Dr Patrick Treacy shares some of his most challenging cases. This month he talks about treating Cutaneous Malignant Melanoma. Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes. They typically occur in the skin but may rarely occur in the mouth, intestines, or eye. In women they most commonly occur on the legs, while in men they are most common on the back. Sometimes they develop from a mole with concerning changes including an increase in size, irregular edges, change in color, itchiness, or skin breakdown

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45Aesthetic Medicine • July/August 2015
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Dr Patrick Treacy shares some of his most challenging cases.
This month he talks about treating s Cutaneous Malignant Melanoma
Dr Treacy’s
CASEBOOK
A
23-year-old Siberian female patient
presented with a changing lesion on her
abdomen. The patient stated the lesion was
present for about two years and it started
off from within a freckle, which started
to grow larger and somewhat darken in appearance.
It had the clinical appearance of a melanoma and the
dermoscopy three-point checklist (designed to allow
non-experts not to miss detection of melanomas) was
used to determine whether this had a high likelihood of
malignancy. It included:
Asymmetry: asymmetry of colour and structure in one or
two perpendicular axes
Atypical network: pigment network with irregular holes
and thick lines
Blue-white structures: there was some evidence of blue-
white veil and regression structures
It was decided the likely diagnosis was a superficial
spreading melanoma and to remove the lesion with a
1cm clearance and work in association with a multi-
disciplinary team. However, it is recommended that
a patient who presents with signs and symptoms
suggestive of melanoma should be referred to a
consultant dermatologist or consultant plastic surgeon
and lesions suspicious of melanoma should not be
removed in primary care.
HISTOPATHOLOGY CONFIRMED THE DIAGNOSIS
Macroscopy: Skin, left inframammary: Skin ellipse, 15 x
9 x 3mm with irregular pigmented lesion, 5 x 7mm, 1cm
from nearest margin.
Microscopy: Skin, left infra-mammary, skin ellipse:
Malignant melanoma, superficial spreading subtype
- Clark level III. Breslow thickness: 1mm. No ulceration
identified No regression identified. Lymphovascular
invasion is not identified. Perineural invasion is not
identified. Mitotic rate is two per 10. Microsatellite
lesions are not identified. Melanoma arises in the
naevus. Margins: - Closest margin (radial): 1cm. Deep
margin: 4mm Prof K Sheahan

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HISTOPATHOLOGY EXPLAINED
The pathologist’s report above includes
a macroscopic description (the naked
eye view), of the specimen and a
microscopic description. The
following features suggest an
invasive melanoma.
Diagnosis of primary
melanoma
Breslow thickness to the
nearest 0.1 mm
Clark level of invasion
Margins of excision i.e. the
normal tissue around the
tumour
Mitotic rate – a measure of how
fast the cells are proliferating
Whether or not there is ulceration
The report includes comments about
cell type and its growth pattern,
invasionofbloodvesselsornerves,inflammatoryresponse,
regression and whether there is associated in-situ disease
Breslow thickness is reported for invasive melanomas.
It is measured vertically in millimetres from the top of
the granular layer (or base of superficial ulceration) to
the deepest point of tumour involvement. It is a strong
predictor of outcome; the thicker the melanoma, the more
likely it is to metastasize.
CLARK LEVEL
Clark level indicates the anatomic plane of invasion. The
deeper the Clark level, the greater the risk of metastasis.
It is useful in predicting outcome in thin tumours, and less
useful for thicker ones
TYPES OF MELANOMA
Melanomas are described according to their appearance
and behaviour. Those that start off as flat patches (i.e. have
Level 1 In situ melanoma
Level 2 Melanoma has invaded papillary dermis
Level 3 Melanoma has filled papillary dermis
Level 4 Melanoma has invaded reticular dermis
Level 5 Melanoma has invaded subcutaneous tissue
a horizontal growth phase) include:
(1)Superficialspreadingmelanoma(SSM)-70%ofall
melanomas
(2)Lentigomalignamelanoma(sundamaged
skinofface,scalpandneck)
(3) Acral lentiginous melanoma (on
soles of feet, palms of hands or under
the nails) (*subungual melanoma)
These superficial forms of
melanoma tend to grow slowly,
but at any time, they may begin to
thicken up or develop a nodule (i.e.
progress to a vertical growth phase).
Melanomas that quickly invade
deeper tissues include:
(1) Nodular melanoma (presenting as
a rapidly enlarging lump) 15–30% of all
melanomas
(2) Spitzoidmelanoma(anodulethatresemblesaSpitznaevus)
(3) Mucosalmelanoma(arisingonlips,eyelids,vulva,penis,anus)
(4) Neurotropic and desmoplastic melanoma (fibrous
tumour with a tendency to nerves)
Histologic factors that affect metastatic potential
include ulceration of the tumour, mitotic rate, presence
of lymphovascular invasion, microsatellites, regression,
perineural invasion, and the presence of lymphocytes
infiltrating the tumour.
WHO IS AT RISK OF MELANOMA?
The main risk factors for developing superficial spreading
melanoma include:
Affluence, Increasing age, female
Fair skin that burns easily. Red or light coloured hair,
Light coloured eyes and light coloured skin (Anglo-Celtic)
(Gandini S et al 2005).
Multiple (5) atypical nevi (moles that are histologically
dysplastic) (Garbe C et al 1994).
Many benign melanocytic naevi person (Ferrone CR et al
2005).
Giant congenital melanotic naevi ≥20cm in diameter
Previousinvasivemelanomaormelanomainsitu(Goggins
WB et al 2003).
Family history of melanoma. Two first-degree relatives
affected (Florrell Sr et al 2005).
UVB (280- 320nm) solar radiation (causing sunburn) is the
The primary mode
of treatment for localised
cutaneous melanoma is surgery.
Surgical margins of 5mm are
currently recommended for
melanoma in situ, and margins
of 1cm are recommended for
melanomas ≤1 mm in depth

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principle cause of melanoma.
UVA may be involved in the pathogenesis of melanoma
(Wang SQ et al 2001).
CHECKING FOR A MELANOMA
Glasgow 7-point checklist
The ABCDs of Melanoma
STAGING OF MELANOMA
Melanoma staging means finding out if the melanoma has
spread from its original site in the skin. The stages are:
TREATMENT OF MELANOMA
The primary mode of treatment for localized cutaneous
melanoma is surgery. Surgical margins of 5mm are
currently recommended for melanoma in situ, and
margins of 1cm are recommended for melanomas ≤1 mm
in depth1. For tumors of intermediate thickness (1–4
mm Breslow depth), randomized prospective studies
show that 2cm margins are appropriate, although 1cm
margins have been proven effective for tumors of 1-2mm
thickness.2,3 Margins of 2cm are recommended for
cutaneous melanomas greater than 4mm in thickness
(high-riskprimaries)topreventpotentiallocalrecurrence
in or around the scar site.
Numerous adjuvant therapies have been investigated
for the treatment of localized cutaneous melanoma
following complete surgical removal. Adjuvant interferon
(IFN) alfa-2b is the only adjuvant therapy approved
by the US Food and Drug Administration for high-risk
melanoma.4 While early-stage melanomas can often be
cured with surgery, more advanced melanomas can be
much harder to treat. But in recent years, newer types
of immunotherapy and targeted therapies have shown a
great deal of promise and have changed the treatment of
this disease.
Major features Minor features
• Change in size • Diameter 7mm
• Irregular shape • Inflammation
• Irregular colour • Oozing
• Change in sensation
A Asymmetry
B Border irregularity
C Colour variation
D Diameter over 6 mm
E Evolving (enlarging, changing)
Stage Characteristics
Level 1 In situ melanoma
Level 2 Melanoma has invaded papillary dermis
Level 3 Melanoma has filled papillary dermis
Level 4 Melanoma has invaded reticular dermis
Level 5 Melanoma has invaded subcutaneous tissue

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REFERENCES
(1) NIH Consensus conference. Diagnosis and treatment of early melanoma.
JAMA. 268(10):1314–9. 9.
(2) Balch CM, Urist MM, Karakousis CP, Smith TJ, Temple WJ, Drzewiecki K, et al.
Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1
to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg.
1993;218(3):262–7.
(3) Veronesi U, Cascinelli N, Adamus J, Balch C, Bandiera D, Barchuk A, et al. Thin
stage I primary cutaneous malignant melanoma. Comparison of excision with
margins of 1 or 3 cm. N Engl J Med.1988;318(18):1159–62.
(4) Veronesi U, Adamus J, Aubert C, Bajetta E, Beretta G, Bonadonna G, et al. A
randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous
melanoma. N Engl J Med. 1982;307(15):913–6.
(5) Rager EL, Bridgeford EP, Ollila DW. Cutaneous melanoma: update on
prevention, screening, diagnosis, and treatment. Am Fam Physician.
2005;72(2):269–76.
(6) Whiteman DC, Whiteman CA, Green AC. Childhood sun exposure as a risk
factor for melanoma: a systematic review of epidemiologic studies. Cancer
Causes Control. 2001;12(1):69–82.
(7) Anderson WF, Pfeiffer RM, Tucker MA, Rosenberg PS. Divergent cancer
pathways for early-onset and late-onset cutaneous malignant melanoma.
Cancer. 2009 Sep 15;115(18):4176-85. doi: 10.1002/cncr.24481. PubMed PMID:
19536874; PubMed Central PMCID: PMC2741537.
(8) Cohn-Cedarmark G, Rutqvist LE, Anderson R et al. Long-term results of a
randomised study by the Swedish Melanoma Study Group on 2-cm versus
5-cm resection margins for patients with cutaneous melanoma with a tumour
thickness of 0.8-2.0mm.Cancer 2000; 89: 1495-1501.
(9) Revised U.K. guidelines for the management of cutaneous melanoma 2010. JR
Marsden, JA Newton-Bishop, L Burrows, M Cook, PG Corrie, NH Cox, ME Gore,
P Lorigan, R MacKie, P Nathan, H Peach, B Powell, C Walker, BJD, Vol. 163, No. 2,
August 2010 (p238-256)
(10) Wang SQ, Setlow R, Berwick M, Polsky D,Marghoob AA, Kopf AW, Bart RS.
Ultraviolet A and melanoma: a review. J Am Acad Dermatol 2001; 44: 837-846.
(11) The prevention, diagnosis, referral and management of melanoma of the skin:
concise guidelines (Newton Bishop J, Bataille V, Gavin A, Lens M, Marsden
J, Mathews T, Ormerod A, Wheelhouse C). Royal College of Physicians and
British Association of Dermatologists. Concise guidance to good practice
series, No 7. London : RCP, September 2007
(12) Cutaneous melanoma: update on prevention, screening, diagnosis, and
treatment. Rager EL, Bridgeford EP, Ollila DW Am Fam Physician. 2005 Jul 15;
72(2):269-76.
(13) Abrahamsen HN, Hamilton-Dutoit SJ, Larsen J, Steiniche T. Sentinel lymph
nodes in malignant melanoma: extended histopathological evaluation
improves diagnostic precision. Cancer 2004; 100: 1683-1691.
(14) Balch CM, Buzaid AC, Soong SJ et al. Final version of the American Joint
Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol
2001; 19: 3635-3648.
(15) Annual report to the nation on the status of cancer, 1973-1999, featuring
implications of age and aging on U.S. cancer burden. Edwards BK, Howe HL,
Ries LA, Thun MJ, Rosenberg HM, Yancik R, Wingo PA, Jemal A, Feigal EG
Cancer. 2002 May 15; 94(10):2766-92.
(16) Gandini S, Sera F, Cattaruzza MS, Pasquini P, Picconi O, Boyle P, Melchi CF.
Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical
naevi. Eur J Cancer 2005; 41: 28-44.
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DrPatrickTreacy is CEO Ailesbury Clinics, chairman of the Irish Association of Cosmetic Doctors and Irish
regional representative of the British College of Aesthetic Medicine (BCAM). He is also president of
the World Trichology Association. Dr Treacy has won a number of awards for his contributions to facial
aesthetics and hair transplants including the AMEC Award in Paris in 2014. Dr Treacy also sits on the
editorial boards of three international journals and features regularly on international television and
radio programmes. He is scientific committee for AMWC Monaco 2015, AMWC Eastern Europe 2015,
AMWC Latin America 2015, RSM ICG7 (London) and Faculty IMCAS Paris 2015 and IMCAS China 2015.
IMMUNOTHERAPY
Drugs that block CTLA-4: Ipilimumab targets CTLA-4,
a protein that normally suppresses the T-cell immune
response, which helps melanoma cells survive. Ipilimumab
has been shown to help people with advanced melanomas
live longer. Combining ipilimumab with GM-CSF is better
than using ipilimumab alone. The combination has fewer
serious side effects.
Drugs that block PD-1 or PD-L1: Melanoma cells also
use pathways in the body to avoid being detected, and a
protein called PD-L1 on their surface helps them evade the
immune system. Two drugs that block PD-1, pembrolizumab
(Keytruda) and nivolumab (Opdivo), are now approved to
treat advanced melanoma.
Melanoma vaccines: These are experimental therapies
that have not yet been proven to be helpful.
CONCLUSION
Skin cancer is the most common malignancy in the
United Kingdom and Ireland.5 Malignant melanoma
is the most deadly cutaneous neoplasm. Numerous
risk factors for development of melanoma have been
identified, including white skin, fair hair, light eyes, sun
sensitivity and a tendency to freckle. Other factors,
include family history of melanoma, dysplastic nevi,
increased numbers of typical nevi, large congenital
nevi and immunosuppression. Although sun exposure
is a risk factor for melanoma, cutaneous melanomas
can also arise in areas of the body not exposed to the
sun. Sun exposure in childhood and having more than
one blistering sunburn in childhood are associated
with an increased risk of melanoma.6 Most melanomas
arise as superficial tumors confined to the epidermis.
The prognosis for melanoma is closely related to the
thickness of the tumour. In order to effectively treat
melanomas, drugs that target proteins that normally
suppresses the T-cell immune response or block ones
that help them evade the immune system provide
the best chance for treating patients with advanced
melanoma. In early studies, combination drugs have
shrunk tumors in about one half of pateints with
melanoma. AM