnosis

A

Dependant on Histological findings
Modified by
-Special tests (e.g. looking for antigen)
Immuno-peroxidase methods
-Chromosomal Analysis doing FISH or Molecular techniques with actual DNA

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4
Q

Recent classification of CNS tumours

A

chromosomal abnormalities really important in diagnosis

Mutants in wildtype

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5
Q

Monoclonality

A

PArticular groupd of cells all deriving form one cell
-important in neoplasia
-e.g. chromosomal abboration in all cells of the tumour all originating form one cell
If you show a collection of cells is monoclonal, good evidence for neoplasm
Monoclonal= Neoplastic
In some situations Monoclonal = Malignant
-But mainly Malignant is Multi-clonal/Polyclonal (increased cel replication therefore more susceptible to mutation)

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6
Q

Monoclonality re Leukemia or Lymphoma

A

Leukemia or Lymphoma not solid
-cannot be benign
If you can show that the collection of cells is monoclonal (all originating from one cell) –> is equivilant to malignant

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7
Q

Multiple Myeloma

A

A Malignant neoplasm of plasma cells
-not normally in big numbers in bone marrow, but do arise in bones
-top of skull can be a eroded out by a collection (collections can destroy bones)
Produces a single antibody molecule (specific with specific affinity)
-if becomes neoplastic then all will produce same chemical/antibody
Conduct Electrophoresis on plasma: (separate out into a, b, and y globulin antibodies)
Monoclonal kappa-light chain producing population
Y gamma Monoclonal band (sharp peak because all been produced by one cell, all chemically the same)
Suppressed normal y globulin
-dense collection of plasma cells in bladder. Staining for chains. Treated for neoplasm.
-can also use lymph nodes and use fluids, mark for Kappa or Landa chains or other antigens, and determine whether major population is monoclonal.

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8
Q

Why Classify Tumours?

A

Because Tumours differ in:

  • Cell of origin (therefore Distribution)
  • Behaviour
  • -> and therefore:
    a. Clinical Presentation
    b. Prognosis
    c. Treatment
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9
Q

Tumour Grading Definition

A

A measure of the RATE of tumour growth based on tumour histology
-e.g. in breast

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10
Q

Tumour Grading

A
Breast: 3-9
2-5 Grade 1
-resembles glands of normal breast (round and open)
5-6 Grade 2
-merging together, few lumen, nuclei more irregular
7-9 Grade 3
-no tubules
-nuclei large and open, big nulceoli with mitotic activity
1. Differentiation
2. Nuclear Changes
-pleomorphism
-enlargement
-hyperchromasia
3. Mitotic Activity
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11
Q

Tumour Staging

A

A measure of the EXTENT of tumour growth based on clinical, radiological and pathological features

  • clinical (breast carcinoma fixed to skin, tumour is growing into derm)
  • radiological (lymph nodes)
  • pathological
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12
Q

Grading and Staging

A

Extent= Rate x Duration
Rate of Growth measures (grading)
Extent of Growth measures (staging)

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13
Q

Rate of Growth measures (Grading)

A
(Pure) Histological grading
Tumour Infiltrating Lymphocytes
Cytogenic Changes
Proliferation indices (how many mitoses/cells seen to be active proliferation)
Suppressor-/ Oncogenes
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14
Q

Extent of Growth measures (Staging)

A
  1. Stage
    - clinical
    - radiological
    - pathological
  2. Serum Markers (proteins produced in large amounts by tumours, identifies extent of tumour)
    - e.g. PSA prostate specific antigen of ten Cancer. 50 likely to be Metastatic
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15
Q

TNM staging system

A

T for Tumour (characterisitcs - size, structures it has invaded)
N for Nodal metastasis (lymph)
M for distant Metastasis (not nodal)

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16
Q

AJCC stage equivilant

A
T1= in submucosa
Dukes stage A= AJCC Stage I (T2N0Mx)
Dukes stage B= AJCC Stage II (T3N0Mx)
Dukes stage C= AJCC Stage 1 (T3N1Mx)
P= pathological
R= radiological/Clinical stage
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17
Q

Spread of Cancer

A

Local Spread (continuous with main tumour)–> fat and neighbouring organs
Metastasis
-Lymphatic spread
-Venous Spread
-Serosal Cavities (e.g. Peritoneum)
-Nerves (e.g. salivary gland or prostatic tumours)

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18
Q

Spread of Cancer Lympahtics

A
Lymphatic vessel
Lymph node
Macroscopic apparent Lymphatic Spread:
-can see tumour on surface of serosa
Lung: Lymphangitis Carcinoma
Breast: Peau d'orange
-rigid 
-unnatural falling
--> tumour has invaded into dermis, blocking some lymphatic channels
-orange peel appearance, skin become oedematis, dips=hair follicles go in, stopping swelling (lymphatic blockage)
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19
Q

Spread to Bone

A

Common
esp. for Axial skeleton (spine , prox limbs)
Multiple myeloma
-Pathological Fracture (little movement breaks weakened bone)
-Hypercalcaemia (high blood calcium levels due to massive destruction of bone
-Pain (collapse of vertebrae, erosion, microfractures) - important for treating cancer patients

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20
Q

Adenocarcinoma grading and staging

A

tubular spaces
invades through muscular wall into peri-coating fat
mucus
=more differentiated = low grade tumour

21
Q

Single Cell Type Neoplasms

A

Epithelial Tumours (surface and glandular)
Melanocytic Tumours
CT tumours (fibrous tissue, cartilage, bone, fat, BV, Smooth muscle, Striated muscle)
Lymph nodes
Bone marrow
CNS

22
Q

3x Main classifications of Neoplasms

A

Single cell type
-most common
-tumours arise in a particular tissue, and replicate the appearance of that tissue with just a single cell type
Mixed tumours
-still single cell monoclonal type, but diverge in different directions
-some salivary gland tumours
Germ Cell Tumours
-testes, ovaries
-any tissue kind can occur as undifferentiated cell, differentaited in many cell directions

23
Q

Surface Epithelium Tumours

A
Flat= Pappilomas (benign)
Round= Carcinoma (malignant)
24
Q

Glandular Epithleium

A

Adenoma (“adeno”= gland) (benign)

Adenocarcinomas (Malignant)

25
Q

Connective Tissue CT tumours

A

“sarcoma” - malignant cancer of CT (bone –> Soft tissue tumours not bone)
Fibrous Tissue (fibroma, fibrosarcoma)
Cartilage (chondroma, chondrosarcoma)
Bone (osteoma, osteosarcoma)
Fat (lipoma, liposarcoma)
Blood Vessels (haemangioma, Angiosarcoma)
Smooth Muscle (Leiomyoma, Leiomyosarcoma)
Striated muscle (Rhabdomyoma, Rhabdomyosarcoma)

26
Q

Lymph node, Bone marrow and CNS Malignant tumours

A

Lymph nodes: Lymphoma
Bone marrow: Leukamia, Multiple Myeioma (occurs in bone marrow but more a lymphoma as it is a plasma cell that is more a lymphoid cell)
CNS: Glioma

27
Q

NZ Cancer deaths

A

Women: Breast, Colorectal, Lung, Endometrium, Pancreas (high as quiet and late presentation), Lymphoma, Stomach, Leukamia, Melanoma (common but on surface so most cured), Brain
Men: Lung, Colorectal, Prostate, Stomach, Lymphoma, Pancreas, Leukamia, Melanoma, Oesophagus, Bladder

28
Q

NZ cancer deaths Carcinomas

A

Women: breast, colorectal, lung, endometrium, pancreas, lymphoma, stomach, leukemia, melanoma, brain
-most carcinomas. carcinomas form bulk of cancers
Men: Lung, colorectal, prostate, stomach, lymphoma, pancreas, leukemia, melanoma, oesophagus, bladder

29
Q

Benign Epithelial tumours

A

Adenomas, Papillomas, Cystadeomas (cystic/fluid filled e.g. ovarian)
Morphology - regular tightly packed cells (adhered. found on surfaces and role to seal/form waterproof barrier through which nutrients and excreted products can be exchanged and kept sealed)
-glands (secretory channels) =Adenomas
Some are premalignant (show dysplasia) - only really LI adenoma and some GI

30
Q

Carcinomas

A

Most common malignant tumours
Preceded by in situ growth phase (severe dysplasia, same sight not invaded into BM (defined by epithelial growth))
-diagnosed as malignant by invasion
Morphology
-cohesive polygonal cells (some highly malignany become less cohesive)
-cytokeratin positive (skin and nail, found in all epithelial cells, even those not producing gross keratin) -if cell has keratin, likely ot be carcinoma
Spread of lymph nodes, bone, viscera
Treatment:
-Mainly surgical
-Variable response to radiation and chemotherapy

31
Q

Macroscopic Epithelial Tumours Glandular

A

Adenoma- LI - protrusive fungating growth
-much larger nuclei (hence darker staining)
Adenocarcinoma - dark change in epithelium nothing to do with carcinoma (melanosis coli)
-helps to contrastnew growth that has occured
-wildly invading, tissue on top starts dying a falling off –> ulceration
(alot of tumours on surface often become ulcerated)
-wild, irregular, invasive
-malignant tubules extending down into submucose(invasive)

32
Q

Carcinoma of the Breast

A

Occurs in a “spiky manner”

-produce alot of collagen/stroma

33
Q

Carcinomas

A
Most common malignant tumours
Preceded by in situ growth phase
-diagnosed as malignant by invasion
Morphology:
-cohesive polygonal cells
-cytokeratin positive
Spread to lymph nodes, bone, viscera
Treatment:
-Mainly Surgical
Variable response to radiation and chemotherapy
34
Q

Embryonic Germ Layers

A

As embryo develops and neural tube closes –> neural crests give rise to neural crest cells –> giving rise to:

  1. autonomic ganglia
  2. schwann cells (produce mylein for peripheral nerves)
  3. cells that go down the nerves, into all tissues onto skin to become melanocytes
    - melanocytes dont differentiate into epithelium where they reside. some grow all over the place, migrating into mucosal surfaces (resulting in melanomas, benign malacitic tumours in anus, mouth, vagina and bladder)
35
Q

Melanocytic Tumours

A

Benign (Naevi) and Malignant (Melanoma)
Common Tumours of skin, also other sites
-benign common
-light skinned people have dozens of naevi around body
Can define in situ phase for melanoma
-normal reside in basal layer of epithelium = natural barrier (stay within and then can invade downwards)
Spread via lymphatics and Blood stream
Treatment: mainly surgery
Morphology
-Spindle cells, round cells, pleomorphic cells
-Cytokeratin Negative, S100 protein Positive
-now have better melanoma marker Sox10

36
Q

Malignant Melanoma Macroscopically

A

-main lesion
-small metastaces
-little metastatic deposits, having travelled through lymphatics
-ulceration - makes prognosis much worse
Microscopic: tumours starts in situ –> then starts growing up into epidermis –> then down into the dermis, to form a thick tumour

37
Q

Normal Connective Tissue

A
Fibrous Tissue
Specialised CT
-muscle
-bone
fibroblasts, capillaries, mast cells
38
Q

Connective Tissue tumours

A

Sarcomas rare (1% of malignant tumours), benign tumours common
Lipoma benign tumour in fat one of most common
Leiomyoma Smooth muscle tumour v common in uterus
Cannot define in situ phase (as tissue in which is arises doesnt have any natural barriers)
Spread via blood stream, mainly to lungs (common metastaces site for sarcomas)
Treatment: Combination treatment. Often surgery + Radiation + Chemotherapy
Morphology
-Spindle cells, Round cells, Pleomorphic cells
-Mainly Cytokeratin Negative
-some special markers (e.g. Smooth muscle tumours ACTIN (raise an antibody for it))

39
Q

Connective Tissue tumours Benign

A

Lipoma- skin -well encapsulated. more common in overweight people, men, around shoulder, arms, back. palapble lump. can easily. take out
Leiomyoma (fibroid)- Uterus - massive distorting mass of smooth muscle overgrowth, rare. usually only few mm and 1/5 woman, just removed.
-SM looks indistinguishable under microscope
-seen better macroscopically as where it starts and finishes

40
Q

Lymphomas

A

Common Tumours (lymph nodes, extra nodal sites) (Hodgkin’s + Non-Hodgkins)
No benign counterpart (all are malignant)
No in situ phase
Spread to other lymph nodes, extra nodal
Treatment: Chemotherapy, radiotherapy (rare localised lymphomas may excise on skin, but most systemic so cant)
-mostly lymphocyte. Stains Endoperoxidase stains to help with antigenic features for classification
Morphology
-Non-cohesive round cells
-Cytokeratin Negative, (Leukocyte Common Antigen Positive)
-help distinguish from poorly differentiated carcinomas and sarcomas

41
Q

Malignant Lymphomas

A

Lymphoma (all malignant)

  • Hodgkins and non-hodgkins
  • B cell ( and T cell)
  • Low and High grade
  • Nodal and Extra nodal (rare, bowel)
  • normally enlarged lymph nodes occuring in big masses, sometimes enlarges out of those nodes, mapping nodes together
42
Q

Hodgkins and non-hodgkins Malignant Lymphomas

A
  1. Hodgkins (characterised my multinucleated Reed-Sternberg cell neoplastic cell. all other cells are reactive cells part of stroma- hence the neoplastic cells are rel. small volume of tumour)
    - mostly B cell lymphomas including Hodgkins Lymphoma
  2. Non-hodgkins
    a) Small cell (low grade)
    b) Large cell (high grade)
43
Q

Leukaemia

A

uncommon
-amy start from myloid series (progenitors which form granulocytes and neutrophils) or lymphoid series (anitgen producing B cells)
=Thicker buffy coat in leukemia
No Benign counterpart
No in situ phase
-Grow very diffusely. Bone marrow –> circulating malignant cells in Blood
-Non space occupying lesion,
Bone Marrow, extramedullary
Treatment: Chemotherapy
Prognosis depends on type
CML
-normla femur would see heamoposetic tissue in top and bottom, and diapsysis woudl contain fatty marrow, but proliferation results in occuping in fatty marrow but red malignant marrow, depressing normal cells
-Also accumulate in spleen (chronic myloid leukemia)
-can also get small tumours (neoplasms)

44
Q

Glial Tumours

A
(brain tumours)
uncommon
Varying grades, but mostly incurable
Restricted to CNS
-dont metastasise outside of CNS
Treatment: surgery, Radiotherapy, Chemo therapy
45
Q

Glial Tumours Astrocytoma grades

A

Astrocytoma Gr2:
-Low grade very diffuse. Very intrusive but dont grow that fast so dont cause Haemorrhage and necrosis
Astrocytoma Gr4/ Glioblastoma:
-Haemorrhage and Necrosis

46
Q

The most aggressive cancers

A

HIGH grade:
Undifferentiated (little round cells. sometimes hard to differentiate from lymphoma, even though have very different treatment)
Poorly differentiated (less resemblance from tissue it originated from)
Anaplastic (worse)
Pleomorphic (cells very variable in size)

47
Q

Undifferentiated tumours

A

-Cant tell what they are on H&E stain
Need special techniques to see ultrastructure or antigens
Distinction from lymphomas

48
Q

Immuno histochemistry

A

Cytokeratin- Carcinoma
Leukocyte Common Antigen - lymphoma
S100- melanoma

49
Q

Connective Tissue Tumours Malignant Osteosarcoma

A

Occur in boys 10-15yrs
unclosed epiphysis- growth plates still present
-white creamy tumour invading into bone marrow, breaking through epiphyseal plate into epiphysis
+ breaks into cortical bone and pushing out periosteum
-these tumours MAKE bone
Triangular features= Cottons Triangle
-Osteoid matrix produced
-poorly undifferentiated cells, dark nucleus, little sytoplasm