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Caveats, Pitfalls, Pratfalls, and Prejudices in the Interpretation of Melanocytic Lesions: the Manipulation of Virtual Images (a glossary in alphabetical order)
Ancillary concepts, features, and phenomena which are involved in, or relate to, neoplastic progressions include the following:
acidophilic body: acidophilic bodies (pale acidophilic bodies or “Kamino” bodies) are approximately the size of neighboring keratinocytes. They may be encountered in junctional nests among melanocytic cells, generally near the attachment of junctional nests to the epidermis, or in the epidermis over areas of junctional activity. They may even be found in dermal nests of tumor cells which are near the dermal-epidermal interface. They somewhat resemble “colloid bodies” of a lichenoid reaction, but usually are less symmetrical in outline and do not show a central zone of pallor (i.e., a central defect as a marker of the site in which a nucleus has undergone lysis). In the face of pale acidophilic bodies, it is difficult to make a distinction, at the light microscopic level, between a necrotic keratinocyte or melanocyte, and aggregates of basement membrane material.
Acidophilic bodies are common in the setting of spindle cell nevus of Spitz type. They are also fairly common in the pigmented spindle cell nevus of Reed. Similar, but less numerous and smaller, bodies may even be identified in common premalignant dysplasias. They may also be encountered in the epidermal component of melanomas and, thus, when identified have no diagnostic utility. Being common in spindle cell “nevi” of Spitz type, they generally become a part of the complement of virtual images which are evoked in evaluating the real images of a suspected Spitz “nevus.”
Anaplasia: This term has various connotations. Perhaps the most appropriate application of this term in regard to neoplasia is found in patterns which are so distinguished that an observer must chose among sarcoma, lymphoma, or carcinoma. Tumors of primitive, uniform, small round cells which, in aggregate, resemble the undifferentiated cells of an embryo also might be characterized as anaplastic.
Anaplasia of small round cell type, in some settings, might be characterized as retrodifferentiation (an expression of neoplasia in which grade is measured by comparisons with patterns found in normal adult, fetal, and embryonal tissue); in undifferentiated, small round cell neoplasms, such as primitive neuroectodermal tumors, the embryologically most primitive component is assigned the highest grade of neoplasia, and assume prime importance in prognostications.
In the skin, melanoblastoma of infancy is an example of a high grade, small, “blue” cell neoplasm. It arises in the setting of a giant congenital nevus, or as a component of neurocutaneous melanosis syndrome; it is distinguished from MDM-like lesions of dermal type (atypical nodular hyperplasias) of giant congenital nevi by size, nuclear atypia, mitotic rate, and malignant potential. It belongs in a category with other blastomas of infancy and childhood, and other peripheral small, round cell tumors, such as Ewing’s tumor and peripheral primitive neuroectodermal tumor, and cutaneous small cell undifferentiated carcinoma (Merkel cell tumor).
The concept of anaplasia also has application for the interpretation of patterns in some high grade malignant neoplasms. At the level of the light microscope, the cells of lesions in this category are large (e.g., large cell anaplasia), markedly atypical, and lack distinguishing characteristics (even those of embryonic tissue). Large cell anaplasia generally is a feature of high grade, undifferentiated tumors.
In regard to melanomas, the designation, anaplasia, has greatest utility in the characterization of large cell, amelanotic lesions (i.e., lesions in which the absence of identifiable cytoplasmic melanin complicates the interpretation of a problematic lesion on routine histologic sections). Such tumors in metastatic sites are commonly interpreted as something other than melanoma. They may be interpreted as undifferentiated carcinoma, sarcoma, or even lymphoma.
Ancient change: Ancient change has specific connotations in the setting of schwannoma and cellular blue nevus. It gives recognition to cytologic pleomorphism, lysis of groups of cells, and characteristic vascular changes. The cellular changes include variations in nuclear size and outline, and dense nuclear chromatin. The lysis of groups of cells, possibly as a result of the release of enzymes into the tissue, may be associated with alterations in the walls of neighboring vessels. The process may be akin to that of apoptosis - a physiologic and pathologic depletion of cells. The process should not be confused with the patterns of neoplastic progression. In the evaluation of the nuclear qualities and a low mitotic rate, ancient change takes on the qualities of a regressive rather than progressive process. It would be a mistake to equate the regressive patterns in cellular blue nevus with the progressive neoplastic changes in the vertical growth component of MDM of the dermal type. Generally, mitotic activity is not a feature of the “ancient” changes in cellular blue nevus (see section on “lymphoid infiltrates”).
Angiogenesis (angioplasia): The capillaries of the papillary dermis are a component of anatomic level II. A vascular plexus is also prominent at the interface between level IV and V. Angiogenesis (angioplasia) is a common accompaniment of stromal reactions at levels II and III. The presence of genetically altered melanocytes, in either the epidermis or the dermis, usually is associated with an augmentation of the vascular plexus of the upper portion of the dermis; angiogenesis is an important component of vertical growth.
A tumor which has entered vertical growth will have acquired the capacity to induce its own stroma (the expanded matrix of a lesion showing typical vertical growth somewhat resembles an hyperplastic papillary dermis). The induced stroma is associated with an expanded vascular plexus; the vascular plexus is sufficient to support the cells of a neoplasm.
In variant vertical growth at level III (widely and regularly spaced nests of tumor cells), limitations on the richness of the vascular plexus may influence the distance at which nests of tumor cells can be spaced, relative to one another. On the other hand, in typical vertical growth at level III (closely spaced nests of tumor cells), the ability of the tumor to induce a stroma with an independent, rich plexus of vessels may allow for a closer, more intimate spacing of nests of tumor cells.
The angiogenesis of cellular immune responses probably differs from that of tumor stroma, but the two phenomena usually are part and parcel.
Ectasia of thin-walled vessels is a common feature in the reticular dermis beneath a vertical growth component. These dilated vessels should be carefully examined for evidence of vascular invasion.
Atypical hyperplasia: Hyperplasia is a general qualifier; it gives recognition to a numerical increase in a specific component. It has application to cells, cellular components, and to stromal components. As a qualifier, a cell or a pattern is identified as being “not of the type.” In general pathology, the qualifier, atypical, commonly is used to characterize cytologic features. To qualify a cell as atypical indicates that the cytologic features are of a type seen in neoplasia, particularly malignancies. Some regenerative changes share cytologic features with malignant cells; they qualify as atypical. If atypia is interpreted as being of regenerative type, then it should be qualified as such (i.e., regenerative atypia). If, locally, there is an increased number of cells, and if those cells are cytologically atypical, then the resulting patterns qualify as atypical hyperplasia.
Cellular host immune response: a cellular lymphoid infiltrate in a neoplasm is generally a marker for a cell mediated immune response.
Lymphoid infiltrates (cellular immune response) are not a feature of uncomplicated typical nevi; they are the hallmark of halo “nevi,” and related variants. In premalignant melanocytic dysplasias, the intensity of a cellular immune response is generally proportional to the degree of the dysplasia (degree of cytologic atypia); although, some high grade dysplasias are relatively devoid of lymphoid infiltrates. Cellular immune responses are a prominent feature of many melanomas at level III, but tend to be an inconspicuous feature of vertical growth components at level IV (migrant growth).
In some high grade dysplasias, in some level III melanomas, and in halo “nevi,” the lymphoid infiltrates tend to be band-like at the interface between the papillary dermis (or tumor stroma in the case of level III melanomas) and the reticular dermis. Infiltrates of lymphocytes may also extend into the nests and intermingle among tumor cells (tumor infiltrating lymphocytes). The latter patterns are merely a modification of the so-called lichenoid reaction with the stipulation that the target cells are melanocytes rather than kerainocytes (the relationships also qualify as halo-nevus-like phenomena).
In intimate association with neoplastic cells, lymphocytes and histiocytes mediate the lysis and destruction of the neoplastic cells. As a result of this interaction, neoplastic cells in nests become more loosely spaced; they are often separated by irregular, small clefts (these clefts, like those in the epithelial domain of inverted follicular keratoses, may be a marker of favored site for the accretive inlay of fibrous tissue; an inlay of fibrous tissue in these defects may partition the nests, and eventuate in an incorporation of the surviving fragments in newly formed dermal mesenchyme; as a consequence, the entrapped nests may appear to have “dropped-off” into the dermis).
The epidermal components of dysplasias, and the radial growth components of melanomas commonly are associated with infiltrates of lymphoid cells in true “lichenoid” patterns. The resulting lytic defects in the epidermal domain contain cellular debris (colloid bodies), lymphocytes and histiocytes. They are the result of the lysis of both normal keratinocytes, and neoplastic melanocytes. In some dysplasias, the lichenoid reaction may, on a given section, mask the nature of the underlying lesion; they may lead to a diagnosis of an inflammatory process (i.e., established or senescent lichenoid reaction). In a similar fashion, a lichenoid reaction may obliterate a melanoma in the primary site (see section on regression). It should be noted that occasionally an independent lichenoid reaction is associated with hyperpigmentation and melanocytic hyperplasia; such an inflammatory reaction may be misdiagnosed as a melanocytic dysplasia.
Admixtures of tumor cells and tumor infiltrating lymphocytes, when identified in melanomas, have been cited in some prognostic statistical analyses as a significant (favorable) variable.
Some melanomas, such as the organoid or “nevoid” variants, tend to be manifested in fascicular patterns, show atypia in uniform patterns, and extend into the reticular dermis in significant pattrns of migrant vertical growth; these lesions rarely show the significant patterns of the more common forms of melanomas; the real images are deceptive. Such lesions, if mistakenly assigned to the category of benign nevus, may lead to later claims of malpractice.
Controversies: The enthusiasm for controversy as introduced into pathology conferences in the 1970”s has somewhat abated. Controversies became a tool to be manipulated for self-aggrandizement, and for the promotion of a following. The popularity of controversies reveals the susceptibility of practicing dermatopathologists to the force of personalities. Controversies are mostly a play upon linguistic symbols rather than a significant manipulation of real and virtual images.
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