Grading and Staging of Cancer Flashcards
What is the difference between grading and staging?
- grade = degree of differentiation, higher the grade, the more aggressive the tumour
( Doesn’t give info about how advanced it is) - stage = extent of tumour spread.
Tumours may spread predictably or unpredictably
4 occasions where we grade and stage tumours?
Grading and staging is:
- used only in malignant tumours (except leukemias) - potentially used in all patients where active treatment is considered - used usually in first occurrence of a tumour - can be applied once diagnosis is made, but refined as more info becomes available
Describe grading
When can it be assessed, when is assessment of grade more accurate?
- degree of differentiation, i.e. similarity to tissue of origin
- can only be assessed histologically
- can be assessed at biopsy or resection of the tumour
- Grade assessment is more accurate at resection, as the whole tumour is seen
What is the difference between a low grade and high grade tumour?
What is the most widespread grading system?
Grade 1 - well differentiated. Resembles tissue of origin
Grade 2 - moderately differentiated. Somewhat resembles original tissue
Grade 3 - poorly or un-differentiated. Doesn’t resemble original tissue, very abnormal + aggressive looking
What are alternative grading systems?
bladder vs kidney vs prostate vs breast
Bladder (low and high grade)
Breast (Bloom-Richardson): grades 1 to 3
Kidney (Fuhrman grades 1 to 4)
Prostate (Gleason grades 1 to 5 but add two of the commonest grade together)
Describe how bladder tumours are graded
Describe how renal carcinoma is graded and what each grade looks like in terms of size, chromatin and nucleoli
Stage 1 – small, hyperchromatic, round
Stage 2 – slightly larger (15um) , w finely granular “open” chromatin, but small inconspicuous nucleoli
Stage 3 – larger (20um) + oval shaped nuclei, w coarse granular chromatin (easily recognizable nucleoli)
Stage 4 – pleomorphic nuclei, hyperchromatic + single/ multiple macronuclei
5 ways tumours spread?
- directly into adjacent tissues (e.g. basal cell carcinoma (Ca) of skin)
- via lymphatics (e.g. Ca breast, colon)
- blood vessels (e.g. renal cell Ca, small cell Ca lung, prostatic Ca, all sarcomas)
- along nerves (e.g. Ca pancreas, prostate)
- across coelomic cavities (e.g. Ca stomach, ovaries)
Describe the patterns of spread
Most tumours vs bone metastases vs colorectal vs CNS tumours
Most tumours spread -> loco-regional lymph nodes, then to rest of body
bone metastases are common in breast, lung, prostate, thyroid and kidney cancers - however, all tumours can potentially spread to bone
Colorectal spread: via portal system -> liver, then -> lungs + rest of body
CNS tumours spread widely within CNS compartment but are usually confined by BBB 🤯
3 ways assessment of staging be done?
– Imaging Eg. Ultrasound scans, X-rays, CT scans, MRI
scans, PET scan
– Tissue biopsy Eg. fine needle aspiration, biopsies, excision of the primary tissue or other organs.
– Surgical exploration Eg. Laparotomy, thoracotomy
main staging system for all cancers?
Gynae vs colorectal vs Hodgkins?
Describe the TNM system
T - tumour size/local growth. T1 to T4 score given based on size
-plus Tx (primary tumour not found), T0 (tumour disappeared), Tis (dysplasia)
N - lymph node metastasis (locoregional). N0 to N1 onwards (depending on tissue)
M - distant metastasis. M0 or M1 (whether there is or isn’t)
Combinations give rise to stages I - IV
‘p-’ denotes staging done pathologically vs clinically
Relate the T staging with breast cancer
T stage
– Tx primary can’t be assessed
– T0 No evidence of primary
– Tis Carcinoma in situ
– T1 <= 2.0cm
– T2 >2.0, <= 5.0cm
– T3 >5.0cm
– T4 any size with direct extension to chest wall or skin
Relate the N staging to breast cancer
- N stage (note: pathological staining different from clinical N)
– Nx can’t be assessed
– N0 no regional nodes involved
– N1 1-3 ipsilateral nodes
– N1(itc) isolated tumour cells (<0.2mm)
– N1(mi) micrometastasis (0.2-2mm)
– N2 4-9 nodes
– N3 >9 nodes
Relate the M staging to breast cancer
M stage
– M0 no distant or systemic metastasis
– M1 metastasis present
Link all of the staging processes to give an overall staging for breast cancer
What is a staging process specific for colorectal cancer?
Dukes’ staging for colorectal cancer
A= confined to bowel wall (80-95% 5y survival)
B= through bowel wall but not in nodes (55-67% 5y survival)
C= involves lymph nodes (30-45% 5y survival) (C1 pericolic nodes, C2 high tie node)
D= Metastatic Bowel Cancer ~ 20% of patients with colorectal cancer present late with distant metastases + are inoperable
What is the staging process specific for lymphoma + describe it?
Ann Arbor staging system for Hodgkin’s disease
Stage I = one node group
Stage II = >1 node group, same side of diaphragm
Stage III = node groups either side of diaphragm
Stage IV = non-lymphoreticular organs involved
(spleen = lymphoreticular organ. Presence of ‘B’ symptoms a poor prognostic feature)
2 Main factors important in tumour
prognosis? + 4 others
Classification (histological subtype)
Grade (differentiation) + stage (spread)
Other features:
Histological: e.g. lymphatic invasion, completeness of resection
Protein expression: e.g. oestrogen receptor, Her-2
Molecular (mutations): e.g. KRAS
Patient fitness and age
3 ways prognosis can be measured?
+ 2 ways this survival can be measured?
Overall survival (OS)
Disease free survival (DFS) or progression free survival (PFS)
Response rate (RR) - related to treatment
Survival can be measured as
- median (in months/years)
- chance of survival at 5 or 10 years (%)
Usually staging affects prognosis more than grading
What current molecular tests are in use?
Breast vs Colorectal vs Lung vs Melanoma
Breast: HER2 amplification (FISH) – predicts sensitivity to Anti-HER2 antibodies (herceptin). Also can test for oestrogren/progesterone receptor positivity
Colorectal: K-RAS mutations (PCR) – predicts resistance to Anti-EGFR antibodies (cetuximab).
Lung: EGFR (PCR) – predicts sensitivity to Anti-EGFR small molecules (gefitinib, erlotinib).
Melanoma: B-RAF (PCR) – predicts sensitivity to Anti-BRAF small molecule (vermurafinib).
