Skin and soft tissue Flashcards
(112 cards)
1
Q
What are the risk factors for BCC?
A
Modifiable risk factors
- Chronic sun damage (strongest predictor of BCC)
- Episodic intense episodes of burning (unlike SCC which is the cumulative sun exposure).
Non-modifiable risk factors
- Increasing age
- Fair skinned - Fitzpatrick type I and II - reduced melanin results in less protection against UV-induced DNA damage.
- Male
- Genetic pre-dispositions
* Gorlin’s syndrome/Nevoid-BCC syndrome
○ Multiple BCCs usually before aged 30
○ Autosomal dominant - PTCH1 gene - leads to activation of the Hegdehog pathway
○ Spina bifida and bifid ribs
○ Hypertelorism (big gap between eyes)
○ Syndactyly
* Xeroderma pigmentosum
* Rombo syndrome
- Immunosuppression (although less so than SCC)
- Radiation exposure.
- Arsenic exposure.
2
Q
What cells do BCC’s arise from?
A
pluripotent epithelial cells in the basal layer of the epidermis.
3
Q
What is Gorline syndrome
A
○ Multiple BCCs usually before aged 30
○ Autosomal dominant - PTCH1 gene - leads to activation of the Hedgehog pathway
○ Spina bifida and bifid ribs
○ Hypertelorism (big gap between eyes)
4
Q
What are the main low risk subtypes of BCC? What are there appearances?
A
Nodular BCC
- Most common type of facial BCC
- Shiny or pearly nodule with a smooth surface.
- May have a central depression thus edges appear rolled.
- Telangiectatic vessels are commonly seen on surface.
Superficial BCC
- most common in younger adults.
- Can look like Bowen disease
- Slightly scaly, irregular plaues
- Thin translucent border.
5
Q
What are the higher risk subtypes of BCC?
A
Morphoiec BCC
- Usually found in mid facial sties
- Waxy, scar like plaque with indistinct borders
- Wide and deep subclinical extension
- May infiltrate cutaneous nerves
Basosquamous
- Mixed BCC and SCC features
- Infiltrative growth pattern
Other high risk subtypes
- Sclerosing BCC
- Infiltrating BCC
6
Q
What are the histological findings of a BCC?
A
- Abnormal growth of the basal cells - deepest layer of epidermis.
- Typical microscopic features of BCC - clumps with ‘palisading nuclei’ (lined up like a fence)
7
Q
What features of a BCC are associated with a poor prognosis.
A
- Higher risk lesions
- Recurrent BCC’s (BCC which has grown in a previous excision site).
- Dense fibrous stroma.
- Evidence of perineural invasion.
- Larger tumours which are ulcerated.
- Immunocompromised and transplant patients
8
Q
What is a “low risk BCC”
A
Low risk BCC is defined as:
Clinical features
* <2cm in diameter
* Located on trunk or extremities (excluding genitalia and hands).
* Well-defined margin.
* Slow growing.
* Immunocompetent patient.
Histological features
* Superficial or nodular type
- Lack of perineural invasion.
9
Q
How do you treat a low risk BCC?
A
Surgical/first line therapy
- Excision with a macroscopic 4-5mm margin. This is gold standard. Adequate microscopic margin is 1mm.
- If margins are positive - should have re-excision. If surgery not possible can consider radiation OR close clinical follow up.
Second line therapy
Recommended for patients who wish to avoid surgery (unsatisfactory cosmetic result or difficulty with wound healing) and are low risk. Options include:
- Imiquimod 5% cream - 5 days per week for 6 weeks until erythema, crusting, and scab formation develops. Stimulates the immune system by activating toll like receptor 7
- Topical fluorouracil 5% - twice daily for 6 weeks.
- Photodynamic therapy.
10
Q
How do you define a “high risk BCC”
A
Clinical
* Tumours >2cm
* Tumours on the head, neck, hands, feet, pre-tibia, and anogenital areas.
* Recurrent lesion.
* Lesions in sites of prior radiation therapy.
* Poorly defined margins
- Immunocompromised paitent.
Histopathological
* Aggressive subtype.
* Perineural invasion
11
Q
What is the treatment for a “high risk BCC”
A
Surgical/first line therapy
- MOHS (mohs micrographic surgery) - is essentially excision, frozen section with margin examination using formalin, followed by re-excision as required.
- Standard surgical excision with 4-6mm macroscopic margin- higher recurrence rate than MOHs. Adequate microscopic margin is 1mm.
- If margins are positive can re-excise OR consider radiation therapy.
MOHs uses special technology to provide rapid formalin fixation to allow for accurate margin assessment (i.e is different to usual “frozen section” which is normally done
Second line therapy
- Radiation therapy - good option for large tumours where surgery would be morbid or for patients who are not surgical candidates. Higher recurrence rate.
Treatments not recommended
Topical therapies such as imiquimod and 5-FU
12
Q
How is cryotherapy given and how does it work?
A
Cryotherapy
- Freeze for 5-15 sec to create a 1-3mm rim of freeze beyond lesion, and then thaw over 20-40 sec
- Perform 2 cycles
- Depth of freeze is 1.5x lateral spread
- Longer freeze-thaw times destroy portions of dermis
- Erythema occurs immediately
- Freezing can cause separation at the dermo epidermal junction and produce a bulla, which usually resolve in a few days
- Avoid freezing areas where nerves lie superficially
- Superficial lesions crust in 7-10 days then falloff
NB: Major issue is no tissue for histology and clearance margin uncertain
13
Q
How does 5-FU cream and imiquimod work?
A
- 5-Fluorouracil (Efudix)
○ Twice daily for 6 weeks.
○ Blocks incorporation of thymidine into DNA - Imiquimod (Aldara)
○ 5 days per week for 6 weeks until erythema, crusting, and scab formation develops.
○ Stimulates the immune system by activating toll like receptor 7
§ Upregulates cytokines
14
Q
What are the risk factors for a cutaneous SCC?
A
- Modifiable
○ UV radiation - cumulative sun exposure (as opposed to intense exposure which causes BCC’s and melanoma).
○ Ionizing radiation - (therapeutic and diagnostic radiation)
○ Smoking- Non-modifiable
○ Geographic variation - more common in areas closer to the equator.
○ Age
○ Fair skin
○ Chronic immunosuppression
○ Chronic inflammation (i.e chronic ulcers, inflammatory dermatoses)
○ HPV - include 5, 8
- Family history
- Non-modifiable
15
Q
What is the pathogenesis of cutaneous SCC?
A
- Multistep process of progressive genetic alterations leading to cutaneous dysplasia then invasion.
- The NOTCH pathway is primarily affected. You also get mutations in tp53 and RAS.
- The keratinocyte is the cell of origin.
- A large proportion of SCC’s will arise from actinic keratosis. Although most actinic keratosis will not turn into an SCC
16
Q
What are some common variants of SCC to be aware of?
A
Keratoacanthoma
- Histologically resemble a well-differentiated SCC
- Origin are the cells of a hair follicle.
- Lesion which rapidly grows, stabilizes, and then usually spontaneously resolves.
- Generally appear as dome shaped with a central keratotic core.
- Leaves a scar.
- Theses lesions should be excised
- If they are clearly involuting you can observe them.
Verrucous carcinoma
- Rare variant that presents with a well-defined, exophytic, cauliflower-like growth that resemble large warts
- SCC induced by HPV
- Can be Anogenital (known as Giant Condyloma acuminatum of Buschke-Lowenstein)
- Can also be on mouth, larynx.
- Can be on the plantar foot (Epithelioma cuniculatum)
Majolin ulcer
- SCC which arises from sites of chronic wounds or scars.
- Chronic inflammation leads to DNA damage and dysregulated cell repair.
- Malignant transformation is very slow, with average latency of 30 years.
17
Q
What are the microscopic features of an SCC?
A
- Large cells with intercellular bridges and keratin pearls.
- Cellular atypia seen in all layers of epidermis.
- Tumour cells infiltrate epidermis, dermis, and adjacent tissue.
- Cellular atypia seen in all layers of epidermis.
18
Q
How do well differentiated and poorly differentiated SCCs differ in macroscopic appearance?
A
- Well differentiated
○ Hyperkeratotic plaque- Poorly differentiated
○ Fleshy, granulomatous papules that lack hyperkeratosis. May ulcerate and have areas of necrosis
- Poorly differentiated
19
Q
What is Bowens disease?
A
- Diagnosed when keratinocyte dysplasia is full thickness of the epidermis without infiltration into the dermis (through the basement membrane)
- Keratinocytes show pleomorphism, hyperchromatic nuclei, and nuclear mitosis.
- Clinical
○ Frequently there is associated thickening of the epidermis.
○ Reddened area
- Rate of progression to an invasive SCC is low - about 1% per year.
20
Q
What features make an SCC high risk?
A
High-Risk SCC Features
1. Clinical Features:
○ Size: >2 cm in diameter.
○ Location: High-risk areas include:
§ H-zone of the face (e.g., periocular region, nose, lips, ears).
§ Genitalia, perianal region, hands, and feet.
○ Recurrence: Recurrent SCC is considered high risk.
○ Immunosuppression: Increased risk in immunosuppressed patients (e.g., organ transplant recipients, chronic lymphocytic leukemia).
○ Rapid Growth: Aggressive growth patterns or ulceration.
2. Histological Features:
○ Depth of Invasion: >4 mm or invasion into subcutaneous fat.
○ Poorly differentiated tumour
○ Perineural Invasion (PNI): Defined as nerves greater than 0.1mm
○ Lymphovascular Invasion (LVI): Presence of tumour cells in lymphatic or vascular spaces.
○ Margins: Positive or close surgical margins.
3. Other Factors:
○ Previous Treatment: Prior radiation or chronic inflammatory conditions in the area (e.g., Marjolin's ulcer).
- Host Factors: History of prior skin cancers, genetic conditions like xeroderma pigmentosum, or Gorlin syndrome.
21
Q
When should you perform staging imaging of an SCC
- what modality should you use?
A
High risk SCC
Generally CT is used to evaulate nodal basin.
CT-PET is funded in NZ prior to undergoing lymphadenectomy or radical surgery.
22
Q
What is the T staging for SCC?
A
T1 - < 2cm
T2 - 2-4cm
T3 - >4cm or PNI or minimal erosion of bone.
T4a - tumour with extensive cortical and medullary bone involvement.
T4b - tumour with invasion through the base of the cranium.
23
Q
N staging for SCC?
A
N1 - isolated ipsilateral node < 3cm in diameter.
N2a - isolated ipsilateral node 3-6cm in diameter.
N2b - multiple ipsilateral nodes <6cm.
N2c - metastasis in contralateral lymph nodes < 6cm.
N3a - metastasis in a lymph node > 6cm.
N3b - nodal metastasis with extra-nodal extension.
24
Q
What is the treatment of a low risk SCC?
A
Standard surgical excision with a 4mm clinical margin.
25
What is the surgical treatment to the primary for a high risk SCC
MOHS
or
Standard surgical excision with 1cm clinical margin.
26
What are indications for adjuvant radiation to the primary for cutaneous SCC?
○ Tumours with positive surgical margins not amendable to further surgery
○ Recurrent SCC
○ Tumours with extensive PNI or large nerve involvement.
- Massive local extension
27
What are the risk factors for melanoma?
- Host factors
○ Age
○ Male
○ Pale skin.
○ Previous cutaneous melanoma.
○ Family history of melanoma.
○ Immunosuppression.
○ Evidence of actinic skin damage.
○ Xeroderma pigmentosum
○ Familial atypical mole and melanoma syndrome.
§ Mutation in p16 tumour suppressor gene
- Environmental factors.
○ UV exposure
○ Sun exposure - history of blistering sunburn when young.
○ Use of sun beds
- Melanocytic Nevus factors
○ >50 melanocytic nevi.
○ >5 atypical nevi.
- Large congenital nevus (>20cm).
28
What are the clinical features of a superficial spreading melanoma?
- Most common subtype - accounts for 70% of all melanomas
- Most are diagnosed as thin, highly curable tumours that are <1mm in thickness.
- Approximately 2/3 arise de-novo, without a pre-existing naevus.
- Has a predilection for the back in males, and lower limbs in females.
- Typically presents as a variably pigmented thin plaque with an irregular border.
- Often have a BRAF V600E mutation.
- Lesion is often multi-coloured
- The ABCDE rule can be used to identify superficial spreading melanomas.
29
What are the clinical features of a nodular melanoma?
- Second most common subtype
- Usually darkly pigmented and uniform in color.
- Sometimes can be amelanotic.
- Can be pedunculated, or polypoid papules or nodules
- Are generally an aggressive lesion - enter vertical growth phase straight away.
- The EFG rule can be used to identify nodular melanomas.
30
What is the ABCDE EFG rule?
Skin examination
- Asymmetry
- Border irregularity
- Colour variation
- Diameter > 6mm
- Evolution
The below is used for nodular
- Elevated
- Firm nodule
- Growing nodule
31
What are the features of Lentigo maligna?
- Lentigo-maligna is a form of melanoma in-situ - to lentigo-maligna melanoma
- Also known as Hutchinson's freckle.
- Lentigo maligna most commonly arises in sun-damaged areas of skin in older individuals and begins as a tan macule
- Often found on the nose, cheeks, upper back, forearms, dorsum of hands.
- The lesion gradually enlarges and may become darker.
- Lentigo maligna in-situ can exist for decades before entering a vertical growth phase and becoming invasive. It has a much slower and lower rate of transformation than other in-situ subtypes.
32
What are the features of Acral lentiginous melanoma?
- Accounts for 75% of melanomas among non-white patients.
- Most commonly occur on the palmar, plantar, and subungual surfaces (i.e. beneath the nail plate).
- Are a generally aggressive subtype.
- Appear as dark brown of black, irregular pigmented macules or patches with ulceration and bleeding.
- Can occasionally be amelanotic
- Subungual melanoma arises from the nail matrix and presents as a longitudinal, brown or black band in the nail.
33
What are the features of desmoplastic melanoma?
- Rare form which has the ability to invade nerve fibers (neurotropism)
- The malignant cells within the dermis are surrounded by an intense desmoplastic reaction (fibrous stroma)
- Lesions are more likely to be amelanotic which results in a delay to diagnosis
- Much more common in males and elderly patients.
- Presents as a slowly enlarging area of thickened skin which may be pigmented
- Have a lower risk of lymph node and distant metastasis
- Have a higher recurrence risk after excision - adjuvant radiotherapy often given to primary site.
34
What are the histopathological findings of melanoma?
- Cells are often in "nests" with "Pagetoid Spread" creating a "Buckshot pattern"
○ This means that little groups of melanocytes are found right throughout the layers of the dermis - above the basal layer where they originate.
- The nests are discohesive, variably sized and shaped with haphazard distribution.
- Lesions lack borders
- Cytological features include nuclear atypia, cellular pleomorphism.
35
What is the ACDEF of subungual melanoma?
- A - African American
- B - brown or black band
- C - change in the nail band
- D - digit most commonly involved - great toe or thumb
- E - extension of pigment onto the proximal or lateral nail fold (Hutchinson's sign)
- F - family history of melanoma
36
What are the dermoscopy findings of a melanoma?
- Atypical and thickened pigment network
- Depigmentation
- Irregular shape/structure
- Irregular brown-black dots
- Atypical vascular pattern
- Multiple colors - especially red and blue
- Areas of bluish/whitish colour
37
What will you see on a melanoma histology report?
It there is an invasive melanoma, the pathologist will comment on the following:
- Diagnosis of primary melanoma
- Breslow Thickness - this is measured in mm from the top of the granular layer (or base of superficial ulceration), to the deepest part of tumour involvement. It is a strong predictor of outcome.
- <1mm - thin melanoma
- 1-4mm - intermediate melanoma
- 4+ - thick melanoma
- Clark level - indicates the anatomic plane of invasion.
- Margins of excision
- Mitotic rate/mm3 (5=high)
- Presence of ulceration
- LVI
- Regression - evidence of regression is favorable.
- PNI
- In-situ component.
Tumour infiltrating lymphocytes - predicts response to PD-1 inhibitor.
38
Describe the Clark levels
I - Confinement to epidermis premalignant/ melanoma in-situ
II - Invasion into Papillary Dermis
III - Filling Papillary Dermis; cells at junction of papillary & reticular dermis
IV - Invasion into Reticular Dermis
V - Invasion into Subcutaneous Fat
39
What is the T staging and N staging for melanoma?
Look it up
40
What are microsatellite, satellite and in-transit metastasis?
Definitions
- Microsatellite
○ Microscopic tumour nests which are <2cm from primary on histopathology only.
- Satellite
○ Macroscopic tumour (visible to the eye) which is <2cm from primary.
- In-transit - Macroscopic metastasis which are >2cm from the primary.
41
When should you take a patient to a melanoma MDM?
- High risk stage II+
- High risk subtype i.e. desmoplastic
- Recurrent melanoma
42
What did the MSLT1 trial look at and show?
- NEJM 2014
- Landmark study looking at patients with a clinically negative nodal basin.
- Melanomas were Breslow thickness > 1mm.
- Control group - WLE and observation of nodal basin with lymphadenectomy if clinical metastasis developed.
- Intervention group - WLE + SLNB with lymphadenectomy if the SLNB was positive.
- There was no difference in melanoma specific survival.
- There was, however, a difference in disease free survival (as patients in the SLNB group were less likely to develop nodal recurrence)
- Patients with a negative SLNB had a better prognosis that patients with a positive SLNB - this established SLNB being useful for prognostication.
- The main takeaway from this study was that SNLB was accurate at predicting prognosis for patients with melanoma AND that diagnosing a positive sentinal may help with nodal disease control (as you would treat their nodal disease)
- This led to the question - does completion lymphadenectomy actually confer a survival benefit (as opposed to just help with local control)
43
What did the MSLT2 trial look at?
- NEJM 2017
- Looked at the role of completion lymphadenectomy after a positive SLNB.
- Randomized two groups - 1 to completion lymphadenectomy and the other to observation.
- The lymphadenectomy group did have better local control and thus DFS, but there was no difference in melanoma specific survival.
- The lymphadenectomy group had much higher wound morbidity (6 vs 24% - lymphoedema)
- Only 10% of patients in the lymphadenectomy group, had a positive additional node (thus you could argue that 90% of patients were overtreated).
- In the observation group - only 20% had a recurrence (which indicates for 80% of patients, the only positive nodes was the SLN)
- This study showed that it is reasonable to observe patients with a positive SLNB, as the majority will not have any further nodes, and that performing a lymphadenectomy doesn't improve survival but does increase morbidity.
NB: De-COG showed the same thing
44
Who should have a sentinal lymph node biopsy?
As a broad rule
- patients with a clinically negative nodal basin
AND
- T1b +
OR
- T1a with high risk features.
For the exam I would say I would use the melanoma institute australia risk prediction tool and if it gave a risk above 5% I would discuss SLNB with the patient.
45
What does the melanoma institute australia risk prediction tool for sentinal lymph node metastasis look at?
- Takes into account:
○ Age
○ Tumour thickness
○ Melanoma subtype
○ Mitosis
○ Ulceration
- LVI
46
How is SLNB performed for melanoma?
Preoperative lymphoscintigraphy
- Tc99 is injected intradermally. This is important as injecting it into the subcutaneous tissue is less effective as there are less lymphatics.
- Inject 4 aliquots 0.5cm from the melanoma or scar.
- A scintigram is then taken to locate where the tracer uptake is - this will tell you what lymphatic basin to explore.
- If no nodes on scintigram - repeat the injection.
- If higher accuracy is required (i.e. head and neck) - a SPECT/CT can be performed.
- A sentinal lymph node is any node with a counts >10% of the hottest node
If there is no tracer uptake
- Should repeat injection
- If still no uptake - should explore the lymph node basins at surgery
- If no SLNB is found at surgery - should observe lymph node basins with serial USS (as opposed to performing lymphadenectomy)
Use of blue dye/Dual protocol technique.
- Iso-sulfane blue is often injected as well to help guide localisation (and maybe reduce the amount of dissection)
- Dual technique reduces false negatives - I would use for the exam. .
- Methylene blue is a/w skin necrosis and is usually avoided
Biopsy technique
- The SLNB is usually performed prior to removal of the primary, in the case of re-injection.
- If the SLNB site is close to the primary, you may want to excise the primary to prevent "shine-through" to the gamma probe.
- You should also examine the path between the primary and nodal basin to find any SLN between the two sites.
- All nodes with a radioactive count 10% or higher compared with the hottest node in that basin should be taken.
- Any palpable node should be taken.
47
What should you do with a patient with a positive sentinal lymph node for melanoma?
Management of a positive sentinal lymph node
- MSLT2 and DeCog showed that a positive sentinal node does not mandate a completion lymphadenectomy.
- Patients should be actively surveilled with regular USS of the nodal basin (every 4 months for the first 2 years).
- CT-PET is also not recommended - it is also not funded for this indication in New Zealand (it is funded for patients with clinically positive nodes).
48
When would you consider an inguinal lymphadectomy?
□ If positive iliac nodes on imaging.
□ Large volume inguinal disease.
- Cloquet's node positive.
49
What are the indications for adjuvant radiotherapy to the primary site?
R1 resection
Desmoplastic melanoma with PNI
Locally recurrent.
50
What are the indications for adjuvant radiotherapy to the lymph node basin?
Adjuvant radiotherapy after lymph node dissection
- This has fallen out of favor as it is relatively morbid, and doesn't improve OS (it does, lower lymph node recurrence rates)
- It is being used less as adjuvant immunotherapy options are superior.
- Where it should be considered if for patients who have had a incomplete pathological response to immunotherapy OR are ineligible for adjuvant immunotherapy and have one of the risk factors below
- This is still relevant to NZ as pembrolizumab is still not funded for adjuvant treatment (just for metastatic or unresectable disease)
Risk factors for local recurrence
- Multiple positive nodes (>3 groin, >2 neck)
- Large nodes (>4cm groin,>3cm neck)
- Extra-nodal spread
- Recurrent disease
51
What should you do when you diagnose an in-transit metastasis
Resection of the metastasis if they are low volume.
SLNB if the patient hasn't had one.
Re-stage the patient.
Give
- adjuvant therapy.
- If patient can't tolerate adjuvant therapy and doesn't have distant metastatic disease - can consider isolated limb infusion.
52
What are the indications for isolated limb infusion?
- Isolated in-transit metastasis which cannot be excised (i.e. large tumour burden)
- Recurrent melanoma
- A primary lesion with a poor prognosis
All of the above occur in the context of patients where systemic therapy has failed or cannot be given (i.e. patient cannot tolerate)
53
How does isolated limb perfusion and isolated limb infusion work?
Procedure for isolated limb perfusion
- The femoral vein and artery or axillary vein and artery are clamped
- The artery and vein are cannulated.
- A pump oxygenator is used to maintain oxygenation of the blood going through the limb.
- Heated cytotoxic mediation is infused - phenylalanine mustard and actinomycin D are commonly used - usually for 90 minutes
Isolated limb infusion
- The femoral artery and vein are accessed with a catheter and a torniquet is used.
- Blood is circulated at a much slower rate and only for 30 minutes
During ILI, the limb becomes very hypoxic which leads to marked acidosis.
54
What is the cell of origin in Merkel cell cancers?
The cell of origin is debated - it is thought that they arise from multipotent stem cells in the basal layer which undergo neuroendocrine transformation when they become malignant.
55
What are the risk factors for Merkel Cell cancer?
- Lighter skin colour
- Increasing age
- Male sex
- Immunosuppression - especially organ transplant patients, HIV, and hematological malignancies.
- Other malignancies increase risk - CLL, multiple myeloma, melanoma.
- UV radiation exposure - more common in sun-exposed areas.
- Merkel cell polyoma virus infection
- Germline mutations in BRCA1, BRCA2, TP53, ATM, are a/w Merkels.
56
What is Merkel cell polyomarvirus and how does it aid in the formation of Merkel cell tumours?
- 60-80% of patients have detectable MCPyV in their specimens.
- Merkel Cell polyomavirus integrates two oncogenes into the host genome - which encode proteins" large tumour antigen" and "small tumour antigen", the DNA mutations assist with immune evasion.
57
What are the histopathological findings of a Merkel cell cancer?
- Immunohistochemical stains are usually required to differentiate it from other poorly differentiated tumours.
- Is seen as a dermal mass which extends into the subcutaneous tissue. It rarely involves the epidermis.
- Nests of monotonous, round, blue cells, containing large basophilic nuclei and minimal cytoplasm - resemble neuroendocrine cells.
- Also express various neuroendocrine markers on histochemistry including chromogranin, synaptophysin, calcitonin, VIP, and somatostatin.
58
T and N staging for Merkels
T1 - < 2cm
T2 - 2-5cm
T3 - 5+cm
T4 - tumour invades bones, cartilages, muscle or fascia.
N1a - micrometastasis
N1b - macrometastasis
59
How would you manage the primary site of a Merkels?
- Traditionally WLE - aim for macroscopic margin of 3cm. 1cm microscopic margin
○ This is still what is recommended in multiple international guidelines (including ESMO)
- Tumours with high risk features should receive adjuvant RT
○ Tumour > 2cm.
○ Microscopically positive or limited surgical margins.
○ LVI
○ Immunosuppression
- Head and neck
60
How should a clinically negative nodal basin be managed for Merkels?
Clinically negative regional lymph nodes
- If the SLNB is negative - they can be observed
- If the SLNB is positive - completion dissection or definitive RT
○ If the completion lymph node dissection reveals multiple involved nodes or extracapsular extension - should consider adjuvant RT.
NB from Peter Lecture:
- Tumours > 2cm - won't perform SLNB but instead will have there nodal basin treated - because the risk of nodal recurrence is high and the patient should be given RT regardless.
- If a patient has a negative SLNB, they may still receive RT if they are perceived high risk - i.e. tumours >2cm, chronic immunosuppression.
61
How should you manage a patients nodal basin with clinically positive nodes for Merkels?
Clinically positive regional nodes
- Should confirm diagnosis with FNA or excision biopsy
- Patients should undergo therapeutic lymph node dissection
○ If there are multiple positive nodes OR extracapsular extension - should receive adjuvant RT
Should also receive adjuvant pembrolizumab
62
What is an atypical nevus and dysplastic nevus?
- A benign lesion which has some clinical features of a melanoma.
○ Characterized by a diameter >5mm, asymmetry, irregular or ill-defined borders, does not match the other nevus, multi-coloured
- If a patient has > 5 atypical nevus - they are at an increased risk of melanoma.
If dysplasia is confirmed on histology - is called a dysplastic nevus.
63
What is the patholophysiology of a melanocytic nevus?
- Lesions evolve with age.
- Initial lesion is located at the dermal-epidermal junction (is thus a junctional nevus).
- With time, nests extend into the dermis and lesions become elevated.
- With further maturation, junctional activity ceases, and the nevus becomes intradermal.
64
What is the histopathology of actinic keratosis
Dysplasia of the lowermost layer of the epidermis (compared with Bowens disease when it is in all layers).
65
What is the treatment of actinic keratosis?
- Cryotherapy using liquid nitrogen
○ 5-10 seconds until lesion goes white.
- Shave, curretage, and electrocautery.
- Excision
- Topical
○ Diclofenac cream 3% - BD for 3 months.
○ 5-FU (Effudix) - BD for 2-8 weeks.
○ Imiquimod cream
Oral retinoids for patients with numerous AK's
66
What is the treatment of cutaneous warts?
Treatment
- Often can be observed as will resolve spontaneously.
- 50% are gone within 6 months and 90% in two years.
- Indications for removal include immunosuppression, presence of complications, or patient preference.
Treatment options
- Topical salicylic acid - works by removing surface skin cells. Give for 3 months.
- Cryotherapy
- Imiquimod
- Laser vaporisation
- NB: Excision is avoided - high risk of recurrence.
67
What is the pathophysiology of a sebaceous cyst?
- Derives from the upper portion of a hair follicle - caused by an occluded pilosebaceous unit.
○ Sebaceous glands drains into hair follicles
○ Sebaceous glands produced sebum which lubricate the hair.
- The occlusion occurs at the follicle, and the cyst is not full of sebum - thus the term "sebaceous cyst" is a misnomer.
- Is filled with keratin and lipid-rich debris.
68
What is the pathophysiology of Keloid and hypertrophic scars?
- Dysregulation of the normal healing process resulting in excessive production of collagen, elastin, proteoglycans and extracellular matrix.
Increased number of fibroblasts and mast cells.
69
What are the differences between a Keloid scar and a hypertrophic scar?
Keloid
- Purplish-red
- Firm, smooth and raised.
- Uncomfortable and itchy.
- Can occur years after injury
- Grow beyond wound edge.
Hypertrophic
- Pink to red
- Slightly raised or flat
- Can be uncomfortable and itchy
- Usually occur within weeks.
- Limited to confines of wound.
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What is the treatment for hypertrophic and keloid scars?
Topical
- Corticosteroid tape
- Topical corticosteroids
- Silicone Gel sheets - moisturizes wound and decreases inflammation.
Intralesional
- Intralesional corticosteroid - triamcinalone
- Bleomycin or 5-FU with triamcinolone is very effective for Keloids. Is generally repeatedly injected after excision of the keloid.
Compression
- Pressure garments, bandages - limited evidence for efficacy
Surgical
Scar revision - high risk of recurrence. Usually have to employ adjunctive treatment (i.e. topical or intralesional therapy) v
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What mutations are associated with pyogenic granulomas?
BRAF and RAS mutations
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What are the clinical features of a pyogenic granuloma?
Small red spot that grows rapidly
Prone to bleeding and ulceration.
Can occur in pregnancy
Can be precipitated by medications - cyclosporin, thyroxin, ETO, anti-TNFa
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What are the treatments for a pyogenic granuloma?
- Non-operative - often regress upon withdrawal of causative agent (i.e. medication)
- Topical - Imiquimod.
- Sclerosing agent - silver nitrate
- Operative - diagnostic uncertainty, symptoms (bleeding, discomfort, cosmesis)
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What is Kaposi's sarcoma?
- Low grade malignancy of the endothelial cells of blood vessels and the lymphatic system.
- Caused by infection with human herpesvirus 8 (HHV8) otherwise known as Kaposi sarcoma herpesvirus (KSHV)
- Tumours can involve the pulmonary, GI, cutaneous, or MSK systems.
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What is the treatment of Kaposi sarcoma?
○ Radiotherapy
○ Cryotherapy
○ Laser therapy
○ Surgical excision
- Intralesional vinca alkaloid
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What is Dupytrens contracture?
Dupuytren’s contracture is a progressive fibroproliferative disorder of the palmar fascia, leading to thickening and shortening of the fascia, resulting in flexion contractures of the fingers, most commonly the ring and little fingers.
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What is Dupytrens associated with?
○ Diabetes mellitus
○ Alcoholism
○ Smoking
○ Epilepsy (associated with long-term use of phenytoin)
- Trauma or repetitive microtrauma (controversial)
- Liver disease
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What is the treatment of Dupytrens contracture?
- Non-Operative:
· Physiotherapy – stretching exercises for early forms
- Local Triamcinolone acetonide into fibrous nodules – may slow progression and injections into synovial sheaths treat episodes of tenosynovitis
- Operative:
· Fasciotomy – Transection of fibrous bands
· Partial Fasciectomy (with Z-plasty to lengthen wound): In conjunction with post-op physio (early active flexion range of motion exercises for grip strength) and night-time splintage in extension
§ Complications: Recurrence common
Dermofasciectomy (with full thickness skin grafting) – associated with lowest risk of recurrence
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What is the classification of ingrown toenails?
- Stage 1 - initial embedding - associated with slight redness and pain.
- Stage 2 - severe inflammation and redness + tenderness. Can be a/w secondary infection
- Stage 3 - formation of granulation tissue which undergoes epithelization and hypertrophy which covers the embedded nail plate.
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What are some conservative treatments for ingrown toenails?
Usually used for Stage 1-2 ingrown nails. Options include:
- Soak foot in warm water 20 minutes BD
- High potency topical steroids
- Cotton nail cast - removing the nail spicule under local and separating the nail edge off the surrounding soft tissue, and placing cotton swab under the nail bed.
- Dental floss
- Taping
- Nail bracing
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What are the virulence factors for group A strep?
- M Protein: Helps evade phagocytosis by inhibiting complement activation.
- Hyaluronidase: Degrades connective tissue and facilitates bacterial spread.
- Streptokinase: Converts plasminogen to plasmin, breaking down fibrin clots and promoting tissue invasion.
- DNases (Streptodornase): Break down neutrophil extracellular traps (NETs) and aid in immune evasion.
- C5a Peptidase: Degrades complement component C5a, reducing neutrophil recruitment.
- Exotoxins (Pyrogenic Toxins A, B, C): Can contribute to systemic effects and toxic shock-like syndrome.
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What are some staph aureus virulence factors?
- Hyaluronidase: Facilitates tissue penetration.
- Coagulase: Converts fibrinogen to fibrin, allowing bacterial clumping and immune evasion.
- Panton-Valentine Leukocidin (PVL): A cytotoxin that destroys leukocytes and contributes to more severe infections, such as necrotizing soft tissue infections.
- Exfoliative Toxins: Can contribute to epidermal damage.
- Lipases and Proteases: Aid in tissue invasion and immune system evasion.
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What are some risk factors for MRSA?
- Healthcare related - Recent hospitalization, incare facility, recent surgery, haemodialysis.
- Patient related - HIV, injecting drugs use, MSM, homelessness
- Environmental related - in prison, military service, crowded living conditions, playing contact sports, works at childcare centers.
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What are the stages of wound healing?
1. Reactive
- Haemostasis
○ Clot provides matrix rich in growth factors and chemokines
○ Acts as a scaffold for migrating leucocytes.
- Inflammation
○ Also get inflammatory vascular changes
○ Within 24 hours neutrophils appear at margins - begin process of sterilizing wound
○ Granulation tissue is made (peak 5 days)
§ Rich in fibroblasts
§ Rich in ground substance - water, glycoproteins, glycosaminoglycans.
§ Angiogenesis occurs driven by VEGF - vessels are leaky which results in tissue oedema.
○ At this stage, wound strength primarily relies on sutures.
2. Regenerative
- Migration and expression of
○ Endothelial cells
○ Connective tissue - provisional matrix.
- Neutrophils get replaced by macrophages
- Granulation tissue is converted to scar composed of fibroblasts and collagen
- After 2 weeks - collagen disposition is the most dominant feature and the vasculature regresses.
○ Rapid increase in wound strength to 50%.
- Epithelialization also occurs with cells growing in from the wound edge.
3. Re-modelling phase
- Constant reabsorption and replacement of collagen along the lines of stress
- Wound contraction occurs due to the action of myofibroblasts
- Have both synthetic function of fibroblasts and contractile capacity of SM cells.
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What factors stimulate affect wound healing?
Factors that affect wound healing
- Local factors
○ Ischaemia
○ Tension
○ Dead space
○ Wound infection
○ Local trauma
○ Chronic tissue factors - lymphoedema
○ Sutures
○ Radiation
- Systemic factors.
○ Age
○ Co-morbidities
○ Shock, hypovolaemia, hypoxia
○ Malnutrition
○ Advanced malignancy
○ Immunosuppression
○ Chemotherapy
- Smoking
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What is a type 1 necrotising fasccitis?
Polymicrobial (type 1) necrotizing infection
- Caused by anaerobic and facultative anaerobic/aerobic bacteria.
- Anaerobic bacteria include - Bacteroides, Clostridium, Pepto streptococcus.
- Facultative anaerobic Enterobacteria include E coli, Klebsiella, Proteus.
- Fournier's gangrene usually falls into this group.
- Usually occurs in older adults or individuals with underlying co-morbidities
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What is the pathogenesis of necrotising soft tissue infection?
- Necrotising fasciitis is a synergistic soft-tissue infection
- There is usually an inciting event often in patients with predisposing factors.
- Inoculation occurs from a skin break or mucocutaneous barrier breach.
- Proliferation of either a single or multiple microbes
- Polymicrobial proliferation includes anaerobe and facultative anaerobes such as Bacteroids, Clostridium, enterobacteria, e coli, Klebsiella or Proteus.
- In cases of a monomicrobial proliferation - this usually involves group A strep or staph aureus.
- Liquefactive necrosis occurs
- Bacteria track along avascular fascial planes.
- Bacterial products such as hyaluronidases, lipases contribute to tissue destruction and organism spread.
- Endotoxins and exotoxins contribute to tissue breakdown.
- Microvascular thrombosis occurs which worsens hypoxia and contributes to necrosis
- There is systemic response with an exaggerated inflammatory response caused by cytokines TNFa and IL-1, IL-6, Il-8
- The coagulation cascade and complement cascade is also activated.
- This results in multi-organ dysfunction, shock, DIC, Death.
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What are the components of the LNIREC score?
WCC
Neuts
CRP
Creatinine
Sodium
Glucose
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What are the bacteria which gas gas gangrene?
Traumatic gas gangrene is commonly caused by Clostridium perfingens
Spontaneous gangrene is caused by Clostridium septicum.
90
What is the pathogenesis of traumatic gas gangrene?
- Often occurs secondary to tissue which is relatively ischaemic - gunshot wounds, compound fractures, retained placenta, heroin injection site etc.
- Clostridium proliferates in the ischaemic environment - which directly causes necrosis.
- There is an absence of a leucocyte infiltration (because the tissue is ischaemic) which is different from Necrotising soft tissue infection.
- Alpha and theta toxins cause local tissue necrosis and contribute to septic shock.
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What is the pathogenesis of spontaneous gas gangrene?
- Occurs via haematogenous seeding of muscle with bacteria (usually Clostridium Septicum) from a GI tract portal of entry.
- Can occur in patients with undiagnosed CRC or previous abdominal radiation.
Pathogenesis
- C septicum can grow in normal tissues and doesn't require anaerobic conditions.
- It produces multiple exotoxins which result in inflammation and cell death.
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Risk factors for hydradanitis suppurativa?
- FHx
- Obesity and insulin resistance.
- Cigarette smoking
- African ethnicity
- Previous acne.
- IBD - especially Crohn's disease
- HTN, DM, dyslipidemia, thyroid disorders, PCOS.
- Drugs - lithium, biologics.
- Syndromes
- PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, and acne).
- PASH syndrome (pyoderma gangrenosum, acne, and suppurative hidradenitis)
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What is the pathophysiology of hydradanitis suppurativa?
- It is important to remember that apocrine glands drain into follicles - thus follicular occlusion will also block apocrine glands.
- Follicular occlusion is the inciting event - occurs due to ductal keratinocyte proliferation causing plugging.
- This results in rupture and inflammation followed by cytokine release, and an inflammatory infiltrate.
- A secondary bacterial infection can be established
Inflammation can become chronic resulting a foreign body reaction resulting in sinus tracts and subcutaneous fibrosis, as well as destruction of hair follicles.
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How is hydradanitis suppurativa graded?
Hurley grading system
- Grade 1 - solitary or multiple isolated abscesses. No sinuses.
- Grade 2 - recurrent abscesses, widely spaced, with sinuses.
- Grade 3 - diffuse involvement of an area, with multiple interconnected abscesses and sinuses.
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What is the non-operative treatment of hydradanitis suppurativa?
General measures
- Weight loss
- Smoking cessation.
- Loose fitting clothes.
- Laser hair removal
- Psychological support
Topical treatments
- Benozyl peroxidase wash
- Topical clindamycin.
- Topical antibiotics - fusidic acid, dapsone.
Systemic antibiotics
- Prolonged course of doxycycline can be useful.
Systemic treatments
- Anti-androgens for females i.e. cyproterone, spironolactone, OCP.
- Steroids for acute flares.
- Isotretinoin
- Steroid sparing agents can be tried - cyclosporin, methotrexate, azathioprine.
- Biologics - Adalimumab is funded in NZ
- Other treatments used include metformin, colchicine, zinc gluconate.
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What is the pathophysiology of pressure ulcers?
- Pressure injuries occur because of an interaction of pressure forces with host-specific factors leading to tissue damage.
- The injuring mechanism is commonly pressure, shearing forces, friction and moisture
- Elevated pressure in the tissues exceeds the arteriolar pressure causing ischaemia
- Results in hypoxia, metabolic waste accumulation and radical oxygen species release.
- Muscle is the most susceptible to pressure injury, followed by subcutaneous fat then skin.
- Malnutrition, sensory loss, immobility, frailty, prolonged lying contribute to pressure injuries.
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How are pressure injuries graded?
Stage 1
- Characterized by intact skin with a localized area of non-blanchable erythema.
Stage 2
- Partial thickness loss of skin with exposed dermis. Fat not visible.
Stage 3
- Full thickness loss of skin with exposed fat.
Stage 4
- Full thickness loss of skin and fat with exposed fascia, muscle, tendon, ligament, cartilage, or bone.
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What is Felon infection?
- Subcutaneous infection of the finger pulp/volar aspect
- Present with swelling of the pulp distal to the phalangeal crease - most common cause is through direct contamination (such as a splinter)
- Most are simple and will resolve spontaneously or with a course of antibiotics and hand elevation
- Infection can track down to the bone causing OM
- Advanced infections should be treated with incision and drainage.
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What is Flexor Tenosynovitis and what are Kanvels signs?
Infection of the tendon sheath
- between A1 pulley at metacarpal head and the insertion of FDP at distal phalynx.
Kanvels signs
- Tenderness along flexor sheath
- Flexed finger posture.
- Pain on passive extension.
- Fusiform swelling of the affected digit
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What are the boundaries of the thenar space?
- Overlies adductor pollicis
- Ulnar boundary is the mid palmar septum (between palmar aponeurosis and third metacarpal)
- Radial boundary is where adductor pollicis joints onto the first metacarpal
- Anterior to the thenar space is the flexor tendon of index finger.
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What are the boundaries of the mid-palmer space?
- Is a continuation of the carpal tunnel.
- Deep to the palmar aponeurosis and flexor tendons (within their sheaths)
- Superficial to the palmer interossei.
- Ulnar aspect is the hypothenar septum (septum between 5th metacarpal and palmar aponeurosis)
- Radial aspect is the mid palmar septum (between the palmar aponeurosis and 3rd metacarpal)
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What are the boundaries of hypothenar space?
- Is located between the hypothenar fascia and 5th metacarpal.
- It contains the hypothenar muscles within it
- It ulnar border is the flexor retinaculum.
- Is radial border is the hypothenar septum (septum between 5th metacarpal and palmar aponeurosis)
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Draw a diagram of the handspaces
Look at my notes
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What is hyperhidrosis?
Hyperhidrosis is secretion of sweat in amounts greater than physiologically needed for thermoregulation.
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What is the diagnostic criteria for hyperhidrosis?
- Focal, visible, excessive sweating of at least 6 months duration without apparent cause
AND (2 of following)
- Bilateral
- Impairs daily activities
- At least one episode per week.
- Onset before age 25
- FHx
- Focal sweating stops during sleep.
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What are eccrine, apocrine, and sebaceous glands?
- There are three types of sweat glands in humans - apocrine, eccrine, and apoeccrine.
- Apocrine glands secrete a milky fluid rich in mucin which is milky and viscous. Bacteria cause the secretion to develop a strong odour. They thus function as a scent bland.
- Apocrine glands empty into a follicle.
- Eccrine glands empty directly onto the skin and secrete sweat which is hypotonic.
- Eccrine glands have sympathetic supply with Ach as its primary neurotransmitter.
Sebaceous glands open onto hair follicles - they secrete sebum which helps skin and hair to maintain moisture
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What is the pathogenesis of hyperhidrosis?
The cause of hyperhidrosis likely relates to an abnormal central response to stress (as the glands and nerve ends themselves are histologically normal)
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Whats the anomalie that exists regarding the innervation of sweat glands?
The anomaly exists though, that post-ganglionic sympathetic nerves going to sweat glands release Ach which acts on a muscarinic receptor (as opposed to adrenaline or noradrenaline). This means that botox can be used for hyperhidrosis
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What are the first and second line therapies for hyperhidrosis?
First line therapy
- Antiperspirants - aluminum based anti-perspirants
- Topical glycopyrronium - anticholinergic drug which inhibits the release of Ach.
Second line therapy
- Botox - blocks release of Ach thus reducing sweating - response after 2 days and can persist for 9 months. Side effects include weakness of the muscles of the hands.
- Anti-cholinergic treatment i.e. oxybutynin.
- Microwave thermolysis - commercial device which focuses microwave energy onto the dermal/adipose interface - administered in two 30 minute sessions 3 months apart.
- Iontophoresis - performed for palmar hyperhidrosis. Placement of hands or feet in tap water through which a an electric current flows - mechanism unknown.
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What problems can occur with thoracic sympthatectomy?
Horners syndrome if the chain is cut to high (as disrupts the cervical sympathetic chain)
Compensatory hyperhidrosis elsewhere
Gustatory sweating
Bradycardia.
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What are the indications for thoracic sympathetectomy?
- Severe symptoms
+
- Onset before aged of 16 and younger than 25 at time of surgery
- HR >55
- Absence of sweating during sleep
- BMI < 28
- No major co-morbidities.
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