Question 4.
(a) Define tumour suppressor genes and protooncogenes and give examples of their normal function.
(8 minutes)
(b) Explain why inherited mutations in tumour suppressor genes are typically associated with increased risk of cancer.
(5 minutes)
(c) Suggest why inherited mutations in protooncogenes are not associated with cancer.
(2 minutes)

Question 4.
An autopsy is performed on a 48-year-old man. The pathology registrar lists the autopsy findings as follows:
• Several large dirty-yellow, rounded masses in the liver;
• Firm nodular lesions in mesenteric fat adjacent to rectosigmoid colon;
• Multiple small (ie several mm average diameter) white nodules in both lungs;
• A large mass in the rectum with firm, thickened underlying bowel wall, apparently
extending into pelvic wall;
• Four small polyps in colon, measuring between 3 and 15mm.
a) Which one of all the lesions mentioned could have been the initial event leading to the other problems?
(3 minutes)
b) Describe the pathobiology and how the lesions are interelated.
(12 minutes)

Question 2.

A 38-year-old woman is investigated because of apparent fertility problems after having tried to get pregnant for 4 years. A pelvic ultrasound is performed as a routine investigation. A large infiltrative pelvic mass, centred around the lower portion of the uterus and cervix, is diagnosed, with some ‘suspicious’ lymph nodes in the pelvis.
Further questioning by the gynaecologist reveals that this woman had her last cervical smear (a screening test for cancer) 8 years ago that apparently showed ‘some mild atypical changes’. She did not bother with any further smears as she believed herself ‘to be too busy’ and ‘after all, only had one partner’.

a) What do you think the likely diagnosis of the pelvic mass is given the history provided?
(2 marks)
b) Outline the cellular and molecular changes that may have occurred in the affected tissue as it changed from ‘normal’ to ‘atypical’ (as reported in the smear 8 years ago), into a ‘large infiltrative pelvic mass’.
(14 marks)
c) Name an agent that is likely to have causative role in this condition.

Question 4 (12 marks in total)
A 25-year-old pop singer detected a lump in her right breast. Investigations revealed that she had an adenocarcinoma (ductal carcinoma) in the right breast. She underwent lumpectomy (partial resection) for the cancer. The pathological staging of the breast cancer is T1N0M0

Question 3.
A young motorcyle rider misjudges a turn and has an accident. He suffers several clean cuts as well as deep irregular and dirty flesh wounds with embedded gravel. He is a tough young man a long way from the next hospital and receives no medical treatment.
a) Describe the process of wound healing over the next 2 weeks for both the clean cuts and the deep and dirty flesh wounds. In your answer, include a description of the gross and microscopic appearances.
(10 marks)
b) What are the potential complications?
(5 marks)
c) What are the factors influencing the healing process?
(5 marks)

Question 6.
Describe the typical macroscopic features of the two main forms of familial colon cancer. For each form describe how the inherited defect contributes to the formation of the cancer. (10 marks)

Question 3 b:
Chronic inflammatory conditions and environmental factors may predispose to malignancy. Give an example of a chronic inflammatory condition which leads to cancer. Describe the mechanisms by which chronic inflammation might contribute to malignant transformation.

Following resuscitation and surgery the resected tumour is sent for analysis. The following is an excerpt from the diagnostic report:
“…..sections demonstrate a poorly differentiated adenocarcinoma which infiltrates the entire thickness of the bowel wall. Focal vascular invasion is noted. There is an area of necrosis with perforation and there is florid serositis, and a foreign-body-type reaction is seen associated with faecal matter….6 of the 17 lymph nodes identified are involved by metastatic cancer…. The proximal and distal surgical margins are free of tumour. The remaining mucosa is largely unremarkable but demonstrates 2 small adenomatous polyps with low-grade dysplasia present, distant from the tumour.”
Question 15.
a) What is the pTNM system?
(3 marks)
b) What is the prognostically relevant information contained in this report?
(3 marks)
c) What are the potential consequences of perforation of the bowel wall in this specimen?
(2 mark)
d) What is the significance of 2 small adenomatous polyps adjacent the tumour?
(2 marks)

Question 16.
An intra-operative swab of the peritoneum was taken.
a) What organisms would you expect to find?
(2 marks)
b) What would be the antibiotic of choice for each of these organisms?
(2 marks)