Diagnostic Pathology of Infectious Disease E-Book

Richard L. Kradin

• Publisher: Elsevier
• Year: 2017
• ISBN:
  9780323508674
• Edition: 2
• Topic: Medicine
• Subtopic: Pathology

Comprehensive and up to date, the Second Edition of Diagnostic Pathology: Infectious Disease, by Dr. Richard Kradin, is an invaluable tool for the accurate diagnosis of any infectious disease?from the common to the most challenging. The organ-based format makes it an especially useful tool for surgical pathologists' daily diagnostic and management issues. High-quality, full-color illustrations and differential diagnosis tables accompany each lesion, clearly depicting how to recognize the morphology of organisms and the spectrum of histological responses that they may cause.

• Addresses the most difficult diagnostic issues that practicing or trainee surgical pathologists face when handling infectious disease tissue specimens.
• Highlights morphological characteristics and landmarks of tissue samples for easy access to information necessary for signing out a specimen.
• Emphasizes the host responses critical in differential diagnosis to serve as a second opinion when non-infectious diagnoses mimic and confound the diagnosis of infection.

• Completely revised with the latest diagnostic support and hot topics in the field:
• • A new chapter on novel techniques in microbiology
  • A new chapter on eye infections
  • New coverage of immunohistochemical staining and other molecular diagnostic techniques
  • New discussions of human papillomavirus, a critical tool in predictive cancer screening
  • New information on infections in the immunocompromised host and related special considerations

1

Introduction

Richard L. Kradin

Infection continues to account for the majority of human diseases. Substantial advances have occurred since the last edition of this textbook in the field of infectious disease. Technological advances have improved diagnostic yields for a variety of diseases. New diseases such a Middle East respiratory syndrome and the Zika virus epidemic have gained worldwide attention. Global travel and the migration of large populations from Africa and the Middle East have brought populations that were previously isolated into contact. The spread of Ebola virus from 2013–2016 from areas of Africa to travelers returning to the United States highlights this issue.

Increasing numbers of therapeutic agents that modify the immune system have led to major breakthroughs in the treatment of hepatitis C, but new antiinflammatory drugs have also increased the numbers of patients who are functionally immunosuppressed. Furthermore, the phenomenon of global warming threatens to foster conditions for new and reemergent diseases.

In response to the challenge of infection, surgical pathologists must continue to render diagnoses from both cytology specimens and biopsies. Both noninvasive and minimally invasive approaches have been developed that call upon the practicing pathologist to opine with respect to smaller samples. Furthermore, in addition to establishing the cause of infection, pathologists must consider a range of disorders in their differential diagnosis with respect to underlying disorders that can mimic the histology of infection.

Whereas the microbiology laboratory and infectious disease specialists have become increasingly skilled in the diagnosis of infectious diseases, the same unfortunately has not been uniformly true of surgical pathologists, who may continue to defer to their clinical colleagues in this area. This choice is fostered by the frustration of trying to identify small numbers of small pathogens and difficulties in diagnosing organisms with accuracy. Taken together, the time, effort, and expense of diagnosing infection can at times seem nongratifying for a busy surgical pathologist.

Nevertheless, the ubiquity of infectious diseases makes it highly unlikely that surgical pathologists can avoid being confronted with the diagnosis of infection in practice, so that it behooves them to be aware of the intricacies of how infection manifests in situ. Fortunately there have been advances in this regard that will assist the surgical pathologist in establishing an accurate diagnosis. Indeed the primary aim of this new edition of the Diagnostic Pathology of Infectious Disease continues to be to rekindle the interest that most surgical pathologists once held for the pathologic diagnosis of infection.

The present text continues to be organized unlike most other textbooks of infectious disease pathology. The contributors continue to be subspecialists in surgical pathology who have established expertise in diagnosing the infections that primarily affect their organ system, and for this reason the text is still organized based on organ system rather than as a litany of specific infectious organisms. As a consequence, the reader will be exposed to these disorders as they are encountered in a subspecialty practice of pathology. The nuances of infectious diagnoses are presented together with their differential diagnosis, so that the reader can better glean from the text how to narrow the differential diagnosis in practice.

The text includes a preliminary discussion of the types of inflammatory responses that can be elicited by various microorganisms and how host defenses modify these responses. There is a detailed explanation of how to apply histochemical stains differentially to narrow the differential diagnosis with respect to morphology of microbes. Advances in the application of immunohistochemical stains, in situ hybridization, and polymerase chain reaction are discussed prior to a discussion of the infections encountered in the major organ systems. New chapters that specifically focus on the role of the microbiology laboratory, as well as specific infections of the orbital region, have been added to this edition.

Because many microorganisms can affect a variety of human tissues, there is necessarily redundancy within the text with respect to their description. However, on balance, the superimposed constraints of tissue microanatomy lead to diversity with respect to the morphologic appearances of infection at different sites, so that repetitiveness in this regard has a didactic purpose. In addition, for the busy practitioner, it is possible to use this text as a single resource with respect to infection in an organ system of specific interest, in a case-dependent fashion, without having to consult a series of subspecialty texts.

As conceived, the present text is still designed to be functionally complete but not encyclopedic, and there is much information with respect to the clinical, epidemiologic, or mechanistic bases of infection that will not be found here. In addition, some exotic parasitic disorders have not been included. Other texts that include these data are available, and at times a pathologist may need to refer to them. However, for the most part, all that is required to diagnose the vast majority of infections can be found within the present revised text.

The diagnosis of infection, comparable to that of neoplasia, requires experience. The morphologic appearances of infection are as diverse as those of malignancy. Because the variations encountered are virtually inexhaustible, no textbook can expect to illustrate all of what is encountered in practice. Indeed, at times textbooks tend to focus on one aspect of an infection and the inexperienced pathologist in this area may be misled in expecting to encounter examples that are comparable to those within selected illustrations. This text cannot replace experience. However, after the diverse appearances of infection are appreciated and accepted, the surgical pathologist may derive substantial pleasure from pondering their fine distinctions and take pride in the growing sense of competence that develops from his or her experience in this area.

2

General Principles in the Diagnosis of Infection

Richard l. Kradin, Vikram Deshpande, A. John Iafrate

Sampling

Diagnosing Infection In Situ

Potential Limits of Biopsy Interpretation

Classification of Patterns of Infection

Histochemical Stains

Hematoxylin and Eosin

Gram Stain

Silver Impregnation

Fungal Stains

Acid-Fast Bacteria Stains

Connective Tissue Stains

Giemsa Stains

Mucicarmine

Melanin Stains

Viral Inclusion Body Stains

Immunohistochemical Methods

Molecular Diagnostics

In Situ Hybridization

Polymerase Chain Reaction

Branch Chain In Situ Hybridization

The identification of infection in biopsied tissues is the primary responsibility of the surgical pathologist. In an age when both noninvasive and minimally invasive approaches and techniques have increased, it is important to revisit the role of the biopsy in the diagnosis of infection (Box 2.1). Isolating microorganisms in the microbiology laboratory is a sensitive and accurate approach to their identification, but it has several important limitations. First, it cannot distinguish infection from colonization, nor can it ascertain the significance of the isolated organism. Only the presence of an organism in situ, together with an expected inflammatory response by the host, constitutes acceptable evidence of its role in infection.

Box 2.1

Role of the Surgical Pathologist in the Diagnosis of Infection

Establish morphologic diagnosis of infection

Assess immunocompetence of the host

Narrow the differential diagnosis of possible pathogens

Confirm results of microbiologic cultures

Refute the relevance of microbiologic cultures

Establish diagnosis unrelated to infection

Identify concomitant infection in a primary inflammatory or neoplastic disorder

Identify new pathogens

For example, consider how to interpret the clinical significance of a fungus isolated from the airways of a patient with bronchiectasis who also has a new pulmonary infiltrate in the setting of immunosuppression. Is the fungal isolate the likely cause of the opportunistic infection, or might it be a benign commensal? Studies have attempted to address this question¹ with guidelines formulated for practice, but these are indeed merely “guidelines” because only identification of a potential pathogen within a site of infection can provide substantive evidence that the fungus is an invasive pathogen. For this and other reasons to be addressed in this text, the pathologic diagnosis of infection is a critical element in formulating optimal therapy.

Sampling

Tissue sampling is fundamentally important in the diagnosis of infection. All excised tissues should be considered as potentially infective. This approach fosters due diligence with respect to the possibility of contagion, as well as thoughtful concern as to how the tissues will be handled to optimize the chances of establishing an accurate diagnosis (Box 2.2). Samples of excised tissues should be harvested by sterile technique and sent to the micr...