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ATYPICAL FIBROXANTHOMA
This tumour occurs most commonly on sun
exposed skin of elderly individuals, and is com-
posed of atypical histiocyte like cells, giant
cells, and spindle cells. Mitotic figures includ-
ing atypical forms are usually readily identifi-
able. It is a diagnosis of exclusion with S100
protein, Melan-A, and pancytokeratin staining
being negative.8 9 More recently, a monomor-
Figure 2 Acral lentiginous melanoma in situ. At low phic spindle cell variant and a pigmented vari-
power there is psoriasiform hyperplasia of the epidermis
with a subtle lentiginous proliferation of melanocytes along ant have been described, which have the clini-
the basal layer. cal and immunohistochemical pattern identical
to typical atypical fibroxanthoma. The former
benign melanocytic lesions from certain sites in variant lacks the prominent cellular pleomor-
the body can, as a normal feature, exhibit phism, being composed predominantly of
architectural and possibly cytological atypia spindle cells,10 whereas the cellular component
(see below). Therefore, care should be exer- of the pigmented variant contains erythrocytes
cised when examining naevi from these sites to and/or haemosiderin in the cytoplasm.11
prevent over diagnosing atypical naevi or
melanoma. BEDNAR TUMOUR
Table 1 Non-melanocytic Pigmented dermatofibrosarcoma protuberans
entities that can mimic It is also important to know whether there
melanocytic lesions has been a previous shave biopsy or incomplete although rare could mimic spindle cell
excision, because regrowth of melanocytes in melanoma.12
Atypical fibroxanthoma scar tissue can mimic melanoma, and create a
Bednar tumour
Clear cell dermatofibroma so called pseudomelanoma phenomenon.5 CLEAR CELL DERMATOFIBROMA
Epithelioid histiocytoma For the remaining lesions that are not readily This is a rare variant of dermatofibroma, which
Extramammary Paget’s classifiable, all the tissue should be examined, tends to occur on the lower limbs of middle
disease
Granular cell tumour with levels cut where appropriate. Before aged adults. Microscopically, it is a well circum-
Mastocytoma agonising and spending time on these cases it is scribed dermal to subcutaneous tumour, which
Metastatic lobular carcinoma important first to exclude lesions that can stains faintly, because over 90% of the constitu-
Mycosis fungoides
Neurothekeoma mimic melanoma and to consider melanocytic ent cells have a clear cytoplasm and stain with
lesions that are recognised entities, and which PAS (periodic acid SchiV). They may mimic
Table 2 Benign could account for the atypical features present balloon cell naevus and/or melanoma, but they
melanocytic entities that within a particular melanocytic lesion. These are S100 protein and cytokeratin negative.13
can mimic thick melanoma other lesions to be considered and excluded
can be categorised as follows: EPITHELIOID HISTIOCYTOMA
Ancient naevus
Balloon cell naevus
+ Non-melanocytic entities that might be This is an unusual and still poorly recognised
Cellular blue naevus clinically pigmented and histologically can variant of dermatofibroma that was first
Combined naevus mimic melanocytic lesions (table 1).
Compound Spitz naevus
described by Edward Wilson-Jones et al in
Deep penetrating naevus + Benign melanocytic entities that can mimic 1989, and typically presents as a nodule on the
Desmoplastic naevus malignant melanoma: extremities.14 It diVers from conventional
Naevus with dermal nodules (1) Those that mimic thick melanoma dermatofibroma in its relatively sharp circum-
(table 2). scription, prominent vascularity, centering on
Table 3 Benign (2) Those that mimic thin melanoma the papillary dermis, predominance of epithe-
melanocytic entities that (table 3).
can mimic thin melanoma lioid cells, and relative lack of other secondary
+ Malignant melanoma variants that can features such as haemosiderin and giant
Acral naevus mimic benign melanocytic lesions (table 4). cells14 15 (figs 3 and 4). A deep seated cellular
Genital naevus + Epidermotropic metastatic melanoma that variant has been recognised.16–19 This entity can
Halo naevus
Junctional/pagetoid Spitz
can mimic primary melanoma and benign mimic other non-fibrohistiocytic tumours such
naevus naevi.
Naevus of infancy
Naevus from special
anatomical sites
Naevus after UV irradiation
Non-melanocytic lesions that can mimic
Pigmented spindle cell naevus melanocytic lesions
Pseudomelanoma These lesions can mostly be excluded if a thor-
ough examination is undertaken and appropri-
Table 4 Malignant ate special stains are performed. Melan-A and
melanoma variants that S100 stains are the most useful to detect
can mimic benign lesions
melanocytic lineage, with S100 being more
Balloon cell melanoma sensitive but less specific than Melan-A. Both
Desmoplastic melanoma stain benign and malignant melanoctyic cells
Regressed melanoma strongly and diVusely, with the exception of
Small (non-Merkel) cell
melanoma Melan-A in desmoplastic melanomas, where
Spitzoid melanoma there is little or no staining.6 7 All of the lesions
Varicose melanoma Figure 3 Epithelioid cell histiocytoma. A cellular dermal
Verrucous naevoid melanoma
in this group are Melan-A negative.7 Most are nodule with a Grenz zone. The lesion extends into deeper
S100 protein negative, with only granular cell tissues.
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are usually exo-endophytic, intradermal prolif- Typically they are non-pigmented, sym-
erations composed of two populations of cells. metrical, and composed of either large epithe-
One population has large pleomorphic nuclei lioid and/or spindle cells. There might be pro-
and might resemble Spitz cells, and the other is nounced cytological atypia, with nuclear atypia
a population of small monomorphous cells. and mitotic figures, and intranuclear inclu-
There might be secondary degenerative sions. The cells should have an infiltrative
changes, which include thrombi, zones of growth pattern at the lower margin, with cells
haemorrhage, pseudoangiomatous pattern, drifting in single fashion between the collagen
thick rims of sclerosis around dilated venules, bundles. The overlying epidermis frequently
and mucin. A few mitotic figures might be shows pseudoepitheliomatous hyperplasia, the
present.28 However, if the mitotic figures are in stroma is oedematous, particularly in the upper
the base of the lesion, are atypical, or portion, and there are Kamino bodies in the
numerous, the diagnosis is almost certainly papillary dermis.40–43 Many authors have em-
that of melanoma.29 phasised that there is no single discriminating
factor for melanoma and compound Spitz
Balloon cell naevus naevi, because virtually every attribute of Spitz
These have the conventional histology of naevi naevi has been described in melanoma.44–50 The
with variable amounts of balloon cells as most dependable discriminating features are
constituent cells. The balloon cells are large, the lack of maturation of the cells at the base,
round to oval, and have abundant clear or pale presence of numerous, deep, or atypical
foamy cytoplasm. They need to be diVerenti- mitoses, and deep extension in a bulbous man-
ated from balloon cell melanoma.30 ner into the fat, which favour a diagnosis of
melanoma over Spitz naevus.51
Cellular blue naevus Spitz lesions that show some of these latter
Blue naevi have traditionally been divided into features and yet lack the full criteria for the
common and cellular blue types but the diagnosis of melanoma have been termed by
separation is artificial because there is frequent some “atypical Spitz lesions”. Barnhill et al
overlap. Lesions, which are predominantly cel- have described these lesions in children and
lular blue naevi, can mimic both primary and young adults.52 In general, they are larger than
secondary melanoma. They can cause diagnos- Spitz naevi, are asymmetric with deep exten-
tic diYculty if they are of a large size, and sion (mean depth, 4.36 mm), show prominent
extend into fat. They are typically unencapsu- cellularity, and have deeply located mitoses,
lated and grow in fascicles or in an alveolar occasional atypical mitoses, and cytological
pattern. They can show mild cytological atypia, with some having dermal nodules with
atypia.31 32 Myxoid change has been described rounded pushing margins. These features are
as a degenerative phenomenon in large lesions similar to those described by Smith et al, also in
and this is associated with cellular pleomor- young adults,50 and he called these lesions
phism and pseudovascular invasion.33 How- malignant Spitz naevi. In Smith’s series, six of
ever, these myxoid areas are in the centre of the the 32 cases had resulted in nodal metastasis,
tumour, and myxoid areas are not a feature of but they could not distinguish histologically
lesions that have been called malignant blue those lesions that did not metastasise from
naevus. Epithelioid and sclerosing variants of those that did. This is similar to Barnhill’s
blue naevus have also been described,34 35 as series, where histology could not separate those
have atypical cellular blue naevi, which exhibit lesions that he called “atypical Spitz tumours”
cytological atypia but have a benign clinical from those that he categorised as “metastasis-
behaviour.36 Features indicating malignancy in ing Spitz naevi”.52
blue naevi like lesions are pronounced cytologi- The problem is further confounded by the
cal atypia, gross variation in pigmentation, foci proposal that there exists a group of Spitz
of necrosis, and numerous mitotic figures.37 tumours in children that will result in nodal
metastasis, but will not progress beyond this
Combined naevus stage. These have been called “malignant Spitz
Any combination of naevi can occur within the naevi” and also “atypical Spitz naevus with
same lesion—for example, Spitz, blue, and metastasis”.50 53 The problem is the length of
common naevi, and this can cause diagnostic follow up. Many, however, would regard these
problems, particularly if there is a deep lesions as spitzoid melanomas.
component.38
Deep penetrating naevus (plexiform spindle cell
Compound Spitz naevus naevus)
Spitz naevi can be junctional, compound, or This was first described by Seab et al in 1989 as
intradermal (desmoplastic naevus). They can a lesion that clinically and histologically can
also be part of a combined naevus. In all these mimic thick melanoma, and occurs predomi-
situations they can cause major diagnostic nantly in the head and neck and upper
problems, with the diVerential diagnosis being extremities of young individuals. Histologi-
melanoma. These lesions form a major compo- cally, they described a symmetrical, wedge
nent of expert referral practices.39 It is particu- shaped lesion, which extended into and had its
larly the deep compound lesions that cause apex in the reticular dermis or fat (fig 8). The
most of the diagnostic problems because they cells are arranged in nests or fascicles inter-
frequently occur in children and young adults, spersed with melanophages (fig 9). The nests
and if diagnosed as melanoma they carry a surround hair follicles, sweat glands, blood ves-
poor prognosis. sels, and nerves. The cells are spindle in
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VARICOSE MELANOMA
Malignant melanoma that arises in skin with
pronounced stasis damage might be over-
looked clinically because of the brownish
discoloration of the skin and, histologically,
because of the stasis changes in the papillary Figure 15 Verrucous small cell melanoma. The lateral
dermis and the ulcerated and atrophic epider- growth spread of the lesion. Taken together with the age of
the patient, the regression favoured a malignant diagnosis.
mis. The absence or obscuring of the superfi-
cial part of the tumour might lead to the diag-
nosis of benign naevus when looking at the types. The terms “minimal deviation
deeper dermal nests.80 melanoma” and “borderline melanoma” have
been used to describe melanomas with a less
aggressive clinical course and less cytological
VERRUCOUS NAEVOID MELANOMA
atypia in their vertical growth component than
This is a heterogeneous group of melanomas,
typical melanomas.63 88 There is no doubt that
which comprises melanomas with a warty
not all melanomas behave in a similar clinical
hyperkeratotic appearance, and others that
manner and some, even though they are in no
resemble papillomatous benign intradermal
doubt malignant, behave in a sometimes
naevi at low power, but at high power can be
surprisingly benign fashion. Whether the term
seen to be cytologically malignant.81–87 How-
minimal deviation is the most appropriate for
ever, a very small proportion will be composed
these lesions remains unresolved. The major
of small naevus like cells, which lack matura-
problem is that the terminology and defining
tion, and have another feature that points to
criteria for minimal deviation lesions appear
melanoma, namely an atypical junctional com-
too vague, with the inclusion of heterogeneous,
ponent, an asymmetric lateral growth pattern,
even possibly benign, melanocytic lesions
or foci of regression in an older individual (figs
under this term, making it diYcult to compare
13–15).
series and produce prognostic data. The situa-
In the past (and even currently), some of
tion has been complicated further by the
these groups might have been called minimal
description of multiple subtypes of minimal
deviation or borderline melanomas, particu-
deviation melanoma.89 Until the problem of
larly the verrucous, small cell, and spitzoid
terminology is resolved, it is advisable to group
together only lesions with very similar histo-
logical features to obtain a clearer picture of the
clinical behaviour of particular types.
experts in the field of melanoma pathology. main problem in these atypical variants is how
The problematic lesions usually fall into one of much variation is “acceptable”. In the lesions
three groups: resembling cellular blue or deep penetrating
+ Atypical, predominantly junctional, naevus naevi, foci of necrosis and deep or atypical
versus early melanoma. mitotic figures suggest that the lesions should
+ Atypical naevoid lesions versus naevoid be regarded as melanoma. The most important
melanoma. of this group are the Spitz with atypical
+ Atypical variants of Spitz/cellular blue/deep features, because of their relative frequency in
penetrating naevi versus thick melanoma. problematic cases, and because many of them
will be from children or young adults. Features
ATYPICAL PREDOMINANTLY JUNCTIONAL NAEVUS causing concern would be deep bulbous exten-
VERSUS EARLY MELANOMA sion, lack of maturation, and the presence of
This is perhaps less of a practical problem, multiple, deep, or atypical mitoses. All of these
because once excised these lesions should cause features are completely unacceptable in an
the patient no further problems. However, it is adolescent and adult, as is the presence of a
important to attempt to achieve the correct pronounced asymmetric junctional melano-
diagnosis. The benign melanocytic entities that cytic growth, particularly if lentiginous. The
can resemble early melanoma should be consid- features that are acceptable in a young child are
ered and they can cause problems if they show contentious. Barnhill and Smith could not
some atypical features. Using pure histology, it readily separate those spitzoid lesions that
might be impossible to separate atypical junc- metastasised from those that did not on histol-
tional Spitz and pigmented spindle cell naevi ogy alone.50 52 Barnhill also suggests that these
from early melanoma. Some lesions may be lesions in children should be divided into high
called dysplastic naevi, but this term should and low risk atypical groups.52
only be used after following strict adherence to
the clinical and histological criteria.67 Conclusions
For this group of lesions it is probably There is a wide spectrum of histological
important to learn the characteristic appear- appearances of melanocytic lesions and in
ances of the diVerent types of in situ melanoma interpreting them the clinical and histological
and the clinical situations in which they occur. features should be considered together. After
The lesion that one of the authors has considering certain non-melanocytic and
described as pigmented lentiginous naevus melanocytic entities, diYculties remain. These
with atypia, which has also been called lentigi- diYculties can even be highlighted by the clini-
nous dysplastic naevus of the elderly, is cal history, when they occur in young adults
probably a precursor to an under recognised and children, or where the lesion comes from a
variant of in situ melanoma (naevoid lentigo special site, such as acral or genital locations.
maligna), which occurs as large macular Consideration should then be given to refer-
lesions, preferentially on the trunk, but also the ring the patient to a recognised expert, but it is
lower limbs of older individuals.92 acknowledged that there is a spectrum of diag-
nostic opinion even between experts.1 47 93 One
ATYPICAL NAEVOID LESIONS VERSUS NAEVOID study showed that there was only moderate
MELANOMA agreement on a group of melanocytic lesions
The group includes naevus like lesions in between recognised experts. These cases had
which the diVerential diagnosis includes small been specifically selected by the experts as
cell melanoma and the verrucous naevoid lesions that they would have considered for
group of melanomas. In the former group, fea- publication to illustrate a typical example of a
tures favouring malignancy include an older particular type of melanocytic lesion.47 Occa-
age, the presence of an in situ melanoma com- sional cases seen in the “British melanoma
ponent, dermal nests that are inappropriately slide club” and “Scottish melanoma group”
large, and reactive stromal features. With the also prompt a range of diagnostic opinions.
verrucous naevoid lesions, the cytological When the lesion is from a middle aged to
features usually clearly discriminate between elderly adult, the diagnostic problems are less,
benign and malignant. However, as mentioned because the weight of evidence in the back-
earlier, warty melanocytic lesions composed of ground of an atypical melanocytic lesion would
cells similar to those seen in small cell favour a malignant diagnosis. The more
melanoma and other lesions that look like a concerning diagnostic problem is the atypical
papillomatous intradermal naevus but have melanocytic lesions in children and young
some other abnormal feature (such as a adults, particularly, the atypical spitzoid le-
spreading edge) are more of a problem. Other sions. Because of their relative rarity, there are
features have to be considered, including the no large series of these childhood lesions with
extent and type of spreading edge, pagetoid long term follow up to give clearer guidance on
invasion, mitotic figures, or areas of regression. diagnostic pointers and prognosis. The few
cases that come to light are usually those that
ATYPICAL SPITZ/CELLULAR BLUE/DEEP have resulted in metastasis, and these are the
PENETRATING LESIONS VERSUS THICK MELANOMA minority of lesions.
Although the cases in this group are probably There is as yet no reliable marker to
small in number, they are potentially the most distinguish benign melanocytes from
important, because they are thick lesions and melanoma cells that can be used in every day
the prognosis is very diVerent depending on practice with clear and unambiguous results.
whether the lesion is benign or malignant. The Some of the newer proliferation markers might
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