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Giant congenital nevi (continued):
Focally, in some giant nevi, or uniformly in some small congenital nevi of infancy and childhood, the patterns at the dermal-epidermal interface share features with those of the premalignant dysplasias as encountered in lesions of the dysplastic “nevus” syndrome. Lentiginous and junctional patterns with asymmetry in the distribution of nests are the preponderant feature. In some examples, the junctional nests are outlined on the dermal side by laminated fibrous tissue (lamellar fibrosis). Dermal components are variable, but are usually represented. These lesions are generally thin and superficial, but some of the nests and even individual cells may extend into the upper portion of the reticular dermis among collagen bundles. Cytologically, these lesions often show moderate to moderately severe atypia. In some examples, the cells at the dermal-epidermal interface have plump hyperchromatic nuclei; they show variations in nuclear size and staining. Upward migration of atypical cells usually is not a prominent feature. The cells in the junctional and the dermal nests are usually finely and uniformly pigmented. The character and distribution of the pigment evokes virtual images of the cells in the junctional nests of SSM. Mitoses are not a feature. In some examples, the nests of atypical cells in the widened papillary dermis are loosely, but regularly, spaced in patterns which resemble those of borderline variant level III invasion. Generally, the sparse lymphoid infiltrates are at variance with what might be expected in lesions showing this degree of cytologic atypia. In some examples, common nevus cells may be represented in the adventitia of vessels of the reticular dermis, or of the skin appendagesl; these patterns tend to reinforce the impression that the lesion may be a variant of congenital nevus. These superficial lesions, if examined without attention to the age of the patient (i.e., first 4 or 5 years of life), may be interpreted as high grade premalignant dysplasias, or even as MDM at thin level III or IV invasion. If the patterns are correlated with age, the lesions qualify as melanocytic dysplasias of infancy and childhood (Helwig). These lesions usually do not qualify as a marker for the classic dysplastic nevus syndrome.
If, in the conceptualization of patterns in congenital nevi, the opposite tack is taken, then all nevus cells of a giant congenital nevus are derived from a population of epidermal cells, and the migrations into the dermis acquire the qualities of an “invasive” process. In this contrary approach, a giant congenital nevus might then be characterized as a more “aggressive” lesion than a small common nevus.
In congenital nevi, ecologic niches for neurocristic migrants include the dermis and epidermis. In normal development, the dermal population of neurocristic effector cells lose their identity in components which become the cellular component of a normal (mature) dermis. In the epidermis, the neurocristic migrants acquire a new identity; they mature into epidermal melanocytes. In evaluating the fate of neurocristic migrants, it is easy to appreciate both the original source, and the nature of the epidermal component. On the other hand, the dermal niche becomes apparent only in the dermal dysplasias- that component which we speak of as “intradermal nevus.” In the dysplastic locus of a congenital nevus, the dermal component would be “dermal” nevus cells; their phenotype would be expressed in fibrogenic and schwannian characteristics. In addition, the matrix in the more extreme examples would acquire the characteristics of a hyperplasia fo the papillary dermis; collagen bundles of these areas would not be of the type seen in a mature reticular dermis. From these observations, precursor dermal effector cells might be characterized as having a role in the preservation of embryonal-type mesenchyme in specific sites in the developing dermis. In normal mature skin, these preserved sites are spoken of as the adventitial dermis. If we take the observations one step further, the adventitial dermsi is, in part, “neuromesenchyme.”
Small congenital nevi are generally mature. As a consequence, a component at the interface of the papillary and reticular dermis is a usual feature, but the interstitial component of the reticular dermis usually is spotty in distribution, and mostly manifested in interstitial patterns in the upper 1/3 of the reticular dermis. The fibrous mat of the reticular dermis usually is well-developed and mature. The component of nevus cells near the interface between the papillary dermis, and the reticular dermis would qualify as a marker associated with faulty development of the reticular dermis. The epithelium over such lesions is predisposed to abnormal melanocytic proliferations in lentiginous and junctional patterns. The predisposition is native to the ecological niche. Such relationships even provide an explanation for phenomena at the dermal-epidermal interface in recurrent nevi.
Dermal melanocytic dysplasia:
Some common dermal nevi are characterized by cytologic atypia, particularly in the component of dermal cells near the dermal-epidermal interface. The cells of the dermal component otherwise are arranged in typical patterns. Dermal nevi showing atypia of this type qualify as atypical “nevi” of the dermal type, but do not qualify as a significant marker for the common dysplastic “nevus” syndrome.
MDM of the dermal type:
MDM of the dermal type is usually a lesion of the cephalad portions of the body, particularly the face. In the confines of a pre-existing nevocytic nevus, usually of the dermal type, a nodule which is circumscribed and expansile, but not encapsulated (i.e., a typical vertical growth component) is the basic requisite for the diagnosis of MDM. Lymphoid infiltrates commonly outline the margins of the vertical growth component, and may extend into the nodule among the tumor cells (tumor infiltrating lymphocytes: halo nevus-like phenomena). The dermal tumor cells usually are rounded in outline (epithelioid); they usually are amelanotic and show variations in nuclear size and staining. The nucleus of each cell usually contains a small, central, acidophilic nucleolus. Mitotic figures usually are rare and scattered. Commonly, the overlying epidermis does not show significant lentiginous and junctional patterns. Spotty junctional patterns may be represented, but often the cells in these nests do not show atypia of the same degree as the neoplastic cells. The dermal component will not appear to have had its origin in the lentiginous and junctional component (from the histologic features, the dermal component is most likely a neoplastic transformation in the population of pre-existing dermal nevus cells). Lesions with these features have also been characterized as “ancient nevus.” Some “ancient nevi” of this type have metastasized.
Some halo nevi are purely dermal in type; they are not associated with lentiginous and junctional patterns. Distinctive cytologic features are common in both MDM of the dermal type and MDM of halo nevus type. Some MDM of dermal type are associated with lymphoid infiltrates in remnants of the pre-existing nevus. With only slight modification of perspective, they would also qualify as dermal variants of MDM of the halo nevus-like type. The overlaps are such that it seems appropriate to characterize MDM of halo nevus-like type and MDM of the dermal type as related variants (Note: nuclear grade I & II; the cells are “epithelioid”).
MDM of the dermal type, when evaluated by Breslow’s criteria, may exceed the limits of thin melanomas (i.e., they may be greater than 1 mm in vertical dimensions). Being low grade lesions with little potential for metastasis, Breslow’s criteria should not be used to provides therapeutic guidelines.
MDM of halo nevus-like type:
Halo nevus is histologically defined by an intimate admixture of lymphocytes and nevus-like cells in the dermis. For most examples, lentiginous and junctional patterns are confined to the epidermis over the dermal component. If lentiginous and junctional components are represented, the lymphoid cells may involve these components to produce a lichenoid reaction. The definition also includes examples in which the patterns are purely lentiginous and junctional, and examples that are purely dermal. The cells in the junctional component are usually spindle shaped, but may be polygonal. They are lightly pigmented, and usually show mild to moderate cytologic atypia with elongated nuclei and delicate chromatin patterns (e.g., nuclear grade I & II). Some degree of atypia is acceptable in the dermal component. The atypia in the dermis may be manifested in the pattern of small (often pigmented) nevus cells with hyperchromatic nuclei that vary in size. Large epithelioid cells with plump nuclei, and dense chromatin occasionally are admixed among the small nevus-like cells. In some examples, the large atypical epithelioid cells are numerous. They may be arranged in clusters among nests of common nevus cells. Occasional mitotic figures are acceptable.
In some examples, the lymphoid infiltrates are also prominent at the dermal-epidermal interface; the lymphoid cells migrate into the epidermis among the melanocytes of both the lentiginous and junctional components. The resulting patterns have lichenoid qualities in which lytic defects in the epidermal domain contain lymphoid cells, histiocytes, and degenerating keratinocytes. Such a lesion may come to look more like a lichenoid reaction at the dermal-epidermal interface than as a variant of nevus.
Of the proposed variants, one variant of MDM of the halo nevus-like type has the greatest relevancy to thin MDM in the setting of the premalignant melanocytic dysplasia - melanoma sequence. It is recognized most often as a thin lesion in prognostic category I (i.e., lesions whose vertical growth component measures less than 1 mm in height). The character of the vertical growth component is often borderline in regard to embodying a readily acceptable pattern (e.g., these small, thin lesions may show only 10 or fewer nests of cells in the vertical growth component on a histologic section). A radial component, which manifests many of the features of a premalignant melanocytic dysplasia (dysplastic “nevus” syndrome) is common; if represented, then the respective lesion qualifies as MDM arising in atypical halo “nevus.” Often in the vertical growth component, the cells form closely clustered nests and fascicles but occasionally are arranged in patternless sheets. In most examples, the degree of cytologic atypia is moderate (minimally deviant cytologically). In vertical growth, the neoplastic cells are often bland and spindle shaped, but some examples are composed of small, round cells which have small, round nuclei, marginated chromatin, and a relatively prominent central, acidophilic nucleolus. Large epithelioid cells are occasionally manifested in vertical growth components. The dermal cells of any remnant of a pre-existing halo “nevus” usually are round cells. They tend to vary in size and to show variations in nuclear size and staining. They are, however, arranged in patterns which are recognizable as variations of those of atypical “nevi,” and are associated with the lymphoid infiltrates of halo nevus-like phenomena (tumor infiltrating lymphocytes).
In some examples of MDM of halo nevus type, the lymphoid response which characterizes halo nevus is also manifested in the vertical growth component. In other examples, the vertical growth component is distinguished by a marked reduction in the intensity of the lymphoid response in comparison with that of the adjacent remnant of halo nevus.
Minimal deviation melanoma of halo nevus-like type is not defined with a limit on the dimension of the vertical growth component. Examples measuring more than 1.5 mm in vertical dimensions are recognizable, but are likely to show more severe atypis in vertical growth. In lesions greater than 1 mm in vertical dimensions, most observers would probably ignore markers for a remnant of a halo nevus, and merely dismiss “thicker” examples (Breslow’s criteria) of this variant as a common melanoma with a rich component of tumor infiltrating lymphocytes.
MDM of halo nevus-like type often are minimally deviant in many aspects; by some criteria, they might be assigned to the category of “nevoid” melanoma. From the available data, progressive disease is unlikely, if the lesion falls within the limits defined for lesions of prognostic category I. Thin MDM of halo nevus-like type are evaluated by the same criteria as thin MDM in the setting of the dysplastic nevus syndrome; they would qualify as examples of borderline neoplasia of indeterminate malignant potential (thin melanoma of halo nevus type).
Halo “nevi” have a life history. Rarely, an example is encountered in which the population of dermal nevus cells shows uniform, mild atypia (nuclear hyperchromatism), but the lymphoid infiltrates are minimal and spotty. In such examples, it is tempting to propose that the nuclear atypism is a marker for a neoplastic transformation, and is the initiator of, rather than a response to, the lymphoid infiltrates (i.e., a neoplastic transformation in which “self” antigens are exposed may precede the appearance of the lymphoid reaction). In fully developed lesions, the lymphoid infiltrates are band-like; the lymphoid cells and histiocytes intermingle among the atypical nevus cells in the dermal nests (i.e., tumor infiltrating lymphocytes). Rarely, histiocytes cluster to form small granulomata. Eosinophils and plasma cells may be a feature.
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