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Malignant melanoma: The histologic manifestations of melanoma are protean. The common variant evolves in stages at the dermal-epidermal
interface. The histologic patterns of precursor lesions (premalignant melanocytic dysplasias) often include a population of nevus-like cells in the underlying dermis, usually at the interface between the papillary
dermis and the reticular dermis. In the evolutionary stages, prior to the emergence of a tumoral component (such a tumoral component, at its beginning, would consist of only 5 or 6 nests of atypical cells in
the papillary dermis; for a clustering with such limited dimensions, the pattern must be additionally characterized as borderline), the dermal patterns are disorganized; the nests are distributed in the dermis in
spotty, irregular patterns. The cells of the dermal component form nests and fascicles; some are independently isolated. An inflammatory component is a basic component of the reaction; it is difficult to assign a
lesion to the melanocytic dysplasia category without attention to the inflammatory reaction. The reaction, in part, is cellular (lymphocytes, and histiocytes) but, in addition, there is a matrical component. In
early stages, the matrical response is sclerosis. The fibrous mat, in the area of the epidermal component, is expanded; it is more densely fibrous (a quality manifested at the histologic level by increased
acidophilia). At the interface with dermal nests of neoplastic cells, the matrical response often takes on a different, distinctive quality. In this stage of evolution, each nest of neoplastic cells tends to become
sequestered in a fibrous matix in which collagen bundles are concentrically laminated. If lymphoid infiltrates are also clustered about the nests of neoplastic cells, there is an opportunity for the inflammatory cells to invade the nests. The response to the infiltrates of lymphocytes among neoplastic melanocytes is lysis and death of some, or all, of the neoplastic cells of some, or all, of the affected nests. This process is one of focal regression; it contributes the asymmetry often manifested in the both the epidermal and the dermal components of an evolving melanocytic dysplasia. There is the alternate route in which the nests of cells are not recognized by the inflammatory process. In this situation, as new nests are delivered to the dermis, the nests, in stratified patterns, tend to be loosely but regularly spaced. The nests tend to be stratified by degree of dysplasia with the least atypical components situated in the deepest portion of the dermal component; the least atypical would thus be the neoplastically oldest population (the population with the longest residence in the dermis). In accounting for this variation in degree of dysplasia, as manifested in different strata, it would seem most reasonable that, at this stage of neoplasia, neoplastic progressions evolve in the population of cells at the dermal-epidermal interface. It would then be reasonable to accept the variations in degrees of atypia, at levels in the dermal strata, as markers for stages in neoplastic progressions.
These patterns, as depicted above, provide insight into the stages through which the dysplasia, with the passage of time, has progressed. In this approach, the utility of the concept
of “Clark’s nevus” is greatly weakened. The dysplasia is a continuum, often progressing from mild dysplasia, in which cells deviate minimally from common nevus cells, to marked dysplasias, in which cells are
indistinguishable from the cells of the dermal component of a fully evolved malignant melanoma. In these early progressions, some stages of neoplasia may be omitted. In attempts to discredit the concept of
melanocytic dysplasia, the opponents have opened the door to medico-legal wrangling. In addition, they have promoted the concept of melanoma in situ. In the application of the latter concept, they extend the
definition to include earlier, and still earlier, evolutionary stages of melanocytic dysplasias in the “in situ” category. Benign, but potentially progressive, “melanomas” have become common; for some, they
masquerade in the guise of “Clark’s nevus.”
The dermal nests of an evolving premalignant melanocytic dysplasia have the potential to escape from their entrapment in fibrous tissue and, by acquisition of new qualities, to
progress to a higher grade of neoplasia. The progressions, for most examples, tend to first manifest themselves at the dermal-epidermal interface. They do so by manifesting higher grades of cytologic atypia and by
compromising the integrity of the epidermal domain. In nests, and individually, the atypical cells migrate into the overlying epidermis. It is for this pattern, in combination with high cytologic grade, that the
designation, melanoma-in-situ, if selected at all, is most appropriate. In a different approach, this combination of features qualifies as the “common final pathway” (i.e., the patterns of a high grade dysplasia)
with the implication that a dysplasia of lower grade, if left undisturbed, will most likely manifest these features prior to the emergence of a vertical growth component. There is the additional implication that the
neoplastic process has exhausted most options that are expressed in degrees of cytologic atypia. Such a lesion can only progress by accommodations in the relationships between tumor cells and stroma. The
accommodations are those that lead to the emergence of an expansile tumor in the dermis (so-called vertical growht).
Vertical growth comes in at least 3 flavors: variant (including a pattern that might be additionally characterized as arrested variant), typical (an expansile solid nodule with a
condensation of inflamed fibrous tissue at the interface between the nodule and the adjacent dermis (by modified Clark’s criteria, this would be a level III lesion; it pushes into the dermis); and migrant vertical
growth (sinuous patterns in which nests and cords of cells infiltrate the reticular dermis among preexisting collagen bundles (by Clark’s criteria, this would be invasion to levels IV and V).
There are other expresions of vertical growth. One is the desmoplastic pattern in which tumor cells individually infiltrate dermis and soft tissue and, in the process, induce a
sclerosing response in the invaded tissue. This is a deceptive form of tumor that tends to be more plaque-like than nodular. It is closely associated with a propensity for the tumor cells to infiltrate peripheral
nerves and to grow along nerves in neurotropic patterns. A variation of the desmoplastic variant is a lesion in which the tumor cells, focally or universally, induce mucinous (myxoid) changes in the stroma.
The actinic form of melanoma is characterized by refractoriness in the epidermal response to a population of neoplastic cells. These forms generally affect the elderly. The skin
(including the epidermis) of the elderly usually shows varying degrees of atrophy; the epidermis tends to be thin and rete ridges usually are effaced. The dermis shows solar elastosis. A dysplasia in this
setting tends to be expressed in dominant lentiginous patterns; nests of cells, early on, are few; they are irregularly spaced along the dermal-epidermal interface. The nests at the dermal-epidermal interface tend
to be oval in outline with the long axis parallel to the surface of the skin. The cells of the lentiginous component are crowded at the dermal-epidermal interface; they are loosely attached to their neighbors and
tend to have prominent dendrites. They crowd the cells of the basal layer early on, and then migrate upward. In the upper reaches of the epidermis, they tend to lie in lacunae and have prominent dendrites. Even with
evidence of upward migration, the dysplasia may be only mild to moderate and the epidermal response (in terms of hyperplasia as seen in high grades of the more common dysplasias) may be subdued. Extension along skin
appendages is a common feature. Often, associated lymphoid infiltrates are mild. There is the option for this variant to eventually progress to a high grade dysplasia that is difficult to distinguish from those seen
in common high grade dysplasias; they then acquire features of a common final pathway. In the latter state, the patterns closely resemble those of the common high grade precursors of superficial spreading melanoma.
In the epidermal component of such high grade variants, tumor giant cells often are a prominent feature. In addition, the cells of the nests tend to be spindle shaped. Such a lesion, if allowed to enter vertical
growth, is likely to be preponderantly a spindle cell variant and fasciculated in vertical growth (migrant patterns into the reticular dermis are common, even in thin lesions. The expression of the option for
lesions of lentigo maligna to progress to a stage of high grade dysplasia should not obscure an appreciation for the nature of the background dysplasia and the clinical setting prior to the “common” event. Lesions
of lentigo maligna and lentigo maligna usually are distinctive and in most stages, they stand
alone as distinctive clinicopathologic entities. In defining lentigo maligna, it is most sensible to define it in the same manner as a lesion of SSM at level I or level II. Lesions, in the actinic category, if confined to level I or level II, qualify as lentigo maligna. All other lesions are melanomas in vertical growth.
There are several histologic and biologic variants of malignant melanoma. Lentiginous variants of melanoma include the acral and the actinic
variants. In addition, many examples of lesions on the arms, the legs, or the trunk might be best classified as lentiginous variants. Acral lentiginous variants are associated with a degree of epidermal hyperplasia
that readily set it apart from actinic variants. Early on, lentiginous variants commonly enter the phase of migrant vertical growth. As a result, these lesions may not produce a well-defined, nodular lesion.
In addition, these lesions usually are expressed in spindle cell and fascicular patterns. All of these features are more common in the lentiginous categories than in that variant which qualifies as classic
superficial spreading melanoma.
Little attention is paid to the cytologic features of a fully evolved melanoma. Cytologic features assume some importance in the desmoplastic and neurotropic categories. Lesions in the
latter two categories have their origin more commonly from lentiginous dysplasias than from a precursor of superficial spreading melanoma. Another variant in which cytologic features are of some importance is the
pleomorphic (sarcomatous) variant.
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