Electron microscopic findings

Abstract A somewhat confusing array of electron microscopic studies has been presented in an effort to review nearly all of the existing literature. The prevailing opinions as well as some of the controversies are summarized below: •• There appears to be essentially no doubt remaining that the elastic fiber is the primary target of the basic pathophysiologic process in PXE and that calcification initially involves the central core of the fiber rather than encrusting or layering on the surface. This is a unique form of calcification seen only in the hereditary and acquired forms of PXE. The mineralized material has been shown to be predominantly calcium carbonate (CaCO 3 ) and calcium phosphate (CaPO 4 ). Much lesser concentrations of several other elements, particularly magnesium, are no doubt present, but their chemical form is less well understood. •• Depending on several factors, but probably duration of disease as the most important, there appear to be two and possibly three general ultrastructural patterns of core elastic fiber calcification: one with a more or less granular, homogenous pattern, which usually shows a more electron-dense peripheral rim; the other consists of heavier, irregular, clumped electron-dense mineral deposits that tend to enlarge and deform the fiber as it becomes increasingly mineralized. Prior to fragmentation, the fiber develops "holes" where dense masses are thought to have dropped out during processing or which may possibly represent spontaneous clearing in the center, leaving an electron-lucent area. •• Unusual granular deposits outside the dermal elastic fibers have been seen by several investigators. The nature and origin of these deposits are uncertain. They have been called "granulofilamentous material," "thready masses," and "particulate granular material" and may or may not show mineralization. This material was reported by some to contain polyanions and proposed by some to represent newly formed elastin or elastic fibers, rich in microfibrillar component, and by others to be old degenerating elastic fibers that have been ruptured by the extreme calcification within the fiber. The amount (or presence) of this material has varied greatly from one study to another, suggesting that it is quite variable and may be related to the severity and/or duration of the skin lesions. It would be of great interest to know if this material is rich in tropoelastin or represented old, degenerate elastic fibers, or if it is in fact related to elastic tissue at all. •• Some investigators have observed needlelike crystalline structures within the mineralized areas and concluded that these represent apatite crystals similar to the chemical composition and configuration of bone apatite. The repeated observation of this phenomenon tends to verify the existence of apatite crystals, at least in some patients or in some stages of mineralization; however, its etiologic or clinical implications are obscure at present. The reason for its variability is not known. It seems logical to propose that the presence of apatite crystals is dependent on the duration of the calcification, although this is also unproven. •• Involvement of collagen is controversial. Some excellent electron micrographic studies have found no changes in collagen, whereas others found the collagen fibers affected in limited areas, showing thin, split, twisted fibers and "flower figures" in cross-section. Occasionally, fibers were split into very thin fibrils and lost their typical periodic banding. Studies on patients from the present group showed the previously reported flower figures plus new findings of unequivocal calcification of collagen fibers in the region of ruptured elastic fibers. Large swollen masses of collagen bundles were seen in old, redundant, drooping skin folds, suggesting that collagen involvement may play a secondary role in the final stages of cutaneous PXE. The presence of an abnormal protease, with primary activity directed at elastic tissue and with collagen as a low-grade, secondary target would theoretically explain both observations. •• The fibroblast, which is probably the unmasked basic culprit in PXE, was ultrastructurally normal in all studies. The cell always showed signs of active protein synthesis, evidenced by much rough endoplasmic reticulum and large cysternae filled with granular material presumed to be precursor material for collagen or elastic fiber synthesis or both. Attempts to identify and separate elastoblasts from fibroblasts ultrastructurally have failed.