Author: Hon A/Prof Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, 2011.
According to New Zealand Cancer Registry data, 2256 invasive melanomas were diagnosed in 2008 and at least 15% were reported as nodular melanoma. There were 371 deaths from all types of melanoma in 2008 (69% were male) and about half of these were nodular melanomas.
In nodular melanoma, malignant melanoma cells proliferate downwards through the skin – this is known as vertical growth. The lesion presents as a nodule (lump) that has been rapidly enlarging over the previous weeks to months. It can arise de novo in normal-appearing skin, or within an existing melanoma of other type.
A nodular melanoma can penetrate deeply within the skin within a few months of its first appearance.
Nodular melanoma accounts for about 15% of melanoma in Australia and New Zealand. Although more common in very fair skin (skin phototype 1 and 2), it may also occur in those who tan quite easily (phototype 3), and occasionally in brown or black skin (phototype 4-6).
Nodular melanoma is more common in males than females. Most are over the age of 50 when it is diagnosed.
The main risk factors for nodular melanoma are:
Nodular melanoma may arise on any site, but is most common on exposed areas of the head and neck.
Nodular melanoma presents as a rapidly enlarging lump (over several weeks to months). The characteristics of nodular melanoma include:
One-third of nodular melanomas are not pigmented. They lack the ABCD melanoma warning signs. (Asymmetry, Border irregularity, Colour variation, large Diameter).
Nodular melanoma is due to the development of malignant pigment cells (melanocytes) along the basal layer of the epidermis. These cells may occasionally arise from an existing melanocytic naevus (about 3%) but commonly arise within another type of melanoma or in previously normal-appearing skin. What triggers the melanocytes to become malignant is unknown, but it is likely to be a series of changes to the DNA. NRAS mutations are often found in patients with nodular melanomas.
It is essential to diagnose nodular melanoma accurately. Clinical diagnosis is aided by dermoscopy and skin biopsy (usually excision biopsy). Those with melanoma that is more than 1 mm thick may be advised to have lymph node biopsy, imaging studies and blood tests.
Dermoscopy, or the use of a dermatoscope, by a dermatologist or other doctor trained in its use can be very helpful in distinguishing nodular melanoma from other skin lesions, such as:
The most frequently observed dermoscopic features of nodular melanoma are:
If the skin lesion is suspicious of nodular melanoma, it should be urgently cut out (excision biopsy). A small biopsy is best avoided, except in unusually large lesions. An incisional or punch biopsy could be misleading.
The pathological diagnosis of melanoma can be very difficult. Nodular melanomas have little or no spread of malignant cells within the epidermis; the melanoma cells are found within the dermis or subcutaneous fat. Extra tests using immunohistochemical stains may be necessary.
The pathologist's report should include a macroscopic description of the specimen and melanoma (the naked eye view), and a microscopic description.
The report may also include comments about the cell type and its growth pattern, invasion of blood vessels or nerves, inflammatory response, regression and whether there is an associated naevus (original mole).
The Breslow thickness is reported for invasive melanomas. It is measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement. It is a strong predictor of outcome; the thicker the melanoma, the more likely it is to metastasise (spread).
The Clark level indicates the anatomic plane of invasion.
|Level 1||In situ melanoma|
|Level 2||Melanoma has invaded papillary dermis|
|Level 3||Melanoma has filled papillary dermis|
|Level 4||Melanoma has invaded reticular dermis|
|Level 5||Melanoma has invaded subcutaneous tissue|
The deeper the Clark level, the greater the risk of metastasis (secondary spread). It is useful in predicting outcome in thin tumours, and less useful for thicker ones in comparison to the value of the Breslow thickness.
The initial treatment of a primary melanoma is to cut it out; the lesion should be completely excised with a 2-3 cm margin of normal tissue. Further treatment depends mainly on the Breslow thickness of the lesion.
After initial excision biopsy; the radial excision margins, measured clinically from the edge of the melanoma, recommended in the The Australian and New Zealand Guidelines for the Management of Melanoma (2008) are shown in the table below. This may necessitate flap or graft to close the wound. Occasionally, the pathologist will report incomplete excision of the melanoma, despite wide margins. This means further surgery or radiotherapy will be recommended to ensure the tumour has been completely removed.
|Melanoma in situ||5mm|
|Melanoma < 1.0mm||1cm|
|Melanoma > 4.0mm||2cm|
Melanoma staging means finding out if the melanoma has spread from its original site in the skin. Most melanoma specialists refer to the American Joint Committee on Cancer (AJCC) cutaneous melanoma staging guidelines (2009). In essence, the stages are:
|Stage 0||In situ melanoma|
|Stage 1||Thin melanoma <2 mm in thickness|
|Stage 2||Thick melanoma > 2 mm in thickness|
|Stage 3||Melanoma spread to involve local lymph nodes|
|Stage 4||Distant metastases have been detected|
If the local lymph nodes are enlarged due to metastatic melanoma, they should be completely removed. This requires a surgical procedure, usually under general anaesthetic. If they are not enlarged, they may be tested to see if there is any microscopic spread of melanoma. The test is known as a sentinel node biopsy.
In New Zealand, many surgeons recommend sentinel node biopsy for melanomas thicker than 1 mm, especially in younger persons. However, although the biopsy may help in staging the cancer, it does not offer any survival advantage. The necessity for sentinel node biopsy is controversial at present.
Lymph nodes containing metastatic melanoma often increase in size quickly. An involved node is usually non-tender and firm to hard in consistency. If this occurs between planned follow-up visits, let your doctor know promptly.
If the melanoma is widespread, other forms of treatment may be necessary, but are not always successful in eradicating the cancer. Immunotherapy, biologics such as ipilimumab, and the BRAF inhibitors dabrafenib and vemurafenib are showing promise.
The main purpose of follow-up is to detect recurrences early but it also offers an opportunity to diagnose a new primary melanoma at the first possible opportunity. A second invasive melanoma occurs in 5-10% patients; an unrelated melanoma in situ affects in more than 20% of melanoma patients.
The Australian and New Zealand Guidelines for the Management of Melanoma (2008) make the following recommendations for follow-up for patients with invasive melanoma.
The follow-up appointments may be undertaken by the patient's general practitioner or specialist or they may be shared.
Follow-up appointments may include:
In those with more advanced primary disease, follow-up may include:
Tests are not typically worthwhile for stage 1/2 melanoma patients unless there are signs or symptoms of disease recurrence or metastasis. And no tests are thought necessary for healthy patients who have remained well for 5 years or longer after removal of their melanoma, whatever stage.
The risk of spread and ultimate death from invasive melanoma depends on several factors, but the main one is the measured thickness of the melanoma at the time it was surgically removed.
The Melanoma Guidelines report that metastases are rare for melanomas <0.75mm and the risk for tumours 0.75–1 mm thick is about 5%. The risk steadily increases with thickness so that melanomas >4 mm have a risk of metastasis of about 40%.
New Zealand statistics gathered by the Cancer Registry between 1994 and 2004 revealed 15,839 invasive melanomas. Of these, 52% were under 0.75 mm in thickness, 22% were between 0.76 and 1.49 mm, 15% were between 1.5 and 3 mm in thickness and 11% were more than 3 mm in thickness. Thicker tumours were slightly more likely to be diagnosed in males, and more likely in older people than younger ones.
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