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Ecological niche, continued:
For cells at level III, the ecological niche is a tumor stroma that resembles an expanded papillary dermis (i.e., pattern III, and variant or typical vertical growth). For level III tumors, host immune response is often best developed at the advancing margin of the vertical growth component. In this niche, the nodule is confined by a band of condensed, inflamed fibrous tissue. The nests of neoplasic cells are components of a community; the respective stroma is community stroma (for some examples, the community stroma will be relatively free of lymphocytes). All the neoplastic cells of the community (i.e., the vertical growth component) are dependent on each other, and on a “community” stroma and its blood supply.
The ecological niche for cells at level IV is locally, and universally, unrestricted. The cells are not dependent on the stroma of a community, but are migrants in the fibrous framework of the pre-existing reticular dermis and subcutis. In addition, they possess the potential to colonize distant organs by their capacity to induce a “migrant” or “universal” stroma in distant sites.
For some observers, cells, which by their cytologic characteristics are “malignant,” and by their affinities, one for the other, have clustered to form isolated nests (without attention to anatomic level), are likely to be assigned to the category of a “malignancy.” They are then assumed to be independent of the needs of normal, and even certain neoplastic, cells to find, and reside in, a niche (this assumption is basic to the philosphy of those who tout the validity of the concept of “melanoma-in-situ” and “one melanoma”). From this perspective (i.e., the perspective of proponents of “one melanoma”), neoplasia is thus reduced to the level of individual cells (i.e., from this perspective, there are malignant cells as well as malignant neoplasms); paradoxically, proponents of the concept of “one melanoma” deny the existence of “malignant cells.”
Epithelioid qualities:
The definition of the qualifier, epithelioid, is a characterization of patterns in which non-epithelial cells are closely clustered to form cellular aggregates; fibrous tissue is relatively excluded among the individual cells. The definition has been extended to embrace distinctive cytologic features, irregardless of the patterns in which the distinctive cells are distributed.
An “epithelioid” cell is plump with cytoplasmic acidophilia. It has a round, eccentric nucleus with variable prominence of nucleoli. Usually, the cells, so designated, are round or polygonal, but the designation also has application for spindle cells (e.g., the cells of many primary epithelioid malignant schwannomas are spindle shaped).
In desmoplastic and neurotropic melanomas, fascicular components focally may be prominent. The resulting patterns are epithelioid, but the cells usually are spindle shaped. In the latter usage of the qualifier, epithelioid, attention is given to both a protoplasmic nature, and the close approximation of the cells forming the fascicles.
Fibroplasia:
In this section, attention is given to relationships between nests of either dysplastic cells or melanoma cells, and their stroma.
In melanomas, the nests formed by clusters of cells have epithelioid qualities. In the nests, cells cluster in a clear, fluid matrix and, in turn, the nests and their interstitial matrix are supported by a fibrous or fibromyxoid stroma. One variant of stroma, as seen at level III, might be characterized as induced or community stroma (it is delicate and the fibers are randomly distributed). Community stroma is an accommodation by stroma for a population of neoplastic cells; it is basic to the definition of level III growth (“invasion,” vertical growth, and “melanoma”).
In another variation, the stromal response might be characterized as reactive (in it, laminated collagen bundles are concentrically arranged about nests of tumor cells) The laminated reactive stroma is a regular feature of most premalignant melanocytic dysplasias. Lamellar fibrosis, as seen in the setting of melanocytic dysplasia, is a form of appositional growth; brightly acidophilic, fibrous lamellae condense at the dermal periphery of many of the junctional nests as they push into the papillary dermis from their attachments at the extremities of rete ridges. Flattened cells, often seen at the periphery of junctional nests, may be facultative fibrogenic cells which have acquired the capacity to contribute to the formation of the laminated fibrous matrix.
The manner in which nests of melanocytic cells in the dermis come to be isolated by circumferential fibrous lamellae is difficult to define by simple observation of the static images of histologic sections. It is accepted that in some manner some of the nests of cells in dysplasias lose their continuity with the epidermis; they “drop-off” into the dermis. Generally, there are few, if any, cells among the fibrous lamellae but, occasionally, individual dysplastic melanocytes are so entrapped. In low grade dysplasias (e.g., mild to moderate atypia), the prominence of fibroplasia of this type is proportional to the degree of cytologic atypia. This type of fibroplasia is not so uniformly a feature in high grade melanocytic dysplasias; in high grade lesions, the degree of lamellar fibrosis roughly is inversely proportional to the degree of dysplasia. From this perspective, the cells of low grade dysplasias seem to have a capacity to induce a specialized, confining stroma; whereas, those of high grade dysplasias have the capacity to release themselves from the confining fibrous lamellae. For some of the dermal nests of melanocytic dysplasias, the encircling fibrous tissue may be uniformly dense, rather than laminated. For lesions showing both lamellar fibrosis and variant vertical growth, the resulting combination qualifies as “arrested” variant vertical growth.
Appositional fibroplasia, whether uniformly dense or distinctly laminated, is common in premalignant melanocytic dysplasias, but is seldom encountered in the confines of a convincing typical vertical growth component. On this basis, nests of cells, confined by fibrous lamellae, might be characterized as having been sequestered. In additon, the lamellae, in toto, might be characterized as a marker for a reaction in either a melanocytic dysplasia or borderline melanoma showing arrested variant vertical growth.
Multiple nests, regularly and widely (loosely) spaced in a widened papillary dermis are to be correlated with the character of the stroma. Such nesting patterns, if associated with a relatively non-inflamed, dense and laminated fibrous matrix, is less likely to be associated with progressive disease than a similar nesting pattern, at a comparable “thickness,” that is associated with a loose, delicate fibrous matrix and markers for host immune response. A thin lesion in which cells of the dermal component form closely spaced nests in an inflamed, delicate fibrous matrix has made a significant step in the transformation from dysplasia to melanoma; the cells of such a dermal component would have made the transition from arrested to progressive variant vertical growth.
The stromal responses at level III represent something more than a reactive hyperplasia of the papillary dermis. A similar stroma may be manifested in deep, recurrent melanomas which are far removed from “level III,” and even might be manifested in metastatic melanomas. In a variety of mesenchymal tissues, melanomas seem to possess a capacity to induce a stroma that is “papillary dermis-like.”
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