|
MORPHOLOGIC AMBIGUITIES
(THEIR IMACT ON THE INTERPRETATION OF HISTOLOGIC
PATTERNS OF MELANOCYTIC LESIONS)
Richard J. Reed, M.D., and Martin Mihm, M.D.
This 15 year old girl presented with a lesion of her back. The lesion was excised.
The lesion was submitted for processing after having been divided in 3 portions.
Microscopically, on two of the three portions, a polypoid lesion was represented. The epidermis showed lentiginous and junctional components. On all three portions, a population of nevus cells was variably
represented in a widened papillary dermis. Significantly, the cells of the lentiginous and junctional components showed moderate cytologic atypia with variations in nuclear size, staining, and orientation. These
features, when combined, identify a portion of the lesion as an “atypical nevus.” On the other hand, markers for host immune response were not a prominent feature; the lack of these markers requires that
qualifications be appended to this interpretation; an atypical nevus lacking such markers is an indeterminate variant, of questionable relationship to the dysplastic nevus syndrome. For atypical nevi of this
indeterminate type in which atypia is represented in the absence of significant markers for host immune response, cytologic atypia, as a measure of a premalignant dysplasia, is of questionable biologic significance
(see Whithers1, 2, &3). Some dysplasias which show the overall features of a common premalignant dysplasia but lack significant markers for host immune response are
encountered in the setting of halo nevus; in this setting, some atypical lesions show halo nevus phenomena, and other lesions show patterns of classic halo nevus. Often in dysplasias of this type, that lack host
immune response but are associated with halo nevi, the nuclei of the dysplastic cells show dense nuclear chromatin that seems to differ from the chromatin patterns of common premalignant dysplasias.
At the opposite extremity of one section in an area showing the most representative portion of the lesion, atypical spindle cells were arranged in a pattern of loosely spaced fascicles in a widened papillary
dermis. Here also, the dermis was relatively free of infiltrates of lymphoid cells. From the superficial to the deep portion of the lesion in this area, there was a reduction in the size of both the spindle cells
(including their nuclei) and the fascicles. These variations in patterns were of a type commonly characterized as “maturation” (a fanciful characterization of variations in patterns at various levels in a
melanocytic lesion). The cytologic atypia, as manifested in the superficial portion of the lesion, was evident even at the deep margin where the lesion extended into the reticular dermis. In view of the variations
in patterns from one side of the lesion to the other, symmetry was not a significant attribute. There were spotty infiltrates of lymphoid cells in this portion of the lesion (i.e., the opposite, and more extensive,
extremity). Lymphocytes were clustered within nests of melanocytic cells and had pushed some of the melanocytic cells aside. In other nests, they were loosely intermingled among the melanocytic cells. In all areas,
the nests associated with lymphoid infiltrates (lymphomelanocytic islands), were composed of atypical melanocytic cells, a distribution exclusive of the population of common nevus cells.
In the interpretation of the lesion, various combinations of virtual images will be examined and compared with the real images as illustrated in the PICTORIALS. The combinations of virtual images to be evaluated in the interpretation of this lesion include parcels which should be accessible for the interpretation of Spitz
nevus and related variants, halo nevus and related variants, and spindle cell nevus and related variants (see Whithers1, 2, & 3, and Index3) . In a
more general fashion, by addressing the combinations of virtual images, the utility of the concept of minimal deviation melanoma, including some examples of nevoid melanoma, can be assessed.
INTRODUCTION
The impact of parcels of virtual images from the stores of an observer will become evident as the respective observer attempts to find the parcel with the greatest number of
images that are congruent with the real images of a histologic section of a problematic lesion.
In the interpretation of this lesion, an observer must rely on information gained from a comparisons of virtual images of cerebral origin. These images, having been mobilized from
stored parcels, become available for comparison with real images of the histologic sections. For this problem lesion, the exercise in which virtual images and real images are compared, becomes a lesson; an
understanding of the nature of the interpretative process is promoted during an examination of the histologic material. The process requires something more than a mere matching of virtual and real images. In an
approach to this lesion, there are multiple optional pathways; it is easy to select a parcel of virtual images (the selection take on the aspects of a pathway) and, thereby, to mold the real images to accommodate
those of the selected parcel (i.e., virtual images are imposed upon, or substituted for, real images We can easily do this; actually, we do it with disturbing regularity. We can do this without any conscious
acknowledgement that we have bent the real images to accommodate those of a selected parcel, or vice versa. A lesion, with ambiguous characteristics, as manifested in this problem lesion, essentially demands that we
make these accommodations; the best we can do is to also admit to ourselves what we are doing, and to then acknowledge our shortcomings in the report and diagnosis.
This is a problematic lesion of uncertain phenotype. The many patterns are illustrated in the PICTORIALS; they are accompanied by legends and comments. In the DISCUSSION,
an attempt is made to put the patterns in perspective, and to structure an interpretation with appropriate guidelines to therapy and prognosis. This is not a lesion that can be assigned to the category of melanoma
without qualifications. One approach would be to assign the lesion to the category of a variant nevus; the virtual images of this selected category would have to be molded to accommodate the real images of the
lesion. Another approach, if the features of the real images are accepted as representing in part a vertical growth pattern, would be to find accommodations for the patterns of the lesions in the parcels of virtual
images of value in defining the variant nevi, but to then mold the parcels to include the patterns of vertical growth and to rename the new category and parcels; the vertical growth-like patterns would require that
the new category be designated as a form of melanoma. In this approach, the lesion becomes a variant melanoma; the category of minimal deviation melanoma offers tools for the interpretation of variant melanomas.
A characterization of the lesion as a “nevoid” melanoma introduces generalities; it assigns no specificities beyond a comparison of the patterns with those of the common nevi; a specific look-alike is not
identified. A review of the literature on “nevoid” melanoma would quickly reveal the lack of discrimination in the category; epithelioid and spindle cell lesions, and variant, as well as typical, vertical growth
patterns are merged. This lack of discrimination makes the category so malleable for the manipulation of parcels of virtual images that the diagnosis becomes one of personal whims. Any assignment of one of a variety
of problematic minimal deviation lesions to the general category of “nevoid” melanoma would not in turn constitute either an exposition of biologic potentials, or an elaboration of meaningful prognostications.
There are many variations in the general category of “nevoid” melanomas as currently defined. The general designation, “nevoid” melanoma, does not then define a prognostic category; it would not, in itself, be an
indication that Breslow’s criteria would be valid.
In an effort to refine the category of Nevoid Melanoma, it might be appropriate to restrict the diagnosis to include only those lesions showing variant vertical growth-like patterns (see the WHITHERS; access the
navigation bars in the margin to the left). The quality of loose spacing of nests of cells in a widened papillary dermis (a quality that defines variant vertical growth-like patterns) is a characteristic also shared
by most of the lesions which daily are classified as nevi. In contrast, the diagnosis of common melanoma ( a label with relevance as a predictor for a likelihood of metastasis) is most appropriate for lesions
showing typical vertical growth (back to back spacing of nests of atypical cells).
The category of MDM of dermal type generally is a repository of virtual images related to the emergence of a vertical growth component (usually in typical patterns) from a population of dermal melanocytes. Such
lesions may have lentiginous and junctional components, but the patterns at the dermal-epidermal interface do not identify the cells of the lentiginous and junctional components as the likely source of the vertical
growth-like component in the dermis. The “atypical nodular hyperplasias” of most giant congenital nevi satisfy the criteria for a diagnosis of MDM of dermal type. They generally are lacking in significant
lentiginous and junctional patterns in the overlying epidermis. The most common example of MDM of dermal type is found in the setting of a small common nevus. This dermal variant of MDM is characterized by
distinctive epithelioid cells in the vertical growth component. These distinctive cells are also encountered in MDM of the halo nevus-like type.
MDM of halo nevus type can be subclassified. In one category, lesions would show the so-called primary configuration (with lentiginous and junctional components which somewhat resemble those of the common
premalignant dysplasias); in this category, it would appear that cells are delivered from an epidermal component into the dermis, and progressions in neoplasia (as measured by degrees of cytologic atypia) occur
first in the lentiginous and junctional component. In the lentiginous and junctional component, the cells most often are pigmented spindle cells, and the nests and fascicles which are delivered to the dermis
generally are composed of similar cells. This type of lesion is difficult to distinguish histologically from a “Spitz variant with halo nevus reaction.” For this variant, only with the advent of a typical vertical
growth component can the primacy of the epidermal component as the primary source of cells in the dermis be set aside (see WHITHERS1, 2, & 3). An alternate neoplastic pathway in the category of MDM of halo nevus-like type is manifested by the emergence of a dermal vertical growth component, apparently
independent of phenomena at the dermal epidermal interface. The latter process is representative of neoplasia expressed in epithelioid, or round cells. Although the patterns in vertical growth are distinctive
and additional uniqueness is provided by the associated lymphoid infiltrates, this variant, simply by evoking images of a melanocytic neoplasm, expressed in epithelioid cytology, is also likely to be dismissed as a
Spitz variant with halo nevus “reaction.” In fact, the cytologic features of both the dermal halo nevus-like variant, and the pure dermal variant (outside the setting of a giant congenital nevus) are
sufficiently similar to suggest that the two are closely related neoplasms.
The pigmented spindle cell variant of MDM might also be considered in the differential diagnosis. This category embraces some of the variants of cellular blue nevus that might otherwise be characterized as
atypical cellular blue nevus. Some examples may represent neoplastic progression in the so-called pigmented spindle cell nevus. Others may be expressions of neoplastic progressions in combined nevus of the common
type.
Spindle cell patterns are commonly expressed in young (thin) lesions in the category of the dysplastic nevus-melanoma sequence. As already indicated, some of these thin lesions in the dysplastic nevus category,
that also show typical vertical growth patterns, qualify as variants of MDM arising in an atypical nevus; they do so simply by the almost universal benignity of such thin lesions following complete excision.
This site is structured in 3 tiers: 1.) a home site, 2.) textual pages, and 3.) pictorial pages. Navigational aids, including bars in the Master Border to the left, are available as an aid in moving from level to
level and page to page. In addition, underlined items in the text at any tier, by the technique of double clicking, will take the reader to relevant sites or illustrations. References are made to external links in
the Master Border; by clicking on the underlined references the reader will be able to access the external site. On one such site (pathology-skin-rjreed.com), there are other programs with discussions of other
variant melanomas: MDMHALO, MDMHALO, METASIZING, NEAR-NEOPLASIA, and MDMLMM.
|
