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Genital nevi, atypical “nevi,” and melanomas:
Nevi of the genital and perineal regions commonly are manifested in compound patterns; the junctional nests commonly are large in comparison with similar components of nevi in other sites in comparable age groups. The genital nevus commonly is removed during the child bearing period of a woman’s life. Similar lesions occur in men, but are less commonly excised. The atypical genital nevus shows lentiginous and junctional, or lentiginous and compound patterns in which the cells menifest varying degrees of atypia. These lesions are characterized by markers for host immune response, and some examples may show scattered mitotic figures even in the population of “common” nevus cells in the deeper portion of the dermis. MDM of genital nevus type shows, in addition to the features listed for atypical genital nevus, the patterns of a vertical growth component. In short, the genital nevus and its neoplastic variations are evaluated by the same criteria as the typical nevi and their neoplastic variations. The genital nevus is not in itself a marker for the dysplastic nevus syndrome. It appears to be an expression of exquisite sensitivity of nevus cells in a particular anatomic site to hormonal factors.
Nevoid melanomas:
Nevoid lesions grotesquely recapitulate the patterns of normal tissue. The designation, nevus, has clinical relevance, usually implying that a lesion is congenital, self-limited, and manifested in patterns that are distortions of those of normal tissue. For the interpretation of patterns in nevocytic nevus, a comparison with the development of tactile corpuscles has been offered as a model. Other observers have proposed that nevocytic nevi are a local surfeit of neurocristic effector cells, as the expression of a failure of these cells to be locally incorporated in the population of normal cells in the early development of the skin. Nevocytic nevi have organoid qualities, a characterization that, in large part, gives recognition to zonal variations in patterns.
Some melanomas have been characterized as “nevoid.” In this extension of usage, recognition is given to patterns which may be confused with those of common nevi: the implication being that such a lesion might be mistaken for a common or variant nevus. Virtual images of common nevi provide the basis for the structuring of new virtual images in which organoid qualities in a melanoma are assigned significance. The patterns of “nevoid” melanomas, as currently and broadly defined, can also be accommodated in the concept of minimal deviation melanoma. Both MDM of halo nevus type, and the dermal type are “nevoid” but have not been included in reports as variants of “nevoid” melanoma. If there is a malignant (metastasizing) counterpart of Spitz “nevus,” such a lesion, in its Spitz-like features, is “nevoid,” but this variant has not been included in reports of “nevoid” melanoma. If all these variant (minimal deviation) melanomas were to be included as “nevoid” variants, the category would become nothing more than a selection of lesions from the broad category of MDM.
Some lesions currently classified as “nevoid” melanoma would also qualify as variants of nodular melanoma. A tumor without a radial growth component, but with a vertical growth component, that is sufficiently developed to be characterized as a nodular, is most likely beyond the borderland of thin melanocytic neoplasia. Melanomas measuring greater than 1 mm in vertical dimensions, that are not associated with a radial growth component, but are so bland in their cytologic features as likely to be mistaken for a benign nevus, might be characterized as “nevoid.” Some pigmented spindle cell melanomas are cytologically deceptive, and are not always associated with a radial growth component. Some of these pigmented spindle cell lesions are cytologically uniform; they have “nevoid” qualities. Such lesions would also qualify as MDM of pigmented spindle cell type.
In one study of “nevoid” melanomas, large and small cell variants were described. It was proposed that “large cell” variants are more aggressive than “small cell” variants. In turn, the reproductions of the large cell variant show solid nesting patterns, and a preponderance of spindle or dendritic cells. Maturation is often emphasized in the diagnosis of “nevoid” melanoma but, in practice, this is not a defining quality. In so-called “large cell” variants of “nevoid” melanomas, maturation has not been a prominent quality. At best, the category of “nevoid” melanoma, as currently defined, is heterogeneous.
A lack of inflammation in “nevoid” melanomas might also be cited as a feature which promotes comparisons with common nevi. From a different perspective, a lack of inflammation might be cited as a feature of poor host immune response. It commonly is a feature of lesions at level IV. Thin melanomas at level IV are likely to show both “maturation” (i.e., stratified variations in cytologic features), and poor host immune response, thus also qualifying as “nevoid.”
In the characterization of a melanoma, any usefulness of the designation, “nevoid,” would have to be found in the biased nature of virtual images of independent observers. Thus, the diagnosis will be favored by some, but of little utility to others. Some melanomas have been misdiagnosed as variants of benign nevus, prompting claims of malpractice. Such lesions usually have been thin, composed of pale cells, often of spindle type, with relatively bland nuclei (low to intermediate nuclear grade and low mitotic rate), fascicular patterns in vertical growth, and with variable patterns of maturation. Such lesions might, or might not, be associated with a significant radial growth component. These features are “nevoid” or “organoid” qualities. Lesions showing these features have been rather non-descript cytologically; many examples are composed of pale spindle cells.
Of all the categories in which the virtual images of variant melanomas are embodied, that of “nevoid” melanoma is most susceptible to the vargaries of individual microscopy. If a review of histologic patterns in a melanoma evokes the virtual images of a nevus, the respective observer is entitled to characterize the lesion as “nevoid” melanoma. If a single, specific lesion is to be characterized as “nevoid” melanoma, a list of basic features might include the following:
1) round, “nevoid” cells with bland cytologic features; atypia most pronounced at the dermal-epidermal interface; evidence of “maturation” at the deep margin
2) for some examples, relatively little spread of lentiginous and junctional components in the epidermis away from the dermal component (a quality that would also qualify the lesion as “nodular” [i.e., no radial growth component])
3) prominent nesting and fascicular patterns in which nests and fascicles are loosely and regularly spaced (patterns of variant vertical growth as defined in concept of MDM
The list might also include:
4) low to intermediate nuclear grade (some examples might be characterized as high grade, but show remarkable nuclear uniformity)
5) minimal markers for host immune response
6) extension of nests of cells into the reticular dermis among collagen bundles (as a consequence, the patterns might evoke virtual images of a peculiar congenital nevus)
7) ideally, the category would be homogeneous
Utilizing the above criteria, the nevoid category is considerably refined, but is not entirely pure. The category would include a fascicular, round cell, variant and typical vertical growth melanomas; and nested, round cell, variant and typical vertical growth melanomas. In this manner, some distinctive round cell melanomas could be removed from the category of nodular melanoma. Common variant vertical growth melanomas often are associated with a remnant of a nevus. Such a lesion would have evolved from a premalignant dysplasia at the dermal-epidermal interface. It would be of a type which would have entered vertical growth by displaying progressive variant vertical growth patterns. Generally, there are abrupt transitions at the interface between variant vertical growth components and remnants of pre-existing nevus; the distinctions are marked by cytologic features and usually by stromal patterns. The nests of dysplastic cells often are entrapped in a dense fibrous stroma (arrested pattern); whereas, the nests of pre-existing nevus cells are supported by a delicate, watery stroma. There is a lack of continuity in the common lesions; in the “nevoid” lesions the patterns of arrested variant vertical growth usually are not a feature; the transition to small nevus-like cells is more continuous; a lack of continuity distinguishes the common melanomas when manifested in variant vertical growth patterns.
So-called small cell “nevoid” melanomas are to be distinguished from small cell melanomas in which the basic patterns do not evoke the initial impression that the process is some variant of nevus. Many small cell melanomas show rather solid vertical growth patterns. In such examples, patterns in which nests of cells are aggregated do not evoke the virtual images of some variant of nevus.
Variant malignant melanoma (a different perspective)
Fascicular or nested, variant vertical growth melanomas:
The current classification of melanoma places emphasis on anatomic site, environmental influences, and radial growth components (patterns of remnants of precursor lesions). In large part, the histologic features of radial growth components (or the absence thereof) are influential. In the concept of MDM, emphasis is placed on the vertical growth component, including cytologic featues, and two alternate patterns, namely variant and typical vertical growth.
In typical vertical growth, nests and fascicles of cells in the vertical growth component are closely and regularly spaced; the nests of cells are supported by a distinctive matrix; as the lesion enlarges, the nests and their stroma push aside, or displace, the connective tissue of the reticular dermis. By the definition herein, a lesion showing typical vertical growth is at level III. For nests or fascicles to infiltrate the reticular dermis among collagen bundles would be a change in the character of the lesion; such infiltrating patterns would represent a transition from level III to level IV invasion (i.e., migrant or diffuse vertical growth).
In variant vertical growth, nests and fascicles of cells in the vertical growth component are widely and regularly spaced; they are not tightly packed back to back. In common, thin melanomas at level III, as encountered in the setting of premalignant dysplasias, a distinctive pattern of variant vertical growth is relatively common; it, usually, is associated with prominent markers for host immune response. Most often the nests of cells are rounded, and the tumor cells are rounded or polygonal. Although this pattern qualifies as variant vertical growth, the entrapment of nests of cells in laminated fibrous tissue additionally qualifies the pattern as arrested variant vertical growth (arrested level III invasion). Arrested variant vertical growth mostly is peculiar to common melanomas and, generally, is a feature of thin lesions. This type of thin lesion is best included in the category of MDM as borderline melanocytic neoplasia. In neoplastic progressions, a lesion showing arrested variant vertical growth at level III may transform into unqualified variant vertical growth at level III, or migrant vertical growth at level IV, or into typical vertical growth (by definition level III invasion). Currently, with few exceptions, nesting patterns are not emphasized in the classification of melanomas.
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