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Anatomic Levels
In the definition of degrees of dysplasia, and of microstages of melanomas, anatomic boundaries and domains have relevance for the interpretation of histologic patterns. In the elaboration of evolutionary stages of melanocytic neoplasia, boundaries and domains serve as markers. Even patterns of host immune response vary depending upon the anatomic domains that have been affected by neoplastic cells. Finally, definitions of anatomic levels have relevance in the formulation of predictions of biologic potentials for various melanocytic neoplasms.
The anatomic boundaries include:
LEVEL I (an epithelial domain): The epidermal or epithelial domain is basically “two dimensional” with its boundary being the dermal-epidermal interface. Neoplasms situated above this boundary are “in situ” without attention to their degree of cytologic atypia, or to an histologic definition of “melanoma.” For neoplasms in general, a definition of this boundary gives recognition to processes which arise in an epithelial domain. Although such neoplasms tend to be confined, for a period, above the boundary between epithelium and stroma, they have a potential to evolve in stages; often the stages are variably correlated with degrees of atypia. This play with linguistic symbols is a more accurate rendering of “in situ” than the currently popular play promoting “melanoma in situ.” It defines the relationship between a population of neoplastic cells, and a limited (primary ) domain, but the definition does not, in itself, connote a degree, or grade of neoplasia.
LEVEL II: Anatomically, level II is the papillary dermis with one boundary being the dermal-epidermal interface, and the other being the interface between the papillary dermis and the reticular dermis. The connective tissue of this level is distinctive in regard to types of collagens, and to the distribution of the individual collagenous fibers (i.e., a delicate meshwork of unit fibrils). It is rich in acid mucopolysaccharides, and has a distinctive component of delicate, arborizing elastic fibers; the elastic fibers are PTAH negative. In its ability to peculiarly adapt to , and nuture, the epidermis, the papillary dermis is stroma in the strict sense of the definition. It, and its resident cells, including ecotatic lymphocytes and histiocytes, are responsive to functional, and clonal changes in the native keratinocytes and melanocytes of the epidermis.
In the evolution of the dysplasias, neoplastic melanocytes commonly migrate from level I to level II. In response to the neoplastic migrants, the stroma, and its ecotatic residents at level II make only limited accommodations for the intrusions of a population of foreign cells; individual cells, and individual nests of cells are accommodated but, initially, the nests are characteristically few in number, and are randomly, and widely spaced. It is possible for a level II lesion to produce widening and fibrosis of the papillary dermis; this pattern marks the interplay between host immune response and neoplastic cells. The interpretation of a lesion showing widening of the papillary dermis, but a level II pattern, might be characterized as a conservative prognostic evaluation; in the face of regressive phenomena, it is uncertain what the patterns might have been at an earlier stage in the evolution of the dysplasia.
In characterizing the relationship between a population of neoplastic cells, and anatomic levels, the deepest level to which neoplastic cells have gained access should be the focus of the evaluation. Thus, in characterizing the dimensionality of a dysplasia at level II, only the component of cells within the papillary dermis are to be evaluated. At level II, the vertical dimensions of the papillary dermis (stroma), and the contours of the affected skin are little altered. The process, as evaluated by the patterns in the dermis, and exclusive of the component in the epidermis, basically retains a “two dimensional” character.
LEVEL III: Level III is a modification of the definition of level II. At level III, recognition is given to spacial distortions of the papillary dermis. The distortions provide evidence that accommodations have been made for expanding clones of neoplastic cells. The pattern in the papillary dermis, in regard to the distribution, and aggregation of nests of foreign cells, acquires a three dimensional quality (at the level of virtual images). A characterization of level III has application in the definition of vertical growth; in this approach, level III patterns are the equivalent of typical vertical growth; an amalgam of real and virtual images transmorgrifies the plane of a histologic section into a three dimensional process. In turn, in the concept of MDM, a three dimensional pattern is the requisite for the recognition of a vertical growth component. Finally, a vertical growth component constitutes the chief distinction between common melanomas and their precursors, the dysplasias.
There are no restrictions on the degree of the expansion of the papillary dermis at level III with the sole exception that the boundaries remain the same as those of level II lesions (specifically, the volume of the papillary dermis in the area of the tumor is modified and augmented). The expansion of the papillary dermis may significantly deform the interfaces between both the papillary dermis and the epidermis, and the reticular dermis and the subcutis (one being distorted upward and the other downward).
The expanded stroma at level III qualifies as a community stroma; it expands in concert with an expanding population of tumor cells. Cells of this community may find their way into the lumens of stromal vessels, and then metastasize.
LEVEL IV: The reticular dermis contributes the domain at level IV; its boundaries are: 1) the interface between the papillary dermis, and the reticular dermis; and 2) the interface between the reticular dermis, and the subcutaneous fat.
The collagenous framework at level IV has its own distinctiveness in regard to types of collagens, and to the patterns in which coarsely bundled collagen fibrils are arranged. Coarse elastic fibers, that are PTAH positive, are dispersed among the collagen bundles in interstitial spaces that are rich in acid mucopolysaccharides.
The reticular dermis does have some peculiar relationship with dermal melanocytes; Dermal melanocytes may be identified as incidental findings in the skin of dark skinned races. Dermal melanocytoses, when identified, reside at level IV ( in addition, tumors of dermal melanocytes, the blue nevi, are lesions of the reticular dermis, although some examples have perifollicular components).
By proper criterial, reticular dermis is not stroma. It has no native role in the nuturing of epithelium, and is not innately responsive to alterations in epithelial kinetics.
At level IV, there is a rich plexus of lymphatics, but the blood vessels are mostly conduits for the distribution of oxygenated blood to levels I & II (or III).
For foreign cells to reside in the reticular dermis, they must have acquired the property of invasive migration without attention to the needs of a community of cells or, in their migrations, individual nests must have acquired the capacity to induce their own stroma independent of other nests of cells. In invasive, as opposed to expansile, migrations, individual cells, and nests and fascicles of cells insinuate among pre-existing collagen bundles of the reticular dermis.
LEVEL V: the boundary for level V is the interface between the reticular dermis and the subcutaneous fat, and the domain is the soft tissue beneath the lower level of the dermis. This level generally has significance as a marker for deep invasion. In addition, a lesion at level V has access to a rich plexus of small and muscular vessels.
Migrations of Melanocytic Cells
(as related to both Anatomic Levels and Aggregate Patterns)
Continuity of pattern: In most nevi, common premalignant melanocytic dysplasias, and melanomas, cells initially proliferate in an epithelial domain. Some of these cells cluster to form nests or fascicles. In current conceptualizations of the evolution of nevi, lentiginous and junctional components are assigned primacy, and dermal components are assumed to be their derivatives. In some manner, some of the cells and nests relinquish their epithelial domain; they come to lie in the dermis. One explanation for this migration is embodied in the concept “dropping off.” Surely, nests of nevus cells commonly “drop off” into the dermis, but not all of the cells in the dermis can be casually dismissed as having had an epidermal origin. Compound nevi may have a dual origin (as proposed by Masson); their deep dermal component may not be a population of migrant cells from the epidermis. In fact, the presence of primary dermal nevus cells may be a stimulus for the growth, and migration of nevus cells in, and from, the epidermis. In typical nevi, nests of cells, that “drop-off” into the dermis, adapt to the patterns of pre-existing nests in a manner that might be characterized as a “continuity of patterns;” the patterns blend. In the growth and maturation of nevi, several generations of nevocytic cells may be stratified in the dermis. In addition, at any selected level, the patterns are comparable but, at different levels, the patterns vary. The transitions from one to the next level are not sharply defined. Continuity of patterns in nevi with epidermal,and dermal components might be characterized as an expression of a basic sameness of cells, even in areas showing transitions in phenotype. If a typical nevocytic nevus with compound patterns is selected as a model, boundaries in regions of transition from one zonal pattern to another (e.g., type A, B, & C patterns) will be found to be ill-defined. In typical nevi, some rounded nests of cells (type A patterns) will merge with fascicles (type B patterns), and fascicles will merge with sheets of cells (type C patterns), all in subtle fashion.
The dermal component of a typical nevus may exert an organizing influence on nests of cells which, having “dropped off” into the dermis, come to lie in close proximity with nests of nevus cells already in the dermis. In this manner, enlargement of one or another of the dermal nests would likely establish “continuity” between two populations of cells. The evolution of “continuity of patterns” in a typical nevus would thus be effected.
“Dropping off” of entire nests of melanocytic cells may not be the only alternative as an explanation for the movement of melanocytic cells from an epidermal domain into the dermis. Eccentric protrusions from junctional nests of cells into the dermis may, by the formation of constrictions near the neck of the protrusions, eventually separate to form daughter nests in the dermis. The mother nests may retain their epidermal domain.
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