Minireview
Submitted: 9.2.2014
Accepted: 8.4.2014
Conflict of interest
None.
Jelena Stojkovic-Filipovic1,
­Harald Kittler2
(1) Clinic of Dermatovenereology,
­Clinical Center of Serbia, Department
of Dermatovenereology, Faculty of
Medicine, University of Belgrade,
­Belgrade, Serbia
(2) Department of Dermatology,
­Medical University of Vienna, Austria
Introduction
Amelanotic/hypomelanotic melanoma (AHM) represents a
subtype of cutaneous melanoma with little or no pigment on
clinical examination [1–3]. Completely amelanotic melano-
mas are rare [2, 3]. Hypomelanotic melanomas with slight
pigmentation are more frequent [2, 3]. Approximately 2–8 %
of all melanomas are AHM [1–5], but the real incidence is
difficult to estimate because they are often misdiagnosed. The
final diagnosis is usually delayed [5]. Similar to the pigmen-
ted variant of melanoma, the anatomic site of AHM differs
by gender [5]. In males they are mainly found on the trunk
and in females on the limbs [5]. Das et al. also described cases
of amelanotic melanoma in the vagina and on the breasts as
unusual sites in females [6]. AHM has been classified into
three groups according to the presence and the amount of
melanin – amelanotic, partially pigmented and lightly colo-
red melanoma [1]. Amelanotic melanoma is characterized by
complete lack of melanin even under dermatoscopy. In parti-
ally pigmented melanoma, pigmentation is found in less than
25 % of the lesion. Light colored lesions have a faint brown
pigmentation that covers more than 25 % of the lesion but
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
DOI: 10.1111/ddg.12368
Dermatoscopy of amelanotic and
hypomelanotic melanoma
Summary
Amelanotic melanoma is a subtype of cutaneous melanoma without pigment.
The clinical diagnosis is challenging because it may mimic benign or malignant
melanocytic and non-melanocytic neoplasms and inflammatory skin diseases. In
synchrony with the improvement of the diagnosis of pigmented lesions, dermatos-
copy may assist the clinician in the diagnosis of non-pigmented skin neoplasms in
general and of amelanotic melanoma in particular. We have searched the literature
to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypo-
melanotic melanomas by dermatoscopy. In addition we present eight consecutive
cases and discuss their clinical and dermatoscopic characteristics in the light of
published data.
without dark brown, blue or black pigmentation [1, 7]. In
accordance with the classification of pigmented melanoma, it
has been suggested that there are two types of AHM, nodu-
lar and superficial spreading melanoma. Like in pigmented
melanomas the nodular variant is said to grow faster than
the superficial spreading variant [8]. To explain the lack of
pigment it has been hypothesized that AHM is a poorly dif-
ferentiated subtype of conventional melanoma [5]. It is also
known that the pigmentation of melanomas depend on skin
phototype and on the genetic background [9].
Any subtype of cutaneous melanoma may be amelanotic,
but it is more common in subungual (25 %) and desmoplastic
melanoma [2, 4]. Most studies do not consider regressive me-
lanoma a subtype of AHM [1, 10]. AHM tends to occur in
sun-exposed skin, especially in older individuals with chro-
nic UV-damage [3, 4]. Clinically, it may appear in various
forms like, for example, as erythematous macule or patch
[3, 4], or as skin-colored nodule with or without ulceration
[3, 4]. Due to different clinical presentation AHM can be
easily misdiagnosed. The spectrum of clinical differential di-
agnosis is wide. AHM can simulate inflammatory diseases
or benign and malignant neoplasms [2]. Like in pigmented
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melanoma, the prognosis of amelanotic melanoma depends
mainly on tumor thickness. Amelanotic type has a poorer
prognosis [5], most probably due to delay of treatment [2].
For unclear reasons the prognosis of the patients with ame-
lanotic metastases is worse than for pigmented metastasis [2].
Dermatoscopy of amelanotic/­
hypomelanotic melanoma
Dermatoscopy (dermoscopy) is a non-invasive technique
that can assist the clinician in the diagnosis of suspicious
skin lesion in general, particularly pigmented skin tumors
[11–18]. It improves diagnostic accuracy for pigmented le-
sions compared to examination with the naked eye [12, 17,
19–21]. Dermatoscopy can also be helpful in the diagnosis
of non-pigmented skin neoplasms [12, 14–16, 22–25]. Al-
though there are many diagnostic algorithms to analyze
pigmented lesions, the dermatoscopic criteria for amelanotic
proliferations are not so well established. Due to the lack
of pigment, other criteria, such as vessel morphology, are
needed to come to the correct diagnosis. Vascular patterns
have already been analyzed and confirmed as a useful clue
in non-pigmented melanocytic neoplasms [1, 3, 7, 23, 24,
26–32]. It has been suggested that, in analogy to pattern
analysis for pigmented skin lesions [11], vascular morpholo-
gy should be analyzed in a structured way based on simple
terminology to avoid misleading and confusing metaphoric
terms [23].
Dermatoscopic evaluation of vascular
structures in AHM
Different types of vessels have been reported in AHM. Due
to the fact that different terminologies have been used, it is
difficult to integrate the reports. As a general rule, vessel
morphology in AHM differs between flat and raised lesions.
In flat lesions vessels as dots predominate whereas in rai-
sed lesions linear vessels becomes more prominent [3, 7, 24,
29, 33].
According to Menzies at al. linear irregular vessels are
the predominant vessel type in AHM [7]. In a series publis-
hed by Jaimes at al. serpentine vessels were found in 85 %
of cases of AHM [27] and in amelanotic cutaneous mela-
noma metastases [34]. Coiled vessels (“glomerular vessels”)
or highly tortuous vessels were also noted [34–36]. Looped
vessels (“hairpin vessels”) have been noted in several pub-
lications on AHM [3, 7, 24, 26, 35, 37, 38]. Menzies et al.
considered it as one of the most predictive vascular features
of AHM [7]. Hairpin vessels have been observed in ame-
lanotic melanoma metastases as well [34]. Vessels as dots
468 © 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
are specific for flat melanocytic lesions, but can be found
in raised lesions as well. Usually they are found in com-
bination with other types of vessels [7, 15, 18, 24, 26, 30,
32, 35, 37–40]. The reported frequency varies from 40 %
(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
amelanotic melanomas [36]. Dotted vessels (red dots) have
been found mainly in flat AHM [3, 7, 24, 29, 33]. Pizzicheta
et al. found combination of dots and irregular linear vessels
as useful criteria in distinguishing AHM from other lesi-
ons [3], and Menzies at al. confirmed it as one of the most
predictive vascular features for AHM [7]. Zalaudek et al.
reported dotted vessels in combination with linear serpen-
tine vessels [24].
Milky red areas/globules have been observed in sever-
al reports of AHM [3, 7, 18, 24, 27, 39, 41]. Pizzicheta et
al. have noted milky red areas in 60 % cases of AHM [3],
and Jaimes et al. in 80 % cases of amelanotic melanoma that
are not nodular subtype [27]. Menzies et al. confirm milky
red-pink areas as a characteristic vascular feature of ame-
lanotic melanoma [7]. Cavicchini et al. found that milky red
globules/areas and linear irregular vessels as the most useful
dermatoscopic features for the diagnosis of truly amelanotic
melanomas [36]. With regard to arrangement of vessels Men-
zies et al. found predominant central vessels as one of the
most positive predictor for AHM [7]. Linear curved vessels
(“comma vessels”), typical for dermal nevi (“Unna nevi”),
have been reported by Menzies et al. as a negative predictive
factor for melanoma [7]. According to a recent suggestion
by Rosendahl et al. it is important to differentiate between
flat and raised amelanotic melanoma [42]. Flat amelanotic
melanomas are typified by polymorphic vessels that include
a pattern of vessels as dots. Nodular amelanotic melanoma
should be suspected in any non-pigmented nodule that lacks
a specific distribution of vascular structures and when a spe-
cific benign diagnosis cannot be made with confidence. They
also pointed out the importance of other clues such as ulcera-
tion and white structures [42].
Other clues
Menzies et al. reported on scar-like depigmentation as
­positive predictor for the diagnosis of AHM [7]. Bories et al
. noted scar-like depigmentation in all lesions (100 %) of ful-
ly regressed melanomas [10]. In the series reported by Puig
et al. 40 % of amelanotic melanomas were ulcerated [9]. Piz-
zicheta et al. reported ulceration in 20 % of amelanotic mela-
nomas [3], and it was one of the characteristics of amelanotic
melanoma in case study of deGiorgi et al. [26]. Ulcerations
were noted with greater frequency in thick compared to thin
AHM [3, 7]. In similar percentage (23 %) ulcerations were
Minireview

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

© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1206
469
 Minireview

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
Minireview
Summary
Dermatoscopy is useful tool to improve the detection of
AHM. Our small case series confirmed that polymorphous
vascular pattern with no specific arrangement of vessels is a
dermatoscopic characteristic of AHM. In flat AHM in par-
ticular the combination of dotted vessels and linear vessels
may be a strong clue to melanoma. Among non-vascular fea-
tures we consider white lines as the most important clue for
AHM. Ulceration/erosion may indicate thicker tumors.
Correspondence to
Harald Kittler, MD
Department of Dermatology, Division of General
­Dermatology
Medical University of Vienna
Währinger Gürtel 18—20
1090 Vienna, Austria
E-mail: harald.kittler@meduniwien.ac.at
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