Conjunctival melanoma and melanosis

Clinical and Experimental Ophthalmology 2008; 36: 786–795
doi: 10.1111/j.1442-9071.2008.01888.x
Perspective
Conjunctival melanoma and melanosis: a reappraisal of
terminology, classification and staging
Bertil Damato MD PhD FRCOphth1 and Sarah E Coupland MBBS PhD FRC Path2
1
Ocular Oncology Service, Royal Liverpool University Hospital, and 2Department of Pathology, School of Cancer Studies, University of
Liverpool, Liverpool, UK
ABSTRACT
INTRODUCTION
This paper aims to stimulate debate on the terminology,
classification, grading and staging of conjunctival melanosis
and melanoma. We audited our results with 76 invasive conjunctival melanomas. Staging according to the sixth edition of
the Tumour Node Metastasis (TNM) system did not correlate well with tumour extent and outcome. Approximately
50% of invasive melanomas were associated with ‘primary
acquired melanosis with atypia’, a term which in our opinion
underestimates the gravity of this disease. We also found
deficiencies in the grading, terminology and classification of
conjunctival melanocytic abnormalities. In summary, we
suggest that the term ‘primary acquired melanosis’ be
reserved for clinical diagnosis. Histologically, this abnormality
can be categorized more precisely as either ‘hypermelanosis’
or ‘conjunctival melanocytic intraepithelial neoplasia
(C-MIN)’. ‘Primary acquired melanosis without atypia’ can be
termed more accurately as ‘C-MIN without atypia’. In view of
the high risk of invasive melanoma, we suggest that ‘primary
acquired melanosis with atypia’ be termed ‘C-MIN’ with
atypia, with the more severe changes regarded as melanoma
in situ. To improve objectivity in the reporting of C-MIN, we
propose a scoring system based on horizontal and vertical
spread and degree of severity of melanocytic atypia. We
suggest that the TNM staging system for conjunctival
melanoma be revised to: (i) include a Tis stage; (ii) take
account of tumour size, quadrant and caruncular involvement; and (iii) improve staging of any local invasion beyond
conjunctiva.
The terminology of conjunctival melanotic abnormalities is
confusing. For example, the noun, ‘melanosis’, which refers to
melanotic pigmentation visible to the naked eye, is used to
encompass both melanin hyper-secretion and melanocytic
proliferation.1 Furthermore, there is disagreement as to
whether melanocytic intraepithelial neoplasia with atypia is
pre-cancerous or cancerous.2,3 As a result, the same disease at
a particular point in the spectrum of malignancy may be
termed ‘primary acquired melanosis with atypia’ (PAM with
atypia) by one pathologist and ‘melanoma in situ’ by another,
possibly risking under-treatment or over-treatment.
Classification of conjunctival melanocytic disorders is
valuable to clinicians and histopathologists considering the
differential diagnosis of a particular case. Various systems
have been developed (see later text), but in our opinion,
these all have limitations, such as including congenital ocular
melanocytosis, which does not involve conjunctiva, being
sub-conjunctival.4
The histological grading of PAM with atypia is variably
described using terms such as ‘mild’ and ‘severe’.5 There is
scope for a system that grades this conjunctival melanocytic intraepithelial neoplasia (C-MIN) more objectively and
reproducibly. This would make it easier to detect progression
when sequential biopsies are performed over a long period
and would enhance communication between the pathologist
and ophthalmologist. Such a scoring system would also facilitate multicentre collaboration when evaluating treatment.
Conjunctival melanomas are staged according to the
Tumour Node Metastasis (TNM) system, developed by the
American Joint Committee on Cancer and the Union International Contre Cancer.6 The objectives of this system are to
stage disease in a standardized fashion so as to enhance
prognostication, treatment planning and multicentre studies.
We feel that the sixth edition categorizes conjunctival melanomas into stages that do not correlate adequately with
Key words: conjunctival neoplasm, disease-specific mortality, melanoma, ophthalmology, pathology.
䊏 Correspondence: Dr Bertil Damato, Ocular Oncology Service, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK. Email:
[email protected]
Received 16 April 2008; accepted 3 October 2008.
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
Conjunctival melanoma and melanosis
Figure 1. Primary
conjunctival
melanosis. (a) Slit-lamp appearance,
showing irregular diffuse conjunctival melanosis. (b) Light micrograph
stained with haematoxylin and
eosin, showing a normal density of
dendritic melanocytes, with no features of atypia and with epithelial
hypermelanosis.
a
prognosis. For example, bulbar conjunctival tumours move
from stage 1 to stage 2 if there is any corneal involvement.
The aims of this article are to highlight shortcomings in
the terminology, classification, grading and staging of conjunctival melanocytic disorders and to stimulate debate on
these topics. It is not the intention to provide an encyclopaedic review of the published literature, which is extensive.
Only references relevant to our suggestions are therefore
cited.
NORMAL
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CONJUNCTIVAL MELANOCYTES
Conjunctival melanocytes are normally dendritic and located
exclusively in the basal layer of the epithelium, where they
are greatly outnumbered by basal squamous cells. The melanocytes secrete melanin into the adjacent epithelium, to
provide protection from ultraviolet light. The amount of
conjunctival melanin is not usually sufficient to be visible to
the naked eye.
b
melanocytes, which may or may not demonstrate cytological
atypia.
Primary conjunctival hypermelanosis
This consists histologically of an increased production of
melanin by melanocytes that are normal in size, location and
number (Fig. 1). These are the histological features of the
cutaneous freckle (ephelis) and could be regarded as such
when they arise as small, faint, melanotic macules in light
skinned individuals. Diffuse bilateral conjunctival melanosis
is more common in individuals with dark skin, such as those
of African or Hispanic origin, in whom the widely used term
‘racial melanosis’ is accepted. Some have advocated the term
‘benign epithelial melanosis’;8 however, according to our
schema, primary conjunctival melanosis is by definition
benign, because cytological features of malignancy are necessarily absent.
Secondary conjunctival melanosis
MELANOSIS
The term, ‘ocular melanosis’, dates back to the early nineteenth century.7 Originally, it included uveal and conjunctival melanomas. Today, it refers to flat, melanotic
pigmentation that is visible on naked eye or slit-lamp
examination. The term ‘melanosis’ tends also to be used to
describe histological appearances of hyperpigmentation,
both intra- and extracellular.2,4 It is also used, inappropriately
in our opinion, to describe a proliferation of melanocytes
within the conjunctival epithelium. We feel it would be
useful to distinguish between these two forms of hyperpigmentation by using the following terms: (i) ‘hypermelanosis’,
to describe over-secretion and increased deposition of
melanin; and (ii) ‘conjunctival melanocytic intraepithelial
neoplasia (C-MIN)’ to refer to an increased population of
This term refers to conjunctival melanosis that is secondary
to an increased deposition of melanin in conjunctival epithelium as a result of: (i) conjunctival lesions such as inclusion
cysts and squamous cell carcinoma (Fig. 2);9 and (ii) systemic
conditions, such as Addison’s disease or treatment with
calcium channel blockers.10 The melanin can be intracellular
as in squamous cell carcinoma, or extracellular, as in Addison’s disease.
NAEVUS
Conjunctival naevi are benign proliferations of melanocytic
naevus cells usually located predominantly in the substantia
propria.11 They vary greatly in their degree of pigmentation.
Histologically, the main types are classified as: junctional
(Fig. 3), compound, subepithelial, Spitz naevus and blue
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
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Damato and Coupland
b
Figure 2. Secondary conjunctival
melanosis, exemplified by pigmented, keratinized squamous cell
carcinoma on the temporal bulbar
conjunctiva adjacent to the limbus.
(a) Slit-lamp appearance. (b) Light
micrograph stained with haematoxylin and eosin (Black arrow
shows melanin within carcinoma;
white arrow shows melanin in macrophages in stroma).
b
Figure 3. Conjunctival naevus. (a)
Slit-lamp appearance. (b) Light
micrograph stained with haematoxylin and eosin. Arrow shows
border between intraepithelial and
sub-epithelial naevus. Cysts are
present in the lower part of the
figure and these are typical of conjunctival naevi.
a
a
naevus. Pure conjunctival intraepithelial naevi can occur but
are exceptionally rare.
includes the palpebral conjunctiva, which is not located on
the ocular surface.
CONJUNCTIVAL MELANOCYTIC
NEOPLASIA (C-MIN)
Conjunctival melanocytic intraepithelial
neoplasia without atypia (syn. primary
acquired melanosis without atypia, benign
conjunctival melanocytosis)
INTRAEPITHELIAL
By definition, all acquired conjunctival melanocytic intraepithelial proliferations are neoplastic. Some might suggest that
the term ‘ocular surface melanocytic neoplasia’ should be
used, because of the recent vogue for referring to conjunctival squamous cell neoplasms as ‘ocular surface squamous
neoplasia’.12 We prefer the adjective ‘conjunctival’, because it
The clinical appearance is that of a unilateral, conjunctival,
melanotic macule, which develops in later life (Fig. 4a). This
pigmentation tends to be irregular and to wax and wane,
gradually becoming more extensive. It can become multifocal.
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
Conjunctival melanoma and melanosis
Figure 4. Conjunctival intraepithelial
melanocytosis
without
atypia. (a) Slit-lamp appearance
showing irregular pigmentation in
superior bulbar conjunctiva. (b)
Light micrograph showing an
increased population of melanocytes, which are located in the basal
layer of the epithelium and which
do not show cytological atypia (haematoxylin and eosin). (c) Light
micrograph showing melanocytes
identified by immunohistochemistry
using MelanA.
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b
a
c
Histologically, there is a diffuse, intraepithelial melanocytic proliferation, with increased numbers of melanocytes
confined to the basal layer of the conjunctival epithelium
(Fig. 4b,c). These melanocytes are either normal or hypertrophic, possibly with an increased number of dendrites, and
show no cytological features of atypia or of malignancy.
This condition is widely called ‘PAM without atypia’;1,2
however, we consider the term to be imprecise, especially as
it also includes hypermelanosis without cellular proliferation
(as mentioned earlier).13 One could consider defining this
condition as ‘conjunctival intraepithelial melanocytic hyperplasia’; however, by definition, hyperplasia indicates that the
cellular proliferation is a reversible response to a physiological stimulus and it is not known whether this is indeed the
case. We propose the term ‘conjunctival melanocytic
intraepithelial neoplasia (C-MIN) without atypia’, because
(i) this proliferation of melanocytes within the conjunctival
epithelium does represent ‘neoplasia’; and (ii) there is both
clinical and experimental evidence suggesting that this condition can undergo transformation and progress to ‘C-MIN
with atypia and ultimately to invasive melanoma’.1
Conjunctival melanocytic intraepithelial
neoplasia (C-MIN) with atypia (syn. primary
acquired melanosis with atypia)
Clinically, this is indistinguishable from C-MIN without
atypia (Fig. 5a). Histologically, it is characterized by a neoplastic melanocytic proliferation with significant cellular
pleomorphism but with no penetration of the basal membrane and, hence, no invasion of the substantia propria. The
melanocytic atypia varies in severity, from a proliferation of
small polyhedral melanocytes, with only subtle cellular pleomorphism, to the presence of large melanocytes or epithelioid cells, usually with prominent nucleoli and possibly with
conspicuous mitotic figures. The atypical melanocytes can be
confined to the basal layer of epithelium or can spread vertically to involve more superficial epithelial layers, eventually
replacing the entire epithelium. In many cases, the atypical
melanocytes clump into ‘nests’, which may either be single,
multifocal with a ‘skip-like pattern’, or confluent in either the
radial or vertical direction (Fig. 5b). In addition, the intraepithelial atypical melanocytes can demonstrate a dissociated
single-cell (pagetoid) spread.
C-MIN with atypia is widely referred to as ‘PAM with
atypia’.1,2,5 We consider the latter term to be imprecise
because the word ‘melanosis’ is vague, as mentioned earlier,
and because it encompasses: (i) melanocytic intraepithelial
neoplasia with mild atypia; (ii) conjunctival melanoma in situ;
as well as (iii) secondary pagetoid spread from an invasive
conjunctival melanoma. The term ‘conjunctival melanocytic
dysplasia’ would be convenient as it incorporates both cytological and architectural disruption as seen in ‘C-MIN’.
However, the term ‘dysplasia’ has fallen out of favour in
pathology circles, particularly when addressing melanocytic
lesions, and is generally applied to pre-malignant changes
involving epithelial cells. We propose the term ‘conjunctiva
melanocytic intraepithelial neoplasia with atypia’ as replacement for ‘PAM with atypia’, because this is indeed a neoplastic process, as indicated by the presence of significant
cytological atypia and the ultimate progression to invasive
melanoma in advanced stages. In addition, this terminology
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
790
Damato and Coupland
a
b
has similar inferences as other intraepithelial neoplasia, in
the conjunctiva and elsewhere.
At present, C-MIN is generally graded as ‘PAM’ with
‘mild’ or ‘severe’ atypia.5 Some also use the term ‘moderate’.4
Such terms are subjective, however, and therefore do show
poor inter- and intra-observer reproducibility. We would
prefer a more objective grading system. The main risk factors
predicting invasive melanoma are degree of cytological
atypia as well as pattern and extent of intraepithelial
infiltration.1,5,14 We suggest grading C-MIN according to: (i)
the pattern of horizontal (radial) spread (i.e. basal, pagetoid,
nesting); (ii) degree of vertical spread from basal layer
towards surface (i.e. basal, <50% of epithelial thickness,
50–90% epithelial thickness and >90% of epithelial thickness); and (iii) grade of cytological atypia (i.e. nuclear size,
abundance of cytoplasm, mitotic rate and nucleoli). We have
prepared a score sheet to facilitate this process, which we are
currently assessing for intra- and inter-observer repeatability
(Fig. 6). This would be useful both clinically and for research
purposes.
Assessment of the extent of melanocytic proliferation is
enhanced by the use of immunohistochemical stains, such as
MelanA/MART-1. Pancytokeratin is useful in demonstrating
the ‘mirror image’ to the MelanA stain, showing the proportion of conjunctival epithelial cells (be they surface epithelia
or inclusion cysts) that have been replaced by the atypical
melanocytes. Imperative in the pathology report are: (i) an
indication as to how much of the conjunctival biopsy is
occupied by these changes, in particular, by the most severe
alterations; and (ii) whether the C-MIN is present in any of
the surgical resection margins. Further clinicopathological
studies are required to correlate these features with the risk of
invasive disease, with and without treatment, and hence the
criteria for surveillance, biopsy and treatment.
CONJUNCTIVAL
MELANOMA IN SITU
Melanoma in situ necessarily precedes all invasive disease,
because most conjunctival melanomas arise from intraepithelial melanocytes.
Figure 5. Conjunctival melanocytic intraepithelial neoplasia. (a)
Slit-lamp appearance, with diffuse,
flat, conjunctival melanosis, with
variable pigmentation. (b) Light
micrograph, showing nests of atypical melanocytes in the basal area of
the epithelium.
Folberg et al. reported that nine out of ten (90%) cases
with vertical (i.e. non-basal) invasion of epithelium by melanocytes with atypia progressed to invasive melanoma. Irrespective of such vertical intraepithelial spread, if the
melanocytic atypia amounted to epithelioid cytology, then
75% of patients developed invasive melanoma as compared
with 4 out of 16 cases (25%).1 Sugiura et al. analysed 29 cases
of ‘PAM with atypia’ and found invasive disease in 15/16
cases with epithelioid melanocytes, even when these were
confined to the basal layer (i.e. showing ‘lentiginous’
growth).14 Shields et al. reported lower rates of invasive melanoma;5 however, this might be because of treatment. We
found C-MIN in 50% of 40 patients with invasive conjunctival melanoma.15 These histological features are broadly
similar to those found in skin and mucous membranes (such
as the oral mucosa), which are generally termed ‘melanoma in
situ’ (Fig. 7). For these reasons, there is an argument for referring to all C-MIN as ‘conjunctival melanoma in situ’. Confirmation of such a hypothesis can only be obtained by
examining the genotypic features of the atypical melanocytes in the various stages of C-MIN and comparing them
with those in the invasive component.
The cut-off between ‘PAM with severe atypia’ and conjunctival melanoma in situ is vague. There seems to be a
general reluctance to refer to C-MIN as conjunctival melanoma in situ unless the abnormal melanocytes have completely replaced the surface epithelial cells. This is possibly
because of concerns that patients and ophthalmologists
might become alarmed, so that excessive treatment is administered, with the risk of causing unnecessary ocular
morbidity.5 These risks need to be weighed against the risk of
metastatic death. In Sugiura’s study, four patients with epithelioid melanocytes (14%) developed metastases by the
completion of their study.14 Our concern is that the term
‘primary acquired melanosis with atypia’ might result in
under-treatment of early intraepithelial non-invasive neoplasia, just when any opportunities for eradicating this lethal
disease might be greatest. Our term ‘conjunctival melanocytic intraepithelial neoplasia’ may be less likely to provide
false reassurance. Interestingly, both Folberg and Sugiura
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
Conjunctival melanoma and melanosis
791
Figure 6. Score sheet for histological grading and staging of conjunctival melanocytic intraepithelial proliferation (includes the spectrum of
melanosis, benign melanocytosis and conjunctival melanoma in situ).
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
792
Damato and Coupland
a
Figure 7. Light micrographs of in
situ cutaneous melanoma. (a) Haematoxylin and eosin. (b) MelanA
stain demonstrating the atypical
melanocytes.
b
a
Figure 8. Invasive
conjunctival
melanoma. (a) Nodular tumour
encircling the limbus. (b) Diffuse
melanoma
with
sub-epithelial
infiltration. Note how the clinical
appearances are similar to those of
melanocytic intraepithelial neoplasia (Fig. 5a).
b
recommend treatment of all patients with any degree of
intraepithelial melanocytic atypia, with the goal of eradicating this disease and minimizing the risk of invasive
melanoma.1,14
Whether intermediate grades of C-MIN are regarded as
pre-malignant disease or melanoma in situ, there are many
patients who are managed by delaying treatment until progressive disease is confirmed by sequential biopsy. In such
cases, it is hoped that our scoring system will enhance communication between pathologist and surgeon so that progressive disease can be detected and treated more quickly.
Patients and ophthalmologists should not be unduly
alarmed by the term ‘conjunctival melanoma in situ’ if it is
explained to them that, with timely and effective treatment, the risk of metastatic spread is minimal, because of
the absence of lymphatic channels in the conjunctival
epithelium.
INVASIVE
Figure 9. Invasive conjunctival melanoma with adjacent intraepithelial disease.
CONJUNCTIVAL MELANOMA
It is conventional practice to label conjunctival melanomas as
‘invasive’ even when this is minimal. Such invasion is a key
point in disease progression, because it provides the melanoma with access to lymphatic channels in the conjunctival
substantia propria, and hence a route for regional and systemic metastases.
Conventionally, invasive conjunctival melanomas are
classified according to whether they originate from intraepithelial neoplasia, a naevus or de novo.2 To our knowledge,
however, there is no convincing evidence that derivation of
a melanoma from a naevus influences outcome in any way.
We would prefer to classify conjunctival melanomas according to factors that influence outcome, that is, according to:
(i) whether they show a discrete or diffuse infiltrative pattern
(Fig. 8a,b); and (ii) whether or not they are associated with
C-MIN, which may consist of either pre-existing melanoma
in situ, secondary spread from the invasive tumour, or both
(Fig. 9).
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
Conjunctival melanoma and melanosis
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Figure 10. (a) Cumulative ‘bubble plot’ showing distribution of invasive conjunctival melanoma according to local tumour recurrence. Each
bubble indicates an area of conjunctiva, with the size of the bubble indicating the percentage of patients showing tumour involvement of that
area. (b) Kaplan–Meier curves showing time to local tumour recurrence according to coronal tumour location. (c) Cumulative ‘bubble plot’
correlating distribution of invasive conjunctiva with metastatic death. (d) Kaplan–Meier curves showing time to metastastic death according
to involvement of caruncle. In (a) and (c), results from left eye were transposed to right eye. From Damato and Coupland.17
CLINICAL
STAGING OF
CONJUNCTIVAL MELANOMA
The TNM system stages tumour size and extent for the
purposes of planning treatment, estimating prognosis, evaluating outcomes and facilitating multicentre studies. The
sixth edition of the TNM system stages conjunctival melanomas as follows: T1 for bulbar tumours; T2 for tumours
involving cornea; T3 for tumours involving non-bulbar conjunctiva; and T4 for tumours invading globe, eyelid skin,
orbit, nasal sinus or brain.6 This system suffers from several
limitations because it: (i) excludes a Tis stage; (ii) takes no
account of tumour size, which is known to influence treatment, if not survival; (iii) implies that corneal invasion
worsens the survival prognosis, although to our knowledge
there is no evidence for this;16 (iv) does not consider tumour
quadrant, whereas our data suggest that medial tumour loca-
tion is associated with a worse prognosis (Fig. 10a,b);17 (v)
merges all non-bulbar conjunctival areas into one group
when our studies suggest that caruncular involvement may
be associated with a worse prognosis than forniceal or palpebral location (Fig. 10c,d);18 (vi) suggests that intraocular
invasion is associated with a worse prognosis than caruncular involvement, whereas the opposite is likely to be the
case, the eye not having any lymphatic channels; and
because it (vii) categorizes eyelid and brain involvement
equally, whereas the latter is likely to be associated with a
lower life-expectancy.
On the basis of our studies, we have made a number of
recommendations to the current TNM committee revising
the sixth to the seventh edition, due for publication in 2009.
Several of our proposals have been accepted: Stages T1 and
T2 invasive melanomas are categorized according to
number of quadrants of conjunctiva affected. Non-bulbar
© 2008 The Authors
Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists
794
Damato and Coupland
conjunctival melanomas are subdivided according to
whether or not the caruncle is involved. T3 tumours
show local invasion beyond conjunctiva to globe, eyelid,
orbit and sinuses. T4 melanomas involve central nervous
system. Further studies are needed to correlate longterm outcomes with baseline disease at the time of initial
treatment.
CLASSIFICATION
OF PIGMENTED LESIONS OF
THE CONJUNCTIVA
Several classifications have been proposed for conjunctival
melanocytic abnormalities. Two in particular are widely
used and these have been developed by the World Health
Organisation and the Armed Forces Institute of Pathology.2,4 Both classifications of conjunctival melanocytic
disease have limitations. First, both include ‘ocular melanosis’, which is non-conjunctival, and a melanocytosis, not
hypermelanosis. Second, both refer to conjunctival melanoma in situ as ‘primary acquired melanosis’. Third, the
WHO classification considers conjunctival melanoma in situ
as ‘pre-cancerous’ (i.e. pre-neoplastic) instead of cancerous.
Furthermore, it does not include naevus in the precancerous group, even though this can give rise to melanoma, albeit rarely.
We propose a different classification, which overcomes
the problems of the WHO and AFIP systems (Table 1).
Table 1. Proposed classification of melanocytic conjunctival
lesions
Melanosis
Primary
Freckle
Racial
Secondary
Ocular disease
Systemic disease
Conjunctival naevus
Junctional naevus
Compound naevus
Subepithelial naevus
Spitz naevus (epithelioid/spindle cell)
Blue naevus
Conjunctival melanocytic intraepithelial neoplasia (C-MIN)
Without atypia
With atypia
Invasive conjunctival melanoma
Without intraepithelial neoplasia (i.e. de novo)
With primary intraepithelial neoplasia
With secondary intraepithelial neoplasia (i.e. pagetoid spread
from invasive tumour)
Secondary conjunctival melanoma
From skin
From uvea
Metastatic conjunctival melanoma
From cutaneous melanoma
C-MIN, conjunctival melanocytic intraepithelial neoplasia.
SUMMARY
AND CONCLUSIONS
In this article, we have highlighted shortcomings in the
terminology and classification of melanosis and conjunctival
melanocytic intraepithelial proliferations and in the staging
of melanoma.
The literature is replete with terms and classifications for
intraepithelial melanocytic proliferations, which must have
seemed as valid to their proponents as our suggestions seem to
us. We accept that, despite its shortcomings, ‘PAM’ may be
here to stay, if only because it comes off the tongue so easily.
We would argue, however, that the term ‘C-MIN’ is more
precise and just as easy to pronounce! Although ocular
oncologists recognize the serious implications of intraepithelial melanocytic neoplasia, our impression from patient referrals to our centre suggests that some general ophthalmologists
and pathologists are being misled by term ‘PAM’ and its
possibly harmless connotations so that treatment may be
sub-optimal.
In 1985, Folberg et al., in their landmark paper, cited Henkind’s astute observation that ‘much of what has been written
about pigmented lesions of the conjunctiva is either anecdotal, speculative, or controversial’.1,18 This situation still persists 23 years later. Multicentre studies are required to
accumulate sufficient evidence for progress to occur, but
these in turn depend on adequate and uniform documentation of disease severity and extent, which we hope this paper
will improve.
ACKNOWLEDGEMENT
Research Support: The Ocular Oncology Service in Liverpool is funded by the National Commissioning Group of the
National Health Service.
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Journal compilation © 2008 Royal Australian and New Zealand College of Ophthalmologists