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Thin Melanomas and Homologies
In the melanocytic neoplastic system at the extremes of the morphologic spectrum of “typical melanomas,” patterns are relatively unambiguous (e.g., the patterns of low grade dysplasias, and of large, bulky melanomas), but a limited portion at the precursory extremity of the spectrum is morphologically and biologically ambiguous. For this limited span, terminology has been molded to accommodate either the implications of a precursor stage, or the implications of a fully evolved melanoma, withour real assurances that the accommodations are biologically accurate, or even relevant. Clearly, the ambiguities are such that the contested patterns might be best assigned to a category of borderline melanocytic neoplasia of indeterminate malignant potential.
In the concept of MDM, there are as many variants (i.e., not of the type) of melanomas as there are variants of nevi. Also, there are no melanomas at patterns I or II; a vertical growth component (i.e., patterns III or IV) is a requisite for the diagnosis of melanoma. In the concept of MDM, special criteria, as an aid in developing a nosology, and in defining prognostic implications which have relevance for the variant patterns, are required.
With criteria of the concept of MDM, and in the settings of both the common dysplasia-melanoma sequence, and MDM of halo nevus type, borderline (i.e., less than 1 mm in vertical dimensions) melanomas share many qualities. In both categories, variable degrees of atypia, and markers for a host immune response are features. The lymphoid response in the halo nevus is distinguished by band-like qualities, and by regular spacing of dermal nests of melanocytic cells in the lymphoid infiltrates. The response usually differs in quantity, and in intimacy from that seen in thin melanomas in the common dysplasia-melanoma sequence. In addition in the component associated with the band-like infiltrates, lamellar fibroplasia is not a prominent feature of a halo nevus variant; it is a feature of atypical examples in which “dropping-off” of nests of cells in a dysplasia-like pattern is an additional feature. It is seen in association with the dermal component that has recently “dropped” into the dermis, and is situated mostly above the band-like infiltrates. Stacks of fibrous lamellae may be a marker of the dermal component in a halo nevus-like variant showing advanced patterns of regression.
The variant of MDM showing common nevus-like features commonly is misdiagnosed as a common nevus; pattern analysis lends itself to this type of error. In this type of lesion, inflammation and fibrosis in the papillary dermis are not prominent features; the absence of these features lends a nevoid quality to the patterns (c17t3P1-4, c18t3P1-5, c21t3P1-4, c22t3P1-7, & c28t3P1-8)
It is common to find a distinctive pattern of cytologic atypia in the dermal component of a halo nevus-like lesion (i.e., the component that is associated with the band-like infiltrates); the cytologic features identify a variant of dermal dysplasia; although, I have not examined the character of the lymphoid infiltrate in halo nevus, it may be different from the reaction in the papillary dermis in association with a lesion in the common dysplasia-melanoma sequence. Both the thin lesions of the common dysplasia-melanoma sequence, and those of the halo nevus category may show areas of regression. Prognostic evaluations of thin lesions are unlikely to identify representatives of either category which have a significant potential for metastasis. For thin melanomas in the categories of MDM arising in common melanocytic dysplasias, MDM of halo nevus-like type, thin lentigo maligna melanoma, thin acral lentiginous melanoma, and even thin SSM at level III (all measuring less thain 1 mm in height), it would be more accurate to assign these lesions to a category of borderline melanocytic neoplasia of indeterminate malignant potential, and to then qualify each as a neoplastic variant on the basis of any other distinguishing characteristics.
From a different perspective, patterns I & II, (i.e., patterns other than vertical growth or patterns III & IV) have also been accepted as delimiters of “melanoma.” The designations,“melanoma-in-situ,” and thin “melanomas” at level II (including examples of “SSM”), acquire the biologic significance of a “melanoma” only on a taxonomic basis; the acquisition merely reflects the willingness of an observer to arbitrarily assign a problem lesion to one, or the other category. From the perspective that only lesions in vertical growth are melanomas (concept of MDM), all dysplasias in the dysplasia-melanoma category (including lesions which otherwise would be included in the above two categories) which show moderately severe to marked atypia (i.e., high grade dysplasias) also qualify as melanocytic neoplasias of indeterminate malignant potential; they additionally qualify as dysplasia variants, being two dimensional lesions represented in patterns I or II).
Histologic diagnosis as a presumption of malignancy:
In the conduct of general surgical pathology, the assignment of a neoplasm to a malignant category on the basis of its histologic patterns is simply an accommodation, one that is based on the supposition that the lesion has either already metastasized or, if left undisturbed, will eventually produce progressive disease with metastases and/or death.
Many histologic attributes have been emphasized in the definition of cutaneous melanoma. The passion with which some observers defend the set of selected attributes - attributes which they will use in formulating diagnoses of melanoma - has politicized all the proposed collections of attributes. A muddle, in which a choice of criteria for the segmentation of melanocytic neoplastic continua rests more on the credentials of the chief proponents than on the relevancy of strict cytologic and histologic criteria to biologic potentials, is the specter facing practicing pathologists. Commercialism and a willingness to accommodate an aggressive surgeon also play a role in the selection of sets of criteria.
In all honest presumptions of malignancy, based solely on the interpretation of the histologic patterns of a primary tumor in its primary site, absoluteness, as the attribute defining the appropriateness of all prospective linguistic assignments (i.e., assignments that anticipate progressive disease, metastases and eventual death), is belied by inherent uncertainties, not the least of which is the capriciousness of neoplastic phenomena.
In cutaneous malignant melanoma (as in most malignancies), the appropriateness of the designation, melanoma, depends upon many variables, the most predictable of which are the presence, and the vertical dimensions of a vertical growth component (with the stipulation that the responsible observer from an examination of the limited two dimensional real images of a histologic section has the wherewithal to translate real images into virtual images, and to then structure a three dimensionality). Note: some proponents of the concept of “one melanoma” readily admit their inability to manipulate virtual images.
For melanomas measuring greater than 3.5 mm in vertical dimensions (“thickness”), the validity of dimensionalities, embodying attributes and relationships which have been imposed by the manipulation of real and virtual images, are easily confirmed. In lesions with such impressive physical attributes, the almost invariable associations with progressive disease lends credence to the embodied darkness of the designation, “melanoma.” At the opposite end of the physical spectrum which corresponds to the first emergence of vertical growth as an expression of neoplastic progressions (i.e., thin pattern III or IV), the criteria for the recognition of a vertical growth component become arbitrary, particularly for lesions showing variant vertical growth, and even more so for lesions in which thin vertical growth components are formed of cells with rather bland, uniform cytologic features (minimal deviation). The likelihood of progressive disease after the removal of a thin, cytologically bland “melanoma” (MDM of the most common type; a thin lesion in vertical growth in the setting of a melanocytic dysplasia) is remote. If the definition of melanoma is extended to include lesions with no vertical growth components (lesions at levels I and II), predictions of the likelihood for metastasis will have been eliminated as a valid correlate. On the other hand, pathologists, who are often engaged by lawyers as “experts,” will, in the examination of materials pertaining to claims of malpractice, commonly encounter such lesions. To even designate thin lesions in vertical growth as “melanoma” is at best a compromise, if the desideratum is to identify lesions which have a significant potential for metastasis.
In the search for the earliest stage of “true melanoma” in the sequence leading from common premalignant melanocytic dysplasias to the common melanomas, efforts continue to be wasted. In the concept of MDM, lesions in this segment of the neoplastic continuum are afforded special significance. Vertical growth, as an embodiment of a set of virtual images defining three dimensionality, is basic to the definition of minimal deviation melanoma. In essence in defining this limited segment, an attempt was made to extrapolate from patterns of vertical growth in “real” (i.e., “thick”) melanomas to the minimal requisites for characterizing a small cluster of nests or fascicles of neoplastic cells as vertical growth. In the concept of MDM, as related to the common dysplasia-melanoma sequence, two strata, each containing 2-3 closely spaced nests or fascicles of neoplastic cells (i.e., 5 or 6 nests in 2 strata) were deemed sufficient. As a corollary, it was stipulated that both atypia of at least moderate degree, and markers for host immune response were required. In the presence of severe atypia, all examples of thin melanoma in this category were, by default, assigned to the category of SSM (i.e., an expression of the common final pathway). In this approach, the requisites were: 1) size (i.e., <1 mm), 2) atypia (features less than those of the common final pathway), and 3) biologic potential (e.g., metastases uncommon and unpredictable). In regards to item 2 in the preceding list, even thin lesions showing the pattern of the common final pathway should be qualified as borderline neoplasia of indeterminate malignant potential.
In the regions immediately adjacent to the vertical growth component of a melanoma, the patterns commonly are pleomorphic. In part, the different clones (as manifested in cytologic variations) are markers for the genetic instability of melanocytic cells in the vicinity of a vertical growth component. With rare exceptions, the cells at the dermal-epidermal interface usually are the most atypical, and by inference the most advanced neoplastically (this inference is based on the assumption that by nature a neoplastic cell is predisposed to progressive deterioration of genetic controls, and that the most advanced stages of neoplasia are correlated with the most bizarre cytologic aberrations). In this approach, the most atypical cells at the dermal-epidermal interface are the youngest; the most differentiated generations, and the least atypical of the neoplastic cells (generally to be found at the deep margin of the vertical growth component) are the oldest, and least deviant generations (minimally deviant clones). Nests, situated between the two extremes, may also show cytologic variations with the implication that clusters of cytologically similar cells are genetically similar and, if locally clustered to form a vertical growth component, or a portion of such a component, provide a locus that is genetically homogeneous; such clustering of nests is evidence of the communal nature of level III lesions. Pleomorphic lesions are commonly stratified in regard to degree of cytologic atypia and, by inference, in regard to genetic heterogeneity.
Prognostications:
Parcelling of collections of real and virtual images in the borderland of melanocytic neoplasia is basic to current efforts at prognostication. The patterns of nevi, premalignant dysplasias, and thin or incipient (minimal deviation) melanomas, all in a borderland of confusing virtual images, are parcelled by pathologists as if, in the performance, the assigned designations come to define the biologic nature of stages in a neoplastic system. The stages have been imposed on a continuum; the presumption that the stages, in reference to individual lesions, have predictibility is an imposition on the nature of neoplasia. The images of “melanoma-in-situ” (4), of thin MDM as manifested in the setting of the dysplasia-melanoma sequence (3,6,7), of severe melanocytic dysplasia (a “common final pathway”) (3), of “borderline”dysplasias and melanomas (7), and of thin SSM, as well as thin acral lentiginous melanoma and lentigo maligna melanoma (i.e., pattern III lesions [5]) do not exist in nature as distinct entities; nature has no need for such distinctions. They are merely linguistic figments embodied in our amalgams of real and virtual images, images that have been crystallized to give intent to our linguistic labels. In the borderland of melanocytic neoplasia, observers, in citing preference for one or another of these conceptualized parcels of borderline neoplastic phenomena, must also admit their inability to reliably predict the malignant potential of a large group of lesions, all of which are representative of an early and common neoplastic pathway. Practically, the importance of the selection of a suitable parcel, and the assignment of an appropriate designation loses significance in the realization that all these problematic lesions should be amenable to a common form of treatment (therapeutic commonness). For either a thin problematic lesion in the premalignant melanocytic dysplasia-melanoma category, a melanoma-in-situ, or a thin SSM (at either level II or III) (8), if adequacy of the original biopsy procedure is problematical, the question of which borderline category is most appropriate for a final assignment is of little consequence, if the assignment carries with it the recommendations for both a conservative re-excision of the area and close follow-up. In fact, all these designations are encompassed in the proposed category of melanocytic neoplasia of indeterminate malignant potential.
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