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Submitted: 9.2.2014 DOI: 10.1111/ddg.12368

Accepted: 8.4.2014
Conflict of interest
None.

Dermatoscopy of amelanotic and

hypomelanotic melanoma

Jelena Stojkovic-Filipovic1, Summary

­Harald Kittler2 Amelanotic melanoma is a subtype of cutaneous melanoma without pigment.
The clinical diagnosis is challenging because it may mimic benign or malignant
(1) Clinic of Dermatovenereology, melanocytic and non-melanocytic neoplasms and inflammatory skin diseases. In
­Clinical Center of Serbia, Department synchrony with the improvement of the diagnosis of pigmented lesions, dermatos-
of Dermatovenereology, Faculty of copy may assist the clinician in the diagnosis of non-pigmented skin neoplasms in
Medicine, University of Belgrade, general and of amelanotic melanoma in particular. We have searched the literature
­Belgrade, Serbia to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypo-
(2) Department of Dermatology, melanotic melanomas by dermatoscopy. In addition we present eight consecutive
­Medical University of Vienna, Austria cases and discuss their clinical and dermatoscopic characteristics in the light of
published data.

Introduction without dark brown, blue or black pigmentation [1, 7]. In

accordance with the classification of pigmented melanoma, it
Amelanotic/hypomelanotic melanoma (AHM) represents a has been suggested that there are two types of AHM, nodu-
subtype of cutaneous melanoma with little or no pigment on lar and superficial spreading melanoma. Like in pigmented
clinical examination [1–3]. Completely amelanotic melano- melanomas the nodular variant is said to grow faster than
mas are rare [2, 3]. Hypomelanotic melanomas with slight the superficial spreading variant [8]. To explain the lack of
pigmentation are more frequent [2, 3]. Approximately 2–8 % pigment it has been hypothesized that AHM is a poorly dif-
of all melanomas are AHM [1–5], but the real incidence is ferentiated subtype of conventional melanoma [5]. It is also
difficult to estimate because they are often misdiagnosed. The known that the pigmentation of melanomas depend on skin
final diagnosis is usually delayed [5]. Similar to the pigmen- phototype and on the genetic background [9].
ted variant of melanoma, the anatomic site of AHM differs Any subtype of cutaneous melanoma may be amelanotic,
by gender [5]. In males they are mainly found on the trunk but it is more common in subungual (25 %) and desmoplastic
and in females on the limbs [5]. Das et al. also described cases melanoma [2, 4]. Most studies do not consider regressive me-
of amelanotic melanoma in the vagina and on the breasts as lanoma a subtype of AHM [1, 10]. AHM tends to occur in
unusual sites in females [6]. AHM has been classified into sun-exposed skin, especially in older individuals with chro-
three groups according to the presence and the amount of nic UV-damage [3, 4]. Clinically, it may appear in various
melanin – amelanotic, partially pigmented and lightly colo- forms like, for example, as erythematous macule or patch
red melanoma [1]. Amelanotic melanoma is characterized by [3, 4], or as skin-colored nodule with or without ulceration
complete lack of melanin even under dermatoscopy. In parti- [3, 4]. Due to different clinical presentation AHM can be
ally pigmented melanoma, pigmentation is found in less than easily misdiagnosed. The spectrum of clinical differential di-
25 % of the lesion. Light colored lesions have a faint brown agnosis is wide. AHM can simulate inflammatory diseases
pigmentation that covers more than 25 % of the lesion but or benign and malignant neoplasms [2]. Like in pigmented

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melanoma, the prognosis of amelanotic melanoma depends are specific for flat melanocytic lesions, but can be found
mainly on tumor thickness. Amelanotic type has a poorer in raised lesions as well. Usually they are found in com-
prognosis [5], most probably due to delay of treatment [2]. bination with other types of vessels [7, 15, 18, 24, 26, 30,
For unclear reasons the prognosis of the patients with ame- 32, 35, 37–40]. The reported frequency varies from 40 %
lanotic metastases is worse than for pigmented metastasis [2]. (Pizzicheta et al.) [3] to 100 % (Bono et al.) [29]. Cavicchini
et al. suggested that dotted vessels should be considered as
the most useful dermatoscopic features for the diagnosis of
Dermatoscopy of amelanotic/­
amelanotic melanomas [36]. Dotted vessels (red dots) have
hypomelanotic melanoma been found mainly in flat AHM [3, 7, 24, 29, 33]. Pizzicheta
et al. found combination of dots and irregular linear vessels
Dermatoscopy (dermoscopy) is a non-invasive technique as useful criteria in distinguishing AHM from other lesi-
that can assist the clinician in the diagnosis of suspicious ons [3], and Menzies at al. confirmed it as one of the most
skin lesion in general, particularly pigmented skin tumors predictive vascular features for AHM [7]. Zalaudek et al.
[11–18]. It improves diagnostic accuracy for pigmented le- reported dotted vessels in combination with linear serpen-
sions compared to examination with the naked eye [12, 17, tine vessels [24].
19–21]. Dermatoscopy can also be helpful in the diagnosis Milky red areas/globules have been observed in sever-
of non-pigmented skin neoplasms [12, 14–16, 22–25]. Al- al reports of AHM [3, 7, 18, 24, 27, 39, 41]. Pizzicheta et
though there are many diagnostic algorithms to analyze al. have noted milky red areas in 60 % cases of AHM [3],
pigmented lesions, the dermatoscopic criteria for amelanotic and Jaimes et al. in 80 % cases of amelanotic melanoma that
proliferations are not so well established. Due to the lack are not nodular subtype [27]. Menzies et al. confirm milky
of pigment, other criteria, such as vessel morphology, are red-pink areas as a characteristic vascular feature of ame-
needed to come to the correct diagnosis. Vascular patterns lanotic melanoma [7]. Cavicchini et al. found that milky red
have already been analyzed and confirmed as a useful clue globules/areas and linear irregular vessels as the most useful
in non-pigmented melanocytic neoplasms [1, 3, 7, 23, 24, dermatoscopic features for the diagnosis of truly amelanotic
26–32]. It has been suggested that, in analogy to pattern melanomas [36]. With regard to arrangement of vessels Men-
analysis for pigmented skin lesions [11], vascular morpholo- zies et al. found predominant central vessels as one of the
gy should be analyzed in a structured way based on simple most positive predictor for AHM [7]. Linear curved vessels
terminology to avoid misleading and confusing metaphoric (“comma vessels”), typical for dermal nevi (“Unna nevi”),
terms [23]. have been reported by Menzies et al. as a negative predictive
factor for melanoma [7]. According to a recent suggestion
Dermatoscopic evaluation of vascular by Rosendahl et al. it is important to differentiate between
flat and raised amelanotic melanoma [42]. Flat amelanotic
structures in AHM melanomas are typified by polymorphic vessels that include
a pattern of vessels as dots. Nodular amelanotic melanoma
Different types of vessels have been reported in AHM. Due should be suspected in any non-pigmented nodule that lacks
to the fact that different terminologies have been used, it is a specific distribution of vascular structures and when a spe-
difficult to integrate the reports. As a general rule, vessel cific benign diagnosis cannot be made with confidence. They
morphology in AHM differs between flat and raised lesions. also pointed out the importance of other clues such as ulcera-
In flat lesions vessels as dots predominate whereas in rai- tion and white structures [42].
sed lesions linear vessels becomes more prominent [3, 7, 24,
29, 33]. Other clues
According to Menzies at al. linear irregular vessels are
the predominant vessel type in AHM [7]. In a series publis- Menzies et al. reported on scar-like depigmentation as
hed by Jaimes at al. serpentine vessels were found in 85 % ­positive predictor for the diagnosis of AHM [7]. Bories et al
of cases of AHM [27] and in amelanotic cutaneous mela- . noted scar-like depigmentation in all lesions (100 %) of ful-
noma metastases [34]. Coiled vessels (“glomerular vessels”) ly regressed melanomas [10]. In the series reported by Puig
or highly tortuous vessels were also noted [34–36]. Looped et al. 40 % of amelanotic melanomas were ulcerated [9]. Piz-
vessels (“hairpin vessels”) have been noted in several pub- zicheta et al. reported ulceration in 20 % of amelanotic mela-
lications on AHM [3, 7, 24, 26, 35, 37, 38]. Menzies et al. nomas [3], and it was one of the characteristics of amelanotic
considered it as one of the most predictive vascular features melanoma in case study of deGiorgi et al. [26]. Ulcerations
of AHM [7]. Hairpin vessels have been observed in ame- were noted with greater frequency in thick compared to thin
lanotic melanoma metastases as well [34]. Vessels as dots AHM [3, 7]. In similar percentage (23 %) ulcerations were

468 © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
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Figure 1  Clinical presentation of all

cases. Flat cases (a–c), an amelanotic
case with flat and elevated parts (d),
elevated (nodular) cases (e–h). Invasion
thickness (a: 1.8 mm, b: 0.7 mm,
c: 1.1 mm, d: 2.2 mm, e; 3.0 mm,
f: 1.1 mm, g: 1.5 mm, h: 1.5 mm)

found in cases of AH melanoma metastases [34]. In the al- Review of eight cases with clinical and
gorithm suggested by Rosendahl et al. ulceration and white
structures are regarded as significant dermatoscopic clues to dermatoscopic evaluation
a malignant diagnosis in general [42] and that white lines are
a clue to amelanotic melanoma in particular. With regard This series included eight patients, five males and three
to the specific problem of differentiating amelanotic mela- ­females. The mean age was 65 years (range 38–86 years).
noma from Spitz nevus the study by Zalaudek et al. deser- The anatomic sites were: lower limb (3 patients), upper limb
ves further attention [43]. They reported that reticular white (2 patients), back (1 patient), trunk-chest (1 patient), head/
lines (white network) are more common in Spitz nevi than neck (1 patient). Three lesions were flat, four were substanti-
in amelanotic or hypomelanotic melanoma. However, they ally elevated (nodular) and one was flat and had an elevated
also stated that this clue is not 100 % specific and does not part (Figure 1). All lesions were pink clinically. Ulcerations/
exclude melanoma and recommend excision of all tumors erosions were noted in two of eight lesions (25 %). Dermat-
that show this pattern [43]. oscopic features as captured with a polarized dermatoscope

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Table 1  Dermatoscopic vascular features of eight amelanotic lesions (melanomas).

Vessel morphology 1 2 3 4 5 6 7 8
Dots + + + + – + – +
Clods + – – – + – – –
Linear straight – – – + + – – –
Linear looped – – – – – – – +
Linear curved + + + + + + + +
Linear serpentine + + + + + + + +
Linear helical – – – – – – – –
Linear coiled + + + + + + + +

Figure 2  Dermatoscopic images of six

of the eight cases. Dermatoscopy of
flat lesions of amelanotic melanoma
with polymorphous vessels (vessels
as dots plus linear vessels) (a–c) and
elevated nodular lesions with polymor-
phous linear vessels and prominent
white lines (d–f).

are given in Table 1 and dermatoscopic images of six cases are lesions. Three lesions had brown eccentric structureless zo-
presented in Figure 2. Three cases (37.5 %) were amelanotic nes, two had brown eccentric reticular pattern, and one had
melanomas and five cases (62.5 %) were hypomelanotic black eccentric clods. White lines and a polymorphic arran-
melanoma with slight pigmentation on the periphery of the gement of vessels were noted in all lesions.

470 © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
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Summary skin lesions. Dermatopathology: Practical & Conceptual 2007;

13: 3.
12 Rosendahl C, Tschandl P, Cameron A, Kittler H. Diagnostic
Dermatoscopy is useful tool to improve the detection of
­accuracy of dermatoscopy for melanocytic and nonmelano-
AHM. Our small case series confirmed that polymorphous
cytic pigmented lesions. J Am Acad Dermatol 2011; 64:
vascular pattern with no specific arrangement of vessels is a 1068–73.
dermatoscopic characteristic of AHM. In flat AHM in par- 13 Braun RP, Rabinovitz HS, Oliviero M et al. Dermoscopy of
ticular the combination of dotted vessels and linear vessels ­pigmented lesions. J Am Acad Dermatol 2005; 52: 109–21.
may be a strong clue to melanoma. Among non-vascular fea- 14 Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in
tures we consider white lines as the most important clue for general dermatology. Dermatology 2006; 212: 7–18.
AHM. Ulceration/erosion may indicate thicker tumors. 15 Argenziano G, Zalaudek I, Ferrara G et al. Dermoscopy
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Harald Kittler, MD
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Department of Dermatology, Division of General
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