PIIS174868151000416X

Journal of Plastic, Reconstructive & Aesthetic Surgery (2010) 63, 1401e1419
Revised UK guidelines for the management

of cutaneous melanoma 2010*,**
J.R. Marsden a,*, J.A. Newton-Bishop b, L. Burrows c, M. Cook d,
P.G. Corrie e, N.H. Cox a, M.E. Gore f, P. Lorigan g, R. MacKie h,
P. Nathan i, H. Peach j, B. Powell k, C. Walker a
a
University Hospital Birmingham, Birmingham B29 6JD, United Kingdom
b
University of Leeds, Leeds LS9 7TF, United Kingdom
c
Salisbury District Hospital, Salisbury SP2 8BJ, United Kingdom
d
Royal Surrey County Hospital NHS Trust, Guildford GU2 7XX, United Kingdom
e
Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, United Kingdom
f
Royal Marsden Hospital, London SW3 6JJ, United Kingdom
g
The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
h
University of Glasgow, Glasgow G12 8QQ, United Kingdom
i
Mount Vernon Hospital, London HA6 2RN, United Kingdom
j
St James’s University Hospital, Leeds LS9 7TF, United Kingdom
k
St George’s Hospital, London SW17 0QT, United Kingdom
KEYWORDS Summary These guidelines for the management of cutaneous melanoma present an
Evidence; evidence-based guidance for treatment, with identification of the strength of evidence avail-
Guideline; able at the time of preparation of the guidelines, and a brief overview of epidemiology, diag-
Investigation; nosis, investigation, and follow-up.
Melanoma; ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons and British
Treatment Association of Dermatologists. All rights reserved.
*
This is an updated guideline prepared for the British Association of Dermatologists (BAD) Clinical Standards Unit, made up of the Therapy &
Guidelines Subcommittee (T&G) and the Audit & Clinical Standards Subcommittee (A&CS). Members of the Clinical Standards Unit are: HK Bell
[Chairman T&G], LC Fuller [Chairman A&CS], NJ Levell, MJ Tidman, PD Yesudian, J Lear, J Hughes, AJ McDonagh, S Punjabi, N Morar, S Wagle
[British National Formulary], SE Hulley [British Dermatological Nursing Group], KJ Lyons [BAD Scientific Administrator], and MF Mohd Mustapa
[BAD Clinical Standards Manager].
These guidelines are published simultaneously in the British Journal of Dermatology (doi: 10.1111/j.1365-2133.2010.09883.x) and the Journal
of Plastic, Reconstructive & Aesthetic Surgery (doi:10.1016/j.bjps.2010.07.006).
**
Guidelines produced in 2002 by the British Association of Dermatologists; reviewed and updated, 2009.
* Corresponding author.
E-mail address: [email protected] (J.R. Marsden).
1748-6815/$ - see front matter ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons and British Association of Dermatologists. All rights reserved.
doi:10.1016/j.bjps.2010.07.006
1402 J.R. Marsden et al.
Guidelines review process and other publications were identified from the PubMed
searches, independent searches carried out by the authors,
These guidelines were initially reviewed at a multidisci- as well as materials collected by the authors as part of their
plinary meeting on 8 November 2007. Those attending were ongoing professional interest in the latest developments in
the authors plus: this clinical area. Levels of evidence to support the guide-
Dermatology: V Doherty, D Roberts, F Wojnarowska, lines are quoted according to the criteria stated in
H Bell, D de Berker, C Harwood, S Bailey, R Barlow, V Bataille, Appendix 1. The consultation process for British Association
L Rhodes of Dermatologists guidelines and their compliance with
Surgery: A Hayes, J Kenealy, G Perks, M Timmins guideline recommendations have been published else-
Specialist Nursing: H Williams, C McGarr, M Sherman, where.1,2 There are arguments in favour of newer guideline
J Davenport, C Wheelhouse grading methods, such as those of GRADE,3 but the authors
Histopathology: N Kirkham, H Rigby, J Theaker believe that the system used here allows greater potential
Imaging: J Smith, P Guest, A Dancey for consensus in areas of conflicting evidence or where
Oncology: N Steven, P Corrie, P Patel, A Goodman, evidence sources are not directly comparable. In some
C Kelly, P Lawton, A Dalgleish instances, this is not due to an absence of high quality
Lay representative: T Fay (Level Ib) trials but because different entry criteria or
Palliative Care: J Speakman, F Calman endpoints preclude direct comparison of results; in other
National Institute for Health and Clinical Excellence: cases interpretation of the clinical significance of results
N Summerton has been challenged. To assist production of unified
Scottish Intercollegiate Guidelines Network: S Qureshi guidelines taking account of these issues, the ‘quality of
Primary Care: P Murchie evidence’ grading used in these guidelines differs
slightly from that used in other British Association
of Dermatologists current guidelines; the strength of
Disclaimer recommendations grading is the same as used in many other
publications. Where no level is quoted the evidence is to be
These guidelines reflect the best published data available regarded as representing Level IV (i.e. a consensus
at the time the report was prepared. Caution should be statement).
exercised in interpreting the data; the results of future The intention of the working party was to agree best
studies may require alteration of the conclusions or recom- practice for the management of melanoma in the belief that
mendations in this report. It may be necessary or even this will promote good standards of care across the whole
desirable to depart from the guidelines in the interests of country. However, they are guidelines only. Care should be
specific patients and special circumstances. Just as adher- individualised wherever appropriate. These guidelines will
ence to the guidelines may not constitute defence against be revised as necessary to reflect changes in practice in light
a claim of negligence, so deviation from them should not be of new evidence.
necessarily deemed negligent.
Integration with national cancer guidance
Contribution to these guidelines has been made by a large
number of clinicians. They have also been endorsed by, or
Multidisciplinary care of the patient is held to be the most
have had input from, representatives of the following groups
desirable model as recommended in the Calman/Hine
or organisations: the UK Melanoma Study Group, the British
report.4 This has been defined by the National Institute for
Association of Dermatologists, the British Association of
Health and Clinical Excellence Improving Outcomes Guidance
Plastic, Reconstructive and Aesthetic Surgeons, the Royal
for People with Skin Tumours Including Melanoma (NICE
College of Physicians, London, the Association of Cancer
IOG).5 Core services will be provided within each Cancer
Physicians, the Royal College of Radiologists, London, the
Network by Local Skin Cancer Multidisciplinary Teams
Royal College of Surgeons, England, the Royal College
(LSMDTs). Specialist services will be provided by Specialist
of Pathologists (pathology section only), the Royal College of
Skin Cancer Multidisciplinary Teams (SSMDTs). For melanoma
General Practitioners, London, and the Department of
there is a clear demarcation of care such that more advanced
Health.
primary melanoma, rare subtypes of melanoma, melanoma in
These consensus guidelines have been drawn up by
children, and patients eligible for trial entry or sentinel lymph
a multidisciplinary working party with membership drawn
node biopsy should be promptly referred for investigation and
from a variety of groups and coordinated by the United
treatment from an LSMDT to an SSMDT (Table 1).
Kingdom Melanoma Study Group (UKMSG), and the British
Association of Dermatologists. The guidelines deal with
aspects of the management of melanoma from its preven-
tion, through the stages of diagnosis and initial treatment Prevention of melanoma
to palliation of advanced disease.
PubMed literature searches for this guidelines revision Individuals, and particularly children, should not get sunburnt
were carried out to identify publications from 2000 to April (Level I).6e9 Meta-analysis of case-control studies provides
2010, with search terms including: melanoma genetics, good evidence that melanoma is predominantly caused by
epidemiology, early diagnosis, risk factors, clinical intermittent intense sun exposure; fair-skinned individuals
features, pathology, surgery, chemotherapy and clinical should therefore limit their recreational exposure through
trials. Relevant materials were also isolated from reviews life (Level I).10 People with freckles, red or blond hair, skin
Revised UK guidelines for the management of cutaneous melanoma 2010 1403
Table 1 Melanoma patients who must be referred from a Local Skin Cancer Multidisciplinary Team to a Specialist Skin Cancer
Multidisciplinary Team (SSMDT) (NICE IOG 2006).5
Patients with melanoma managed by other site specialist teams (e.g. gynaecological, mucosal and head and neck
(excluding ocular))
Patients with stage IB or higher primary melanoma when sentinel lymph node biopsy (SLNB) is available within their
Network. In the absence of SLNB then patients with stage IIB or higher should be referred to the SSMDT (American Joint
Committee on Cancer (AJCC) staging system)
Patients with melanoma at any stage who are eligible for clinical trials that have been approved at cancer network level
Patients with multiple primary melanomas
Children and young adults under 19 years with melanoma
Any patient with metastatic melanoma diagnosed at presentation or on follow-up
Patients with giant congenital naevi where there is suspicion of malignant transformation
Patients with skin lesions of uncertain malignant potential
which burns in the sun, increased numbers of naevi, and those Lesions which are suspicious for melanoma should not be
with a family history of melanoma are at increased risk and removed in primary care. This is because clinico-pathological
should heed this advice. correlation is vital for diagnostic accuracy, which in turn
Adequate sun exposure to allow vitamin D synthesis, or determines prognosis and defines adjuvant treatment
sufficient dietary intake of vitamin D3, is essential to human options, and because diagnostic surgery requires specialist
health; insufficiency of vitamin D is now recognised to be training. Early recognition of melanoma presents the best
common.11 It would therefore be inappropriate to greatly opportunity for cure 15,19e22 (Level III, Grade A).
limit sun exposure in people without the risk factors listed All patients presenting with an atypical melanocytic
above. Recent studies have shown that in UK vitamin D levels lesion or a large number of moles should have a complete
are often suboptimal in melanoma patients, and are lower in skin examination and assessment of risk factors. The der-
fair-skinned people.12,13 Fair-skinned people who avoid the moscope is a useful tool for the trained clinician screening
sun rigorously to reduce the risk of melanoma should consider pigmented lesions, as it can increase diagnostic accuracy.23
supplementing their intake of vitamin D3 in the absence of It is also useful for monitoring multiple pigmented lesions
medical contraindications. where photography of dermoscopic images provides a record
There is evidence from a recent meta-analysis that sun- of change (Level Ia, Grade A). Recommendations for LSMDT
bed usage does increase the risk of melanoma, particularly record-keeping of clinical features are proposed in Table 2.
under the age of 35 years, and therefore it is recommended
that this should be avoided (Level Ia).14 Screening and surveillance of high-risk individuals
Referral and clinical diagnosis
There are some individuals at higher risk of melanoma who
should be considered for referral to specialist clinics. These
Melanoma remains relatively uncommon and therefore the individuals can be divided broadly into two groups based
opportunity to develop diagnostic skills is limited in primary upon the degree of risk:
care. All lesions suspicious of melanoma should be referred
urgently under the 2-week rule to local screening services
usually run by dermatologists. In England and Wales, this
would be to an LSMDT. In Scotland, referral should be made to
a local Rapid Access Cancer Clinic according to Scottish
Cancer Referral Guidelines. The seven-point checklist or the Table 2 Recommendations for Local Skin Cancer Multi-
ABCD rule may be helpful in the identification of melanomas disciplinary Team record-keeping of clinical features.
although they are more sensitive than specific.15e18 Urgent As a minimum the following should be included:
referral to the LSMDT is indicated where there is: History (the presence or absence of these changes
should be recorded)
A new mole appearing after the onset of puberty which Duration of the lesion
is changing in shape, colour or size Change in size
A long-standing mole which is changing in shape, colour Change in colour
or size Change in shape
Any mole which has three or more colours or has lost its Symptoms (itching, bleeding, etc.)
symmetry Examination
A mole which is itching or bleeding Site
Any new persistent skin lesion especially if growing, if Size (maximum diameter)
pigmented or vascular in appearance, and if the diag- Elevation (flat, palpable, nodular)
nosis is not clear Description (irregular margins, irregular pigmentation
A new pigmented line in a nail especially where there is and if ulceration is present)
associated damage to the nail (Level III, Grade B)
A lesion growing under a nail.
1. Individuals at moderate increased risk (approximately 8498-cc94b378312a.pdf. Recommendations for screening and
8e10 times that of the general population) should be surveillance of high-risk individuals are summarised in Table 3.
counselled about this risk and taught how to self-
examine for changing naevi, but long-term follow-up is
not usual. Such patients are those with either a previous Biopsy of suspected melanoma
primary melanoma, or large numbers of moles some of
which may be clinically atypical (Level Ia, Grade B).24e28 A lesion suspected to be melanoma, or where melanoma
Organ transplant recipients are also at this level of needs to be excluded, should be photographed, and then
increased risk (Level III, Grade B).29,30 excised completely. The axis of excision should be
2. Those at greatly increased risk of melanoma (more orientated to facilitate possible subsequent wide local
than 10 times that of the general population). Patients excision; generally on the limb this will be along the long
with a giant congenital pigmented hairy naevus (defini- axis. If uncertain, direct referral to the multidisciplinary
tions include ‘20 cm or more in diameter’ and ‘5% of team (MDT) will allow appropriate planning for future
body surface area’) should be monitored by an expert for surgery. The excision biopsy should include the whole
their lifetime because of the risk of malignant change, tumour with a clinical margin of 2 mm of normal skin, and
which is significant but poorly quantified (Level III, Grade a cuff of fat. This allows confirmation of the diagnosis by
B).31,32 Excision biopsy of suspicious areas in large examination of the entire lesion, such that subsequent
congenital naevi may be necessary but requires expert definitive treatment can be based on Breslow
histopathological review. Patients with a strong family thickness.35e37
history of melanoma are also at greatly increased risk. In Diagnostic shave biopsies should not be performed since
some families, most clearly in mainland Europe and they may lead to incorrect diagnosis due to sampling error,
North America, families at risk of melanoma are also at and make accurate pathological staging of the lesion
increased risk of pancreatic cancer.33 Those with three impossible (Level III). For the same reasons partial removal
or more cases of melanoma or pancreatic cancer in the of naevi for diagnosis must be avoided and partial removal
family should be referred to appropriate clinics of a melanocytic naevus may result in a clinical and
managing inherited predisposition to cancer (involving pathological picture very like melanoma (pseudomela-
dermatologists and/or clinical geneticists) for counsel- noma). This gives rise to needless anxiety and is avoidable.
ling. It is the consensus of the Melanoma Genetics Incisional or punch biopsy is occasionally acceptable, for
Consortium (www.genomel.org) that it is premature to example in the differential diagnosis of lentigo maligna
suggest gene testing routinely but this may change as (LM) on the face or of acral melanoma, but there is no
more is known of the genes predisposing to melanoma.34 place for either incisional or punch biopsy outside the skin
The risk to families associated with the presence of two cancer MDT (Level III). It is acceptable in certain circum-
family members affected with melanoma is lower. In stances to excise the lesion entirely but without repair,
these families, if affected individuals also have the and to dress the wound while awaiting definitive
atypical mole syndrome, or if there is a history of pathology.
multiple primary melanomas in an individual or pancre- Biopsies of possible subungual melanomas should be
atic cancer, then referral should also be made for carried out by surgeons regularly doing so. The nail should
counselling; otherwise family members should probably be removed sufficiently for the nail matrix to be adequately
be considered at moderately increased risk. sampled: clinically obvious tumour should be biopsied if
present.
All of the above individuals at increased risk of melanoma Prophylactic excision of naevi, or of small (<5 cm
should be advised on the specific changes that suggest mela- diameter) congenital naevi in the absence of suspicious
noma and encouraged to undertake monthly skin self-exami- features is not recommended (Level III, Grade D).
nation (Level III, Grade B). Close-up and distant photography Full clinical details should be supplied on the histopa-
may be a useful adjunct to detecting early melanoma in either thology form, including history of the lesion, relevant
of these high-risk groups (Level III). They should be given previous history, site and differential diagnosis. All mela-
written information and access to images of moles and melanocytic lesions excised for whatever reason must be sent
nomas. Such images are available at: www.genomel.org or for histopathological review to the pathologist associated
www.rcplondon.ac.uk/pubs/contents/f36b1656-cc74-4867- with the LSMDT or SSMDT.
Table 3 Recommendations for screening and surveillance of high-risk individuals.

Patients who are at moderately increased risk of melanoma should be advised of this and taught how to self-examine. This
includes patients with atypical mole phenotype, those with a previous melanoma, and organ transplant recipients (Level Ia,
Grade B).
Patients with giant congenital pigmented naevi are at increased risk of melanoma and require long-term follow-up (Level
IIIa, Grade B).
Individuals with a family history of three or more cases of melanoma, or of pancreatic cancer, should be referred to
a clinical geneticist or specialised dermatology services for counselling. Those with two cases in the family may also benefit,
especially if one of the cases had multiple primary melanomas or the atypical mole phenotype (Level IIa, Grade B).
The diagnosis of melanoma, both in situ and invasive, melanomas 1.0 mm.40,41 It should be recorded as
should be given or supervised by doctors who have number of mitoses per mm2 in the area of greatest
received advanced communication skills training, number of mitoses in the vertical growth phase (VGP).
following local policies for breaking bad news. A skin It has prognostic value at all thicknesses.
cancer trained nurse should be present to provide
continuing support. Histologic subtypes. Desmoplastic melanoma with or
without neurotropism should be recorded because of its
Histopathology different biological behaviour and clinical outcome.42
The subtypes superficial spreading, nodular, lentigo
General comments maligna and acral lentiginous melanomas have good
clinico-pathological correlation, but their prognostic
The Royal College of Pathologists has produced a minimum value has not been established.
dataset which should be included in the histopathology
report.38 Double reporting is recommended for all mela- Margins of excision. This indicates whether excision is
nomas and all naevi showing severe dysplasia if resources complete and the minimum margin of excision to peripheral
allow this to be achieved within 14 days.5 and deep aspects measured in millimetres. If the excision
or re-excision is not complete, whether the tumour is in
situ or invasive at the resection margin should be indicated.
The histopathology report When possible a statement should be made of whether the
lesion is primary or secondary melanoma.
The report should include the following:
Pathological staging. Staging using TNM and AJCC (Table 4),
Clinical information and coding, e.g. SNOMED, should be given.41
Site of the tumour Growth phase. Invasive melanoma without a vertical

Type of surgical procedure: excision or re-excision, growth phase (VGP) is termed microinvasion.43 The
incision biopsy, punch biopsy assessment of microstaging criteria should be applied to
Any other relevant clinical information the VGP only.
Regression. The presence or absence of tumour regression

Macroscopic description has not been shown consistently to affect long-term
outcome. Until its relevance is clear it should be reported
Contour, colour and size of the tumour and the excised skin as segmental replacement of melanoma by fibrosis, since
specimen in millimetres. this is subject to less observer variation.44
Microscopy Tumour infiltrating lymphocytes (TILs). It remains unclear

whether TILs have prognostic value.40 The categories
absent, non-brisk and brisk are subject to wide observer
Presence or absence of ulceration. Ulceration has prog- variation. ‘Absent’ indicates no lymphocytes infiltrating
nostic value, and its presence should be confirmed micro- among the tumour cells, but does not exclude
scopically as full-thickness loss of epidermis with reactive lymphocytes in the surrounding dermis. ‘Non-brisk’ is
changes which include a fibrinous exudate and attenuation a patchy or discontinuous infiltrate either among the
or acanthosis of the adjacent epidermis. These distinguish peripheral cells or in the centre of the tumour, whereas
true ulceration from artefact.39 ‘brisk’ is a continuous infiltrate but may be confined to
peripheral cells. These are qualified as mild, moderate or
Thickness. The tumour should be measured from the severe in intensity.
granular layer of the overlying epidermis to the deepest
cells in the dermis judged to be malignant, to the nearest Lymphatic or vascular invasion. Vascular or lymphatic
0.1 mm. Ulcerated tumours should be measured from the infiltration has prognostic value, and its presence should be
base of the ulcer. Tumour forming a sheath around recorded even though it is infrequently observed.45
appendages should be excluded when measuring thickness
except when the melanoma extends out into the adjacent Perineural infiltration. Perineural infiltration occurring
reticular dermis when it should be measured in the beyond the main bulk of the tumour correlates with
conventional manner. In the presence of histological increased local recurrence. It is most commonly associated
regression thickness measurements should be of the with desmoplastic melanoma.46
residual melanoma. Microsatellites should not be included Microsatellites. These are defined as islands of tumour
in thickness measurements (Level III, Grade B). >0.05 mm in the tissue beneath the main invasive mass of
melanoma, but separated from it by 0.3 mm of normal
Mitotic count. The number of mitoses has prognostic collagen (i.e. not tumour stroma or sclerosis of regres-
value and is now included in the American Joint sion).47 Current AJCC staging also requires that satellites
Committee on Cancer (AJCC) staging system for must be intralymphatic, which has not previously been
Table 4 The 2009 American Joint Committee on Cancer (AJCC) staging system.
Stage Primary tumour (pT) Lymph nodes (LN) Metastases (M)
IA <1 mm, no ulceration, mitosis
<1/mm2
IB <1 mm, with ulceration or
mitoses 1/mm2*
1.01e2 mm, no ulceration
IIA 1.01e2 mm with ulceration
2.01e4 mm, no ulceration
IIB 2.01e4 mm, with ulceration
>4 mm, no ulceration
IIC >4 mm, with ulceration
IIIA Any Breslow’s thickness, no Micro-metastases 1e3 nodes
ulceration
IIIB Any Breslow’s thickness, with Micro-metastases 1e3 nodes
ulceration
Any Breslow’s thickness, no 1e3 palpable metastatic nodes
ulceration
Any Breslow’s thickness, no No nodes, but in-transit or
ulceration satellite metastasis/es
IIIC Any Breslow’s thickness, with Up to 3 palpable lymph nodes
ulceration
Any Breslow’s thickness, with 4 or more nodes or matted
or without ulceration nodes or in-transit disease
þ lymph nodes
Any Breslow’s thickness, with No nodes, but in-transit or
ulceration satellite metastasis/es
IV, M1a Skin, subcutaneous or distal
nodal disease
IV, M1b Lung metastases
IV, M1c All other sites or any other sites
of metastases
with raised lactate
dehydrogenase
* In the rare circumstances where mitotic count cannot be accurately determined, a Clark level of invasion of either IV or V can be used
to define T1b melanoma. Every patient with melanoma should be accurately staged using the AJCC system; this may include performing
a sentinel lymph node biopsy when this is recommended by the Specialist Skin Cancer Multidisciplinary Team. Staging should be updated
following relapse.
required; this may be subject to revision. Microsatellites Equivocal lesions

are predictive of regional lymph node metastases; this is
reflected by stage N2c. It may not be possible to distinguish pathologically between
a melanoma and a benign melanocytic lesion. Such patients
Precursor naevus. The presence of contiguous melanocytic must be referred to the SSMDT for clinical and pathological
naevus should be recorded. review. A decision to treat as a melanoma should be made
by the SSMDT in discussion with the patient. Thickness
Clark level of dermal invasion. This is a less reliable indi- should be measured as for melanoma.
cator of prognosis than thickness and is subject to poor
observer agreement. It is not used to define T1 melanomas Sentinel lymph node pathology
in the 2009 AJCC staging system, except that Clark levels IV
or V may be used for defining T1b melanoma in rare Pathological assessment
instances when mitotic count cannot be determined in This needs to be done in a standardised way so that findings
a non-ulcerated T1 melanoma. between centres are comparable (Level III, Grade B).
Requirements for microscopy of melanoma Dissection

The dissection should be either by bivalving or multiple
These are given in Table 5. slicing, although the former is recommended.48e50
sentinel lymph nodes and/or distant metastases in patients

Table 5 Requirements for microscopy of melanoma.
with primary melanoma 53e58 (Level IIa, Grade E).
Ulceration Growth phase
Thickness Regression
Mitotic counta Tumour-infiltrating Sentinel lymph node biopsy and ultrasound/fine
Histologic subtype lymphocytes needle aspiration cytology
Margins of excision Lymphatic or
Pathological staging vascular invasion Sentinel lymph node biopsy (SLNB), as discussed later, has
Perineural invasion high sensitivity and specificity for diagnosing subclinical
Microsatellitesb regional lymph node involvement.
a Ultrasound and fine needle aspiration cytology (FNAC) is
Mitotic count is included in the 2009 AJCC staging system.
b
Microsatellites are not included in thickness measurement.
the next best method but quoted sensitivities range from
4.7% to 80%, with the higher sensitivities being achieved
only by sentinel node mapping and FNAC of the sentinel
node in all cases regardless of morphological appear-
A minimum of six serial sections should be taken, but ance.59e62 Further staging by CT imaging following a posi-
a higher incidence of metastases is detected by extended tive sentinel lymph node, and prior to completion
step sectioning with immunohistochemistry at each level. lymphadenectomy, has a very low yield.63e65 Consequently
The clinical relevance of the smaller metastases detected this should be done only after discussion with an informed
by these extended procedures is still unclear. patient and the SSMDT (Level IIa, Grade D).
Staining Stage III and IV melanoma

Use of haematoxylin and eosin and immunohistochemistry
is essential. S100 and Melan A are most favoured immuno- In stage III and IV melanoma, imaging strategies will be
histochemical stains but a composite method such as Pan- planned by the SSMDT.
Mel is also appropriate. CT scanning of the head, chest, abdomen and pelvis will
normally adequately exclude metastases, and is most
Assessment of tumour burden relevant in stage III melanoma before planning regional
This gives additional prognostic information. The following lymph node dissection and regional chemotherapy. If
are recommended: patients are considering entry to an adjuvant study
Assessing the depth of the metastasis from the inner following lymphadenectomy, the timing of scans should be
aspect of the sentinel lymph node capsule; categorising the determined by the SSMDT to avoid duplication.
metastasis according to its site, either subcapsular or When stage IV disease is suspected clinically, CT scan-
parenchymal; measuring the maximum dimension of the ning of the head and whole body should be considered.
largest confluent group of melanoma cells.50e52 Further imaging will be determined by symptoms, clinical
trial protocols, and for clarification or reassessment of
Completion lymphadenectomy specimens previous imaging findings. Generally, the added yield of
The pathological examination of regional nodes dissected PET/CT is unlikely to be clinically relevant in established
following positive sentinel lymph node biopsy should stage IV melanoma (Level III, Grade D). Where meta-
include an attempt to examine all lymph nodes at least at stasectomy is planned, PET/CT may be useful in excluding
one level, and count the number involved. The presence of disease that might make surgery inappropriate. Serum
extracapsular spread and involvement of perinodal fat lactate dehydrogenase (LDH) should be done in all patients
should be recorded, together with the size of the tumour- with suspected stage IV melanoma.
free margin. The use of immunohistochemistry such as S100 There is no indication for a bone scan in staging except
or Melan A facilitates this. where symptoms point to possible bone disease. Staging
investigations are summarised in Table 6.
Investigations and imaging
Treatment of the primary lesion
Stage I and II melanoma
Surgery is the only curative treatment for melanoma.
Routine investigations are not required for asymptomatic Following excision for diagnosis and for measurement of
patients with primary melanoma. Blood tests are unhelpful. microscopic Breslow thickness, a wider and deeper margin
Routine computed tomography (CT) is not recommended is taken to ensure complete removal of the primary lesion,
for patients with stage I and II melanoma as this has a very and to remove any micro metastases. The depth of the
low incidence of true-positive and high incidence of false- therapeutic excision has conventionally been to the muscle
positive findings. Patients with particularly high-risk fascia or deeper, and there is no evidence to support
primary melanoma may undergo staging investigations if altering this approach.
deemed appropriate by the SSMDT and/or as a pre-requisite Lateral surgical excision margins for invasive melanoma
to trial entry. There is no indication for routine imaging depend on Breslow thickness and are based on five rando-
with any other modality including plain X-ray, position mised controlled trials (RCTs) including about 3300
emission tomography (PET)/CT and magnetic resonance patients, and a National Institutes of Health Consensus
imaging (MRI). PET/CT is not effective in detecting positive Panel.66e73 However, only one of these studies is
difficult to detect. Topical treatment with imiquimod is

Table 6 Staging investigations for melanoma.
as yet of unproven value so should only be used in the
Patients with stage I, II, and IIIA melanoma should not context of a clinical trial.82 If the patient with LM is
routinely be staged by imaging or other methods as the treated by non-surgical means then the reason for this
true positive pick-up rate is low and the false-positive choice should be discussed and clearly documented by
rate is high (Level IIa, Grade E). the MDT.
Patients with stage IIIB or C should be imaged by CT of Local recurrence of LM occurs in about 5% of patients by
head, chest, abdomen and pelvis prior to surgery after 2 years.77 Excision with micrographic control of surgical
SSMDT review (Level IIa, Grade A). margins should be considered, although histological clear-
Patients with stage IV melanoma should be imaged ance is often difficult to define.83 In situ melanoma on acral
according to clinical need and SSMDT review. Lactate and genital skin is also associated with a higher risk of local
dehydrogenase should also be measured (Level III, recurrence, but this is less common in other types of in situ
Grade A). melanoma. In theory, in situ melanoma should not meta-
SSMDT, Specialist Skin Cancer Multidisciplinary Team. stasise, but occasional cases do recur. This may be due to
histological regression obscuring a more advanced tumour,
missed microinvasion, or progression after incomplete
adequately powered, and two provide little scope for removal of in situ disease.
detecting reduced disease-free or overall survival due to
narrow margins.68,69,71 Most exclude melanoma on the head Melanoma up to 1.0 mm Breslow thickness
and neck and/or extremities.74 A recent systematic review
estimated overall survival in favour of wide excision
There have been three RCTs of patients with melanomas
(hazard ratio 1.04; 95% confidence interval 0.95e1.15;
in this thickness band.66,68,69,73 The recommended surgical
P Z 0.40), although the difference was not significant.
margins are based on the World Health Organisation
Therefore a small, but potentially important, difference in
(WHO) Melanoma Co-operative Group Trial 10.66,73 This
overall survival between wide and narrow excision margins
randomised trial compared 1 cm and 3 cm margins for
cannot be confidently ruled out. Current randomised trial
melanomas up to 2 mm thick. No local metastases, and
evidence is insufficient to address optimal excision margins
similar overall survival, were seen in patients with mela-
for primary cutaneous melanoma.75
nomas < 1 mm in depth with either excision margin.
The recommended surgical margins are those measured
However, this was based on analysis of data from only 359
clinically at the time of surgery, but adequacy of excision
patients. The French and Swedish studies compared 2 cm
should be subsequently confirmed by review of re-excision
with 5 cm margins, and the latter only included patients
histology, making an adjustment for average shrinkage of
with melanomas 0.8 mm or more in thickness in this
20%.76 The final decision about the size of the margin should
group.68,69 A 1 cm margin is deemed safe for this group
be made by the MDT, after discussion with the patient. The
(Level Ib, Grade A).
recommendation should be made with consideration of
functional and cosmetic implications of the margin chosen.
Melanoma 1.01e2.0 mm Breslow thickness
All patients with primary melanoma stage IB and higher
should be referred before treatment to an SSMDT when this
provides a SLNB service. When the SSMDT does not provide There have been four randomised studies that have
this, all primary melanomas stage IIB or IIC should be included patients in this category. The WHO study showed
referred. There are no RCT data for margin size for LM or a small excess of local metastasis as first site of relapse in
other in situ melanoma. the 1 cm margins group.66,73 There was no difference in
overall survival between 1 and 3 cm margins but the study
was inadequately powered to detect this. The Intergroup
Lentigo maligna and in situ superficial Melanoma Trial compared 2 vs. 4 cm margins of excision for
spreading melanoma lesions of 1e4 mm in thickness.67,70 No difference was seen
between the two groups in either local recurrence or
LM and other in situ melanomas have no potential for survival. Two other studies have included patients with
metastatic spread and the aim should be to excise the melanomas up to 2 mm, also treated with either 2 or 5 cm
lesion completely with a clear histological margin, although margins.68,69 There was no difference in outcome between
margin size remains undefined. No further treatment is the groups. The 1 vs. 3 cm, 2 vs. 4 cm, and 2 vs. 5 cm
then required. studies cannot be directly compared, but no study using
LM is best treated by complete excision because of 2 cm margins as one comparator has shown any advantage
the risk of subclinical microinvasion. This may be missed of wider margins than this. However, narrower margins
on incisional biopsy due to sampling error.73 The risk of trials have either not been performed (e.g. 1 vs. 2 cm
progression to invasive melanoma is poorly quantified, margins) or have been underpowered, and do not permit
and in the very elderly may be unlikely within their a definite conclusion that a 1 cm margin is adequate.
lifespan. Therefore, for some particular clinical situa- Evidence to date shows that a minimum margin of 1 cm is
tions, treatment by other methods such as radiotherapy, required, although 2 cm margins are equally appropriate.
or observation only, may be appropriate.77e81 There is The final decision will be determined by anatomical site,
little evidence to support the use of cryotherapy, and MDT review, and after discussion with an informed patient
this treatment may make subsequent progression (Level Ib, Grade A).
Melanoma 2.01e4.0 mm Breslow thickness surgical treatment planning and investigations can run in
parallel. There is no place for elective lymph node dissec-
The Intergroup Melanoma Trial showed no difference in tion in the management of primary melanoma unless this is
rates of local metastasis between patients treated with unavoidable because the primary melanoma lies over the
2 cm and those treated with 4 cm margins.67 However, lymph node basin (Level Ib, Grade A). Patients should have
longer follow-up showed reduced overall survival in the access to a skin cancer specialist nurse when relapse is
2 cm margins group, although this fell just short of reaching suspected.
statistical significance.70 The results of a randomised trial
with 3 cm margins showed significantly increased rates of Clinically node-negative patients
locoregional recurrence in patients treated with 1 cm
margins, and a reduction in melanoma-specific survival, SLNB was developed as a means of identifying the first
again just short of significance, although no difference in lymph node draining the skin in which the melanoma ari-
overall survival.71 The significance of this is unclear, and ses.84 The procedure is carried out at the same time as
the 2 vs. 4 cm and 1 vs. 3 cm trials cannot be directly definitive wider excision of the primary melanoma.85 SLNB
compared. Until the resulting uncertainty is resolved, gives information about prognosis, and is increasingly used
which may not happen as the number of patients required in conjunction with adjuvant therapy clinical trials.
to detect a difference between 2 and 3 cm margins is Patients with melanoma of Breslow thickness 1.2e3.5 mm
considerable, the default position should be to minimise and a positive SLNB have a 75% 5-year survival compared
locoregional and distant metastatic risk. Therefore with 90% if the SLNB is negative.86 SLNB is normally
a minimum 2 cm margin is required in this group, although considered for patients with melanoma 1 mm, when
3 cm margins are equally appropriate. The final decision about 20% are positive; however the risk of a positive SLNB
will be determined by anatomical site, need for skin in a melanoma <1.0 mm is still 5%.86,87 The procedure is
grafting, MDT review, and after discussion with an informed associated with a 5% morbidity, which is less than that seen
patient (Level Ib, Grade A). with complete nodal dissection. In patients with a positive
SLNB, 20% have pathological evidence of metastases in
Melanoma greater than 4 mm in thickness additional regional nodes.84 Patients with a positive SLNB
usually choose to proceed to completion lymphadenec-
The risk of locoregional and distant metastasis is 50% or more tomy. In about 5% it is not possible to identify the sentinel
in this group. Nonetheless, the same surgical objectives apply node either on lymphoscintigraphy, at surgery, or both.
to minimise locoregional and distant metastatic risk. There is Patients should be aware of this limitation. The relevance
only one randomised study which includes melanomas thicker of increasingly detailed evaluation of the sentinel node and
than 4 mm.71 This trial compared 1 cm with 3 cm margins. The its correlation with prognosis remains to be defined.88
results show a significant increase in locoregional recurrence MSLT-1 showed no overall 5-year survival benefit following
when 1 cm margins are used, and a reduction in melanoma- SLNB and completion lymphadenectomy, and it is unclear
specific survival just short of significance, although no whether SLNB improves local control of lymph node
difference in overall survival. As there are no data that basins.85,86 A final report with longer follow-up is awaited.
margins smaller than 3 cm are as effective, the evidence Recommendations for the management of clinically
suggests 3 cm margins for this group. There is no evidence that node-negative patients are summarised in Table 8.
margins greater than 3 cm are required. The final decision will
be determined by anatomical site, need for skin grafting, MDT Management of patients with clinically or
review, and after discussion with an informed patient (Level
Ib, Grade B).
radiologically suspicious lymph nodes
Recommended surgical excision margins are summarised
in Table 7. FNAC of nodes is recommended when there is clinical doubt
about the significance of the nodes. If there is a negative
FNAC result but ongoing suspicion, then the FNA should be
Management of lymph node basins repeated or an image-guided core biopsy arranged.
Open biopsy is recommended when there is clinical
Investigation and management of lymph node basins in suspicion even in the presence of negative FNACs in which
melanoma patients should be carried out by SSMDTs so that lymphocytes have been successfully aspirated. If open
Table 7 Recommended surgical excision margins.

Breslow thickness Excision margins Level of evidence Grading of evidence
In situ 5 mm margins to achieve III B
complete histological
excision
<1 mm 1 cm Ib A
1.01e2 mm 1e2 cm Ib A
2.1e4 mm 2e3 cm Ib A
>4 mm 3 cm Ib B
A single positive superficial inguinal sentinel node

Table 8 Recommendations for the management of clini-
(Level Ib, Grade A).
cally node-negative patients.
There is no role for elective lymph node dissection A pelvic LND should be considered in the presence of:
(Level I, Grade E)
Sentinel node biopsy can be considered in stage IB
More than one 1 clinically palpable inguinal and/or
melanoma and upwards in SSMDTs (Level Ia, Grade A)
femoral triangle node/s
Patients should be introduced to the concept of SLNB as
CT or ultrasound evidence of more than one inguinal
a staging procedure but should also understand that it
and/or femoral triangle node/s, or of pelvic node
has no proven therapeutic value
involvement
Surgical risks of SLNB, the possibility of failure to find
More than one microscopically involved node at SLNB
a SLN, and of a false-negative result, should also be
A conglomerate of inguinal or femoral triangle lymph
explained
nodes
SNLB, sentinel lymph node biopsy Microscopic or macroscopic involvement of Cloquet’s
node (Level III, Grade B).
biopsy is performed, the incision must be such as to allow Cervical nodal recurrence should be treated by either
subsequent complete formal block dissection of the surgeons in the SSMDT specialising in head and neck skin
regional nodes without compromise. It should only be done cancer including melanoma or by a head and neck MDT with
by SSMDT members.5 a special interest in melanoma.5 A comprehensive, and not
Exploration or removal of a mass within a nodal basin a selective, neck dissection should be performed (Level III,
which drains a known primary melanoma site, and prior to Grade A). The term ‘comprehensive’ allows either:
definitive surgical treatment, may increase the risk of
melanoma recurrence in that basin.89 Any melanoma patient A radical dissection of levels 1e5
who develops a mass in a nodal basin should be referred Modified radical e the above, sparing spinal accessory
urgently to the SSMDT, and without prior investigation, for nerve, internal jugular vein and sternocleidomastoid
investigation and treatment planning (Level III, Grade B). muscle
Extended radical e radical dissection including parotid
Management of patients with confirmed and/or posterior occipital chain.
positive lymph node metastasis The risk of further locoregional recurrence is 16e32%
despite comprehensive surgery.101,102
Radical lymph node dissections (LNDs) should only be per-
formed by SSMDT members who do a combined minimum of
15 axillary and groin block dissections for skin cancer each Locoregional recurrent melanoma: skin
year.5,90 and soft tissues
Preoperative staging investigations should be carried out
as already discussed for stage III melanoma. If such staging Surgery is the treatment of choice for single local or
is not feasible prior to surgery, and surgery is considered regional metastases. Excision should be clinically and
necessary even if distant metastatic disease were to be histologically complete, but a wide margin is not
detected, then a chest X-ray and LDH is recommended. required. Multiple small (<1 cm) dermal lesions respond
The block dissection specimen should be marked and well to treatment with the CO2 laser.103 Dermal disease
orientated for the pathologist. Axillary LND for melanoma which is progressing despite surgery or laser, and
should include all nodes in levels IeIII, and this may require subcutaneous or deeper limb metastases, should be
either resection or division of pectoralis minor. The considered for regional chemotherapy with isolated limb
management of inguinal lymph node metastases is contro- infusion (ILI) with melphalan and actinomycin D, or with
versial. Between 30% and 44% of patients with clinically isolated limb perfusion (ILP) 104,105 (Level IIb, Grade B).
involved superficial inguinal nodes will have involved pelvic ILI is less invasive than ILP, and can be more easily
nodes, and the risk increases with the number of involved repeated, but may be less effective.105 ILI is suitable for
superficial nodes.91e97 If Cloquet’s node is positive the risk patients with low volume (<5 cm) disease and those with
of pelvic node involvement ranges from 44% to 90%.93,96,97 co-morbidities which prevent ILP. Patients with bulky
There is no reported increased morbidity associated with disease (>5 cm) may be more likely to benefit from ILP
combined pelvic and superficial node dissection.94 using melphalan with tumour necrosis factor, but
Following ilioinguinal dissection for palpable inguinal a recent trial comparing this combination with melphalan
disease 5-year survival varies with extent of pelvic alone did not confirm additional benefit from adding
involvement: 49% with one pelvic node, 28% with two to TNF.106 Radiotherapy may be considered for disease
three nodes, and 7% with more than three nodes.97e100 which cannot otherwise be controlled. Selected patients
suitable for ILI/ILP should be referred to specialised
A superficial inguinal LND should be considered in the
centres. The role of electrochemotherapy using intrale-
presence of:
sional or systemic bleomycin is still being evaluated.
A single clinically involved inguinal node or femoral Recommendations for locoregional recurrent melanoma
triangle node are given in Table 9.
lymphadenectomy.110 Eligible patients were 1 parotid, 2

Table 9 Recommendations for locoregional recurrent
cervical or axillary or 3 groin nodes, or extra nodal spread
melanoma.
of tumour, or node diameter 3 cm in neck or axilla or
Nodes clinically suspicious for melanoma should be 4 cm in the groin. Interim results show a 15% improvement
sampled using fine needle aspiration cytology (FNAC) in local control following radiotherapy, but there was no
prior to carrying out formal block dissection. If FNAC is effect on overall survival. There are no data yet on
negative although lymphocytes were seen, a core or morbidity following this treatment, and so at present the
open biopsy should be performed if suspicion remains risk:benefit of adjuvant radiotherapy is unclear. If there is
(Level III, Grade B) clinical or histological doubt about the adequacy of surgery
Prior to lymph node dissection, performed by an following recurrence, or about the feasibility of salvage
expert,5 staging by CT scan should be carried out other surgery, adjuvant radiotherapy may be considered by the
than where this would mean undue delay (Level III, SSMDT (Level Ib, Grade B).
Grade B)
The treatment of locoregional recurrence in a limb is
palliative. Surgical excision, CO2 laser, or isolated limb Occult primary melanoma
infusion or perfusion may be considered (Level IIb,
Grade B) Patients with occult primary melanoma may present with
a solitary metastasis, lymph node disease, or systemic
disease. Such patients should be referred promptly to the
SSMDT for investigation and treatment planning. All
Adjuvant therapy patients should have a thorough examination of the skin.
Occult primary uveal tract melanoma nearly always causes
There is no evidence of a survival benefit for adjuvant liver metastases before these are apparent at other sites;
chemotherapy in patients with melanoma.107 This includes searching for a uveal tract primary in a patient with occult
adjuvant regional chemotherapy using ILP, and therefore nodal disease is not appropriate. For patients presenting
ILI.108 with inguinal lymphadenopathy, examination of the genital
Interferon has been evaluated in low-, intermediate- and urinary tracts, and ano rectum is especially relevant.
and high-risk patients using various doses and schedules. A All patients should be staged with CT scans of head, chest,
recent individual patient data meta-analysis concluded abdomen and pelvis. A number of reports from institution-
that interferon was associated with a significant impact on based series suggest that patients presenting with stage III
relapse-free survival and a small effect on overall survival disease from an unknown primary have a better prognosis
(5-year survival benefit 3%, P < 0.05).109 However, the than patients with a similar stage and a known
benefit was seen across all interferon regimens, and was primary.111,112 One published series suggested a survival
greatest in those with ulcerated melanomas. There was no advantage in patients with stage IV disease from an
clear indication as to optimum dose or duration. The results unknown primary compared with those with a declared
are awaited of further analysis including more recent data. primary.113
Interferon is not recommended as standard of care for Patients presenting with lymph node disease from an
adjuvant therapy of primary or stage III melanoma (Level occult primary involving a single lymph node basin, should
Ia, Grade A). This is because its effect on disease-free be presumed to have regional rather than distant metas-
survival is of uncertain clinical relevance, and although tasis, and treated as for stage III disease with lymph node
overall survival is improved in meta-analysis, the effect is block dissection.
small and associated with significant drug toxicity.
Prospective studies are required to establish whether Metastatic disease
a subset of patients who derive most benefit can be
identified.
All patients should have access to a skin cancer clinical
Clinical trials of adjuvant melanoma vaccines have not
nurse specialist and a palliative care team providing
so far been successful.
expertise in symptom control and psychosocial support.
Patients should be offered entry into adjuvant clinical
Links should be made with community cancer support
trials approved by the local Cancer Network. They should
networks as soon as possible. All patients with metastatic
have access to a melanoma specialist who is conversant
disease should have access to an oncologist specialising in
with current melanoma adjuvant trials, and who is able to
melanoma for management advice.
ensure their access to such studies. Details may be found on
Selected patients who relapse with oligometastatic
the websites of the National Cancer Research Network, and
disease may benefit from metastatectomy. Although this
the European Organisation for Research and Treatment of
has not been evaluated in a prospective randomised trial,
Cancer.
median survival of 21 months for selected surgically treated
patients has been reported 114e119 (Level IIb, Grade B).
Adjuvant radiotherapy No systemic therapy has been shown to extend survival
significantly. Dacarbazine is a standard chemotherapy
The Tasmanian Radiation Oncology Group (TROG) has outside a clinical trial, although its benefits are limited,
completed a randomised study of adjuvant radiotherapy to and it is ineffective in brain metastases (Level IIa, Grade C).
dissected nodal basins, 48 Gy in 20 fractions, in 250 patients The oral dacarbazine derivative temozolomide has greater
with a high (>25%) risk of local recurrence following central nervous system (CNS) penetration but has not
shown significant clinical advantages over dacarbazine in There is no medical reason to justify delaying conception
two multicentre clinical trials.120,121 Biochemotherapy (the after a diagnosis of melanoma (Level IIa) but the social and
addition of biologically active agents such as interferon- family effects of developing recurrent melanoma during
a and interleukin-2 to chemotherapy) increases response pregnancy or after birth are great.127,130 It is proper there-
rates and toxicity but does not significantly increase overall fore to counsel a woman in the reproductive age range about
survival.122 The same is true for combination chemo- her risk of recurrence over time so that she and her partner
therapy, and so this is not recommended other than in can make their decision about conception with adequate
highly selected patients in whom palliation is dependent information. These social or family considerations may also
upon maximising response in symptomatic deposits. High be relevant to a male patient whose partner is pregnant or if
dose interleukin-2 has not been evaluated in a randomised he and his partner are considering a pregnancy.
phase III trial although a small minority of patients may There is no evidence that the use of the oral contra-
experience durable complete responses.123 ceptive pill plays any role in the natural history of mela-
Patients with elevated LDH have a reduced likelihood of noma (Level Ia).130e133 Decisions about the use of the
benefiting from currently available systemic treatment. contraceptive pill should be made on the basis of health
Given the limited benefits with standard systemic therapy, issues other than melanoma.
all patients with metastatic melanoma should be consid- There is no evidence that hormone replacement therapy
ered for entry into clinical trials of novel therapies. plays any role in the natural history of melanoma,130,132
Patients with CNS metastases have a poor prognosis. neither does it worsen prognosis in stage I and II mela-
Surgery or stereotactic radiotherapy should be considered noma (Level IIa).133 Decisions about use of hormone
for selected patients with limited disease.114,115,124e126 replacement therapy should be made on the basis of health
The benefits of treating patients with cerebral metas- issues other than melanoma.
tases with whole brain radiotherapy are limited, but may In pregnancy, staging using X-rays should be avoided
sometimes have palliative value. Supportive care is where possible, especially in the first trimester. MRI should
therefore the most appropriate strategy for many patients be used in preference to CT scan, where feasible.
(Level IIb, Grade B). Because chemotherapy does not have a survival benefit
Spinal cord compression should be treated surgically if in stage IV disease its use in pregnancy requires careful
feasible, but multiple sites of disease, poor prognosis and discussion. Use of chemotherapy agents in the first
poor performance status may make this inappropriate. trimester should be avoided. There are case reports of the
Radiotherapy may be useful for palliation of rapidly successful birth of normal babies who were exposed to
enlarging or painful metastases involving soft tissues and dacarbazine in utero later in pregnancy, but this does not
bones (Level IIb, Grade B). exclude later toxicity. Melanoma can metastasise to the
Recommendations for metastatic disease are shown in placenta and to the fetus more frequently than any other
Table 10. solid tumour. This has a poor prognosis for both mother and
baby. At delivery in patients with stage IV melanoma the
Melanoma, hormone replacement therapy placenta should be examined for melanoma.
Recommendations regarding pregnancy and hormone
and pregnancy
replacement therapy are summarised in Table 11.
There is no evidence that melanoma at or near the time of
Use of drugs in melanoma patients
pregnancy adversely affects prognosis.127 Breslow thick-
ness, site and presence of ulceration are still the key
There are theoretical reasons to suggest that L-DOPA may
determinants of outcome, and are not different from
have an adverse effect on patients with melanoma. There
a control population.128,132 The outcomes of pregnancy for
are no data to support this idea however, and such an
both mother and baby are not worsened (Level IIa).128,129
association seems unlikely.134 The use of immunosuppres-
Surgical treatment should be determined in the normal
sants after melanoma is a cause for concern. The results of
way, but the risks of exposure to ionising radiation and blue
a recent cohort study of patients with rheumatoid arthritis
dye during sentinel node biopsy will need special
consideration.
Table 11 Recommendations regarding pregnancy and
Table 10 Recommendations for metastatic disease. hormone replacement therapy.
All patients should be managed by Specialist Skin Pregnancy with primary melanoma
Cancer Multidisciplinary Teams.5 No worsening of prognosis
Surgery should be considered for oligometastatic No increase in adverse outcomes for mother or baby
disease at sites such as the skin, brain or bowel (Level Pregnancy in advanced melanoma
IIb, Grade B), or to prevent pain or ulceration. Placental and fetal metastases possible in stage IV
Radiotherapy may have a palliative role in the treat- disease
ment of metastases (Level II, Grade B). Oral contraceptives and melanoma
Standard chemotherapy is dacarbazine although its role No increased risk of melanoma
is palliative (Level II, Grade C). Hormone replacement therapy
Patients with stage IV melanoma should be considered No increased risk of melanoma
for entry to clinical trials. No worsening of prognosis
treated with biologic agents showed an increased risk of Care can be shared with primary care, but only if the
melanoma (odds ration 2.3, 95% confidence interval secondary care team has defined and explained to the primary
0.9e5.4).135 However, there is usually little that can be done care team what is required, and only if the primary care team
to avoid these drugs without an unacceptable loss of quality are prepared to accept responsibility for this. In the event of
of life. Their use after treatment of primary or secondary suspected recurrence, even after discharge from follow-up, it
melanoma should be discussed between the prescribing is recommended that the patient contact the secondary care
doctors and patients, and the decision to continue their use team directly to avoid possible delay in diagnosis.
and their dosage should be subject to ongoing review Screening asymptomatic clinically normal patients with
following a diagnosis of melanoma (Level III, Grade C). lymph node ultrasound is sensitive and can detect nodal
disease, but this has not been shown to be useful in primary
Organ and blood donation melanoma follow-up.142 The same applies to CT and PET
imaging. These investigations should not be used outside
The decision about whether organs or tissue are suitable for a clinical trial.
transplant is made on an individualised basis, taking into
account the patient’s medical history.136 A melanoma In situ melanoma
patient would not normally be considered as a donor.
Patients with a surgically treated single in situ melanoma
Follow-up do not require follow-up, as there is no risk of metastasis.
They require a return visit after complete excision to
There are three main reasons for follow-up after treatment explain the diagnosis, cheque the whole skin for further
of primary cutaneous melanoma. The first is to detect primary melanoma/s, and to teach self-examination for
recurrence when further treatment can improve the prog- a new primary melanoma. Clinical nurse specialist support
nosis, the second is to detect further primary melanomas may be required despite the absence of metastatic risk.
and the third is to provide support, information, and
education. The proportion of patients with melanoma who Stage IA melanoma
have impaired health-related quality of life is comparable
to other cancers, and their needs for psychosocial support Patients with invasive primary cutaneous melanoma
are likely to be similar.137 Provision of this is an important <1.0 mm have a 5-year disease-free survival of over 90% or
part of MDT management.138 There are no RCTs which have better. A recent review of 430 patients with melanomas
formally evaluated follow-up. Numerous follow-up regi- <0.5 mm showed no recurrences at 5e15 years follow-up
mens have been reviewed but few are evidence- but 4% of patients developed a second primary melanoma
based.139e141 Sixty-two percent of all recurrences were over this period.143 Patients with invasive, non-ulcerated
detected by patients themselves in one review, but defi- primary tumours 0.5e1.0 mm thick have only slightly worse
nition of patient or doctor detection is unclear and other 5-year disease-free survival, and are in the same stage
series emphasise the importance of physician-detected group. Therefore, for stage IA patients a series of two to
recurrence.134 Patient opinion was equally divided as to four visits over up to 12 months is suggested to teach self-
whether follow-up visits were reassuring or provoked examination, and then they may be discharged from regular
further anxiety. There is little evidence of survival advan- follow-up (Level III, Grade B).
tage following self-detection of metastases.139e141 Most
first relapses occur in the 5 years following diagnosis, but Stage IB and IIA melanoma
there is a significant risk of later first relapse; both patients
and their doctors should be aware of this. This group are at 15e35% risk of recurrence, but most of
A primary melanoma follow-up clinic should be provided this risk is in years 2e4. Once they have learnt how to self-
by an MDT of dermatologists and surgeons with clinical nurse examine for locoregional metastasis and new primaries,
specialist support, and there should be continuity of care. and understand how to promptly access the follow-up team
Patients should be taught to self-examine to detect locore- for suspected recurrence, they should be seen every 3
gional recurrence and new primary melanoma. Photography months for 3 years, then 6-monthly to 5 years. No routine
can be useful for follow-up of patients who also have atyp- investigations are required (Level III, Grade B).
ical moles. Patients should routinely be examined for
locoregional and distant metastases, and the whole skin
should be checked for new primary melanomas. A defined Stage IIB and IIC melanoma
rapid-access pathway must be provided to all patients and
GPs for suspected recurrence. Suspected new primary This group are at 40e70% risk of recurrence. Most of this risk is
melanoma should be referred as normal through the 2-week in years 2e4. They should be taught self-examination and
wait system. For Scotland this needs to be compliant with seen 3-monthly for 3 years, and 6-monthly to 5 years. No
the 62-day rule. Follow-up of patients with AJCC stage III and routine investigations are required (Level III, Grade B).
IV disease should be led by melanoma SSMDTs.
Follow-up intervals and duration should be tailored to Sentinel lymph node biopsy
the stage group of the primary melanoma and therefore to
the risk of recurrence. The follow-up plan should be agreed Patients who have had a negative SLNB should be followed
between the patient and the responsible doctors. up on the basis of Breslow thickness.
Most patients who have had a positive SLNB will have had Improving Outcomes Guidance for People with Skin
a completion lymphadenectomy. As these patients now Tumours including Melanoma; February 2006, available
have at least stage IIIA disease, their follow-up should be at: www.nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/
supervised by the SSMDT, and entry into appropriate trials pdf]
considered. Risk of recurrence depends on the extent of 2. Comparison and appropriateness of stated clinical, and
sentinel lymph node involvement, and may be less than for measured histological, surgical margins [referenced to
some with stage II melanoma. They should be followed up the standards described in these guidelines]
as for stages IBeIIC melanoma (Level III, Grade B). 3. Use of investigations at diagnosis in primary melanoma
by stage grouping [referenced to the standards
Stage IIIB, IIIC, and resected stage IV melanoma described in these guidelines]
The risk of further metastasis in this group is high. Many will Acknowledgements
be eligible for adjuvant trials. Those outside trials should be
seen 3-monthly for 3 years from the date of staging, 6- The authorship team would like to acknowledge the
monthly to 5 years, then annually to 10 years by an SSMDT. contribution to these guidelines made by the late Dr Neil
Investigations should be carried out on the basis of clinical Cox. Neil worked tirelessly to improve care for patients,
need, and may include CT surveillance if considered appro- and his clear thinking, expert knowledge and generous
priate by the SSMDT. This might be used to monitor a site nature were invaluable to us. We shall miss him greatly.
considered at high risk of relapse. The SSMDT will need to
balance the use of follow-up investigations for this group
against the need for early detection of further stages III and
IV disease. Early detection facilitates both effective treat- Conflicts of interest
ment and trial entry (Level III, Grade B).
None declared.
Unresectable stage IV melanoma
References
These patients should be followed up and investigated by
the SSMDT according to clinical need. They may be eligible 1. Griffiths CE. The British Association of Dermatologists’
for clinical trials. guidelines for the management of skin disease. Br J Dermatol
1999;141:396e7.
2. Cox NH, Williams HC. The British Association of dermatolo-
Clinical trials gists therapeutic guidelines: can we AGREE? Br J Dermatol
2003;148:621e5.
Many patients will be in clinical trials. These will have 3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging
defined follow-up intervals which should be adhered to. consensus on rating quality of evidence and strength of
Follow-up for melanoma is detailed in Table 12. recommendations. Br Med J 2008;336:924e6.
4. Calman K, Hine D. Report by the Advisory Group on Cancer
Services to the Chief Medical Officers of England and Wales.
Table 12 Follow-up for melanoma. Department of Health/Welsh Office; 1995.
Patients with in situ melanomas do not require follow- 5. National Institute for Health and Clinical Excellence (NICE).
up Improving Outcomes Guidance for People with Skin Tumours
including Melanoma, www.nice.org.uk/nicemedia/pdf/CSG_
Patients with invasive melanomas have differing risk of
Skin_Manual/pdf; February 2006 (last accessed 25.05.10).
relapse according to their stage group
6. Marks R, Whiteman D. Sunburn and melanoma: how strong is
Patients with stage IA melanoma should be seen two to the evidence? Br Med J 1994;308:75e6.
four times over up to 12 months, then discharged 7. Whiteman D, Green A. Melanoma and sunburn. Cancer Causes
Patients with stage IBeIIIA melanoma should be seen 3- Control 1994;5:564e72.
monthly for 3 years, then 6-monthly to 5 years 8. Armstrong BK. Epidemiology of malignant melanoma: inter-
Patients with stage IIIB and IIIC and resected stage IV mittent or total accumulated exposure to the sun? J Dermatol
melanoma should be seen 3-monthly for 3 years, then 6- Surg Oncol 1988;14:835e49.
monthly to 5 years, then annually to 10 years 9. Armstrong B, Kricker A. Sun exposure causes both non-
Patients with unresectable stage IV melanoma are seen melanocytic skin cancer and malignant melanoma. Proc
Environ UV Radiat Health Effects; 1993:106e13.
according to need
10. Gandini S, Sera F, Cattaruzza MS, et al. Meta-analysis of risk
(Level III, Grade B)
factors for cutaneous melanoma: III. Family history, actinic
damage and phenotypic factors. Eur J Cancer 2005;41:2040e59.
11. Holick MF. High prevalence of vitamin D inadequacy and
Audit points implications for health. Mayo Clin Proc 2006;81:353e73.
12. Newton-Bishop J, Beswick S, Randerson-Moor J, et al. Serum
25-hydroxyvitamin D3 levels are associated with Breslow
The following are suggested points for audit: thickness at presentation, and survival from melanoma. J Clin
Oncol 2009;27:5439e44.
1. Timeliness and appropriateness of referral from LSMDT to 13. Randerson-Moor JA, Taylor JC, Elliott F, et al. Vitamin D
SSMDT [referenced to the standard described in National receptor gene polymorphisms, serum 25-hydroxyvitamin D
Institute for Health and Clinical Excellence (NICE) levels and melanoma: UK case-control comparisons and
a meta-analysis of published VDR data. Eur J Cancer 2009;45: 35. Lederman JS, Sober AJ. Does biopsy type influence survival in
3271e81. clinical stage I cutaneous melanoma? J Am Acad Dermatol
14. International Agency for Research on Cancer Working Group on 1985;13:983e7.
Artificial Ultraviolet Light and Skin Cancer. The association of 36. Lees VC, Briggs JC. Effect of initial biopsy procedure on
use of sunbeds with cutaneous melanoma and other skin prognosis in stage I invasive cutaneous malignant melanoma:
cancers: a systematic review. Int J Cancer 2007;120:1116e22. review of 1086 patients. Br J Surg 1991;78:1108e10.
15. McGovern TW, Litaker MS. Clinical predictors of malignant 37. Austin JR, Byers RM, Brown WD, et al. Influence of biopsy on
pigmented lesions. A comparison of the Glasgow seven-point the prognosis of cutaneous melanoma of the head and neck.
checklist and the American Cancer Society’s ABCDs of pig- Head Neck 1996;18:107e17.
mented lesions. J Dermatol Surg Oncol 1992;18:22e6. 38. Association of Directors of Anatomic and Surgical Pathology.
16. Abbasi NR, Shaw HM, Rigel DS, et al. Early diagnosis of cuta- Recommendations for the reporting of tissues removed as
neous melanoma: revisiting the ABCD criteria. J Am Med Assoc part of the surgical treatment of cutaneous melanoma. Pathol
2004;292:2771e6. Int 1998;48:168e70.
17. MacKie RM. Clinical Dermatology. 5th ed. Oxford University 39. Spatz A, Cook M, Elder D, et al. Interobserver reproducibility
Press; 2003. p. 345e346. of ulceration assessment in primary cutaneous melanomas.
18. Du Vivier AWP, Williams HC, Brett JV, et al. How do malignant Eur J Cancer 2003;39:1861e5.
melanomas present and does this correlate with the seven- 40. Gimotty PA, Guerry D, Ming ME, et al. Thin primary cutaneous
point check-list? Clin Exp Dermatol 1991;16:344e7. malignant melanoma: a prognostic tree for 10-year metastasis
19. Cox NH, Madan V, Sanders T, et al. skin cancer ‘two-week is more accurate than American Joint Committee on Cancer
rule’ proforma: assessment of potential modifications to staging. J Clin Oncol 2004;22:3668e76.
improve referral accuracy. Br J Dermatol 2008;158:1293e8. 41. Edge SE, Byrd DR, Compton CC, et al., editors. Melanoma of
20. Melia J, Cooper EJ, Frost T, et al. Cancer research campaign the skin. AJCC Cancer Staging Manual. 7th ed. New York, NY:
health education programme to promote the early detection Springer; 2009.
of cutaneous malignant melanoma. I. Work-load and referral 42. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic
patterns. Br J Dermatol 1995;132:405e13. melanoma: a pathologically and clinically distinct form of
21. Melia J. Early detection of cutaneous malignant melanoma in cutaneous melanoma. Ann Surg Oncol 2005;12:207e13.
Britain. Int J Epidemiol 1995;24:S39e44. 43. Elder DE, Murphy GF. Malignant Tumours (Melanoma and
22. MacKie RM, Hole D, Hunter JAA, et al. Cutaneous malignant Related Lesions). Armed Forces Institute of Pathology; 1990.
melanoma in Scotland: incidence, survival, and mortality, p. 103e205.
1979e94. The Scottish Melanoma Group. Br Med J 1997;315: 44. Kaur C, Thomas RJ, Desai N, et al. The correlation of
1117e21. regression in primary melanoma with sentinel lymph node
23. Braun RP, Oliviero M, Kolm I. Dermoscopy: what’s new? Clin status. J Clin Pathol 2008;61:297e300.
Dermatol 2009;27:26e34. 45. Straume O, Akslan LA. Independent prognostic importance of
24. Melia J. Changing incidence and mortality from cutaneous vascular invasion in nodular melanoma. Cancer 1996;78:1211e9.
malignant melanoma. Br Med J 1997;315:1106e7. 46. Quinn MJ, Crotty KA, Thomson JP, et al. Desmoplastic and
25. Parkin DM, Muir CS. Cancer incidence in five continents: desmoplastic neurotropic melanoma experience with 280
comparability and quality of data. IARC Sci Publ 1992;120: patients. Cancer 1998;83:1128e35.
45e173. 47. Harrist TJ, Rigel DS, Day Jr CL, et al. Microscopic satellites are
26. Rhodes AR, Weinstock MA, Fitzpatrick TB, et al. Risk factors more highly associated with regional lymph node metastases
for cutaneous melanoma. A practical method of recognizing than is primary melanoma thickness. Cancer 1984;53:2183e7.
pre-disposed individuals. J Am Med Assoc 1987;258:3146e54. 48. Cook MG, Di Palma S. Pathology of sentinel lymph nodes for
27. Newton JA, Bataille V, Griffiths K, et al. How common is the melanoma. J Clin Pathol 2008;61:897e902.
atypical mole syndrome phenotype in apparently sporadic 49. Cochran AJ. Surgical pathology remains pivotal in the evaluation
melanoma? J Am Acad Dermatol 1993;29:989e96. of ‘sentinel’ lymph nodes. Am J Surg Pathol 1999;23:1169e72.
28. Bataille V, Newton Bishop JA, Sasieni P, et al. Risk of cuta- 50. Starz H, Balda BR, Kramer KU, et al. A micromorphometry-
neous melanoma in relation to the numbers, types and sites of based concept for routine classification of sentinel lymph
naevi: a case-control study. Br J Cancer 1996;73:1605e11. node metastases and its clinical relevance for patients with
29. Le Mire L, Hollowood K, Gray D, et al. Melanomas in renal melanoma. Cancer 2001;91:2110e21.
transplant recipients. Br J Dermatol 2006;154:472e7. 51. Dewar DJ, Newell B, Green MA, et al. The microanatomic
30. Brown VL, Matin RN, Cerio R, et al. Melanomas in renal location of metastatic melanoma in sentinel lymph nodes
transplant recipients: the London experience and invitation predicts nonsentinel lymph node involvement. J Clin Oncol
to participate in a European study. Br J Dermatol 2007;156: 2004;22:3345e9.
165e7. 52. van Akkooi AC, de Wilt JH, Verhoef C, et al. The Rotterdam
31. Marghoob AA, Schoenbach SP, Kopf AW, et al. Large congen- criteria for sentinel node tumor load: the simplest prognostic
ital melanocytic nevi and the risk for the development of factor? J Clin Oncol 2008;26:2011.
malignant melanoma. A prospective study. Arch Dermatol 53. Basseres N, Grob JJ, Richard MA, et al. Cost-effectiveness of
1996;132:170e5. surveillance of stage I melanoma. A retrospective appraisal
32. Illig L, Weidner F, Hundeiker M, et al. Congenital nevi less based on a 10-year experience in a dermatology department
than or equal to 10 cm as precursors to melanoma: 52 cases, in France. Dermatology 1995;191:199e203.
a review, and a new conception. Arch Dermatol 1985;121: 54. Khansur T, Sanders J, Das SK. Evaluation of staging workup in
1274e81. malignant melanoma. Arch Surg 1989;124:847e9.
33. Goldstein AM, Chan M, Harland M, et al. High-risk melanoma 55. Yancovitz M, Finelt N, Warycha MA, et al. Role of radiologic
susceptibility genes and pancreatic cancer, neural system imaging at the time of initial diagnosis of stage T1b-T3b
tumors, and uveal melanoma across GenoMEL. Cancer Res melanoma. Cancer 2007;110:1107e14.
2006;66:9818e28. 56. Maubec E, Lumbroso J, Masson F, et al. F-18 fluorodeoxy-D-
34. Leachman SA, Carucci J, Kohlmann W, et al. Selection criteria glucose positron emission tomography scan in the initial
for genetic assessment of patients with familial melanoma. J evaluation of patients with a primary melanoma thicker than
Am Acad Dermatol 2009;61:677.e1e677.e14. 4 mm. Melanoma Res 2007;17:147e54.
57. Clark PB, Soo V, Krass J, et al. Futility of fluorodeoxyglucose F 76. Silverman MK, Golomb FM, Kopf AW, et al. Verification of
18 positron emission tomography in initial evaluation of a formula for determination of pre-excision surgical margins
patients with T2 to T4 melanoma. Arch Surg 2006;141:284e8. from fixed-tissue melanoma specimens. J Am Acad Dermatol
58. Wagner JD, Schauwecker D, Davidson D, et al. Prospective 1992;27:214e9.
study of fluorodeoxyglucose positron emission tomography 77. Preston P, Matey P, Marsden JR, et al. Surgical treatment of
imaging of lymph node basins in melanoma patients undergoing lentigo maligna using 2 mm excision margins. Br J Dermatol
sentinel lymph node biopsy. J Clin Oncol 1999;17:1508e15. 2003;149:109e10.
59. van Rijk MC, Teertstra HJ, Peterse JL, et al. Ultrasonography 78. Mahendran RM, Newton-Bishop JA. Survey of U.K. current
and fine-needle aspiration cytology in the preoperative practice in the treatment of lentigo maligna. Br J Dermatol
assessment of melanoma patients eligible for sentinel node 2001;144:71e6.
biopsy. Ann Surg Oncol 2006;13:1511e6. 79. Schmid-Wendtner MH, Brunner B, Konz B, et al. Fractionated
60. Sibon C, Chagnon S, Tchakérian A, et al. The contribution of radiotherapy of lentigo maligna and lentigo maligna mela-
high-resolution ultrasonography in preoperatively detecting noma in 64 patients. J Am Acad Dermatol 2000;43:477e82.
sentinel-node metastases in melanoma patients. Melanoma 80. Tsang RW, Liu FF, Wells W, et al. Lentigo maligna of the head
Res 2007;17:233e7. and neck. Results of treatment by radiotherapy. Arch Der-
61. Starritt EC, Uren RF, Scolyer RA, et al. Ultrasound examination matol 1994;130:1008e12.
of sentinel nodes in the initial assessment of patients with 81. Pitman GH, Kopf AW, Bart RS, et al. Treatment of lentigo
primary cutaneous melanoma. Ann Surg Oncol 2005;12:18e23. maligna and lentigo maligna melanoma. J Dermatol Surg
62. Voit C, Kron M, Schäfer G, et al. Ultrasound-guided fine Oncol 1979;5:727e37.
needle aspiration cytology prior to sentinel node biopsy in 82. Rajpar S, Marsden JR. Imiquimod in the treatment of lentigo
melanoma patients. Ann Surg Oncol 2006;13:1682e9. maligna. Br J Dermatol 2006;155:653e6.
63. Aloia TA, Gershenwald JE, Andtbacka RH, et al. Utility of 83. Walling HW, Scupham RK, Bean AK, et al. Staged excision
computed tomography and magnetic resonance imaging staging versus Mohs micrographic surgery for lentigo maligna and len-
before completion lymphadenectomy in patients with sentinel tigo maligna melanoma. J Am Acad Dermatol 2007;57:659e64.
lymph node-positive melanoma. J Clin Oncol 2006;24:2858e65. 84. Morton DL, Wen DR, Wong JH, et al. Technical details of
64. Horn J, Lock-Anderson J, Sjøstrand H, et al. Routine use of intraoperative lymphatic mapping for early stage melanoma.
FDG-PET scans in melanoma patients with positive sentinel Arch Surg 1992;127:392e9.
node biopsy. Eur J Nucl Mol Imaging 2006;33:887e92. 85. Morton D, Thompson J, Cochrane A, et al. Sentinel-node
65. Constantinidou A, Hofman M, O’Doherty M, et al. Routine biopsy or nodal observation in melanoma. N Engl J Med 2006;
positron emission tomography and emission tomography/- 355:1307e17.
computed tomography in melanoma staging with positive 86. Morton DL, Cochran AJ, Thompson JF, et al. Sentinel node biopsy
sentinel node biopsy is of limited benefit. Melanoma Res for early stage melanoma e Accuracy and morbidity in MSLT-1,
2008;18:56e60. an international multicentre trial. Ann Surg 2005;242:302e13.
66. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primary 87. Wright BE, Scheri RP, Ye X, et al. Importance of sentinel
cutaneous malignant melanoma. Comparison of excision with lymph node biopsy in patients with thin melanoma. Arch Surg
margins of 1 or 3 cm. N Engl J Med 1988;318:1159e62. 2008;143:892e9.
67. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2 cm 88. Li W, Stall A, Shivers SC, et al. Clinical relevance of molecular
surgical margins for intermediate-thickness melanomas staging for melanoma: comparison of RT-PCR and immuno-
(1e4 mm): results of a multi-institutional randomized surgical histochemistry staining in sentinel lymph nodes of patients
trial. Ann Surg 1993;218:262e7. with melanoma. Ann Surg 2000;231:795e803.
68. Cohn-Cedermark G, Rutqvist LE, Andersson R, et al. Long term 89. Nathansohn N, Schachter J, Gutman H. Patterns of recurrence
results of a randomized study by the Swedish Melanoma Study in patients with melanoma after radical lymph node dissec-
Group on 2 cm versus 5 cm resection margins for patients with tion. Arch Surg 2005;140:1172e7.
cutaneous melanoma with a tumor thickness of 0.8e2.0 mm. 90. National Cancer Peer Review Programme. Manual for Cancer
Cancer 2000;89:1495e501. Services 2008: Skin Measures. 08e2J-212. Available at:
69. Khayat D, Rixe O, Martin G, et al. Surgical margins in cuta- http://www.library.nhs.uk/integratedSearch/viewResource.
neous melanoma (2 cm versus 5 cm for lesions measuring less aspx?resID=299673 (last accessed 25.05.10)
than 2.1-mm thick). Long-term results of a large European 91. Karakousis CP, Emrich LJ, Rao U, et al. Groin dissection in
Multicentric Phase III study. Cancer 2003;97:1941e6. malignant melanoma. Am J Surg 1986;152:491e5.
70. Balch C, Soong SJ, Smith T, et al. Long term results of 92. Badgwell B, Xing Y, Gershenwald JE, et al. Pelvic lymph node
a prospective surgical trial comparing 2 cm vs. 4 cm excision dissection is beneficial in subsets of patients with node-posi-
margins for 740 patients with 1e4 mm melanomas. Ann Surg tive melanoma. Ann Surg Oncol 2007;14:2867e75.
Oncol 2001;8:101e8. 93. Finck SJ, Giuliano, Mann BD, et al. Result of ilioinguinal
71. Thomas J, Newton-Bishop J, A’Hern R, et al. Excision margins dissection for stage I melanoma. Ann Surg 1982;196:180e6.
in high-risk malignant melanoma. N Engl J Med 2004;350: 94. Sterne GD, Murray DS, Grimley RP. Ilioinguinal block dissec-
757e66. tion for malignant melanoma. Br J Surg 1995;82:1057e9.
72. NIH Consensus Conference. Diagnosis and treatment of early 95. Essner R, Scheri R, Kavanagh M, et al. Surgical management of
melanoma. J Am Med Assoc 1992;268:1314e9. the groin lymph nodes in melanoma in the era of sentinel
73. Veronesi U, Cascinelli N. Narrow excision (1 cm margin) e lymph node dissection. Arch Surg 2006;141:877e82.
a safe procedure for thin cutaneous melanoma. Arch Surg 96. Shen P, Conforti A, Essner R, et al. Is the node of cloquet the
1991;126:438e41. sentinel node for the iliac/obturator node group? The Cancer
74. Lens M, Nathan P, Bataille V. Excision margins for primary J 2000;6:93e7.
cutaneous melanoma: updated pooled analysis of randomized 97. Hughes TMD, A’Hern R, Thomas J, et al. Prognosis and surgical
controlled trials. Arch Surg 2007;142:885e91. management of patients with palpable inguinal lymph node
75. Sladden MJ, Balch C, Barzilai DA, et al. Surgical excision margins metastases from melanoma. Br J Surg 2000;87:892e901.
for primary cutaneous melanoma. Cochrane Database Syst Rev; 98. Karakousis CP, Driscoll DL. Positive deep nodes in the groin and
2009;. doi:10.1002/14651858.CD004835.pub2. CD004835. survival in malignant melanoma. Am J Surg 1996;171:421e2.
99. Balch CM, Ross MI. Melanoma patients with iliac nodal 120. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase
metastases can be cured. Ann Surg Oncol 1999;6:230e1. III study of temozolomide versus dacarbazine in the treatment
100. Strobbe LJA, Jonk A, et al. Positive iliac and obturator nodes of patients with advanced metastatic malignant melanoma.
in melanoma: survival and prognostic factors. Ann Surg Oncol J Clin Oncol 2000;18:158e66.
1999;6:255e62. 121. Patel P, Suciu S, Mortier L, et al. Extended schedule escalated
101. O’Brien CJ, Coates AS, Petersen-Schaefer K, et al. Experience dose temozolomide versus dacarbazine in stage IV malignant
with 998 cutaneous melanoma of the head and neck over 30 melanoma; final results of the randomised phase 3 study
years. Am J Surg 1991;182:86e91. (EORTC 18032). Ann Oncol 2009;19:viii3.
102. Turkula LD, Woods J. Limited or selective nodal dissection for 122. Ives NJ, Stowe RL, et al. Chemotherapy compared with bio-
malignant melanoma of the head and neck. Am J Surg 1984; chemotherapy for the treatment of metastatic melanoma:
148:446e8. a meta-analysis of 18 trials involving 2,621 patients. J Clin
103. Hill S, Thomas JM. Use of the carbon dioxide laser to manage Oncol 2007;25:5426e34.
cutaneous metastases from malignant melanoma. Br J Surg 123. Tarhini AA, Kirkwood JM, et al. Durable complete responses
1996;83:509e12. with high-dose bolus interleukin-2 in patients with metastatic
104. Thompson JF, Kam PC. Current status of isolated limb infusion melanoma who have experienced progression after bio-
with mild hyperthermia for melanoma. Int J Hyperthermia chemotherapy. J Clin Oncol 2007;25:3802e7.
2008;24:219e25. 124. Zacest AC, Besser M, Stevens G, et al. Surgical management
105. Beasley GM, Petersen RP, Yoo J, et al. Isolated limb infusion of of cerebral metastases from melanoma: outcome in 147
in-transit malignant melanoma of the extremity: a well- patients treated at a single institution over two decades.
tolerated but less effective alternative to hyperthermic iso- J Neurosurg 2002;96:552e8.
lated limb perfusion. Ann Surg Oncol 2008;15:2195e205. 125. Mori Y, Kondziolka D, Flickinger JC, et al. Stereotactic radi-
106. Cornett WR, McCall LM, Petersen RP, et al. Randomized osurgery for cerebral metastatic melanoma: factors affecting
multicenter trial of hyperthermic isolated limb perfusion with local disease control and survival. Int J Radiat Oncol Biol Phys
melphalan alone compared with melphalan plus tumor 1998;42:581e9.
necrosis factor: American College of Surgeons Oncology Group 126. Selek U, Chang E, Hassenbusch 3rd SJ, et al. Stereotactic radi-
Trial Z0020. J Clin Oncol 2006;24:4196e201. osurgical treatment in 103 patients for 153 cerebral melanoma
107. Veronesi U, Adamus J, Aubert C, et al. A randomised trial of metastases. Int J Radiat Oncol Biol Phys 2004;59:1097e106.
adjuvant chemotherapy and immunotherapy in cutaneous 127. Lens MB, Rosdahl I, Ahlbom A, et al. Effect of pregnancy on
melanoma. N Engl J Med 1982;307:913e6. survival in women with cutaneous malignant melanoma.
108. Koops HS, Vaglini M, Suciu S, et al. Prophylactic isolated limb J Clin Oncol 2004;22:4369e75.
perfusion for localized, high-risk limb melanoma: results of 128. O’Meara AT, Cress R, Xing G, et al. Malignant melanoma in
a multicenter randomized phase III trial. European Organi- pregnancy. A population-based evaluation. Cancer 2005;103:
zation for Research and Treatment of Cancer Malignant 1217e26.
Melanoma Cooperative Group Protocol 18832, the World 129. Daryanani D, Plukker JT, De Hullu JA, et al. Pregnancy and
Health Organization Melanoma Program Trial 15, and the early-stage melanoma. Cancer 2003;97:2248e53.
North American Perfusion Group Southwest Oncology Group- 130. Naldi L, Altieri A, Imberti GL, et al. Oncology study group of the
8593. J Clin Oncol 1998;16:2906e12. Italian Group for Epidemiologic Research in Dermatology
109. Wheatley K, Ives N, Eggermont A, et al. Adjuvant therapy for (GISED). Cutaneous malignant melanoma in women. Phenotypic
melanoma: an individual patient meta-analysis of randomised characteristics, sun exposure, and hormonal factors: a case-
trials. J Clin Oncol 2007;25:8526. control study from Italy. Ann Epidemiol 2005;15:545e50.
110. Henderson MA, Burmeister B, Thompson JF, et al. Adjuvant 131. Karagas MR, Stukel TA, Dykes J, et al. A pooled analysis of 10
radiotherapy and regional lymph node field control in melanoma case-control studies of melanoma and oral contraceptive use.
patients after lymphadenectomy: Results of an intergroup Br J Cancer 2002;86:1085e92.
randomized trial. J Clin Oncol 2009;27:18 [Suppl; abstr LBA9084]. 132. Lea CS, Holly EA, Hartge P, et al. Reproductive risk factors for
111. Chang P, Knapper WH. Metastatic melanoma of unknown cutaneous melanoma in women: a case-control study. Am J
primary. Cancer 1982;49:1106e11. Epidemiol 2007;165:505e13.
112. Lee CC, Faries MB, Wanek LA, et al. Improved survival after 133. MacKie RM, Bray CA. Hormone replacement therapy after
lymphadenectomy for nodal metastasis from an unknown surgery for stage I or II cutaneous melanoma. Br J Cancer
primary melanoma. J Clin Oncol 2008;26:535e41. 2004;90:770e2.
113. Lee CC, Faries MB, Wanek LA, et al. Improved survival for 134. Siple J, Schneider D, Wanlass W, et al. Levodopa therapy and
stage IV melanoma from an unknown primary site. J Clin risk of malignant melanoma. Ann Pharm 2000;34:382e5.
Oncol 2009;27:3489e95. 135. Wolfe F, Michaud K. Biologic treatment of rheumatoid
114. Patchell RA, Tibbs PA, Walsh JW, et al. A randomised trial of arthritis and the risk of malignancy: analyses from a large US
surgery in the treatment of single metastases of the brain. observational study. Arthritis Rheum 2007;56:2886e95.
N Engl J Med 1990;322:494e500. 136. NHS Blood and Transplant. Organ Donation: How to Become
115. Miller JD. Surgical excision for single cerebral metastasis? a Donor. www.organdonation.nhs.uk/ukt/how_to_become_
Lancet 1993;341:1566. a_donor/how_to_become_a_donor.jsp (last accessed
116. Sondak V, Liu P, Warneke J, et al. Surgical resection for stage 25.05.10).
IV melanoma: a Southwest Oncology Group Trial (S9430). 137. Cornish D, Holterhues C, van der Poll-Franse L, et al. A
J Clin Oncol 2006; 24(Suppl.): 8019 (Abstract). systematic review of health-related quality of life in cuta-
117. Overett TK, Shiu MH. Surgical treatment of distant meta- neous melanoma. Ann Oncol 2009;20(Suppl 6):51e8.
static melanoma. Indications and results. Cancer 1985;56: 138. Sollner W, Zschocke I, Augustin M. Melanoma patients:
1222e30. psychosocial stress, coping with illness and social support. A
118. Meyer T, Merkel S, Goehl J, et al. Surgical therapy for distant systematic review. Psychother Psychosom Med Psychol 1998;
metastases of malignant melanoma. Cancer 2000;89: 48:338e48.
1983e91. 139. Francken AB, Bastiannet E, Hoekstra HJ. Follow up in patients
119. Essner R, Lee GH, et al. Contemporary surgical treatment of with localized primary melanoma. Lancet Oncol 2005;6:
advanced-stage melanoma. Arch Surg 2004;139:961e7. 608e21.
140. Hofmann U, Szedlak M, Ritgen W, et al. Primary staging and Patients with giant congenital pigmented naevi are at
follow up in melanoma patients-monocenter evaluation of increased risk of melanoma and require long-term follow-
methods costs and patient survival. Br J Cancer 2002;87:151e7. up
141. Garbe C, Hauschild A, Volkenandt M, et al. Evidence and inter- The prophylactic excision of small congenital naevi is
disciplinary consensus-based German guidelines: diagnosis and
not recommended
surveillance of melanoma. Melanoma Res 2007;17:393e9.
142. Balfounta ML, Beauchet A, Chagnon S, et al. Ultrasonography
Individuals with a family history of three or more cases
or palpation for detection of melanoma nodal invasion: of melanoma should be referred to a Clinical Geneticist
a meta-analysis. Lancet Oncol 2004;5:673e80. or specialised dermatology services for counselling.
143. Einwachter-Thompson J, MacKie RM. An evidence base for Those with two cases in the family may also benefit,
reconsidering current follow-up guidelines for patients with especially if one of the cases had multiple primary
cutaneous melanoma less than 0.5 mm thick at diagnosis. Br J melanomas or the atypical mole syndrome
Dermatol 2008;159:337e41.
Requirements for microscopy of melanoma
Summary of 2010 guidelines for management
of melanoma Essential Ulceration Thickness Mitotic count
Histological Margins of Pathological
(See full manuscript for details of evidence and recom- subtype excision staging
mendation gradings)
Desirable Level of dermal Growth phase Regression
Melanoma patients who must be referred from the invasion
Local Skin Cancer Multidisciplinary Team to the Tumour infiltrating Lymphatic or
Specialist Skin Cancer Multidisciplinary Team lymphocytes vascular invasion
Perineural Microsatellites
Patients with stage IB or higher primary melanoma when invasion
sentinel lymph node biopsy (SLNB) is available within
their Network. In the absence of SLNB then patients with
Surgical wider excision margins for primary
stage IIB or higher should be referred to the SSMDT
melanoma
Patients with melanoma stage I or above who are
eligible for clinical trials that have been approved at
Cancer Network level Breslow thickness Lateral excision margins
Patients with melanoma managed by other site to muscle or muscle fascia
specialist teams, e.g. gynaecological, mucosal and
head and neck (excluding ocular) In situ 5 mm margins to achieve complete
Patients with multiple primary melanomas histological excision
Children younger than 19 years with melanoma <1 mm 1 cm
Any patient with metastatic melanoma diagnosed at 1.01e2 mm 1e2 cm
presentation or on follow-up 2.1e4 mm 2e3 cm
Patients with giant congenital naevi where there is >4 mm 3 cm
suspicion of malignant transformation
Patients with skin lesions of uncertain malignant
potential
Staging investigations for melanoma
Recommendations for Local Skin Cancer Stages I, II, and IIIA melanoma patients should not routinely
Multidisciplinary Team record keeping of clinical be staged by imaging or other methods as the true-positive
features pick-up rate is low and the false-positive rate is high
Stages IIIB or C patients should be imaged by CT prior to
surgery and with SSMDT review
See: National Institute for Health and Clinical Excellence
Stage IV melanoma patients should be imaged accord-
(NICE) Improving Outcomes Guidance for People with
ing to clinical need and SSMDT review; lactate dehy-
Skin Tumours including Melanoma. February 2006. www.
drogenase should also be measured
nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/pdf
Recommendations for the management of clinically
node-negative patients
Recommendations for screening and surveillance of
high-risk individuals There is no role for elective lymph node dissection
(Level I, Grade E)
Patients who are at moderately increased risk of Sentinel lymph node biopsy (SLNB) can be considered in
melanoma should be advised of this and taught how to stage IB melanoma and upwards in SSMDTs (Level IIa,
self-examine. This includes patients with atypical mole Grade C)
phenotype, those with a previous melanoma, and organ SLNB is a staging procedure with no proven therapeutic
transplant recipients value
Surgical risks of SLNB, and of a false-negative result, Follow-up of melanoma patients

should also be explained
Patients with in situ melanomas do not require follow-up
Recommendations for locoregional recurrent
Patients with stage IA melanomas should be seen
melanoma two to four times over up to 12 months then
discharged
All patients should be managed by SSMDTs. Patients with stage IBeIIIA melanomas should be
Nodes clinically suspicious for melanoma should be seen 3-monthly for 3 years, then 6-monthly to 5
sampled using fine needle aspiration cytology (FNAC) years
prior to carrying out formal block dissection. If FNAC is Patients with stage IIIB and IIIC and resected stage
negative although lymphocytes were seen, a core or IV melanoma should be seen 3-monthly for 3
open biopsy should be performed if suspicion remains years, 6-monthly to 5 years, then annually to 10
Prior to formal dissection, performed by an expert, years
staging by CT scan should be carried out other than Patients with unresectable stage IV melanomas are
where this would mean undue delay (Level III, Grade B) seen according to need
The treatment of locoregional limb recurrence is palli-
ative and, depending on extent and response, includes
excision or CO2 laser, isolated limb infusion or perfusion Appendix 1. Definition of the levels of
evidence used in preparation of the guidelines
Recommendations for metastatic disease
All patients should be managed by SSMDTs

Surgery should be considered for oligometastatic Level Type of evidence
disease at sites such as the skin, brain or gut, or to
prevent pain or ulceration Ia Evidence obtained from meta-analysis of
Radiotherapy may have a palliative role in the treat- randomised controlled trials, or meta-analysis of
ment of metastases epidemiological studies
Standard chemotherapy is dacarbazine although its role Ib Evidence obtained from at least one randomised
is palliative controlled trial
Patients with stage IV melanoma should be considered IIa Evidence obtained from at least one well-designed
for entry to clinical trials controlled study without randomisation
IIb Evidence obtained from at least one other type of
well-designed quasi-experimental study
III Evidence obtained from well-designed non-
Pregnancy, oral contraceptives and hormone
experimental descriptive studies, such as
replacement therapy
comparative studies, correlation studies and case
studies
IV Evidence obtained from expert committee reports
or opinions and/or clinical experience of
Pregnancy in Oral Hormone respected authorities
melanoma contraceptives replacement
therapy Grade of recommendation
No worsening of No increased No increased A There is good evidence to support the use of the
prognosis risk of melanoma risk of melanoma procedure
No increase in No worsening of B There is fair evidence to support the use of the
adverse prognosis procedure
outcomes for C There is poor evidence to support the use of the
mother or baby procedure
Placental D There is fair evidence to support the rejection of
metastases the use of the procedure
possible in E There is good evidence to support the rejection of
stage IV disease the use of the procedure

PIIS174868151000416X

Uploaded by

Copyright:

Available Formats

PIIS174868151000416X

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

PIIS174868151000416X

Uploaded by

Copyright:

Available Formats

Journal of Plastic, Reconstructive & Aesthetic Surgery (2010) 63, 1401e1419

Revised UK guidelines for the management

Table 3 Recommendations for screening and surveillance of high-risk individuals.

Site of the tumour Growth phase. Invasive melanoma without a vertical

Regression. The presence or absence of tumour regression

Microscopy Tumour infiltrating lymphocytes (TILs). It remains unclear

required; this may be subject to revision. Microsatellites Equivocal lesions

Requirements for microscopy of melanoma Dissection

sentinel lymph nodes and/or distant metastases in patients

Staining Stage III and IV melanoma

difficult to detect. Topical treatment with imiquimod is

Table 7 Recommended surgical excision margins.

A single positive superficial inguinal sentinel node

lymphadenectomy.110 Eligible patients were 1 parotid, 2

Surgical risks of SLNB, and of a false-negative result, Follow-up of melanoma patients

All patients should be managed by SSMDTs

You might also like

PIIS174868151000416X

Uploaded by

Copyright:

Available Formats

PIIS174868151000416X

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

PIIS174868151000416X

Uploaded by

Copyright:

Available Formats

Journal of Plastic, Reconstructive & Aesthetic Surgery (2010) 63, 1401e1419

Revised UK guidelines for the management

Table 3 Recommendations for screening and surveillance of high-risk individuals.

Site of the tumour Growth phase. Invasive melanoma without a vertical

Regression. The presence or absence of tumour regression

Microscopy Tumour infiltrating lymphocytes (TILs). It remains unclear

required; this may be subject to revision. Microsatellites Equivocal lesions

Requirements for microscopy of melanoma Dissection

sentinel lymph nodes and/or distant metastases in patients

Staining Stage III and IV melanoma

difficult to detect. Topical treatment with imiquimod is

Table 7 Recommended surgical excision margins.

A single positive superficial inguinal sentinel node

lymphadenectomy.110 Eligible patients were 1 parotid, 2

Surgical risks of SLNB, and of a false-negative result, Follow-up of melanoma patients

All patients should be managed by SSMDTs

You might also like

lymphadenectomy.110 Eligible patients were 1 parotid, 2