Surgical oncology

Question 1

MEN1

Answer 1

Autosomal dominant condition
Mutation in MEN1 gene on chromosome 11, tumour supressor gene coding for MENIN protein
Tumorus: 3 P’s
- Parathyroidism - usually multigland. 90%
- Pancreatic neuroendocrine tumours 60-80%
Pituitary tumours 50%
Other stuff:
- lipomas
- Foregut NET’s (bronchus, thymus, duodenum, stomach)

Question 2

MEN2a
MEN2b

Answer 2

Autosomal dominantly inherited condition due to mutation of the RET proto-ongogene on chromosome 10 which codes for MEN2 protein. This is a receptor tyrosine kinase which when mutated leads to gain of function and uncontrolled growth.
2a: Phaeo, Medullary thyroid cancer in 30’s, primary hyperparathyroidism (often multigland).
- also cutaneous lichen amyloidosis, neuromas of lips and tongue
2b: Very agressive and early medullary thyroid Ca, phaeo. No parathyroid.
- Also Hirschprungs

Question 3

Lynch syndrome

Answer 3

Autosomal dominantly inherited mutation of one of the mismatch repair genes MLH1, MSH2, MSH6, PMS2 via microsatellite instability, leading to impaired regulation of DNA transcription
Causes CRC at a young age (50%, 45%, 20%, 10% with the above subtypes)
Cancers are: (LAMPS)
- Lymphocyte infiltrating (TILS)
- Assocatied cancers - CESOPUPS colorectal, endometrial (particularly MSH6), stomach, ovarian, pancreatic, urothelial, brain, skin
- Mucinous and metachronous
- Proximal cancers (right sides), poorly differentiated
- BRAF negative

Question 4

FAP

Answer 4

Autosomal dominant inherited condiiton due to germline mutation of APC gene - tumour suppressor gene leading to increased B catenin cell signalling via the WNT pathway and proliferation of intestinal crypt cells.
Early and increased progression throught he adenoma-carcinoma pathway, early devel of hundreds of polyps which leads to a 100% risk of CRC over lifetime.
ABC3D3EFGH
Adenomas
B bone abnormalities
C olorectal cancer
C NS tumours
C HRPE
D esmoids
D duodenal polyps (Spigelman criteria)
D dental (supranumbery teeth
E ndocrine (thryoid)
F fundic gland polyps
G ardeners syndrome
H epatomas.

Question 5

Spigelman criteria

Answer 5

Severity classification system describing the frequency of endoscopic surveillance required for FAP patients with duodenal polyps.
Based on 4 factors (number of polyps, size of polyps, histological subtype and degree of dysplasia).

Question 6

Immunohistochemistry stains
- GIST
- Merkel
- Melanoma
- HCC

Answer 6

• GIST: CD117, DOG1
  -Merkel cell: neurofilament, CDK20
  -Melanoma: S100, MelanA, CDKN2a C-KIT for acral cancers
• HCC: GPC3, HSP70

Question 7

Peutz Jegher syndrome

Answer 7

Autosomal dominant condition with STK11 mutation which is a tumour suppressor gene.
B-CHOMPT
B reast
C -colorectal
H- hamartomatous polyps
O -ovarian
M - mucocutaneous pigmentation
P- pancreas
T - testicular

Question 8

Juvenile polyposis syndrome

Answer 8

Autosomal dominant mutation of SMAD4 gene (in 50% of cases)
- CHUP
C- colorectal cancer
H- hamartomatous polyps
U upper GI (duodenal and gastric Ca)
P - pancreatic