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The patterns in “recurrent nevi” have relevance to both the phenomena of “continuity of patterns,” and to “dropping off.” In recurrent nevi, and junctional components of the “recurrence” are confined to the epidermal domain over the scar. In fully developed lesions, nests of similar cells will also be found in the dermal scar near the dermal-epidermal interface. The dermal aggregates are often represented in the patterns of rounded, loosely spaced nests, and usually are not associated with impressive markers for host immune response. The lack of significant cellular immune response should serve as a note of caution, if the observer is considering a diagnosis of either a significant melanocytic dysplasia, or an early melanoma (minimal deviation melanoma). In recurrent nevus, the patterns are monomorphic with only one nesting pattern represented in the scar. In contrast, in typical compound nevus, patterns are variable, often in a stratified pattern; the variations are sometimes given recognition by characterizing them as type A, B, or C. One explanation for the lack of “maturation” (continuity of patterns) is that the scar isolates the nests that have “dropped off” into the dermis from organizing influences of any remnant of the pre-existing nevus, or the related nerve plexus (i.e., continuity is seldom, if ever, established between nests, which have “dropped off” into the scarred dermis, and any remnant of nevus in the underlying dermis). In a recurrent nevus, the scar would appear to have effectively isolated the evolving components near the dermal-epidermal interface; as an example of a maturation arrest, type B & C patterns, as well as continuity of patterns, generally are not expressed.
Anatomic Levels, Histologic Patterns, and Integration of the Two
LEVEL I (epithelial domain):
1. Lentiginous patterns: Each melanocyte of the normal epidermis has a rather fixed relationship with a localized collection of keratinocytes. In melanocytic hyperplasias, the numerical relationships between individual melanocytes and a packet of functionally related keratinocytes may be altered. Lentiginous patterns are a marker for a population of migrating melanocytes that preferentially reside among basal keratinocytes. If melanocytes are hyperplastic, and closely spaced in the basal layer of the epidermis and, if the hyperplasia is “spontaneous,” the resulting lesion qualifies as a lentigo. If, in addition to an increase in the number of melanocytes per unit area of epidermal domain, there is cytologic atypia of the respective melanocytes, then the resulting lesion is both lentiginous and atypical. Commonly, there are other histologic associations for lesions of the latter type.
2. Junctional patterns: In lesions with prominent junctional components, dysplastic or neoplastic cells may have acquired a cohesiveness that precludes a diffuse spread of cells in the basal layer away from their site of origin (i.e., significant lentiginous spread).
If, in a locus of lentiginous melanocytic hyperplasia, some of the affected melanocytes cluster to form nests or fascicles, then the resulting pattern is both lentiginous and junctional. If cells of such lesions are cytologically atypical then, like the atypical lentigines, there usually are other histologic associations.
Histologic patterns, that can be accommodated within the limits imposed by the definition of Level I qualify as pattern I.
LEVEL II and beyond (dermal domain):
3. Compound and dermal: Nests of melanocytic cells solely in the dermis qualify the respective lesion as a dermal variant. If a dermal component is combined with a lentiginous and junctional component, then the resulting lesion is compound. Atypia, usually in association with other markers, may also be manifested in this category.
Histologic patterns which can be accommodated within the limits imposed by the definition of LEVELS I-IV qualify as patterns I-IV respectively.
Cytologic atypia and degrees of dysplasias:
Pure lentiginous dysplasias (lesions which are both lentiginous and atypical) are often uniformly cellular in the basal layer of the epidermis. In lentiginous and junction (or compound) dysplasias, the neoplastic cells of the lentiginous component tend to be more spotty in distribution. As an explanation for this paradox, neoplasic cells, in the transition from lentiginous patterns to lentiginous and junctional patterns, may migrate from the diffuse lentiginous component to collect in scattered junctional nests (thereby depleting the lentiginous component), or the two phenomena are markers for distinct and separate stages of neoplasia.
In assigning a degree of atypia to the melanocytic dysplasias, the relative preponderance of junctional over lentiginous components is proportional to the degree of cytologic atypia (dysplasia). As a corollary, with advancing degrees of atypia, cells clustered in nests tend to overshadow any associated lentiginous components. This dictum is supported by the prominence of nesting patterns in the epidermis in the radial growth component of superficial spreading melanoma. On the other hand, some dysplasias may evolve to moderately severe atypia showing a preponderance of lentiginous patterns (i.e., acral and actinic variants). Lentiginous, as well as lentiginous and junctional, lesions are pattern I processes.
Cytologic atypia, degrees of atypia, and their relationship to degrees of dysplasia:
Learned responses are basic to success in microscopy. Degrees of atypia are defined on the basis of learned responses that include an appreciation of nuclear grades. Some practitioners have characterized the promotion of nuclear grades as a hoax, and have characterized promoters of nuclear grades as miscreants.
An appreciation of degrees of atypia is dependent upon a rich store of virtual images. For those, who have incorporated nuclear grades in their store of virtual images, there are various approaches. Dysplasias with both mild to moderate atypia, and markers for host immune response (lymphoid infiltrates, and lamellar or diffuse appositional fibroplasia at the dermal-epidermal interface) qualify as low-grade variants (i.e., incipient dysplasias). High-grade dysplasias (lesions with moderately severe to severe [marked] atypia, with prominent upward migration of atypical melanocytes in the epidermis, with markers for host immune response, and with patterns of either level I or II growth [patterns I or II]) qualify as borderline [high grade] variants [i.e., incipient melanomas]. They qualify as borderline melanocytic neoplasia of indeterminate malignant potential (dysplasia variant).
Four degrees of dysplasia, based primarily on degrees of cellular atypia, can be defined:
1. Mild atypia, as manifested in premalignant melanocytic dysplasias, is often characterized by pigmented cells with slight variations in nuclear size. Occasional cells show a large, somewhat elongated nucleus with dense, smudgy chromatin. Cellular atypia in the dysplasias is evaluated in the population of cells at the dermal-epidermal interface, and preferably in junctional nests of cells. Loss of nuclear polarity among the melanocytic cells in junctional nests is an additional aid in recognizing mild degrees of atypia. Mitoses are rare.
2. Moderate atypia is characterized by a tendency for nests of cells to be larger, more numerous, and more closely (although irregularly) spaced in the epidermis. Nuclei are fairly uniform in size; disparities in nuclear size and orientation may be less apparent than in mild atypia. Many of the nuclei contain a small central nucleolus.
3. Moderately severe atypia is characterized by more regularly spaced nests, and by variations in nuclear size and staining. Nucleoli are more regularly, and prominently, represented; they are plump and acidophilic. In size and staining, they are comparable to the nucleoli of neighboring keratinocytes of the stratum malphigii. Upward migration of neoplastic cells is a feature of both moderately severe, and marked atypia (or dysplasia, since atypia is the most reliable correlate of degree of dysplasia).
4. Severe atypia, in many examples, is simply an extension of the changes seen in moderately severe atypias. Often, the nuclei are intermediate in size, and chromatin is dense. In other examples, nuclei are plump, and rounded with marginated chromatin. In either variation, nucleoli are large, and acidophilic. In examples in which nuclear chromatin is uniformly dense, the nucleolar characteristics are difficult to evaluate. Mitoses are more frequent in the moderately severe, and marked dysplasias. A distinctive form of epidermal hyperplasia in which the superficial unit (i.e., the population of cells showing terminal differentiation) is primarily affected is characteristic of severe dysplasias; this alteration is a regular feature of the epidermis in lesions of superficial spreading melanomas; the patterns are embraced in the concept of the common final pathway (c16t3P1-3 & c27t3P1-6). In moderately severe dysplasias, this hyperplasia is less striking.
Cytologic atypia as correlated with degrees of dysplasia:
In dysplasias, pattern I (level I growth) and pattern II (level II growth) are acceptable. In mild dysplasias, the lentiginous component, and any associated junctional components are often irregular in distribution at the dermal-epidermal interface. Pure lentiginous dysplasias are more likely to be uniform in distribution at the dermal-epidermal interface. If a junctional component is represented, its cells are to be evaluated in assigning degrees of dysplasia. In mild dysplasias, the junctional nests tend to be small, few in number, and irregularly spaced. They each consist of as few as ten (or even fewer) cells. The neoplastic cells are often pigmented, commonly are somewhat spindle shaped, and show mild nuclear atypia. The host immune response is mild and spotty. Lamellar fibrosis is often poorly developed. By definition, dermal nests are few in number, and widely spaced (dysplasias are limited to patterns I & II.
In moderate dysplasias, the lentiginous and junctional components are more uniform in distribution (the junctional components are not preponderantly represented at the extremities of rete ridges as in mild dysplasias). Atypia is moderate. Usually, the cells are pigmented. The junctional nests are larger, and contain more cells than do those of mild dysplasias. Dermal nests are more frequent than in mild dysplasias. Dermal fibrosis, often in concentricaly laminated patterns, is a prominent feature. The lymphoid infiltrates are more prominent than in the mild dysplasias, and are mostly perivascular.
In moderately severe dysplasia, junctional components usually overshadow the lentiginous components. Mitoses are more common than in moderate dysplasias (generally, the mitotic rate in the junctional components of a dysplasia is proportional to the degree of dysplasia). Loss of cellular cohesion with upward migration of both individual cells, and nests of cells into the stratum malpighii is a significant aid in making a distinction between moderate, and moderately severe dysplasias, but in some examples of moderately severe dysplasias, upward migration is not a prominent feature. The lentiginous and junctional components may involve skin appendages. Dermal nests are common but, by definition, are widely and randomly spaced. Dermal fibrosis and lymphoid infiltrates often are prominent features.
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