DISCUSSION (part 1)
chapter 3, tier2, textual level
In certain reparative processes, histiocytes and fibroblasts are functionally interdependent. The relationships are manifested in wound bealing (hhh). The functional versatility of histiocytes is manifested in granuloma annulare. In such a lesion, histiocytes in various guises are admixed in the palisades bordering zones of fibrolysis or necrosis; they also are represented among collagen bundles in the adjacent dermis. Fibroblasts are activated. The recent demonstration of dendritic histiocytes in a variety of “fibrohistiocytic” disorders has provided additional evidence of the interrelationships.
In the interpretations by Wilson-Jones, et al (g), the native cells of “epithelioid cell histiocytoma” were immunoreactive for factor XIIIa. In recognition of this seminal quality, lesions were assigned to a histiocytic category. In our cases of a similar type (adventitial cellular myxofibroblastoma), small dendritic cells, which were immunoreactive for either S-100 protein or factor XIIIa, are interspersed among the more characteristic tumor cells, and were richly sprinkled in the adjacent dermis. Cytologically, the immunoreactive dendritic cells could be easily distinguished from the native tumor cells. The identity of the lesion reported by Mehregan, et al (k), with epithelioid cell histiocytoma, as characterized by Wilson-Jones, et al (g), has not been established.
The relationships between factor XIIIa (+) dendritic histiocytes and native tumor cells are basically the same in both adventitial cellular myxofibroblastomas and dermatofibromas, including the sclerosing hemangioma variant. Similar relationships between histiocytes and pericytes have been observed in hemangiopericytoma (e). The designation, “dendrocytoma,” seems to be inappropriate for any of these three lesions.
In adventitial myxofibroblastoma, only a few dendritic histiocytes, and focal collections of tumor cells are immunoreactive for S-100 protein. The tumor cells generally are less reactive than the dendritic histiocytes. The immunoreactive tumor cells mostly are rounded or angulated in outline but, in one example, small clusters of spindle cells also are reactive. In adventitial myxofibroblastoma, patterns and relationships of S-100 (+) histiocytes with the epithelioid cells, and of factor XIIIa (+) histiocytes with the epithelioid cells are comparable. The two types of resident dendritic cells are neither equally, nor universally, represented.
In both dermatofibromas and adventitial myxofibroblastomas, the relationships between dendritic cells and tumor cells provide evidence of poorly understood interactions between cells of the dendritic reticular system and supporting mesenchyme, including blood vasculature. The factor XIIIa (+) dendritic histiocytes of adventitial myxofibroblastoma are closely apposed to some of the tumor cells; their dendrites are intertwined about some of the tumor cells in sustentacular relationships. The intimacy of the dendritic histiocytes with the tumor cells is best interpreted as the morphologic expression of functional adaptations. In addition, in the walls of some of the sclerotic vessels in adventitial myxofibroblastoma, the distinctive tumor cells, in areas showing fibrous components, are individually isolated in a delicate fibrous matrix. In these areas, the tumor cells appear to have an intimate relationship with the vascular component.
In some examples, the surface, or even the cytoplasm of some of the tumor cells are reactive for either S-100 protein or factor XIIIa. The cytoplasm of the few tumor cells which are immunoreactive for factor XIIIa are uniformly and faintly stained. As an explanation for these relationships, the metabolites (S-100 protein and factor XIIIa) of the dendritic histiocytes may have been liberated into the stroma of the tumor. For those examples in which the cytoplasm of the tumor cells are faintly stained, the product of the dendritic histiocytes may have been imbibed by, or even transferred directly to, the respective cells. Factor XIIIa may be a metabolite which influences the function, or differentiation of mesenchymal cells. Perhaps, it is an activation factor.
In all instances, immunoreactions must be cautiously interpreted in combination with microscopic findings. A high percentage of immunoreactive cells in problem lesions does not, in turn, identify the reactive cells as the “native” cells. In some disorders, reactions between native mesenchymal cells, and migrant inflammatory cells (e.g., histiocytes) induce a flood of migrant histiocytes into the dermis. In problematic lesions, that are rich in dendritic histiocytes, electron microscopy may be an aid in resolving conflicts. In the evaluation of the nature of a problematic fibrous or myxomatous lesion, the presence of a high component of dendritic histiocytes is not necessarily evidence of an inflammatory process. Certainly, hemangiopericytoma, a lesion rich in dendritic histiocytes, is not an inflammatory process. Local dendrocytosis is descriptive of the relationships between mesenchymal cells and dendritic histiocytes in a variety of inflammatory and neoplastic processes. Although the nature of the basic cell type in adventitial myxofibroblastoma has remained uncertain by both light microscopy and immunohistochemistry, histiocytic qualities and epithelioid cellular aggregates were implicit in the designation, “epithelioid cell histiocytoma (g).” In the latter lesion, cells were focally clustered in epithelioid patterns, and many were immunoreactive for factor XIIIa (i.e., histiocytoid qualities) (g). Histiocytoid qualities are evident in our evaluations of similar materials. The basic tumor cells of adventitial myxofibroblastoma are both rounded and spindle shaped; they tend to have prominent cell processes. Some are weakly and variably positive for lysozyme and alpha-1 anti-chymotrypsin. These histiocytoid qualities do not, in turn, identify the tumor cells as derivatives of hematopoietic monocytes.
The native tumor cells of adventitial cellular myxofibroblastoma, with the exception of scattered clusters showing a weak reaction, are not immunoreactive with antibodies for S-100 protein or factor XIIIa. In the face of these negative or weak immunoreactions, a characterization of the respective fibroblastic cells as facultative histiocytes would be inappropriate.
The cells of adventitial cellular myxofibroblastoma are associated with a fibromyxomatous matrix; albeit, in most examples, the matrix is inconspicuous at the level of the light microscope. In a few examples, scattered, plump tumor cells are mucicarminophilic; they are muciparous and qualify as “myxoblasts.” Adventitial myxofibroblastoma has a peculiar predilection for stroma, particularly the adventitial dermis. Conceptually, adventitial dermis is primal; it retains, in post-natal life, the attributes of embryonal mesenchymal. It is delicately myxomatous, and rich in type III collagen. Adventitial cellular myxofibroblastoma seems to qualify as a neoplasm of adventitial mesenchyme.