Longitudinal melanonychias

Nilton Di Chiacchio, MD, PhD

a,

, Beth S. Ruben, MD
b
,
Walter Refkalevsky Loureiro, MD
a
a
Dermatology Clinic, Hospital do Servidor Pblico Municipal de So Paulo, Sao Paulo, Brazil
b
Departments of Dermatology and Pathology, Dermatopathology Service, University of California, San Francisco, California
Abstract Melanonychia is black or brown pigmentation that appears in the fingernails and toenails. The
pigment can come from exogenous sources, such as bacteria or fungal infection, tar, or blood. Endogenous
causes include aberrant melanin production in the nail bed, resulting in a longitudinal presentation.
Melanonychia can indicate the presence of cancerous growths, as well as infection. Diagnostic measures,
including dermatoscopy, biopsy, and histopathology, can determine the cause and direct the course of
treatment. Malignant lesions should be excised, and underlying infections should be addressed with
antibiotics or antifungals. Benign lesions and hyperpigmentation may benefit froma wait-and-see approach.
2013 Elsevier Inc. All rights reserved.
Introduction
Melanonychia is defined as a brown or black pigmentation
ona fingernail or toenail. It may be due to exogenous pigments,
including tobacco, dirt, or tar; fungi such as black molds;
bacteria such as Pseudomonas aeruginosa and Proteus spp; or
blood. In these cases, the clinical feature is variable according
to its etiology. A thorough history, dermatoscopy of nail plate,
direct examination of nail scales, and cultures for fungi and
bacteria may aid in the diagnosis.
1
Melanonychia, caused by
melanin produced by the nail matrix, is almost always seen as a
longitudinal band and, therefore, called longitudinal melano-
nychia (LM). Longitudinal melanonychia can be caused by
nonmalignant diseases that include nevi of the nail matrix, nail
matrix lentigo, and a number of inflammatory, traumatic, or
iatrogenic nail disorders due to an activation of the nail matrix
melanocytes (hypermelanosis).
2,3
LM may indicate an early
stage of nail melanoma, and its diagnosis remains a challenge
for dermatologists.
4
Melanonychia diagnosis is based on clinical history,
worrisome clinical features, and the ABCDEF rule.
5
In this
rule, A stands for age (the peak of incidence occurs from the
fifth to the seventh decade) and African Americans, Asians,
and native Americans. Bstands for a brown to black band with
breadth of 3 mm or more and variegated borders. C stands for
change in the nail band. D stands for the digit most commonly
involved. E stands for extension of the discoloration into the
cuticle or nail fold, and F stands for family or personal history
of dysplastic nevus or melanoma.
5
Dermatoscopy of nail plate,
nail matrix, and nail bed can help, but histological examination
remains the gold standard for diagnosis.
History
Data from the clinical history may be useful in the
diagnosis of melanonychia. Drugs may induce pigmentation
in several nails by toxicity of the nail epithelia.
6
Blood

Corresponding author. Tel.: +55 119 81829703; fax: +55 112 9798931.
E-mail address: ndichia@terra.com.br (N. Di Chiacchio).
0738-081X/$ see front matter 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clindermatol.2013.06.007
Clinics in Dermatology (2013) 31, 594601
thinners, such as aspirin, facilitate subungual hemorrhage,
especially when associated with trauma.
2
Although trauma
is commonly reported in patients with nail melanoma, its
role in the pathogenesis of the disease process is not
established.
7
The disease duration and growth characteristics
of the abnormality are important information since fast
growth and a short history, although not pathognomonic, are
concerning. In the same way, any change in color and shape
is also relevant.
Clinical features
The sudden appearance of a pigmented band in a
previously normal nail plate; inhomogeneous pigmentation,
with bands or lines of different colors; presence of nail plate
fissuring, or splitting, especially in the distal part of nail
plate; rapid enlargement of an existing band; a proximal part
of the band that is broader than the distal (triangular shape)
(Figure 1); and blurred lateral borders are considered
worrisome clinical features in adults, but not pathognomon-
ic.
3
In children, these signs are not considered as concerning,
and they can be present in benign lesions, particularly nevi,
but they cannot be overlooked (Figure 2). Despite the fact
that nail melanoma is rare in children, it does exist
8,9
(Figure 3).
Pigmentation of the periungual skin, also known as the
Hutchinson sign, is the spread of brown-black pigment seen
on the adjacent cuticle and proximal and/or lateral and/or
distal nail folds. It is not to be considered pathognomonic of
nail melanoma, but a presumptive sign. It represents a
clinical sign of the radial growth phase of nail melanoma
(Figure 4). When it is present, an excisional biopsy to
exclude nail melanoma should be done. Some researchers
have described two different patterns of hyponychium
pigmentation in benign melanocytic nevi and nail melano-
mas with the use of dermatoscope.
11
A brushy linear
structure across the skin was observed in nevi, and a
haphazard pigmentation distributed in a disorderly fashion
over the entire surface was seen in melanomas.
10,11
Periungual hyperpigmentation may occur in Bowen's
disease of the nail or in dark pigmented bands where the
pigmentation is visible through the transparent nail fold
simulating Hutchinson's sign. In both cases, this sign is
known as pseudo-Hutchinson sign.
10,11
(Figure 5).
Fig. 1 The proximal part of pigmented band is wider than the
distal (triangular shape).
Fig. 2 Distal nail plate fissuring in childs finger. The
hystopathologic examination showed a nevus.
Fig. 3 In situ subungual melanoma in a child of 6 years of age.
Fig. 4 Hutchinson sign. In panel A: pigmentation of the proximal
nail fold. In panel B: pigmentation of lateral and distal nail fold.
Both cases were melanomas.
595 Longitudinal melanonychias
In an effort to improve the early detection of subungual
melanoma, some researchers developed the ABCDEF rule
Age; Band, Breadth, and Border; Change; Digit involved,
Dominant hand; Extension; Family or personal history).
5
According to a recent report, the rule does not improve the
diagnostic accuracy of subungual melanomas.
4
Dermatoscopy of nail plate
Dermatoscopy of nail plate is a noninvasive method that
helps to narrow the differential diagnosis of pigmented
lesions of the nail. Two kinds of devices are available based
on the presence or absence of polarized light.
12,13
A
dermatoscope without polarized light needs a contact gel
such as ultrasound gel because its decreased viscosity
permits it to stay on the nail plate, fill any concavities
without rolling off, and allow light refraction.
14
The
polarized light device does not need contact with the nail
plate; thus, gel is not necessary. Some criteria of longitudinal
melanonychia can be evaluated by dermatoscopy
12
:
1. A gray pigmented band composed of multiple thin
homogeneous grayish lines means hyperpigmentation
due to a melanocytic activation (hypermelanosis) fre-
quently seen in cases of drug-induced pigmentation and
ethnic pigmentation.
12,13
2. A brown pigmented band composed of multiple thin
brown lines due to melanocytic hyperplasia, as seen in a
nevus lentigo or melanoma. The brown lines can be
regular or irregular according to parallelism, spacing,
thickness, and color. The regular pattern means a benign
pole and is usually associated with a homogenous brown
background band. The color of the individual lines within
the band can vary from light brown to black. The spacing
between the lines is regular, and the thickness of the lines
is relatively uniform throughout the band. An irregular
pattern means a malignant pole; the lines appear with
irregular spacing and thickness and disruption of
parallelism. The color of the individual lines varies from
light brown to black
12,13
(Figure 6).
Dermatoscopy of nail matrix and bed
Dermatoscopy of the nail matrix and bed is an
intraoperative procedure indicated in suspicious cases
when biopsy of the nail matrix is performed.
14
The polarized
light device is better for this kind of dermatoscopy because it
does not need contact with the lesion. After distal block
anesthesia, the proximal nail fold is reclined, and the third
proximal part or total nail plate is dissected and separated
from nail bed. Removal of the nail plate is very important
because it allows for fine visualization of pigmentation,
revealing aspects not observed when the nail plate is
interposed. The advantage of polarized light dermatoscopy
is that there is no necessity to touch the surgical wound. The
Fig. 5 Bowen disease of nail unit. Pigmentation of proximal and
lateral folds.
Fig. 6 Nail plate dermatoscopy. In panel A: light brown fine lines (hypermelanosis). In panels B and C: regular pigmented lines with
different thickness and colors (nevus and lentigo respectively). In panel D: lines with irregular spacing and thickness and disruption of
parallelism (melanoma).
596 N. Di Chiacchio et al.
criteria evaluated are similar to those used in dermatoscopy
of the nail plate. Briefly, a gray lesion with multiple thin lines
means melanocytic activation, while a brown lesion means
melanocytic hyperplasia. Parallelism, spacing, thickness,
and color of lines are also evaluated. Two others structures
can be observed: globules and blotches. The presence of
globules is pathologically correlated with the presence of cell
nests. The blotches seen in some cases are correlated with the
presence of a large amount of pigment, which often masks
the globules. Four different patterns of melanonychia were
validated for intraoperative dermatoscopy of the nail matrix:
regular gray, regular brown, regular brown with globules or
blotches, and irregular pattern. Regular gray pattern is
associated with melanonychia due to melanocyte activation.
Melanocytic activation produces pigmentation only on the
basal layer, which could explain the gray or light brown
coloration. The regular brown pattern is associated with
typical melanocytic hyperplasia. The larger amount of
pigment produced by melanocytic proliferation explains
the brown coloration. The regular brown pattern with
globules or blotches is associated with melanocytic nevi.
The irregular pattern is associated with melanoma. The
irregular morphology is explained by the disorganized
proliferation of atypical cells. The presence of irregular
globules correlates with atypical cell nests. Cell proliferation
produces thick longitudinal lines with spread of the
pigmentation to adjacent regions. Irregular blotches due to
a large amount of pigment may be observed in this pattern
(Figure 7).
Differential diagnosis
Suspected melanonychia should be differentiated from
that due to melanin and without melanin. History, clinical
appearance, and dermatoscopy are important tools for the
differential diagnosis. In cases of melanonychia due to other
pigments, the shape of pigmentation is variable according to
the pigment involved and rarely appears as a longitudinal
black/brown streak.
Subungual hematoma appears as an irregular area or even
as a transverse streak from dark red to black. Irregular edges
of the pigmentation and a small area of leukonychia that
grows outward with the nail are considered clues to the
diagnosis.
15
Reddish-black globules and streaks are ob-
served by dermatoscopy of the nail plate
2
(Figure 8). The
diagnosis of subungual hematoma does not rule out a
coincident nail tumor.
Nail pigmentation due to fungi may appear as a
longitudinal band, but almost always with irregular edges
and colors. It may be caused by species of dematiaceous or
nondermatiaceous fungi
2,16
(Figure 9).
Melanonychia due to melanin is referred to as longitudi-
nal melanonychia (LM) by its clinical appearance. Hyper-
melanosis may be present in one or multiple digits. Its color
is grayish or light brown with regular thin lines and is easily
seen by dermatoscopy of nail plate. The cause of
hypermelanosis is defined by a thorough history and/or
histological examination. Clinically, lentigos and nevi
produce regular longitudinal brown or black streaks without
worrying clinical features. It is important to remember that in
children these features may appear in benign lesions.
2
Conversely, melanomas appear as a longitudinal band but are
almost never associated with concerning clinical features.
Fig. 7 The four patterns described for dermatoscopy of nail matrix and bed.
Fig. 8 Subungual hematoma due to a trauma. Globules, streaks,
and leukonychia can be observed.
597 Longitudinal melanonychias
Dermatoscopy of the nail plate may be considered a tool for
the differential diagnosis of benign or malignant lesions, but
it is not as informative as dermatoscopy of the nail matrix
and bed, despite its invasiveness.
Biopsy
Suspicious cases of melanonychia must be biopsied. The
physician should consult the patients history, clinical
features, and dermatoscopy findings to decide whether to
proceed with a biopsy or not. In case of doubt, nail matrix
biopsy avoids a misdiagnosis.
According Braun et al,
2
a biopsy is indicated in the
following cases:
1. The presence of an isolated pigmented band on a single
digit that develops during the fourth to sixth decade of
life. Although melanoma can be seen in children, it is a
very rare event.
2. Nail pigmentation that develops abruptly in a previously
normal nail plate.
3. Pigmentation that suddenly becomes darker or larger or
when the pigment becomes blurred near the nail matrix.
4. Acquired pigmentation of the thumb, index finger, or
large toe.
5. Pigment that develops after a history of digital trauma and
in which subungual hematoma has been ruled out.
6. Any acquired lesion in patients with a personal history
of melanoma.
7. If the pigmentation is associated with nail dystrophy,
including partial nail destruction or absence of the
nail plate.
8. If pigmentation of the periungual skin (including lateral
nail folds) is found to be present (Hutchinsons sign). This
includes pigment of the cuticle or hyponychium.
Another point rarely discussed is whether or not the
patient wants the lesion removed when biopsy is not
indicated. Many patients dont like to see a black/brown
band on their digit. In cases of multiple melanonychia due to
drugs or race, the patient is informed about the impossibility
of multiple excisions and recurrences. In front of a simple
band on a single digit, the patient should be advised about the
possibility of nail dystrophy before the procedure.
After the decision to biopsy, the best technique should be
chosen. One study
17
proposed an algorithm for biopsying
longitudinal melanonychia, suggesting lateral longitudinal
excision for a laterally located pigmented band, full-
thickness excision or biopsy for high likelihood of invasive
melanoma, a 3-mm punch excision for lesions smaller than 3
mm of the proximal or distal nail matrix, and matrix shave
biopsy for lesions with 3 mm or more of the proximal or
distal nail matrix. Even though these techniques are well
indicated, we believe that the main point for a good
procedure is the direct view of the pigmented lesion and
the complete removal of the lesion. For that, the proximal
nail fold must be reclined and the proximal half of the nail
plate detached. Besides allowing a complete view of the
lesion and surrounding region, this method also allows for
intraoperative dermatoscopy, providing useful information
for the differential diagnosis of melanonychias
18
(Figure 10).
Fig. 9 Melanonychia striata due to a fungi.
Fig. 10 3 mm biopsy. In panel A: melanonychia of the fifth right toenail. In panel B: incision by punch (3 mm). In panel C: wound produced
after excision of the specimen.
598 N. Di Chiacchio et al.
The shave matrix biopsy, better called tangential exci-
sion,
19
is the best choice in the majority of cases for an
excisional biopsy, as it avoids the concerns of post-operative
nail plate dystrophy. It is indicated in all cases of
melanonychias. The specimen removed needs an experienced
histological technician and pathologist to follow the specimen
processing; given these individuals, it allows material for a
histopathological diagnosis
20
(Figure 11).
Histopathology
Despite assessment of clinical features, the ABCDEF
rules, and dermatoscopy as adjunct tools in the diagnosis of
melanonychia, histopathological examination remains
the gold standard.
3
An understanding of the particular
histologic anatomy of the nail unit is essential for an
optimal diagnosis of melanocytic lesions in this locale.
These lesions have similar features to melanocytic pro-
liferations at other cutaneous sites, but there are other
emerging diagnostic criteria.
The density of nail matrix melanocytes is lower than in
normal skin, and they are inconspicuous in the normal matrix.
They may be found in a suprabasilar position, especially in the
proximal matrix. In the distal matrix, approximately 50% of
melanocytes synthesize melanin. In the nail bed, melanocytes
are even fewer and do not synthesize melanin.
21,22
This explains
why melanoma originating in the nail bed is often amelanotic.
Four common histologic entities explain most examples
of longitudinal melanonychia: melanocytic activation
(hypermelanosis), lentigo (benign melanocytic hyperplasia),
nevus, and melanoma.
15
Melanocytic activation is the most common cause of
melanonychia in adults
23
and consists mainly of hyperpigmen-
tation of the nail matrix epithelium without an increase in the
number of melanocytes. The normal density of melanocytes in
the nail matrix is 49 per mm interval or 200 per square mm in
histologicsections.
22,24
Themelanocytesareoftendendritic, and
there may be scattered melanophages.
15
Both melanocytes and
melanin pigment can be difficult to discern in routine sections,
Fig. 11 Tangential excision of the pigmented lesion. In panel A: Proximal nail fold and nail plate are reclined. In panel B: The blade runs
tangentially under the pigmented lesion. In panel C: The specimen is easily removed.
Fig. 12 Junctional nevus of nail matrix: regular nests of
melanocytes are evident in the distal matrix (200x magnification).
Fig. 13 Melanoma in situ of the nail unit: Atypical melano-
cytes in irregular array throughout the nail matrix and bed
epithelium, with irregular melanin granules within the nail plate
(200x magnification).
599 Longitudinal melanonychias
and thus immunostaining is used to quantify melanocytes.
Additionally, Fontana staining may be required to identify
melanin to confirma diagnosis of melanocytic activation.
Lentigo consists of a slight or moderate increase in the
number of singlematrical melanocytes, generallyintherangeof
1531 per mm interval.
24
Dendritic melanocytes can be seen,
and cytologic atypia should be limited. Also in lentigines, a
sparse infiltrate of melanophages may be observed.
15
Immu-
nostaining can be helpful to quantify melanocytic density,
especially in heavily melanized lesions, in which the epithelial
pigmentation can obscure melanocytes. Markers of melanocy-
tic nuclei, such as MiTF and SOX-10, performed with a red
chromogen, are optimal for accuratelyestablishingmelanocytic
density. Melan-Aas a melanosome marker can overemphasize
melanocytic density. S100 protein may be variable in this
location, and its use may lead to an underestimation.
15
Nevi of the nail unit are usually junctional and rarely
compounded. The ordinary type is the most frequent, and nail
nevi are the most common cause of melanonychia in
children.
25
Some features of nail unit nevi are similar to acral
nevi. There is usually a lentiginous pattern of melanocytes in
early lesions. Melanocytes can be larger and more hyperchro-
matic. The cell nests can be irregular or slightly confluent,
depending in part on the sectioning of the nevus in relation to
the ridge pattern of the epithelium, with a more regular pattern
observed in infrequently usedtransverse sections. Melanocytes
may be present in limited fashion above the basal layer. This is
a worrisome feature more extensively seen in melanoma, in
which melanocytes can even be found in the nail plate.
15
The
nail fold epitheliummay also be involved, but this should be in
a nested and circumscribed fashion. Nevi with pigmented
epithelioid melanocytes, blue nevi, and Spitz nevi of nail
matrix are rarely reported
2628
(Figure 12).
Making a diagnosis of melanoma of the nail unit remains a
challenge even for experts, mainly with respect to early
lesions. Criteria useful in establishing a diagnosis include poor
circumscription; the density of intraepidermal melanocytes
(range of 39136 in one study)
24
; an irregular distribution of
melanocytes, including marked confluence of nests; degree of
suprabasal scatter; cytologic atypia; a lymphocytic infiltrate;
and anisodendrocytosis (variation of dendrite size, also seen in
acral melanoma).
7,15
Although the Breslow thickness can be
measured, the correlation of thickness and prognosis may not
be the same as for skin melanoma elsewhere. Clarks levels
cannot be established in the same manner. There is no distinct
papillary dermis or subcutis in the nail unit proper, although
these are present in periungual acral skin and can be used in
establishing conventional Clarks levels, if involved. Level V
can be reported as involvement of the phalangeal periosteum
or bone
6,29
(Figure 13).
Treatment
The treatment of melanonychia depends on the etiology of
the pigmented lesion and the patient. The possibilities for
Fig. 14 Tangential excision for the treatment of melanonychias. In panel A: longitudinal melanonychia of the second right fingernail. In
panel B: after total excision of the pigmented lesion. In panel C: after 12 months without nail plate dystrophy.
Fig. 15 Functional surgery for the treatment of in situ subungual melanoma of the left great toe. In panel A: triangular shape of the
pigmented lesion. In panel B: nail unit completely removed. In panel C: wound produced. In panel D: healing by second intention after
2 months.
600 N. Di Chiacchio et al.
benign lesions are wait-and-see and excision. When surgery is
chosen, patients should be advised of the possibility of nail
plate dystrophy. Hypermelanosis does not need any treatment;
even when removed, recurrence is frequent. Nevi and lentigos
are the most difficult cases for deciding upon a course of
action. Wait-and-see is unacceptable due to the possibility of
malignant transformation. In children, this possibility is very
rare, but it exists. Tangential excision is the best option when
surgery is chosen. It allows a complete removal of the lesion
with minimal or no nail plate dystrophy (Figure 14).
Surgical treatments for subungual melanomas in situ
changed fromradical surgeries to conservative ones, removing
the whole nail unit with phalange preservation.
30
The defect
can be repaired either by skin graft or second intention
healing
31
(Figure 15). The procedure allows a good cosmetic
and functional outcome, and the prognosis is not changed.
32
Finally, amputation remains the best option for invasive
melanomas, trying whenever possible to preserve the
functionality
33
(Figure 16).
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Fig. 16 Amputation for the treatment of invasive subungual
melanoma. In panel A: longitudinal melanonychia with a
distal and lateral Hutchinson sign. In panel B: after amputation of
distal phalanx.
601 Longitudinal melanonychias