Amelanotic melanoma

Author: Aamenah Al-Ani, Medical Student, University of Auckland, New Zealand. DermNet NZ Editor-in-Chief: A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. January 2018.

What is amelanotic melanoma?

Amelanotic melanoma is a form of melanoma in which the malignant cells have little to no pigment. The term “amelanotic” is often used to indicate lesions that are only partially devoid of pigment whilst truly amelanotic melanoma (lacking all pigment) is rare [1].

Who gets amelanotic melanoma?

Amelanotic melanoma accounts for approximately 1–8% of all melanomas. The incidence of truly amelanotic melanoma is difficult to estimate, given that many hypopigmented lesions are labelled as amelanotic [1].

Risk factors for developing amelanotic melanoma include:

What causes amelanotic melanoma?

Melanoma is caused by malignant pigment cells (melanocytes). The development of malignancy in melanocytes is due to genetic changes in DNA but how and why this occurs is largely unknown. The melanoma cells in amelanotic melanoma cannot produce mature melanin granules, which results in lesions that lack pigment.

To account for the lack of pigment, three models have been proposed. 

What are the clinical features of amelanotic melanoma? 

Amelanotic melanomas are classically described as skin coloured. A significant proportion are red, pink or erythematous. Typical early lesions present as asymmetrical macular lesions that may be uniformly pink or red and which may have faint light pigmentation of tan, brown or grey at the periphery. The borders may be well- or ill-defined [4].

Any subtype of melanoma can be amelanotic.

Amelanotic melanomas may not display the clinical ABCD criteria (Asymmetry, Border irregularity, Colour variation, large Diameter) that are classically used as melanoma warning signs. Patients and clinicians may not be alert to suspect nonpigmented lesions as melanoma and so amelanotic melanomas are often misdiagnosed. Expanding the ABCD warning signs to include the 3 R’s (Red, Raised, Recent change) may help screen for amelanotic melanoma [6].

How is amelanotic melanoma diagnosed?

Clinical features

Amelanotic melanomas have little to no pigment and can be clinically challenging to diagnose.

A patient’s history of change in a lesion is an important factor in amelanotic lesions and amelanotic melanoma should be considered in the differential diagnosis.

Examination of the entire skin surface is also important, as sun damage and other pigmented lesions may provide clinical clues that a non/hypopigmented lesion may be an amelanotic melanoma


Dermoscopy, the examination of a lesion using a dermatoscope, can be helpful in the diagnosis of suspicious lesions. Vessel morphology should be evaluated carefully if lesions lacking pigmentation.

Characteristic dermoscopic features of amelanotic melanoma are:


Lesions that are suspicious of amelanotic melanoma should be excised with a 2–3 mm clinical margin and sent for pathological diagnosis (excision biopsy).

Amelanotic melanoma can have varied histopathologic appearances. Amelanotic melanoma can masquerade as a number of non-melanocytic neoplasms [7].

Pathology report

The pathologist’s report includes both a macroscopic and microscopic description of the excised lesion:

The report may also include comments about the cell type and its growth pattern, invasion of blood vessels or nerves, inflammatory response, regression, immunohistochemistry and whether there is any associated original benign melanocytic lesion [8].

What is Breslow thickness?

The Breslow thickness is reported for invasive melanomas. It is the vertical measurement in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement. The Breslow thickness is the single most important local prognostic factor in primary melanoma, as thicker melanomas are more likely to metastasise (spread) [8,9].

What is the Clark level of invasion?

The Clark level indicates the anatomic plane of invasion. This is useful for predicting outcome in thin tumours and less useful for thicker ones in comparison to the value of the Breslow thickness [8,9].

What is the differential diagnosis for amelanotic melanoma?

Clinically, amelanotic melanoma may present as an erythematous scaly macule, plaque or nodule with irregular borders, mimicking numerous other skin lesions such as:

What is the treatment for amelanotic melanoma?

Amelanotic melanoma is treated in the same way that a pigmented melanoma is treated.

After diagnostic excision, the next step is wide local excision of the wound with a 1–2 cm margin of normal tissue. The extent of surgery depends on Breslow thickness of the melanoma and its site. Amelanotic melanomas may be incompletely excised despite the recommended margins as the margins are often difficult to define. Comprehensive histological examination including immunohistochemical staining helps determine the edge of the tumour. Further re-excision may be necessary. The recommended margins in the provisional New Zealand Standards for the Management of Patients with Melanoma (2014) are shown below:

Sentinel lymph node biopsy may be discussed with patients with melanomas thicker than 0.8mm. This can provide staging and prognostic information [9].

Amelanotic melanoma can metastasise (spread to distant sites such as lymph nodes or elsewhere in the body). These cases require individualised treatment which may include surgery, radiotherapy, chemotherapy or targeted therapy.

What happens at follow-up for amelanotic melanoma?

Follow-up is an important part of management for amelanotic melanoma because it allows opportunity to detect recurrences early. Moreover, it allows the chance to detect new primary melanomas at the earliest opportunity. A second invasive melanoma occurs in 5–10% of patients and an unrelated melanoma in situ affects more than 20% of patients [8].

The Australian and New Zealand Guidelines for the Management of Melanoma (2008) recommend the following for follow-up for patients with invasive melanoma:

What is the outcome for amelanotic melanoma?

The prognosis of amelanotic melanoma is similar to that of pigmented melanomas. Prognostic factors include the Breslow thickness of the melanoma at time of excision (this is considered to be most important factor), location, patient age and sex. Importantly, because of their atypical clinical features, amelanotic melanomas may have a delay in diagnosis and consequently are often more advanced than pigmented melanomas when diagnosed [5]. 

The risk of metastasis is directly related to the Breslow thickness, with thicker melanomas more likely to metastasise. The Australian and New Zealand Guidelines for the Management of Melanoma report that metastases are rare for thin melanomas (< 0.75 mm) with the risk increasing to 5% for melanomas 0.75–1.00 mm thick. Melanomas thicker than 4.0 mm have a significantly higher risk of metastasis of 40% [9].  

Related information

Email Newsletter

Would you like to receive our dermatology updates by email?


Submit your images

We're seeking high-quality photos of skin diseases.  


Machine diagnosis

Watch DermNet's proposal to create a 'Skin Disease Image Recognition Tool' - winner of the 2017 'Clinicians' Challenge Active Award' by the NZ Ministry of Health and HiNZ.

Subscribe to our mailing list

* indicates required
DermNet NZ Newsletter