[Calcifications in temporal arteries -- their morphogenesis in comparison to physiological osteogenesis]. / Verkalkungen der Temporalarterien -- Ihre Morphogenese im Vergleich zur physiologischen Osteogenese.

OBJECTIVE: Vascular calcification, traditionally regarded as a dystrophic process, has recently been interpreted as a bone-like biologically regulated phenomenon. Because temporal arteries which also contain calcifications are easily available from biopsies of older individuals with suspected giant cell arteritis, we studied the morphogenesis of this calcification in comparison with the development of fetal bone. MATERIAL AND METHODS: Formaldehyde fixed arteries were processed in paraffin sections and investigated by light-, transmission-, and scanning electron microscopy. The atomic composition of the calcifications was estimated by X-ray microanalysis. Fetal bone, also fixed with formaldehyde, was investigated using identical methods. RESULTS: Early calcifications are often present as focal or diffuse granular mediacalcinosis. With increasing age, calcified granules appear in association with the internal elastic membranes and progress to sheet-like calcifications. Ultrastructurally calcospherites, not rarely exhibiting the Liesegang phenomenon, are the hallmark of early calcifications. In advanced sheet-like calcification calcospherites could be detected as components of the calcified lumps. Calcospherites also appear in endochondral calcification, but are absent in calcified osteoid. The ultrastructure of calcospherites in provisional endochondral ossification differs from that in vascular calcification. Instead of corpuscles as with the Liesegang phenomenon, radial clusters of needle-like crystals resembling apatite are present. While calcospherites of the tunica media often contain a high amount of magnesium, calcified sheets as well as bone exhibited in contrast a low magnesium content. CONCLUSIONS: It is concluded that, comparable to granular mediacalcinosis of the aorta, development of calcified arteriosclerotic plaques, and Mönckeberg's disease, calcification of small muscular temporal arteries is also initially a calcospherite-dependent process. It is generally accepted that these calcified corpuscles represent remnants of calcified necrotic or apoptotic cells. In the phase of confluence with the appearance of sheet-like calcification, a low bone-like magnesium content that differs from the high amount in the isolated medial calcospherites was measured. This finding, together with the observation that calcified sheets contain calcospherites, supports the hypothesis that vascular calcification in general is different from bone formation and has to be regarded as a biphasic process initiated by the appearance of calcospherites and followed by a secondary calcifying phase with the formation of bone-like apatite that leads to rock hard lumps of calcified vessels.

[Morphogenesis of media calcinosis in Mönckeberg disease. Light microscopy, scanning electron microscopy and roentgen microanalysis findings]. / Morphogenese der Mediakalzinose des Morbus Mönckeberg. Lichtmikroskopische, rasterelektronenmikroskopische und röntgenmikroanalytische Untersuchungsbefunde.

OBJECTIVE: In contrast to granular mediacalcinosis of the aorta, Mönckeberg's disease is characterized by the occurrence of sheet-like calcification. It is usually said that the pathogenesis of this calcification is unknown. MATERIAL AND METHODS: To obtain some insight into the mechanism leading to this calcification, we performed light microscopic, scanning electron microscopic and X-ray microanalysis investigations on femoral arteries from autopsies. RESULTS: By light microscopy preferentially sheet-like calcifications of different size appeared. In the alizarin red S stain in the neighborhood of these compact structures calcified globules were observed. By SEM in the neighborhood of the compact areas calcified granules were found; the compact structures themselves consisted of granules sticking one onto the other. X-ray microanalysis exhibited high contents of calcium and phosphorus in the compact calcifications; they also showed a minor content of magnesium. Isolated granules inside the compact calcifications showed a nearly identical composition, while granules outside in the surrounding media consisted preferentially from calcium and phosphorus, but they exhibited a slight higher magnesium content. CONCLUSIONS: It is concluded that Mönckeberg's media calcification is due to dystrophic calcification. Calcified matrix vesicles from necrotic cells, as it is assumed for the pathogenesis of the calcification of arteriosclerotic plaques (31), are interpreted as precursors of the solid calcifications which may develop by confluence and sticking one onto the other of calcified globules.

[Does arteriosclerotic calcinosis of vessel walls imitate osteogenesis? Pathomorphological studies of arteriosclerotic plaque]. / Imitiert die arteriosklerotische Gefässwandverkalkung die Osteogenese? Pathomorphologische Untersuchungen an arteriosklerotischen Beeten.

OBJECTIVE: For it is supposed that calcification of arteriosclerotic plaques imitates osteogenesis, it was studied whether the morphology of different stages of calcification supports such an assumption. MATERIAL AND METHODS: Investigations were performed on one operation specimen of a dissecting aneurysm of the aorta and five human autopsy aortas. From different arteriosclerotic plaques, paraffin sections without and after EDTA-decalcification were prepared. Light microscopic, scanning (SEM) and transmission electron microscopic (TEM) investigations as well as X-ray microanalysis were performed. RESULTS: By light microscopy, it became obvious that the intensity of calcification of arteriosclerotic plaques is not reflected by the conventional H&E stain--the real amount of calcium-phosphorus deposits becomes only evident by using a special stain, such as the alizarin red S reaction. In the SEM, arteriosclerotic plaques with granular calcification were characterized by accumulations of isolated calcified globules often reflecting the structure of necrotic cells. TEM exhibited even accumulations of calcified bodies corresponding to the shape of cells; cell remnants were present in the neighborhood. X-ray microanalysis of the granules detected calcium and phosphorus and a relative high content of magnesium, reflecting the composition of calcospherites in granular media calcification (71). By SEM, solid calcifications exhibited associations of calcified bodies resembling those of the isolated granules in early calcification but with one stuck onto the other. X-ray microanalysis revealed that these deposits are characterized by high amounts of calcium and phosphorus and a minor component of magnesium in comparison to the isolated granules. CONCLUSIONS: From the investigations it is concluded that calcification of arteriosclerotic plaques imitates the process of granular media calcification which is assumed as "dystrophic" calcification of fragments of necrotic cells. The hypothesis of a "regulated" calcification as it occurs in cartilage or bone cannot be supported for the development of the calcified plaques; however, it cannot be excluded that proteins that are associated with osteogenesis participate in the transition of calcification to ossification in the vessel wall.

[Association of silver granules with elastic fibers in amalgam reaction of mouth mucosa]. / Die Assoziation von Silbergranula mit elastischen Fasern bei der Amalgamose der Mundschleimhaut.

OBJECTIVE: Discoloration of the oral mucosa due to amalgam may appear histologically merely as brown pigmentation of the fibrous extracellular matrix. It was the aim of these investigations to identify the fibrous component that contains silver granules. METHODS: Biopsy specimens from seven patients with clinically diagnosed amalgam tattoos were investigated by light and electron microscopy as well as by X-ray microanalysis. RESULTS: Light microscopy revealed small brown discolored fibers in all specimens; in sections stained with Weigert's resorcinfuchsin, they appeared dark violet. Scanning electron microscopy revealed metallic granules associated with thin fibers; by X-ray microanalysis, they exhibited preferentially peaks for silver and sulfur. Transmission electron microscopy detected only electron-dense particles in elastic fibers. CONCLUSIONS: With the different morphological methods, silver granules of amalgam tattoos were exclusively detected within elastic fibers. This result indicates that granular brown discoloration of the matrix fibrils is due to silver impregnation of elastic fibers. Therefore, the histopathological diagnosis of amalgam tattoo is possible even in the absence of larger amalgam particles with black appearance.

[Granular media calcinosis of the aorta. Structural findings, historical review and pathogenetic significance]. / Granuläre Mediakalzinose der Aorta. Strukturelle Befunde, historischer Rückblick und pathogenetische Bedeutung.

Granular mediacalcinosis of the aorta seems to be a forgotten phenomenon that had been intensively investigated at the beginning of the past century. Without knowledge of this older literature we were, first of all, astonished to find in histological sections from aortic aneurysms, appearing "normal" in the H&E stain, severe calcifications of the media in von Kóssa and Alizarin red S stained sections. Therefore, 24 operation specimens of aneurysms were investigated with several morphological methods. In all cases, light microscopy exhibited granular medial calcification with a slight increase of the severity in specimens from older patients. Scanning electron microscopy on paraffin sections revealed calcified globules with diameters of about 1 micron localized between the elastic laminae. By transmission electron microscopy these calcospherites occupied the space between the elastic laminae. X-ray microanalysis exhibited high amounts of calcium and phosphorus and a smaller amount of magnesium. This atomic composition supports the findings of Reid and Andersen (69) indicating that these calcifications are due to the deposition of whitlockite. These morphological findings are supplemented by a review of the older literature. The biological significance of this calcification remains unknown. On the one hand, it may be responsible for the increasing stiffness of the aorta in older age groups--and, on the other hand, a pathogenetic role for the development of dissecting aneurysms cannot be excluded. This may be supported by the effect of beta-aminopropionitril in lathyric rats with destruction of the interlaminar fibers, described by Nakashima and Sueishi (65): it seems possible that a focal increased calcification in the human aorta may disturb the connection between the elastic laminae, thus, facilitating their separation.

[Mixed tophi. Calcium pyrophosphate dihydrate crystals in gout tophi]. / Mischtophi. Kalziumpyrophosphat-Dihydrat-Kristalle in Gichttophi.

Calcification of tophi is a well-known secondary phenomenon in gout. Because there are no data available on the nature of the calcium component, light and scanning electron microscopic as well as X-ray microanalysis studies were performed on calcified tophi. In unstained histological slides, urate crystals were detected as negative birefringent needles; after incubation of the slides in distilled water, the urate crystals had disappeared, only positive birefringent calcium pyrophosphate dihydrate (CPPD) crystals of different size remained. An identical result was obtained by scanning electron microscopy. By X-ray microanalysis, peaks for calcium and phosphorus were measured, indicating the presence of CPPD. The occurrence of CPPD crystals in urate tophi as well as in foreign body granulomata indicates that the occurrence of CPPD is not restricted to articular tissues. The biochemical mechanism leading to the appearance of these crystals remains unknown, but it may be assumed that an increase of connective tissue destruction may be responsible for this calcification process.