Current Topics in Pathology – serie

Specialists from diverse disciplines discuss the important topics of Tissue Repair and Fibrosis. The Role of Myofibroblast. The Myofibroblast is implicated in many processes, such as tissue repair,fibrosis, and stromal reaction to tumors. This book seeks to provide an overview of the knowledge accumulated since this cell was first describes 25 years ago. Discussions focusses on three main topics: - Cellular and molecular biology of fibroblast and myofibroblasts - Wound healing: experimental models, and - Human fibrocontracted diseases.

Specialists from diverse disciplines discuss the important topics of Tissue Repair and Fibrosis. The Role of Myofibroblast. The Myofibroblast is implicated in many processes, such as tissue repair,fibrosis, and stromal reaction to tumors. This book seeks to provide an overview of the knowledge accumulated since this cell was first describes 25 years ago. Discussions focusses on three main topics: - Cellular and molecular biology of fibroblast and myofibroblasts - Wound healing: experimental models, and - Human fibrocontracted diseases.

With contributions by numerous experts

In commissioning this volume of Current Topics in Pathology, the editor of the series, Prof. Sir Colin Berry, asked me to produce something "which is aimed at the general pathologist but from the point of view of the neuropathologist who knows what is not being done well". This was easier said than done. Many aspects of neuropathology are encountered only infrequently in general pathology and are best dealt with by re­ ferral of material to a specialist unit. Others need more extensive investigation than is practicable in a general pathology setting. Yet neurological disorders in general are common and are encountered by general histopathologists, paediatric and forensic pathologists on a daily basis, particularly in autopsy practice. In inviting contributions to this volume of Current Topics in Pathology, I therefore biased the con­ tents towards disorders in which the conduct of the autopsy and the initial approach to neuropathological investigation are of critical importance in making the diagnosis. The authors all have a wealth of experience and expertise and I believe that this is reflected in their approach, which is both personal and practical. Indeed, the emphasis in this book is very much on the provision of practical advice. All of the chapters contain guidelines on the conduct of autopsies as well as infor­ mation on the macroscopic and basic histological assessment of the nervous system in the relevant disorders.

General pathologists see many biopsies from transplanted organs but few are in large enough centres so that this forms the bulk of their work. The book describes the changes which can be observed in transplantation in all of the major organ systems that are routinely transplanted and there are accounts of the pathology of infections and of the immunological difficulties that are faced by these patients. The volume will be a valuable guide for those who wish to braoden their knowledge in this field.

In recent years, a series of excellent textbooks have been published dealing with pathology of the thyroid gland. The present volume of CURRENT TOPICS IN PATHOLOGY provides further information for both pathologists and clinicians interested in the thyroid gland. The contributions deal with surgical pathology of the thyroid as well as with basic aspects of thyroid metabolism, hormone transport, and growth factors in thyroid cells. The topics covered in this book should mainly be considered as adjuncts to common textbooks on thyroid pathology. The contributions should help pathologists in their routine diagnosis and should stimulate further thyroid research.

The early development of the mammalian embryo belongs to a period which, for the student, provides the particularly deep fascination connected with the processes of germination of the fIrst tender buds of life. Moreover, developmental biology encompasses a very large part of biology; if broadly dermed - almost all of it. The same is true for the fIeld of pathology if the manifold possibilities of disorders of the orderly arranged pathways of developmental processes are considered. Normal development in its earliest steps - and it would be diffI­ cult to see it otherwise - means the functioning of very intricate systems of complex inter­ dependent cycles controlled by structural, genetic, physiological and biochemical determi­ nants. However, disturbances interfering with them in their very different ways, can lead to fetal death, disorders of growth and differentiation, malformation and disease, sometimes as late as in the next generation or later. This is, indeed, the concern of the pathologist to whom and to whose interest in developmental pathology, this book is dedicated. The outlines of the present volume were conceived at a symposium on "Control of early em­ bryogenesis and factors responsible for failure of embryonic development" held May 1-4, 1974 in Travemtinde and sponsored by the Deutsche Forschungsgemeinschaft. Almost fIfty active participants attended this conference. At the time and in keeping with the purpose of the conference, publication of the proceedings was not envisaged.

Immunology, in all its facets of immunochemistry, humoral immunity, cellular immunity, immunodiagnosis, and immunotherapy, is currently the most rapidly advancing discipline of clinical and experimental oncology. But as in most developing subjects, it is continually beset with problems of methodology and nomenclature, both of which are often intertwined. Indicative of this problem are our circular definitions of antigen and antibody. Another fre­ quent problem is the use of the words "specific" and "associated" when characterizing re­ actions to tumors or the antigenic properties of neoplasms. When applied to cancer, these terms are obviously very dependent upon the methods used to demonstrate these qualities. Indeed, the very diverse nature and multitude of types of cancer preclude our making gen­ eralizations or categorical statements regarding tumor "specificity. " Similar problems arise when one considers that many antigens found in malignant tumors share certain properties with embryonic or fetal tissues. First, these observations emphasize a lack of true tumor specificity, for which reason the category of oncofetal antigens has been established. Second, whether or not such antigens are truly oncofetal depends upon the method of detection used, and it has been found that here too specificity decreases as the antigen assay increases in sen­ sitivity. Thus, whether substances can be truly oncofetal in nature still remains a matter of debate, and such terms must therefore be used in an operational sense.

In 1967 cardiologists in Switzerland were struck by the sudden increase in the number of cases of so-called primary pulmonary hypertensive disease (PPHD). Up untill966, the cardiology centers in Switzerland had not seen more than one or two cases a year, but this number suddenly multiplied by ten or twenty times. At the June 1968 meeting ofthe Swiss Society of Cardiology, Gurtner et al. (1968b) presented a paper which raised the question whether the vascular types of cor pulmonale had increased. They also raised the question about the possible responsibility of environmental factors, such as toxins or drugs, in causing this increase. Krrihenbuhl et al. (1968) first suggested the possible responsibility of anorexigenic drugs, but no proof was provided. Soon after this, the cardiology team in Bem (Gurtner et al., 1968a) published their report, which resumed and completed the above-mentioned prelim- inary communication; 31 cases of PPHD, among which 17 had taken an anorexigenic drug, aminorex fumarate (Menocil, Cilag), were reported.The importance of this work was soon recognized and it was followed by several meetings (in Vienna, Hannover, and Burgenstock) and two round tables sponsored by the Swiss Society of Cardiology (in Montreux and Basel).

(North American) Blastomycosis is caused by the dimorphic fungus Blastomyces dermati- tidis, first described by Gilchrist andStokes in 1896. The perfect stage was grown by Mc- Donough and Lewis in 1967 and is known as Ajellomyces dermatitidis. In the body and on appropriate media at 37 C, the organism presents itself as a round, thick-walled budding yeast cell, characteristically with a broad porus between mother and daughter cells. The yeast cell is multinucleated. For many years, North America was assumed to be the only place where blastomycosis was found, but recent demonstration of indigenous African cases changed this impression (Emmons et al., 1964). Within the United States, more cases are seen in Kentucky, Ohio, the Carolinas, Illinois, Michigan, Wisconsin, Iowa, Tennessee, Arkansas, and the Virginias than in the remainder of the country (Chick, 1971). In Mexico, occasionally, and in the provinces of Canada adjacent to the endemic areas of the United States, endemic blasto- mycosis has been recognized. Soil has been long suspected as the habitat for the fungus, but recovery from soil has seldom been successful (Denton and Di Salvo, 1964).The primary infection is, as a rule, pulmonary with frequent secondary foci in skin, bone, male genital system, and, eventually, spares no organ in widely disseminated cases. The rare cases of primary cutaneous blastomycosis are consequences of accidental percutaneous laboratory infection. These can be clinically easily differentiated from the average case of secondary hematogenous spread to the skin (Landay and Schwarz, 1971).

1. Concepts on the Causal Genesis of Human Intestinal Tumors The action of chemical substances has a significant role in the genesis of human tumors. It is assumed that most human tumors are induced by exogenous chemical noxae (Schmahl, 1970;Heidelberger, 1975; and others). In the course of intensive efforts to discover the principles of tumor etiology, important insights have resulted in recent years. These are that chemical carcinogens do not only arise as products of our tech­ nological civilization, but that they also occur in nature as potent solitary carcinogens and cocarcinogens (e. g. , as plant products). For review, see Hecker (1972) and Preuss­ mann (1975). Not only "complete" carcinogens are significant for the genesis of tu­ mors, but also substances which are first transformed to the actual carcinogenic com­ pound in the organism (Schmahl, 1975). The causal significance of exogenous noxae in carcinogenesis is indicated by the fact emphasized by Bauer (1963) that malignant tumors occur predilectively at those sites in the body which are in direct or indirect contact with the environment. This applies especially to the intestinal tract.

The morphological behaviour of leucocytes* leaving the blood has been studied for more than a hundred years and can be described in some detail, but the mechanisms involved are for the most part still unclear. Following an inflammatory stimulus, dy- namic changes occur in small blood vessels near the inflamed site and are followed by margination of leucocytes and by their adherence to the endovascular surface of endo- out of the vessel in the gaps between endothelial thelial cells. The leucocytes migrate cells and move towards the noxious stimulus, directed presumably by chemotactic gra- dients. Having reached the gradient source, they may engage in phagocytosis, killing and digestion of micro-organisms or of damaged tissue. In this review, we deal with the adhesive properties of leucocytes, which have US1,l;ll- ly been measured in vitro, and with their possible relevance to the leucocyte-endo- We also deal with the locomotion of leucocytes, its machinery thelial cell interaction.

Few subjects in gynecology, let alone in medicine in general, have provoked such inter­ est or study as cervical cancer. Although the wealth of monographs and books publish­ ed on the subject would seem to obviate the need for more, the great advances made in the medical sciences and in gynecological experience and techniques in recent years call for, if not require, a new book on cervical cancer to bring together the latest ideas and trends in its methods of study, diagnosis, and treatment. Although precancerous lesions have become more common, the number of women developing invasive cervical carcinomas has not increased, owing in part to programs of patient education, in part to screening examinations sponsored by the government. The gynecologist is now able to detect with well-tried and proved techniques precan­ cerous states of the cervix, and to treat these effectively before they become invasive cancer. Accordingly, recent interests in cervical cancer have shifted from the classic descrip­ tion of invasive carcinoma to newer studies of cause, diagnosis, therapy, and terminol­ ogy of its precursors. As the reader will learn, epidemiological studies as guides for the future account for, and justifiably so, an important part of this book. New knowledge about changes in the morphology of cervical carcinoma confirms its dependency on hormonal stimulation. Furthermore, modem experiences serve to explain which therapy is best. Overlapping of concepts and opinions between some chapters could not be avoided.

The enormous importance of the diseases of the locomotor system in all populations and the large component of general clinical practice which they represent have not, in the past, been matched by an appropriate pathological effort. Increasing expectation of an active and long life has resulted in a great increase in specialisation in Rheumatology and rehabilitation of those with crippling diseases. This volume presents many of the pathological advances that have followed this clini­ cal interest, beginning with reviews of changes in biological materials obtained by in­ vasive investigation of joints, continuing with an account of therapy Goint replace­ ment) and also describing a "new" hazard - hyperbaric injury. Experimental models of joint disease are also described as are other entities such as crystal deposition dis­ ease. A detailed consideration of the electron microscopy of bone tumours is included since this data is not widely available in current texts. Finally, the role of the HLA system in rheumatic disease is included, indicating the value of close co-operation between clinician and pathologist in defining and link­ ing the various rheumatic syndromes. London Contents Examination of Synovial Fluid. With 9 Figures P.A. Revell ........................................... . The Synovial Biopsy. With 20 Figures F. Eulderink. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25 Tissue Reactions to Joint Prostheses and the Products of Wear and Corrosion. With 20 Figures P.A. Revell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73 Bone and Joint Diseases in Workers Exposed to Hyperbaric Conditions.

The extension of clinical, endoscopic, and bioptic lung examination proce- dures and function analyses has resulted in more detailed knowledge of the pathology and pathogenetic factors of numerous bronchopulmonary dis- eases. Morphometric, histochemical, ultrastructural, and immunologic ex- amination methods are now constituent parts oflung pathology. This volume, written by numerous experts treats the special subjects of bronchial system pathology, pulmonary circulation, inflammatory and fibrous lung tissue diseases, and borderline areas oflung tumors. With regard to the results, some of which have been obtained experimentally, great im- portance has been attached to the presentation of the applied morphometric, histochemical, immunologic, and ultrastructural investigation methods. The book is intended to improve and extend the discussion between clinicians and morphologists. For the majority of lung diseases, which are discussed in detail in chapters dedicated to the morphological aspects, definitive cat- egorization and assessment of the findings are only possible if clinical picture and disease progress are known.Furthermore, the fmdings documented here, which can be grasped morphologically, provide important indications for the evaluation and classification of syndromes and for prophylactic clinical measures. I would like to thank Professor Grundmann, who initiated this volume, and the contributing authors. Special appreciation and recognition are due the staff of Springer-Verlag for their cooperation and for the organization, printing, and perfect illustration of the contributions. Bochum K. -M. Milller Contents Methods and Results of Postmortem Studies of Airway Dynamics in Normal Lungs and Lungs with Minimal Obstruction. With 11 Figures W. Wierich ...

In any histopathology department, cutaneous biopsies form the major part of the workload. In many instances these may be readily dealt with by experienced pathologists and their documentation represents an essential step in organising therapy. However, in a number of areas dramatic changes have occurred in dermatopathology. The rapidly changing incidence of pigmented lesions of the skin and the availability of diagnostic cell markers in the complex cutaneous lymphomas have meant that for many pathologists a review in these fields will be valu- able. The distribution and pattern of skin pigmentation may allow us to make important assertions and draw importantconclusions about the genetics of skin disease, but also about human variability. Cutane- ous vasculitis is a difficult problem where clinicopathological consulta- tion is vital in diagnosis and the review presented has been written with this verymuch in mind. In the same way, many diagnostic difficul- ties exist in assessing buttous lesions in the skin and for this reason a review was invited.Finally, our understanding of certain skin diseases has been radical- ly altered by knowledge of the dynamics of the changes seen, a field which has also beenstudied with advantage inother systemsin patholo- gy. This volume is intended as an aide to those many pathologists and dermatologists who, often together, are responsible for the pro- vision of clinical care in this demanding field. London C. L. BERRY Contents Melanoma and Other Melanocytic Skin Lesions. With 8 Figures D. WEEDON . Cutaneous Vasculitis.

Increasing specialisation in pathology reflects the progressive changes in medical practise. The advent of a specialist with a new interest in a hospital or clinic may present the pathologist with a need to extend his or her knowledge to be able to work closely with the clinical practi­ tioner in order to provide adequate clinical care. Some sub-specialisations are long established, such a one is neu­ ropathology. However, an exclusive specialist practise is generally con­ fined to neurosurgical centres and much neuropathology is of necessity, executed by geneni.l pathologists. The areas covered by this volume are those which are commonly managed by the generalist. Professor Adams' account of how the skull and brain should be examined here will give confidence to many by defining a good technique and the careful description of various kinds of vascular injury lesions resulting from raised intracranial pressure will help to clarify repeated difficulty. More subtle forms of damage are also considered in detail. Professor Weller provides a detailed account of how the central nervous system may be examined in a way which permits all of us to prepare material which will allow adequate investigation of central nervous system disease and the proper examination of peripheral nerves. This chapter will become a "handbook" and will be of interest to those in training and established practitioners. Muscle biopsy is also dealt with; this is an area of investigative concern for many gener­ alists. The role of that singular neuropathological technique is very clearly emphasized.

New methods in immunocytochemistry and hybridization techniques enable the pathologist active in diagnosis to clarify more effectively problems in the classification and prognosis of tumors. By adopting these methods into his diagnostic repertoire it will be possible to create a closer, more productive connection between morphological diagnosis and clinical work. This volume gives the reader an up-to-date general survey from international experts of the method, technique and practical application of these new procedures.