Preface to the first edition

There can hardly be a disease or pathological process where electron microscopy has not added new details and dimensions to existing knowledge. The innumerable published papers and books on the ultrastructure of tissues altered by disease or experimental procedures bear eloquent testimony to the many major contributions made by this technique.

Although the student interested in the pathology of certain systems, organs and tissues such as liver (David, 1964), muscle (Mair and Tomé, 1972), synovial joints (Ghadially and Roy, 1969), kidney (Dalton and Haguenau, 1967) and peripheral nervous system (Babel et al., 1970) is now catered for and excellent books dealing with the ultrastructure of normal cells and tissues are available (e.g. Fawcett, 1966; Porter and Bonneville, 1973); Lentz, 1971; Rhodin, 1974), there is as yet no book from which one may learn in a systematic fashion about the numerous changes that occur in cellular organelles and inclusions as a result of disease or experimental procedures. On confronting an unfamiliar or unknown morphological alteration in some particular cellular structure the questions that arise are: (1) has this been seen before? (2) if so, in what situations has such a change been seen? (3) what is the significance of the change? and (4) how can one retrieve information on this point from the formidable, scattered literature on the ultrastructure of normal and pathological tissues?

It is my hope that this book will help to answer such questions and serve as a brief textbook and atlas of cellular pathology at the ultrastructural level. Within its covers I have collected, classified, described and illustrated various alterations that are known to occur in cellular organelles and inclusions as a result of changing physiological states, diseases and experimental situations.

In keeping with the traditional practice adopted in many past pathology texts, each chapter commences with a discourse on normal structure and function. This is followed by essays devoted to various morphological alterations that have hitherto been witnessed. The introduction and preliminary essays on well known normal structures (e.g. nucleus and mitochondria) are, of necessity, brief. They do little more than set the scene and outline the classification and nomenclature employed. The advanced electron microscopist may find that some of the passages in these essays are of a rather elementary nature, but this material is included on the assumption that some readers may not be too familiar with current electron microscopic concepts and topics. Less well known normal structures (e.g. rod-shaped tubular bodies and nuclear bodies) are dealt with more fully, for information on such structures is often not easy to find and unfamiliarity with such structures is likely to lead to errors of interpretation.

The sections dealing with morphological alterations and lesions follow a fairly standard pattern in most instances. A brief introduction dealing with matters such as definition, nomenclature, correlations with light microscopy, and historical aspects of the subject is followed by a morphological description supported by accompanying illustrations. After this comes a section where I have listed the sites and situations in which the particular morphological alteration has been seen and the authors who have reported its occurrence. This section often contains numerous references. (Some readers may find these lists irksome, but they are essential for the research worker and student seeking further information.) Then follows a discussion and interpretation of the morphological change under survey. The principle I have followed here is to present as many known theories and ideas as possible even though I may not be in sympathy with some of them. I have also often indicated what I have come to think about the matter as a result of my own studies and reading of the literature. However, I do not feel that an author should judge every issue, and I have, at times, done little more than report as faithfully as I can the views propounded by others. Not all essays follow the above-mentioned pattern for there are instances where the story is told more profitably within a different format. For example, instead of devoting a section to every change in mitochondrial morphology which has been suspected as representing an involuting or degenerating mitochondrion, I have collected these changes into a section entitled ‘mitochondrial involution and elimination’.

One of the functions I would like this book to serve is as a gateway to the relevant literature. Since this is not a book primarily devoted to normal structure and function (even though a substantial number of pages are devoted to such matters), the references in sections dealing with well known normal structures are somewhat sparse. When dealing with little known normal structures or with alterations and lesions, I have tried to include virtually every reference on the subject that I am aware of. When such citations are few they are all presented in the text; when too many, I have included review articles and also tried to include the earliest and latest paper on the topic.

Although the format is designed primarily for those who examine pathological tissues with the electron microscope, I hope that this book will also be of interest to the teacher of pathology and the practising pathologist. This book is not for the individual who has no knowledge of cell fine structure at all (there can be few who fall into this category today!) nor is it for the expert ultrastructural pathologist. It is addressed to the much larger intermediate group of workers who may wish to acquire a basic knowledge of general ultrastructural pathology on which they may pursue their own special interests with greater confidence and a wider understanding.

The teacher of pathology attempting to relate classic pathology with the now familiar concepts of cell ultrastructure has had to search through a wide variety of books and journals and at best may only find patchy information. The hospital pathologist, similarly, has up to now had little reason to embark on the exhausting pursuit through the published literature, often in journals which are not on his usual reading list, in search of clues which might lead to a better understanding, or an earlier or more precise diagnosis of human disease. However, in some fields such as the interpretation of the liver, renal and muscle biopsy and the diagnosis of viral and storage diseases and certain tumours the electron microscope is already proving its worth. The scope of electron microscopy will undoubtedly extend into wider areas of diagnostic histopathology. Further, more and more papers in journals of pathology now incorporate the results of ultrastructural studies, and the reader unfamiliar with the range and limitations of electron microscope technology may well be at a loss in attempting to interpret published work.

Today it is not possible to present to the student an up-to-date account of many pathological processes and disease states without discussing ultrastructural changes. Cell injury, cloudy swelling, necrosis, fatty degeneration of the liver, the detoxification of many drugs by the liver, brown atrophy of the heart and lipofuscin, pigmentary disorders of the skin and melanomas, haemorrhage, haemosiderin, erythrophagocytosis and siderosomes, glycogen storage diseases, lipoidoses, Wilson’s disease, silicosis, rheumatoid arthritis and melanosis coli are all better understood by virtue of a knowledge of the underlying fine structural changes.

Correlations between light and electron microscopic findings are singularly interesting and satisfying and I have lost no opportunity of dwelling upon such matters. However, the function of electron microscopy is not simply the resolving of old controversies bequeathed by light microscopists. Electron microscopy is a science in its own right with its practitioners, problems and preoccupations. Many structures such as the endoplasmic reticulum and polyribosomes were unheard of in the light microscopic era, while the structural details of others such as the nucleolus, centrioles and cilia were but poorly resolved. The presence of the nuclear envelope and the cell membrane were suspected and the existence of the Golgi complex doubted. Clearly, alterations in such structures belong to the realms of ultrastructual pathology, and correlations with light microscopy are often tenuous and at times non-existent. Such findings may not have a direct appeal to the light microscopist but such matters cannot be ignored for they have materially altered our thinking about cellular physiology and pathology. Indeed, the main preoccupation of this book is with such matters, but I hope that I have presented this material in a manner which will make interesting reading for both light and electron microscopists.