< Current issue
Dermatopathology: Practical & Conceptual January - March 1997
New Concept: Melanocytic Dysplasia, Dysplastic Nevus, and Dysplastic Nevus Syndrome: Myth! Part IV
Daniela Massi, M.D.
Timothy Nielsen, M.D.
A. Bernard Ackerman, M.D.
From Seminars in Diagnostic Pathology
1. Terms and Phrases in the Title and the Abstract of the Article in Seminars in Diagnostic Pathology Not Yet Defined in Comprehensible, Repeatable Fashion
2. Critique of Positions of Clark
Changed Little or Not at All Since 1978
3. Critique of Positions of Clark
Changed Radically Since 1978
From the British Medical Bulletin
A. Examples of Impenetrable Language
B. Examples of Unsupported Speculations and Dizzying Definitions
C. A Critique of Positions of Clark
Changed Radically Since 1978
Two Articles by Clark
Summary of our Position Concerning DN and DNS as Elicited by A Series of Questions About Them
Summary of our Position Concerning DN and DNS as Elicited by A Series of Questions About Them
1. Does the DN exist?
There surely is a nevus to which more than 20 names have been given in the past 20 years, among them B-K mole, DN, and Clark's nevus. That nevus is just as distinctive as are Spitz's nevus, Unna's nevus, Miescher's nevus, Ota's nevus, Masson's nevus, etc.
2. Is the term DN appropriate?
The designation "DN" is no more appropriate than Spitz's own original title (1950) for another type of nevus, i.e., "melanoma of childhood." The appellation "Spitz's nevus" is far less confusing to physicians and patients than the previous names for it, i.e., "melanoma of childhood," "juvenile melanoma," and "benign juvenile melanoma"; "Clark's nevus" is much less bewildering to physicians and patients than "B-K mole," "large atypical mole," and "dysplastic nevus." In short, so-called dysplastic nevus is no more "dysplastic" than Spitz's nevus is melanomatous and, for that reason, is more aptly designated eponymically, i.e., "Clark's nevus." Curiously, Spitz's nevi are sometimes associated with striking nuclear atypia of melanocytes, but no matter how extraordinary the extent of nuclear atypia, those nevi never are considered by pathologists to be "dysplastic." In contrast, so-called DN display no nuclear atypia of melanocytes, yet histopathologists universally call them "dysplastic."
3. Is there a difference between a DN and a Clark's nevus?
Clark's nevus is a synonym for DN (and "B-K mole," "large atypical mole," and more than a score of other names for the same nevus), just as Spitz's nevus is a synonym for spindle and epithelioid cell nevus (and juvenile melanoma, benign juvenile melanoma, and more than a score of other appellations for the same nevus). Although those who call this nevus DN or Clark's nevus are referring to the very same nevus, the criteria that they employ to identify it, clinically and histopathologically, are different. For example, for Clark the criteria for histopathologic diagnosis of a compound type of DN are persistent lentiginous melanocytic hyperplasia, atypical melanocytic hyperplasia, lamellar fibroplasia, concentric eosinophilic fibroplasia, and lymphocytic infiltrates, whereas for Ackerman they are the silhouette of a benign neoplasm, slight elevation, and nests of monomorphous melanocytes confined to the dermo-epidermal junction and papillary dermis.
4. What is the prevalence of Clark's nevus in Caucasians?
By puberty, the vast majority (about 90%) of Caucasians have at least one Clark's nevus. Clark's nevus is the commonest type of melanocytic nevus.
5. Is diagnosis of Clark's nevus based on clinical features, histologic findings, or both?
In most instances, Clark's nevus is easily recognized clinically, being relatively symmetrical, well circumscribed, small (usually less than 5 mm in greatest diameter), flat or slightly elevated, sometimes gently mamillated, and uniformly pigmented (fawn, tan, or brown). Histopathologically, Clark's nevi are easily diagnosable, e.g., when compound, they are symmetrical and slightly elevated, and nests of monomorphous melanocytes are confined to the dermo-epidermal junction and papillary dermis. In brief, a Clark's nevus usually is readily identifiable, clinically and histopathologically. Of course, there are exceptions: rarely Clark's nevi may resemble melanoma clinically by being asymmetrical and multi-colored, and may simulate melanoma histopathologically when traumatized by virtue of melanocytes being positioned well above the dermo-epidermal junction.
6. How repeatable are clinical features and histopathologic findings in Clark's nevi?
In the vast majority of instances, clinical and histopathologic findings in Clark's nevi are just as repeatable as are those for every kind of nevus. Variations are much greater in Spitz's nevi than in Clark's nevi, e.g., clinically red or black, and histopathologically nuclei monomorphous or strikingly pleomorphic.
7. What is the differential diagnosis of Clark's nevus, clinically and histopathologically?
In most instances, there is no differential diagnosis of Clark's nevus, clinically and histopathologically, any more than there is a differential diagnosis in most instances of nevus spilus, "blue nevus,"and giant hairy nevus. Rarely, Clark's nevi may mimic melanoma clinically by virtue of large size, asymmetry, scalloped border, and variegation of pigment. Histopathologically, Clark's nevi are so characteristic that hardly ever do they pose problems in differential diagnosis.
8. Is cytological atypia essential for diagnosis of Clark's nevus?
Nuclear atypia, random or otherwise, is not seen in Clark's nevi, unlike the situation in Spitz's nevus where it is encountered in about a third of specimens.
9. Are "shoulders" invariable in Clark's nevi?
"Shoulders" are nearly invariable in the compound type of Clark's nevi, but the distance that the junctional component extends beyond the intradermal component of the nevus varies, i.e., from a millimeter to more than a centimeter. Junctional and intradermal types of Clark's nevi have no "shoulders" for obvious reasons.
10. Is the histopathologic finding of "shoulders" specific for Clark's nevi?
"Shoulders," i.e., the extension of the junction component beyond the intradermal component of a nevus, are not unique to Clark's nevi. They are observed commonly in a variety of types of melanocytic nevi, e.g., some Spitz's nevi, some Miescher's nevi, and some other distinctive types of superficial congenital melanocytic nevi.
11. Does "histologic dysplasia" correlate with "clinical atypia" in Clark's nevi?
Because neither "histologic dysplastic" nor "clinical atypia" have ever been defined in a repeatable lucid fashion, the question cannot be answered cogently and coherently.
12. Is Clark's nevus a potential or actual precursor of melanoma? In other words, is Clark's nevus premalignant?
All normal melanocytes on all anatomic sites, including the skin, eye, and meninges, have the capability to become melanocytes of melanoma. That is also true of epidermal melanocytes at the periphery of Clark's and other types of nevi. In actuality, less than 1/100th of 1% of all Clark's nevi ever eventuate in melanoma. Other types of melanocytic nevi besides Clark's nevi may be the locus rarely for development of melanoma, e.g., acquired nevi such as Unna's nevi and congenital nevi of different kinds, e.g., Miescher's, giant hairy, and "blue."
13. What is the incidence of Clark's nevi in continuity with melanomas?
Less than 25% of all melanomas in Caucasians begin in a pre-existing Clark's nevus, whereas hardly ever do melanomas in Asians and Africans begin in Clark's nevi. In short, the vast majority of melanomas worldwide begin de novo and not in association with a nevus.
14. Is "melanocytic dysplasia" a sensitive and specific marker of risk for melanoma?
"Melanocytic dysplasia" has never been defined in a repeatable, lucid fashion and, therefore, no meaningful answer to the question can be given. If "melanocytic dysplasia" is shorthand for "shoulders" of a melanocytic nevus, then that phenomenon is neither a sensitive nor a specific marker of risk for melanoma.
15. In the absence of a personal or family history of melanoma, does a single Clark's nevus or even many of them imply increased risk of melanoma?
A single Clark's nevus has no implication whatsoever of increased risk for melanoma. The evidence seems to indicate that the presence of many Clark's nevi, e.g., scores or even hundreds of them, do indicate increased risk for melanoma, even in the absence of a personal or family history of melanoma. The larger the Clark's nevi, the greater the risk for melanoma seems to be. The situation is analogous to that of congenital melanocytic nevi: a person with a single small congenital nevus is at much less risk for developing melanoma in that nevus than is a person with a giant congenital nevus. The analogy breaks down in regard to site of development of melanoma in persons with many Clark's nevi and in those with a giant congenital nevus: most melanomas that develop in persons with many Clark's nevi begin de novo, i.e., not in continuity with a nevus, whereas melanomas in persons with a giant congenital nevus almost always begin within that nevus.
16. Does the presence of DN in patients with a personal and/or family history of melanoma increase the risk for development of melanoma?
Risk for melanoma in the context of a personal and/or family history of melanoma seems to be a function of genetic disposition to melanoma and is not related to the presence of DN.
17. How many DN are necessary to qualify a person as having DNS?
Because the term "melanocytic dysplasia," on which the concept of DN turns, has never been defined in repeatable lucid fashion, and because criteria for dysplastic nevus, clinically and histopathologically, are not agreed on, there can be no agreed on definition of DNS — and there is none.
18. Does a diagnosis of DNS indicate increased risk for melanoma?
Because there is no uninimity about definition of DNS (Elder and co-authors, in 1980, contended that a single DN was sufficient to qualify a person as having the syndrome, whereas Kopf and co-workers require at least a hundred of those nevi), any relationship between DNS and increased risk of melanoma is pure conjecture.
19. Is "clinical atypia" of a nevus, alone, correlated with risk of melanoma?
"Clinical atypia" of a nevus has never been defined in a repeatable comprehensible way. If by clinical atypia is meant simulation by a nevus of melanoma clinically, then there is no correlation whatsoever with risk for melanoma. When a reputedly "clinically atypical nevus" is examined by conventional microscopy, typical findings of a Clark's nevus, devoid of nuclear atypia, are observed.
20. Do melanomas in patients with hundreds of Clark's nevi arise de novo or in continuity with a nevus?
Most melanomas in patients with both familial melanoma and in persons with many Clark's nevi arise de novo and not in continuity with a pre-existing nevus.
21. Should a Clark's nevus be biopsied and, if so, why and how?
If a nevus is diagnosed with confidence clinically as being of Clark's type, then there is no reason to biopsy it. The neoplasm is benign and risk of melanoma developing in a Clark's nevus is negligible. If, however, a lesion poses a problem in differential diagnosis clinically, i.e., Clark's nevus vs. melanoma, a biopsy must be performed to resolve the matter. Histopathologic findings in Clark's nevi are opposite those in melanomas. The biopsy specimen should be taken by scalpel excision in toto and with margins sufficient to ensure that the lesion has been removed completely. If that has been done as judged by margins examined by microscopy, no additional surgery is necessary irrespective of whether the diagnosis by a histopathologist is Clark's nevus or melanoma.
22. If a lesion proves to be a Clark's nevus by examination histopathologically and has not been removed completely, should it be?
If a diagnosis of Clark's nevus is made in sections studied by a competent histopathologist, then no further procedure is necessary because the lesion is benign and risk for development of melanoma in the residuum of it is negligible.
23. Should a patient with one or more DN be followed at periodic intervals and, if so, why and how often?
Ideally, every human being should have a complete skin examination approximately once a year to ensure that no malignant neoplasm, especially a melanoma, has developed. That luxury is not available to the vast majority of human beings in the world. A person with a single Clark's nevus is not at increased risk for melanoma, but one with scores or hundreds of such nevi may be. For that reason, a complete skin examination by a competent clinician schooled in nuance of pigmented lesions will help enable detection of a melanoma when it is still small and flat and, therefore, curable by complete simple excision. Should any pigmented lesion(s) suspected of being melanoma be detected by clinical examination, they should be biopsied by excision in toto.
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