Clinical guidelines for the recognition of melanoma of the foot and nail unit
© Bristow et al; licensee BioMed Central Ltd. 2010
Received: 7 June 2010
Accepted: 1 November 2010
Published: 1 November 2010
Malignant melanoma is a life threatening skin tumour which may arise on the foot. The prognosis for the condition is good when lesions are diagnosed and treated early. However, lesions arising on the soles and within the nail unit can be difficult to recognise leading to delays in diagnosis. These guidelines have been drafted to alert health care practitioners to the early signs of the disease so an early diagnosis can be sought.
Overview and scope of the guidelines
Melanoma is a life threatening but potentially treatable form of cancer if diagnosed and managed at an early stage. Guidelines have been published to assist healthcare workers in the recognition of malignant melanoma of the skin . However, early melanoma arising on the foot, particularly within the nail unit and on the plantar surface, can be difficult to recognise. Consequently, this can lead to delays in diagnosis. Melanoma arising on the foot carries a particularly poor prognosis when compared to melanoma arising at other body sites [2–4]. As there are no consistent features of an early melanoma, these guidelines have been drafted to alert health care workers to the signs which may suggest melanoma and therefore warrant a specialist referral. A melanoma recognised and diagnosed at an early stage can dramatically increase a patient's chances of survival.
This guide has been produced as a reference for health care professionals who may be confronted with pigmented and amelanotic lesions on the foot. It has been split into two sections-melanoma on the skin of the foot and melanoma in the nail. The paper is designed to act as a guide in deciding whether a presenting lesion should be referred on. It is not designed to be a diagnostic tool-confirmation of diagnosis can only be secured though appropriate biopsy, histological examination and specialist interpretation. Furthermore, it is appreciated that melanoma is not the only malignant skin tumour arising on the foot. However, these guidelines should alert practitioners to any skin lesions of the foot exhibiting unusual features. If there is any doubt, a second opinion should be sought. At a local level, foot clinics may wish to establish links with their local dermatology and oncology services to facilitate rapid referral pathways.
What is a melanoma and how common is it?
A melanoma is a malignant tumour (cancer) arising from the pigment producing cell of the skin, the melanocyte. The number of cases of malignant melanoma worldwide is increasing faster than any other form of cancer amongst Caucasians . When compared to other forms of skin cancer, the disease is relatively uncommon . However in the UK, like much of the world, the incidence of cutaneous melanoma continues to rise accounting for the majority of skin cancer deaths. It has been calculated that the lifetime risk for an individual developing the disease is 1:120 for men and 1:95 for women . Currently there are around 8500 new cases annually in the UK with around 1800 melanoma related deaths . Cutaneous melanoma can develop on any skin and mucosal surface. The lower limb is the location of around 30% of all primary cutaneous melanomas, with women are more highly represented in this group, and foot and ankle lesions representing around 3-15% of all cutaneous melanomas .
Who is likely to develop melanoma?
There is a relationship between ultra-violet (UV) exposure and the development of melanoma on sun exposed sites. Data has demonstrated that in particular that irregular and intense exposure to sunlight significantly increases the risk of melanoma . However, the relevance of UV light on non-exposed areas such as the plantar surface of the foot the role is not so clear.
Melanoma is a rare occurrence before puberty, but shows a gradual increase in incidence from the age of fifteen, peaking at around the age of fifty. Around 80% of lesions occur between the ages of 20-74 years . White populations have a much greater risk of developing the disease than Hispanics, Asians and Afro-Caribbeans. Although non-white races overall have a much lower rate of the disease, they are most likely to develop melanoma in acral locations such as the palmar, plantar surfaces and nail bed [11–15].
Recognised risk factors for the development of melanoma
General Risk Factors
Risk factors for plantar melanoma*
• Intense and intermittent sunlight and UV radiation exposure
• High numbers of benign naevi and dysplastic naevi
• Family history of melanoma
• A personal history of 3 or more severe sunburns
• Immunosuppression (including organ transplant recipients)
• Blue or green eye colour
• Presence of freckles
• Inability to tan
• Red hair colour
• High total naevus body counts
• Pre-existing naevi on the soles
• History of penetrating injury
• Exposure to agricultural chemicals
Types of melanoma
Acral lentiginous melanoma (ALM)
This type of melanoma is characterised by having an extensive component running as a layer of malignant melanocytes within the basal layer of the epidermis, giving rise to the term "lentiginous". The term "acral" defines the location which is of the extremities, namely the skin of the hands and feet, including the nail unit. ALM is the only type of MM which arises equally across all skin types and is frequently observed in darker skin types and represents about half of the melanoma occurring on the hands and feet. In the early stages, the clinical symptoms for this type of melanoma maybe very subtle such as an ill defined macule or patch of light brown or grey discolouration of the skin.
Nodular melanoma (NM)
Nodular melanoma is characterised by a prominent vertical component to the invasion of the tumour when viewed under the microscope. This typically corresponds to a pigmented lesion which may appear nodular to the naked eye. This lesion is more often seen in older patients.
Superficial spreading melanoma (SSM)
is the most common of the four types so called because of its radial growth phrase (lateral spread) before becoming invasive. It may arise de novo or in a pre-existing mole. This type has been most frequently reported arising on the dorsum of the foot .
Lentigo maligna (LM)
is a type of in situ melanoma, found almost exclusively on the face and neck of older adults in the setting of sun damage. Lentigo maligna may progress to lentigo maligna melanoma which is a lentigo maligna with an area of dermal invasion.
A large proportion of melanoma are discovered by patients and relatives . Unfortunately, for many patients, the foot is difficult to see and is seldom checked. Consequently, changes may not be readily observed or noted by the patient. Chiropodists/Podiatrists can play an important role in screening the foot and leg.
The prognosis for melanoma corresponds to the histological (Breslow) thickness of the excised tumour. This represents a measure of depth of invasion of the tumour into the dermis. For example, a < 1 mm thick lesion has a five year survival rate of 95%, whilst a > 4 mm thickness holds a 50% chance of survival at five years. As depth of tumour is partly related to its age early identification of suspect lesions is paramount .
It is suggested that at an initial appointment details of any pigmented or solitary lesion arising on the feet is recorded in the patient's notes with a description including location, size, colour and shape. Inclusion of accurate measurements can be more objective. The examination must be comprehensive and include interdigital areas and the plantar surface.
When assessing lesions, a history of trauma should not exclude the possibility of a melanoma. Evidence suggests many cases of melanoma are brought to the attention of the patient by co-incidental trauma and injury. The role of trauma in the aetiology of melanoma remains controversial, but it may bring the patient's attention to an existing lesion.
The ABCDE acronym
Asymmetry. One half of the lesion is not identical to the other.
Border. A lesion with an irregular, ragged or indistinct border.
Lesion has more than one Colour present within it.
Diameter. The lesion has a diameter of greater than 6 mm.
Evolution. Any change in the lesion in terms of size, shape or colour.
The utility of the standard ABCDE system for plantar and nail lesions has been questioned owing to the variation in presentation on the plantar surface and within the nail unit compared to other areas of the skin [21–23]. Moreover, data has highlighted how melanoma on the foot holds a poorer prognosis than melanoma elsewhere due to delays in presentation and misdiagnosis of the condition [23–25] particularly so when located in the periungual areas, beneath or around the nails . Lack of pigmentation in suspect pedal lesions can compound the problem. Many misdiagnoses are made in favour of more benign conditions such as:
Ingrowing toe nail
The "CUBED" acronym for foot melanoma
Coloured lesions where any part is not skin colour.
Uncertain diagnosis. Any lesion that does not have a definite diagnosis
Bleeding lesions on the foot or under the nail, whether the bleeding is direct bleeding or oozing of fluid. This includes chronic "granulation tissue".
Enlargement or deterioration of a lesion or ulcer despite therapy
Delay in healing of any lesion beyond 2 months.
Clinical judgement should identify lesions which appear "unusual" in their form or have atypical features. For example, the appearance of a suspicious foot ulcer in a patient without the normal risk factors (neuropathy, diabetes etc) should raise concerns as to the correct diagnosis. Furthermore, when individual skin lesions don't respond to a treatment in the normal, timely manner the original diagnosis should be re-considered.
Dermoscopy has been demonstrated to be a useful adjunct in the visual assessment of pigmented lesions to detect potential melanoma on acral skin  however, such equipment requires training and knowledge before use. Readers are referred to the article by Bristow and Bowling .
Nail unit melanoma
Like elsewhere on the foot, melanoma of the nail unit (NUM) is typically diagnosed at a later stage in its evolution than melanoma at most other body sites. Accordingly, the tumours are thicker and there is a worse prognosis than for other melanoma. A large UK survey of 4 regions demonstrated that NUM represented 1.4% of melanoma over a 10 year period, giving an incidence of 1 per million of population per year. The 5 year survival of this group was 51%, where those with a Breslow thickness of less than 2.5 mm had a 5 year survival of 88% and those for which the thickness was 2.5 mm or greater, had a 44% 5 year survival rate .
Presentation of melanoma in the nail unit
Differential diagnosis: Melanoma or haematoma?
Causes of melanonychia compared with those of subungual bleeding
Benign racial melanonychia
Indirect microtrauma-end on repetitive trauma
Haemorrhagic tendency lowering threshold for effects of trauma. eg
• Lichen planus
• Chronic paronychia
• squamous cell carcinoma
• HIV disease or medication
• pyogenic granuloma
Benign melanocyte activation
Bowen's disease (in situ squamous cell carcinoma)
Features of longitudinal melanonychia compared with those of subungual bleeding-all features are generally true, but there can be individual exceptions
The duration of history is from 3-6 months upwards to 20 years or more
The duration of history is rarely more than 6 months and is typically shorter
A history of trauma is quite common
A history of trauma or precipitating activity is quite common
Lateral margins within the nail are mainly straight and longitudinally oriented
Lateral margins may be irregular
Where margins merges with the nail fold, pigment may spread onto nail fold (Hutchinson's sign)
Pigment rarely extends from beneath the nail plate
There are rarely any detectable transverse features
There may be a proximal transverse groove and/or transverse white mark within the nail
In the absence of clinical tumour, nail plate pigmentation is in continuity with a single zone
Haemorrhage may be broken up into a number of zones
• continuous pigment between proximal nail fold and distal free edge
• Pigment may not be continuous in the longitudinal axis, with clear nail at either the proximal or distal margin
• in the transverse axis, pigment may vary-whereas in the longitudinal axis it remains largely constant
• Pigment may vary in any axis
• There may be longitudinal flecks of darker pigment within the background pigment of the nail
• Droplets of blood may be seen separated from the main zone of pigmentation
• Pigment is mainly brown black
• Blood may be seen as a discrete layer of material on the lower aspect of the nail plate at the free margin
• Pigment may be purple black, with increasing red hues at margins. It is rarely brown
Pigment arising solely within the nail bed with normal matrix and nail folds is not likely to be a melanoma
Where melanoma involves the nail bed, there will be a history of the disease starting in the nail matrix or nail fold.
The shape of the outline of the pigmentation is also a useful clue. Blood may present as small irregular pools within the nail bed, with adjacent puddles or drops of purplish brown discoloration. By contrast, longitudinal melanonychia arises as a well organised band of similar width throughout the longitudinal axis, arising in the matrix and extending to the distal edge.
An anecdotal clinical observation is that traumatic causes of subungual bleeding are associated with a proximal white transverse band in many instances . This is more common for trauma to digits of the hand than the foot. The band is likely to represent a physical disturbance to nail production associated with the episode of trauma which in turn will make the nail less translucent for a brief zone. This white band is not seen in melanocytic causes of nail discoloration.
What is the likely cause of the longitudinal melanonychia?
Evolution of the pigmentation is diagnostically useful, but not reliable as a means of ensuring that the source of pigment is benign. Whereas blood may be distinguished from melanin over a period of a few months, the characterisation of a benign or malignant source of melanin is less easy. Pigment that does not change is not necessarily benign, however the longitudinal melanonychia that increases in width or variety of pigment is more likely to represent malignancy than one that is static. One exception to this is longitudinal melanonychia in children where the pigment arises in a subungual naevus which changes as the child matures . Quite dramatic nail pigmentation can evolve quickly from a benign lesion and biopsy would rarely be undertaken in this group. A further exception is the evolution of a pigmented streak that comes to be associated with other pigmented streaks on other nails of the hands and feet. This indicates a systemic process and is common in dark skinned races, those taking certain drugs and in a condition termed Laugier Hunziker syndrome. Laugier Hunziker syndrome is increased patchy pigmentation of mucosae of the mouth and/or genitals, associated with multiple homogenous pigmented longitudinal bands in the nails. It is common for this problem to present with one nail in the first instance and hence the value in making a proper examination of all nails and other areas as appropriate . Multiple pigmented bands in dark skinned people may also initially be noted in one nail alone, but are soon detected in others.
The abnormal nail plate associated with pigment
A nail plate that is structurally altered presents a different scenario. Where there is a longitudinal melanonychia associated with loss of nail integrity this raises concern and needs immediate assessment. In other instances, the pigment may be broken up or scattered within a creamy yellow nail plate. Where there is no preceding history of longitudinal melanonychia, this may represent a pigmented onychomycosis with damage to the nail plate. This can be difficult to assess. Unlike melanocytic pigment which starts in the matrix, the pattern of onychomycosis usually extends from the distal free edge with proximal progression. Early reassurance can be given if the pigmented change and dystrophic nail can all be trimmed away with no disturbance of surrounding skin and there is no sign of a more proximal origin to the pathology. Suspicion of fungus should always be explored by mycological assessment and in particular culture. There is a wide variety of potential organisms [37, 38]. Some of the pigmented fungi are non-dermatophytes and may represent a therapeutic challenge likely to be surmounted only if the pathogen is known.
The ABCDE of nail melanoma after Levit 
Age Range 20-90, peak 5th -7th decades.
Band (nail band): Pigment (brown-black). Breadth > 3 mm. Border (irregular/blurred).
Change: rapid increase in size/growth rate of nail band. Lack of change: failure of nail dystrophy to improve despite adequate treatment.
Digit Involved: Thumb > hallux > index finger > single digit > multiple digits.
Extension: Extension of pigment to involve proximal or lateral nail fold (hutchinson's sign) or free edge of nail plate.
Family or personal history: Of previous melanoma or dysplastic nevus.
Amelanotic tumour of the nail unit
Amelanotic melanoma arises in the nail unit as it is does at other acral locations, at a rate higher than other body sites. The lack of overt pigment appears to delay the diagnosis further, which in turn affects prognosis . There may sometimes be small pigmented tints to an otherwise pink or granulomatous mass . The differential diagnosis of amelanotic melanoma is considered for all pyogenic granuloma, which is a common benign diagnosis presenting as a vascular nodule. Pyogenic granuloma is usually found on the fingers or toes, bleeds easily and does not readily remit. In Dermatological practice, a pyogenic granuloma would normally be surgically removed. This provides histology to ensure that it was not a melanoma at the same time as resolving the clinical complaint. In biological terms, pyogenic granuloma has much in common with the granulation tissue of ingrowing toenail. Amelanotic melanoma presenting as a granulating mass of the nail fold can be interpreted as an ingrowing nail. This is a well recognised pitfall in podiatry and a potential cause of delayed diagnosis which compromises prognosis [40–43]. Where practice entails cauterising or simply dressing fleshy granulomatous masses of the extremities there is a significant risk of leaving a malignancy undiagnosed. In the authors' experience patients with advanced amelanotic melanoma of the hand or foot often say "they treated it with dressings for the last X months and it just wouldn't heal". Although this article is examining presentation and diagnosis of acral melanoma, squamous cell carcinoma can also present this way and hence the value in asking for histological assessment of any lesion that does not resolve in 2 months, but which oozes or bleeds or has no clear diagnosis. Concern is greatest when the tumour causes disturbance of nail integrity as it arises in the nail matrix and destroys the specialised nail matrix epithelium such that it can not produce nail.
In conclusion, NUM is best detected early if all clinicians and patients have a low threshold for asking for advice early. In particular this means avoiding prolonged periods of conservative management of change in the nail or periungual tissues that are limited to one digit and do not respond promptly to appropriate treatment. For less advanced lesions, where there is only altered pigment, if such pigmentation is limited to a single digit and cannot confidently be attributed to a single episode of subungual bleeding then expert advice should be sought. In all instances, although general practitioners are a good source of general assessment, they typically do not have any experience of NUM. We would recommend assessment by a Dermatologist.
If a melanoma is suspected, the normal route for referral would be to a general practitioner. Occasionally, direct referral to the dermatology department may be possible, but local policies will dictate this. Under current NICE guidelines in the UK, patients with suspected melanoma should be seen by a specialist within two weeks of presentation. As a diagnosis of melanoma is relatively uncommon and can only be made after a full professional assessment and biopsy, practitioners should be cautious and not speculative when giving any advice to the patient about potential diagnoses to prevent any unnecessary alarm and concern. A point to emphasise to all patients is that it is important to know the diagnosis of what is being treated. If that diagnosis is not clear, or becomes unclear due to unusual clinical response to development, then both patient and the practitioner need the benefit of a clear diagnosis.
Melanoma can occur on any part of the foot, including the nail unit, in all ethnic groups and skin types.
Early recognition and diagnosis can significantly improve prognosis.
Melanoma of the foot is frequently misdiagnosed, especially when lesions are amelanotic or arise within the nail unit.
The use of the "ABCDE" and "CUBED" acronyms may improve practitioner's assessment of unusual lesions.
Any skin or nail lesion arising on the foot with an unclear diagnosis, which deteriorates or fails to heal within two months despite treatment or exhibits unusual features should be reassessed, and referred if considered appropriate..
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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