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"Dysplastic Nevus" as a legitimate phrase?


Mark A. Hurt MD

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It has often been said of melanocytic nevi, which many designate as “dysplastic,” that such nevi are “intermediate” between the so-called “common” or “ordinary” melanocytic nevus and melanoma.

Clark wrote, famously, that they (i.e., dysplastic nevi) were the “formal histogenetic precursors” of melanoma if “the pathway of differentiation was not followed” that is usually present in the “common acquired melanocytic nevus.”

But what of control skin, and what of other patterns of melanocytic nevi? Aren't [i]they[/i] also precursors of melanoma?

And more: what of the [i]actual[/i] natural history of a melanocytic nevus of [i]any[/i] pattern; what is [i]it's[/i] status in relation to melanoma? Oddly enough, Clark, himself, provided a clue, as follows:


[quote]Of course, when atypia is present in the precursor lesions, pathologists, who commonly think backward when looking at neoplastic systems, call such lesions premalignant, a common practice that gives lesions with atypical cells an unwarranted, ominous significance. The vast majority of such lesions are not precursors of anything. "They are dead-ends of neo-plastic development, terminal products with no neoplastic future ahead of them." According to Foulds, a critical student of neoplasia, "These terms [precancerous and preneoplastic] have been troublemakers for half a century or more and are best avoided. Without being accurately descriptive, they are unreliably prophetic."[/quote]

Perhaps we should challenge the notion that the phrase "dysplastic nevus" has any merit. I think it doesn't. What do you think, and why?


Reference:

Clark WH Jr, Elder DE, Guerry D 4th, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 1984 Dec;15(12):1147-65. PubMed PMID: 6500548
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Interesting topic again Dr. Hurt.

I definitely believe in/ diagnose dysplastic naevi. The term has clinical relevance, as I do believe that someone with 2 or more moderate-severe dysplastic (I agree that the term 'dysplasia' needs a better objective definition- but don't think this is possible!) naevi (or having the so called Dysplastic naevus syndrome) is at a higher risk of melanoma than someone who hasn't.


I like your theory that even normal skin is a precursor for a melanoma, and that is in keeping with my argument [url="https://dermpathpro.com/blog/14/entry-120-prolonging-the-debate-about-precursors-of-invasive-squamous-cell-carcinoma/"]in this blog post[/url]. I take it that you endorse my view point? Yes I agree that by your logic/ reasoning, even normal cells are precursors- or in fact if you take only 'potential' (wrongly so) into consideration, normal cells are also malignant! But the reason we do not call them malignant or precursor lesions is that the probability of that potential manifesting, is extremely low/ negligible. So there are sound/ logical practical reasons, not to call normal cells malignant or premalignant!

If we abandon the term dysplastic naevi (lack of consensus on the definition of 'dysplastic' is not a valid enough reason for me)- you would have to replace the term with yet another synonym (there are enough already!), as dysplastic naevi are neither benign nor malignant. I however do agree that all dysplastic naevi are not necessarily premalignant either.

I think there are two kinds of 'dysplastic' naevi:

Type 1. Those that are 'dysplastic' from the outset, but do not progress any further = the 'dead-ends' that Clark described.

Type 2. Those lesions that are excised en-route to becoming a melanoma (i.e. a melanoma excised in the very early stage). I am sure we have all seen enough cases of severe dysplastic naevi bordering on melanoma in-situ; and within the same lesion- seeing areas or definite invasion, and what one would term as 'mild-moderate' dysplasia in the more benign looking component. These spectrum of changes are not uncommonly seen within the same lesion, endorsing the view that[u]in some cases[/u], melanoma does evolve from a benign precursor, with 'dysplastic' changes being seen en-route to evolution of a full blown melanoma.

A melanoma has to start small, when it might just show cellular and architectural atypia, not fully developed enough to call it a melanoma. Thus, some of these early cases might be diagnosed as 'dysplastic', as one cannot diagnose a melanoma at that stage. I do not think that on histological grounds alone, it is possible to differentiate the 'dead-end' dysplastic naevi (type 1), from the 'early-melanoma' dysplastic naevi (type 2). In the absence of molecular evidence, we would have to club them together for the moment and keep that term. For practical purposes- even the Type 2 Dysplastic nevus I mentioned, has an excellent prognosis, when excised in the eary stages.

The difference between a type 1 and type 2 naevus, I believe is the clinical history. Most patients with the 'dead'end' dysplastic naevi- report no history of recent change as they are dysplastic from the outset and have been like that since their conception. They are usually picked up on routine clinical inspection and excised for precautionary reasons. However, the ones that have shown changes of evolution on clinical or dermoscopic grounds, are probably the 2nd type (possibly evolving into a melanoma). However, this is simply my theory and it is impossible for anyone to prove me wrong or right, as the very act of excising a naevus, would change the natural course of what it would have been a.k.a. [url="http://www.youtube.com/watch?v=DfPeprQ7oGc"]double slit experiment- observer effect[/url].

One might chose to call them all malignant (by the 'potential' theory!). However not all 'dysplastic' looking naevi evolve into melanoma (not as far as current evidence goes) and therefore this argument does not sound right to me.

Regardless, having multiple dysplastic naevi is certainly a proven risk factor to developing melanoma (though not necessarily in the dysplastic naevi themselves). Thus, I strongly endorse keeping this term.
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Robledo F. Rocha

Posted

Carcinogenesis is a cellular phenomenon. Only individual cells can give rise to tumors. An entire lesion cannot transform into a tumor, but one of its individual cells can. Bearing in mind this basic principle of tumor pathogenesis, it’s hard to consider the so-called dysplastic nevus as a precursor of cutaneous melanoma or as an intermediate melanocytic lesion in-between the progression from a banal nevus to melanoma.

In their sporadic and solitary forms, the so-called dysplastic nevi are merely variants of banal nevi. Thus, the risk for melanoma in the so-called dysplastic nevi is as high as in any other banal nevi and as in any part of the skin without discernible melanocytic proliferation.

The dearth of standardized clinical and microscopic criteria for the so-called dysplastic nevi brings an additional problem. Why we can trust in their supposed predictive value if their very diagnosis lacks interobserver reproducibility in many cases? It’s not uncommon to find “dysplastic” findings, both clinically and microscopically, in an otherwise bland-appearing nevus that doesn’t cause any concern. And experts disagree whether cytological atypia is an essential diagnostic criterion or not, so a consensus conference recommended the term “nevus with architectural disorder” over “dysplastic nevus”…

On the other hand, caution is warranted when dealing with familial cases, the B-K mole syndrome. After all the evidence provided, particularly in regard to CDKN2A gene mutations, individuals do exist at increased risk for melanoma just because they descend from families in which multiple primary melanomas were much more common than expected in the general population. The problem is, again, the dearth of standardized clinical and microscopic criteria, remaining as the only reliable criterion the increased number of blood kindreds affected. Of course this is insufficient for prevent melanoma, because nobody can predict exactly neither where, nor when a malignant tumor will arise, since melanoma can arise from any melanocytes of these individuals, including the melanocytes residing in normal-appearing epidermis and in other body parts, not only from their “atypical moles”.

I’m aware that I’m going in the opposite way to the clinical dermatologists belief, which may be checked in the above Dr. Attili’s comment and in the [url="http://www.ncbi.nlm.nih.gov/pubmed/?term=Management+of+dysplastic+nevi%3A+a+survey+of+fellows+of+the+American+Academy+of+Dermatology"]fellows of the American Academy of Dermatology’s opinion[/url]. That’s why I sign out my cases of so-called dysplastic nevus as Clark’s nevus, and I add a final note explaining the different viewpoints about this controversial melanocytic lesion.
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[quote name='Robledo F. Rocha' timestamp='1385327711']
Carcinogenesis is a cellular phenomenon. Only individual cells can give rise to tumors. An entire lesion cannot transform into a tumor, but one of its individual cells can. Bearing in mind this basic principle of tumor pathogenesis, it’s hard to consider the so-called dysplastic nevus as a precursor of cutaneous melanoma or as an intermediate melanocytic lesion in-between the progression from a banal nevus to melanoma.


[u]Dear Dr. Robledo. I would argue that my Type 2 dysplastic nevus described above, is a tumour in itself (formed from propagation of a single neoplastc cell). Thus it may well be an intermediary between a banal nevus and melanoma.[/u]


In their sporadic and solitary forms, the so-called dysplastic nevi are merely variants of banal nevi. Thus, the risk for melanoma in the so-called dysplastic nevi is as high as in any other banal nevi and as in any part of the skin without discernible melanocytic proliferation.

[u]Yes, This argument holds good for the Type 1 dysplastic Naevi that I described. However, can you distinguish this from the type 2 dysplastic nevus or do you not agree that the type 2 exists? If you do not agree, then do you think that melanoma manifests suddenly with all its full blown features, without evolving from a single neoplastic cell, multiplying and spreading up and down etc (when it would look just like a dysplastic nevus i.e. type 2)?[/u]

The dearth of standardized clinical and microscopic criteria for the so-called dysplastic nevi brings an additional problem. Why we can trust in their supposed predictive value if their very diagnosis lacks interobserver reproducibility in many cases?

[u]This variability also exists in the diagnosis of melanoma. Is that reason enough to say melanoma does not exist??[/u] [u]Having said that, there is reasonable concordance among pathologists in the UK as far as grading dysplastic naevi is concerned (based on my experience of working around various centers).[/u]

It’s not uncommon to find “dysplastic” findings, both clinically and microscopically, in an otherwise bland-appearing nevus that doesn’t cause any concern. And experts disagree whether cytological atypia is an essential diagnostic criterion or not, so a consensus conference recommended the term “nevus with architectural disorder” over “dysplastic nevus”…

[u]This is speculative. No one can prove or disprove whether these cytologically 'dysplastic' features are of concern or 'normal', as these are lesions with extremely good prognosis, [/u][u]regardless of terminology.[/u][u] So the numbers needed to treat, in any prospective study, for practical purposes, would not be suffice to reach statistical significance. That doesn't mean that we can conclude that such lesions are therefore benign! It just means that we 'do not know'.[/u]

On the other hand, caution is warranted when dealing with familial cases, the B-K mole syndrome. After all the evidence provided, particularly in regard to CDKN2A gene mutations, individuals do exist at increased risk for melanoma just because they descend from families in which multiple primary melanomas were much more common than expected in the general population. The problem is, again, the dearth of standardized clinical and microscopic criteria, remaining as the only reliable criterion the increased number of blood kindreds affected. Of course this is insufficient for prevent melanoma, because nobody can predict exactly neither where, nor when a malignant tumor will arise, since melanoma can arise from any melanocytes of these individuals, including the melanocytes residing in normal-appearing epidermis and in other body parts, not only from their “atypical moles”.


I’m aware that I’m going in the opposite way to the clinical dermatologists belief, which may be checked in the above Dr. Attili’s comment and in the [url="http://www.ncbi.nlm.nih.gov/pubmed/?term=Management+of+dysplastic+nevi%3A+a+survey+of+fellows+of+the+American+Academy+of+Dermatology"]fellows of the American Academy of Dermatology’s opinion[/url]. That’s why I sign out my cases of so-called dysplastic nevus as Clark’s nevus, and I add a final note explaining the different viewpoints about this controversial melanocytic lesion.

[u]I have mentioned this before in reply to Dr. Hurt's post. What matters most is the clinico-pathological correlation. Neither the clinician nor the pathologist can claim ultimate supremacy. However, as a clinician I have direct responsibility to the patient and have to do the 'right' thing and in this case that means to be safe and say that the evidence is not enough to call these lesions benign. This for practical purposes these lesions are deemed premalignant and treated as such. [/u]

[u]I am surprised that the proponents of the 'anti-dysplastic naevus campaign' can be so confident that 'dysplastic naevus' DOES NOT EXIST. [/u][u]The simple fact that you call it 'clark's nevus' is testament to the fact that you do not believe that it is entirely benign. If you do believe it is benign- why give it another name? Just sign it out as a benign nevus? Sorry I don't mean this to be personal. But this applies to everyone arguing in favour of a dysplastic nevus (of mild-severe degrees) being benign- If you don't think it is 'dysplastic' and truly believe in that, please sign them out as 'Benign nevus'. Why sign that out as 'Clark's Naevus' if after all it is still benign? Wouldn't that avoid confusion and keep things simple? I am confident, no one would have the courage to do that, unless perhaps in naevi showing mild grades of dysplasia, where it does not really matter![/u]



[/quote]
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Mark A. Hurt MD

Posted

I want to make clear that I regard the so-called "dysplastic" nevus as just a pattern of a melanocytic nevus, similar, in principle, to an Unna's nevus, a Miescher's nevus, a Sutton's nevus, a Zitelli's nevus and on an on. These nevi are patterns of benign melanocytic proliferations. Some are hamartomas; others are benign neoplasms.

As Clark indicated in his writings, when melanoma arises in the field of a nevus, it is a focal phenomenon; I agree with him on this point. It arises either within a cell of the nevus, a control melanocyte within the nevus, or from a melanocyte outside of the nevus that collides eventually with the nevus. The entire nevus doesn't transform, but a cell does.

The fact that some people are moley or that they have had a melanoma or that they might have a family history of melanoma doesn't change the fact that an individual lesion arises from a cell; it does not transform wholesale from a benign lesion. And more, the individual lesion that is identified later is either nevus or melanoma but not both at the same time and in the same respect.

As to the precursor issue, above I stated that:

[quote][color=#282828][font=arial, verdana, tahoma, sans-serif][size=4]But what of control skin, and what of other patterns of melanocytic nevi? Aren't [/size][/font][/color][i]they[/i][color=#282828][font=arial, verdana, tahoma, sans-serif][size=4] also precursors of melanoma?[/size][/font][/color][size=4][/quote][/size]

[size=4]To clarify this, I mean that the cells of a melanoma have to arise from somewhere by some means. A melanoma is derived -- by whatever mechanism or mechanisms -- from a melanocyte, and that melanocyte can reside in control skin, as a control melanocyte [u][i]in[/i][/u] a nevus, or an abnormal melanocyte [u][i]of[/i][/u] a nevus.[/size]

[size=4]Finally, on the issue of an intermediate lesion, I profoundly disagree with this concept. The lesion is either benign or malignant or it can develop a focus of malignancy within the benign lesion. It is not somewhere between benign and malignant. That is a metaphysical and logical impossibility. It is a violation of Aristotle's law of non-contradiction.[/size]
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Dear Dr. Hurt. I very much agree with you as far as one type of dysplastic nevus is concerned.

However I do not believe that dysplastic nevus is a single entity. I believe it might also represent a melanoma in its early stages of evolution.

Can you say with 100% certainty that a melanoma when it starts off in the junction, from a single cell and multiplies and spread horizontally and vertically, looks like a melanoma from the beginning? Do you not think that it would very much look and progress like a dysplastic nevus- from benign-mild dysplasia-moderate & Severe dysplasia?

I am not talking of the lesions that have a completely benign component within and focal dysplasia. I am talking of lesions that have a dysplastic architecture (and cellularity) throughout.

Even if the lesions have a benign component within- that doesn't exclude malignant transformation of a benign lesion does it?. Even If the theory that malignant melanocytes might secrete cytokines which cause secondary changes within the benign component is true, that does not quite exclude the ability of a melanoma to arise from a benign nevus does it?


However in both these scenario's- in the very early stages the changes would not be full blown enough to call the lesion a melanoma, as the criteria (current) for diagnosis, would not have manifest.

Would you agree with this?


Secondly- I would like you to think of a prospective study designed to disprove the presumption that a dysplastic naevus is pre-malignant. Can you think of a practical study design (with enough power/ numbers) that would be able to disprove that theory i.e. prove that dysplastic naevi are benign. I certainly think that the answer is NO. In which case, we are all guessing. Correct? So we are arguing whether your guess is mine or yours?

We are in the age of evidence based medicine and if the evidence to prove something as not being benign is absent, particularly when there is ample circumstantial evidence (with melanoma being associated with adjacent dysplastic naevi), one would have to deem dysplastic naevi as being pre-malignant, in the best interests of the patient, on clinical grounds, particularly when there is a history of change. Dermoscopically most of these dysplastic naevi are easy to recognise and are mainly
excised on grounds of change in dermoscopic pattern.


However, would certainly be interested in your thoughts/ arguments.

Regards

Sasi
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Robledo F. Rocha

Posted

Dear Dr. Attili,

Yes, Clark’s nevus, or dysplastic nevus, if you prefer, really exists. So does Spitz’s nevus, Reed’s nevus, special site nevus and so forth. But I think all of them are nothing more than variants of banal nevus. All of them don’t predict by themselves any increased risk for melanoma. They deserved distinctive names because their morphologic characteristics are fairly different from the banal nevus and might entrap reckless observers.

Melanoma can arise from an individual melanocyte within a dysplastic nevus, what you call “dysplastic nevus type 2”. This doesn’t mean that dysplastic nevus is a precursor of melanoma or an intermediate melanocytic lesion. Since dysplastic nevus is comprised of melanocytes, anyone of its constituent cells can give rise to a melanoma. In this case, a dysplastic nevus coexists with a melanoma. Conversely, a melanoma that arose from normal-appearing skin can encroach upon an adjacent dysplastic nevus. Now, a dysplastic nevus collides with a melanoma. As both phenomena can occur, it’s impossible to establish which one is taking place in many cases, if this really matters to prognostic evaluation or therapeutic decision.

It’s worth pointing out that melanoma can arise from an individual melanocyte within any variant of banal nevus, [url="https://dermpathpro.com/difficult_opinion_cases_1/_/case-do031-r33"]like in this example[/url].

I’ve decided to sign out my cases as Clark’s nevus, and not as banal nevus, because, according to my above comment, the overwhelming majority of clinical dermatologists take a contrary view on this issue. To make clear for them and for the patients that there are still controversies regarding the predictive value of dysplastic nevus, I briefly explain the opposing opinions in a final note.

Oh yeah, I keep away from the adjective “dysplastic” in order to avoid the ominous interpretation that word might render.

Best regards,
Robledo
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Robledo F. Rocha

Posted

[color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=3][u][background=rgb(247, 247, 247)](...) As a clinician I have direct responsibility to the patient and have to do the 'right' thing and in this case that means to be safe and say that the evidence is not enough to call these lesions benign.[/background][/u][/size][/font][/color]

In my opinion, the most appropriate approach would be enlighten the patient about the controversy surrounding "dysplastic nevus". The enlightned patient will reach by himself or herself the decision whose outcome only affects his or her own body and health. This is called [url="http://www.ncbi.nlm.nih.gov/pubmed/22773162"]free and informed consent[/url]. Even then, I think that the majority of the patients, if not all, will not choose the expectant or conservative management.
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I do not quite understand or agree with the logic behind calling dysplastic naevi benign, but I think we better agree to disagree and leave it at that.

[quote name='Robledo F. Rocha' timestamp='1385395436']
In my opinion, the most appropriate approach would be enlighten the patient about the controversy surrounding "dysplastic nevus". The enlightned patient will reach by himself or herself the decision whose outcome only affects his or her own body and health. This is called [url="http://www.ncbi.nlm.nih.gov/pubmed/22773162"]free and informed consent[/url]. Even than, I think that the majority of the patients, if not all, will not choose the expectant or conservative management.
[/quote]

'Informed consent' is quite an abused term as one can inform the patient of whatever information the clinician wishes to inform them about and sway the patient either way. The clinician has in most cases, the power to convince the patient that one particular treatment works better than the other, irrespective of whether that is actually true or not.

In any case- my usual practice is to tell patients that they had a slightly unusual mole which was cut out and should not cause any further problems. In the extremely rare occasions where it was incompletely excised, I do advice re-excision to be on the safe side, but say that it is not cancerous. I do not use the word 'pre-malignant' in explaining it to the patient. - this is my practical approach.
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Robledo F. Rocha

Posted

In a letter to the editor, Dr. Chen succeeded in summarising the main discussion point about dysplastic nevus:

“There has been long-standing controversy and heated debate concerning the validity of the term dysplastic nevus. In examining the pros and cons of the argument, one will find that the debate is not really about what one observes with his or her eyes both clinically and microscopically, but what one believes. Those who believe in the sequential multistep tumorigenesis theory will defend the term and concept of dysplastic nevus with might and passion. By contrast, those who do not believe in the multistep tumorigenesis theory will dismiss dysplastic nevus as a bogus term and concept.”

[url="http://journals.lww.com/amjdermatopathology/Citation/2010/12000/The_Dysplastic_Nevus_Controversy__It_Is_Not_About.26.aspx"]Chen S. The dysplastic nevus controversy: it is not about the nevus per se but one’s belief in the multistep tumorigenesis theory. Am J Dermatopathol 2010;32(8):858-859.[/url]
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Many Thanks for the reference Dr. Rocha. I found a few other interesting articles and even one by [url="http://journals.lww.com/amjdermatopathology/Citation/2009/12000/Diagnosis___Not_Prognosis,_Not_Potential,_Not.5.aspx"]Dr. Hurt himself[/url] on this issue, all of which made an amusing read. :)

Despite Dr. Hurt's quite harsh (surprisingly) & personal criticism ('Worse yet is the proposition that the spectrum consists of benign neoplasms "transforming" into malignant ones, which is a sure sign of a mind out of focus'.

'The example of melanocytic nevi existing as a continuous spectrum to melanoma is, in my opinion, the most notorious example of illogical thinking that exists in the field of dermatopathology')

of the believers in the multi-step tumorigenesis theory, I am afraid I am not convinced and would have to agree with you that Dr. Chen summarised it quite nicely.

On a different note, I find the following statement in Dr. Hurt's article, contradictory to the rest of the text:

'Stated another way: diagnosis
implies potential, prognosis, and risk because one cannot
identify the diagnostic criteria without first having had the
opportunity to observe a range of outcomes and learn to
identify fundamental criteria observable from those outcomes.'

So diagnosis, potential, prognosis etc are all interlinked and whether one likes it or not- making a diagnosis, has implications on prognosis. If diagnosis implies prognosis anyway, is it a sin to spell out that implication/ prognosis, in the diagnosis itself?

Diagnosis is defined according to the Oxford dictionary as 'the identification of the nature of an illness or other problem by examination of the symptoms'.

Identification of the nature of an illness- to my understanding means the prognosis/ outcome.

Dr. Hurt in his article quoted the Merriam-Webster dictionary for the definition ( ‘‘the art or act of identifying a disease). However, the [url="http://www.merriam-webster.com/dictionary/diagnosis"]Merriam-Webster dictionary[/url]that Dr. Hurt has referenced also defines 'Diagnosis' as:

[color=#000000][b] a: i[/b]nvestigation or analysis of the cause or nature of a condition, situation, or problem [/color][color=#000000]<[i]diagnosis[/i] of engine trouble>[/color]

[color=#000000][[b]b[/b] [b]:[/b] a statement or conclusion from such an analysis[/color]


[color=#000000]So I am afraid, I would again have to point out the inconsistency in the text. [/color]


Obviously all of this at the end of the day is just academic and makes for good arguments and counter arguments. What is important at the end of the day is what you tell and explain to your patient and how you treat him/ her.. That is what defines a good doctor. :)
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Mark A. Hurt MD

Posted

As promised, my comments to those of Dr. Attili:

[quote][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]However I do not believe that dysplastic nevus is a single entity. I believe it might also represent a melanoma in its early stages of evolution.[/size][/font][/color]

[color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]Can you say with 100% certainty that a melanoma when it starts off in the junction, from a single cell and multiplies and spread horizontally and vertically, looks like a melanoma from the beginning? Do you not think that it would very much look and progress like a dysplastic nevus- from benign-mild dysplasia-moderate & Severe dysplasia? [/size][/font][/color]


[color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]I am not talking of the lesions that have a completely benign component within and focal dysplasia. I am talking of lesions that have a dysplastic architecture (and cellularity) throughout.[/size][/font][/color][/quote]

Sasi, here, there is a problem. A melanocytic proliferation is either nevus or melanoma from its inception (excepting physiologic hyperplasia). The [u][i]identification[/i][/u] of that lesion as nevus or melanoma is another matter.

What a lesion [u][i]is[/i][/u], is a metaphysical issue; the lesion is nevus or melanoma, and it cannot be both or neither at the same time and in the same respect. Its [u][i]identification[/i][/u] as nevus or melanoma can be difficult at multiple levels because of ignorance, mimicry, or both.


[quote][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]Even if the lesions have a benign component within- that doesn't exclude malignant transformation of a benign lesion does it?. Even If the theory that malignant melanocytes might secrete cytokines which cause secondary changes within the benign component is true, that does not quite exclude the ability of a melanoma to arise from a benign nevus does it? [/size][/font][/color][size=4][/quote][/size]

[size=4]Sasi, l[/size][size=4]esions don't transform, but individual [u][i]cells[/i][/u] do. Whatever happens in these cells is such that a single cell gives rise to the phenomenon that we, eventually, identify as a melanoma -- once they have multiplied sufficiently. That neoplasm can occur [i]de novo[/i] or in conjunction with a nevus. Thus, a lesion does not "transform." If this were the case, there would be no point in attempting to differentiate between benign and malignant neoplasms; we would have to consider all of them as if they were malignant.[/size]


[quote][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]However in both these scenario's- in the very early stages the changes would not be full blown enough to call the lesion a melanoma, as the criteria (current) for diagnosis, would not have manifest.[/size][/font][/color]

[color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]Would you agree with this?[/size][/font][/color][/quote]

I agree in the sense of [u][i]identification[/i][/u]. The lesion is what it is. That task of diagnosis is identification. That certainly [u][i]can[/i][/u] be a difficult process, one prone to error.


[quote][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]Secondly- I would like you to think of a prospective study designed to disprove the presumption that a dysplastic naevus is pre-malignant. Can you think of a practical study design (with enough power/ numbers) that would be able to disprove that theory i.e. prove that dysplastic naevi are benign. I certainly think that the answer is NO. In which case, we are all guessing. Correct? So we are arguing whether your guess is mine or yours?[/size][/font][/color][size=4][/quote][/size]

Here, the very concept of pre-malignant is invalid. The assertion that a lesion is [u][i]pre[/i][/u]-malignant is to claim knowledge that the lesion will become the malignancy. Thus, the lesion is already malignant, albeit a rudimentary malignancy. By the way, the [u][i]onus of proof principle[/i][/u] asserts that the burden of proof rests on one who asserts the positive, not the negative. Even Clark asserted that "dysplastic" nevi were benign. His associates and students advocated the "intermediate" position for these lesions. Look it up. What Clark actually said will surprise you.

You might be interested in reading my monograph with Francois Milette and Bernie Ackerman on "Dysplasia & Atypia" (2009). I think we dispelled many myths on this subject.

Best for the season from

Mark
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Thanks Dr. Hurt. Season's wishes to you too.

You have infact nailed this in your one statement.

[quote name='Mark A. Hurt MD' timestamp='1385953621']
[color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]I agree in the sense of [/size][/font][/color][u][i]identification[/i][/u][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4]. The lesion is what it is. That task of diagnosis is identification. That certainly [/size][/font][/color][u][i]can[/i][/u][color=#1C2837][font=arial, verdana, tahoma, sans-serif][size=4] be a difficult process, one prone to error.[/size][/font][/color]
[/quote]


If one cannot identify A from B (irrespective of whether one believes A & B are different), then for practical purposes A & B would have to be considered & Treated the same. There is no other rational argument here, in my view.
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