Original Paper
Dermatology 2016;232:177–184 Received: August 9, 2015
DOI: 10.1159/000441293
The Prognosis of Nail Apparatus
Melanoma: 20 Years of Experience from
a Single Institute
Emi Dika Annalisa Patrizi Pier Alessandro Fanti Marco Adriano Chessa
Camilla Reggiani Alessia Barisani Bianca Maria Piraccini
Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
Key Words
Nail melanoma · Subungual melanoma · Prognosis ·
Breslow thickness · Mitosis · Functional surgery · Surgical
excision · Management
Abstract
Introduction and Objectives: Nail apparatus melanoma
(NAM) is an uncommon tumor, especially in Caucasians. The
prognosis of patients affected by NAM was analyzed and cor-
related with the histopathological criteria and the surgical
management of the tumors. Materials and Methods: We col-
lected data regarding NAM referred to the Skin Cancer Unit
of the Dermatology Department of the University of Bologna,
from 1992 to January 2012. Results: Out of 1,327 melanoma
cases diagnosed between 1992 and 2012, 42 patients were
affected by NAM (2.93%). All the patients were Caucasian.
Two deceased patients with insufficient medical records and
1 woman with a personal history of breast cancer were ex-
cluded. Thirty-nine cases entered this study: 24 were wom-
en (67%) and 15 men (33%). The mean age at diagnosis of
NAM was 57.3 years (range 29–88 years). Statistical analyses
showed that prognosis was significantly correlated with the
© 2016 S. Karger AG, Basel
1018–8665/16/2322–0177$39.50/0
E-Mail karger@karger.com
www.karger.com/drm
Accepted after revision: September 23, 2015
Published online: January 16, 2016
Breslow thickness (≥/<2 mm; p = 0.02), regression (p < 0.0001)
and ulceration (p = 0.04). Regarding surgical management,
Kaplan-Meier’s test pointed out that performing functional
surgery compared to disarticulation did not correlate with a
better prognosis of patients (p = 0.08). Conclusions: In our
experience, the surgical management (disarticulation with
respect to functional surgical excision) did not influence the
prognosis of NAM patients. The latter was affected by the his-
topathological characteristics (Breslow thickness, regression
and mitoses) and location (fingers vs. foot).
© 2016 S. Karger AG, Basel
Introduction
Nail apparatus melanoma (NAM) is a rare tumor, es-
pecially in Caucasians. The NAM incidence varies ac-
cording to different geographic areas and different popu-
lations. In Australia its incidence has been reported to be
0.31% of all cutaneous melanoma [1], 1.4% in England [2]
and 2.8% in Scotland [3]. The rates of incidence are much
higher in non-Caucasian people, representing up to 23%
of melanomas in Japanese [4], 17% in Hong Kong Chi-
Annalisa Patrizi
Dermatology, Department of Experimental, Diagnostic and Specialty Medicine
University of Bologna
Via Massarenti 1, IT–40138 Bologna (Italy)
E-Mail annalisa.patrizi @ unibo.it
nese [5] and 25% in Afro-Americans. Because of its rarity,
there are only a few studies focused specifically on NAM
management [6, 7]. Most authors include NAM in the
group of cases of acral lentiginous melanoma [8, 9]. We
herein report our single institute experience regarding
the prognosis of NAM patients in correlation with the
tumors’ histopathological characteristics and the surgical
management.
Materials and Methods
For further details, see the supplementary materials (for all on-
line suppl. material, see www.karger.com/doi/10.1159/000441293)
[10–12] (fig. 1).
Results
Out of 1,327 melanoma cases diagnosed from 1992 un-
til 2012, 42 patients were affected by NAM (2.93%). All
the patients were Caucasian. Two deceased patients with
insufficient medical records and 1 woman with a person-
al history of breast cancer were excluded. Thirty-nine cas-
es entered this study: 24 women (67%) and 15 men (33%).
The mean age at diagnosis of NAM was 57.3 years (range
29–88 years). Prognosis did not differ significantly con-
sidering age (p = 0.75) and gender (p = 0.49) of the pa-
tients (fig. 2a, b).
Most NAMs were localized in the thumb (17/39;
43.6%) and in the great toe (9/39; 23%). The other loca-
tions, in decreasing order, were other fingers (4 cases sec-
ond and 3 cases other fingernails) and other toes (6 cases).
NAM of fingers was correlated with a better prognosis
than that of the toes, in the Kaplan-Meier analysis (fig. 2c).
Clinical pictures showed nail plate abnormalities in 28
patients (70% of cases) and the presence of longitudinal
melanonychia in 20 (50%; fig. 3a, b). Pigmentation of the
proximal and lateral nail fold (Hutchinson sign) was ob-
served in 5 patients (12.8%; fig 3c, d). Other signs and
symptoms included a nonhealing wound or an ulcerated
mass of the nail bed and bleeding.
Previous misdiagnoses were frequently referred in our
series. ‘Delay’ was defined as at least 3–6 months from the
time a patient first noticed an abnormality on the in-
volved nail (e.g. discoloration, nonhealing ulcer, nail
plate splitting) till the diagnostic biopsy. Information re-
garding this interval was available for 27 patients (69%);
25/27 patients (92.6%) had a delayed diagnosis. The me-
dian delay time was 48 months.
178 Dermatology 2016;232:177–184
DOI: 10.1159/000441293
Data regarding NAM, referred to the Skin Cancer Unit of the
Dermatology Division, University of Bologna, from 1992
to January 2012, were collected
Inclusion criteria: age >18 years; available (1) clinical data,
(2) histopathological slides, (3) at least 3 years of follow-up
Exclusion criteria: patients affected by multiple cancers
Evaluation of NAM patients’ prognosis on the basis of:
(1) clinical and histopathological criteria of tumors;
(2) type of surgical management: disarticulation of the affected
phalanx with respect to functional surgical excision
Statistics
The Kaplan-Meier test was performed investigating correlations
between patients’ overall survival and the type of surgical
procedure, histopathological findings (NAM Breslow, histological
ulceration and mitoses) and the clinical data (NAM location,
patients’ sex and age at diagnosis)
Fisher’s exact test was used to further evaluate the association
between the investigated tumor variables with prognosis
Fig. 1. Flowchart of Materials and Methods.
A longitudinal incisional biopsy was diagnostic in all
cases. Thirty patients were treated after the latter with
functional surgery, 9 patients with disarticulation of the
last phalanx (fig.  4, 5). The median Breslow thickness
was 2.6 mm (range 0.4–6; table 1). Thin NAMs (Breslow
<1 mm) were mainly localized on the nail matrix (6 cas-
es), whereas in thick NAMs (Breslow >1 mm) the nail bed
was mostly involved (33 cases).
The presence of vascular involvement was detected in
2/39 specimens, inflammatory infiltrate in 10/39, mitosis
in 26/39, regression in 9/39 and ulceration in 24/39 pa-
tients.
The Kaplan-Meier test showed a statistically signifi-
cant correlation between Breslow thickness (<2 mm; p =
0.02), regression (p = 0.0005) and ulceration (p = 0.04)
and patient survival (table 2), identifying these three cri-
teria as negative prognostic factors (fig. 6a, b, d).
Even though all NAM specimens of deceased patients
were positive for the presence of mitosis at the histopath-
ological examination (fig. 6c), the log-rank test was not
statistically significant (p = 0.068).
Two out of 30 patients who underwent functional sur-
gery (fig. 4) had a local recurrence, after 12 and 20 months,
respectively. The disarticulation of the last phalanx was
further performed in these patients (fig. 5). Among the 9
Dika/Patrizi/Fanti/Chessa/Reggiani/
Barisani/Piraccini
 Color version available online
100
96
88 90

Survival probability (%)

Survival probability (%)

80 80
72 70
64
60
56
48 50
40 40
32 Age 30 Sex
24 <60 years Female
20
16
>60 years 10 Male
8
0 0
0 2 4 6 8 10 0 2 4 6 8 10
a Time (years) b Time (years)

100
90

Survival probability (%)

80
70
60
50
40
30 Extremity
Fig. 2. Correlation of the survival outcome
20 Foot
in patients affected by NAM and their age Hand
10
(a; </>60 years; p = 0.75), gender (b; p =
0
0.49) and localization of tumors (c; hand 0 2 4 6 8 10
vs. foot; p = 0.117). The p value is based on c Time (years)
the log-rank test.

Color version available online

a b

Fig. 3. a NAM of the big toe, presenting

with a nail plate dystrophic ulcerated lon-
gitudinal melanonychia. b NAM of the
third digit of the hand. c, d Clinical and
dermoscopic features of NAM extended to
c d
two phalanxes.

Nail Apparatus Melanoma Prognosis Dermatology 2016;232:177–184 179

DOI: 10.1159/000441293
 Color version available online
a b

Fig. 4. a–c Intraoperative aspects of NAM

treated with functional surgery. d Repair of
the surgical defect with a hyaluronic acid-
c d
based dressing.

Color version available online

a b

Fig. 5. a Recurrence of NAM of the first

digit treated with functional surgery. b–d
Intraoperative aspects of last phalanx dis-
c d
articulation.

patients who underwent phalanx disarticulation as first
choice, 8 underwent amputation of the last phalanx and
1 amputation at the tarsal-metatarsal level (melanoma
was extended to two phalanxes; fig. 3c, d).
The sentinel lymph node was positive in 3/15 patients.
Complete lymphadenectomy was performed on all 3 pa-
tients.
Six out of 39 (15%) patients died due to the develop-
ment of multiple visceral metastases (median Breslow
thickness 3.96 mm). The mean time for the development
of metastasis was 3.5 years (range 1–6). One patient died
because of other causes (cardiovascular disease) 16 years
after diagnosis of NAM. Twenty-nine out of 39 (74%) pa-
tients were disease free in the last follow-up visit.

180 Dermatology 2016;232:177–184 Dika/Patrizi/Fanti/Chessa/Reggiani/

DOI: 10.1159/000441293 Barisani/Piraccini
 Table 1. Clinical and histopathological findings of 39 patients diagnosed during 1992 – 2012 stratified by func-
tional surgery and amputation

Functional surgery Amputation Total

Patients 30 9 39
Sex
Male 10 5 15
Female 20 4 24
Age
Mean age, years 59.2 58.3 57.3 (range 29 – 88)
<60 years 11 4 15
>60 years 19 5 24
Breslow thickness
Median, mm 2.3 3.2 2.6 (range 0.4 – 6)
≤1 mm (T1) 6 0 6
>1 to ≤2 mm (T2) 10 1 11
>2 to ≤4 mm (T3) 12 3 15
>4 mm (T4) 2 5 7
Histopathological ulceration
Present 15 9 24
Absent 15 0 15
Mitosis
Present 17 9 26
Absent 13 0 13
Sentinel biopsy
Positive 1 2 3
Negative 8 4 12
Not done 21 3 24
Regression
Present 4 5 9
Absent 26 4 30
Extremity
Hand 19 5 24
Foot 11 4 15
Prognosis
Deceased from metastasis 3 3 6
Deceased from other causes 0 1 1
Disease free 25 4 29
Nodal recurrences currently under treatment 2 1 3

Table 2. Univariate analysis for overall survival of patients affected by NAM

Clinical features OR 95% CI Fisher’s exact

test

Age <60 vs. >60 years 0.77 0.12 – 4.82 p = 1.00

Male vs. female gender 0.57 0.1 – 3.23 p = 0.66
Hand vs. foot 0.25 0.04 – 1.58 p = 0.18
Histological features
Breslow >2 mm (stage III–IV) vs. Breslow ≤2 mm (stage I–II) 13.79 0.72 – 264.5 p = 0.027
Presence vs. absence of mitosis 8.56 0.44 – 164.78 p = 0.08
Presence vs. absence of histological ulceration 10.89 0.57 – 209.06 p = 0.065
Presence vs. absence of regression 50 4.3 – 581.3 p = 0.0005
Surgical procedure
Amputation vs. functional surgery 4.5 0.72 – 28.01 p = 0.12

Nail Apparatus Melanoma Prognosis Dermatology 2016;232:177–184 181

DOI: 10.1159/000441293
 Color version available online
100 100
90 90

Survival probability (%)

Survival probability (%)

80 80
70 70
60 60
50 50
40 40
30 Breslow 30 Histological ulceration
20 •2 mm 20 Nu ulceration
10 >2 mm 10 Ulceration
0 0
0 2 4 6 8 10 0 2 4 6 8 10
a Time (years) b Time (years)

100 100
90 90
Survival probability (%)

Survival probability (%)

80 80
70 70
60 60
50 50
40 40
30 Mitosis 30
Regression
20 No 20
Fig. 6. Correlation between survival out- No regression
10 Yes 10
come of patients and NAM histopatho- Regression
0 0
logical characteristics. a Breslow thickness 0 2 4 6 8 10 0 2 4 6 8 10
(p = 0.02). b Ulceration (p = 0.04). c Mito- c Time (years) d Time (years)
sis (p = 0.068). d Regression (p = 0.0005).

Color version available online

Regarding surgical management of these patients, sta-
tistical analyses performing the Kaplan-Meier test showed 100
that functional surgery compared with amputation did 90
Survival probability (%)

not correlate with a better prognosis in patients with stag- 80

70
es I and II (fig. 7; table 2). 60
50
40
Discussion 30 Surgical procedure
20 Amputation
10 Functional excision
The prognosis of NAM in Caucasian patients is labo- 0
rious to evaluate due to the exiguity of data. Most studies 0 2 4 6 8 10
refer to single center experiences, reporting relatively Time (years)

small series if compared to cutaneous melanoma [8].

With regard to studies focused on tumor biology and
mutation analyses, there are only very few reports spe-
cifically concentrated on NAM [13]. The survival rates at
5 years range from 18 to 58% [14–16]. Since its first de-
scription in 1834 by Alexis Boyer, first surgeon to Napo-
leon, and the further definition of NAM characteristics
in 1886 by Sir Jonathan Hutchinson, most authors con-
tinue to report a delayed diagnosis [17]. Most frequently
NAM is misdiagnosed as a nail infection: mainly onycho-
mycosis, subungual hematoma, traumatic injury or ac-
quired nevus [8–21]. Delayed diagnosis and advanced
Fig. 7. Correlation between survival outcome of patients and the
surgical management of NAM (amputation vs. functional sur-
gery).
disease at the time of treatment may contribute to poor
outcomes.
Recent studies have focused on the correlation be-
tween surgical procedures and NAM prognosis [22–24].
Controversies regarding treatment have persisted for de-
cades. The surgical management of NAM and the recom-

182 Dermatology 2016;232:177–184 Dika/Patrizi/Fanti/Chessa/Reggiani/

DOI: 10.1159/000441293 Barisani/Piraccini
mendation for digit amputation have been influenced
mainly by two factors: (1) early studies on cutaneous ma-
lignant melanoma, not NAM specifically, that promoted
wide local excision as the treatment of choice, and (2) the
peculiar anatomy of the nail unit, which is characterized
by a very thin soft tissue between the nail unit and the
bone of the distal phalanx.
Recent series reported that the resection level of am-
putation does not influence the prognosis [16]. The con-
servative approach, performing Mohs surgery or the so-
called functional surgical excision, consisting in an en
bloc NAM excision (including proximal fold, matrix,
nail bed, hyponychium, with a 6-mm lateral margin
around the anatomical delineating structures and down
to the bone [10]) has shown a good outcome with low
rates of recurrences, especially in cases of NAM in situ
or NAM with a Breslow thickness <1 mm [25, 26]. De-
spite this tendency toward a more conservative excision
with a good outcome, no series are large enough to per-
mit definitive surgical guidelines. Most cases of NAM
treated with functional surgery report in situ or thin
NAMs, with Breslow thickness <1 mm. Good prognosis
of NAM and no recurrences after functional surgery of
tumors presenting a Breslow thickness >1 mm have re-
cently been reported in 3 patients by Nakamura et al.
[23], in another 3 by Rayatt et al. [27] and in a single case
by Smock et al. [28]. The series of NAM we report here
is the largest that includes patients with intermediate
Breslow thickness (10 cases) with a conservative man-
agement and a long-term follow-up. Local recurrences
or distant metastases were not observed in these pa-
tients.
In conclusion, in our experience functional surgery
compared to amputation did not correlate with a better
prognosis, even in patients presenting with an intermedi-
ate Breslow tumor thickness (NAM 1–2 mm). Prognosis
was affected by the histopathological characteristics
(Breslow thickness and mitoses) and location (fingers vs.
foot) of NAM. The limitations of the study are the limited
number of cases and the retrospective assessment of the
data.
Larger series and multicenter prospective studies are
necessary to overcome the latter issues.
Statement of Ethics
Surgical samples and data used in this study were obtained in
the course of institutional diagnostic services. The investigation
described was carried out on residual biopsy sections following
diagnostic analysis, providing that all the patients’ data were kept
anonymous.
Disclosure Statement
The authors declare no funding sources supporting the work
and no conflicts of interest.

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