Grading and staging of cancer Flashcards
What is the difference between tumour grade and stage?
Grading = how aggressive the tumour is - degree of differentiation
Staging = how far the tumour has spread
Describe grading
When can it be assessed, when is assessment of grade more accurate?
- Can only be assessed by tumour tissue under microscope
- Usually a biopsy, but examination of whole resected tumour more accurate
- A well-differentiated tumour resembles normal tissue of origin
- Grade 1-3 (well, moderately or poorly differentiated)
What is the nuclear to cytoplasmic ratio (N:C) in
cancer cells?
What is anaplasia?
Normal cells have a low nuclear to cytoplasmic ratio (N:C)
Cancer cells have high N:C
Extreme pleomorphism and nuclear atypia is called anaplasia
How is the cytology (appearance) and architecture (arrangement) of a low grade and high grade tumour different?
Cytology:
Low grade:
- Low N:C ratio
- Uniform nuclear size
- Bland nuclear chromatin pattern
- Cells well spaced out
High grade:
- High N:C ratio
- Variation in size
- Coarse, dark chromatin
- Crowded, overlapping cells
ARCHITECTURE
Low grade:
- Forms organised structures
- Less infiltrative
- Lower mitotic activity
- Less necrosis
High grade:
- Poorly organised
- Infiltrated widely
- Higher mitotic activity
- More necrosis
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)
5 ways tumours spread?
1) Directly into adjacent tissues (e.g. basal cell carcinoma (Ca) of skin)
2) Via lymphatics (e.g. Ca breast, colon)
3) Blood vessels (e.g. renal cell Ca, small cell Ca lung, prostatic Ca, all sarcomas)
4) Along nerves (e.g. Ca pancreas, prostate)
5) Across coelomic cavities (e.g. Ca stomach, ovaries)
How does cancer spread via the lymphatics?
Most cancers spread to regional lymph nodes
Some spread to particular sites
3 ways assessment of staging be done?
– Imaging Eg. Ultrasound, X-rays, CT, MRI and PET scan
– Tissue biopsy Eg. fine needle aspiration (tumour, lymph nodes)
– Surgical exploration Eg. Laparotomy, thoracotomy
Main staging system for all cancers?
Gynae vs colorectal vs Hodgkins?
TNM
FIGO
Ann Arbor
Dukes
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
3 Main factors important in tumour
prognosis? + 3 others
- Stage
- Grade
- Tumour type
- Histological
- Surgical (complete vs incomplete resection)
- Molecular (particular mutations)
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).
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