, . 182: 247–249 (1997)

EDITORIAL

DIAGNOSTIC DISCORD WITH MELANOMA

SUMMARY

The study of the Pathology Panel of the Dutch Melanoma Working Party highlights the great difficulty in achieving uniformdiagnostic assessment of melanoma. Their solution is to set up a national reference panel and to focus continuing medical education onidentified areas of particular difficulty. This could be appropriate for other countries, although selection of referees and funding may beproblematic. It may also be timely to consider whether melanoma terminology can be rationalized to make it more likely to be reportedconsistently by pathologists whilst still providing sufficient information for proper patient management. Alternatively the reporting ofmost melanocytic lesions could be confined to pathologists who specialise in this subject, a practice which has evolved for other areas ofpathology. This would facilitate the maintenance of standards and uniformity among that smaller group, but it would not avoid the needfor a continuing awareness among all pathologists of the diagnostic pitfalls which abound in the area of melanocytic lesions. ? 1997 byJohn Wiley & Sons, Ltd.

J. Pathol. 182: 247–248, 1997.No. of Figures 0. No of Tables 0. No. of References 10.

KEY WORDS—melanoma; diagnosis; observer variation; continuing medical education

The diagnosis of melanoma is justifiably regarded asproblematic. This difficulty cannot be resolved clinically1so that the definitive diagnosis rests entirely on thehistopathologists, but numerous studies of diagnosticagreement do not inspire confidence in their abilityalways to diagnose these lesions accurately. Even agroup who are presumed to be leading internationalexperts in the diagnosis of melanoma demonstratedconspicuous lack of agreement in their conclusions.2This American study is not alone in featuring melanomaas a diagnostic problem. The same order of discrepancywas described in Italian3 and British4 studies. It shouldbe noted, however, that in the work by Farmer et al.2and Cook et al.,4 the cases studied were specificallyselected as difficult examples or included selected cate-gories of cases with the most diagnostic difficulty.Complete concordance of diagnosis seems impossibleto achieve, even by pathologists with great experienceof the subject and international standing, so the anec-dotal apprehension of melanoma diagnosis by generalpathologists is not surprising. Definitive diagnosis is onemajor hurdle, but current management of melanomarequires, in addition, more detailed microstaging assess-ment. Each of the criteria which can be included inthese prognostic assessments, which may range throughthickness, mitotic counts, tumour infiltrating lym-phocytes, growth phase, and presence of regression, issubjective or at best a semi-quantitative assessmentsubject to its own observer variation. Whether or notthese prognostic features are mentioned in reports, letalone accurately evaluated, is also subject to markedvariation.5The study reported in the current issue of the journal,

from the Pathology Panel of the Dutch MelanomaWorking Party,6 is a very welcome contribution to thediscussion on how the diagnosis of melanocytic lesionsshould be approached. They have organized a three-

member group of pathologists to provide a quick (within1 week) second opinion to Dutch pathologists. It isorganized so that each member of the group decideswhether he can give a confident answer by himself, orwhether the case is sufficiently complex to justify allthree of the group being involved. In this way, a verylarge number of cases are reviewed annually. The Dutchgroup has demonstrated the need for the service, in that13 per cent of cases submitted as invasive melanomaswere considered benign by the panel and 14 per cent ofcases thought initially to be common acquired naeviwere thought to be melanoma by the expert group. Thisunderestimates the diagnostic discordance, since inaddition to the above discordance large numbers ofcases submitted as Spitz naevi, dysplastic naevi ormelanoma in situ were also thought to be invasivemelanoma by the reference group. The Dutch PathologyPanel for Melanoma identified the frequency of dis-crepant opinions and also noted that these were particu-larly focused in the differential diagnosis of Spitz anddysplastic naevi and in young people.The difficulty in being certain of a diagnosis of

malignancy is, of course, well known in many tumours;morphology is only an approximate guide to biologicalbehaviour. Melanoma is just one example, althoughmore problematic than most. It is so because it is atumour which shows only subtle histological changes inits progression from benign to malignant and yet theassociated changes in biological potential are dramatic.It is a tumour that whilst still having a very smallvolume, may metastasize widely and be at that stageextremely refractory to all forms of therapy. On theother hand, a melanoma which has a large surface areaand similar depth of invasion may be without metastaticpotential. Furthermore, these problems may occur inyoung patients and certainly with increasing incidence,so that they are no longer rare. Active research is being

CCC 0022–3417/97/070247–03 $17.50 Received 20 January 1997? 1997 by John Wiley & Sons, Ltd. Accepted 20 January 1997

directed towards finding additional markers of biologi-cal aggression to improve the accuracy of prognosis, butas yet none has been sufficiently convincing to replacethe existing histological parameters.The Dutch solution6 is to set up a national reference

panel to provide a back-stop for resolving problematiccases. They also advocate that continuing educationshould be focused on known difficult areas, such as Spitzor dysplastic naevi, as a way of minimizing diagnosticerrors.Total diagnostic accuracy is the ideal for all histo-

pathologists but bearing in mind the nature of thediscipline, is this an achievable objective? Ackerman,7 incommenting on this subject, has emphasized the impos-sibility of unanimity and encouraged us, and perhaps thewider audience of clinicians and patients, to be morerealistic about our role. Our responsibility is to offeran interpretation of morphological changes and givean informed opinion as to the likely behaviour of anidentified lesion. That opinion should be based oncurrent knowledge and practice, but remains an opinionand not an absolute fact. There is no current way ofestablishing the ‘right’ diagnosis, other than relying onthe wisdom of those who are respected as authorities intheir field. With melanoma, there are countless casesof thick lesions which have not metastasized as mighthave been expected and thin ones which have. Therewill always be cases which are judged even by veryexperienced pathologists to be benign, only some timelater for them to be proved wrong.This is not, however, a recommendation for a mini-

malist approach. It is still necessary to put one’s besteffort into achieving diagnostic accuracy, which will bepossible in the vast majority of unselected cases,8 or eventhe majority of selected difficult cases.6 The questionshould therefore be considered whether anything morecan or should be done to achieve a higher level ofagreement and better correlation with outcome. TheBritish Cancer Research Campaign (CRC) MelanomaPathology Panel showed that with uniform use of care-fully worded definitions of a simplified nomenclature,general pathologists could show a marked improvementin their concordance.9 This nomenclature, derived froma study of thin melanocytic lesions,4 simplified thediagnostic groups into those which appeared to haverelevance for management of patients. It includes epi-dermal or junctional lesions with atypia (melanocyticintraepidermal neoplasia), atypical melanocytic lesionswith dermal invasion but judged not to have metastaticpotential (microinvasion), and invasive melanoma withfeatures suggesting metastatic potential. The markedimprovement of diagnostic uniformity is a desirableobjective, but the concept of non-metastasis associatedwith microinvasion described by Elder and Murphy10requires more corroboration.In the meantime, expecting the body of pathologists

to accept a new nomenclature with universal enthusiasmis a little unrealistic. Alternatively, should we advocatethe Dutch model?6 It is not clear whether their system isfully or partly funded or whether it is entirely dependenton the charitable enthusiasm of the appointed referees.In the present health service environment in some other

countries including Britain, extra funding or manpowermay be important in securing the co-operation ofsuitable ‘experts’.In many countries a more informal provision of

second opinions has evolved. This should be based onthe perception of the referring pathologist that theperson selected will provide a reliable second opinion.It is possible, however, that the selection may bebased on other factors, such as the referring pathol-ogist’s limited knowledge of experts in the particulararea, friendship with the ‘expert’, geographical prox-imity, speed of response, or a feeling that the refereeis likely not to be disagreeable. These may be argu-ments for national appointees as referees, but there ismuch to be said for the friendly, current non-coercivesystem. In any case, the referred material may form alarge workload for the referee, however chosen. Thisextra workload may have been acceptable in earliertimes when there was less accountability for timespent and considerably less general workload perpathologist, but it is questionable whether it cancontinue indefinitely without some compensatorysupport.There have been some discussions about mechanisms

of payment for such work, which in Britain have rangedfrom an altruistic continuing resolve not to charge, tothe routine submission of an account to the referringdoctor or his employers on behalf of the ‘expert’ path-ologist. The lack of uniformity of proceduresuggests that some directive or agreed action wouldbe desirable in order to ensure that professional ratherthan financial criteria are used for selection of a secondopinion.The Dutch solution,6 if funded centrally, could be one

alternative. A precedent exists in Britain for centralfunding of specialist medical services, in the form of theNational Specialist Commissioning Advisory Group,and it could be extended to fund the provision ofhistological second opinions. This would, however, leavethe problem of selection of the experts, an invidious taskto be taken on, and by whom? Furthermore, this systemdepends on the preliminary recognition of problemcases by the referring pathologist. The number of casesconfidently but wrongly diagnosed would remainunidentified, although there is some evidence that thismay be a small proportion.8Another alternative would be to follow the precedent

established for renal biopsies, bone tumours, and otherspecial areas, and ensure that all melanocytic lesions arereported by a specialist. This is tending to happen bydegrees, as dermatopathology is being accepted as amajor sub-speciality within pathology. It may be furtherencouraged by the trend to cancer centres, which maytake over the increasingly complex management ofinvasive melanoma.Whichever of these options is chosen, or more likely

evolves, the primary diagnosis of any melanocytic lesionwhich is other than banal will often rest with the generalpathologist, so arguably the most important majorrecommendation of Veenhuizen et al.6 is that thereshould be continuing medical education focused onknown problem areas of melanoma pathology. Whether

248 EDITORIAL

? 1997 by John Wiley & Sons, Ltd. , . 182: 247–249 (1997)

this should be in the form of yet more unfunded EQA,or the setting up of a national panel, or some otherscheme, it is to be hoped that the work of the Dutchgroup will provoke constructive discussion. An agreedsolution could be applied to other areas of diagnosticpathology.

M. G. C11Histopathology, The Royal Surrey County Hospital,

Egerton Road,Guildford,

Surrey GU2 5XX, U.K.

REFERENCES

1.Curley RK, Cook MG, Fallowfield ME, Marsden RA. Accuracy in clinicaldiagnosis of pigmented lesions. Br Med J 1989; 299: 16–18.

2. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologicdiagnosis of melanoma and melanocytic naevi between expert patholgists.Hum Pathol 1996; 27: 528–531.

3. Corona R, Mele A, Amini M, et al. Interobserver variability on thehistopathologic diagnosis of cutaneous melanoma and other pigmented skinlesions. J Clin Oncol 1996; 14: 1218–1223.

4. Cook MG, Clarke TJ, Humphreys S, et al. The evaluation of diagnostic andprognostic criteria and the terminology of thin cutaneous melanoma by theCRC Melanoma Pathology Panel. Histopathology 1996; 28: 497–512.

5. Miller JM, Slater DN. Do histopathology reports of primary cutaneousmelanoma contain enough essential information? J Clin Pathol 1996; 49:202–204.

6. Veenhuizen KCW, De Wit PEJ, Mooi WJ, Scheffer E, Verbeek ALM,Ruiter DJ. Quality assessment by expert opinion in melanoma pathology:experience of the Pathology Panel of the Dutch Melanoma Working Party.J Pathol 1997; 182: 266–272.

7. Ackerman AB. Discordance among expert pathologists in diagnosis ofmelanocytic neoplasms. Hum Pathol 1996; 27: 1115–1116.

8. De Wit PEJ, Van’t Hof-Grootenboer B, Ruiter DJ, et al. Validity of thehistopathological criteria used for diagnosing dysplastic naevi. An inter-observer study by the pathology subgroup of the EORTC MelanomaCo-operative Group. Eur J Cancer 1993; 29a: 831–839.

9. Cook MG, Clarke TJ, Humphreys S, et al. A nationwide survey of observervariation in the diagnosis of thin cutaneous malignant melanoma includingthe MIN terminology. J Clin Pathol 1997; 50: 1–4.

10. Elder DE, Murphy GF. Malignant tumours (Melanomas and relatedlesions). In: Rosai J, ed. Melanocytic Tumours of the Skin, Vol. 2. Atlas ofTumour Pathology. Washington: AFIP, 1991; 103–205.

249EDITORIAL

? 1997 by John Wiley & Sons, Ltd. , . 182: 247–249 (1997)