Melanoma

Question 1

Where in the skin are melanocytes found?

Answer 1

Basal layer of the epidermis

Question 2

Name 3 types melanin

Answer 2

• Eumelanin: most common. Brown and black pigment. Better shield against uv
• pheomelanin: red/yellow pigment. More uv induced reactive oxygen species leading to greater DNA damage
Neuromelanin

Question 3

Which gene determines skin colour?

Answer 3

Mc1r. Fully functional = more eumelanin

Question 4

Risk factors malignant melanoma? (10)

Answer 4

Environmental
• uv radiation exposure.

Host
• elderly >50
• fair skinned
• common acquired and atypical dysplastic naevi (>6mm, flat, irregular border, colour variation) especially if multiple and large
• male
• chronic immune suppression: prior cancer (chronic lymphocytic leukemia and non-hodgkin lymphoma ), AIDS, post-transplant

Genetics
• NRAS gene mutation: sun exposed areas, modular melanoma
• BRAF: intermittent childhood exposed skin
• kit: chronically sun exposed areas
• pten:
• family history (cdkn2a gene mutation)
• less common = nucleotide excision repair ner gene → xeroderma pigmentosum

Question 5

Name 5 types cutaneous malignant melanoma

Answer 5

• Superficial spreading: most common 70%
• nodular melanoma: 15-30%
• lentigo maligna 10-15%
Acral lentiginous 2-8%
• desmoplastic melanoma very rare

Question 6

Where does superficial spreading cutaneous malignant melanoma commonly occur?

Answer 6

Female: leg
Male: back

Question 7

Characteristic features of superficial spreading cutaneous malignant melanoma? (5)

Answer 7

• Usually female leg, male back
• diagnosed 5th decade
• flat
• slow growing
• enlarge radially (lateral)

Question 8

Characteristic features of nodular cutaneous malignant melanoma? (5)

Answer 8

• 6th decade
• male > female
• common sites: head, neck, trunk, legs
• rapidly enlarging, may ulcerate and haemorrhage
• lack typical abcde warning signs with worse prognosis, usually in vertical growth phase at time of diagnosis

Question 9

Characteristic features of lentigo maligna cutaneous malignant melanoma? (4)

Answer 9

• 8th decade
• chronically sun damaged areas: head, neck, forearms.
• initially flat variegated (different colours) pigmented macule with irregular edges
• later = central nodule indicating transition to vertical growth phase

Question 10

Characteristic features of acral lentiginous cutaneous malignant melanoma? (5)

Answer 10

• Exclusively on sole, palm and subungal (under nail thumb or great toe ) locations
• most common type dark skinned elderly
• asymmetric brown-black nodule with variegation in colour and irregular borders
• subungal: diffuse nail discolouration, longitudinal pigmented band (melonychia strata) or growth in nail bed. Pigmented spread to lateral nail folds or prox nail fold= Hutchinson sign, pathognomonic
• poorer prognosis

Question 11

Characteristic features of desmoplastic cutaneous malignant melanoma? (4)

Answer 11

• Older males
• head and neck
• 50% amelanotic scar, 50% overlying lm (lentigo maligna) or SSM (superficial spreading)
• deeply invasive. May be extremely painful of neurotropic
Rare

Question 12

Differential diagnosis for superficial spreading melanoma? (4)

Answer 12

• Atypical naevus
• melanocytic naevi
• seborrheic keratosis
• superficial basal cell carcinoma

Question 13

Differential diagnosis for nodular melanoma? (5)

Answer 13

• Blue naevus
• pigmented basal cell carcinoma
• squamous cell carcinoma
• kaposi sarcoma
• angiosarcoma

Question 14

Differential diagnosis for lentigo maligna melanoma? (5)

Answer 14

• Solar lentigo
• ephelids
• pigmented actinic keratosis
• superficial bcc
• seborrhoeic keratosis

Question 15

Differential diagnosis for acral lentigenous melanoma? (5)

Answer 15

• Plantar warts
• haematoma
• pyogenic granuloma palmoplantar naevus
• glomus tumour
• haemorrhage under nail
• onychomycosis Bowens disease

Question 16

Differential diagnosis for desmoplastic melanoma? (4)

Answer 16

• sclerosing blue naevi
• dermato fibroma
• leiomyosarcoma
• malignant fibrous histocytoma

Question 17

Examination of melanoma?

Answer 17

Abcde
• asymmetry
• border irregularities
. Colour variegation
• diameter > 6mm
• elevation

Question 18

Investigations and diagnosis melanoma?

Answer 18

• Dermoscopy to reduce number of biopsies benign lesions and increased diagnostic accuracy
• biopsy if suspicious from most elevated or darkest area of lesion
- narrow margin (2mm) complete elliptical excision biopsy best
- punch
- shave
- avoid wide excisions, not as accurate histology
- full thickness of large

Question 19

staging melanoma?

Answer 19

TNM

Tumour
‘Tis:
T1: ≤1 mm in thickness
T 2: 1,01-2 mm
T3:2,01-4 mm
T 4: > 4 mm
A and b for each: with (B) or without (a) ulceration

Regional lymph nodes
N1:1 node
- A: micrometastasis
-B: macro

N2:2-3 nodes
A-micro
B-macro
C- in transit mets/satellite without metastatic nodes
N3: ≥4 metastatic nodes, or matted, or in transit mets/satellite with metastatic nodes

Metastasis
M1a: skin, subcutaneous or distant lymph nodes
M 1 b: lung
m1c: all other visceral sets or distant metastasis to any site with elevated serum ldh

Question 20

Clinical staging 1-4 melanoma?

Answer 20

• Stage 1: t1a - T 2 a no MO
• stage 2: t2b - t4 b no m0
• stage 3:≥ n1
• stage 4: M1

Question 21

Melanoma treatment? (5)

Answer 21

• Wide local excision! 1-2 cm excision around primary tumour
• for regional lymph nodes: complete lymph node dissection, also prophylactic for breslow stage 3-5 (>1,5mm deep )
• alternative if can’t do surgery: topical imiquimod 5% cream
• radiation: can be primary (melanoma in situ and lymph mets if surgery not possible), adjuvant or palliative!
• adjuvant therapy: intralesional injection, local ablation therapy, regional therapy, systemic

Question 22

Indications for sentinel lymph node biopsy for melanoma? (6)

Answer 22

• T 2-T4
• t1b with adverse features eg ulceration, lymphovascular invasion, high mitotic rate
• patients <40 with other adverse histology features in T1a and t1b
• incomplete biopsy of primary tumour with positive margins
• Clark’s histology levels 2-4 (beyond epidermis )
. Breslow stage 3- 5 (>1.5mm deep)

Contraindication = advanced age, poor functional status, comorbid condition

Question 23

How do sentinel lymph node biopsy for melanoma?

Answer 23

Pre-operative lymphatic mapping (lymphoscintigraphy) with blue dye injection around primary tumour and gamma probe localisation with Tc 99 sulfur colloids, to identify and remove.

Question 24

Which type of melanoma will require adjuvant radiotherapy?

Answer 24

Desmoplastic melanoma

Question 25

Name 4 adjuvant therapy options for melanoma

Answer 25

• Intralesional injection: t-vec, bce, IFN, il 2
• local ablation therapy: topical imiquimod
• regional therapy: isolated limb infusion/perfusion with Melphalan
• systemic therapy: IFN alpha 2b, immunotherapy, BRAF inhibitors, checkpoint inhibitors
• radiotherapy

Question 26

Describe Clark’s levels of histology for melanoma.

Answer 26

• Level 1: melanoma cells confined to epidermis
• level 2: invasion of single cells or very small nests of melanoma into papillary dermis
• level 3: melanoma cells full and expand the papillary dermis
• level 4: invasion into reticular dermis
• level 5 : Invasion of subcutaneous fat

Question 27

Describe Breslow’s classification for melanoma and prognosis

Answer 27

• Stage 1: 0,75 mm deep
• stage 2: 0,76-1,5
• stage 3: 1,51-2,25
• stage 4: 2,26 -3,0
• stage 5: > 3mm

Stage 1 and 2 better prognosis
stage 3-5 high risk metastasis, will benefit from prophylactic lymph node dissection