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Clinics in Dermatology (2013) 31, 602617

Nail tumors
Bertrand Richert, MD, PhD , Pauline Lecerf, MD, Marie Caucanas, MD,
Josette Andr, MD
Department of Dermatology, University Hospitals Brugmann, St Pierre and Queen Fabiolas Children Hospital,
Universit Libre de Bruxelles, CHU Saint Pierre, Rue Haute 322, 1000 Brussels, Belgium

Abstract Most neoplasms of the nail apparatus have different clinical appearances, courses, and biological
behaviors as compared with similar tumors located elsewhere on the skin. Some of these tumors are unique
to the nail, such as onychomatricoma. As a general rule, benign lesions respect the general architecture of the
nail apparatus, whereas malignant ones are destructive. Our review covers the most common nail tumors,
from benign ones to the most frequent nail malignancy, the squamous cell carcinoma, which actually is the
greatest simulator. We will also discuss new approaches to the diagnosis and treatment of melanoma of the
nail apparatus. Physicians should be aware of these conditions and their management.
2013 Elsevier Inc. All rights reserved.

Benign tumors
Pyogenic granuloma
Nail pyogenic granuloma (PG) is a relatively common
acquired benign vascular tumor that frequently involves the
nail apparatus, including the periungual tissues and the nail
bed. Nail PG is due to different causes that act through
various pathogenetic mechanisms. Histopathology shows
similar features in every type of PG, irrespective of the
original cause and location. When there is a single PG,
especially if it involves the nail bed, histological examination
is necessary to rule out malignant melanoma.
Most cases of nail PG involve one of the following types:
1. Drug-induced PG
A main characteristic of drug-induced PG is the involvement of multiple nails of both fingers and toes. Several
Corresponding author. Tel.: + 32 2 535 43 79; fax: + 32 2 477 31 11.
E-mail address: bertrand.richert@chu-brugmann.be (B. Richert).
0738-081X/$ see front matter 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clindermatol.2013.06.014

cases have been reported during treatment with retinoids


(eg, systemic acitretin, systemic isotretinoin, systemic
etretinate, topical retinoic acid, topical tazarotene).1-5 The
onset of painful periungual PG as a possible side effect of
antiretroviral therapy (especially with indinavir and
lamivudine) for human immunodeficiency virus infection
has also been known for several years.1,6-8 The administration of the following antineoplastic therapies can also
induce multiple PGs: epidermal growth factor receptor
inhibitors (eg, cetuximab, gefitinib)1; agents of the
fluoropyrimidine family (eg, capecitabine)9-11; systemic
5-fluorouracil12; agents of the taxane family (eg, docetaxel,
paclitaxel)1,13,14 (Figure 1); mitozanthrones15; and cyclosporine.16 One recent case of multiple eruptive PG has
been reported in association with anti-CD20 antibody
treatment for severe rheumatoid arthritis.17
2. PG caused by local mechanical traumas
PG can appear after local traumas, including ingrown
nails, retronychia,18 and friction during a long walk19
(Figure 2). Among self-induced nail trauma, onychotillomania, onychophagia, and aggressive manicuring may be

Management of benign and malignant tumors of the nail apparatus

Fig. 1 Pyogenic granulomas of the nail bed in a patient


undergoing chemotherapy with taxanes.

responsible for the development of PG.20 PG can also


occur after penetration of a foreign body within the nail
tissue or after an acute mechanical trauma.
3. PG caused by peripheral nerve injury
Different conditions, all of which involve peripheral nerve
injury, are associated with the development of nail
changes and PG of the proximal nail fold. Cast
immobilization has been reported as a possible cause of
periungual PG21; an improper cast application may
induce peripheral nerve damage, probably in response
to mechanical compression. Patients complain of moderate paresthesia and pain during cast wearing and develop
painful onychomadesis, periungual swelling, and PG
involving the proximal nail fold a few days after cast
removal. Similar nail changes are observed with reflex
sympathetic dystrophy.22 The development of periungual
PG has also been reported after Guillain-Barr syndrome,23 in patients with hemiplegia,24 and after several
episodes of oxygen desaturation.25
4. PG due to inflammatory systemic diseases
Multiple periungual PGs of several fingernails and
toenails were reported in patients with inflammatory
systemic diseases, such as cutaneous sarcoidosis, psoriasis, and seronegative spondyloarthritis.1
Treatment must be chosen in accordance with the cause
of the PG. If the PG is the result of local trauma, the first

Fig. 2 Pyogenic granuloma of the distal nail bed as a result of


friction in a patient with obvious hallux erectus.

603

thing to do is to remove the trauma (eg, nail avulsion with


retronychia, surgical removal of a foreign body, cutting an
onycholytic nail for a frictional PG, stopping nail
manipulation with onychotillomania); the PG may then be
treated with topical steroids and antibiotics or with
curettage. If PG is the result of drugs, topical medications
or curettage may be effective, but usually a decrease in the
drug dose is necessary, especially for retinoids and
antitumoral drugs. In cases of antiretroviral therapy, topical
treatment or curettage can be effective; in nonresponding
cases, the replacement of the drug that is inducing the PG
with a different agent is necessary. PG caused by cast
immobilization usually heals with topical steroid treatment.
PG caused by reflex sympathetic dystrophy or systemic
disease is more difficult to treat and often requires several
cycles of topical therapies or surgical removal.1

Glomus tumor
A glomus tumor is very common on the hand and
represents about 1% to 2% of all hand tumors.26 It arises
especially at the fingertips, because the glomus bodies of
Masson are numerous at that location. In up to 90% of the
cases, this condition affects women who are about 45 years
old.27 There are two main clinical presentations:
1. A small reddish or bluish spot of several millimeters (b 10
mm) in diameter that can be seen through the nail plate
(Figure 3, A).
2. A longitudinal erythronychia with distal notching or
overlying longitudinal fissure.
Pain is the leading symptom; it may be spontaneous or
provoked by the slightest trauma. Pinpoint pain occurs, and
this involves throbbing and exacerbation with pressure and
with variations in temperature, especially cold. Sometimes,
the pain is worse at night. One case reported that even
applying polish to the nail was unbearable.28
Several clinical tests are available for the clinical
diagnosis of glomus tumors. The first one is the Love pin
test, which involves probing with a blunt instrument (eg,
paperclip, pencil) to determine the most tender area. The
Hildreth test involves applying an inflatable cuff to the arm,
inflating it to more than 300 mm Hg of pressure, and then
repeating the Love pin test; the test is positive if the patient
does not experience any pain with probing. The cold
sensitivity test should result in increased pain with exposure
to cold (eg, an ice cube). One paper revealed that the cold
sensitivity test was 100% sensitive, specific, and accurate29;
the Hildreth test was found to be 71.4% sensitive, 100%
specific, and 78% accurate, and the Love pin test was found
to be 100% sensitive and 78% accurate. Additional help may
come from transillumination.30 Some researchers consider
clinical exploration to be typical enough to confirm the
diagnosis and exact location of a digital glomus tumor.31 The
differential diagnosis includes all causes of onychalgia, but it

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B. Richert et al.
Glomus tumors show a high signal in T2-weighted images and
a strong enhancement after gadolinium injection; however, the
signal behavior may vary with the histologic nature (eg,
vascular, cellular, myxoid) of the lesion.36 The tumor limits are
usually sharp, with a peripheral pseudocapsule that results
from a reactional response of the surrounding connective
tissue. This capsule shows a very low signal on all sequences
and seems to be incomplete in about 25% of cases.37 Cortical
erosion that is only revealed by MRI is very common. MRI is
used to accurately determine the spatial location of the tumor
so that a precise and radical surgical resection can be
performed.38 It may also help with the detection of multiple
glomus tumors in the same fingertip.37 Recurrences were
previously thought to be the result of the incomplete removal
of the original tumor, but they may actually be attributed to
small, synchronous, satellite lesions.39 A series of 75 cases
involved a global recurrence rate of 17%, but no recurrence
was observed in the group of patients who underwent
preoperative MRI or ultrasound studies.40
The only treatment of this condition is the surgical
removal of the tumor, which results in the resolution of
symptoms. Some surgeons favor the direct approach after
nail plate avulsion through the nail bed (see Figure 3, B and
C) or the matrix with meticulous repair.41,42 An alternate
approach is the lateral incision. This incision allows for the
exposure of the dorsal distal phalanx without violating the
matrix, thereby reducing the risk of postoperative deformity.43 This lateral approach offers a more narrow view of the
tumor with a higher chance of incomplete excision as
compared with the transungual approach.27,44 It should be
recommended for lesions that are deep seated proximally.45

Subungual exostosis

Fig. 3 A, A painless glomus tumor. Note the bluish spot under


the nail plate. B, After nail plate avulsion. The tumor is clearly
visible. C, The direct surgical approach through the nail bed, with a
longitudinal excision and extirpation of the tumor.

is important to note that, in some very rare instances, the


glomus tumor may be totally painless and appear only as a
bluish or reddish dot.
Plain radiographs show bone erosion in 50% of cases.27,32
Doppler ultrasound studies have been able to confirm
diagnosis, but they often fail for small tumors (ie, b 2
mm).33 Recent developments in high-variable frequency
ultrasound have made it possible to identify small glomus
tumors in real time and with high resolution. The procedure
does not require the administration of intravenous contrast
media, and it provides good information about blood flow and
the surrounding structures.34 Glomus tumors are a main
indication for the use of magnetic resonance imaging (MRI) of
the nail unit.35 MRI is preferable because it offers the highest
sensitivity and a better assessment of the extent of the lesion.

Subungual exostosis (SE) is an isolated, slow-growing,


benign osteochondral outgrowth. Although most authors
consider SE to be a distinct clinicopathologic entity,46 some
lump this condition in with the osteochondromas.47 Trauma
seems to be the most important etiologic factor.48 Individuals
who are in their 20s are those who are mostly affected.48-50 The
sex ratio varies from series to series, but it is most probably 1:1.
All large series have shown that the great toenail is selectively
affected in 75% of cases.48,49,51 The involvement of lesser
toenails or fingernails (ie, the thumb and index fingers) has
been observed in 10% to 15% of cases.51-53
The proliferation involved with this condition usually
elevates the nail plate and then emerges from the hyponychium or sometimes from a lateral sulcus. The tumor may
exhibit a porcelain white hue with telangiectasia running on its
surface during the early stages. Often, a collarette delineates
the tumor (Figure 4). With time, the proliferation is covered
with thick hyperkeratosis. Centrodorsal lesions may present as
red patches seen through the nail plate, with or without
onycholysis. Erosion and infection of the nail bed may
give rise to a subungual pyogenic-like outgrowth.54 The
association of nail deformity with pain is highly suggestive

Management of benign and malignant tumors of the nail apparatus

605

Fig. 5
Fig. 4 Subungual exostosis. The tumor is lifting up the distal plate.
Note the collarette and the telangiectasias running on its surface.

of SE, but pain is not always present. The differential


diagnosis includes verruca vulgaris, fibrokeratoma, pyogenic
granuloma, squamous cell carcinoma (SCC), ingrown toenail
and amelanotic melanoma.
Radiographic examination is paramount for the diagnosis
of SE; however, early lesions that are mostly formed from
cartilage may be not visible. There is progressive calcification and the formation of a trabecular pattern of bone. During
the end stage, the trabecular bone at the base of the exostosis
connects to the underlying phalanx. The exostosis appears
smaller on a radiograph as compared with the intraoperative
findings as a result of the radiolucency of the cartilaginous
cap that constitutes the bulk of the tumor.49,55
Treatment involves the resection of the outgrowth under
full aseptic conditions. Complete resection, including the base
of implantation into the cortex of the phalanx, is needed; in
other words, until the spongy bone is visualized.54 Different
surgical approaches are possible in accordance with the
location and size of the SE. Dissection is difficult, because
the tumor has most often thinned the nail bed. When possible,
the bed is lifted in two flaps to expose the whole tumor. The
tumor is removed with a bone rongeur, the cavity is filled with
Gelfoam or Surgicel, and the flaps are put back in place,
trimmed to adequate size, and cautiously sutured. There is
often a discrete distal onycholysis as a result of nail bed
destruction from the tumor itself rather than from the surgical
procedure.54,56 Healing by secondary intention is another
option with excellent outcome, even for very large defects.49,54

Myxoid pseudocyst type A.

and the joint was demonstrated in more than 85% of cases in a


study that involved MRI.61 In two cases, occupation was
incriminated by increasing the pressure within the joint, with
subsequent capsule rupture.59,62,63
The clinical features of MPCs depend on their location
in the nail apparatus. De Berker classified MPCs into
three subtypes62,64:
Type A: With this most common presentation, the MPC
presents as a translucent, dome-shaped, smooth-surfaced,
asymptomatic nodule that arises on the dorsum of the
digit and that is located between the crease of the distal
interphalangeal joint and the proximal nail fold. It mostly
lies lateral to the midline, and it rarely exceeds 10 mm in
diameter65 (Figure 5).
Type B: The MPC is beneath the proximal nail fold;
pressure on the underlying matrix produces a longitudinal
grooving in the nail plate that is facing the MPC. The
groove often varies in depth according to the fluctuating
volume of the cyst. A small keratotic tip protruding from
under the proximal nail fold may be observed (Figure 6).
Type C: In some rare instances, the MPC may extend
beneath the nail matrix; this can be more difficult to
recognize. The findings of a red lunula, an isolated pincer
fingernail, and a variable destruction of the proximal part
of the nail plate should suggest the diagnosis (Figure 7).
Fingernails are mainly affected by MPCs, but the
involvement of toenails is possible. MPCs are usually
solitary, but multiple MPCs (ie, two or three) may occur in

Myxoid pseudocyst
Myxoid pseudocysts (MPCs) are quite common. Their
exact incidence and prevalence are not known, although it is
estimated that women are affected more than twice as often as
men.57 It is now believed that MPCs occur as a result of a
leakage of synovial fluid through a breach in the joint capsule
of the distal interphalangeal joint.58 This phenomenon is
promoted by the presence of osteophytes and the reduction of
the joint space from osteoarthritis.59 A study demonstrated
radiologic evidence of primary interphalangeal osteoarthritis
in 75% of MPC cases.60 Communication between the MPCs

Fig. 6

Myxoid pseudocyst type B.

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B. Richert et al.

the same individual.60,63 In most instances, MPCs are


asymptomatic, but they may be visually concerning and
thus may bother the patient. Sometimes, pain from pressure
within the cyst is unbearable, and the patient will personally
puncture the MPC and express the cysts content for relief.
The diagnosis is made clinically with MPC types A and B. In
case of doubt, an MPC can be punctured with a 16G needle
to allow some translucent jelly (ie, mucoid gel with a high
content of hyaluronic acid) to come out. MRI is a useful tool
for MPC that shows a low signal in T1-weighted images and
a very high signal in T2-weighted images.61 The main
differential diagnosis is fibrokeratoma with type B.
Numerous treatments have been recommended for this
condition, with the aim of obliterating the leakage from the
joint by inducing a fibrosis around the capsule. For fearful
and older persons, a nonaggressive approach should be
proposed: repeated drainage associated with compressive
dressings for several years have been shown to have a cure
rate of 72%.66 After drainage, two cycles of 20 seconds of
cryotherapy followed by compressive dressings resulted in a
cure rate of 56% to 86%.67,68 Audebert proposed a treatment
that involved the injection of sclerosants.69 Although this
was successful for a large number of cases, its use should be
limited as a result of the severe unexpected sides effects that
were encountered, including permanent nail dystrophy and
joint stiffness. A carbon dioxide laser was tried in a small
series of 10 patients and result in a 100% cure rate.70 More
recently, infrared coagulation has been proposed.71 None of
these techniques has been able to reach the high rate of
success (ie, N 95%) that has been achieved with surgery.
Hand surgeons usually remove the osteophytes and clean
the joint capsule. This leads to very good results, but this
aggressive surgery may result in the restriction of joint
mobility (ie, 25%), and the postoperative period is long
and painful for the patients.72 It has been shown that skin
excision and osteophyte removal are not required. 73
Methylene-blueguided surgery for the ligature of the
leakage of joint fluid is a very elegant, quick, and effective
technique that provides a very high success rate of 94% for
MPC of the fingers. For the toes, the technique reaches only
57%; this is most likely because, in this location, the pressure
of fluid escaping from the joint is increased by the weight of

Fig. 7

Myxoid pseudocyst type C (submatricial).

the standing position. 58 This procedure is also very


comfortable for the patient.

Fibrokeratoma
Acquired ungual fibrokeratoma (AFK) is a solitary,
benign, skin-colored, asymptomatic nodule with a hyperkeratotic tip and a narrow base that occurs mostly in the
periungual area. It has also been called garlic clove
fibroma.74 Trauma is thought to be a major causative factor.
Most AFKs emerge from the most proximal part of the
ventral aspect of the proximal nail fold. Their pressure on the
underlying thin matrix is responsible for the arising of a
longitudinal groove that runs the whole length of the plate
(Figure 8). Their sizes vary considerably from tiny to
prominent, and they may sometimes be bifid. Rarely, AFKs
originate from within the matrix and grow into the nail plate
to eventually emerge in the middle of the nail; these
intraungual fibrokeratomas are also called dissecting ungual
fibrokeratomas because they divide the nail plate (Figure 9).
Subungual fibrokeratomas that arise from the nail bed are
also rare (Figure 10). Histology is mandatory, because
Bowen's disease may present a pseudofibrokeratoma.75,76
The multiple lesions associated with tuberous sclerosis are
called Koenen tumors. They develop most commonly on the
toes around the time of puberty, and their number increases
with age (Figure 11). A thorough examination of the
integument confirms the diagnosis. No histologic difference
has been found between isolated AFKs and Koenen tumors.77
Treatment is surgical. After the complete exposition of the
base of the tumor according to its location (eg, reclining the
proximal nail fold for those that originate from its
undersurface, avulsion of the plate for the subungual ones),
its very base is severed. Superficial removal would result in
a recurrence.

Subungual keratoacanthoma
Subungual keratoacanthoma (SUKA) is a rare, benign,
rapidly growing, aggressive tumor that is usually situated

Fig. 8 Fibrokeratoma arising from the undersurface of the


proximal nail fold and pressing onto the underlying matrix, thereby
resulting in a longitudinal groove.

Management of benign and malignant tumors of the nail apparatus

Fig. 9 Fibrokeratoma arising from the matrix and dissecting the


plate (intraungual fibrokeratoma).

below the edge of the nail plate or in the most distal portion
of the nail bed. Its clinical presentation is stereotyped and
associated with a painful distal tip caused by an underlying
bony erosion when visualized with radiography. In a review
of 61 cases in 2001, the tumor occurred in men in 75% of
cases and was most predominant on the first three fingers,
particularly the thumb. The great toenail was affected in one
case only. Lesions were polydigital in 10 cases.78
SUKA is a rapidly growing tumor that can emerge within
weeks; it is always painful, and it is most often located on the
distal part of the nail bed. The lesion may start as a small and
painful keratotic nodule that is visible beneath the free edge
of the nail and that grows rapidly into a 1- to 2-cm lesion
within 4 to 8 weeks. Its typical gross appearance is a domeshaped nodule with a central plug of horny material filling
the crater (Figure 12). The lesion rapidly plunges deeper and
erodes the underlying bony phalanx. If the SUKA is located
more proximally under the nail fold, it may present as a
painful chronic paronychia.78,79 In women, the existence of
multiple SUKA may represent a late manifestation of
incontinentia pigmenti.
The pathogenesis of SUKA is still not understood. The
roles of trauma, 78 oncogenic human papillomavirus
(HPV),80 and, in one case, steel wool81 have been suggested
but never confirmed. There is a marked dyskeratosis in the
cutaneous lesions of the verrucous stage of IP as well as the
subungual tumors of IP, which suggests an increased

Fig. 10

Fibrokeratoma of the nail bed.

607

Fig. 11

Koenen tumors in a tuberous sclerosis.

apoptosis. Most cases of IP are caused by mutations in the


nuclear factor (NF-) essential modulator gene, which
intervenes in apoptosis regulation.82
The medical imaging of SUKA confirms the diagnosis.
Standard radiography consistently demonstrates a welldefined cup-shaped erosion of the underlying bone. The
margins of the radiological defect show no evidence of
sclerosis or any sign of periosteal reaction.83 This lytic effect
may be attributed to the very rapid compression caused by
the tumor rather than to tumor invasion itself.84 Long-term
radiologic follow up of SUKA is rare. Some patients had a
complete absence of reossification,81 whereas others demonstrated some partial reconstitution of the bony defect.85 In
one case report, there was a spontaneous regression with full
reossification.86 Ultrasonography reveals a well-circumscribed, mixed-echoic mass. MRI demonstrates intermediate
intensity on T1-weigthed images and mixed signal intensity
on T2-weighted images. A peripheral thin rim of contrast
enhancement suggests an inflammatory reaction in the
surrounding tissue. 87 The diagnosis of distal digital
keratoacanthoma relies on the rapid growth of the lesion
and the constant pain in association with medical imaging
and histology.
The three main differential diagnoses for SUKA are
epidermoid implantation cyst, subungual wart, and SCC.
SCC is also the main histologic differential diagnosis, which
remains difficult; the tumor is frequently diagnosed histologically as a SCC, keratoacanthoma type. Stoll reports that
the histological features have the same general configuration

Fig. 12

Distal subungual keratoacanthoma.

608
as keratoacanthoma elsewhere, but they tend to be more
vertically oriented and to exhibit more dyskeratotic cells,
fewer neutrophils and eosinophils, and little or no fibrosis at
their base.88 Distinguishing keratoacanthoma from welldifferentiated SCC is sometimes difficult. Recent evidence
indicates that the nuclear factor kappa-B p50 subunit and
cortactin may be useful to distinguish between these two
conditions. Both the p50 subunit and cortactin had higher
levels of expression in keratoacanthoma than in SCC. Both
were localized to the basal cell layer of keratoacanthoma,
whereas they were scattered without polarity throughout the
SCC lesions.89 The expression of Ki-67 is much stronger in
SCC than in SUKA. In SUKA, if Ki-67 expression is
present, it is weak and localized to the basal cell layer.90
Previous recommendations for the treatment of SUKA
have been divergent, ranging from conservative local
excision to aggressive amputation. A review of 18 cases
treated with curettage showed that 86% of lesions did not
recur.85 The first-line treatment, therefore, is the removal of
the entire tumor with curettage of the cavity.91 Some authors
suggest Mohs micrographic surgery to limit any risk of
recurrence; however, this technique seems hardly feasible for
the curettage of a bony cavity.92 Most recurrences occur
within the first 5 months postoperatively, but long-term
follow up is mandatory, because recurrences have been
observed after as long as 22 months.78,91 Amputation should
be only considered for patients with multiple recurrences,
when massive bony destruction is present, or when SCC
cannot be ruled out.78,93 For painful subungual tumors of
incontinentia pigmenti, the first choice for treatment should
be acitretin.82

Onychomatricoma
Onychomatricoma is a rare benign tumor of the matrix that
was first described 20 years ago.94 Similar tumors of the nail
matrix have also been reported as onychoblastoma, unguioblastoma, and unguioblastic fibroma.95,96 This is a slowgrowing, painless tumor for which most patients seek medical
care only years after onset, mostly for cosmetic or functional
concerns. The vast majority of cases have been reported
among Caucasians and especially in Europe. The origins of
this condition remain obscure, and its presence among
individuals of African descent has been exceptionally
mentioned.97 Only one case has been clinically identified in
a child, but because no surgery was performed, there was no
confirmation of the diagnosis.98 The tumor affects mainly the
digit (75%), and it involves the middle finger in two thirds of
cases.99 Some cases have been reported on the lesser toes,100
and exceptional cases have involved several digits.101
Several clinical signs are striking enough to either make
the diagnosis or at least to arouse suspicion:
Longitudinal thickening of a part of the nail plate that
often spares a portion of the normal pinkish nail

B. Richert et al.
Transverse and longitudinal overcurvature of the affected
portion of the nail
Xanthonychia of the affected part of the affected nail
Longitudinal ridging that is sometimes quite prominent
on the surface of the nail
Splinter hemorrhages that are mostly proximal but
sometimes distal
Honeycomb cavities at the frontal margin of the thickened
nail plate
A nodule may be seen at the base of the longitudinal nail
dystrophy102 (Figure 13). Several unusual clinical variants
have been described, including a giant form103 an association
with dorsal pterygium,104,105 onychomycosis,106 or longitudinal melanonychia.106 Dermatoscopy helps with diagnosis
by demonstrating multiple perforations of the nail plate at its
free border. Recently, researchers reported that the analysis
of a nail clipping is a fast and minimally invasive method to
achieve the correct diagnosis of onychomatricoma by
differentiating onychomatricoma from subungual tumors
and excluding fungal infection with a periodic acid-Schiff
stain.107 Ultrasonic examination also seems promising. A
recent study demonstrated a hyperechoic tumoral lesion
affecting the matrix zone with hyperechoic linear spots and
projections into the interplate space.108 Magnetic resonance
imaging is typical; it reveals a tumor that is emerging from
the nail matrix with the same signal as normal epithelium and
with processes that extend into the thickened nail plate.109
Nail avulsion can be diagnostic as it exposes a villous tumor
emerging from the matrix that is evocative of a sea anemone;
the nail appears as a thickened funnel storing the filamentous
digitations of the matrix that fit into the holes of the proximal
nail extremity (Figure 14). Those digitations are onychogenic and responsible for the thickening of the nail plate.
Their length may occasionally be as such that clipping of the
free edge induces bleeding.110 Clinical features are characteristic, but onychomycosis and Bowen disease111 should be
ruled out.
The surgical removal of the tumor is the only option, and
the tumor should only be shaved. Because it is impossible to
replace the plate (which is altered and should undergo

Fig. 13 Onychomatricoma. Note the swelling of the proximal


nail fold and the xanthonychia.

Management of benign and malignant tumors of the nail apparatus

609

Fig. 14 Avulsion reveals the villous tumor on the matrix and the
funnel-shaped plate.

Fig. 15 Superficial acral fibromyxoma. Compare this with the


image shown in Figure 4.

histological examination), it may be wise to slide some tulle


gras under the proximal nail fold and secure it with two
stitches. This will avoid any adherence between the ventral
part of the proximal nail fold and the matrix, which could
result in pterygium. After 3 weeks, the tulle gras may be
removed; at that time, the matrix will already have healed
and synthesized some keratin.41
Histology of the surgical specimen is unique: the distal zone
is characterized by multiple glove finger papillary projections
covered by a matrix-type epithelium that is devoid of stratum
granulosum and that keratinizes through an eosinophilic
keratogenous zone. The proximal zone, which corresponds
with the peduncle, is dome-shaped in transverse sections. It is
lined by a papillomatous matrix-type epithelium with vertically
oriented deep invaginations into the stroma. These invaginations surround optically empty cavities in a characteristic
V-shaped configuration. The recognition of matrix-type epithelium with V-shaped depressions is crucial to make the diagnosis
of onychomatricoma on fragmented or incomplete specimens,
which lack the glove finger papillary projections.112

focally positive.116,117 A large series of 124 cases showed


that no tumor of this type had metastasized.117
Complete surgical excision and careful follow up are
suggested, despite digital fibromyxomas benign course.118
Some cases may suggest myxoid dermatofibrosarcoma,
which carries a completely different prognosis.115

Superficial acral fibromyxoma (digital fibromyxoma)


Superficial acral fibromyxoma is a rare, slow-growing,
soft-tissue tumor that has a predilection for the subungual
and periungual regions of the fingers and toes in adults.113
The clinical presentation has not been fully detailed, because
this condition is mostly a histological discovery. Some
reports mention a dome-shaped, well-circumscribed, whitish
to pinkish firm tumor (sometimes with a collarette at its base)
lifting up the plate, which is covered with very thin cracked
hyperkeratosis (Figure 15); if the tumor is located deeply in
the lateral nail fold, there will be a swollen fold covered with
normal skin.114,115 Histology demonstrates a well-circumscribed, unencapsulated tumor located in the dermis or the
subcutis, with only rare extension into the bone. It is
composed of stellate and spindled cells embedded in a
myxoid matrix, often with accentuated vasculature and
increased numbers of mast cells. Nuclear atypia is slight or
absent, and mitotic figures are infrequent. Immunohistochemically, 69% to 90% of cases are positive for CD34.
CD99 and epithelial membrane antigen (EMA) can also be

Malignant tumors
Squamous cell carcinoma
SCC is the most frequent malignant tumor at the nail
apparatus. The in situ form, which is restricted to the
epidermis without disruption of the basal membrane, is
called Bowen disease. It is weakly aggressive, and slowly
evolves over several years. The prognosis for both in situ and
invasive forms of SCC is very good: metastases are
exceptional, 119,120 and only three deaths have been
reported.121-123 It may occur at any age during adulthood,
with a peak incidence between the ages of 50 and 69 years.
Men with SCC outnumber women with SCC at a ratio of 2:1.
Fingernails are selectively affected, especially the thumb, the
index finger, and the middle finger.124 The condition is
mainly monodactylic, but uncommon polydactylic forms
have also been reported.125-127
Of the multiple suggested causative factors (eg, ionizing
radiation, arsenic, pesticides, dyskeratosis congenita), it has
been demonstrated that oncogenic HPV plays a major role. It
is estimated that, through genitodigital transmission, HPV is
responsible for SCC of the nail apparatus (both the in situ and
invasive forms) in up to 60% of cases. Of these, serotype 16
has been isolated in 75% of cases.124 Other serotypes have
been more recently identified, including 2, 6, 11, 18, 26, 31,
34, 35, 56, 58, and 73.119,128-130 Almost one third of patients
with SCC of the nail apparatus have a history of HPVassociated genital disease (ie, genital warts, dysplasia, or
cancer of the cervix or anogenital region) or a sexual partner
with such a history. The average time between the onset of
the genital disease and the appearance of the nail tumor is
approximately 12 years. It seems that the risk of developing

610

B. Richert et al.

an aggressive or multiple form of HPV-associated SCC of


the nail apparatus is not correlated with the patients
immunity status. SCCs of the nail apparatus, whether they
are associated with HPV or not, have a similar rate of
metastasis of 2% to 3%.124
The clinical presentation of SCC is proteiform; it often
appears as a clinically misleading benign lesion, which
delays the diagnosis.131 The differential diagnosis encompasses verruca vulgaris, onychomycosis, subungual exostosis, epidermoid cyst, bacterial paronychia, fibrokeratoma, and
onychomatricoma. The malignant process may develop in the
epithelium of the paronychium or from the nail bed.
Subungual involvement is the most common finding. SCC
mostly presents with onycholysis, and clipping away of the
detached nail plate shows partial or extensive hyperkeratosis
of the nail bed or even a verrucous mass (Figure 16).
Onycholysis may be associated with oozing from an
ulceration of the nail bed. In some instances, partial nail
loss exposes the tumor, thereby indicating involvement of the
matrix. When involving the periungual area, the most
common encountered patterns are a hyperkeratotic, papillomatous, or warty proliferation associated with scaling or
erosions of the nail fold (Figure 17). Periungual swelling may
result from deep tumor proliferation or a paronychia132 with
erythema caused by inflammation as a result of infection.
Fissure or ulceration of the lateral nail groove, which is
sometimes crusted with granulation-like tissue beneath the
scab, may also be observed.30 Pain is uncommon.121,133
Some subungual hyperkeratosis may be treacherous: there
may be longitudinal erythronychia with onychopapilloma,134 fibrokeratoma,76,75 or subungual hyperkeratosis
that is evocative of an onychomatricoma.111 The presence of
a longitudinal melanonychia is a clue to Bowen's disease
when it is associated with localized hyperkeratosis of the nail
bed or folds135-138 (Figure 18). This presentation has been
linked to HPV 16136 and HPV 56.139,140 Pseudo-Hutchinson
sign is particularly misleading, because it evokes melanoma.141 The key to diagnosis is the pathological examination.
The picture of Bowen's disease at the nail apparatus is
identical to that of Bowen's disease in other skin areas.142
The most important feature is the intact basement membrane
that defines the in situ form.

Fig. 16

Subungual Bowen disease.

Fig. 17

Periungual Bowen's disease.

The treatment of SCC is functional surgery, and the


complete removal of the whole lesion is mandatory. Partial nail
removal may be performed in some instances, with closure
with a bridge flap. For large lesions, the complete removal of
the nail apparatus with healing by secondary intention or
grafting is indicated. Surgical excision with histological
control of the margins is recommended. Limited excision
with micrographic control of the margins on fixed tissue
(vertical sections) was proposed by Dalle and colleagues, but a
56% recurrence rate was observed with this technique.121 The
cause for this high recurrence rate may result from the fact that
this study dealt with a majority of invasive SCC. Mohs surgery
at the nail apparatus is a challenge, mostly because of the
peculiar anatomic area.121,133 This is the most effective
surgical technique, but data indicate a 20% mean recurrence
rate as compared with a 3% recurrence rate for all cutaneous
SCC.124 One series on 25 cases reported an 8% recurrence rate
with 5 years of follow up.143 Another recent series of 15 cases
had no recurrence at 2 to 3 years of follow up.144 The high
recurrence rate with any treatment may be explained by the
viral origin of the condition. Long-term follow up that includes
the examination of all nails and the biopsy of any suspicious
changes is therefore mandatory.
Bone involvement is seen in less than 20% of
patients.145,146 If bony involvement is demonstrated by
radiography or during the pathological examination of the
surgical specimen, amputation of the distal phalanx is

Fig. 18 Discrete subungual hyperkeratosis of the lateral fold


associated with longitudinal melanonychia (Bowen disease).

Management of benign and malignant tumors of the nail apparatus


indicated.30,93,121,133,147,148 Some nonsurgical treatments
have been reported, including imiquimod cream,149 5fluorouracil cream141,150 with or without prior curettage,
photodynamic therapy,151,152 and intra-arterial infusion with
methotrexate.153 None of these techniques, however, allows
for the histologic controls of the tumor margins. These
should be considered as treatment options for special cases,
when surgery is not feasible.

Verrucous carcinoma
Thirteen cases of verrucous carcinoma involving the nail
apparatus have been reported in the literature. This is a rare,
highly keratinizing variant of SCC that is characterized by
local aggressiveness but a low potential for metastasis. The
plantar form is also known as epithelioma cuniculatum.154
The clinical presentation is often misleading; this condition
often appears as a warty lesion that increases in size with time.
The nail beds of the thumb, the great toenail, and the fifth
toenail are the most common locations. A case involving the
fourth finger was recently reported.155 Long evolving lesions
with papillomatous digitations are quite typical. Mohs surgery
or en bloc excision followed by a full-thickness graft155 is the
treatment of choice, but, in advanced cases, amputation may
be mandatory. One case was successfully treated with the
intra-arterial infusion of methotrexate.156

Melanoma
Nail apparatus melanoma (NAM) is rare; according to
several series, it accounts for 0.18% to 2.8% of all cutaneous
melanomas.157 The estimated incidence reaches 0.1 per
100,000 people per year.158 The relative incidence of NAM
among African and Asian individuals is much higher than
that found among Caucasians: about 25% of melanomas are
located in the nail apparatus in Japanese and African
Americans, but the absolute incidence of NAM may well
be similar for all racial groups.157 The average age of onset is
during the sixth and seventh decades. NAM is unusual in
children, with only 13 reported cases to date.159 The thumb
and the great toenail are most frequently affected,160
probably as a result of the larger proportion of matrix on
these digits.161 NAM mainly arises from the nail matrix, but
it is also found in the nail bed and the lateral folds, which are
structures that contain melanocytes.162 Although trauma has
often been mentioned as a potential causative factor, no link
has been established with certainty.163 Ultraviolet radiation
is not responsible either: the nail plate acts as a barrier,164 the
matrix area where the melanoma arises is not directly
exposed to sunlight, and the similar frequency of NAM
among dark- and fair-skinned races suggests that pigmentation is not protective.157
In 76% of cases, NAM develops in the matrix; its first
symptom is a longitudinal melanonychia.165 The use of the
ABCDEF rule was suggested to help the clinician detect

611

suspicious melanonychia and to improve the early detection


of NAM. In this rule, A stands for age, Asian, and African
American; B stands for brown, black, breadth, and
borders; C stands for change or absence of change, despite
adequate treatment; D stands for digits (eg, thumb, hallux,
index finger); E stands for extension of pigment
(Hutchinson sign); and F stands for familial history of
melanoma.166 Hutchinson sign describes the presence of
pigment on the proximal, lateral, or distal fold, which
represents the radial growth phase of subungual melanoma.
Its presence dictates the removal of the entire affected part of
the nail unit without prior incisional biopsy (Figure 19). This
is important to allow the pathologist to make the correct
diagnosis.167 Incisional biopsy of the periungual pigmentation is not sufficient to accurately diagnose NAM, so it
should not be performed. Although Hutchinson sign is
highly suggestive of melanoma, it is not pathognomonic: one
should remember pseudo-Hutchinson sign, which corresponds with the visualization of pigment through the
cuticle.168 Dermatoscopic examination should complete the
examination. The suggestive pattern of NAM includes a
brown background with brown to black lines that are
irregular in coloration, irregularly spaced, and variable with
regard to thickness and interruption of parallelism.162,169,170
To increase the sensitivity and specificity of dermatoscopy,
some authors have proposed the direct examination of the
matrix and the nail bed after nail avulsion. These authors
examined 100 consecutive pigmented bands and identified
four dermatoscopic patterns: a regular gray pattern (hypermelanosis); a regular brown pattern (benign melanocytic
hyperplasia); a regular brown pattern with globules or
blotches (melanocytic nevi); and an irregular pattern
(melanoma). These patterns showed high sensitivity and
specificity; however, nail matrix dermatoscopy is an invasive
procedure that cannot be routinely performed in all cases of
longitudinal melanonychia.171 Very recently, a French team
performed an intraoperative reflection confocal microscopy
examination on a series of 9 pigmented matrix lesions and
demonstrated that this technique is an efficient diagnostic
approach for melanonychia striata that allows for the
extemporaneous diagnosis of malignancy.172 This process

Fig. 19 Hutchinson sign. The whole nail unit was removed and
demonstrated a melanoma in situ.

612
can therefore serve as a one-step surgical treatment for in situ
or minimally invasive melanoma, thereby dramatically
reducing the duration of postoperative disability.
Various excisional biopsy techniques have been described
to ensure histological diagnosis and to limit the risk of
postoperative dystrophy for a lesion that could turn out to be
benign.173 Incisional biopsy is not recommended, because it
does not allow for the complete histological examination of
the pigmented lesion.
In 30% of cases, NAM arises from the nail bed and
presents as a nodule that may be pigmented, an ulceration
with bleeding, an isolated fold pigmentation, an unexplained
monodactylic paronychia, or a partial destruction of the nail
plate.174 One should remember that about 20% to 30% of
cases of NAM are amelanotic.157 This condition is even
more treacherous when it manifests as a monodactylic
onychorrhexis.175
Unfortunately, the diagnosis of NAM is very often delayed,
and this is associated with a poor prognosis. This delay may be
attributed to patients who do not initially suspect the diagnosis
of cancer at that site and consult their physicians at a late stage
of disease, when swelling, ulceration, oozing or bleeding
occur. These clinical features are already associated with a
thick Breslow index.176 Only one third of patients with
longitudinal melanonychia seek medical advice157 (Figure 20).
The overall accuracy of dermatologists with regard to the
diagnosis of nail matrix melanoma presenting as a longitudinal
melanonychia remains low; it ranged from 46% to 55% in a
test of dermatologists with different levels of clinical
experience, and the level of expertise did not statistically
influence the correct diagnosis.177 The 5-year survival rate
was 88% for patients with a Breslow thickness of less than
2.5 mm and only 40% for patients with a thickness of more
than 2.5 mm.161
Until recently, traditional treatment was amputation at the
metacarpophalangeal joint. Some studies have demonstrated
that the level of amputation did not affect patient survival, as
long as the tumor was entirely excised.157,158,178 There are
no randomized or prospective studies that compare ampu-

Fig. 20 Long-lasting longitudinal melanonychia. Several doctors


told the patient that this was nothing. After several years, the nail
split at its base, and a nodule appeared. Melanoma was diagnosed,
with a Breslow depth of 1.6 mm. The patient underwent distal
amputation and lymph node dissection.

B. Richert et al.
tation with local excision or that study different levels of
amputation. Available scientific data come from retrospective studies. These involved bias with regard to the choice of
the treatment: more distal amputation or local excision was
performed for less invasive lesions, whereas, for those
lesions with a thicker Breslow depth, amputation was
chosen. No study in the literature was able to demonstrate
a prognostic benefit in terms of survival or avoidance of local
recurrence and satellite or in-transit metastasis if a digit or toe
underwent complete amputation as compared with resection
in or distal to the proximal interphalangeal joint.179
Excision margins of nail apparatus melanoma remain
controversial. NAM poses a difficult challenge as a result of
the lack of surrounding tissue.180 It is difficult to add extradeep margins unless amputation or the removal of a layer of
bone occurs, because the matrix is fixed to the bone. There is
little available data to evaluate amputation through the distal
interphalangeal joint.158 Recent studies have evaluated local
excision. Moerhle et al. have compared the treatment of
NAM in 62 patients. All thicknesses were considered
together, which resulted in a mean thickness of 1.68 mm
(Breslow depth, 1 to 4 mm). Thirty-one cases were treated
with conservative functional surgery (ie, the removal of the
whole nail unit with resection of the processus unguicularis),
and 31 cases involved distal phalanx amputation. The
researchers did not find any significant differences in
recurrence or survival rate in the two groups that reached
92% in both areas at 5 years.179 More and more authors
report treating in situ and microinvasive NAM (Breslow
depth, b 0.5 mm) with the en bloc removal of the nail unit
with 5 to 10-mm margins, sometimes with a removal of a
layer of underlying bone,181 followed by a full-thickness
skin graft180,182-185 or the use of artificial dermis.186 These
reports have involved excellent survival rates as well as
optimal cosmetic and functional results. Several case series
have reported Mohs surgery, with encouraging results.187,188
Care should be taken to carefully remove the lateral horns of
the matrix, because they are the most common locations of
marginal recurrence188. However, this conservative approach still remains controversial.189,190
In routine clinical practice, two groups should be
distinguished: in situ melanomas and invasive melanomas.
For in situ melanomas, a complete resection of the nail unit
with histological control of the margins should be proposed
to the patient in accordance with the location of the tumor
and the patients occupation. This discussion should involve
the patient, his or her family, and the multidisciplinary
oncologic team. Special attention should be given to the
thumb, because it is the only opposable finger and it allows
for the grabbing and holding of objects. This is also true for
the big toe due to its main role as a support point and an
insertion site of important muscles for balance. Invasive
melanomas should undergo the most functional amputation
possible, depending on the tumor thickness.191 Adjuvant
systemic chemotherapy, isolated limb perfusion, and routine
elective lymph node dissection have been used, but no

Management of benign and malignant tumors of the nail apparatus


survival benefits have been demonstrated. Early diagnosis
and excision of the tumor is the only treatment that has been
demonstrated to increase survival.157

Basal cell carcinoma


Basal cell carcinoma (BCC) is the least common at the
nail apparatus; around 20 cases have been reported in the
English literature. The average age of diagnosis is 65 years.
The thumb is the most frequently involved digit, followed by
the hallux.192 The delay to diagnosis ranged from 8 months
to 40 years, with the average being 10 years. The clinical
presentation of BCC varies considerably and is evocative of
either chronic paronychia, pyogenic granuloma, amelanotic
melanoma, SCC, a bacterial or mycotic infection, a habit
tic,193 or longitudinal melanonychia.192,194 A case of BCC
developed in a radiodermatitis of the proximal nail fold of a
pulmanologist195; another occurred in a worker who dealt
with azo pigment.196 The classic clinical BCC presentation
observed on the skinwith nodules, a pearly border crusting
was encountered in only a minority of cases. Mohs
surgery was the first-choice treatment in the vast majority of
cases, with excellent outcomes.197 Some patients also
underwent excision and/or amputation.198

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