Critique (part 2)
Chapter 6, tier 2, textual level
Dendritic histiocytes of a different type also reside in the dermis, and seem to favor the adventitia of vessels. They are immunoreactive for factor XIIIa (c,r,hh,tt), and have been described in the dermis in a variety of processes. Similar cells, that are immunoreactive for S-100 protein, are relatively common in the same population. Some of the cells in these populations may be concomitantly reactive for both S-100 protein and factor XIIIa . For example in an uncommon dermal fibrohistiocytic lesion, dendritic histiocytes are reactive for both factor XIIIa and S-100 protein (personal communication - Donald Pulitzer). In these lesions, the tumor cells are acidophilic, plump, and dendritic. They are closely aggregated and molded to their neighbors. Eosinophils are admixed among the dendritic histiocytes. On the basis of numerical representation, it would appear that many, if not most, of the cells share both antigens. If there is a “dermal dendrocytoma,” this unreported lesion seems to qualify. These observations suggest that these two antigens are not mutually exclusive. Positive immunoreactions for S-100 protein and factor XIIIa may identify cell functions which are neither peculiar to the histiocytic category nor restricted, one or the other, to distinct populations of dermal dendritic histiocytes.
A role for a “sentinel” cell in the adventitia of blood vessels (a portal for the ingress and egress of materials) might be anticipated; such cells would be ideally situated to monitor the milieu in a site of metabolic exchanges. Factor XIIIa (+) dendritic histiocytes are likely candidates. If appropriately stimulated, they might function as both an immune sentinel [S-100 (+)] and as a mediator in perivascular phenomena [factor XIIIa (+)].
In our study of dematofibromas, stellate fibroblasts of the reticular dermis seem to be the native cells in most examples. They provide the cellular, and matrical bulk of the tumor. Factor XIIIa (+) dendritic histiocytes may be simply residents in most dermatofibromas. They are also represented in subcutaneous fibrous histiocytomas (b). The immunoreactive dendritic cells of dermatofibromas mostly are inconspicuous on routine H & E stained sections. With specific immunoreactions, they are numerous in the dermis adjacent to, and are variably represented among, the fibroblastic cells of a dermatofibroma. In most examples, they are less numerous in the more central portions of a dermatofibroma. The designation, dermal dendrocytoma (f), if both fibroblasts and histiocytes are to be characterized as dendrocytes, is appropriate only if dermatofibromas are reactions rather than neoplasms. The available evidence neither establishes factor XIIIa (+) dendritic histiocytes as the source of the native tumor cells, nor identifies them as a unique attribute of dermatofibromas. If dermal dendritic histiocytes (so-called dendrocytes) were to be characterized as absolute and exclusive, then, by fiat, all other dermal lesions with a high component of factor XIIIa (+) cells would become variants of dermatofibroma (“dermal dendrocytoma”), including adventitial cellular myxofibroblastoma (“epithelioid cell histiocytoma”). The conflicting interpretations of patterns in dermatofibromas point up the problems in making distinctions with immunologic markers between cells which are native to, and those which are resident in, a neoplasm.
Some observers have classified dermatofibroma as an inflammatory process. Presumably, in this approach, the high component of dendritic histiocytes has been accepted as a marker of an inflammatory process; the associated component of hyperplastic mesenchymal (fibroblastic) cells must then be interpreted as merely a reaction in the site of inflammation. If this approach were valid, then adventitial cellular myxofibroblastoma might also be characterized as inflammation. From a different perspective, the combined features of a dermatofibroma might be better compared to the process of repair than inflammation. The patterns in some dermatofibromas might be compared with the patterns seen in the repair of tissue. It would be proper to speak of a “microvascular unit” in the characterization of granulation tissue.
Clearly, dermatofibroma is a tumor. Inflammation is a process mediated at the level of inflammatory cells. Inflammation is occasionally a prominent feature of a dermatofibroma (usually in association with a high component of plasma cells), but most examples are relatively free of inflammation.
The tumoral qualities of many dermatofibromas, and of adventitial cellular myxofibroblastomas are more in keeping with neoplasia. Some dermatofibromas are locally progressive; they may attain impressive dimensions [e.g., aneurysmal sclerosing hemangioma (ggg)]; they are autonomous; such lesions often show a population of atypical histiocytes. Some dermatofibromas are best characterized as neoplasms and, for some examples, the neoplastic cells may be histiocytes. The category of dermatofibroma may be heterogeneous.
In the past, problematic lesions often have been characterized as fibrohistiocytic in type on the basis of imprecise criteria. Although it would appear that fibroblasts, independent of facultative histiocytes, have regained a place in neoplasia, the interdependence of fibroblasts and histiocytes tends to lead us back to a unitary concept embracing both fibroblasts and histiocytes. The concept of dermal dendrocytoma, as a tumor of a single line of cells (the “dermal dendrocytes”), was not so great an advance over the concept of fibrous histiocytoma, as a tumor of facultative histiocytes; the choice was more in the nature of a desire to sponsor a new designation. Once some of the cells were identified as fibroblasts, independent of divergent phenotypic expressions by histiocytes, a proposal that dermatofibroma is a tumor of a mesenchymal complex, embracing vessels, fibroblasts, and dendritic histiocytes might seem appropriate. Perhaps, there are examples of dermatofibroma which are fibroblast-rich dendritic histiocytomas. For lesions in this category, it seems to be exceedingly difficult to get away from the concept of a histiocyte that functions as a fibroblast.
In the interpretation of morphologic patterns in some problematic lesions, cells of uncertain lineage, with some of the features of histiocytes, often are characterized as histiocytoid. In certain contexts, cells with complex cytoplasmic processes also might qualify as histiocytoid (or even histiocytic); the activated synoviocyte is an example. Lesions, which are replete with dendritic histiocytes, also may qualify as “histiocytoid” (some dermatofibromas may be examples). Some vascular lesions have been qualified as histiocytoid variants (epithelioid hemangioma and hemangioendothelioma).
Epithelioid, as a qualifier, has been subverted from a characterization of epithelium-like collections of cells to a characterization of cells which are rounded in outline and acidophilic (g). In this subversion, epithelioid cells also are histiocytoid. In practice, the designation, “epithelioid,” is best reserved for patterns in which non-epithelial cells are clustered with little or no intervening fibrous matrix. In the latter context, both spindle and round cells are acceptable (in both nesting and fascicular arrangements). As an example, in granulomas, activated histiocytes are tightly clustered; the resulting patterns are “epithelioid.” Individual histiocytes of granulomas are rounded but, as units, are not epithelioid. With a soft tissue tumor as a second example, the designation, epithelioid sarcoma, is appropriate, if attention is given to patterns in which the cells are nested. In epithelioid sarcoma, both round and spindle cells are represented. Incidentally, some of the component cells of epithelioid sarcoma are histiocytoid; they are acidophilic and rounded. As a final example, “epithelioid hemangioendothelioma,” as a designation for a group of distinctive vascular tumors (ss), might be characterized as inaccurate. In the latter disorder, cells are plump and rounded (histiocytoid) but the arrangement of the cells is endothelioid rather than epithelioid. The distinctive cells probably are transformed, high endothelial cells.
In current usage, the qualifiers, histiocytoid and epithelioid, commonly are equated. In the characterization of “epithelioid cell histiocytoma” (g), recognition was given to cytologic features (i.e., plump, round cells) but, in such lesions, whorls of plump, round cells can be properly characterized as having epithelioid qualities; the patterns in which the cells of adventitial myxofibroblastoma are aggregated identifies cellular examples as “epithelioid” cell lesions, if not as a variant of histiocytoma.