Definitions for the levels of evidence (Ia-IV) and grades of recommendations (A-E) are presented at the end of the "Major Recommendations" field.
Prevention of Melanoma
Individuals, and particularly children, should not get sunburnt (Level I). Meta-analysis of case–control studies provides good evidence that melanoma is caused predominantly by intermittent intense sun exposure; fair-skinned individuals should therefore limit their recreational exposure through life (Level I).
There is evidence from a recent meta-analysis that sunbed usage does increase the risk of melanoma, particularly under the age of 35 years, and therefore it is recommended that this should be avoided (Level Ia).
Referral and Clinical Diagnosis
Melanoma Patients Who Must Be Referred from the Local Skin Cancer Multidisciplinary Team to the Specialist Skin Cancer Multidisciplinary Team (SSMDT)
- 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 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 younger than 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
Lesions which are suspicious for melanoma should not be removed in primary care. This is because clinicopathological correlation is vital for diagnostic accuracy, which in turn determines prognosis and defines adjuvant treatment options, and because diagnostic surgery requires specialist training. Early recognition of melanoma presents the best opportunity for cure (Level III, Grade A).
All patients presenting with an atypical melanocytic lesion or a large number of moles should have a complete skin examination and assessment of risk factors. The dermoscope is a useful tool for the trained clinician screening pigmented lesions, as it can increase diagnostic accuracy. It is also useful for monitoring multiple pigmented lesions where photography of dermoscopic images provides a record of change (Level Ia, Grade A).
Recommendations for Local Skin Cancer Multidisciplinary Team Record Keeping of Clinical Features
As a minimum the following should be included:
- History (the presence or absence of these changes should be recorded)
- Duration of the lesion
- Change in size
- Change in colour
- Change in shape
- Symptoms (itching, bleeding etc.)
- Size (maximum diameter)
- Elevation (flat, palpable, nodular)
- Description (irregular margins, irregular pigmentation and if ulceration is present) (Level III, Grade B)
Screening and Surveillance of High-Risk Individuals
All individuals at increased risk of melanoma should be advised on the specific changes that suggest melanoma and encouraged to undertake monthly skin self-examination (Level III, Grade B). Close-up and distant photography may be a useful adjunct to detecting early melanoma in either of these high-risk groups (Level III). They should be given written information and access to images of moles and melanomas.
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 specialized 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).
Biopsy of Suspected Melanoma
A lesion suspected to be melanoma, or where melanoma needs to be excluded, should be photographed, and then excised completely. The axis of excision should be orientated to facilitate possible subsequent wide local excision; generally on the limb this will be along the long axis. If uncertain, direct referral to the multidisciplinary team (MDT) will allow appropriate planning for future surgery. The excision biopsy should include the whole tumour with a clinical margin of 2 mm of normal skin, and a cuff of fat. This allows confirmation of the diagnosis by examination of the entire lesion, such that subsequent definitive treatment can be based on Breslow thickness.
Diagnostic shave biopsies should not be performed as they may lead to incorrect diagnosis due to sampling error, and make accurate pathological staging of the lesion impossible (Level III). For the same reasons partial removal of naevi for diagnosis must be avoided and partial removal of a melanocytic naevus may result in a clinical and pathological picture very like melanoma (pseudomelanoma). This gives rise to needless anxiety and is avoidable. Incisional or punch biopsy is occasionally acceptable, for example in the differential diagnosis of lentigo maligna (LM) on the face or of acral melanoma, but there is no place for either incisional or punch biopsy outside the skin cancer MDT (Level III). It is acceptable in certain circumstances to excise the lesion entirely but without repair, and to dress the wound while awaiting definitive pathology.
Biopsies of possible subungual melanomas should be carried out by surgeons regularly doing so. The nail should be removed sufficiently for the nail matrix to be adequately sampled: clinically obvious tumour should be biopsied if present. Prophylactic excision of naevi, or of small (<5 cm diameter) congenital naevi in the absence of suspicious features is not recommended (Level III, Grade D).
Full clinical details should be supplied on the histopathology form, including history of the lesion, relevant previous history, site and differential diagnosis. All melanocytic lesions excised for whatever reason must be sent for histopathological review to the pathologist associated with the Local Skin Cancer Multidisciplinary Team (LSMDT) or SSMDT.
The diagnosis of melanoma, both in situ and invasive, should be given or supervised by doctors who have received advanced communication skills training, following local policies for breaking bad news. A skin cancer trained nurse should be present to provide continuing support.
The Royal College of Pathologists has produced a minimum dataset which should be included in the histopathology report. Double reporting is recommended for all melanomas and all naevi showing severe dysplasia if resources allow this to be achieved within 14 days.
The Histopathology Report
The report should include the following:
- Site of the tumour
- Type of surgical procedure: excision or re-excision, incision biopsy, punch biopsy
- Any other relevant clinical information
Contour, colour and size of the tumour and the excised skin specimen in millimetres.
- Presence or absence of ulceration
- Thickness - In the presence of histological regression thickness measurements should be of the residual melanoma. Microsatellites should not be included in thickness measurements (Level III, Grade B).
- Mitotic count
- Histological subtypes
- Margins of excision
- Pathological staging
- Growth phase
- Tumour-infiltrating lymphocytes
- Lymphatic or vascular invasion
- Perineural infiltration
- Precursor naevus
- Clark level of dermal invasion
Sentinel Lymph Node Pathology
This needs to be done in a standardized way so that findings between centers are comparable (Level III, Grade B).
The dissection should be either by bivalving or multiple slicing, although the former is recommended. A minimum of six serial sections should be taken, but a higher incidence of metastases is detected by extended step sectioning with immunohistochemistry at each level.
Use of haematoxylin and eosin and immunohistochemistry is essential. S100 and Melan A are most favoured immunohistochemical stains but a composite method such as PanMel is also appropriate.
Assessment of Tumour Burden
This gives additional prognostic information. The following are recommended:
Assessing the depth of the metastasis from the inner aspect of the sentinel lymph node capsule; categorizing the metastasis according to its site, either subcapsular or parenchymal; measuring the maximum dimension of the largest confluent group of melanoma cells.
Completion Lymphadenectomy Specimens
The pathological examination of regional nodes dissected following positive SLNB should include an attempt to examine all lymph nodes at least at one level, and count the number involved. The presence of extracapsular spread and involvement of perinodal fat should be recorded together with the size of the tumour-free margin. The use of immunohistochemistry such as S100 or Melan A facilitates this.
Investigations and Imaging
Stage I and II Melanoma
Routine investigations are not required for asymptomatic patients with primary melanoma. Blood tests are unhelpful.
Routine computed tomography (CT) is not recommended for patients with stage I and II melanoma as this has a very low incidence of true-positive and high incidence of false-positive findings. Patients with particularly high-risk primary melanoma may undergo staging investigations if deemed appropriate by the SSMDT and/or as a prerequisite to trial entry. There is no indication for routine imaging with any other modality including plain X-ray, positron emission tomography (PET)/CT and magnetic resonance imaging (MRI). PET/CT is not effective in detecting positive sentinel lymph nodes and/or distant metastases in patients with primary melanoma (Level IIa, Grade E).
Sentinel Lymph Node Biopsy and Ultrasound/Fine Needle Aspiration Cytology
SLNB, as discussed later, has high sensitivity and specificity for diagnosing subclinical regional lymph node involvement.
Ultrasound and fine needle aspiration cytology (FNAC) is 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 appearance. Further staging by CT imaging following a positive sentinel lymph node, and prior to completion lymphadenectomy, has a very low yield. Consequently this should be done only after discussion with an informed patient and the SSMDT (Level IIa, Grade D).
Stage III and IV Melanoma
In stage III and IV melanoma, imaging strategies will be planned by the SSMDT.
CT scanning of the head, chest, abdomen and pelvis will normally adequately exclude metastases, and is most relevant in stage III melanoma before planning regional lymph node dissection (LND) and regional chemotherapy. If patients are considering entry to an adjuvant study following lymphadenectomy, the timing of scans should be determined by the SSMDT to avoid duplication. When stage IV disease is suspected clinically, CT scanning of the head and whole body should be considered. Further imaging will be determined by symptoms, clinical trial protocols, and for clarification or reassessment of previous imaging findings. Generally, the added yield of PET/CT is unlikely to be clinically relevant in established stage IV melanoma (Level III, Grade D).
Staging Investigations for Melanoma
- Patients with stage I, II and IIIA melanoma should not routinely be staged by imaging or other methods as the true-positive pick-up rate is low and the false-positive rate is high (Level IIa, Grade E)
- Patients with stage IIIB or IIIC melanoma should be imaged by computed tomography of head, chest, abdomen and pelvis prior to surgery after SSMDT review (Level IIa, Grade A)
- Patients with stage IV melanoma should be imaged according to clinical need and SSMDT review. Lactate dehydrogenase should also be measured (Level III, Grade A)
Treatment of the Primary Lesion
Surgery is the only curative treatment for melanoma. Following excision for diagnosis and for measurement of microscopic Breslow thickness, a wider and deeper margin is taken to ensure complete removal of the primary lesion, and to remove any micrometastases. The depth of the therapeutic excision has conventionally been to the muscle fascia or deeper, and there is no evidence to support altering this approach.
Recommended Surgical Excision Margins (Summary)
||Level of Evidence
||Grading of Evidence
||5-mm margins to achieve complete histological excision
Management of Lymph Node Basins
Investigation and management of lymph node basins in melanoma patients should be carried out by SSMDTs so that surgical treatment planning and investigations can run in parallel. There is no place for elective LND in the management of primary melanoma unless this is unavoidable because the primary melanoma lies over the lymph node basin (Level Ib, Grade A). Patients should have access to a skin cancer specialist nurse when relapse is suspected.
Recommendations for the Management of Clinically Node-Negative Patients
- There is no role for elective lymph node dissection (Level I, Grade E)
- SLNB can be considered in stage IB melanoma and upwards in Specialist Skin Cancer Multidisciplinary Teams (Level Ia, Grade A)
- Patients should be introduced to the concept of SLNB as a staging procedure but should also understand that it has no proven therapeutic value
- Surgical risks of SLNB, the possibility of failure to find a sentinel lymph node, and of a false-negative result, should also be explained
Management of Patients with Clinically or Radiologically Suspicious Lymph Nodes
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 fine needle aspiration should be repeated or an image-guided core biopsy arranged.
Open biopsy is recommended when there is clinical suspicion even in the presence of negative FNACs in which lymphocytes have been successfully aspirated. If open biopsy is performed, the incision must be such as to allow subsequent complete formal block dissection of the regional nodes without compromise. It should be done only by SSMDT members.
Exploration or removal of a mass within a nodal basin which drains a known primary melanoma site, and prior to definitive surgical treatment, may increase the risk of melanoma recurrence in that basin. Any melanoma patient who develops a mass in a nodal basin should be referred urgently to the SSMDT, and without prior investigation, for investigation and treatment planning (Level III, Grade B).
Management of Patients with Confirmed Positive Lymph Node Metastasis
Radical LND should be performed only by SSMDT members who do a combined minimum of 15 axillary and groin block dissections for skin cancer each year.
Preoperative staging investigations should be carried out as already discussed for stage III melanoma. If such staging is not feasible prior to surgery, and surgery is considered necessary even if distant metastatic disease were to be detected, then a chest X-ray and lactate dehydrogenase (LDH) measurement is recommended.
The block dissection specimen should be marked and orientated for the pathologist. Axillary LND for melanoma should include all nodes in levels I–III, and this may require either resection or division of pectoralis minor. The management of inguinal lymph node metastases is controversial.
A superficial inguinal LND should be considered in the presence of:
- A single clinically involved inguinal node or femoral triangle node
- A single positive superficial inguinal sentinel node (Level Ib, Grade A)
A pelvic lymph node dissection should be considered in the presence of:
- More than one clinically palpable inguinal and/or femoral triangle node/s
- CT or ultrasound evidence of more than one inguinal and/or femoral triangle node/s, or of pelvic node involvement
- More than one microscopically involved node at SLNB
- A conglomerate of inguinal or femoral triangle lymph nodes
- Microscopic or macroscopic involvement of Cloquet's node (Level III, Grade B)
Cervical nodal recurrence should be treated either by surgeons in the SSMDT specializing in head and neck skin cancer including melanoma or by a head and neck MDT with a special interest in melanoma. A comprehensive, and not a selective, neck dissection should be performed (Level III, Grade A).
Locoregional Recurrent Melanoma: Skin and Soft Tissues
Surgery is the treatment of choice for single local or regional metastases. Excision should be clinically and histologically complete, but a wide margin is not required. Multiple small (<1 cm) dermal lesions respond well to treatment with the CO2 laser. Dermal disease which is progressing despite surgery or laser, and subcutaneous or deeper limb metastases, should be considered for regional chemotherapy with isolated limb infusion (ILI) with melphalan and actinomycin D, or with isolated limb perfusion (ILP) (Level IIb, Grade B).
Recommendations for Locoregional Recurrent Melanoma
- Nodes clinically suspicious for melanoma should be sampled using fine needle aspiration cytology (FNAC) prior to carrying out formal block dissection. If FNAC is negative although lymphocytes were seen, a core or open biopsy should be performed if suspicion remains (Level III, Grade B)
- Prior to lymph node dissection, performed by an expert, staging by computed tomographic scan should be carried out other than where this would mean undue delay (Level III, Grade B)
- The treatment of locoregional recurrence in a limb is palliative. Surgical excision, CO2 laser, or isolated limb infusion or perfusion may be considered (Level IIb, Grade B)
There is no evidence of a survival benefit for adjuvant chemotherapy in patients with melanoma. This includes adjuvant regional chemotherapy using ILP, and therefore ILI.
Interferon is not recommended as standard of care for adjuvant therapy of primary or stage III melanoma (Level Ia, Grade A).
Patients should be offered entry into adjuvant clinical trials approved by the local Cancer Network.
If there is clinical or histological doubt about the adequacy of surgery following recurrence, or about the feasibility of salvage surgery, adjuvant radiotherapy may be considered by the SSMDT (Level Ib, Grade B).
Occult Primary Melanoma
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.
Patients presenting with lymph node disease from an occult primary involving a single lymph node basin should be presumed to have regional rather than distant metastasis, and treated as for stage III disease with lymph node block dissection.
The benefits of treating patients with cerebral metastases with whole-brain radiotherapy are limited, but this may sometimes have palliative value. Supportive care is therefore the most appropriate strategy for many patients (Level IIb, Grade B).
Spinal cord compression should be treated surgically if feasible, but multiple sites of disease, poor prognosis and poor performance status may make this inappropriate. Radiotherapy may be useful for palliation of rapidly enlarging or painful metastases involving soft tissues and bones (Level IIb, Grade B)
Recommendations for Metastatic Disease
- All patients should be managed by Specialist Skin Cancer Multidisciplinary Teams
- Surgery should be considered for oligometastatic disease at sites such as the skin, brain or bowel (Level IIb, Grade B), or to prevent pain or ulceration
- Radiotherapy may have a palliative role in the treatment of metastases (Level II, Grade B)
- Standard chemotherapy is dacarbazine although its role is palliative (Level II, Grade C)
- Patients with stage IV melanoma should be considered for entry to clinical trials
Melanoma, Hormone Replacement Therapy and Pregnancy
Surgical treatment should be determined in the normal way, but the risks of exposure to ionizing radiation and blue dye during sentinel node biopsy will need special consideration.
There is no medical reason to justify delaying conception after a diagnosis of melanoma (Level IIa) but the social and family effects of developing recurrent melanoma during pregnancy or after birth are great.
Recommendations Regarding Pregnancy and Hormone Replacement Therapy
Pregnancy with Primary Melanoma
- No worsening of prognosis
- No increase in adverse outcomes for mother or baby
Pregnancy in Advanced Melanoma
- Placental and fetal metastases possible in stage IV disease
Oral Contraceptives and Melanoma
- No increased risk of melanoma
Hormone Replacement Therapy
- No increased risk of melanoma
- No worsening of prognosis
Use of Drugs in Melanoma Patients
The use of immunosuppressants after melanoma is a cause for concern. However, there is usually little that can be done to avoid these drugs without an unacceptable loss of quality of life. Their use after treatment of primary or secondary melanoma should be discussed between the prescribing doctors and patients, and the decision to continue their use and their dosage should be subject to ongoing review following a diagnosis of melanoma (Level III, Grade C).
Organ and Blood Donation
The decision about whether organs or tissue are suitable for transplant is made on an individualized basis, taking into account the patient's medical history. A melanoma patient would not normally be considered as a donor.
Sentinel Lymph Node Biopsy
Patients who have had a negative SLNB should be followed up on the basis of Breslow thickness. Most patients who have had a positive SLNB will have had a completion lymphadenectomy. As these patients now have at least stage IIIA disease, their follow up should be supervised by the SSMDT, and entry into appropriate trials considered. Risk of recurrence depends on extent of sentinel lymph node involvement, and may be less than for some with stage II melanoma. They should be followed up as for stage IB–IIC melanoma (Level III, Grade B).
Follow-up of Melanoma Patients
- Patients with in situ melanomas do not require follow up
- Patients with invasive melanomas have differing risk of relapse according to their stage group
- Patients with stage IA melanoma should be seen two to four times over up to 12 months, then discharged
- Patients with stage IB–IIIA melanoma should be seen 3-monthly for 3 years, then 6-monthly to 5 years
- Patients with stage IIIB and IIIC and resected stage IV melanoma should be seen 3-monthly for 3 years, then 6-monthly to 5 years, then annually to 10 years
- Patients with unresectable stage IV melanoma are seen according to need
(Level III, Grade B)
Level of Evidence
Ia - Evidence obtained from meta-analysis of randomized controlled trials, or meta-analysis of epidemiological studies
Ib - Evidence obtained from at least one randomized controlled trial
IIa - Evidence obtained from at least one well-designed controlled study without randomization
IIb - Evidence obtained from at least one other type of well-designed quasi-experimental study
III - Evidence obtained from well-designed nonexperimental descriptive studies, such as comparative studies, correlation studies and case studies
IV - Evidence obtained from expert committee reports or opinions and⁄or clinical experience of respected authorities
Grade of Recommendation
- There is good evidence to support the use of the procedure.
- There is fair evidence to support the use of the procedure.
- There is poor evidence to support the use of the procedure.
- There is fair evidence to support the rejection of the use of the procedure.
- There is good evidence to support the rejection of the use of the procedure.