Table Of ContentHistopathologic Diagnosis of Invasive Mycoses
Written by one of the very few pathologists who has real expertise in this field, this book is a comprehensive key for the iden-
tification of fungal infections in tissues. With updated terminology and presentation, all invasive mycoses types are covered,
detailing their epidemiology, pathology, histomorphology of fungal elements, and differential diagnoses. Each of the separate
fungal groups has a good combination of text and high-quality illustrations, which is a critical feature for clinicians to state the
mycopathological diagnoses.
Key Features
1. Elaborates on the histological observations of both the pathological reaction and the histomorphology of fungal ele-
ments, guiding the reader in the right direction for obtaining a diagnosis of the infection.
2. Includes key observations that can be a game changer for infectious diseases specialists and histopathologists study-
ing the combination of fungal morphology and host response.
3. Follows a logical layout, structure, and organization with a wealth of high-quality illustrations of the various fungi
in tissues elucidated by different stains.
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http://taylor andfrancis.com
Histopathologic Diagnosis
of Invasive Mycoses
Henrik Elvang Jensen
Professor of Pathology
Section for Pathobiology
Faculty of Health and Medical Sciences
University of Copenhagen, Denmark
First edition published 2023
by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742
and by CRC Press
4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor & Francis Group, LLC
© 2023 Henrik Elvang Jensen
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Library of Congress Cataloging‑in‑Publication Data
Names: Jensen, Henrik Elvang, author.
Title: Histopathologic diagnosis of invasive mycoses / by Henrik Elvang Jensen.
Description: First edition. | Boca Raton, FL : Taylor & Francis, 2023. | Includes bibliographical
references and index.
Identifiers: LCCN 2022042619 (print) | LCCN 2022042620 (ebook) | ISBN 9781032306704 (paperback) |
ISBN 9781032306711 (hardback) | ISBN 9781003306177 (ebook)
Subjects: MESH: Invasive Fungal Infections | Mycoses--diagnosis | Mycoses--physiopathology |
Diagnosis, Differential
Classification: LCC RA644.M92 (print) | LCC RA644.M92 (ebook) | NLM WC 450 |
DDC 616.9/69--dc23/eng/20220919
LC record available at https://lccn.loc.gov/2022042619
LC ebook record available at https://lccn.loc.gov/2022042620
ISBN: 978-1-032-30671-1 (hbk)
ISBN: 978-1-032-30670-4 (pbk)
ISBN: 978-1-003-30617-7 (ebk)
DOI: 10.1201/9781003306177
Typeset in Minion
by KnowledgeWorks Global Ltd.
Contents
Preface vii
About the author viii
1 Introduction 1
2 Histopathological classification of invasive mycoses 8
3 Histopathological staining of invasive fungi 16
4 Pathomorphological identification of invasive fungi 27
5 Identification of invasive fungi using in situ techniques 40
6 Glossary of medical mycology 51
7 Aspergillosis 53
8 Fusariosis 68
9 Scedosporiosis and lomentosporiosis 79
10 Mucormycosis 86
11 Entomophthoromycosis 96
12 Pythiosis 102
13 Hyalohyphomycosis, minor 108
14 Phaeohyphomycosis 117
15 Chromoblastomycosis 123
16 Mycetomas 127
17 Candidosis 138
18 Trichosporonosis 149
19 Cryptococcosis 153
20 Blastomycosis 159
v
vi Contents
21 Histoplasmosis capsulati 164
22 Histoplasmosis duboisii 169
23 Paracoccidioidomycosis 174
24 Sporotrichosis 180
25 Talaromycosis 184
26 Pneumocystosis 189
27 Lacaziosis 194
28 Coccidioidomycosis 199
29 Adiaspiromycosis 204
30 Rhinosporidiosis 209
31 Rare mycoses 214
32 Algoses 223
Index 227
Preface
For nearly 40 years, I have had the privilege of receiving The text of this book is separated into 32 chapters and
fungal infection cases from all over the world for diagnostic supplemented by approximately 300 histological figures
consultation. Therefore, I have been able to collect several (i.e., photographs) that illustrate the mycoses described in
cases covering almost every type of invasive fungal infec- each chapter. Following an introduction to invasive myco-
tion in humans and animals. Moreover, I have delivered ses, there are five chapters describing invasive mycoses from
annual lectures and courses on the histomorphological the pathological viewpoint: 1) Histopathological classifica-
diagnosis of mycoses in several countries and arranged pre- tion of invasive mycoses, 2) Histopathological staining of
congress workshops at different world congresses including invasive fungi, 3) Pathomorphological identification of
the International Society for Human and Animal Mycology invasive fungi, 4) Identification of invasive fungi using in
(ISHAM) congresses in Berlin (2012), Melbourne (2015), situ techniques, and 5) Glossary of medical mycology. Next,
and Amsterdam (2018). I have also published more than the particular invasive mycoses and lesions caused by each
100 peer-reviewed papers and chapters in textbooks and pathogen are described in separate chapters. Each of these
co-authored international guidelines for the histopatho- chapters has an updated list of references, which are cited
logical diagnosis of invasive mycoses. As I see it, the major in the text. The text of each chapter has been separated into
problem for pathologists and clinicians is that they are not the following sections: 1) Introduction, 2) Epidemiology, 3)
regularly confronted with fungal infections (in contrast to Pathology, 4) Histomorphology of fungi and related patho-
bacterial and viral infections) unless they are working in gens, 5) Differential diagnoses, and 6) References.
regions where these infections are endemic. Moreover, most I hope that the book, which is dedicated to the histo-
invasive mycoses are symptomatically and clinically non- pathological diagnosis of invasive mycoses and lesions of
specific. Therefore, many invasive mycotic infections are related pathogens, will be not only of value for both medi-
not diagnosed until a tissue sample has been collected and cal and veterinary pathologists and clinicians in general but
processed for histopathology, at which time it is crucial to also a guide to a variety of specialists in different medical
obtain trustworthy data based on the pathology and histo- disciplines, especially those working on infectious diseases,
morphology of the fungal elements present in the sample haematology, oncology, and in critical care units.
(i.e., to reach the correct diagnosis, which is needed for Finally, I would like to express my very special thanks to
appropriate therapy). In recent years, several new molecu- Dennis Brok for his enthusiasm in the editing and layout of the
lar techniques have been developed to diagnose mycoses in many photomicrographs. I am grateful for the skilful assis-
tissue samples; however, these techniques do not differen- tance provided by laboratory technicians Betina G. Andersen
tiate between colonization, dormancy, or contamination and Elisabeth W. Petersen. Thanks also go to Benedicte
with fungi and true tissue invasion. Therefore, confirming Kragh and Nicole L. Henriksen for their editorial work.
that results from molecular techniques are consistent with
the pathology and fungal histomorphology of the tissue is Henrik Elvang Jensen
paramount. Histopathology remains the gold standard for Professor of Pathology
obtaining trustworthy diagnoses of invasive mycoses. University of Copenhagen, Denmark
vii
About the author
Professor Henrik Elvang Jensen has served as a patholo- arranged pre-congress workshops at different world con-
gist for nearly 40 years and has had the privilege of receiv- gresses including the ISHAM congresses in Berlin (2012),
ing fungal infection cases from all over the world for Melbourne (2015), and Amsterdam (2018) on the same
diagnostic consultation. Therefore, he has been able to topic. During the years, he has published more than 100
collect several cases of almost all kinds of invasive fungal peer-reviewed papers and several chapters in textbooks
infections in humans and animals. Moreover, he has, on a and is a co-author of more international guidelines, all
yearly basis, given lectures and courses on the histomor- dealing with the histopathological diagnosis of invasive
phological diagnosis of mycoses in several countries and mycoses.
viii
1
Introduction
Invasive mycoses (i.e., invasive fungal infections) are clinical specimens, including fresh and formalin-fixed tissue
becoming more common in the human population world- specimens. Due to the risk of false negative and false positive
wide for many reasons (1, 2). In particular, more people are results from the cultures as well as the non-culture-based
at risk of acquiring opportunistic fungal infections due to diagnostic tests for mycotic infections, an examination
ageing populations, immunosuppression associated with should always be complemented by histopathology when
transplantation, cancer therapy, immunosuppressive dis- diagnosing fungal infections. This is especially important
eases, and metabolic diseases such as diabetes mellitus (1). for invasive mycoses caused by opportunistic pathogenic
Coronavirus disease 2019 (COVID-19) has contributed to fungi. The diagnosis and management of invasive myco-
a rise in mucormycosis cases, especially in India. Here, the ses still rely on recognizing the interactions between fungi,
predisposing factors include uncontrolled diabetes and sys- related pathogens, and the host (1).
temic corticosteroid treatments, which reduce the inflam- Many non-culture-based techniques are not applicable
mation in the lungs of COVID-19 patients (2). In India, for unusual or rare fungal pathogens, and molecular and
mucormycosis has become known as “black fungus” due to non-culture-based laboratory techniques will only identify
the colonization of blood vessels following invasive infec- the targets that they have been designed to detect. Isolation
tion by the fungi, which results in thrombosis and tissue of fungi from tissues may also be problematic, and several
death (infarct formation) and typically turns the tissue weeks may be needed to obtain results for some pathogens
black. Notably, however, the disease termed “black fungus” (e.g., Histoplasma and Paracoccidioides). Moreover, when a
is caused by hyaline fungi (i.e., members of the Mucorales; mycosis is not suspected clinically (often, they are mistaken
Fig. 1.1) and not by the black fungi (dematiaceous/phaeoid for inflammation due to non-mycotic agents or neoplasms),
fungi), which are the cause of phaeohyphomycosis and the whole biopsy specimen may be fixed in formalin and
chromoblastomycosis (Fig. 1.2). embedded in paraffin wax when used for pathological exam-
Ideally, a fungal pathogen is diagnosed from typical ination. Therefore, portions are not available for culture (5).
clinical symptoms by identifying the fungus within lesions In these cases, histopathological and immunohistological
accompanied by a host reaction and subsequently by iden- techniques together with in situ hybridization may be the
tifying the infectious agent from culture or by molecular only means of establishing an aetiological diagnosis in the
techniques (3). Unfortunately, this is rarely achieved, espe- absence of new biopsies. However, for some fungal patho-
cially for invasive mycoses. Moreover, patients with fungal gens, the formalin-fixed and paraffin-embedded tissue may
infections frequently have other diseases, which may mask be used to identify fungi using PCR techniques (4, 6). As
fungal-related symptoms. Due to the non-specific nature of described above, samples sent for histopathology may not
clinical symptoms including radiological observations, a be suspected of exhibiting a fungal infection. However,
trustworthy diagnosis usually depends on clinical and labo- mycoses should always be considered a possibility for sus-
ratory tests like mycological cultivation, diverse molecular ceptible (e.g., immunosuppressed) patients or patients from
techniques, and the application of histopathology. These locations linked to pathogenic fungi, such as coccidioido-
tests may include detecting the following: 1) fungal antigens mycosis in the southwest United States or Cryptococcus gat-
in fluids such as serum, spinal fluid, bronchoalveolar lavage, tii in southwest Canada on Vancouver Island (1). Although
and urine; 2) anti-fungal antibodies; 3) fungal metabo- the morphology of fungal elements within tissues may pro-
lites such as D-arabinitol; and 4) cell wall markers such as vide a tentative diagnosis, it may be impossible to provide
(1, 3)-β-D-glucan and galactomannan (4). In recent years, an unambiguous diagnosis based on morphological details
several molecular techniques have been developed to diag- alone. This is due to the morphological similarities among
nose invasive mycoses, which may identify fungi rapidly tissue forms of several fungal genera or the presence of
and accurately (1, 4). In particular, polymerase chain reac- sparse or atypical fungal elements (Fig. 1.3) (7, 8).
tion (PCR)-based techniques may be used for the non-cul- Histopathological examinations may complement the
ture-based diagnosis of fungal infections in blood and other diagnosis of diseases caused by fungi and related pathogens.
DOI: 10.1201/9781003306177-1 1
