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Dropping off: Alternately, some cells individually may “drop off” from the epidermis into the dermis; they may individually migrate out of a junctional nest, or the lentiginous component into the dermis. In the evolution of lamellar fibrosis, as manifested in premalignant melanocytic dysplasias, some of the dysplastic cells at the periphery of the affected nests apparently become entrapped in the dermis among coarse fibrous lamellae; occasional isolated neoplastic cells are found among coarse lamellae in areas of lamellar fibrosis at the periphery of junctional nests in dysplasias. This process of entrappment may contribute to the formation of nests of cells in the dermis.
The lichenoid process, if part of a melanocytic dysplasia, is associated with the formation of a delicate fibromyxoid matrix at the dermal-epidermal interface (i.e., accretive fibrosis at the dermal-epidermal interface with focal incorporation of a limited portion of the damaged epidermal domain into the dermis). In such areas, junctional nests are not sharply defined at their interface with the dermis (i.e., basement membranes are incomplete). Individual neoplastic cells may become entrapped in this delicate fibrous tissue and may contribute to the dermal population.
In the histologic examination of both typical nevi, and low grade dysplasias (atypical nevi), efforts to identify junctional nests in the process of “dropping off” from the epidermis into the dermis are seldom rewarded. In melanocytic dysplasias, clefts are commonly observed at the interface between junctional nests, and the overlying epidermis. These clefts appear to be artefacts but, perhaps, have significance as a marker for a potential space into which fibrocytes may extend and, by modification of the matrix, effect a true separation between a junctional nest and the epidermis. Similar clefts are common in Spitz-like variants; they have become one additional real image that, having been incorporated in our stores of virtual images, is commonly cited as an aid in the diagnosis of a Spitz lesion.
Rarely, in dysplastic nevi, clefts, containing flattened, dyskeratotic keratinocytes (apoptotic cells?) that are loosely attached to their neighbors, define a potential line of cleavage between the domains of keratinocytes and junctional nests of melanocytes. The detachment (dropping off) of junctional nests could involve a cellular process affecting interface keratinocytes which are adjacent to junctional nests. Such a process, involving interface keratinocytes, if confirmed, would be akin to that of apoptosis. In the resulting defect, connective tissue would extend from the papillary dermis into a defect in the junctional domain. In the process of inlaying fibrous tissue into the defect, remnants of the junctional nests would become entrapped in a newly formed portion of the dermal domain. As the end result, junctional nests, or portions thereof, would appear to have “dropped off” into the dermis.
The so-called “pale acidophilic bodies” (Kamino bodies) of a Spitz nevus may be markers for the residua of a modified form of apoptosis in which the interface between a fascicle of tumor cells and the epidermis is modified. The modifications may facilitate the “dropping off” of some of the affected fascicles. Some of the material that has been characterized as Kamino bodies apparently represents basement membrane material; some of the “acidophilic bodies” seem to be necrotic cells.
Subsequent divisions of solitary, sequestered melanocytic cells, and their descendants in the dermis, or of portions of junctional nests, whether as sequelae of lamellar fibrosis, or in response to a modified lichenoid reaction would lead to the formation of nests of similar cells in the dermis. For a premalignant melanocytic dysplasia, a lesion showing some, or all, of these variant patterns of “dropping off” would be one with a potention to undergo a transition to vertical growth.
Obviously, I cannot explain the mechanism of “dropping off.” I have, however, at least searched for the relevant patterns.
In premalignant melanocytic dysplasias (and related atypical, or dysplastic nevi), continuity of patterns is usually interrupted. The dysplastic cells form rounded nests, or fascicles; some of the aggregates of cells “drop off” into the dermis. Those in the dermis establish little, or no, continuity with any remnant of a pre-existing nevus in the underlying dermis. In part, this loss of continuity is a result of the host immune response with condensations of fibrous tissue around the newly immigrated nests of dysplastic cells (e.g., lamellar, or appositional fibroplasia). The lack of continuity in premalignant melanocytic dysplasias may also reflect a diminution in the number of optional phenotypes, as neoplasia progresses from nevus, to dysplasia, to melanoma (i.e., genotypic restrictions of the expression of phenotypes in neoplastic progressions). In these virtual images, dysplastic cells are genotypically isolated in the dermis; they have lost the sameness that, regardless of phenotypic expressions, characterizes typical nevus cells. The migrants, by their altered genotype, may have lost the capacity to establish continuity with any remnants of a nevus in the underlying dermis.
Without respect for the patterns of the nests of neoplastic cells in the dermis, to equate the “dropping off” of parts, or all of some of the junctional nests with “invasion” (i.e., micro-invasion) would raise the specter of a diagnosis of melanoma. As one example, if the degree of atypia in the epidermal component of a melanocytic neoplasm is severe (marked), then the presence of nests of similar cells that have “dropped off” into the dermis (predicated on only a few nests of atypical cells, widely and randomly distributed in the papillary dermis) would be sufficient for a diagnosis of superficial spreading melanoma at level II (Clark’s criteria), or micro-invasive melanoma (Elder). In addition, in the setting of actinically damaged skin, such a combination (with the stipulation that there is atypia, but with no requisites as to the degree of atypia) would, by certain criteria, be sufficient for a diagnosis of lentigo maligna melanoma (Clark’s and Mihm’s criteria). If the above examples of diagnostic criteria (as embodied in currently popular conceptualizations of melanoma) are validated, an assignment of lesions with pure lentiginous and junctional components, and with marked cytologic atypia to the category of “melanoma-in-situ” (i.e., the concept of “one melanoma”) becomes a significant, but confining, accommodation. Once having made such an accommodation in routine practice, it is likely that the criteria for the requisite degree of atypia will subsequently be relaxed; lesions with lesser degress of atypia would be admitted to the category of melanoma-in-situ. All these accommodations have been proposed. In turn, many pathologists have adopted the proposals. In this act, they have validated the accommodations. In promoting the concept of “melanoma-in-situ,” the criteria have become sufficiently relaxed to provide ambiguities between “melanoma-in-situ,” and lesions such as acral nevi and dysplasias, or recurrent nevi (“pseudomelanoma”).
In the discussions of “dropping off,” the isolation of nests of cells was emphasized. The “dropping off” of individual cells may portend an expression of a phenotyptic option that is different from those available to cells in nests. Herein, by definition, melanocytes of lentiginous components are migrants (they move freely in the basal unit of the epidermis and, on occasion, may find their way individually into the dermis). In this process, the migration of individual cells from a lentiginous component, to the exclusion of any contributions from the junctional components, may favor the expression of desmoplastic properties. In the evolution of desmoplastic melanoma, cells might migrate individually from a lentiginous component in the epidermis into the dermis; in their new domain, they then acquire fibroblastic, or fibrogenic properties, or induce fibroplasia.
MDM of the dermal type, and melanoblastoma of infancy as encountered in the setting of giant congenital nevus often seem to evolve without the participation of a junctional component, and without a contribution of comparable neoplastic cells that have “dropped off” into the dermis. Malignant melanomas of cellular blue nevus type, including atypical cellular blue nevus (MDM of cellular blue nevus type), usually are of dermal origin. Some patterns in MDM offer evidence that the dermal component of a nevus may undergo neoplastic progressions independent of phenomena at the dermal-epidermal interface.
Some nevi recur following a biopsy. Often, in this sequence, a superficial shave of a typical nevus will have been the initial procedure. In some examples, a low grade (or rarely a high grade) dysplasia, rather than a typical nevus, will have been sampled. The changes over the scar in the recurrent lesions are basically the same, whether the initial lesions have been a typical or an atypical nevus (dysplasia). In the recurrences, a remnant of a typical nevus often, but not invariably, will be represented in the dermis beneath an area of dermal fibrosis (scar). In most examples, the pattern at the dermal-epidermal interface is lentiginous and junctional, and the degree of atypia is mild to moderate, even if the original lesion was a typical nevus with no component of dysplastic cells. The recurrent cells are usually uniformly, and finely pigmented. Mitoses may be a feature. In some examples, a dermal component of recurrent cells in rounded nests, or fascicles may also be represented. It is important to record the lack of markers for host immune response in the recurrent portions of these lesions. The lack of both lamellar fibrosis, and significant inflammation in the area of fibrosis are features which usually allow the pathologist to recognize these lesions, and to avoid the mistake of diagnosing them as significant dysplasias, or even thin melanomas showing variant vertical growth (e.g., in some examples, nests of cells are widely and regularly spaced in the scar; they could be misinterpreted as variant vertical growth).
Recurrent nevi in typical patterns may be encountered in the biopsy site of an atypical nevus (premalignant melanocytic dysplasia). Such lesions, in themselves, do not qualify as recurrent atypical nevi. Only if the recurrence is associated with remnants of the original dysplasia, and only if the lentiginous and junctional components of the dysplasia extend in the epidermis away from the zone of dermal fibrosis, is it appropriate to characterize the lesion as atypical recurrent nevus (i.e., cytologic atypia within the “recurrent” portion is not the determinant in the characterization of a recurrent nevus as an atypical variant). It may be that the population of “nevus” cells over the area of dermal fibrosis in a recurrent nevus is distinct from any remnant of a dysplasia in the neighboring epidermis.
A recurrent nevus is not simply a hyperplasia of melanocytes in a biopsy site. Clearly, the cells of a recurrent nevus recapitulate some of the patterns of a typical nevus, but the process is distinguished by a maturation arrest at the stage of type A patterns. It has been proposed that recurrent nevi arise from populations of cells in follicular epithelium. If so, then there must be nevus cell components in follicles that are not appreciated on routine sections. The cells of a recurrent nevus are confined to the epidermis over the biopsy site; they do not extend laterally into normal epidermis away from the biopsy site. It would appear that the dermis in the area of both the original nevus and the recurrence is specially favored to promote the growth of nevus cells (an ecological niche). A remnant of nevus is not always identified in the dermis beneath a recurrent nevus; therefore, a remnant in the dermis does not appear to be a requisite for the development of the lesion. The stroma in the site of the nevus may be predisposed to promote the growth of nevus cells in recurrent nevus. A nerve plexus may be the dermal component which provides the stimulus. In recurrent nevi, lentiginous and junctional components are universal; whereas, a dermal component is less frequent. This sequence speaks against the proposition that the nevus cells in recurrent nevus are derived from a pre-existing dermal population of nevus cells.
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