CHAPTER 07 : SKIN Flashcards

Question

What is the epidemiology of melanoma?

Answer 1

``` <5% of skin cancer cases 75%-90% of all skin cancer mortalities UK 6/100,000 Commonest cancer of young adults Lifetime risk 0.5% F:M 2:1 ```

Answer 2

- Mutations in the BRAF gene allow for BRAF to signal independently of upstream cues, and results in overactive downstream signaling. - This leads to excessive cell proliferation and survival, independent of growth factors ``` Oncogenic BRAF has been implicated in: ~50% of melanoma tumors ~40% of papillary thyroid tumors ~30% of serous ovarian tumors ~10% of colorectal tumors ~10% of prostate tumors ``` Vemurafenib is an orally available, selective BRAF (V-raf murine sarcoma viral oncogene homolog B1) inhibitor for patients with unresectable or metastatic melanoma that tests positive for the BRAF V600E mutation

Answer 3

``` Risk factors PPARENTS Premalignant lesions (giant CMN, acquired MN, dysplastic naevi, lentigo maligna) Previous melanoma (3-5% of 2nd) Age Race Economic status (higher 3x risk) atypical Naevus syndrome (>100 atypicals) Fitzpatrick Type skin 1&2 Sunburn ```

Answer 4

FHx (5-12% have +ve FHx) 1st degree relative 1.8 RR BRAF proto-oncogene mutation (assoc w papillary thyroid ca, colorectal ca, non-small cell lung ca, leukaemia tumour suppressor genes, oncogenes CDKN2A gene mutation (regulates cell cycle during G1 checkpoint) dysplastic naevus syndrome (Familial atypical multiple mole melanoma FAMMM xeroderma pigmentosum

Answer 5

Acquired melanocytic naevus, dysplastic dermal melanocytoses pigmented BCC, basal cell papilloma, blue naevus, AK pyogenic granuloma (amelanotic), SCC

Answer 6

Glasgow 7-point checklist (Mackie) Major (SSC - Size, Shape, Colour) 1 Change in size 2 Irregular shape (esp. SSM and LMM not nodular) 3 Irregular colour Minor (DISC diameter, Inflammation, sensory, crusting /bleeding) 4 Over 7mm 5 Inflammation 6 Oozing 7 Altered sensation/itch Any major or any 3 minor = suspicious - biopsy whole lesion with 2mm margin ``` American ABCD System: A = asymmetry B = border irregular C = colour more than 1 D = diameter over 6mm E = elevation (late feature) Plaster on mole = bad sign ```

Answer 7

Specimen (site) Specimen type (excision, incisional (etc) Gross description (size, max diameter, nodule, border, pigmentation) Histology (LM, SS, nod, AL, desmoplastic, neurotropic, other) Growth phase (insitu, invasive, radial, vertical) ``` Breslow thickness mm Clark level ulceration lymphatic / blood vessel invasion perineural invasion regression microsatellites co-existent naevus mitotic rate tumour infiltrating lymphocytes ``` Excision margins deep and peripheral Pathological staging TNM

Answer 8

check H&E staining - older, more crude newer FISH - fluorescent in situ hybridisation genomic hybridisation Tyrosinase (PCR) S-100 – detects progression TA-90 – risk of mets HLA-DQB1*0301 – experimental, identifies metastasis prone pts

Answer 9

``` from granular layer to deepest melanoma cell Clark 1969 I epidermis II into papillary III all papillary IV invasion of reticular V invasion of sc fat ```

Answer 10

Stage Ia: 95%, Ib: 90% Stage IIa: 80%, IIb: 65%, IIc: 45% Stage IIIa: 65%, IIIb: 50%, IIIc: 25% Stage IV: 8%

Answer 11

TX - Primary tumor cannot be assessed (shave biopsy, regressed primary) Tis - Melanoma in situ T1 - ≤1.0 mm (a: without ulceration, b: with ulceration) T2 - 1.01-2.0 mm (a: without ulceration, b: with ulceration) T3 - 2.01-4.0 mm (a: without ulceration, b: with ulceration) T4 - < 4.0 mm (a: without ulceration, b: with ulceration)

Answer 12

N classification is as follows: N1 - 1 lymph node; a: micrometastasis (clinically occult), b: macrometastasis (clinically apparent) N2 - 2-3 lymph nodes; a: micrometastasis, b: macrometastasis, c: in transit met(s), satellite(s), without metastatic lymph nodes (N2a: 2-3 nodes positive for micrometastasis; N2b: 2-3 nodes positive for macrometastasis; N2c: In transit met(s) or satellite(s) without metastatic nodes) N3 - 4 or more metastatic nodes or matted nodes or in-transit metastases or satellite(s) with metastatic node(s) Note that micrometastases are diagnosed after elective or sentinel lymphadenectomy. Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension. M classification is as follows: M1a - Distant skin, subcutaneous, or nodal metastases, normal lactate dehydrogenase (LDH) level M1b - Lung metastases, normal LDH level M1c - All other visceral metastases or any distant metastases with an elevated LDH level

Answer 13

Stage 0 - Tis, N0, M0 Stage IA - T1a, N0, M0 Stage IB - T1b, N0, M0; T2b, N0, M0 Stage IIA - T2b, N0, M0; T3a, N0, M0 Stage IIB - T3b, N0, M0; T4a, N0, M0 Stage IIC - T4b, N0, M0 Stage III - Any T, N 1-3, M0 Stage IIIA - pT1-4a, N1a, M0; pT1-4a, N2a, M0 Stage IIIB - pT1-4b, N1a, M0; pT1-4b, N2a, M0; pT1-4a, N1b, M0; pT1-4a, N2b, M0; pT1-4a/b, N2c, M0 Stage IIIC - pT1-4b, N1b, M0; pT1-4b, N2b, M0; any T, N3, M0 Stage IV - Any T, Any N, Any M

Answer 14

*1.0-cm margin for primary melanomas less than 1.0 mm in thickness. (Diagnosis and treatment of early melanoma. NIH Con- sensus Development Conference. January 27–29, 1992. Consensus statement/NIH Consensus Development Conference 1992) *1.0-cm margin may also be effective for lesions up to 2 mm in thickness. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary cutaneous malignant melanoma: comparison of excision with margins of 1 or 3 cm. N Engl J Med. 1988 *1.0 - 2.0 cm margins are commonly used for lesions between 2 and 4 mm in thickness. *2.0-cm margin may be most appropriate for melanomas 4 mm or more in thickness. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2cm surgical margins for intermediate-thickness melanomas (1–4 mm): Results of a multi-institutional randomized surgical trial. Ann Surg. 1993 Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4 mm) primary melanoma. Ann Surg Oncol. 1998 *Margins greater than 2.0 cm do not appear to contribute significantly either to survival or local control Heaton (as above) McKinnon JG, Starritt EC, Scolyer RA, et al. Histopathologic excision margin affects local recurrence rate: analysis of 2681 patients with melanomas < or =2 mm thick. Ann Surg. 2005

Answer 15

 WHO Trial - Veronesi et al (NEJM 1988) - Thin MM For melanomas less than 2 mm there was no difference in survival between 1 and 3 cm excision however 3 patients with 1cm excisions had local recurrence vs. none with wider excision.  Balch et al (Ann Surg 1993) - Intermediate to Thick For intermediate thickness melanomas 1-4 mm there was no difference between 2 and 4 cm excision margins. Karakousis (Ann Surg Oncol) also found that 2 cm margins were as effective as 4 cm in local control of intermediate thickness (1-4 mm) melanoma  UK melanoma study group/BAPS trial (Meiron Thomas 2004) - Thick MM 1cm v 3 cm in 2mm or thicker MM 1 cm margin is assoc with greater risk of local recurrent but NO different in overall survival at 60 months.  Heaton et al. (Ann Surg oncol 1998) found that there was no difference between excisional margins of < 2 cm and > 2 cm in thick lesions but this was a retrospective study.

Answer 16

WHO trial (Veronesi 1988) - thin MM 2mm - 1cm vs 3cm excision margins - 1cm: greater risk of local recurrence - no survival benefit at 60mths Heaton (1998) retrospective - thick lesions - no diff b/t 2cm excision margins Gillgren Scandinavian study 2011 Lancet - 936pts - >2mm (Clinical stage IIA-C) - 2 cm vs 4cm excision margins - There was no significant difference in overall survival (65% in both groups; P = .69) or recurrence-free survival (56% in both groups; P = .82) between the 2 approaches at 5 years

Answer 17

Veronesi WHO trials (1998) - no survival benefit

Answer 18

``` SNB only investigation that upstages from II-III or clinically palpable nodes MSLT-1 trial (Morton et al 2006) - 1.2 - 3.5mm - SLNB vs watch and wait - provides prognostic indicator - SLNB +ve proceed to CLND - 6% survival benefit ```

Answer 19

SLNB if offered CXR CT liver USS

Answer 20

clinical staging 0 Tis IA T1a 95 IB T1b or T2a 90 IIA T2b or T3a 80 IIB T3b or T4a 65 IIC T4b 45 III Any T, N+, No M (clinical) IIIA no ulceration N1a or 2a 65 IIIB ulcerated N1a or b 50 no ulceration N1b/2b/2c IIIC ulcerated N1b/2b/2c 25 ulc / no ulc N3 IV Any M 8%

Answer 21

IIIa - SLNB positive microscopic disease IIIb - clinically palpable macroscopic disease IIIc - intransit mets Pts with clinical stage III and pathological IIIB are given high dose interferon in most units MSLT 2 trial - looking at +ve SLNB - immediate CLND or watch and wait. Veronesi WHO - 2 prospective trials showed no benefit Balch (1996) and Cascinelli (1998) found benefit in immediate CLND

Answer 22

``` Chemotherapy - 15% response Immunomodulatory agents (high dose interferon, cisplatin, IL2) - marginal effect on survival Radiotherapy (local, cerebral mets) ANTI CTLA4 AB TRIALS Tremelimumab IgG2 & Ipilimumab ```

Answer 23

1. Immunotherapy - Ipilimumab - Interleukin-2 (IL-2) 2. Signal transduction inhibitors - Vemurafenib (for patients who test positive for the BRAF V600 mutation). 3. Chemotherapy 4. Palliative local therapy

Answer 24

tumours of mechanoreceptors of neural crest origin worst prognosis of all skin lesions 50% H&N, elderly resembles oat cell ca of lung (CXR to rule out lung primary) locally aggressive, metastasise Rx - WLE and DXT

Answer 25

Malignant tumour of eccrine glands mainly scalp ACC usu in salivary, lacrimal and mucous glands of URT Rx WLE, not DXT sensitive

Answer 26

malignant growth differentiating towards sebaceous epithelium rare (0.2% of all skin cancers) 3rd most common eyelid tumours 50% periorbital, yellowish nodules, mets uncommon Rx WLE

Answer 27

Malignant epithelial tumour of sweat glands rare, middle age + painful reddish nodules with dermis, firm/hard, irregular can met WLE +/- SLNB

Answer 28

Ant - pec major & minor Post - LD, teres major & subscapularis Med - serratus, 1st 4 ribs & intercostals Lat - humerus, coracobrachialis, biceps apex - 1st rib, scapula, clavicle, subclavius Base - axillary fascia, fat, skin

Answer 29

``` long thoracic thoracodorsal medial pectoral lateral pectoral Intercostobrachial - usu sacrificed ```

Answer 30

``` SALSAP 1st - superior thoracic 2nd - thoracoacromial - lateral thoracic 3rd - subscapular - anterior circumflex humeral - posterior circumflex humeral ```

Answer 31

``` Femoral Triangle Borders o Medial border of sartorius o Medial border of Adductor Longus o Inguinal Ligament o Floor – Iliopsoas and Pectineus o Roof – Fascia ```

Answer 32

Longitudinal / lazy S - good access to femoral triangle - can be extended superiorly if ilioinguinal dissection needed Transverse incision - poor visualisation of apex of triangle - theoretically increases chances of lymphoedema

Answer 33

2cm medial to ASIS under fascia overlying sartorius

Answer 34

``` external iliac nodes (skeletonise EIA) obturator nodes (in obturator fat pad) ```

Answer 35

``` o Curvilinear Incision o Thick medial and lateral flaps o Identify apex, medial and lateral borders o Elevate tissue off femoral N, A, V o Ligate long saphenous o mark specimen o Identify lat cut n of thigh o perform sartorius switch o if iliac node dissection performed, no need to divide ligament (send as 2 specimens) ```

Answer 36

BAPRAS guidelines Definite - macroscopic disease in iliac/obturator nodes - 2+ inguinal nodes (micro/macro) - Cloquet +ve (- +ve SNB above ligament)

Answer 37

``` Seborrhoeic Keratosis Digital Fibrokeratoma Keratoacanthoma Actinic Keratosis Bowens Others - Squamous papilloma, viral wart, keratin horn, ```

Answer 38

 Hair follicles → Trichilemmal cyst, Trichofolliculoma, Tricholemmoma, Tricho-epithelioma, Pilomatrixoma (Benign Calcifying Epithelioma of Malherbe) (ghost cells on histo)  Sebaceous Glands → Sebaceous Adenoma, Sebaceous Hyperplasia, Sebaceous Naevus of Jadassohn  Sweat Gland - Eccrine Gland → Syringoma, Acrospiroma (Eccrine poroma), Cylindroma  Neural Tissue → Neurofibroma

Answer 39

Naevus cell naevi Congenital → Giant hairy naevus (GHN) or Non GHN. Acquired → Junctional, Compound, Intradermal Special → Spitz, Dysplastic, Halo Melanocytic naevi Epidermal → Ephelis, Lentigo, Café-au-lait patch, Becker’s naevus, Albright’s syndrome. Dermal → blue naevus, Mongolian blue spot, Naevus of Ota, Naevus of Ito

Answer 40

Epidermoid cysts Pilar cysts Milia Xanthelasma

Answer 41

Light Amplification by Stimulated Emission of Radiation

Answer 42

A device that transforms 1 type of energy (electrical) into optical energy - Laser medium is energised to excite electrons into a higher energy state. - As electrons move back into a stable orbit, it emits a photon of light of a particular wavelength. - These photons hit other excited electrons producing more photons. - The photons are reflected back and forth by 2 mirrors to put them in phase and parallel to each other. - One of the mirrors only partly reflects – allowing some photons to escape. light beam is - collimated - monochromatic (single wavelength) - coherent (in phase) Q-Switching = Pulsed - ‘giant pulse formation’ – produces a short-pulsed output beam - if full bath = energy, like suddenly taking bottom of bath away - dump of energy

Answer 43

1. Ablation of vascular lesions (a) haemangioma, capillary malformation - pulsed yellow dye (b) venous & venolymphatic malformn - KTP / Nd:Yag 2. Skin resurfacing - CO2, Erbium:Yag (water) 3. Benign cutaneous lesions - CO2 4. Benign pigmented lesions - IPL, diode, ruby 5. Hair removal - Long Pulsed Ruby, Long Pulsed Alexandrite, diode, Nd:YAG, IPL 6. Tattoo removal - Q-Switched Nd:Yag, Ruby, Alexandrite

Answer 44

``` Class IV devices Potential fire eye & skin hazard Safety equipment - wavelength specific goggles - warning signs - windows covered - remove / cover all reflective surfaces, incl instruments ``` wet drapes to protect patient from scatter be aware of laser use near oxygen source plume hazards - use special masks, plume evacuator, shave bulk of lesion 1st lasers operated only by those who have received formal training in laser theory, control techniques, and operation, laser nurse fire extinguishers

Answer 45

STARR - scattered - transmitted - absorbed - light energy transferred to target cells and turned into heat energy, causing coagulation and vaporisation - reflected - refracted

Answer 46

1. Energy source - electricity (argon) - flashlamp (PDL) - another laser (CO2) 2. Laser medium (solid or gas) 3. Laser cavity (resonator) ``` active medium excitation mechanism feedback mechanism (high reflectance mirror), output coupler (partially transmissive mirror) ```

Answer 47

1. The Epidermis → Epithelial Tumours  Seborrhoeic Keratosis,  Digital Fibrokeratoma,  Keratoacanthoma,  Actinic Keratosis  Others - Squamous papilloma, viral wart, , keratin horn, Bowens 2. The Dermis  Hair follicles → Trichilemmal cyst, Trichofolliculoma, Tricholemmoma, Tricho-epithelioma, Pilomatrixoma (Benign Calcifying Epithelioma of Malherbe)  Sebaceous Glands → Sebaceous Adenoma, Sebaceous Hyperplasia, Sebaceous Naevus of Jadassohn  Sweat Gland - Eccrine Gland → Syringoma, Acrospiroma (Eccrine poroma), Cylindroma  Neural Tissue → Neurofibroma

Answer 48

``` 3. Cysts  Epidermoid cysts  Pilar Cysts  Milia  Xanthelasma 4. Pigmented Lesions  Naevus cell naevi  Melanocytic naevi ```

Answer 49

SK = Seborrhoeic Wart, Senile Wart, Basal Cell Papilloma Incidence - M=F, Over 50, Caucasians - Stucco Keratosis – non pig SK on limbs - Dermatosis papulosa nigra – multiple facial SK, dark skin, early onset Aetiology - Familial – AD - Inflammatory dermatosis - Visceral malignancy manifestation - Oestrogen administration Pathology - Accumulated immature keratinocytes b/n basal and keratinizing layers - Acanthosis – thickening of epidermis - Elongated dermal papillae - Rarely malignant transformation (SCC) Clinical - Verrucous plaque - Face hands and upper trunk - May be pigmented - May bleed, get inflamed, itch, shed, reform Treatment - Curettage or excision - Cryotherapy - Topical TCA

Answer 50

- Rapidly evolving tumour → resolves - Keratinizing squamous cells originating in pilosebaceous follicles Incidence - Caucasian, 40+, M>F 3:1, 1/3 freq of SCC Aetiology - Sun, Coal, Tar, carcinogenic hydrocarbons, Injury and infection inc SSG donors, Assoc with Ca larynx, internal ca, leukaemia, deficient cell-mediated immunity. Pathology - Keratin-filled crypt, Rapidly dividing squamous cells from skin appendages, Atypical mitosis and loss of polarity Clinical - Globular tumour - Keratin plug or horn - Radial symmetry - Resolution after 6 weeks ~ 3 months, leaves depressed scar - Face, dorsum hand - Ferguson-Smith syndrome (single gene mutation on West Scotland) → AD + multiple self healing epitheliomas which look and behave as KA. - Torre’s syndrome = multiple internal malignancies, KA’s and sebaceous adenomas - Distinguish from SCC Treatment - Excise to get good specimen - Spontaneous resolution leaves unsightly scar - 5 FU and radiotherapy shorten time to resolution

Answer 51

- Scaly crusted areas in sun exposed areas of elderly pts - 20-25% develop into SCC Treatment - Efudix (5FU) or - Solaraze (Diclofenac) gel

Answer 52

Others Digital fibrokeratoma - papillary / keratotic outgrowth in finger near joint Squamous papilloma - Skin tag or acrochordons → excise Viral Warts - HPV → cryotherapy or curettage Keratin Horn - Hard protruding lump of cornified material, Likely to have an AK or SCC in the base Bowens - Red scaly lesion on the legs of elderly patients, Histology resembles SCC, limited to epidermis → in situ, can progress to SCC so worth removing

Answer 53

Hair follicle Sebaceous gland Sweat gland Neural tissue

Answer 54

1. Trichilemmal cyst - Sebaceous cyst of hairy skin - Scalp, F>M, middle age, AD - Rupture → cell proliferation, occasional malignant change Treat → excision 2. Trichofolliculoma - Multiple malformed hair roots arising from an enlarged follicle canal - Keratin-filed crater, mainly face - White Hairs from a central punctum - Histology like BCC But contain keratin-filled macrocysts 3. Tricholemmoma - Hair follicle tumour – clinically like BCC - Small warty papules - Cowden’s syndrome → Multiple facial tricholemmomas, Keratoses on palms and soles, Oral polyps, Breast Cancer in 50% of patients - Plaques of squamous cells containing glycogen - Face, middle aged → elderly men

Answer 55

4. Tricho-epithelioma - Epithelial tumour differentiating towards hair follicle cells - Rare, at puberty, AD - Path – rounded masses of fusiform cells, Keratin filled lacunae - Malignant change to BCC - Clinical – pinkish nodules, cheeks and eyelids and NL folds, (around mouth) - often misdiagnosed as BCC, or MM if pigmented - Treatment – Excision Pilomatrixoma (Benign Calcifying Epithelioma of Malherbe) - Hamartoma of dead calcified cells which resemble hair matrix - Uncommon, M assoc with myotonia atrophica - Path – Well circumscribed dermal tumour, cells mature out to inner layers - Central calcification and ghost cells, no basophilic granules - Clinical – Dermal, s/c tumour, Head/neck/upper limb. - Stony Hard lesion on the face of a child. - Treat by excision

Answer 56

1. Sebaceous Adenoma (Sebaceous Carcinoma) 2. Sebaceous Hyperplasia 3. Sebaceous Naevi (of Jadassohn) (Organoid Naevus)

Answer 57

1. Sebaceous Adenoma → smooth papules on scalp of elderly - Benign tumour of incompletely differentiated sebaceous cells - Rare, mainly elderly - Path – multilobular tumour of upper dermis, small basophilic sebaceous matrix cells and larger cells with fat globules - Clinical Ulcers/plaques/sessile/pedunculated Yellowish, Face/scalp, Sudden ↑ growth - Treat – Excision, Radiosensitive

Answer 58

- Small yellowish lesions usually found on face → can look clinically like BCC - Severe seb hyperplasia of nose = rhinophyma

Answer 59

- Normally present at birth but usually enlarges and becomes raised in puberty, due to hyperplasia of the sebaceous glands. - Usually removed - 20-30% chance of mailgnant transformation → BCC / mixed appendigeal tumour (rare)

Answer 60

1. Syringoma 2. Acrospiroma 3. Cylindroma

Answer 61

aka Papillary Eccrine Adenoma - Benign tumour of eccrine sweat gland origin - Uncommon, F>M, adolescence, multiple with Downs Path - Convoluted sweat ducts in upper dermis, tail like (tadpole) projections of cells Clinical - Small yellow dermal papules ,<3mm, Cystic, release clear fluid on injury, - Chest face neck, may look like tricho-epithelioma or xanthelasma Treatment - Excision, Intralesional desiccation, Laser

Answer 62

- Tumour from eccrine sweat duct epithelium - Epidermal, juxta or dermal - Eccrine poroma commonest - M=F, middle age, usually acral Path - Sweat gland duct proliferation, cells with glycogen and glycolic enzymes - Overlying hyperkeratosis. Malignant change (malignant eccrine poroma) reported Clinical - Hyperkeratotic plaque on sole or palm, may ulcerate Treatment – Excision

Answer 63

- Derived from coiled part of sweat gland (part secretory and part duct) - Uncommon F>M 2:1, Often AD, Early adult Path - columns of cells with hyaline between large and small (peripheral) cell types Clinical - Scalp and adjacent skin. Pinkish fleshy tumours, Hairless and multiple, maybe painful - Large or multiple = Turban tumour - Malignant change very rare - Distinguish from trichilemmal cyst Treat – excision

Answer 64

Neurofibroma - Skin coloured nodules composed of neural tissue and keratin - Neurofibromatosis (von Recklinghausen’s disease) = Multiple cutaneous NF, 6 or more café-au-lait patches >1.5 cm, axillary freckling, Lisch nodules on the iris (ocular neurofibromatosis)

Answer 65

NF Classification o Type 1 → most common with features above o Type 2 → assoc with CNS NF’s – very rare o 3rd Type – Schwannomatosis – very painful, very rare o Plexiform neurofibromas - large infiltrative lesions found in the head or neck region - more diffuse, may cause neurological deficit, risk of malignancy transformation- pain, rapid growth, go hard, neuro compression, rapid met spread - wound complications common following their excision - chromosome 17q - 1/3500 prevalence - 1/2500 births ``` 2 or more of- o Axillary Freckling o 6 or > Cafe au lait patches o Iris Lisch nodules o Thickening (glioma) of optic n. o Bony abnormality ```

Answer 66

Congenital dermoids - Entrapment of epidermis during facial development. (a) Angular dermoid - most common - Usually located in submuscular plane towards outer corner of the eye (b) Midline dermoid - anywhere between forehead and nasal tip - May have deep intracranial extension → preop scan needed.

Answer 67

= Epidermoid Cyst - Young and middle aged - Inflammation and obstruction of pilosebaceous follicles Path - Epidermal lining, keratin and break down products + sebum secreted by sebaceous glands Clinical - Dermal spherical cyst, Tethered epidermis, Enlarge, Suppurate via punctum - Gardener’s syndrome → multiple cysts + osteomas of jaw + polyposis coli Treat – complete excision

Answer 68

Implantation dermoids - After trauma → trapping of segment of epidermis in dermis Pilar cysts - Similar to epidermoid cysts but occur on scalp Milia - Small intra-epidermal cysts usually on cheeks - Treat by needle enucleation Xanthelasma - Accumulation of lipid within the skin - Usually around eyes - Treat by excision → vertical to avoid ectropion

Answer 69

Cutaneous hamartomas usually incorporating a proliferation of Sebaceous glands = sebaceous naevus Melanocytes = melanocytic naevus Vascular tissue = vascular naevus

Answer 70

Association of EN with developmental anomalies of other organ systems Proteus syndrome - overgrowth syndrome, multiple sites Sebaceous naevus syndrome - with neurological features (seizures, developmental delay, palsied, structural abnormalities of the brain) Becker's naevus syndrome - Beckers naevus with unilateral pectoral hypoplasia and skeletal abnormalities

Answer 71

- derived from neural crest - Spindle shaped clear cells, contain a dark nucleus + dendritic processes Melanin is synthesized within melanocytes from dihydroxyphenylalanine (DOPA) → tyrosine - Melanin accumulates in vesicles within melanocytes called melanosomes - Melanosomes are distributed to surrounding cells via long dendritic processes - number of melanocytes does NOT vary bn races - ↑ pigmentation is due to ↑ production - Melanin production is stimulated by sunlight and (MSH) melanocyte-stimulating hormone (pituitary) Naevus Cells - Melanocyte leaves epidermis and enters dermis = Naevus cell - They are round rather than spindle shaped - DO NOT have dendritic processes - Tend to congregate in nests

Answer 72

Malignant melanocytic lesion = malignant melanoma Benign → melanocyte or naevus cell o Naevus cell lesion = congenital or acquired o Melanocytic lesions arise in = epidermis or dermis Naevus Cell Naevi Congenital → Giant hairy naevus (GHN) or Non GHN. Acquired → Junctional, Compound, Intradermal Special → Spitz, Dysplastic, Halo Melanocytic Naevi Epidermal → Ephelis, Lentigo, Café-au-lait patch, Becker’s naevus, Albright’s syndrome. Dermal → blue naevus, Mongolian blue spot, Naevus of Ota, Naevus of Ito

Answer 73

- >20cm in adult or > 5% BSA - Malignant transformation of any CMN = 0.7-2.4% (prev 2-4% or up to 40% in some series) - MM in CMN 4-14% (5%) Risk highest in 1st 10yrs of life - worse prognosis than other MM - Leptomeningeal melanosis assoc with GHN = very poor prognosis - Rarely can get tumours of neural or mesenchymal origin e.g. rhabdomyosarcoma or liposarcoma - Treatment → controversial - Pigment more superficial in early neonatal period then goes deeper? → excise, dermabrade, laser, curette may work BUT ↑↑ blood loss for neonate. Superficial excision can develop residual black areas later → leopard skin type appearance. - Debatable if superficial excision prevents malignant change. - Can excise later during childhood → wide undermining and direct closure, tissue expansion, skin grafting, integra resurfacing. - Some advise just to watch and excise any changing areas. - Little prospective data on incidence of malignant change or impact of Rx.

Answer 74

1) untreated CMNs can lighten spontaneously, sometimes dramatically; 2) routine surgery with current techniques has not been shown to reduce the risk of malignancy in CMNs and is therefore for cosmetic reasons only; 3) early surgery has not been shown to be advantageous and carries increased anaesthetic risk; 4) there is some evidence that surgical intervention may adversely affect the behaviour of the CMN cells. As a result, our current practice is based on the following guidelines: 1) patients are treated in a MDT setting which includes paediatric dermatology, plastic surgery and neuroradiology, with access to neurology, neurosurgery and oncology; 2) serial photographs are taken at yearly intervals to assess spontaneous lightening; 3) all routine surgery is delayed for at least the first year; 4) patients with facial CMNs (either the principal lesion or large satellites) are offered surgery for cosmetic reasons; 5) patients with a single, easily excisable CMN are offered surgery for cosmetic reasons; 6) All families are made aware of the possibility of spontaneous lightening and the possibility that surgery may have effects on the behaviour of naevus cells

Answer 75

Risk of melanoma proportional to size of nevus. Large CMN: 6.3-12.2%. (40% of the malignant melanomas observed in children) Giant CMN: 2-42% (Lifetime expert monitoring 50% of the malignancies develop by 3 years of age, 60% by childhood, and 70% by puberty GOSH paper - more likely to be lower

Answer 76

Rare in infancy, appear in childhood and adolescence, less appear in early adulthood, stable numbers in middle age. 1. Junctional Naevi - Flat Smooth and irregularly pigmented, usually in the young - Nests of naevus cells clustered around the epidermal/dermal junction 2. Compound Naevi - Round well-circumscribed slightly raised lesions - Nests of naevus cells clustered at epidermal/dermal junction extending into dermis 3. Intradermal Naevi - Dome shaped lesions, non-pigmented or hairy - Usu adults, composed of nests of naevus cells clustered within dermis

Answer 77

1. Spitz Naevus (juvenile melanoma) - See 7.4 Melanoma 2. Dysplastic Naevi - Irregular outline, Patchy pigmentation - >5mm - Atypical naevus (atypical mole) syndrome = >100 dysplastic naevi in 1 pt – associated with ↑ risk MM (risk also related to FHx) 3. Halo Naevus - Naevus surrounded with depigmented area of skin - Relatively common in older children and teenagers - Tend to regress leaving a small scar - Antimelanoma antibodies have been detected in some pts with halo naevi - Treatment → expectant

Answer 78

1. Ephelis → freckle - Normal number of melanocytes but ↑ production - Disappear in the absence of sunlight 2. Lentigo - ↑ number of melanocytes - Persist without sunlight - 3 types a) lentigo simplex → young and middle aged b) lentigo senilis → elderly c) solar lentigo → after sun exposure 3. Café-au-lait patch - Pale brown patch - >6 lesions > 1.5cm = neurofibromatosis. Becker’s Naevus - Dark patch on the shoulder, normally appears during adolescence and may become hairy Albright’s syndrome (see 5.4 Cleft) - Pigmented skin lesions, Fibrous dysplasia, Precocious puberty.

Answer 79

1. Blue naevus - Round areas of blue/black colouration - Arrested migration of melanocytes bound for dermal/epidermal junction - Differential diagnosis - melanoma 2. Mongolian blue spot - Bluish grey pigmentation over the sacrum - Present in 90% of Mongolian infants 3. Naevus of Ota - Bluish pigment of the sclera and adjacent periorbital skin - Caused by intradermal melanocytes, prevalent among Japanese 4. Naevus of Ito - Blue-grey discolouration around the shoulder - Intradermal melanocytes - Rare in Caucasians but common in Japanese

Answer 80

>100 melanocytic naevi measuring 6-15mm Present at birth Increase in number around puberty 10% risk of melanoma

Answer 81

``` 1882 Kaposi “Xeroderma pigmentosum” Rare, AD Photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development Defect in nucleotide excision repair Deficiency in thiamine dimerase M=F, all races Identified by age 2 <20 yrs: 1000-fold increase in the incidence of NMSC and melanoma Mean patient age of skin cancer is 8 yrs Actinic damage between 1-2 yrs of age ```

Answer 82

Skin colour Burns I very white / freckled always II white usually III white - olive sometimes IV brown rarely V dark brown v rarely VI black never

Answer 83

Absolute - unrealistic expectations - poor general health and nutritional status isotretinoin therapy last 6mths complete absence of intact pilosebaceous units on face active infections / open wounds Relative resurfacing procedure last 3-12mths recent facial surgery w excess undermining e.g. facelift hx of abnormal scarring / delayed wound healing hx of DXT hx of rosacea, web dermatitis, atopic dermatitis, psoriasis, vitiligo)

Answer 84

Moderate increase in risk (8-10x popn) - Previous Melanoma: 3-5% chance 2nd primary - Organ transplant patients Greatly increased risk (>10x popn) - Atypical mole syndrome - Giant congenital pigmented hairy naevus - Strong FH (>3 cases pancreatic ca. / melanoma) - Dysplastic naevus - Xeroderma pigmentosum - Lentigo maligna

Answer 85

Trial, Excision plan, N, F/U, Local Control, Survival Veronesi (WHO) New Eng J Med 1988 1 vs 3cm MM0.8-2.0mm trunk or extremities 989 11 No diff No diff ``` Balch (Intergroup Melanoma Surgical Trial) Ann Surg Oncol 2001 2 vs 4cm MM 1-4mm trunk/UL 468 10 No diff No diff ``` ``` Khayat (French Co-operative Study) Cancer 2003 2 vs 5cm MM2cm 900 5 Inc. local rec with 1cm margin No diff ```

Answer 86

If Clinically node –ve:- - SLNB – “can be considered” in stage >IB - No proven therapeutic value - Only assists in prognosis - Significant risks, false –ve etc. If Node +ve:- FNAC (+/- repeat or open biopsy) Radical LND (SSMDT member >15/yr), CT and LDH

Answer 87

1st node draining area of lesion NICE Guideline (2006) - Centres with experience of SLNB - ONLY in context of trials More accurate staging No survival benefit Small decrease in disease-free survival Delineation of populations for trials SLNB positivity depends on stage of primary SLNB negative pts have better D-F Survival

Answer 88

Superficial inguinal LND - Single clinically involved ing. / fem. triangle node - Single +ve superficial ing. SLN Pelvic LND - >1 palpable ing. +⁄or fem. triangle node - CT / USS evidence: >1 ing. +⁄or fem. triangle node or pelvic node involvement - >1 microscopically involved node at SLNB - Conglomerate of ing. / fem. triangle LNs - Microscopic /macroscopic involvement of Cloquet’s node

Answer 89

Excision / Laser ablation Progressive disease: ILI (5cm) Radiotherapy Electrochemotherapy using bleomycin under evaluation

Answer 90

Interferon: - Significantly increase relapse-free survival - Inc overall survival - Greatest benefit if Stage IIB/III-n1 Decarbazine: alkylating agent Melanoma vaccines: unsuccessful so far DXT: 48Gy in 20 fractions

Answer 91

Selective BRAF inhibitors - Vemurafenib: 6-10/12 increase in median survival - S/E: SCC (KA type) CTLA-4 monoclonal antibodies - Ipilimumab (human IgG1), for advanced metastatic melanoma - Dose: 3mg/kg every 3/52 for 3/12 - block cytotoxic T- lymphocyte- associated antigen 4 (CTLA-4), a negative regulator of T cells, and thereby augment T-cell activation and proliferation

Answer 92

- 1269 pts: 60% SLNB, 40% observed - Median follow up 5 yrs - No overall survival benefit to early vs. delayed CLND - Prognostic indicator: significant decrease in overall 5yr survival with positive SLN (90.2% vs. 72.3%) ~20% of SLND +ve pts will have +ve nodes on CLND, of which 65% will have only 1 node

Answer 93

Pts stratified according to BT, ulceration and size of SLN mets Pts then randomised to CLND + observation or Serial USS of SNB basin and CLND if node recurrence

Answer 94

``` in situ (5-10mm) less than 1mm (1cm) 1 to 2mm (1-2cm) 2 to 4mm (2cm) greater than 4mm (2-3cm) ``` Excise down to fascia No diff in local recurrence rates whether fascia is excised or not

Answer 95

Excision biopsy 2mm margins Incision biopsy if greater than 1.5cm (MDT) Shave incision if subungal melanoma (only by SSMDT member)

Answer 96

Stage I,II +IIIA: No further investigation Stage IIIB or C: CT head, chest, abdo + pelvis Stage IV: According to clinical need + LDH

Answer 97

SLN = first node in the lymphatic basin that drains the lesion and is the node at greatest risk for the development of metastasis Standard for SLNB is a triple diagnostic approach (a) lymphoscintography (b) blue dye dermal infiltration and (c) localisation with gamma probe - requires appropriate surgical expertise - specialist nuclear medicine services - serial sectioning and immunohistochemistry techniques Indicated in >1mm / Clark level 4 / >4mm (subset of node -ve pts with good prognosis)

Answer 98

- continuation of inguinal incision, lateral to femoral vessels - incise through external and internal oblique, retract peritoneum medially to reveal retroperitoneal space - identify ureter and preserve - excise all obturator and ext iliac nodes - mark specimen (excise as 2 specimens, as inguinal ligament division is associated with greater morbidity)

Answer 99

Ilioinguinal dissection offers a survival benefit in patients with palpable positive inguinal nodes compared with inguinal block dissection of the femoral triangle nodes Sterne Br J Surg (1995) Ilioinguinal block dissection for malignant melanoma. Karakousis Br J Surg (1994) Groin dissection in malignant melanoma.