Postgrad Med J: first published as 10.1136/pgmj.38.435.25 on 1 January 1962. Downloaded from POSTGRAD MED. J. (I962), 38, 25 THE MORPHOLOGY, TERMINOLOGX, AND PATHOGENESIS OF ARTERIAL PLAQUES C.uJ. SCHWARTZ,'M.D. AND J. R. A. MITCHELL, M.B., B.Sc., MJ.C.P. Department of the Regius Professor of Medicine, Radcliffe Infirmary, Oxford ... a scientific survey which is to throw light on yellow pultaceous material. It is in this sense that theproblem ofarteriosclerosis in all its various aspects atheroma has been recently defined by WHO must be based upon a clear delimitation of that term'. (I958) as a' . plaque in which fatty softening is -Aschoff (1933). predominant'. All w9uld be well if workers were THE lack of precision of terms such as arterio- to limit its use to a particular type of plaque, but sclerosis, atheroma and atherosclerosis was em- atheroma, atherosclerosis and arteriosclerosis are phasized by Rabson (I954), who showed that they currently used as synonyms for a wide variety of have different meanings for different pathologists, arterial lesions. These terms, therefore, lack a and they are used to describe widely different types clear and reproducible meaning. of lesions, including many bizarre varieties of We considered, therefore, that an attempt experimentally induced arterial disease. should be made to describe the range of macro- Lobstein (I833) first coined the word arterio- scopic plaques which can be recognized on the sclerosis, which he applied as a generic term to all intimal surface of the major arteries (aorta, forms of arterial hardening. From its inception, carotid, iliac) and define the histological characteristics of by copyright. therefore, the term arteriosclerosis lacked pre- these plaques. Some observations resulting from cision and this difficulty was recognized by Klotz such a study are presented. (I906), who, in suggesting that it be retained in a generic sense, emphasized the need for recognition Macroscopic ofthe different varieties of disease which were to be Types of Arterial Plaque included under this general heading. M6nckeberg Four types of lesion are recognizable on the (1903) described one form of arterial hardening, luminal surface of the major arteries: namely, medial calcification, and stressed that this (i) Flat Sudanophilic Plaques (Fatty Streaks). change was a pathological entity unrelated to the In the unstained vessel these are seen as white or other types of arteriosclerosis. If the term yellow areas. They show considerable variation http://pmj.bmj.com/ arteriosclerosis is used in the sense in which it in size and shape, from small spots no larger than a was introduced, to cover all types of arterial har- pin head to larger areas covering many square dening, it serves no useful purpose; if used in any centimetres (Fig. i). These flat lesions stain other context it serves only to confuse an already intensely with the fat-stain Sudan-IV and are complex problem. sharply demarcated from the surrounding intima. Of all the terms used to describe the various When an artery is sectioned transversely through plaques occurring in the large arteries of man, such a plaque no other macroscopic feature is to atherosclerosis and atheroma are the least well- be found, and in particular no areas of pultaceous on September 25, 2021 by guest. Protected defined and most frequently misused. The word material are seen in the depths. atherosclerosis was introduced by Felix Marchand (ii) Raised Sudanophilic Plaques are white or (I904) to include the various arterial lesions con- yellow in the unstained artery and with Sudan-IV sidered as 'arteriosclerosis' and to emphasize the staining they show a considerable variability in presence of lipid material in certain of the lesions. staining intensity. There is a wide variation in Atherosclerosis is therefore nothing more than a size and shape, but in general the smallest complex alternative for arteriosclerosis and suffers raised lesions are larger than the smallest flat in consequence from the same lack of specificity. plaques. In transverse section the deeper parts of According to Pare (I575), the term atheroma such plaques commonly contain a white or yellow was used in the ancient Greek literature to describe pultaceous material. any cystic space or sac containing a gruel-like (iii) Raised White Plaques (Fibrous Plaques) material. It was first applied to arterial pathology have a firm non-sudanophilic surface. Transverse by von Haller (I755) to describe a particular type sections show that beneath the white surface layer of arterial plaque which on sectioning exuded a there is almost invariably a mass of yellow pul- Postgrad Med J: first published as 10.1136/pgmj.38.435.25 on 1 January 1962. Downloaded from 26 POSTGRADUATE MEDICAL JOURNAL January I962 ulceration, it has never been seen on the surface of a flat lesion. When ulceration is present on a raised plaque it is commonly accompanied by calcification. Microscopic Appearances of the Flat Sudanophilic Plaque These lesions affect the intima and there are no characteristic changes in the other arterial coats. The intima shows a variable but slight thickening consisting of fat-laden macrophages in a fine mesh- work of fibrous and elastic tissue (Fig. 2). Sudan-stained frozen sections show that these plaques contain many fat globules both in macro- phages and extracellularly. There is usually a marked difference in the amount of lipid in the intimal and medial coats, the dividing line being the internal elastic lamina along which considerable fatty deposits may be found, even when the intima shows relatively little fat elsewhere, and this striking concentration of fat along the intimal side of the internal elastic lamina is a feature of this type of lesion. The media may or may not show fatty changes, and when medial fat is present it occurs as fine globules, generally smaller than those found in the intima and showing a tendencyby copyright. to iS. http://pmj.bmj.com/ :e on September 25, 2021 by guest. Protected FIG. i.-Aorta from a male aged 30, stained with Sudan- IV, showing fatty streaking. Note the fan-shaped distribution of sudanophilia in the thoracic segment, the sparing around the mouths of the intercostal arteries, and the localization of the fatty streaking along the midline posteriorly down to the level of the coeliac axis. taceous material similar to that observed in the raised sudanophilic plaques. (iv) Complicated Plaques are those showing cal- cification, surface ulceration, thrombosis or hzemor- FIG. 2.-Frozen section through an aortic fatty streak of rhage. 66-year-old male. The lipid appears as black Calcification can be recognized as grey or globules in a fibro-elastic stroma. Note the normal white areas which are often umbilicated and, like media. Sudan-IV x IOO. Postgrad Med J: first published as 10.1136/pgmj.38.435.25 on 1 January 1962. Downloaded from ffanuarv I962 SCHWARTZ and MITCHELL: Arterial Plaques 27 align along the medial elastic fibres. The medial fat appears to be largely extracellular. It should be emphasized that medial fat need not be associ- ated with the presence of flat sudanophilic plaques in the intima, but can occur in otherwise normal arteries. Within the intimal fatty streaks scattered small round cells morphologically similar to small lymphocytes, together with an occasional plasma cell and fibroblast, are sometimes seen. Other types of cells have not, been encountered, while cellular infiltration of the media and adventitia does not occur. Occasionally the internal elastic lamina shows a hyaline thickening and fragmenta- tion, but even in such instances the media is well preserved. Calcification of the media and internal elastic lamina has been seen in association with the FIG. 3.-Human coronary artery, showing complete flat sudanophilic plaque, particularly in the internal occlusion with thrombus, areas of revascularization, a large intramural hxmorrhage, cholesterol-clefted and common iliac arteries, but it has also been lipid deposits, extensive fibrosis and medial thin- observed in these sites in the absence of intimal ning. Scattered foci of adventitial lymphocytes are lesions, suggesting that it is not an integral com- also present. Masson's trichrome x IO. ponent of this type of lesion. On staining with azure-A and periodic acid- Schiff (PAS) there is no constant tinctorial pattern, lations of fat, although there may be intra- and while material staining with phosphotungstic-acid- extracellular surface deposits, and it is these sur- haematoxylin (PTAH)-' fibrin '-has never been face accumulations only which distinguish raised found on the surface, within or beneath these sudanophilic from raised white plaques. by copyright. plaques. These flat fatty plaques are devoid of Prominent metachromatic staining is very fre- histologically demonstrable vessels, while the vas- quently found in the fibrous tissue of the raised cularity of the medial and adventitial coats does plaques. The staining density is greatest in the not differ from that found in normal arteries. depths of the plaque and around the lacunar spaces, while in general there is little surface meta- Microscopic Appearances of Raised Arterial chromasia, except when organizing thrombus is Plaques present. The fibrous tissue is PTAH and generally Although three types of raised arterial plaque PAS negative. can be distinguished on the basis of their macro- (ii) Elastosis. The laminated elastic tissue which http://pmj.bmj.com/ scopic appearance, no clear distinction can be made occurs in areas of fibrosis has already been men- between them histologically, the three types having tioned. In some sections the spacing and align- essentially similar characteristics. ment ofthe lamina! suggests formation in successive (i) Fibrosis. Dense bundles of collagen are layers in an episodic fashion, and in many instances found in every elevated plaque, often forming such areas of elastosis closely resemble the changes thick layers on the luminal surface, and in the which occur in organizing arterial thrombus.