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8. cellular blue nevus
a. atypical cellular blue “nevus”
b. melanoma arising in cellular blue nevus
c. melanoma arising in deep neurocristic melanocytic hamartoma (generally a process affecting an area corresponding to the distribution of the trigeminal nerve)
9. giant congenital nevus (and some small variants)
a. borderline dysplasias of infancy and childhood
b. MDM of dermal type
c. MDM arising in atypical congenital “nevus”
d. melanoblastoma of infancy
10. acral nevus
a. atypical acral “nevus”
b. acral lentiginous melanoma
11. nevus in sun-damaged skin
a. senile lentigo
b. lentigo maligna
c. lentigo maligna melanoma
Variant Melanomas (general discussion)
Melanoma variants as defined on the basis of unique cytologic features, stromal relationships, and host immune response:
Many of the variant lesions, as anticipated in the preceding section, are poorly documented. For poorly defined variants, whose biologic potential is poorly understood, our only current options have been an assignment to either a benign or premalignant category, or to the common (typical) melanoma categories. These compromises relate to a willingness on the part of most observers, in the assignment of unusual lesions to specific categories, to restrict their optione to the major categories, and to use these limited categories as defaults. For other examples or observers, if some of the cytologic features of a problematic lesion overlap with those of some of the variant nevi, there is hesitancy to then assign these “nevus-like” lesions to the category of common melanoma: in the face of such a dilemma, the tendency is to compromise; in the act, a melanoma may be assigned to a benign category.
The recognition of variant “nevi” and dysplasias requires the evocation of virtual images. From an examination of real images, as routine endeavors in the daily practice of pathology, appropriate sets of virtual are elicited.
The identification of a vertical growth component is generally accepted to be a requisite for the recognition of a common melanoma; the utility of Breslow’s criteria provides testimony as to the utility of a vertical growth component in the diagnosis of melanoma; in the absence of a vertical growth component, there would be little to measure. The dissenters, who promote diagnoses of melanoma-in situ and melanoma at level II, are mostly engaged in linguistic masquerades; they are tilting at Quixotic windmills). An appreciation for the nature of the background lesion in which a vertical growth component exists should also provoke virtual images of a precursor in the act of transforming into a melanoma. In large part, the concept of MDM placed great emphasis on a vertical growth component; in addition, any associated, but less significant patterns were to be accepted as a marker for a remnant of a precursor lesion. In the concept, an attempt was made to define criteria for the recognition of the role of variant “nevi” or dysplasias in the evolution of variant melanomas.
Some melanomas have been dismissed as entities because collected series have not included an example. For instance, it has been stated that there are no “true melanomas’ of giant congenital nevi in infancy; the respective reviewers, having not personally encountered examples which were associated with metastasis and death, simply have dismissed the possibility.
Many lesions, which are distinctive histologically, have been assigned to the category of nodular melanoma (a waste-basket category). Others, of a similar or different nature, have been assigned to a “nevoid” category of melanoma. The latter option has become fashionable. Many lesions, which currently are being assigned to the “nevoid” category, show features that overlap with some of the lesions in the category of MDM (e.g., pigmented spindle cell melanoma of the minimal deviation type). Some examples of nevoid melanoma are bland and organoid (truly nevus-like, hence, MDM of common nevus-like type). Cytologically, some of these organoid lesions (with nevus-like patterns) are of high grade.
In the characterization of typical melanomas, emphasis is placed on the patterns in radial growth, or on the absence of a radial growth component. If, instead, attention is paid to patterns in vertical growth components, the classification of melanoma is greatly expanded. In this alternate approach, there are as many variants of melanoma as variants of “nevi.” In addition, for each variant of “nevus,” there is an atypical counterpart in which the epidermal features overlap with those in the epidermis of the common premalignant melanocytic dysplasias. In this approach, variants of MDM can be given recognition, but the baggage, that has been imposed on the designation, is avoided. The variant melanomas have identity mainly as the counterparts of the variant “nevi” (e.g., Spitz “nevus,” combined “nevus,” blue nevus, etc.). They also would qualify as variant minimal deviation melanomas. For the most part, emphasis has been placed on lesions showing typical vertical growth. Some of these variant lesions deserve recognition as variants of melanoma on the basis of distinctive patterns of variant vertical growth. The concept of melanocytic neoplasia of indeterminate malignant potential also has application for variant melanomas.
Balloon cell transformation:
In some melanocytic lesions, an alteration of cytoplasmic organelles produces a pattern in which cells, individually and in clusters, have more abundant, vacuolated cytoplasm. In balloon cell “nevi,” the organoid patterns of a common nevus are preserved.
Balloon cell transformation is common in the setting of premalignant melanocytic dysplasias, but may be encountered in the dermal component of a nevus in the absence of other markers for melanocytic dysplasia.
In balloon cell melanomas, the presence of balloon cells complicates the interpretation of patterns, and tends to cloud the distinctions between a nevus cell variant and a melanoma. Organoid patterns, which are characteristic of balloon cell nevi, are not preserved in balloon cell melanomas. The nuclei of the balloon cells of a melanoma tend to be plump with open chromatin patterns, and a prominent central nucleolus. Mitoses are also a feature of balloon cell melanomas.
The balloon cell changes of a melanoma may uniformly affect all of the tumor cells, or may be focal in a background of more common patterns of melanomas. They also may 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 biased in balloon cell melanomas.
In lesions with balloon cell components, some of the affected cells contain widely spaced melanin granules in the cytoplasm; perhaps, balloon cell transformation is a process related to demelanization of cytoplasm.
Combined “nevi:”
In part, the characterization of variants of “nevi” is based upon distinctive cytologic features of the cells in each variant and on patterns. In examples in which two or more cell types are represented in a single lesion, the patterns of the respective nevi are combined (i.e., combined “nevi”). In combined nevi, components of typical nevus cells are admixed with those of some other type of nevus, such as deep penetrating “nevus” (common type), blue nevus, cellular blue nevus, or Spitz “nevus.”
In one variation of the common form of combined nevus, fascicles of pigmented spindle cells are loosely, and regularly, spaced in a condensed fibrous matrix to form an expansile nodule. Remnants of a typical nevus (a population of typical nevus cells) mostly are outside the confines of the nodule. The nodule might be mistaken for the vertical growth component of a melanoma, but the cytologic features and the fasciculated patterns are no different from examples of combined nevus in which the fascicles of pigmented spindle cells are interspersed among nests of common nevus cells, or collagen bundles of the reticular dermis.
Borderline melanocytic neoplasia of dermal type (giant congenital nevus variant, nuclear grade 1 & II):
A great deal of effort has been expended in the definition of congenital nevus. At a clinical level, the definition seems obvious enough, but becomes complicated in the search for criteria validating 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). 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 of regional lymph nodes. As one 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. In the development of the fault, neurocristic effector cells accumulate locally; there is an inverse relationship between the number of neurocristic effector cells and the development (maturation) of the reticular dermis (R J Reed).
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 a measure of the potential for neoplastic transformations. The related neoplastic system then takes on the characteristics of the dysplasia-blastoma category (R J Reed).
A lentiginous component has been characterized as a distorted recapitulation of the behavior of melanocytes as they populate the epidermis in developing skin. The junctional components have been characterized as an atavism in which cells revert to a more primitive phenotype, and lose their “right of domain” in the mature epidermis. In these virtual images, the cells in the junctional nests will have reverted to a primitive phenotype, one in which the primitive phenotype of neurocristic migrants is approached. They become phenotypically indifferent. If they migrate into the dermis and establish continuity with dermal nevus cells, they tend to relinquish melanocytic properties, and to then express the phenotype of dermal effector cells with potentials for fibrogenesis and Schwann cell-like properties.
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 sufeit of neurocristic effector cells. These cells are displaced from the interstitium of the reticular dermis. They accumulate in more primitive (i.e., more fetal-like) mesenchyme such as the interface between the papillary dermis and the reticular dermis, the adventitia of vessels, and the adventitia of the adnexa. In some examples, the dermal component is inconspicuous, and 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 diffferentiation of a surfeit of neurocristic migrants has been variably arrested. It is expressed in diverse aggregate patterns, and variable cytologic patterns. The patterns of giant congenital nevi has been embodied in virtual images which can be used to assess degrees of immaturity. In immature variants, cells are richly distributed at all levels of the reticular dermis, and 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 incorporations appear to be weak in the zone between the reticular dermis and the papillary dermis (a transition zone of phenotypic expressions; a zone of phenotypic ambiguity).
Nodules which 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 tend to show mild to moderate cytologic disparity (and atypia). The nodules tend to be symmetrically expansile, but some examples are plaque-like. They usually present as band-like infiltrates of cells at the interface between the reticular dermis and the papillary dermis (similar nodules occasionally arise in the reticular dermis in immature variants). In the nodules, cytologic disparity is evident, if comparisons of the cells of the nodules and of nevus cells in the neighboring dermis are made. In addition, mitoses, if represented, are likely to be found only in these nodules. In the concept of MDM, lesions of this type would satisfy most of the requisites for the recognition of a typical vertical growth component, and for the diagnosis 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 of no immediate threat to the patient. They 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 may be identified.
These observations relate to nodules which develop in some giant congenital nevi in infancy. In older patients, atypical lentiginous and junctional components often are a significant feature. In such lesions, any related nodule shares most features with melanomas that arise in the setting of the dysplastic “nevus” syndrome.
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. By implication, this type could be related in an evolutionary sequence to MDM of the dermal type (atypical nodular hyperplasias) in giant congenital nevi, These rare and remarkable lesions (melanoblastomas of infancy) are composed of primitive, dark blue, undifferentiated malignant cells. By usual criteria, these lesions are acceptable as an additional example of primitive neuroectodermal malignancies of infancy and childhood. Some fof these lesions may also manifest patterns of diverse 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 or disseminated disease. These lesions are a strong contradiction of the adage that “melanomas” arising in infancy in giant congenital nevi do not metastasize. In adults, melanoma in giant congenital nevi may be either of the dermal type, or the premalignant melanocytic dysplasia type (i.e., a type which evolves in common patterns at the dermal-epidermal interface).
Myxoid malignant melanoma:
Myxoid melanoma is a rare variant. It is distinguished by distinctive cells, and by stromal responses in the vertical growth component. The cells tend to be “epithelioid” (rounded or polygonal). They have scanty, deeply basophilic cytoplasm and plump, irregular, densely chromatic nuclei. The cells tend to cluster in small nests, or to be individually isolated in a myxoid matrix in the vertical growth component. The matrix is purely myxoid, and intensely basophilic. The myxoid changes are maintained in recurrences. Myxoid melanoma seems to be a variant of desmoplastic melanoma, and to have a relationship with lentiginous variants of melanoma. In adults, some examples may be the adult counterpart of melanoblastoma of infancy; they are perhaps more common in the setting of the lentiginous melanomas than SSM. Myxoid melanoma may be manifested in the vertical growth of the mucosal melanomas in the absence of demonstrable lentiginous components in the site selected for biopsy. In local recurrences, in lesions lacking a primary configuration, and if mostly subcutaneous in location, this lesion may be misinterpreted as a soft tissue sarcoma. These myxoid melanocytic malignancies, if involving the vagina or the oral cavity, may be mistaken for myxoid soft tissue sarcomas such as rhabdomyosarcoma, leiomyosarcoma, or liposarcoma.
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