Their Fig 2.—Back of 27-year-old woman who had four primary malignant melanomas. Pattern and appearance of moles in patient with numerous lesions. Compare with Fig 6 for appearance of B-K moles sparse in number. Proband, family M.

Their Fig 3.—Constellation of moles from right posterior should of patient shown in Fig 2. Variability in form from lesion to lesion is shown.

Their Fig 4.—Left and Right. Backs of two brothers, both of whom had malignant melanoma. Two sisters also had mole pattern almost identical to pattern illustrated in right figure.

Their Fig 5.—Back of 27-year-old woman in April 1972. Note lesion in black circle. Compare with lesion No. 3 in Fig 6 and with Fig 6, inset, which show lesion 41/2 years later. Proband, family G.

Their Fig 6 and Inset.—Same patient as in Fig 5. Photograph taken November 1976. Transformation of B-K mole into malignant melanoma. Lesion indicated as No. 3 and, in closer view, in inset, is malignant melanoma of superficial spreading type. Histology of transformed lesion is shown in Fig 12, 13, and 14. Proband, family G.

Clark et al.: "The affected patient may have fewer than ten B-K moles or he or she may have 100 or more moles."

Critique: Nearly every article about the subject of B-K moles by Clark and collaborators published subsequent to this one, and by other students of the subject, gives a different range of numbers of nevi requisite for diagnosis of the B-K mole syndrome; the numbers differ greatly from article to article. If the diagnosis really turns on a number, it would be helpful to know precisely what that number is.

Clark et al.: "A single prototypic B-K mole is about 10 mm 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. If one views four or five B-K moles as a group, there is striking variability from one mole to the next. The differences between B-K moles and ordinary acquired melanocytic nevi are summarized in Table 2 [our Fig. 3]."

Critique: The description of B-K moles clinically by Clark and co-workers fulfills all four of the "ABCDs" claimed by Friedman et al. to be criteria for diagnosis clinically of melanoma, namely, Asymmetry, Borderline irregularity, Color variability, and Diameter more than 6.0 mm.4 The mnemonic is ineffective because it applies equally to nevi of B-K and other types, e.g., some congenital nevi and acquired Spitz's nevi, and to melanomas.⁵ In an overwhelming majority of instances, so-called B-K moles are diametric to melanomas clinically, histopathologically, and biologically. Furthermore, the authors do not characterize, exactly, what they mean by ordinary melanocytic nevus. The description of CAN in Fig. 3 (their Table 2) does not apply to other common types of acquired melanocytic nevi, e.g. those named eponymically for Spitz and Unna.(6)

Clark et al.: "Histology is required for diagnosis of B-K moles. Microscopically, one sees a compound melanocytic nevus."

Critique: Clark and co-workers seem to imply that there are neither junctional nor intradermal expressions of B-K moles. Because shoulders (junctional melanocytic components that extend beyond the intradermal component of a nevus) are seen only in compound nevi and because "shoulders" was synonymous with "dysplasia" for Clark and his followers, it was inevitable that wholly junctional or entirely intradermal nevi would not qualify as DN in their schema. In actuality, virtually all acquired compound acquired nevi begin junctional, become compound, and end intradermal. In the sentence just quoted, Clark et al. acknowledge, straightforwardly, that the B-K mole is simply a melanocytic nevus.

Clark et al.: "Such [dysplastic] changes are superimposed on the compound melanocytic nevus and include atypical melanocytic hyperplasia, mesenchymal changes in the papillary dermis, and lymphocytic infiltrate."

Critique: The findings just described and pictured in Fig. 4 (their Fig. 7) are not superimposed on a compound nevus, but are integral features of the particular type of acquired melanocytic nevus dubbed by Clark et al. "B-K mole." Because the "changes" do not represent alterations of a pre-existing CAN, but are essential components of the nevus from its inception, the legitimacy of the distinction that Clark et al. draw between B-K (dysplastic) moles and CAN, and the authenticity of the concepts of melanocytic dysplasia and precursor lesions are called into question. The conclusions of those co-workers are flawed because they are predicated on the misconception that what they designate CAN are different from what they term B-K moles. Had they biopsied CAN, they would have found the same histopathologic changes as they did in B-K moles. They then may have inferred, correctly, that CAN are simply smaller, more smooth bordered, and more uniformly colored examples of B-K mole, i.e., stereotypical representations of it. By selecting for biopsy only the exceptional expression of B-K mole, i.e., "funny looking moles" that fulfill the ABCD's, Clark and co-workers came to the erroneous conclusion that B-K moles are different from what they considered to be small CAN and that B-K moles were uncommon. In actuality, their CAN are DN, and DN are the commonest type of all melanocytic nevi.

Clark et al.: "The term 'atypical melanocytic hyperplasia,' as used by us, is synonymous with 'melanocytic dysplasia,' i.e., individual melanocytes or small cluster of melanocytes that have some of the structural features of malignant melanocytes, but whose potential for development into obvious melanoma is obscure."

Critique: Here, for the first time, Clark and associates equate "atypical melanocytic hyperplasia" with "melanocytic dysplasia." In articles published in the ensuing years, the authors used "dysplasia" as a synonym for "cytologic atypia," for "aberrant differentiation plus atypia," and for a host of variations on these themes. The equation of both hyperplasia and atypia with dysplasia is contrary to basic principles of classic pathology, hyperplasia denoting an increase in number of cells and atypia indicating abnormalities of nuclei. These authors contend, repeatedly, that atypia is requisite for diagnosis of a B-K mole and that atypia identifies the lesions as premalignant. According to them, the photomicrograph in Fig. 5 (their Fig. 9) shows atypical melanocytes, but, to our eye, nuclei in those melanocytes are not atypical. That is our experience for melanocytes of B-K moles in general. In contrast, atypia of melanocytes may be striking in some Spitz's nevi, but, curiously, those nevi never are referred to as dysplastic by Clark or by any other pathologist. Never has the subject been addressed of why some Spitz's nevi, with their striking "architectural disorder" (scatter of melanocytes at all levels of the epidermis) and extraordinary cytologic atypia (remarkable pleomorphism of nuclei and sometimes abnormal mitotic figures), are not considered the quintessential dysplastic nevus. The nevus said to be dysplastic (DN) is characterized by melanocytes, disposed both as solitary units and in nests, confined exclusively to the dermo-epidermal junction and by nuclei of melanocytes that are small and monomorphous. Moreover, Spitz's nevi, irrespective of the degree of nuclear atypia, are not "premalignant."

Clark et al.: "The situation is precisely analogous to cervical dysplasia and senile keratoses: foci of squamous cells have some of the structural features of malignancy, but may remain indolent, regress completely, or progress to obvious carcinoma."

Critique: Progression from hyperplasia to "dysplasia" to neoplasia is a theory (the multi-step theory of carcinogenesis) that has yet to be proven for either epithelial or non-epithelial proliferations in the skin. Solar keratosis is not a dysplasia; it is a squamous-cell carcinoma at a very early stage of that malignant neoplastic process, analogous to radiation keratosis, arsenical keratosis, and Bowen's disease. Because those terms are synonymous with embryonic squamous-cell carcinoma, no boundary has ever been established (and never will) for where solar keratosis, arsenical keratosis, and Bowen's disease end and squamous-cell carcinoma begins. Solar keratosis cannot transform into squamous-cell carcinoma because it is a squamous-cell carcinoma! No authentic analogy can be drawn between a nevus of any kind and a solar keratosis. The same is true for so-called cervical dysplasia that , parenthetically, has yet to be defined in a repeatable way (as also is the case for dysplasia in any organ).⁷

Clark et al.: "The individual melanocytes [within the epidermis of B-K moles] are large and relatively pale; mitotic figures may be observed."

Critique: Nuclei of melanocytes in the epidermis of so-called B-K moles are small, oval, and monomorphous. Mitoses are extremely rare in B-K moles; hardly ever are they seen. It should be noted that large size and pallor do not constitute nuclear atypia; pleomorphism and hyperchromasia do.

Clark et al.: "Occasionally one sees a B-K mole that only has atypical melanocytes, mesenchymal changes, and a lymphocytic infiltrate. No features of a compound melanocytic nevus are demonstrated [Fig. 11] (our Fig. 6). Such observations suggest the de novo appearance of atypical melanocytes, lymphocytic infiltration, and fibroblasts."

Critique: This observation that pertains to a junctional type of B-K mole is not surprising, describing as it does a relatively early stage in the evolution of that particular melanocytic nevus. In time, the lesion progresses to become compound and then intradermal, just as does a lesion of other types of acquired melanocytic nevi. In short, mesenchymal changes, a lymphocytic infiltrate, and melancytes devoid of nuclear atypia are expected in many junctional B-K moles.

Clark et al.: "The atypical melanocytes of B-K moles are present focally within nevi. Multiple sections may be necessary to demonstrate them."

Critique: Later, in 1984, the authors termed this supposed finding of atypical melanocytes present focally in B-K moles "random cytologic atypia." We, in contrast, have been unable to discern notable atypia of nuclei of melanocytes in any of these nevi. In fact, Clark et al. are not really describing cytologic atypia; large size and relative pallor do not qualify as atypia. In addition to being large, nuclei must be hyperchromatic and pleomorphic in order to qualify as atypical.

Clark et al.: "The delicate fibroplasia and new blood vessel formation are focal and present early in B-K moles, but are extensive and appear as the regressive phenomenon rather late in the developmental biology of malignant melanoma of the superficial spreading type."

Critique: Fibroplasia in B-K moles (i.e., "lamellar" and "concentric") is very different from the fibroplasia that signifies regression of melanoma. So-called concentric and lamellar fibroplasia, which represent a continuum, are seen often in B-K moles and, episodically, in melanoma when melanocytes of that proliferation are positioned almost entirely at the dermo-epidermal junction at bases of elongated rete ridges. Neither "lamellar" nor "concentric" fibroplasia is observed in melanomas in the process of regressing or that have regressed. Regression of melanoma assumes two very different histopathologic patterns that have been referred to as "fibrosis" and "melanosis."⁸ Fibrosis in that circumstance occurs in a thickened papillary dermis devoid of any lamellar or concentric arrangement of bundles of collagen.

Clark et al.: "There are at least three explanations of the nature of B-K moles: (1) The lesions are atypical melanocytic lesions that occur in melanoma patients; (2) the complete B-K mole syndrome appears in childhood; and (3) the B-K moles are the result of focal transformation that occurs within heritable, distinctive melanocytic nevi."

Critique: B-K moles occur overwhelmingly in persons who have neither personal nor family histories of melanoma, develop in adults as well as in children, tend to appear in large numbers especially at puberty, but may arise any time during adulthood, and do not represent a transformation of melanocytes in a pre-existing nevus. They are, in their entirety and from the outset, a particular type of acquired melanocytic nevus, and the commonest one at that.