PBL 31

Question 1

Pathophysiology of cervical cancer

1. Mechanism
2. Risk factors
3. Clinical presentation
4. Testing and treatment

Answer 1

1. Mechanism
   - Oncogenic DNA virus w/high risk strains 16 & 18
   - The virus infects cervical epithelial cells where it produces viral proteins E6 and E7
   - E6 binds p53 - inactivates p53 so it is unable to induce cell death in the event of abnormal DNA. It stimulates ubiquitin attachment to p53, causing destruction by ubiquitination
   - E7 binds Rb and inactivates it. Rb usually binds and inactivates E2F, but with Rb inactivated, E2F can now activate expression of genes involved in cell proliferation
   - All of this produces cervical epithelial neoplasia and consequently cervical cancer
2. Risk factors
   - Exposing skin to strong sunlight
   - Sexual partners: having multiple, having unprotected sex
   - Smoking
   - HPV infection
   - Chlamydia infection
   - Age
   - Family history
   - Immunocompromised
   - Birth control pills
   - Multiple full-term pregnancies
3. Clinical presentation
   - Abnormal vaginal bleeding: after sex, after menopause, between periods, having longer periods, after douching.
   - Signs of more advanced disease: swelling of legs, problems urinating/bowel movement, blood in the urine
4. Testing and treatment
   - HPV test - look for abnormal cells
   - Colposcopy following abnormal HPV test - then biopsy if needed

Question 2

Characteristics of a good screening programme

Answer 2

1. Detection of a disease at a stage when treatment can be more effective than it would be after the patient develops signs and symptoms
2. Identification of risk factors that increase likelihood of developing the disease and use of this knowledge to prevent or lessen the disease by modifying risk factors
3. High sensitivity and specificity - Capable of correctly identifying a high proportion of disease in its pre-clinical state
4. Reasonable in cost
5. Be safe to administer
6. Widely available

Question 3

Pathophysiology of eczema

Answer 3

1. Mechanism
   - Inflammatory, chronically relapsing, non-contagious and pruritic skin disease
   - Interplay between genetics and skin barrier function

• Type 1 IgE mediated hypersensitivity reaction
• IgE dysregulation, genetic factors, disruption of the epidermal barrier and defects in the cutaneous cell-mediated immune response
• Inflammation and cellular responses in eczema have been seen to downregulate the expression of FILAGGRIN and other proteins which disrupts the ability of the skin to repair barrier dysfunction
• Filaggrin is an important protein in the structure of the epidermis, and the FLG gene mutation is present in around 9% of the population.
• Filaggrin is important in the formation of the corneocyte, as well as intracellular metabolites which contribute to the stratum corneum hydration and pH, hence mutation of this gene causes reduction or complete absence of epidermal FLD and its degradation products, which lead to dysfunction of the epidermis and reduced barrier function!

2. Risk & trigger factors
   - FLG mutation
   - Being born to an older mother or by caesarean section
   - Being overweight
   - Having a high birth weight
   - Being breastfed during infancy
   - Using antibiotics in infancy
   - ENVIRONMENTAL TRIGGERS:
3. House dust mites
4. Allergen exposure
5. Irritants: soap, dust, chemicals, cigarette smoke, hot climate, pollen, mould
6. Clinical presentation
   - Itchy, erythematous, dry scaly patches which are rough and leathery
   - Swollen or cracked skin
   - More common on face and extensor aspects of limbs in infants and flexor aspects in children and adults - antecubital and popliteal fossae, arms, legs, face and neck
   - Rash
   - Hives
   - Increased lines on the palms of the hands and feet
   - May show nail dystrophy and ridging of nails
7. Diagnosis and treatment
   - No lab test is needed to identify, mostly visually
   - Possible patch testing to rule out other skin diseases
   - Corticosteroid creams or ointment
   - Antibiotic cream
   - Oral corticosteroids: control inflammation

Question 4

Different types of eczema

Answer 4

1. Atopic dermatitis
2. Contact dermatitis
3. Dyshidrotic dermatitis
4. Hand eczema
5. Neurodermatitis
6. Nummular eczema
7. Stasis dermatitis

Question 5

Definition of lichenifications

Answer 5

Hard, thickened areas of skin due to repeated rubbing or scratching

Question 6

Definition of naevus

Answer 6

Flat mole with single uniform colour

Question 7

Open comedone vs closed comedone

Answer 7

Open = enlarged hair follicle opening filled with melanin, that’s why they appear black

Closed = small, raised, non-inflamed spot

Question 8

Papule definition

Answer 8

Superficial red inflamted spot WITHOUT pus

Question 9

Pustule

Answer 9

Raised red lesions, pus-containing

Question 10

Identification and analysis of a mole (cancerous)

Answer 10

ABCDE
Asymmetrical - melanoma = non-uniform shape. Non-cancerous are uniform and symmetrical

Borders - melanoma = non-defined borders and irregular in shape. Non-cancerous = smooth, well-defined borders

Colour - melanoma = more than one colour or shape. Non-cancerous moles are typically one colour

Diameter - Melanoma = usually larger than 6mm in diameter

Enlarging - Melanoma = often changes characteristics such as size, shape or colour

Analysis - remove a sample of tissue for analysis

Question 11

Purpura definition

Answer 11

Red or purple colour which does not blanch on pressure

Question 12

Risk factors for skin cancer

Answer 12

• Excessive UV light exposure
• History of sunburn
• Degree of skin pigmentation
• Use of tanning bed
• Airplane workers
• Having many moles or unusual moles
• Weakened immune system
• Genetics

Question 13

Different types and mechanism of skin cancer

Answer 13

Types
1. Basal-cell carcinoma
2. Squamous-cell carcinoma
3. Malignant melanoma
ABCDE

Mechanism

• Sunlight exposure
• Formation of pyrimidine dimers
• DNA repair removes most of the UV-induced damage but not all crosslinks are excised
• Cumulative DNA damage leads to mutations
• Sunlight depresses the local immune system
• Decreasing immune surveillance for new tumour cells

Question 14

Process of cancer metastasis (routes and steps)

Answer 14

Routes

1. Lymphatic spread
2. Haematogenous spread
3. Transcoelomic
4. Transplantation or implantation

Steps of metastasis

1. Separation from the primary tumour
2. Invasion through tissues around the initial lesion and penetration of their basement membranes
3. Entry into the blood vessels and survival within blood (haematogenous spread)
4. Entry into lymphatics (lymphatic spread)
5. Reaching the distant organs like lungs, liver, brain, bone etc
6. Formation of a new lesion along with new blood vessels feeding the tumour (angiogenesis)

Question 15

Explain Breslow’s depth & its stages

Answer 15

Description of how deeply tumour cells have invaded
Stage 1: Less than or equal to 0.75mm
Stage 2: 0.76-1.50mm
Stage 3: 1.51-2.25mm
Stage 4: 2.26-3.00mm
Stage 5: Greater than 3.00mm

> 4mm has a 5 year survival rate of 50%
2.1-4mm = 60-75%
1-2mm = 80-96%
<1mm = 95-100%

Question 16

Explain Clark’s level of melanoma invasion

Answer 16

Level 1 - Confined to epidermis
Level 2 - Invasion into papillary dermis
Level 3 - Invasion to the junction of papillary and reticular dermis
Level 4 - Invasion into reticular dermis
Level 5 - Invasion into the subcutaneous fat

Question 17

Explain TNM staging

Answer 17

T - Tumour = extent of the primary tumour, based on the presence, size and extension of the primary tumour

N - Nodes = extend of cancer within the nearby lymph nodes. N scores based on whether there’s a cancer in nearby lymph nodes, and number of regions of nodes with cancer

M - Metastasis = The M score tells you if the cancer has spread to distant sites, M0 means no spread, M1 means there is cancer in distant sites