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Dermatopathology: Practical & Conceptual April - June 2007
4. New Heights: Most “large dysplastic nevi” are really small congenital nevi!
Yaqin Zhang, M.D.
A. Bernard Ackerman, M.D.
superficial congenital nevus
At the outset of a discussion of a thesis such as ours, it is essential to define, albeit arbitrarily, what is meant by us in regard to "large" and "small" melanocytic nevi designated "dysplastic." "Large" here refers to 10 mm or more in diameter greatest and "small" to 5 mm or less, that being in keeping with the use of those words by Clark and followers of him.
In 1976, the notion of a precursor lesion to melanoma (B-K mole) was introduced by Wallace H. Clark, Jr., at the Advanced Dermatopathology Course of the American Academy of Dermatology, that program being directed by one of us (ABA). In 1978, Clark et al. reported on two kindreds with familial melanoma, describing what they perceived to be peculiar nevi that were common in members of those families and that tended to eventuation in melanoma, the manuscript sent to the
Archives of Dermatology
having been reviewed by one of us (ABA).[
] When B-K moles were present in number (the range being wide, i.e., fewer than 10 and more than 100) in a particular person, the individual was said by Clark et al. to have the "B-K mole syndrome," it, according to them, being associated with a risk increased markedly for development of melanoma. Although the moles varied in size (5 mm to 15 mm), outline, and color, it was the largeness of them that the coworkers emphasized as being a major feature clinical distinguishing of them from what they called "common acquired nevi." What follows are some quotations
from two "early" publications of Clark and coworkers in which large size, i.e., 10 mm or more in diameter, of B-K moles is referred to specifically:
A single prototypic B-K mole is about 10mm in diameter, is irregular in outline, and is a haphazard mixture of tan, brown, black, and pink. While seemingly flat on inspection, the B-K mole commonly has a small palpable dermal component."
"These lesions were flat, were often greater than 10mm in diameter, and were haphazardly colored with areas that were black, blue, pink, and sometimes depigmented."
"The prototype B-K mole is irregular in outline, measures approximately 10 mm in diameter, and contains a mixture of tan, brown, black, and pink pigment. On inspection, these moles appear flat, but often there is a minor palpable dermal component."
By 1980, the size of the nevi, whose name had evolved in just two years from "B-K mole" through "large atypical mole" to "dysplastic nevus," again was said by Clark and collaborators to be greater than that of "common acquired nevi," but the number given by them then was simply "greater than 5mm." This is what they had to say in regard to aspects morphologic, including size, of dysplastic nevi:
"Clinically, these [dysplastic] naevi are morphologically atypical: irregular in outline, variably pigmented (often with pink hues), and with a macular component. Typically, but not invariably, they display considerable lesion-to-lesion variability, are larger (>5mm) and more numerous than common acquired naevi, and may occur in locations generally spared by ordinary naevi, including the scalp, female breast, and buttocks."
] In that same year, 1980, Elder, Clark, and colleagues continued to stress that size of the so-called dysplastic nevus was larger than of a "common acquired nevus," but without providing any numbers to support their contention. This is what they wrote:
"The prototypic dysplastic nevus is larger than common acquired nevi and is irregular in outline and color."
In 1981, Elder, Clark, and fellow workers presented information confusing about the size of "dysplastic nevi," they doing that in these words:
"The prototypic lesion is usually, but not invariably, larger than common acquired nevi, which are not often greater than 5mm in maximum diameter. The dysplastic nevus may measure 1012 mm or greater and is irregular in shape and in outline."
By 1985, however, Greene, Clark, and associates called attention yet again to the "fact" that dysplastic nevi could be as large as 15 mm in diameter. This is how they put it: "
Ordinary moles are also present in persons with the dysplastic nevus syndrome. Ranging from 6 to 15mm in diameter, dysplastic nevi are typically, but not invariably, larger than ordinary moles."
] Never did the coworkers make clear precisely what they meant by "ordinary moles," just as was the case for what they termed "common acquired nevi," the reason most likely for that omission being there is no such thing as "ordinary," "common," "banal," and "normal" moles; those "entities" purported have never been defined because they do not exist. In 1985, too, Elder made some comments startling about size in the context of the subject of congenital nevi versus acquired nevi, a major type of the latter for him being the "dysplastic nevus." This is what he said:
"24% of congenital nevi, but not acquired nevi, were larger than 15 mm. Thus, a size of 16 mm or greater in a population of nevi in children was diagnositc of a congenital nevus, with a specificity of 100%. These data should not be applied uncritically to a population in adults, in whom large nevi (such as dysplastic nevi) may be more common than in children. . . . In an adult, a nevus larger than 16 mm is very likely a congenital nevus, and, in a lesion of this size, a corroborative parental history that the lesion was a 'birthmark' is quite probable. A more difficult problem is posed by 'small' or 'very small' congenital nevi, whose size and other clinical characteristics overlap those of acquired nevi."
] In short, for Elder, as of 1985, a nevus 16 mm or more in diameter greatest, whether in a child or an adult, was congenital. It may be inferred that Elder would not have quibbled over 1 mm and, therefore, a so-called dysplastic nevus 15 mm in diameter might be intuited to really be a congenital nevus.
In 1988, Clark, himself, underlined how important was the size, as well as the number, of "dysplastic nevi" pertinent to the issue of the "dysplastic nevus syndrome," he expressing that idea in this sentence: "
One should inquire as to whether or not other family members have a large number of moles or unusually large moles."
] By 1989, Clark's description clinical of a "dysplastic nevus" included size at times being more than 10 mm in diameter. This is how he phrased it:
"If one views a cluster of dysplastic nevi, they are all different from each other. Variability in form is the rule. A prototype is >5mm and may be 10mm or more in width. Some portion of the lesion is flat and many have an elevated area. The colors are haphazard mixtures of brown, tan, dark brown, and pink. Outlines are irregular and margins hazy."
By 1993, Elder, in his criteria for "Histological melanocytic dysplasia versus common nevus," conceded that a "dysplastic nevus" was merely greater than 4.0 mm in diameter. His
] contrasts the size of a "dysplastic nevus" with that of a "common nevus." In the same article, Elder made a claim in his
in regard to the size of "dysplastic nevus" relative to that of radial growth phase melanoma, namely, only uncommonly is it more than 10 mm in diameter. Many other students of the subject besides Clark and acolytes of him commented on the large size of "dysplastic nevi." For example, Lynch, who preferred the term "familial atypical multiple mole" to "dysplastic nevus," wrote in 1978 that such a mole could be as large as 2 cm. This is what Lynch averred about the matter:
"There were approximately 300 moles of variable size (2 mm to 2 cm) and color (brown, pink, and red). Borders of many of these moles were irregular and showed evidence of pigment leakage."
] The nevi to which Lynch was alluding almost certainly were "congenital," not "dysplastic" ones "acquired."
In 1983, Rhodes et al. admitted that even though they selected "dysplastic nevi" for inclusion in studies based on large size of nevi, they were very much alert to the fact that dysplastic nevi could be less than 5 mm in diameter, a size they considered to be small. This is how they formulated that proposition:
"Although we selected our DMN [dysplastic melanocytic nevi] for relatively large size and skin surface distortion, we would not exclude the diagnosis of DMN (or melanoma) on the basis of gross size or surface characteristics. We are aware of histologically dysplastic and malignant melanocytic tumors that are small, i.e., <5mm."
] In 1986, Kelly made clear that for him a "dysplastic nevus" had to be more than 5 mm in diameter. This is what he averred:
"Six clinical features in a melanocytic nevus was [sic] considered to suggest dysplasia: ill-defined border, irregular pigmentation within the lesion, erythema, accentuated skin markings ("pebbled" or "cobblestoned"), an irregular border and large size (maximum diameter, > 5.0mm)."
] Kelly, like Rhodes et al., seemed to be oblivious to the reality that an acquired nevus 5 mm in greatest diameter made its appearance in every instance at a size considerably smaller than that.
In 1987, Rhodes et al. commented on the size of "dysplastic moles" in contrast to that of "common acquired moles," them cut-off being 5 mm, the argument by them being that "dysplastic moles" were larger than that and that "common acquired moles" were smaller. This is what they said:
"Most common acquired moles are smaller than 5mm in diameter, distort the skin surface at least slightly, are evenly pigmented or speckled symmetrically, and have well-demarcated and smooth borders . . . In contrast to common acquired moles, dysplastic moles usually are large (>5mm in diameter) relative to a surface that is only slightly raised or raised in the center and flat at the edges."
] Ackerman, in 1989 in an exchange of ideas with Clark about the character of the "dysplastic nevus," made these statements germane to size
: "It should be noted that the melanocytic nevus once known as the "large atypical mole" because it was said to be greater usually than 1.0 cm in diameter, is now acknowledged by Dr Clark to be as small as about 5.0mm in diameter. At an even earlier stage, that nevus must be much smaller, doubtlessly less than 1.0mm is diameter. In short, all 'large atypical moles' begin as tiny melanocytic nevi, many of which remain small."
In 1997, Knoell et al. opined about the size of "dysplastic melanocytic nevi" to the effect that they were more than 5 mm in diameter. This is what they wrote:
"The following clinical criteria for DMN were established to aid in the proper identification of these lesions: irregular perimeter, size exceeding 5mm in diameter, background erythema, and variegated color (shades of browns, tans, blacks, and reds."
In 2002, Kaddu et al. asserted that so-called dysplastic nevi were much smaller on average than superficial congenital nevi. This is how they expressed that vision:
"Benign melanocytic naevus (BMN) components categorized as dysplastic nevi were characterized mainly by a flat or slightly elevated, relatively small (mean horizontal diameter 2.4 mm, range 0.513mm), mostly compound melanocytic proliferation. . . . BMN components categorized as superficial congenital nevi showed a flat or neoplastic, relatively small (mean horizontal diameter 3mm, range 0525mm), mainly dermal but sometimes compound melanocytic proliferation."
The problem of consequence for Kaddu and colleagues, like for everyone else before them who addressed the matter of size in regard to "dysplastic nevi," "superficial congenital nevi," and "common acquired nevi," is their failure to set forth differentiating criteria morphologic, i.e., clinical and histopathologic, that enables distinction among those three kinds of nevi. That being the case, what was deemed by one group of coworkers to be a "dysplastic nevus" could very well be considered by another group to be a "superficial congenital nevus." In brief, it is near certain that groups various were comparing "apples and oranges." In 2003, Braun-Falco et al. adhered to the emerging "party line" concerning size of "dysplastic nevi," to wit, they were more than 5 mm in diameter. This is what they said about it then:
"The clinical definition of an atypical naevus ("dysplastic naevus" or "naevus with architectural disorder and cytological atypia of melanocytes") stresses size larger than 5mm in diameter as a major diagnostic criterion."
In 2006, Dusza et al. advised that for them "larger nevi" of type "dysplastic" were 5 mm or more in diameter. This is what they wrote:
"The study population comprised of 10 patients with clinically dysplastic (atypical)nevi and at least 8 larger nevi, (> or =5mm) on their trunk."
Although in 1978, Clark and associates emphasized repeatedly the large size of the nevus that at first was designated by them "B-K mole" and then "large atypical mole" before being dubbed "dysplastic nevus," by 1989 ,Clark, himself, was to make this admission riveting:
"Sometimes I cannot distinguish these lesions [small congenital nevi] from dysplastic nevi. In some such instances, patients have had the dysplastic nevus syndrome and I have speculated that the dysplasia was a new event occurring at the shoulder of a small congenital melanocytic nevus. . . . In fact, they [the dysplastic findings] are usually most distinctive in large, variably colored nevi. It is reasonable that the melanocytic lesions in patients with the dysplastic nevus syndrome, clinical, have diverse histologic patterns . . ."
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