Virtual Images (giant congenital 
nevi &MDM) I 09

 

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melanomas. Inflammation may not be a prominent feature. The lack of significant inflammation may provide a "nevoid" quality to the patterns; such a lack might lead to the imposition of the virtual images of a balloon cell nevus on the real images of a balloon cell melanoma.

For some examples, the balloon cell changes of a melanoma uniformly affect all of the tumor cells; for other examples, the changes are focal in a background of more common patterns of melanomas. They may also be represented in metastases. The abundant cytoplasm of individual balloon cells affects the size of the respective nests and, in turn, probably affects the vertical dimensions of the vertical growth component. Prognostications, as based on Breslow's measurement, may be adversely biased in balloon cell melanomas.

Congenital nevus: A great deal of effort has been expended in the definition of "congenital nevus." At a clinical level, the characterization seems obvious enough for extensive lesions, but becomes complicated in the search for criteria to validate the diagnosis of "giant" variants. At a histologic level, the most characteristic pattern in a giant congenital nevus is that of a sheet of nevus cells at the interface between the papillary dermis and the reticular dermis, in combination with adventitial, adnexal, and interstitial collections of nevus cells in the underlying reticular dermis (and, in some examples, in the subcutis). Representation of lentiginous and junctional components is variable. In some examples, clusters of nevus cells may be found in the subendothelial area of muscular vessels at the lower margin of the dermis. Deposits of nevus cells may also be encountered in the capsule, and parenchyma of regional lymph nodes.

In congenital nevi, ecologic niches for neurocristic migrants, including both the dermis and the epidermis, are variously populated by an excessive number of cells, all with the characteristics of some variant of melanocytic nevus. In normal development, the dermal population of migrant neurocristic effector cells loses its identity in the cellular population of a mature dermis. In the epidermis, the cells acquire a new identity, they mature into epidermal melanocytes. It thus is easy to appreciate both the source, and the nature, of the contribution of neurocristic cells to the epidermis in developing and mature skin. On the other hand, the dermal niche become apparent in post-natal life only in the dermal dysplasias that we speak of as "intradermal nevus." It should be noted that mesenchymal (neuromesenchymal) components are sometimes represented in giant nevi.

In a dysplastic locus, the dermal component would be "dermal" nevus cells with their phenotype expressed in fibrogenic, and/or schwannian characteristics. In addition, the matrix in the more severe examples would acquire the characteristic of a hyperplasia of the papillary dermis. From these observations, precursor effector cells of the developing dermis might be characterized as having a role in the preservation of embryonal-like mesenchyme in specific sites. In normal mature skin, these preserved sites are spoken of as the adventitial dermis. If we take the observations one step further, the adventitial dermis is ”neuromesenchyme."

Small congenital nevi are generally mature. As a consequence, a component at the interface of the papillary dermis and the 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 incorporation of neurocristic migrants in the collagenous framework of the both the papillary and the reticular dermis. The epithelium over such lesions is predisposed to abnormal melanocytic proliferations in lentiginous and junctional patterns. This predisposition is native to the local ecological niche. The relationships are such that they might even provide an explanation for phenomena at the dermal-epidermal interface in recurrent nevi.

Dermal melanocytic dysplasia (as pertaining to dermal patterns, but without distinctions between common and giant nevi): In the developing embryo the “dermis" is a primitive, cellular mesenchyme. In adult skin, fibrous tissue with some of the same primitive characteristics are preserved in sites such as the papillary dermis, the adventitia of the vessels, and the adventitia of the adnexa. It might be proposed that neurocristic derivatives normally lose their right of domain in the dense fibrous tissue of the reticular dermis during normal development of the skin. In contrast, they persist as fibrocytic components of the papillary dermis, and as melanocytes in the epidermis in mature, normal skin. They are necessary for the preservation of the primitive nature of the papillary dermis, for interactions between epidermis and papillary dermis, and for the interactions between hair bulbs and papillae.

The migration of nevus cells with emphasis on the phenomena in giant congenital nevi: If, in the conceptualization of patterns in giant congenital nevi, our virtual images are focused on a movement of cells from the epidermal domain into the dermis, then all nevus cells of a giant congenital nevus are derived from a population of epidermal cells. The migrations into the dermis would thus 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 typical nevus: the more extensive dermal "invasion" could be cited as evidence.

As an alternate explanation for all these components and patterns, the distribution of nevus cells has been characterized as an expression of a fault in the development of the reticular dermis (Reed). In the fault, neurocristic effector cells accumulate locally; there is an inverse relationship between the number of neurocristic effector cells (i.e., nevus cells) and the development of the fibrous mat of the reticular dermis (Reed)

The distribution of nevus cells in the reticular dermis, the cellularity of the dermal component, and the quality of the fibrous mat might all be relevant in the characterization of the relative maturity of a giant congenital nevus.

In immature examples, the cells tend to be widespread in the interstitium of a poorly developed reticular dermis (i.e., the collagenous fibrous mat of the reticular dermis is poorly developed). In mature examples, the fibrous mat is well developed but there is a surfeit of neurocristic effector cells at various levels of the reticular dermis - often involving its full-thickness. These cells are displaced from the interstitium of the collagenous framework of the reticular dermis; they accumulate in more primitive   (i.e., more fetal-like) mesenchyme. In an immature variant, in the areas of immaturity - and hypercellularity - the elastic fibers are preserved but rather uniform in outline and rigid.

In some examples of congenital nevi, the dermal component is inconspicuous; the most striking features are lentiginous and junctional components in which cytologic atypia is often prominent, but markers for host immune response are minimal. Lentiginous and junctional components are common in the epidermis over examples with extensive involvement of the reticular dermis, but are not a universal feature. The dermal component may be extensive, and even immature, in the absence of lentiginous and junctional components. The two phenomena seem to be independent, but commonly associated. Giant congenital nevus is a remarkable dysplasia in which the development of a surfeit of neurocristic migrants has been arrested. It is expressed in diverse aggregate patterns, and variable cytologic patterns.

The pattern of giant congenital nevi has been embodied in virtual images which can be used to assess degrees of immaturity (Reed). In immature variants, cells are richly distributed at all levels of the reticular dermis; the collagenous fibrous matrix of the reticular dermis is poorly developed. Maturation progresses from the deep portions of the reticular dermis to the interface between the reticular dermis and the papillary dermis. In less cellular [i.e., more mature) examples, it is convenient to characterize the reduction in degree of cellularity in the reticular dermis as a consequence of the incorporation of neurocristic migrants into the population of dermal mesenchymal cells (i.e., phenomena as embodied in the virtual images relating to maturation)]. The stimulus for such incorporation appear to be weak in the zone between the reticular dermis and the papillary dermis. As a consequence, even in examples with a well- developed fibrous matrix throughout the reticular dermis, a plaque of nevus cells often persists at the interface between the papillary and the reticular dermis (a zone of phenotypic ambiguity) .

Virtual images, as they relate to giant congenital nevi, can be molded to accommodate a dysplastic process with variations in degrees of differentiation (immaturity). In the concept of giant congenital nevus, wherein a defect in the maturation of the dermis is a relevant virtual image, degrees of immaturity become the measure of the potential for neoplastic transformations. In this approach, an immature giant congenital nevus (i.e., a lesion that is cellular throughout the reticular dermis, and is associated with a poorly developed fibrous mat) has a greater potential for the expression of higher grades of neoplasia than a mature giant congenital nevus. The related neoplastic system then takes on the characteristics of a process in the dysplasia-blastoma category (Reed) .

MDM-like lesions in giant congenital nevi: Nodules that develop in giant congenital nevi in infancy, are of two types. The most common pattern (and type) is one of multinodularity (lumpy, bumpy nevi). The nodules show mild to moderate cytologic disparity (and atypia); they tend to be symmetrically expansile, but some examples are plaque-like. They arise in the band-like infiltrates of cells at the interface between the reticular dermis and the papillary dermis (similar nodules occasionally may arise in the reticular dermis in immature variants). In the nodules, cytologic disparity is evident, if comparisons of the cells of the nodules with those of nevus cells in the neighboring dermis are made. In addition, mitoses, if represented, are likely to be found only in these nodules. Often the overlying epidermis shows little or no evidence of a significant lentiginous and junctional premalignant melanocytic dysplasia. Markers for host immune response are usually inconspicuous, both within, and at the margins of, the nodules. In the concept of MDM, lesions of this type would satisfy most of the requisites for the recognition of a vertical growth component, and for the diagnosis of MDM of giant congenital nevus type (a variant of MDM of the dermal type) (note: nuclear grade I & II) They have also been characterized as atypical nodular hyperplasias, or proliferative nodules. They are no immediate threat to the patient, and are not an indication for immediate and total excision of the giant congenital nevus. If regional lymph nodes are sampled, capsular and parenchymal inclusions of cells which are cytologically similar to those of the nodules are sometimes identified. These cellular nodules in the setting of giant congenital nevus qualify as either MDM- like nodules of dermal type or borderline melanocytic neoplasia of dermal type (giant congenital nevus variant - nuclear grade I & II). These observations relate to nodules that develop in some giant congenital nevi in infancy.

The second type of nodular growth arising in giant congenital nevi in infancy also appears to be relatively independent of phenomena at the dermal-epidermal interface but qualifies as a high-grade malignancy. By implication, these rare tumors could be related in an evolutionary sequence to MDM-like nodules of the dermal type in giant congenital nevi. These remarkable lesions are composed of primitive, dark blue, undifferentiated malignant cells; they qualify as melanoblastoma of infancy. By the usual criteria, melanoblastomas are acceptable as an additional example of primitive neuroectodermal malignancies of infancy and childhood. Some of these lesions may also manifest patterns of divergent differentiation (e.g., rhabdomyoblastic differentiation) (note: nuclear grade III in "small cell," or blastomatous, patterns). Like other blastomas of infancy, these lesions are a serious, and immediate, threat to the patient. The nodule should be widely excised, and the patient carefully evaluated and followed for evidence of metastatic and disseminated disease. Bone metastases were a feature of one example. Melanoblastomas of infancy are a strong contradiction of the adage that "melanomas" arising in infancy in giant congenital nevi do not metastasize.

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 usually are 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 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 dermal nests are usually finely, and uniformly, pigmented. The character and distribution of the pigment evokes virtual images of the cells in junctional nests in SSM. Mitoses are not a prominent feature. In some examples, the nests of atypical cells in the widened papillary dermis are loosely, but regularly, spaced in patterns that resemble 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 the adventitia of the skin appendages; these patterns tend to reinforce the impression that the lesion represents 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. Similar lesions have been described by Helwig, et al (). These lesions do not qualify as a marker for the dysplastic nevus syndrome.

In adults, melanoma in giant congenital nevi may be either of the dermal type, or the premalignant melanocytic dysplasia type which evolves in common patterns at the dermal-epidermal interface. In older patients in whom a nodule appears in a long standing giant congenital nevi, atypical lentiginous and junctional components often are represented over the nodule. The patterns in toto share features with most melanomas that arise in the setting of the dysplastic nevus syndrome, and include prominent markers for host immune response.

MDM of the dermal type: Some typical 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; they do not qualify as a marker for the dyplastic nevus syndrome. Atypia of this type is of questionable significance, but perhaps has a role in the evolution of some nevus-like, or even dermal, variants of melanoma.

MDM of the dermal type is usually a lesion of the cephalad portions of the body, particularly the face. In the confines of a preexisting nevocytic nevus, usually of the dermal type, a nodule is circumscribed and expansile, but not encapsulated. Lymphoid infiltrates commonly outline the margins of the vertical growth component and 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), and usually are amelanotic. They 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 tumor 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 preexisting dermal nevus cells). Lesions with these features have also been characterized as "ancient nevus."

Distinctive cytologic features are common in both MDM of the dermal type and MDM of the halo nevus type. Some MDM of dermal type are associated with lymphoid infiltrates in remnants of the preexisting nevus. Some halo nevi are purely dermal in type; they are not associated with lentiginous and junctional patterns. With only slight modification of perspective, some examples of MDM of the dermal type would also qualify as dermal variants of MDM of the halo nevus type. The overlaps are such that it is tempting to propose that MDM of halo nevus type and MDM of the dermal type are related variants (note: nuclear grade I - II and cells are "epithelioid").

MDM of 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 cytologically low grade lesions with possibly little potential for metastasis, Breslow's criteria should not be used to provide therapeutic guidelines.

MDM of halo nevus 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. 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 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 cells. In some example, 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; they migrate into the epidermis among the melanocytes of both the lentiginous and the 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 a nevus.

Some examples are purely lentiginous and junctional. They are characterized by band- like infiltrates of lymphocytes in the papillary dermis. The infiltrates of lymphoid cells migrate into the basal unit of the epidermis, and into the junctional nests at the dermal-epidermal interface. The resulting patterns have a lichenoid quality. In some examples, the infiltrates may mask any associated component of "nevus cells;" the process may be misinterpreted as a lichenoid process, such as lichenoid keratosis. Many pathologists might be hesitant to classify a lesion without a dermal component as a variant of halo nevus. Occasional examples are purely dermal with no lentiginous or junctional components. If a purely dermal lesion is associated with prominent markers for host immune response and additionally..........

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