General Dysplasia-Carcinoma Sequence

Question 1

What is the general dysplasia-carcinoma sequence

Answer 1

1. +/- metaplasia (adaptive)
2. Mutation leading to mild dysplasia in basal epithelia
3. Moderate dysplasia - Accumulation of mutations & proliferation to partial thickness of epithelia
4. Severe dysplasia - accumulation of mutations, clonal expansion to full thickness of epithelium
5. Carcinoma in situ = sever dysplasia of full thickness which out breach of BM/barrier defining invasion
6. Breach of BM/barrier to invade stroma = malignant carcinoma

Question 2

What are some examples of adaptive metaplasia that can lead to dysplasia-carcinoma sequence?

Answer 2

Barette’s oesophagitis - metaplasia of sqamous eipthelium to glandular (columnar epithelium) in response to GORD + intestinal metaplasia (goblet cells)

Chronic inflammation in smoking - sqamous metaplasia in the bronchioles in response to smoke

Chronic gastritis - intestinal metaplasia

Question 3

What is a carcinoma in situ example that does not arise from metaplasia?

Answer 3

Ductal carcinoma of the breast doesn’t have a metaplastic precursor

Question 4

What barrier is considered invasion in:
Cervical
Oesophageal
Colon
Breast 
Prostate ?

Answer 4

Cervical - BM
Oesophageal - BM
Colon - Muscularis mucosae 
Breast - myoepithelial cell layer 
Prostate - basal cell layer

Question 5

Why is there are difference in the barrier defining invasion in some organs?

Answer 5

Access/Location of the lymphatics

In colon cancer the lymphatics are within the submucosa therefore invasion must be past the muscularis mucosae