Untitled
Untitled
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Clinical Dermatopathology
Atlas of Clinical
Dermatopathology
Infectious and Parasitic
Dermatoses
Editor-in-Chief
Günter Burg MD
Department of Dermatology
University of Zurich
Zurich
Switzerland
Associate Editors
Heinz Kutzner MD
Department of Dermatology
Institute of Dermatopathology
Friedrichshafen
Germany
Werner Kempf MD
Kempf und Pfaltz Histologische Diagnostik, Zurich, Switzerland
Department of Dermatology
University of Zurich
Zurich
Switzerland
Omar Sangueza MD
Departments of Pathology and Dermatology
Wake Forest School of Medicine
Winston‐Salem
NC, USA
This edition first published 2021
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Library of Congress Cataloging‐in‐Publication Data
Names: Burg, Günter, author. | Kutzner, Heinz, author. | Kempf, Werner,
author. | Feit, Josef, author. | Sangueza, Omar P., author.
Title: Atlas of clinical dermatopathology : infectious and parasitic
dermatoses / Editor-in-chief Günter Burg ; associate editors, Heinz Kutzner,
Werner Kempf, Josef Feit, Omar Sangueza.
Description: Hoboken, NJ : Wiley-Blackwell, 2021. | Includes
bibliographical references and index.
Identifiers: LCCN 2020028076 (print) | LCCN 2020028077 (ebook) |
ISBN 9781119647065 (hardback) | ISBN 9781119647089 (adobe pdf) |
ISBN 9781119647058 (epub)
Subjects: MESH: Skin Diseases, Infectious | Atlas
Classification: LCC RL201 (print) | LCC RL201 (ebook) | NLM WR 17 | DDC
616.5/2–dc23
LC record available at https://lccn.loc.gov/2020028076
LC ebook record available at https://lccn.loc.gov/2020028077
Cover Design: Wiley
Cover Images: © Günter Burg, © Heinz Kutzner, © Werner Kempf
Set in 10/13pt Meridien by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1
To our families and teachers
Contents
Forewordxi
1.4 Mycobacterial Infections 29
Acknowledgmentsxiii
1.4.1 Tuberculosis Cutis 29
1 BACTERIAL INFECTIONS 1 1.4.1.1 Primary
1.1 Staphylococcal and Tuberculosis of
Streptococcal Infections 2 the Skin 30
1.1.1 Impetigo Contagiosa 2 1.4.1.2 BCG Vaccination
1.1.2 Ostiofolliculitis (Bockardt) 4 Granuloma30
1.1.3 Pseudomonas (Gram‐ 1.4.1.3 Differential
Negative) Folliculitis Diagnosis: Lupus
(Whirlpool/Hot Tub Miliaris
Dermatitis)5 Disseminatus
1.1.4 Perianal Streptococcal Faciei (LMDF) 31
Dermatitis6 1.4.1.4 Lupus Vulgaris (LV) 32
1.1.5 Differential Diagnosis: 1.4.1.5 Variant:
Acne Papulopustulosa 7 Tuberculosis
1.1.6 Differential Diagnosis: (Lupus) Cutis
Pseudofolliculitis Barbae 8 Verrucosa34
1.1.7 Ecthyma Gangrenosum 8 1.4.1.6 Variant:
1.1.8 Abscess 10 Tuberculosis
1.1.9 Furuncle 11 Cutis Colliquativa
1.1.10 Carbuncle 12 (Scrofuloderma)35
1.1.11 Erysipelas (Cellulitis) 13 1.4.1.7 Lichen
1.1.12 Phlegmon 15 Scrofulosorum
1.1.13 Necrotizing Fasciitis (Tuberculosis
(Streptococcal Gangrene)° 17 Cutis Lichenoides) 36
1.1.14 Hidradenitis Suppurativa 1.4.1.8 Papulonecrotic
(Acne Inversa) 17 Tuberculid37
1.2 Other Bacterial Infections: 1.4.1.9 Erythema
Corynebacteria18 Induratum
1.2.1 Erythrasma 18 Bazin38
1.2.2 Pitted Keratolysis 1.4.2 Atypical Mycobacteriosis:
(Keratoma Sulcatum) 19 Fish Tank (Swimming
1.2.3 Trichobacteriosis Pool) Granuloma 39
(Trichomycosis) Palmellina 20 1.4.3 Leprosy (Hansen Disease) 40
1.2.4 Erysipeloid 21 1.4.3.1 Tuberculoid
1.2.5 Anthrax 22 Leprosy41
1.2.6 Nocardiosis 23 1.4.3.2 Borderline Leprosy 42
1.2.7 Rhinoscleroma 24 1.4.3.3 Lepromatous
1.3 Rochalimaea/Bartonellae 25 Leprosy43
1.3.1 Bacillary Angiomatosis 1.4.3.4 Variant: Histoid
and Cat Scratch Disease 25 Lepromatous45
1.3.2 Verruga Peruana 27 1.4.3.5 Variant: Erythema
1.3.3 Differential Diagnosis: Nodosum
Pyogenic Granuloma (Lobular Leprosum46
Capillary Hemangioma; 1.4.4 Buruli Ulcer 47
Botryomycosis)28 1.5 Actinomycosis 48
vii
viii Contents
°no pictures
Foreword
A myriad of microbes live in us, on us, and Since CFs and HFs are nonspecific in
around us in a symbiotic or parasitic relation many cases, searching for bacterial or
ship, fighting with our local cutaneous or sys fungal pathogens using special stains,
temic defense mechanisms. Without claim of microbiologic cultures, or PCR probes
being comprehensive or of following standard may be helpful tools in confirming the
biologic taxonomies, this third volume on diagnosis.
clinical dermatopathology contains more
Editor‐in‐Chief
than 100 infectious and parasitic dermatoses,
Günter Burg
the clinical features (CFs) and histological fea
tures (HFs) of which are described with short Associate Editors
concise text and information in bullet‐point Heinz Kutzner
style. They are illustrated in over 600 high‐ Werner Kempf
resolution pictures with annotations. A final Josef Feit
chapter deals with sepsis. Omar Sangueza
xi
Acknowledgments
xiii
C H APT ER 1
Bacterial Infections
CHAPTER MENU
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
1
2 CHAPTER 1: Bacterial Infections
Multiple pustular
lesions with
crusts in the face
Subcorneal pustule,
spongiosis, and
edema in the upper
dermis (right)
Subcorneal pustules
filled with neutrophils ,
Subcorneal blister,
acantholysis, slight
acanthosis,
inflammatory
infiltrate in the upper
dermis
Acantholysis of
granular layer.
Superficial blister
with neutrophils
Inset
Gram-positive
bacteria (cocci)
within the blister
1.1.2 Ostiofolliculitis (Bockardt)
Small dome-shaped
pustules, involving
the upper
part of the follicle
Accumulation of
neutrophils within the
ostium of the follicle
Disseminated
pustules on the
buttocks and the leg
Intra-and perifollicular
mixed cellular
infiltrate ,
HF: Reference
• Follicles, with follicle walls partly ruptured Mazza, J., Borkin, M., Buchholz, R., & Deleo,
• Acneiform intra‐ and perifollicular V. (2013). Pseudomonas folliculitis con-
inflammatory infiltrate, predominantly tracted from rubber gloves: A public health
neutrophilic concern. J Am Acad Dermatol, 69(2),
• Plasma cells and eosinophils may be e93–94.
present Yu, Y., Cheng, A. S., Wang, L., Dunne, W. M., &
Bayliss, S. J. (2007). Hot tub folliculitis or hot
DD: Acne; other bacterial, fungal (pity-
hand‐foot syndrome caused by Pseudomonas
rosporum) or viral (HIV‐associated) folli-
aeruginosa. J Am Acad Dermatol, 57(4),
culitis; demodex folliculitis.
596–600.
Circumscribed
perianal erythema
(left)
Nonspecific
lymphocytic infiltrate
with some eosinophils
and plasma cells
(middle and right)
This is caused by group B β‐hemolytic strep DD: Erysipelas; fungal infection; contact
tococci. Similar symptoms may more fre- dermatitis; psoriasis; Langerhans cell his-
quently be caused by perianal allergic, tiocytosis; zinc deficiency/acrodermatitis
toxic, seborrheic, or atopic dermatitis. enteropathica; intertrigo; lichen planus.
CF: Circumscribed pruritic eczematous
erythema in the gluteal and perianal Reference
region, mostly by bacterial dissemination
Kahlke, V., Jongen, J., Peleikis, H. G., &
from the upper respiratory tract, most
Herbst, R. A. (2013). Perianal streptococcal
commonly in young children but also in
dermatitis in adults: Its association with
adults.
pruritic anorectal diseases is mainly caused
HF: Variable nonspecific histologic fea- by group B Streptococci. Colorectal Dis,
tures. Diagnosis depends on positive swab 15(5), 602–607.
for β‐hemolytic streptococci. The rationale Serban, E. D. (2018). Perianal infectious der-
for taking a biopsy may lie in the exclu- matitis: An underdiagnosed, unremitting
sion of other conditions (differential diag- and stubborn condition. World J Clin Pediatr,
noses; see below). 7(4), 89–104.
1.1: Staphylococcal and Streptococcal Infections 7
Acne
papulopustulosa
(left)
Pseudofolliculitis
barbae (right
Ruptured
pilosebaceous
unit
Neutrophilic
infiltrate (left)
and granulomatous ,
reaction with
multinucleated cells
(right)
Figures 1.1.5 and 1.1.6 Differential Diagnosis: Acne Papulopustulosa and Pseudofolliculitis Barbae.
1.1.7 Ecthyma Gangrenosum
Initial erythema,
pustule, and
dermal inflammation
on the leg, evolving
into necrotic
ulceration (left)
Superficial ulceration
with necrosis and
dermal inflammatory
infiltrate (right)
Neutrophilic dermal
infiltrate, spreading
between collagen ,
bundles (“Indian file”)
(right)
Signs of septic
vasculitis:
thrombosed vessel
with paucicellular
infiltrate and
perivascular bacteria
(anti-staphylococcal
immunostain)
The term ecthyma is used in various seman- • Signs of septic vasculitis may be pre-
tic combinations, which show different sent (thrombosed postcapillary venules
etiologies: Ecthyma simplex is a superficial with very sparse adjacent inflamma-
ulcerating form of impetigo with “punched‐ tory infiltrate)
out” sharp borders. Ecthyma contagiosum • Gram‐positive cocci, often adjacent to
(orf) is caused by parapox infection (orf thrombosed vessels
virus; see below). • Sharply circumscribed “punched‐out”
Ecthyma gangrenosum is an ulcerative deep ulceration
variant of septic vasculitis caused by group • Debris and necrotic material within the
A streptococci or S. aureus. It commonly is ulcer
found in tropical areas, in children, or in • Mostly neutrophilic dermal infiltrate
patients with impaired immunity. DD: Ulcerating suppurative inflammation
CF: Starting with diffuse erythema, followed and septic vasculitis of other causes; reac-
by massive edema, pustulation and rapid tive perforating dermatosis (acute prurigo).
ulceration, often as sequela to minor trauma;
rapid evolution into sharply circumscribed Reference
deep ulceration with distinct borders. The
Greene, S. L., Su, W. P., & Muller, S. A. (1984).
limbs of children (buttocks) are preferentially
Ecthyma gangrenosum: Report of clinical,
affected. Dissemination may occur (requiring
histopathologic, and bacteriologic aspects of
rapid response with antibiotic treatment!). eight cases. J Am Acad Dermatol, 11(5 Pt 1),
Healing with scar formation. 781–787.
HF:
• Initially massive edema with subtle
mixed inflammatory infiltrate
10 CHAPTER 1: Bacterial Infections
1.1.8 Abscess
Pseudocystic
dermal necrosis with
neutrophils, debris,
and bacteria
(antistaphylococcal
immunostain)
(below left and right)
Figure 1.1.8 Abscess.
CF: Mostly painful and highly inflamed HF: Intradermal necrosis and massive sup-
intradermal accumulation of pus, opening puration with intradermal pseudocystic
and draining to the surface. accumulation of neutrophils and debris.
DD: Furuncle; carbuncle; ecthyma.
1.1: Staphylococcal and Streptococcal Infections 11
1.1.9 Furuncle
Dermal and
intrafollicular
abscess formation
Necrosis, debris,
predominantly
neutrophilic intra-and
perifollicular infiltrate
Figure 1.1.9 Furuncle.
1.1.10 Carbuncle
Carbuncle showing
pus from multiple
notches and draining
pores (left)
Dermal and
intrafollicular infiltrate
with necrosis,
neutrophils and
multinuclear giant ,
cells next to the
follicle (top right and
bottom)
Inset: mulinucleated
giant cells
Figure 1.1.10 Carbuncle.
1.1.11 Erysipelas (Cellulitis)
Edema, dilated
lymphatic vessels
(middle), and
sparse neutrophilic
infiltrate between
collagen bundles
(bottom)
Erythematous
swelling and blister
formation on the arm
Subepidermal
blister, fibrosis,
necrosis with diffuse
and perivascular
neutrophilic infiltrate
(right)
Dilated lymphatic
vessels and
perivascular
neutrophilic infiltrate
Perivascular
infiltrate, also
involving the vessel
lumen and vessel
wall (right)
CF: Following infection with streptococci involvement, necrosis and blister forma-
type A via interdigital maceration or tion, which may be hemorrhagic.
small defects, sharply demarcated periph- Associated general symptoms are fever,
erally spreading warm and painful ery- chills, and swelling of the regional lymph
thema develops along superficial lymph nodes. Erysipelas has a tendency to recur.
vessels, preferentially on the lower legs, HF:
arms, or face. Lymphedema is a predis- • Dermal edema
posing factor. Nosologic relationship • Dilated capillaries and lymphatic vessels
exists to phlegmon and necrotizing cel- • Sparse mixed interstitial and perivas-
lulitis. Cellulitis is a maximal variant of cular infiltrate with neutrophils and
erysipelas with dermal and subcutaneous eosinophils
1.1: Staphylococcal and Streptococcal Infections 15
• Neutrophils in vessel walls and dilated DD: Contact dermatitis, rosacea, lupus
lymphatic vessels erythematosus, seborrheic dermatitis: in
• Occasionally subepidermal blister these conditions, fever and chills are char-
formation acteristically lacking.
• Fibrosis in recurrent cases
1.1.12 Phlegmon
Edematous swelling
and inflammation
with erosion and
ulceration on the
hand (left)
Necrosis of
epidermal and
superficial dermal
structures
(upper right and
middle)
Necrotic changes of
the dermis with
diffuse neutrophilic
infiltrate
Figure 1.1.12.1 Phlegmon.
16 CHAPTER 1: Bacterial Infections
Subepidermal bulla.
Necrosis and
inflammatory
infiltrate in the
dermis
Clusters of bacteria
between collagen
bundles (middle and
bottom, arrow)
Dermal abscess, ,
necrosis, and
draining to the
surface
Inflammatory
infiltrate around
apocrine structures
and in the fat.
Septal scarring
CF: Areas rich in apocrine glands, such as DD: Granuloma inguinale; Crohn’s disease;
axillae, groin, or buttocks, are preferen- Pemphigus benignus familiaris (Hailey‐
tially involved, showing painful purulent, Hailey); Actinomycosis; chronic fungal
furunculoid nodules and scarring with infection; Langerhans cell histiocytosis.
sinuses and fistulas. The disease is associ-
ated with acne conglobata. Reference
HF: Jemec, G. B., & Hansen, U. (1996). Histology
• Dermal abscesses, draining to the surface of hidradenitis suppurativa. J Am Acad
• Mixed inflammatory infiltrate Dermatol, 34(6), 994–999.
• Neutrophils predominate Kalen, J. E., Shokeen, D., Mislankar, M., Wangia,
• Lymphocytes, plasma cells, eosinophils, M., & Motaparthi, K. (2018). Langerhans cell
and fibrosis in later stages histiocytosis with clinical and histologic features
• Granulomatous reactions with multi- of hidradenitis suppurativa: Brief report and
review. Am J Dermatopathol, 40(7), 502–505.
nucleated giant cells
Prens, E., & Deckers, I. (2015). Pathophysiology
• Scarring fibrosis and destruction of
of hidradenitis suppurativa: An update. J Am
adnexal structures Acad Dermatol, 73(5 Suppl 1), S8–11.
Corynebacteria ,
within the compact
corneal layer (PAS)
Figure 1.2.1 Erythrasma.
1.2: Other Bacterial Infections: Corynebacteria 19
Steplike erosion of
the cornified layer
(right)
CF: This disorder, which formerly was (UVA light), revealing red fluorescence
considered to be a fungal infection, in due to bacterial protoporphyrin.
truth is caused by corynebacteria DD: Piedra; hair casts; taenia amiantacea.
(Corynebacterium tenuis), forming white‐
yellow, red or black, difficult‐to‐remove, Reference
compact deposits along the hair shafts, Rho, N. K., & Kim, B. J. (2008). A corynebac-
preferentially in the axillae, where hyper- terial triad: Prevalence of erythrasma and
hidrosis is a predisposing factor. trichomycosis axillaris in soldiers with pit-
HF: The diagnosis is made clinically, or by ted keratolysis. J Am Acad Dermatol, 58(2
microscopic examination of plucked hair Suppl), S57–58.
shafts, or preferentially with Wood’s lamp
1.2: Other Bacterial Infections: Corynebacteria 21
1.2.4 Erysipeloid
Well-circumscribed
violaceus macular
lesion on the dorsum
of fingers and back
of the hand
Perivascular
and interstitial
infiltrate of
lymphocytes and
neutrophils. Dilated
lymphatic vessels
Figure 1.2.4 Erysipeloid.
This rare, acute, mostly self‐limited infection, • Diffuse superficial and deep polymor-
resembling erysipelas, is caused by the gram‐ phous inflammatory infiltrate showing
positive bacillus Erysipelothrix rhusiopathiae. lymphocytes, neutrophils, eosinophils,
Infections result from direct contact with and plasma cells
swine or contaminated animal material. • Organisms in most cases cannot be
Systemic symptoms, which are commonly detected with histological staining
encountered in erysipelas, as well as lym- • Microbiology/molecular pathology
phangitis and lymphadenitis, are lacking. from skin specimens reveals infectious
CF: The painful violaceous, macular, well‐ organisms
circumscribed lesion usually evolves from DD: Erysipelas; erythema migrans; con-
pinpoint injuries on the hands or fingers and tact dermatitis.
slowly spreads peripherally with central clear-
ing. There may be slight diffuse swelling.
HF: Reference
• Dermal edema Varella, T. C., & Nico, M. M. (2005). Erysipeloid.
• Dilatation of lymphatic vessels Int J Dermatol, 44(6), 497–498.
22 CHAPTER 1: Bacterial Infections
1.2.5 Anthrax
Abscess formation in
the dermis and
gram-positive rods
(inset)
Figure 1.2.5 Anthrax.
The gram‐positive Bacillus anthracis finally turns black in the center (“pustula
spawns permanent spores that are resist- maligna”).
ant in harsh environment, thrive in tis- HF:
sue, and produce exotoxins. Farmers, • Striking edema in the upper dermis
veterinarians, butchers, and slaughter- • Hemorrhage
house workers are especially vulnerable • Necrosis
to infection. Remarkably, anthrax spores • Diffuse lymphocytic and neutrophilic
have been misused as biological weapons infiltrate in the dermis
(respiratory infection). • Abscess formation
CF: In cutaneous anthrax infection, • Gram‐positive, markedly elongated
striking edema develops at the inocula- bacterial rods
tion site. A pustule forms, which
DD: Sporotrichosis; orf; arthropod bite reac-
becomes hemorrhagic, necrotic, and
tion; staphylococcal infection; tularemia.
1.2: Other Bacterial Infections: Corynebacteria 23
1.2.6 Nocardiosis
Abscesses on the
limb along lymphatic
vessels (left and
right)
Accumulation of
neutrophils (left) and
surrounding
amorphous
eosinophilic
grains (right)
,
Figure 1.2.6 Nocardiosis. Source: The images top left and right is modified from Fukuda et al. (2008).
Lymphocutaneous type of nocardiosis caused by Nocardia brasiliensis: a case report and
review of primary cutaneous nocardiosis caused by N. brasiliensis reported in Japan.
J Dermatol, 35(6), 346-353. The images bottom left and right is modified from Bandeira
et al. (2019). Primary cutaneous nocardiosis. J Dtsch Dermatol Ges. doi:10.1111/ddg.13770.
1.2.7 Rhinoscleroma
Granulomatous
growth on the nasal
mucosa, spreading to
the oral mucosa (left)
Pseudo-
carcinomatous
hyperplasia and
dense dermal
inflammatory
infiltrate (right)
Mixed cellular
infiltrate, showing
lymphocytes,
neutrophilic
granulocytes, and
many plasma
cells (left)
Large macrophages
with foamy
cytoplasm
(Mikulicz cells)
(right)
Figure 1.2.7 Rhinoscleroma.
• Large macrophages with foamy cyto- Efared, B., Hammas, N., Gabrielle, A. E., Ben
plasm and bacilli (Mikulicz cells) Mansour, N., El Fatemi, H., & Chbani, L.
• Special stains: silver, Gram, Giemsa, (2018). Rhinoscleroma: A chronic infectious
PAS (Russell bodies) disease of poor areas with characteristic his-
tological features – report of a series of six
DD: Leishmaniasis, NK/T-cell lymphoma. cases. Trop Doct, 48(1), 33–35.
Reference
1.3 Rochalimaea/Bartonellae
Ahmed, A. R., El‐Badawy, Z. H., Mohamed, I. R.,
& Abdelhameed, W. A. (2015). Rhinoscleroma: Gram‐negative bacteria (Bartonella hense
A detailed histopathological diagnostic insight. lae or Bartonella quintana; formerly
Int J Clin Exp Pathol, 8(7), 8438–8445. Rochalimaea) are the causative agent in
Castanedo Cazares, J. P., & Martinez Rosales, bacillary angiomatosis, cat scratch disease‚
K. I. (2015). Images in clinical medicine.
and in verruga peruana.
Rhinoscleroma. N Engl J Med, 372(25), e33.
Bacillary angiomatosis:
nodules in a patient
with AIDS (left) *
Bacillary angiomatosis:
vascular proliferation
with neutrophilic ,
infiltrate (middle left)
and karyorrhexis
(bottom)*
Immunostain with
anti-Bartonella
antibody (right)
Electron microscopy
of Bartonella
Henselae (right)
Inset: bacterial
clusters*
Figure 1.3.1 Bacillary Angiomatosis and Cat Scratch Disease (top right).
*Source: Burg et al. (2019). Atlas of Dermatopathology: Tumors, Nevi, and Cysts (p. 273). Oxford: Wiley.
26 CHAPTER 1: Bacterial Infections
1.3.2 Verruga Peruana
Multiple nodules on
the legs
Vascular proliferation
and neutrophilic
infiltrate (upper right
and middle)
,
Intracytoplasmic
Bartonella
bacilliformis.
Grocott stain
CF: Dermal papules and nodules, pedun- HF: Corresponds to bacillary angiomato-
culated, eroded or verrucous, resembling sis, albeit with exclusively intracytoplas-
bacillary angiomatosis. Verruga peruana is mic bacteria (Rocha–Lima bodies), while
the late stage of Oroya fever that is caused in bacillary angiomatosis infectious organ-
by Bartonella bacilliformis, almost exclu- isms thrive purely extracellularly.
sively in the Andes Mountains (Peru). DD: See bacillary angiomatosis.
Infectious vectors are sandflies.
28 CHAPTER 1: Bacterial Infections
Exophytic vascular
partially eroded
lesion on the finger
Lobular arrangement
of capillary tufts
separated by broad
fibrous septa
Primary tuberculosis
on the leg
(left)
Mycobacteria
(Ziehl–Neelsen)
(right)
Papulopustular
lesion with erythema
Granulomatous
infiltrate in the dermis
CF: Papulopustular reaction with erythema. BCG vaccination: Case report and review of
HF: Granulomatous inflammation with the literature. J Dermatolog Treat, 22(6),
predominant epithelioid granulomas at 315–318.
the site of previous BCG vaccination. Lyu, S. M., Choi, Y. W., Oh, C. W., Choi, H. Y.,
& Byun, J. Y. (2013). Granulomatous reac-
DD: Insect bite; furuncle.
tion after BCG vaccination histologically
mimicking reticulohistiocytoma. Eur J
Reference
Dermatol, 23(4), 527–528.
Keijsers, R. R., Bovenschen, H. J., & Seyger, M.
M. (2011). Cutaneous complication after
Lympho-histiocytic
infiltrate with
neutrophils
(short arrow)
Palisading
granulomatous
infiltrate
(long arrow)
Central caseating
necrosis
(red arrowhead)
LMDF originally was considered to be a • All special stains and PCR for infectious
tuberculid, but eventually was subsumed organisms are negative
under the spectrum of granulomatous DD: Acne; rosacea; verrucae planae.
rosacea or acne agminata. However, the
disease occurs also in extrafacial areas. Reference
CF: Tiny reddish brown papules, simulating
Chougule, A., Chatterjee, D., Yadav, R., Sethi, S.,
acne (syn. Acne agminata and acnitis).
De, D., & Saikia, U. N. (2018). Granulomatous
HF:
rosacea versus lupus miliaris disseminatus
• Small well‐circumscribed interfollicular faciei‐2 faces of facial granulomatous disor-
superficial granulomas in the upper dermis der: A clinicohistological and molecular study.
• Admixture of neutrophils Am J Dermatopathol, 40(11), 819–823.
• Marked central caseating necrosis Schaarschmidt, M. L., Schlich, M., Staub, J.,
devoid of any organisms Schmieder, A., Goerdt, S., & Peitsch, W. K.
• Peripheral wreath of densely packed (2017). Lupus miliaris disseminatus faciei:
Not only a facial dermatosis. Acta Derm
histiocytes and multinucleate giant cells
Venereol, 97(5), 655–656.
Atrophic slightly
scaling reddish
brown plaque with
scarring
Epidermal atrophy
overlying dermal
granulomatous
infiltrate
Epithelioid cell
granulomas
(left) with central
caseation necrosis
(right) surrounded by
lymphocytes
and plasma cells
Hyperkeratotic
lesions on the chin
Fungating lesion
with draining follicular
sinuses (perforating
granulomatous
inflammation)
(top right and middle)
Acanthosis and
papillomatosis (left);
dermal granuloma
with multinucleated
giant cells (right)
Variant of lupus vulgaris with overlying ver- Lim, J. A., Tan, W. C., Khor, B. T., Hukam
rucous (pseudocarcinomatous) epidermis. Gopal Chand, S. D., & Palanivelu, T. (2017).
Early onset of squamous cell carcinoma aris-
Reference ing from tuberculosis verrucosa cutis. J Am
Coll Clin Wound Spec, 9(1–3), 35–38.
Chahar, M., Dhali, T. K., & D’Souza, P. (2015).
Multifocal tuberculosis verrucosa cutis.
Dermatol Online J, 21(1).
1.4: Mycobacterial Infections 35
Ulceration, fistulation,
and necrosis in the
neck area
Epidermal
hyperplasia overlying
perforating dermal
granulomatous
infiltrate with
caseation necrosis
Mixed cellular
infiltrate with
Langhans giant cell
(left)
Mycobacteria
(Ziehl–Neelsen stain;
arrows) (right)
Chronic subcutaneous variant of tubercu- nodes in the head and neck area. Typical
losis with underlying normergic immune are painless swelling and ulceration with
status. necrosis and fistulation, leading to adher-
CF: Skin involvement may result from per ence of the overlying skin and finally scar
continuitatem draining infected lymph formation.
36 CHAPTER 1: Bacterial Infections
HF: Reference
• Nonspecific epidermal hyperplasia Gupta, M., Gupta, M., & Kaur, R. (2013).
• Massive necrosis Tuberculosis colliquativa cutis of the cheek:
• Tuberculoid granulomas with Langhans An extremely uncommon manifestation of
giant cells primary extrapulmonary tuberculosis. BMJ
• Mixed inflammatory infiltrate with lym- Case Rep, 2013.
phocytes, plasma cells, and neutrophils Tur, E., Brenner, S., & Meiron, Y. (1996).
• Tuberculous pus Scrofuloderma (tuberculosis colliquativa
cutis). Br J Dermatol, 134(2), 350–352.
DD: Actinomycosis; deep fungal infec-
tions; lymphogranuloma; tertiary syphilis
(gumma).
Disseminated
papules on the leg
(left) and on the trunk
(right)
Camacho, D., Pielasinski, U., Revelles, J. M., mimicking lichen planus. Am J Dermatopathol,
Gorgolas, M., Manzarbeitia, F., Kutzner, H., 33(2), 186–191.
& Requena, L. (2011). Lichen scrofulosorum
1.4.1.8 Papulonecrotic Tuberculid
Papulonecrotic
lesions on the
legs*
Caseating granuloma
with central necrosis
(middle)* and
Langhans giant cells
(right)
Contusiform and
infiltrated
lesions on the
calves (left)*
Mixed
granulomaous
infiltrate in the deep
dermis and subcutis
(top right and middle)
Vasculitis of
medium-sized
arteria within the
panniculus.
Adjacent
granulomatous
infiltrate
Hyperkeratotic
lesion
Verruciform
epidermal
hyperplasia
with hyperkeratosis
Diffuse suppurative
granuloma formation
Multinucleated
giant cell containing
mycobacteria
(Ziehl–Neelsen)
(arrow)
1.4.3.1 Tuberculoid Leprosy
Hypopigmented
lesion in the neck
(left)
Thickened nerve
(right, arrow)
Granulomatous
infiltrate in the dermis
without grenz zone
(middle) and with
multinucleated giant
cells (bottom)
1.4.3.2 Borderline Leprosy
Ill-defined
hypopigmented
and anesthetic
lesion on the arm
(left)
Disseminated
granulomatous
infiltrates (left)
Perivascular
granulomatous
infiltrates with
thickened nerve (*)
Mycobacteria in
borderline
lepromatous leprosy
(Ziehl–Neelsen stain)
1.4.3.3 Lepromatous Leprosy
Erythematous
confluent macules
and plaques (left)
Facies leonina
(right)
Atrophy of the
epidermis; small
grenz zone. Dense
infiltrate in the dermis
(left)
Thickened nerve in
the subcutis (right)
Nodular infiltrates of
histoid cells in the
dermis (top and
bottom); (H&E left;
Fite-Faraco right)
This is an uncommon variant of leproma- • High bacillary index, without globi for-
tous leprosy occurring in patients with mation of lepra bacilli
lepromatous leprosy and inadequate or • Histologic variants comprise pure fuso-
irregular therapy. cellular, fusocellular with epithelioid
CF: Single or multiple well demarcated component, and fusocellular with vacu-
dermatofibroma‐like cutaneous and sub- olated (foamy) cells
cutaneous deep-seating nodules arising DD: Fibrous histiocytoma (dermatofi-
on normal skin. broma); keloid; erythema nodosum lepro-
HF: sum; sarcoidosis; reticulohistiocytosis;
• Atrophy of the epidermis cutaneous metastases; atypical mycobac-
• Subepidermal grenz zone teriosis; molluscum.
• Interlacing bundles of spindle‐shaped
fusiform histiocytes in the dermis Reference
arranged in storiform or crisscross Kalla, G., Purohit, S., & Vyas, M. C. (2000).
pattern Histoid, a clinical variant of multibacillary
46 CHAPTER 1: Bacterial Infections
leprosy: Report from so‐called nonendemic Rodrigues Daxbacher, E. L., Cabrera Pereira, J.
areas. Int J Lepr Other Mycobact Dis, 68(3), P., Ramos de Oliveira, S., Duarte Tortelly, V.,
267–271. Carneiro, S., & Jeunon, T. (2020). The impor-
Punia, R. P. S., Dhingra, H., Baliyan, A., Handa, tance of the biopsy technique in the diagno-
U., Mohan, H., & Thami, G. P. (2017). sis of histoid leprosy. Am J Dermatopathol,
Clinicopathologic spectrum of histoid lepra 42(2),125–128.
International Journal of Current Research, 9(5),
50765–50769.
Soft (tender)
nodules on the
arm (left)
Inflammatory infiltrate
in the deep dermis
and subcutis
(right)
Anti-BCG staining
(right)
1.5 Actinomycosis
Indurated swelling
(left) and
submandibular
abscess (right)
Pseudo-
carcinomatous
hyperplasia with
draining sinuses
Mixed cellular
inflammatory
infiltrate in the dermis
with “sulfur granules”
(left and top right),
containing a plethora
of bacterial rods
(bottom right)
Figure 1.5 Actinomycosis.
Ixodes ricinus
in action (left top)
Ixodes ricinus
and Borrelia
Burgdorferi in
dark-field microscopy
(left bottom)
Annular erythema
(top middle and
below).
Moulage (top right)
Mononuclear
infiltrate in
the upper dermis
Perivascular and
interstitial
lymphohistiocytic
infiltrate with
few plasma cells
(left). Pseudo-rosette
pattern around
free-floating collagen
fibers (right, arrows)
CF: ECM, which is typically an erythema- ◦◦ Plasma cells, with diffuse splaying in
tous, slowly expanding annular patch, the upper dermis, may be rare
appears at the site of a previous tick bite. • Center of the lesion
A few weeks later, after the erythema has
◦◦ Eczematous changes of the epidermis
faded, a papule or a small nodule (lym-
◦◦ Chitinous remnants of the tick
phadenosis cutis benigna, lymphocytoma
(hypostome)
cutis: see below) may develop at the site
◦◦ Slight edema with dilated blood vessels
of the tick bite or at a distant site, follow-
◦◦ Mixed inflammatory cell infiltrate
ing hematogenous spread of the spiro-
◦◦ Eosinophils (early stages) and plasma
chetes (stage II).
cells (advanced stages) commonly
HF: The diagnosis is based on the patient’s
occur
history, clinical presentation, and serologic
◦◦ Granulomatous reaction (advanced
tests/PCR, respectively. Immunohisto
lesions)
chemical demonstration of spirochetes is
◦◦ Spirochetes can be identified only
rarely feasible. In the center of the lesion,
in exceptional cases (immunohisto-
chitinous remnants of the tick (hypos-
chemistry)
tome) and a neutrophil‐rich inflamma-
tory infiltrate followed by granulomatous DD: Erysipelas; insect bite; acute urticaria
changes may occur. (hives); tinea; all other annular (allergic)
erythemas.
• Erythematous patch or peripheral
annular rims Reference
◦◦ Missing or only slight spongiosis with
exocytosis Celebi Cherukuri, N., Roth, C. G., Aggarwal,
◦◦ Sparse patchy lymphoplasmacytic N., Ho, J., Gehris, R., & Akilov, O. E. (2016).
Cutaneous small/medium CD4+ pleomor-
perivascular or interstitial (Indian file‐
phic T‐cell lymphoma‐like nodule in a
like) infiltrate in the upper dermis
patient with erythema chronicum migrans.
◦◦ Eosinophils in early stages more
Am J Dermatopathol, 38(6), 448–452.
frequent Wilson, T. C., Legler, A., Madison, K. C., Fairley,
◦◦ Interstitial lymphohistiocytic infiltrate, J. A., & Swick, B. L. (2012). Erythema
sometimes in pseudo‐rosette pattern migrans: A spectrum of histopathologic
around free‐floating collagen fibers changes. Am J Dermatopathol, 34(8), 834–837.
52 CHAPTER 1: Bacterial Infections
Erythematous
pseudolymphomatous
swelling of the concha
(left)
Follicular infiltrates
(right)
Germinal center
formation (left) with
tingible body
macrophages (right)
In Europe, in a minority of cases pseudo- nose, nipples, inguinal area, and the
lymphomatous infiltrates most commonly scrotum.
occur some weeks after infection with HF: Nodular dermal infiltrates, mainly
Borrelia burgdorferi at the site of a previous located in the upper and mid‐dermis, occa-
tick bite (Ixodes ricinus). sionally extending into the deep dermis.
CF: Mostly solitary, rarely multiple or dis- • Preserved subepidermal grenz zone
seminated soft red, sharply bordered nod- • Dense and diffuse lymphoid infiltrates
ules on the head, preferentially on the ear • Reactive lymph follicles
lobes. Other predilectional sites are the
54 CHAPTER 1: Bacterial Infections
Plaque-like
violaceous indurated
lesions on the legs
(left)
Diffuse
granulomatous
dermal infiltrates
and interstitial foci
between thickened
collagen bundles
(top right and below)
• Preserved elastic fiber network; no Breier, F., Khanakah, G., Stanek, G., Kunz, G.,
scarring Aberer, E., Schmidt, B., & Tappeiner, G.
(2001). Isolation and polymerase chain reac-
DD: Remarkably, a similar – if not identi-
tion typing of Borrelia afzelii from a skin
cal – histopathological pattern (biopsy taken
lesion in a seronegative patient with general-
from inflamed periphery/lilac ring) may be ized ulcerating bullous lichen sclerosus et
encountered in morphea/scleroderma, atrophicus. Br J Dermatol, 144(2), 387–392.
interstitial granulomatous dermatitis (in Breier, F. H., Aberer, E., Stanek, G., Khanakaha,
conjunction with rheumatoid arthritis or G., Schlick, A., & Tappeiner, G. (1999).
with other autoimmune disorders), and Isolation of Borrelia afzelii from circum-
interstitial granulomatous drug reactions. scribed scleroderma. Br J Dermatol, 140(5),
925–930.
Reference Wackernagel, A., Bergmann, A. R., & Aberer,
E. (2005). Acute exacerbation of systemic
Aberer, E., Klade, H., Stanek, G., & Gebhart, scleroderma in Borrelia burgdorferi infec-
W. (1991). Borrelia burgdorferi and different tion. J Eur Acad Dermatol Venereol, 19(1),
types of morphea. Dermatologica, 182(3), 93–96.
145–154.
Slightly violaceous
discoloration and
puffy swelling of
the right hand
Scarce perivascular
infiltrate. Loss of
elastic fibers (not
shown in H&E stain)
in the upper dermis
Atrophy of the
epidermis.
Loss of papillae
Band-like
subepidermal
inflammatory
infiltrate with coarse
collagen fibres
(pseudo-MF
pattern)
Abundance of
plasma cells
f ungoides (“Pseudo‐MF” pattern of borrelio- Kempf, W., Kazakov, D. V., Hubscher, E.,
sis) both clinically and histologically. Gugerli, O., Gerbig, A. W., Schmid,
DD: Anetoderma; atrophoderma of Pasini R., . . . Kutzner, H. (2015). Cutaneous bor-
and Pierini; varicose veins; actinic reticu- reliosis associated with T cell‐predominant
infiltrates: A diagnostic challenge. J Am Acad
loid – with histopathological morphological
Dermatol, 72(4), 683–689.
overlap, albeit clinically completely different.
Tee, S. I., Martinez‐Escaname, M., Zuriel, D.,
Fried, I., Wolf, I., Massone, C., & Cerroni, L.
Reference (2013). Acrodermatitis chronica atrophicans
with pseudolymphomatous infiltrates. Am J
Gulseren, D., Cerroni, L., Hofmann‐Wellenhof, Dermatopathol, 35(3), 338–342.
R., & Arzberger, E. (2018). Correlation of Zalaudek, I., Leinweber, B., Kerl, H., & Mullegger,
reflectance confocal microscopy and der- R. R. (2005). Acrodermatitis chronica atrophi-
matopathology findings in a case of cans in a 15‐year‐old girl misdiagnosed as
Acrodermatitis chronica atrophicans. Am J venous insufficiency for 6 years. J Am Acad
Dermatopathol, 40(5), 367–370. Dermatol, 52(6), 1091–1094.
Red fibro-sclerotic
(juxta-articular)
nodules on the elbow
(left).
Moulage (bottom)
Abundant fibrosis
and sclerosis
with sparse
lymphohistiocytic
infiltrate (top right,
bottom left, and right)
1.7 Venereal Diseases
1.7.1 Gonorrhea
Discharge of pus
from urethra
Intracellular
(gram-negative)
diplococci (right)
Figure 1.7.1 Gonorrhea.
60 CHAPTER 1: Bacterial Infections
1.7.2.1 Stage I
Primary lesion
On the penis (left)
and on labia (middle)
Spirochetes in
dark-field microscopy
(right)
CF: After an incubation period of about microscopy) and by serological tests, which
2–3 weeks, ulcus durum (chancre) – the become reactive/positive 2–3 weeks after
first visible manifestation of T. pallidum primary infection (specific IgM antibodies).
infection – develops at the primary site of HF:
infectious entry, typically at the penis • Shallow ulceration, often with serum
(sulcus coronarius), vulva, cervix uteri, and debris
perianal skin, lips, or oral cavity. The ulcer • Accompanying edema
is painless; there is always associated • Dense mixed inflammatory infiltrate
regional lymphadenitis. • Abundant plasma cells
At this early stage of disease, diagnosis • Dilated postcapillary venules with
can be established by the direct demonstra- swelling of endothelial cells
tion of spirochetes (smears; dark field
1.7: Venereal Diseases 61
1.7.2.2 Stage II
Papulosquamous
lesions on the trunk
and in the face
Psoriasiform lichenoid
inflammatory pattern
with dense plasma
cell-rich infiltrate in
the papillary dermis
Inflammatory infiltrate
containing many
plasma cells (left)
Treponema pallidum
immunostain (right)
CF: In the early secondary stage of syphi- DD: Pityriasis lichenoides et varioliformis
lis (8–12 weeks after infection), distinct acuta (PLEVA); pustular psoriasis; lym-
tiny macules (roseola) may appear on phomatoid papulosis; cutaneous lym-
trunk and extremities, that are easily phoma (mycosis fungoides); drug reaction;
overlooked and regress spontaneously. In tick bites; leprosy.
the late stage of secondary syphilis
(>2 years after untreated infection), dis- Reference
seminated small papules and papulosqua- Alessi, E., Innocenti, M., & Ragusa, G. (1983).
mous lesions may appear on head, trunk, Secondary syphilis. Clinical morphology and
extremities, and on mucous membranes, histopathology. Am J Dermatopathol, 5(1),
presenting as plaques and patches on the 11–17.
palms and soles (“pustular psoriasis”) or Jordaan, H. F. (1988). Secondary syphilis. A
as condyloma‐like lesions in the anogeni- clinicopathological study. Am J Dermatopathol,
tal region. 10(5), 399–409.
HF: Pettit, C., McMurray, S., Randall, M. B., Jones,
A., & Fisher, K. (2019). Highlighting a potential
• Macular lesions: Nonspecific sparse
pitfall: Positive Treponema pallidum immuno-
interstitial infiltrate; few plasma cells as histochemical stain in a patient without syphi-
a telltale sign of infectious origin lis. Am J Dermatopathol, 41(12), 924–926.
• Maculopapular lesions in late secondary Rosa, G., Bennett, D., & Piliang, M. P. (2015).
syphilis Eosinophil‐rich syphilis: A report of four
◦◦ Interface dermatitis; often associated cases. J Cutan Pathol, 42(8), 554–558.
with spongiosis with subcorneal Rysgaard, C., Alexander, E., & Swick, B. L.
spongiform pustulation (2014). Nodular secondary syphilis with
◦◦ Dermal edema associated granulomatous inflammation:
◦◦ Superficial and deep perivascular and Case report and literature review. J Cutan
Pathol, 41(4), 370–379.
interstitial infiltrate
◦◦ Mixed infiltrate: lymphocytes, histio- 1.7.2.3 Stage III°
cytes, mostly scattered – occasionally CF: Two years after primary infection, the
numerous – eosinophils course of disease – provided there was no
◦◦ Sheets or small focal clusters of plasma appropriate treatment – reaches its third,
cells – as a clue to the diagnosis latent stage. Clinical symptoms are mani-
◦◦ Histiocyte‐predominant granuloma- fold: gummatous superficial or deep ulcer-
tous features at advanced stages ating skin lesions, cardiovascular (aorta),
◦◦ Spirochetes may be detected either by peripheral and central neurologic symp-
Warthin–Starry silver stain or immu- toms (progressive paralysis, tabes dorsalis).
nohistochemically, preferentially in HF:
the upper dermis and epidermis
• Small granulomas composed of epithe-
• Verruciform condylomata lata – with
lioid cells and multinucleated giant cells
markedly spongiform pustulation – and
• Lymphohistiocytic infiltrates with
ulcerating lues maligna – with broad
plasma cells
shallow ulcers and massive debris – are
• Dilated vessels with swollen endothelia
variants of secondary syphilis at special
• Central caseating necrosis
sites, preferentially in immunocompro-
mised patients. Spirochetes may be DD: Sarcoidosis; tuberculosis; leprosy;
abundant in these conditions leishmaniasis (advanced).
1.7: Venereal Diseases 63
Elongated bacterial
rods in swab smears
(middle and right)
Pseudocarcinomatous
hyperplasia and
ulceration in the
genital area (left)
Calymmatobacterium
granulomatis in
macrophage
(Donovan bodies)
(right). Electron
microscopy (inset)
Swelling of inguinal
lymph node (left).
Chlamydia in lymph
node (immunostain
with anti-
Chlamydia antibody)
(right)
This sexually transmitted infection caused or in the rectum. In stage II, the regional
by Chlamydia trachomatis should not be lymph node is involved (bubo), which
confused with another, sound‐alike vene- shows abscess formation with ulceration
real infection – granuloma inguinale (syn: and draining to the surface. Stricture and
granuloma venereum) – which is caused fibrosis in stage III (elephantiasis) eventu-
by the gram‐negative bacterium Calymma ally evolve into massive lymphatic edema
tobacterium granulomatis. and urethral‐vaginal fistulas.
CF: Primary lesion (stage I) is an ulcerating HF: Unspecific findings with ulceration
papulopustule, usually in the genital region and granulomatous abscess formation.
1.8: Rickettsial Infections 65
1.8 Rickettsial Infections
Pox-like
papulopustular lesion
with central black
necrosis (eschar) on
the leg (left)
Lymphocytic infiltrate
(top right,
middle left)
Occlusive vasculitis
with focal thrombi
(right)
HF: Histologic changes of solitary lesion, DD: Mosquito bite; furuncle; leishmania-
for example, in Mediterranean tick fever: sis; ecthyma; orf; anthrax (solitary lesion
• Flat ulcer with superficial necrosis and with eschar).
crust formation (eschar)
• Superficial and deep perivascular Reference
infiltrate Montenegro, M. R., Mansueto, S., Hegarty, B.
• Focal leukocytoclastic vasculitis with C., & Walker, D. H. (1983). The histology of
small thrombi (telltale sign) “taches noires” of boutonneuse fever and
• Organisms may be demonstrated immu- demonstration of Rickettsia conorii in them
nohistochemically or by immunofluo- by immunofluorescence. Virchows Arch A
rescence. Rickettsiae often thrive within Pathol Anat Histopathol, 400(3), 309–317.
the walls of small inflamed vessels
Initial scarlatiniform
eruption (left),
evolving into
widespread
desquamation
(right)
Exclusively
subcorneal flaccid
blister, limited to the
granular layer
Also known as dermatitis exfoliativa neo- of the superficial epidermal layers, resem-
natorum, Ritter [von Rittershain] disease, bling acute burn. Causative agent is the
staphylococcal Lyell syndrome, Pemphigus toxin‐producing (exfoliative toxins A and
neonatorum. B) Staphylococcus aureus, often of phage
Toxin‐mediated epidermolytic derma- group II.
tosis, primarily in small children, charac- CF: Initially, there is a mild scarlatiniform
terized by erythema and widespread loss rash with associated fever. Widespread
1.9: Dermatoses Associated with Bacterial Infections 67
erythema evolves into marked tenderness • Frozen sections preferred for rapid
with small unstable flaccid bullae that diagnosis
quickly erode and lead to burn‐like loss of DD: Toxic epidermal necrolysis (TEN) show-
superficial epithelial layers. The clinical ing full‐thickness epidermal detachment.
course often is acute with systemically ill
patients. Reference
HF:
Cribier, B., Piemont, Y., & Grosshans, E. (1994).
• Subcorneal acantholysis and blister for- Staphylococcal scalded skin syndrome in
mation with a marked split high in the adults. A clinical review illustrated with a new
epidermis case. J Am Acad Dermatol, 30(2 Pt 2), 319–324.
• Blister roof composed exclusively of stra- de Dobbeleer, G., & Achten, G. (1975).
tum corneum (versus blister formation Staphylococcal scalded skin syndrome. An
in TEN, where full‐thickness epidermal ultrastructural study. J Cutan Pathol, 2(2), 91–98.
blister roof occurs) Elston, D. M., Stratman, E. J., & Miller, S. J.
• Little or no inflammatory infiltrate (2016). Skin biopsy: Biopsy issues in specific
diseases. J Am Acad Dermatol, 74(1), 1–16.
Numerous apoptotic
keratinocytes (arrow)
throughout the
entire epidermis,
evolving into
epidermal necrosis
Incipient
papulopustular lesion
with erythema (left)
Inflammatory
reaction and fibrosis
in the dermis and
subcutis (right)
Subepidermal edema
and ulceration with
undermined border
Neutrophil-rich
cellular infiltrate.
Secondary vasculitis
and hemorrhage
1.10.2 Infantile Acropustulosis
Multiple pustules on
sole and heel (left
and middle)
Resolving lesions
with collarette scales
and crust
(right)
Unilocular
subcorneal pustule,
with many
neutrophils and
eosinophils
CF: At birth or during the first year of • Bacteria or fungi are not demonstrable
life, pruritic pustules with an erythema- with special stains
tous base occur on hands and feet, resolv- DD: Scabies; impetigo; pustular psoriasis;
ing with collarette‐type scale‐crusts, in acrodermatitis continua suppurativa
most cases within two years. Unknown Hallopeau; IgA bullous dermatosis; IgA
etiology. pemphigus.
HF:
• Unilocular, subcorneal or intraepider- Reference
mal vesicle or pustule Hürlimann, A., Wüthrich, B., & Burg, G.
• Sparse spongiosis at the periphery of (1992). Infantile Akropustulose. Z Hautkr,
the lesion 67(12), 1073–1079.
• Pustules contain a mixed round cell Paloni, G., Berti, I., & Cutrone, M. (2013).
infiltrate, with predominant neutrophils Acropustulosis of infancy. Arch Dis Child Fetal
and eosinophils Neonatal Ed, 98(4), F340.
1.10: Dermatoses Mimicking Bacterial Infections 71
Generalized
pustular exanthema
Massive
subepidermal edema
with neutrophils and
scale crust
• Almost always erythrocyte extravasation Poeschl, M. D., Hurley, M. Y., Goyal, S. D., &
• Leukocytoclastic vasculitis may be pre- Vidal, C. I. (2014). Targetoid eruptions: Acute
sent (facultative) generalized exanthematous pustulosis. Am J
Dermatopathol, 36(10), 827–828, 838.
DD: Pustular psoriasis; Sweet syndrome;
Sidoroff, A., Halevy, S., Bavinck, J. N., Vaillant,
Sneddon–Wilkinson syndrome; impetigo; L., & Roujeau, J. C. (2001). Acute general-
Drug Rash with Eosinophilia and Systemic ized exanthematous pustulosis (AGEP) – a
Symptoms (DRESS); leukocytoclastic vas- clinical reaction pattern. J Cutan Pathol,
culitis; incipient stage of erysipelas. 28(3), 113–119.
Vyas, N. S., Charifa, A., Desman, G. T., &
McNiff, J. M. (2019). Distinguishing pustular
Reference
psoriasis and acute generalized exanthema-
Ballmer, B. K., Widmer, M., & Burg, G. (1993). tous pustulosis on the basis of plasmacytoid
Acetylsalicylsäure‐induzierte generalisierte dendritic cells and MxA protein. J Cutan
Pustulose. Schweiz med Wschr, 123, 542–546. Pathol, 46(5), 317–326.
1.10.4 Psoriasis Pustulosa
Myriads of tiny
pustules on
erythematous ground
on the back (left) and
palm (right top)
Erosive pustulosis on
the thumb in
acrodermatitis
continua suppurative
Hallopeau
(right below)
Intraepidermal
pustule with adjacent
psoriasiform
acanthosis.
Sparse infiltrate in
the dermis.
Note characteristic
spongiform
pustulation at the
periphery of the
pustule (arrow)
Papular lesions
following therapy
with mitixantrone
(left)
Neutrophils below
the stratum corneum
and the epidermis -
in vicinity of
acrosyringium (middle)
Apoptotic
keratinocytes
(arrows)
within the sweat duct
epithelium (right)
Widespread pustules
and erosions
on the scalp (left)
Subcorneal pustule
and necrosis
(top right)
Nonspecific
interstitial infiltrate
and dermal collagen
degeneration
(bottom right)
Rare disease of unknown etiology, pri- CF: Crusty erosions and pustules on the
marily seen in elderly patients. A nosologic scalp.
relationship with pyoderma gangrenosum HF: Erosive pustular dermatitis of the
has been suggested. scalp may mimic a plethora of superficial
1.10: Dermatoses Mimicking Bacterial Infections 75
Fungal Infections
CHAPTER MENU
2.1 Superficial Cutaneous Fungal Infections 2.3 Systemic Mycoses (Deep Fungal Infections)
2.1.1 Variants: Tinea Corporis; Tinea Faciei 2.3.1 Cryptococcosis (Torulosis, European
2.1.2 Variants: Tinea Barbae; Tinea Capitis Blastomycosis)
(Trichophytia) 2.3.2 North American Blastomycosis
2.1.3 Granuloma Trichophyticum (Majocchi’s (Blastomycosis, Chicago Disease)
Granuloma) 2.3.3 Lobomycosis (Lobo Disease, Keloidal
2.1.4 Candidiasis (Moniliasis) Blastomycosis, Blastomycoid
2.1.5 Candida Tropicalis and Candida Granuloma)
Lipolytica 2.3.4 Histoplasmosis
2.1.6 Pityriasis (Tinea) Versicolor 2.3.5 Coccidioidomycosis (Desert or Valley
2.1.7 Variant: Malassezia (Pityrosporum) Fever, San Joaquin Fever)
Folliculitis 2.3.6 Paracoccidioidomycosis (South
2.1.8 Differential Diagnosis: Seborrheic American Blastomycosis)
Dermatitis 2.3.7 Emmonsiosis
2.1.9 Tinea Nigra 2.4 Opportunistic Fungal Infections
2.1.10 Piedra (Trichomycosis Nodosa Alba 2.4.1 Aspergillosis (Alternaria)
and Nigra)° 2.4.2 Zygomycosis (Mucormycosis;
2.2 Subcutaneous Mycoses Phycomycosis)
2.2.1 Sporotrichosis 2.4.3 Hyalohyphomycosis
2.2.2 Mycetoma (Madura Foot) 2.4.4 Phaeohyphomycosis
2.2.3 Chromo(blasto)mycosis (Dermatitis 2.4.5 Protothecosis, Cutaneous
Verrucosa)
°no pictures
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
77
78 CHAPTER 2: Fungal Infections
Compact
cornified layer
Sparse dermal
infiltrate
Hyphae in the
cornified layer.
PAS stain (arrows)
The term “tinea” in conjunction with the site example, tinea (taenia) amiantacea, which is
of infection (tinea corporis, capitis, barbae, a bacterial infection. Clinical features largely
manus, pedis, inguinalis) commonly charac- depend on the anatomic site (glabrous or
terizes a cutaneous infection with dermato- non‐glabrous skin, intertriginous sites,
phytes. As always in dermatology, there are mucous membranes). Tinea corporis is the
confusing “sound‐alike” exceptions of prototypical infection with dermatophytes.
nomenclature with no nosological relation- CF: Small pustules, crusts and scaling with
ship to classic fungal infection at all, for centrifugal growth, and tendency to
80 CHAPTER 2: Fungal Infections
Diffuse inflammation,
pustules, and crusts
in the beard region
(left)
Diffuse and
perifollicular infiltrate
in the dermis
(right)
Peri- and
intrafollicular
inflammatory infiltrate
with predominant
neutrophils and
fungi (arrows) in and
around hair shafts
(PAS left; HE top
right; Grocott bottom
right)
Predominantly
eosinophilic
inflammatory
infiltrate with fungal
organisms in follicle
ostium (PAS below)
Fungal infection of the hair. Tinea favosa • Hyphae and spores within (endotrich)
(favus) is an endemic variant due to infec- and around (exotrich) the hair shaft
tion by Trichophyton schoenleinii, mostly on DD: Eczema; bacterial folliculitis; alope-
the head of children. cia areata; lichen planopilaris; mucinosis
CF: Inflammatory plaques and infiltration follicularis.
of the skin with pustules, crusts‚ and
(temporary) hair loss. Reference
HF:
Amer, M., Helmy, A., & Amer, A. (2017).
• Neutrophil‐predominant mixed inflam- Trichoscopy as a useful method to differenti-
matory infiltrate throughout the dermis ate tinea capitis from alopecia areata in chil-
• Hair follicle with neutrophils and incipi- dren at Zagazig University Hospitals. Int J
ent abscess formation Dermatol, 56(1), 116–120.
• Follicular and perifollicular debris and El‐Taweel, A. E., El‐Esawy, F., & Abdel‐
granulomatous infiltrate (late) Salam, O. (2014). Different trichoscopic
82 CHAPTER 2: Fungal Infections
features of tinea capitis and alopecia areata Case report and review]. Hautarzt, 70(8),
in pediatric patients. Dermatol Res Pract, 601–611.
2014, 848763. Singh, S., Sondhi, P., Yadav, S., & Ali, F. (2017).
Kirsten, H., Haiduk, J., Nenoff, P., Uhrlass, S., Tinea barbae presenting as kerion. Indian J
Ziemer, M., & Simon, J. C. (2019). [Tinea barbae Dermatol Venereol Leprol, 83(6), 741.
profunda due to Trichophyton mentagrophytes:
Granulomatous
infiltrate in the
dermis with
predominant granulocytes
2.1.4 Candidiasis (Moniliasis)
Superficial and
intertriginous, oral,
interdigital, and
paronychial
infections with
Candida albicans
Intracorneal spores
and hyphae (arrow)
Branching hyphae in
the corneal layer.
PAS stain
Pustular lesion
with abscess and
necrosis (left) and
fungal elements
(PAS right)
Candida lipolytica
Dense
granulomatous
infiltrate in the dermis
(left). Numerous
spores are seen
within multinucleated
giant cells
(PAS right)
These are rare mostly systemic infections, Candida tropicalis. J Am Acad Dermatol, 16(3 Pt
seen preferentially in neutropenic or 1), 623–624.
immunocompromised patients. Walsh, T. J., Salkin, I. F., Dixon, D. M., &
Hurd, N. J. (1989). Clinical, microbiological,
Reference and experimental animal studies of
Candida lipolytica. J Clin Microbiol, 27(5),
Benson, P. M., Roth, R. R., & Hicks, C. B. (1987). 927–931.
Nodular subcutaneous abscesses caused by
86 CHAPTER 2: Fungal Infections
Hyperpigmented
(winter, left) and
hypopigmented
(summer; middle and
right) scaling lesions
on the trunk
Inconspicuous
hyphae and spores
in H&E stain:
so-called invisible
dermatosis. Very
subtle or no
inflammatory reaction
The dimorphic lipophilic yeast Malassezia form in healthy skin to a pathogenic myce-
furfur (Pityrosporum ovale or orbiculare) is part lial form in diseased skin. Azelaic acid,
of the normal skin flora and presents with which is produced by the yeasts, blocks mel-
varying phenotypes. Hyphae and spores anin synthesis and serves as a blanching
may regularly be found in the follicle ostia. agent, which in conjunction with the UV‐
Massive expansion of Malassezia colonies shielding effect of the overlying scales at
preferentially affects young adults during affected sites accounts for the changes in
summer months, mostly in humid climates, skin color: whitish in the summer and
with hyperhidrosis and occlusive dressing, brownish in the winter.
but also immunocompromised patients CF: Small, sharply demarcated hypo‐ or
with subfebrile body temperature (telltale hyperpigmented leaf‐like or geographical
sign). Pityriasis versicolor is a result of the patches with discrete pityriasiform scal-
yeast’s transformation from a saprophytic ing, preferentially on the trunk.
2.1: Superficial Cutaneous Fungal Infections 87
Agminated acneiform
lesions
Infection of hair follicles, preferentially in DD: Acne; “Mallorca acne”; other forms
immunocompromised patients. of infectious and non‐infectious folliculi-
CF: Monomorphic eruption of small tis; neonatal cephalic pustulosis.
acneiform lesions, mostly on the trunk.
HF: Reference
• Malassezia furfur, hyphae and spores, Clemmensen, O. J., & Hagdrup, H. (1991).
within follicle and follicle ostium Splendore‐Hoeppli phenomenon in Pity
• Dense perifollicular infiltrate with pre- rosporum folliculitis (pseudoactinomycosis
dominant neutrophils of the skin). J Cutan Pathol, 18(4), 293–297.
• Neutrophils in follicular wall Sina, B., Kauffman, C. L., & Samorodin, C. S.
• Perifollicular debris and granulomatous (1995). Intrafollicular mucin deposits in
Pityrosporum folliculitis. J Am Acad Dermatol,
infiltration (late)
32(5 Pt 1), 807–809.
Psoriasiform
acanthosis and
papillomatosis with
mounds of
parakeratosis around
the follicle ostia
(telltale sign)
CF: Erythema and scaling, preferentially HF: Psoriasiform acanthosis and hyper-
in the centrofacial area, breast, scalp. parakeratosis overlying hair follicle ostia,
exocytosis of neutrophils.
2.1.9 Tinea Nigra
Pigmented macule
on the palm
produced by
melanin-synthesizing
hyphae
Pigmented hyphae in
the cornified layer
(arrow middle: H&E
bottom: PAS left and
Grocott right)
Str.corneum
Superficial mycotic infection by the geo- HF: Elongated empty spaces and gaps
philic and dematiaceous mold Hortaea wer- within the thickened cornified layer,
neckii (formerly Exophiala werneckii). often associated with cloudy whitish foci
CF: Preferentially in tropical climates, a where PAS stain may show pigmented
circumscribed asymptomatic lentiginous hyphae and spores. Although Hortaea
hyperpigmentation occurs on the soles, werneckii is a melanin‐producing fungus,
rarely on the palms. Clinically diagnosis is immunohistochemical stains with anti‐
usually missed as the lesions appear to be melanocytic antibodies (HMB45) are
of melanocytic origin. usually negative.
90 CHAPTER 2: Fungal Infections
°no pictures
2.2 Subcutaneous Mycoses
2.2.1 Sporotrichosis
Linear “sprotrichoid”
spreading nodules on
the lower arm (left)
Inflammatory
granulomatous
dermal infiltrate
(middle)
Yeasts in
multinucleated cells
(right, arrow)
Granulomatous
inflammation;
yeasts in giant cells
(PAS left)
Yeasts (Grocott
middle and PAS
right, arrows)
DD: Other deep fungal and mycobacte- of cutaneous sporotrichosis in Rio de Janeiro:
rial infections, leprosy, syphilis, A series of 119 consecutive cases. J Cutan
leishmaniasis. Pathol, 38(1), 25–32.
Rodriguez, G., & Sarmiento, L. (1998). The
asteroid bodies of sporotrichosis. Am J
Reference Dermatopathol, 20(3), 246–249.
Zhang, Y. Q., Xu, X. G., Zhang, M., Jiang, P., Zhou,
Quintella, L. P., Passos, S. R., do Vale, A. C., X. Y., Li, Z. Z., & Zhang, M. F. (2011). Sporo
Galhardo, M. C., Barros, M. B., Cuzzi, trichosis: Clinical and histopathological mani
T., . . . Schubach Ade, O. (2011). Histopathology festations. Am J Dermatopathol, 33(3), 296–302.
Verrucous lesions on
the hand (left)
Acanthosis and
papillomatosis.
Diffuse inflammatory
infiltrate in the
upper dermis
(right)
Pigmented spores
and hyphae (arrows)
Inset:
Grocott
Several darkly pigmented fungi that thrive in evolving into a papillomatous plaque with
soil and in decaying wood, mostly in tropical verrucous hyperkeratosis. These lesions
and subtropical areas, cause chromoblastosis. may enlarge to wide verrucous plaques,
Sites of predilection are the feet where infec- covering most of the foot.
tion occurs mostly via banal superficial HF:
wounds. Five organisms are responsible for • Acanthosis and papillomatosis
most cases: Fonsecaea pedrosoi, Phialophora ver- • Variable hyperkeratosis, often associ-
rucosa, Fonsecaea compacta, Cladosporium carrio- ated with marked pseudocarcinomatous
nii, and Rhinocladiella aquaspersa. hyperplasia
CF: At the site of inoculation – mostly the • Granulomatous infiltrate in the dermis
feet – a slowly growing papule occurs, with small abscesses
2.3: Systemic Mycoses (Deep Fungal Infections) 93
Molluscoid lesions on
the arm (left)
Pseudobullous
molluscoid lesion
(right)
Schematic drawing
of cryptococci with
distinct “halo”
(left)
Cryptococci with
mucoid capsules
(middle-right and
bottom)
Granulomatous
infiltrate with
multinucleated cells
containing spores
(top and middle)
Cryptococci in the
dermis and in
multinucleated cells.
PAS stain (left)
Cryptococci:
Grocott stain
(right)
Verrucous plaques
on the nose
(left)
Granulomatous
infiltrate in the dermis
(right)
Intraepidermal and
dermal abscesses
(left)
Multinucleated cells
harboring fungi
(middle-right and
bottom left;
Grocott stain)
Schematic drawing
of blastomycetic
spores within
multinucleated cell
(right)
Keloidal nodules on
the earlobe (left)
Granulomatous
inflammation
with plethora
of fungi, intra- and
extracellularly
(left and right)
Multinucleated
histiocyte
(Langhans cell) with
asteroid body
(left, long arrow) and
adjacent spore
(left, short arrow)
Grocott (middle).
Schematic drawing
(right)
2.3.4 Histoplasmosis
Nodular lesions on
the back
Granulomatous
infiltrate (left) with
spores in
macrophages
(PAS right)
PAS-positive spores
in macrophages
and extracellular
(left PAS; inset:
Grocott; right anti-
BCG antibody
staining)
Swelling and
superficial ulceration
of the elbow
(left).
Granulomatous
infiltrate in the dermis
(right)
Inflammatory
infiltrate composed
of histiocytes,
lymphocytes,
plasma cells, and
eosinophils
(left and right)
Large spherules,
replete with
endospores (arrows
left and right, and
bottom: schematic
drawing)
Midfacial swelling
and inflammation
with involvement of
the nasal mucosa
(left)
Ulcerating lesion on
the lip and nose
(right) (Courtesy of
R. Azambuja, M.D.;
Brasilia)
Granulomatous
inflammation with
yeasts showing
telltale
“steering-wheel”
configuration (inset).
(PAS, right)
2.3.7 Emmonsiosis
Papular and
ulcerating lesion on
the upper arm
(left)
Massive
granulomatous
infiltrate in the dermis
(right)
Intracellular and
extracellular budding
of yeast-like
elements.
Inset: Grocott stain
Inflammatory
induration with
papulopustules (left)
Branching hyphae
and spores in the
dermis (circle)
Ulcerating and
necrotic lesion on the
face (left)
Large hyphae
(arrows)
amid dense
inflammatory
infiltrate.
Grocott (right)
DD: Aspergillosis (hyphae with typical Requena, L., Sitthinamsuwan, P., Santonja, C.,
septa and not branching at right angles); Fernandez‐Figueras, M. T., Rodriguez‐
granulomatous pyoderma. Peralto, J. L., Argenyi, Z., . . . Kutzner, H.
(2012). Cutaneous and mucosal mucormy-
Reference cosis mimicking pancreatic panniculitis and
gouty panniculitis. J Am Acad Dermatol, 66(6),
Geller, J. D., Peters, M. S., & Su, W. P. (1993). 975–984.
Cutaneous mucormycosis resembling super- Umbert, I. J., & Su, W. P. (1989). Cutaneous
ficial granulomatous pyoderma in an immu- mucormycosis. J Am Acad Dermatol, 21(6),
nocompetent host. J Am Acad Dermatol, 1232–1234.
29(3), 462–465.
2.4.3 Hyalohyphomycosis
Subcutaneous
nodular lesion (left)
due to Fusarium
solani
Dense nodular
infiltrate in the dermis
(right)
The relevant infectious organisms are DD: Other deep fungal infections;
Fusarium and Pseudallescheria boydii that ecthyma gangrenosum; bacterial abscess;
are hyaline, colorless molds, ubiquitously squamous cell carcinoma.
present in soil. These molds are glassy
(hyalo‐), non‐pigmented, and have sep- Reference
tate hyphae. Arrese, J. E., Pierard‐Franchimont, C., &
CF: Superficial hemorrhagic and necrotic Pierard, G. E. (1996). Fatal hyalohyphomy-
skin lesions, ecthyma gangrenosum‐like cosis following Fusarium onychomycosis in
flat ulcers, subcutaneous nodular and an immunocompromised patient. Am J
mycetoma‐like infiltrates are found Dermatopathol, 18(2), 196–198.
mostly in immunocompromised patients. Bushelman, S. J., Callen, J. P., Roth, D. N., &
Secondary infection of superficial wounds Cohen, L. M. (1995). Disseminated Fusarium
may occur. solani infection. J Am Acad Dermatol, 32(2 Pt
HF: Inflamed nodules and eschars with 2), 346–351.
Griffin, T. D., McFarland, J. P., & Johnson, W.
ischemic necrosis, resulting from septic
C. (1991). Hyalohyphomycosis masquerad-
fungus‐invasion into vessels. PAS‐positive
ing as squamous cell carcinoma. J Cutan
fungi.
Pathol, 18(2), 116–119.
106 CHAPTER 2: Fungal Infections
2.4.4 Phaeohyphomycosis
Pseudocyst
with granulomatous
infiltrate (right)
Pigmented spores
and hyphae
(left, arrows)
PAS (right)
CF: The term dematiaceous denotes organ- • Abundant budding spores and branch-
isms, in particular fungi, which produce a ing pigmented hyphae
dark pigment. This group of pathogenic • Demonstration of melanin by Fontana‐
organisms causes the fungal infections phae- Masson stain
ohyphomycosis (phaeo‐ also meaning pig- DD: Chromoblastomycosis; mycetomas.
mented) and chromoblastomycosis, which
may present with various clinical symptoms,
ranging from superficial pigmented lesions Reference
as tinea nigra to subcutaneous nodules and
fulminant abscess formation. Systemic dis- Kapatia, G., Pandey, T., Kakkar, N., Kaur, H., &
semination via hematogenic spread in Verma, R. (2019). Facial phaeohyphomyco-
sis in an immunocompetent individual: A
immunocompromised patients results in a
rare presentation of a rare fungus. Am J
severe life‐threatening condition.
Dermatopathol, 41(2), 137–139.
HF: Ronan, S. G., Uzoaru, I., Nadimpalli, V.,
• Pseudocystic and dermal neutrophilic Guitart, J., & Manaligod, J. R. (1993).
abscesses Primary cutaneous phaeohyphomycosis:
• Granulomatous inflammation with Report of seven cases. J Cutan Pathol, 20(3),
plasma cells 223–228.
2.4: Opportunistic Fungal Infections 107
2.4.5 Protothecosis, Cutaneous
CF: Prototheca wickerhamii and Prototheca zopfi, DD: Granulomatous foreign body reac-
achlorophyllic algae, are ubiquitous present tions; deep mycoses.
in soil, plants, and contaminated water.
When entering skin wounds in immuno- Reference
compromised patients, they may produce a Hillesheim, P. B., & Bahrami, S. (2011).
nodular and ulcerating inflammation. Cutaneous protothecosis. Arch Pathol Lab
HF: Inflammatory reaction with necrotiz- Med, 135(7), 941–944.
ing and caseating granuloma, containing Walsh, S. V., Johnson, R. A., & Tahan, S. R.
algae extracellularly or within giant cells. (1998). Protothecosis: An unusual cause of
Typically, the large, round organisms chronic subcutaneous and soft tissue infec-
show internal septation with endospores. tion. Am J Dermatopathol, 20(4), 379–382.
C H APT ER 3
Viral Infections
CHAPTER MENU
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
109
110 CHAPTER 3: Viral Infections
Viruses (DNA and RNA) are obligate reaching from inconspicuous exanthemas
intracellular parasites. Their replication
to papules, vesicles, and necrotic lesions.
depends on the metabolism of the host These morphological patterns allow for a
cells. Viruses, due to their tropisms for dif- more practical and clinical approach
ferent tissues (epithelia, endothelia, nerv- toward differentiation of the various viral
ous system, vascular structures), cause a dermatoses than the taxonomy of viruses.
plethora of clinical cutaneous symptoms,
Herpes simplex on
the lips (left), penis
(middle), and finger
(right))
• Secondary leukocytoclastic vasculitis Laggis, C., Wada, D., Shah, A., & Zussman, J.
exclusively in VZV infection (this virus is (2020). Eosinophils are surprisingly common
both epitheliotropic and endotheliotropic) in biopsy specimens of cutaneous herpes
• Concomitant cytomegalovirus infection simplex virus and varicella zoster virus infec-
tions: Results of a comprehensive histo-
may alter the histological features
pathologic and clinical appraisal. J Cutan
DD: Other viral eruptions; drug eruption; Pathol, 47(1), 6–11.
acute graft‐versus‐host reaction; erythema Pomerantz, H., Wang, H., Heilman, E. R.,
multiforme; non‐viral ulcers; pyoderma Sharon, V. R., & Gottesman, S. P. (2020).
gangrenosum; Rickettsiosis. Peculiar vegetative tumor‐like genital herpes
simplex nodules with brisk tissue eosino-
Reference philia in patients with human immunodefi-
ciency virus infection. J Cutan Pathol, 7(2),
Boyd, A. S., Zwerner, J. P., & Miller, J. L.
150–153.
(2012). Herpes simplex virus‐induced plas-
Saunderson, R. B., Tng, V., Watson, A., &
macytic atypia. J Cutan Pathol, 39(2),
Scurry, J. (2016). Perianal herpes simplex
270–273.
virus infection misdiagnosed with pyoderma
Garib, G., Hughey, L. C., Elmets, C. A., Cafardi,
gangrenosum: Case of the month from the
J. A., & Andea, A. A. (2013). Atypical pres-
Case Consultation Committee of the
entation of exophytic herpes simplex virus
International Society for the Study of
type 2 with concurrent cytomegalovirus
Vulvovaginal Disease. J Low Genit Tract Dis,
infection: A significant pitfall in diagnosis.
20(2), e14–15.
Am J Dermatopathol, 35(3), 371–376.
3.1.2 Varizella/Zoster Virus (VZV/HHV-3)
Varicella
(chickenpox)
(left and right)
Herpes zoster
(shingles). Segmental
and generalized
lesions (left and right)
Necrotizing zoster
(bottom right)
Intraepidermal
blisters (left)
Blister with
acantholytic
keratinocytes
containing viral
material
(immuno-stain with
anti-VZV antibody,
right)
Ballooned necrotic
keratinocytes with
“steel-gray” nuclei.
Few multinucleated
keratinocytes. (left)
Immunostain with
anti-VZV antibody
(right)
Gelöste
Ball. Ballons
Degen.
CF: Highly contagious viral disease, which c haracteristically sparing the palms and soles.
primarily affects the respiratory tract and Cutaneous lesions usually are in different
then spreads hematogenously, producing a stages of evolution, showing early lesions
characteristic polymorphic papulovesicular and older necrotizing lesions with crust for-
eruption, involving almost all parts of the mation side by side (the so‐called metachro-
integument as well as the palate, but nous synchrony of cutaneous lesions).
3.1: Herpes Viruses 113
Acantholytic and
necrotic (ballooned)
keratinocytes with
smudged nuclei
Syncytial
multinucleated
keratinocytes with
“steel-gray” nuclei
(middle and bottom)
H&E stain
Immunohistochemical
detection of
varicella-zoster virus
with anti-VZV
antibody
“Zoster incognito”:
note sparing of the
epidermis.
Necrosis of only hair
follicle and
sebaceous glands
(“sebaceitis”) with
dense inflammatory
reaction
Epidermal necrosis
Obliterating, mostly
leukocytoclastic,
vasculitis: swelling of
vessel walls,
prominent thrombi,
neutrophils, and
neutrophilic dust
(middle and below)
The VZV is both epitheliotropic and endo- Synchronous involvement of both cuta-
theliotropic‚ which explains the involve- neous sites and internal organs (e.g. liver)
ment of adjacent vessels in cutaneous VZV is not unusual in herpes zoster.
infection/herpes zoster. Lesions of herpes
zoster may be hemorrhagic‚ and adjacent Reference
leukocytoclastic vasculitis is not unusual. Burgard, B., Smola, S., Vogt, T., & Muller, C. S.
Remarkably, concomitant vasculopathic L. (2018). Small vessel vasculitis in herpes
changes may occur remotely from the site zoster – discussion of current aspects of vari-
of the cutaneous infection, for example, cella zoster virus vasculopathy. Am J
in the brain or in internal organs. Dermatopathol, 40(8), 602–604.
3.1: Herpes Viruses 117
Monomorphous non-
epidermotropic
infiltrate of lymphoid
cells
Hairy leukoplakia on
the lateral site of the
tongue (left, circle)
Three-layered
sandwich pattern
(“red-white-red”) with
superficial eosinophilic
jagged parakeratosis,
overlying pale
edematous acanthosis
with edematous clear
cells (right)
Pale epithelial clear
cells with edema in
the middle-mucosa
Nuclear EBV
(EBER in situ
hybridization, right)
Multiple perianal
ulcers (middle)
Acanthosis,
papillomatosis,
dermal infiltrate
(right)
Pathognomonic
large stromal or
endothelial cells
with swollen nuclei
(arrows, left)
Anti-CMV
immunostain (bottom
right)
The infection starts with viremia, follow- CF: The skin is only rarely involved,
ing primary oropharyngeal inoculation showing small blisters with superficial
with the cytomegalovirus. Preferentially ulceration and scale crust formation.
immunosuppressed and post‐transplant HF: A telltale sign are swollen and slightly
patients are at risk of infection. detached endothelial cells with intracyto-
Pathognomonic in the skin are small plasmic round basophilic inclusions
ulcers, but other clinical presentations of (“owl’s eye” cells). Rarely, these virus‐
cytomegalovirus infection are not laden cells may also be found in other tis-
unusual. sue components (fibroblasts).
DD: Ecthyma contagiosum.
Rubella-like macular
viral rash
Erythematous
patches, pityriasiform
scales, and telltale
peripheral collarette
(left)
Acanthosis and
patchy
hyperkeratosis.
Erythrocytes within
superficial infiltrate
(right)
Hyperparakeratosis.
Superficial edema,
and inflammatory
infiltrate; moderate
exocytosis
Signs of acute
inflammation:
erythrocytes within
the epidermis
and within the upper
dermis (arrow); no
signs of vasculitis
Macular lesions on
the soles (left)
Bizarre thin-walled
jagged vessels in the
upper dermis
(right top and bottom)
Vascular slits in
conjunction with
regular vessels (top
right and bottom left)
Thin-walled, newly
formed vascular
spaces, engulfing
preexisting vessels
(arrows)
(“promontory sign”)
(right)
Nodular lesions in a
patient with AIDS
(left and top right)
Nodular lesions in
the dermis (bottom
right)
Dense proliferation of
monomorphic
spindle cells without
significant
pleomorphism.
Slit-like vascular
spaces filled with
erythrocytes
Eosinophilic
phagocytosed
erythrocytes
(“hyaline globules”)
(arrows)
Bizarre lymphatic
spaces in the upper
and mid-dermis
closely reminiscent of
progressive
lymphangioma
Jagged vascular
spaces amid a
dense collagenous
stroma (left)
“Promontory sign”
(right)
Concentric rings of
small lymphocytes
penetrated by
interfollicular
capillaries
CF: Castleman’s disease (CAD) is an unu- cells within the interfollicular areas.
sual lymphoid hyperplasia. The disease Subtle hyalinization of vessel walls
may be systemic or localized and can DD: Glomeruloid hemangioma; follicular
involve lymph nodes and extra nodal lymphoma.
sites. Cutaneous CAD characteristically
presents with solitary or multiple asymp- Reference
tomatic nodules on the trunk. The plasma
Chan, J. K., Fletcher, C. D., Hicklin, G. A., &
cell‐rich variant of multicentric CAD in
Rosai, J. (1990). Glomeruloid hemangioma.
HIV patients is associated with HHV-8.
A distinctive cutaneous lesion of multicentric
HF: Castleman’s disease associated with POEMS
• Nodular, well‐circumscribed round cell syndrome. Am J Surg Pathol, 14(11),
infiltrate in the dermis and subcutis 1036–1046.
• Prominent follicular growth pattern Chen, H., Xue, Y., Jiang, Y., Zeng, X., & Sun, J.
with atrophic germinal centers F. (2012). Cutaneous and systemic plasmacy-
• Concentric rings of small lymphocytes, tosis showing histopathologic features as
mixed‐type Castleman disease: A case report.
penetrated by interfollicular capillaries
Am J Dermatopathol, 34(5), 553–556.
• Germinal centers with multinucleated
Naghashpour, M., Cualing, H. D., Szabunio,
giant cells of the Warthin–Finkeldey type
M., & Bui, M. M. (2010). Hyaline‐vascular
(that are usually encountered in measles) Castleman disease: A rare cause of solitary
• Mixed infiltrate of epithelioid histio- subcutaneous soft tissue mass. Am J
cytes and lymphoplasmacytoid B‐cells. Dermatopathol, 32(3), 293–297.
Pronounced vascularity with large num- Yang, S. G., Cho, K. H., Bang, Y. J., & Kim, C.
bers of small vessels and thickened hya- W. (1998). A case of glomeruloid hemangi-
linized vessel walls oma associated with multicentric Castleman’s
• The plasma cellular type of CAD con- disease. Am J Dermatopathol, 20(3), 266–270.
tains abundant sheets of mature plasma
Verrucae vulgares on
the fingers (left) and
on the tip of the nose
(right)
“Digitate” verrucous
epidermal
hyperplasia
Hypergranulosis
(long arrow)
Koilocytes
(short arrow)
Subepidermal
inflammatory infiltrate
Plantar warts
Pincer-like collarette
with central verrucous
acanthopapilloma
(upper right and
bottom left)
Anti-HPV L1
immunostain of HPV
viral capsid (upper
right/bottom)
Koilocytes (arrows)
under basket-weave
orthokeratosis
Cauliflower-
like proliferations
(left)
Acanthosis,
papillomatosis;
dilated vessels;
no hyperkeratosis
(right)
Flat verruciform
papules (left)
Flat papules
on the glans penis
Acanthosis,
papillomatosis, (right)
Enlarged
epithelial cells,
atypical mitoses
(arrows), pyknoses
Multiple verrucae in
EV (right)
Plump acanthosis
and papillomatosis
Enlarged
keratinocytes with
basophilic cytoplasm
(“blue cells”)
(arrows)
3.3.1 Measles
Measles exanthema
on trunk, extremities,
face, and palate
(Koplik spots, arrow)
Predominantly
lymphocytic
perivascular infiltrate,
swelling of vessel
walls (middle and
bottom)
Measles is caused by an RNA paramyxovi- trunk, and extremities. Lesions may get
rus. Non‐vaccinated young children are at hemorrhagic. Mucosal involvement is
a particularly high risk of infection due to common: typical Koplik spots on the pal-
the high contagious potential of the mea- ate are a telltale sign of measles infection.
sles virus. HF:
CF: Following a prodromal phase with • Follicular necrotic keratinocytes and
fever and general malaise, skin lesions small intraepidermal clusters of follicu-
appear as a generalized eruption of red locentric necrotic keratinocytes are the
macules and papules, starting behind the leading histopathological criterion of
ears and spreading to the face, neck, measles virus infection
3.4: Parvovirus Infections and Coxsackievirus Infections 139
Tiny hemorrhagic
papules in a
“gloves-and-socks
pattern” (left and
right)
Sparse perivascular
lymphocytic infiltrate
in the upper dermal
plexus (bottom left)
Immunostain with
anti-PVB19 antibody
showing virus capsid
within endothelia
(bottom right)
Eroded blisters on
the palate (left)
Blisters on fingers,
sole, and palm (right)
Spongiotic vesicle
and ballooning
epidermal necrosis
(insert)
The highly contagious disease caused by CF: The infection primarily involves
Coxsackievirus A16 commonly affects chil- palms, soles, buttocks, and palate with
dren and adolescents. The highly conta- conspicuous intact blisters at the acral
gious Coxsackie virus A16 is a member of sites and eroded erythematous lesions on
the Picornaviridae family of small RNA the mucous membrane. The buttocks may
viruses. Enterovirus 71 and others may show eruptive small vesicles with rapid
induce identical clinical symptoms. subsequent erosion. There may be a slight
142 CHAPTER 3: Viral Infections
Multiple spiny
keratotic papules on
the forehead (left)
Accumulation of
granular
parakeratotic debris
within hair follicles
(right)
Electron microscopy
of intranuclear
polyoma virus
structures (right
bottom)
Follicular spicules of
the nose in multiple
myeloma (left)
Immunoglobulins in
follicular ostium. IgM
immunostain (inset)
(Courtesy of
L. Requena, MD,
Madrid)
This rare folliculocentric cutaneous dis- (2012). Ultrastructural and molecular confir-
ease is commonly associated with human mation of the trichodysplasia spinulosa‐asso-
polyoma virus infection (Trichodysplasia ciated polyomavirus in biopsies of patients
spinulosa human polyoma virus/Ts‐HPyV) with trichodysplasia spinulosa. J Cutan Pathol,
39(11), 1004–1009.
in immunocompromised patients.
Kadam, P., Pan, T., Gates, R., Rivetz, J., Rady, P.,
CF: Small, follicle‐bound, spiny, keratotic
Tyring, S., & Carlson, J. A. (2017). Detection
papules mostly on the face, resembling fine
of beta‐human papillomavirus in a child with
hairs or follicular spicules. Subsequently, polyomavirus‐associated trichodysplasia spi-
eyebrows and eyelashes disappear due to nulosa. Am J Dermatopathol, 39(12), 928–931.
destruction of hair follicle epithelium. Kaddu, S., Soyer, H. P., & Kerl, H. (1995).
HF: Palmar filiform hyperkeratosis: A new para-
• Granular hair shafts with coarse kerato- neoplastic syndrome? J Am Acad Dermatol,
hyalin granules 33(2 Pt 2), 337–340.
Matthews, M. R., Wang, R. C., Reddick, R. L.,
• Accumulation of granular parakeratotic
Saldivar, V. A., & Browning, J. C. (2011).
debris within hair follicle
Viral‐associated trichodysplasia spinulosa: A
• Disorganized eosinophilic inner
case with electron microscopic and molecu-
root sheath cells with few necrotic lar detection of the trichodysplasia spinu-
keratinocytes losa‐associated human polyomavirus. J
• Conspicuously large trichohyalin gran- Cutan Pathol, 38(5), 420–431.
ules within keratinocytes of inner root Nazzaro, P., Argentieri, R., Balus, L., Bassetti,
sheath F., Fazio, M., Giacalone, B., & Ponno, R.
DD: Warts; keratosis pilaris; ulerythema (1974). [Paraneoplastic syndrome with pap-
ulo‐keratosic lesions of the extremities and
ophryogenes; follicular spicules of the nose,
diffuse spinulose pilar keratosis]. Ann
associated with multiple myeloma (para-
Dermatol Syphiligr (Paris), 101(4), 411–413.
neoplastic (Nazzaro) syndrome).
Paul, C., Fermand, J. P., Flageul, B., Caux, F.,
Duterque, M., Dubertret, L., & Aractingi, S.
Reference
(1995). Hyperkeratotic spicules and mono-
Elaba, Z., Hughey, L., Isayeva, T., Weeks, B., clonal gammopathy. J Am Acad Dermatol,
Solovan, C., Solovastru, L., & Andea, A. 33(2 Pt 2), 346–351.
144 CHAPTER 3: Viral Infections
Requena, L., Sarasa, J. L., Ortiz Masllorens, F., nose: A peculiar cutaneous manifestation of
Martin, L., Pique, E., Olivares, M., … Gomez multiple myeloma with cryoglobulinemia.
Octavio, J. (1995). Follicular spicules of the J Am Acad Dermatol, 32(5 Pt 2), 834–839.
Tumor plaques on
cheek and nose
Inset: CK20-positive
tumor cells with
characteristic
perinuclear dot-like
positivity
Figure 3.5.2 Merkel Cell Carcinoma (Primary Neuroendocrine Carcinoma of the Skin; Trabecular
Carcinoma of Toker).
Source: Burg et al. (2019). Atlas of Dermatopathology: Tumors, Nevi, and Cysts (pp. 360, 361).
Oxford: Wiley.
3.5: Polyoma Virus Infections 145
Miraflor, A. P., LeBoit, P. E., & Hirschman, S. A. Histologically, in acute lesions, there is
(2016). Intraepidermal Merkel cell carci- prominent reticular degeneration and
noma with pagetoid Bowen’s disease. J Cutan necrosis of the epidermis, ballooning, and
Pathol, 43(11), 921–926. necrosis of keratinocytes. Blister formation
Mitteldorf, C., Mertz, K. D., Fernandez‐
may be minimal. Multinucleated giant
Figueras, M. T., Schmid, M., Tronnier, M., &
cells can be present. Accompanying papil-
Kempf, W. (2012). Detection of Merkel cell
lary edema with erythrocyte extravasation
polyomavirus and human papillomaviruses
in Merkel cell carcinoma combined with and inflammatory infiltrate consisting of
squamous cell carcinoma in immunocompe- lymphocytes, neutrophils, and eosinophils
tent European patients. Am J Dermatopathol, is seen in the upper and mid‐dermis.
34(5), 506–510. DD: Due to their significant morphologi-
Succaria, F., Radfar, A., & Bhawan, J. (2014). cal overlap, poxvirus infections are
Merkel cell carcinoma (primary neuroendo- exceedingly difficult to differentiate from
crine carcinoma of skin) mimicking basal cell each other (e.g. variola vera versus mon-
carcinoma with review of different histo- key pox). Advanced molecular diagnostic
pathologic features. Am J Dermatopathol, methods (PCR; sequencing methodology;
36(2), 160–166.
electron microscopy/negative staining) in
Veija, T., Kero, M., Koljonen, V., & Bohling, T.
conjunction with clinical and historical
(2019). ALK and EGFR expression by immu-
data are mandatory. Remarkably, poxvi-
nohistochemistry are associated with Merkel
cell polyomavirus status in Merkel cell carci- ruses, in particular monkey pox, are
noma. Histopathology, 74(6), 829–835. endemic in large parts of Africa
(Democratic Republic of the Congo);
acute infections with monkey pox may
3.6 Poxviruses mimic variola vera; impetigo contagiosa;
Poxviruses are large complex DNA viruses, dermatitis due to mites; varicella; pustula
comprising the family of orthopox viruses maligna (anthrax).
(cowpox/catpox, monkey pox, vaccinia,
Reference
and variola), parapoxviruses (ecthyma
contagiosum/orf and milker’s nodule), Asiran Serdar, Z., Yasar, S., Demirkesen, C., &
and molluscum pox viruses. Aktas Karabay, E. (2018). Poxvirus‐induced
vascular angiogenesis mimicking pyogenic
3.6.1 Orthopox Virus Infections granuloma. Am J Dermatopathol, 40(9),
Orthopox virus infections have clinical e126–129.
and histological features in common. Molina‐Ruiz, A. M., Santonja, C., Rutten, A.,
Differences may be subtle. Cerroni, L., Kutzner, H., & Requena, L.
Clinically, there usually is erythematous (2015). Immunohistochemistry in the diag-
swelling at the site of inoculation with a nosis of cutaneous viral infections‐ part II:
papulovesicular eruption, evolving into Cutaneous viral infections by parvoviruses,
poxviruses, paramyxoviridae, picornaviri-
umbilicated pustules with focal hemor-
dae, retroviruses and filoviruses. Am J
rhagic necrosis and crust formation.
Dermatopathol, 37(2), 93–106.
3.6: Poxviruses 147
Massive
inflammatory infiltrate
in the dermis
Inset: papulopustular
lesion with central
necrosis
Ballooning
degeneration and
necrosis of
keratinocytes. Telltale
large intracytoplasmic
globular deposits of
virus capsid (right,
arrow)
Field voles, rats, and mice are the natural the conjunctivae is particularly dangerous
reservoir of the virus. Transmission to and often clinically missed. Deer pox (in
humans occurs via cats or directly via rats hunters) may cause identical symptoms.
that are kept by young people as pets.
Remarkably, a high percentage of cats Reference
harbor not only cowpox virus but also Nasemann, T., Mayr, A., Schaeg, G., Kimmig,
Bartonella under their claws and conse- W., & Mahnel, H. (1987). [Cowpox virus
quently are a great infectious peril for infection in a young girl]. Hautarzt, 38(7),
immunocompromised people. Symptoms 414–418.
include a mild fever and lymphadenopa- Wienecke, R., Wolff, H., Schaller, M., Meyer,
thy. Rarely, lesions may present with mas- H., & Plewig, G. (2000). Cowpox virus infec-
sive edema, erythema, focal blistering, tion in an 11‐year‐old girl. J Am Acad
and large black eschars. Involvement of Dermatol, 42(5 Pt 2), 892–894.
148 CHAPTER 3: Viral Infections
Papulopustular
lesion with central
necrosis (left)
Schematic drawing
of histopathologic
changes in variola
(right). Original
artwork: Table XXV
from PG Unna’s
Histologischer Atlas
zur Pathologie der
Haut, Leipzig 1910
Moulage (Museum
Zürich) showing
Smallpox (Variola
Vera) (left)
Intraepidermal
vesicles and reticular
degeneration of the
epidermis. Necrosis
and hemorrhage in
the upper dermis.
Dense inflammatory
Infiltrate (left)
The causative agent is Parapoxvirus ovis (orf • Dermal round cell infiltrate, often studded
virus). Goats, sheep‚ and lambs are the natu- with multiple CD30‐positive lymphocytes
ral reservoir of the virus. Infection occurs via and CD123‐positive plasmacytoid den-
direct animal contact (shepherds, butchers). dritic cells (remarkably an almost identical
CF: Marked erythematous swelling at the immunophenotype may be found in
site of inoculation with erythema and iris‐ inflamed molluscum contagiosum)
like edematous blister formation, often • Excessive neovascularization of densely
hemorrhagic and crusted, followed by packed capillaries and venules may
eschar formation. occur beneath the lesion, often suggest-
HF: ing a benign vascular tumor
• Reticular degeneration of upper parts of DD: Erythema multiforme; milker’s nod-
epidermis with telltale “tricolore sign” ule; pyogenic granuloma.
showing blue‐white‐red tinged epider-
mal layers Reference
• Marked ballooning of keratinocytes Asiran Serdar, Z., Yasar, S., Demirkesen, C., &
• Eosinophilic intracytoplasmic inclu- Aktas Karabay, E. (2018). Poxvirus‐induced
sions of virus capsid in keratinocytes vascular angiogenesis mimicking pyogenic
(Guarnieri bodies) granuloma. Am J Dermatopathol, 40(9),
• Necrosis and hemorrhage (late) e126–129.
Crusty lesion on a
cow’s udder (left)
DD: Ecthyma contagiosum; insect bite; Milker’s nodule in a healthy young woman.
bacterial folliculitis. J Am Acad Dermatol, 49(5), 910–911.
Werner, B., Massone, C., Kerl, H., & Cerroni, L.
Reference (2008). Large CD30‐positive cells in benign,
atypical lymphoid infiltrates of the skin. J
Werchniak, A. E., Herfort, O. P., Farrell, T. J., Cutan Pathol, 35(12), 1100–1107.
Connolly, K. S., & Baughman, R. D. (2003).
Grouped umbilicated
papules
Crateriform
symmetric tumor with
molluscum bodies
Molluscum bodies
(metachromatic
intracytoplasmic
inclusions: basophilic
virus capsid)
(arrows)
CF: Molluscum poxvirus is the causative are mostly multiple, inflamed, or eczema-
agent. Typically, children and immuno- tous. Characteristically, the lesions are ele-
compromised patients are affected. Lesions vated papules with a central dell.
152 CHAPTER 3: Viral Infections
Asymmetric
periflexural
exanthema (left)
(courtesy of
R. Fölster-Holst,
M.D., Kiel)
Mild perivascular,
lymphohistiocytic
inflammation
(top right)
Immunohistochemical
staining with anti-
PVB19 antibody:
virus capsid within the
cytoplasm of the
endothelial cells
(bottom right, arrows)
The disease occurs in children and in demonstration of parvovirus B19 viral protein
adults. 2 in periflexural exanthema in an adult, sup-
CF: Tiny papules, asymmetrically, distrib- porting antibody‐dependent enhancement as
uted preferentially in the unilateral axil- means of endothelial uptake of the virus. Am J
Dermatopathol, 40(2), e19–e24.
lary region of one side of the trunk.
Santonja, C., Requena, L., Polo Sabau, J., &
HF: Sparse perivascular, mostly lympho-
Pielasinski Rodriguez, U. (2018). Image gal-
cytic inflammation.
lery: Immunohistochemical detection of par-
DD: Pityriasis rosea; drug reaction; con- vovirus B19 VP2 in periflexural primary
tact dermatitis; Gianotti–Crosti syndrome. infection in an adult female patient. Br J
Dermatol, 178(1), e65.
Reference
Santonja, C., Pielasinski, U., Polo, J., Kutzner, H.,
& Requena, L. (2018). Immunohistochemical
3.7.2 Eruptive Pseudoangiomatosis
Tiny erythematous
papules on the arm,
surrounded by a faint
hypopigmented halo
(left, arrows). Ectatic
small vessels in the
dermis (right)
Small papules
Pityriasiform
parakeratosis on top
of slight spongiotic
dermatitis with focal
vacuolization. Sparse
lymphohistiocytic
infiltrate (right)
Predominantly
lymphocytic infiltrate
with spongiotic
dermatitis
Vacuolization at
junctional zone.
Exocytosis of
lymphocytes.
Apoptotic
keratinocytes
• Band‐like lymphocytic infiltrate in the Kim, J. E., Yun, W. J., Mun, S. K., Yoon, G. S.,
upper dermis with interface pattern Huh, J., Choi, J. H., & Chang, S. (2011).
• Remarkably, lymphomatoid papulosis Pityriasis lichenoides et varioliformis
type D may present with identical mor- acuta and pityriasis lichenoides chronica:
Comparison of lesional T‐cell subsets and
phology as pityriasis lichenoides, albeit
investigation of viral associations. J Cutan
with a high number of intraepidermal
Pathol, 38(8), 649–656.
CD30‐positive lymphocytes
Nanda, A., Alshalfan, F., Al‐Otaibi, M., Al‐
• PLEVA (acute variant of PL): Thick Sabah, H., & Rajy, J. M. (2013). Febrile
scale‐crust with necrotic epithelia, ulceronecrotic Mucha‐Habermann disease
often overlying flat erosion, with adja- (pityriasis lichenoides et varioliformis acuta
cent dense epidermotropic CD8‐positive fulminans) associated with parvovirus infec-
round cell infiltrate (interface type), and tion. Am J Dermatopathol, 35(4), 503–506.
necrotic keratinocytes Tomasini, D., Tomasini, C. F., Cerri, A., Sangalli,
G., Palmedo, G., Hantschke, M., & Kutzner,
DD: Drug eruption; small plaque eruptive
H. (2004). Pityriasis lichenoides: A cytotoxic
psoriasis; lymphomatoid papulosis type D
T‐cell‐mediated skin disorder. Evidence of
(with predominant CD30‐positive epider-
human parvovirus B19 DNA in nine cases.
motropic round cells). J Cutan Pathol, 31(8), 531–538.
Zaaroura, H., Sahar, D., Bick, T., & Bergman, R.
Reference (2018). Relationship between pityriasis
Benmaman, O., & Sanchez, J. L. (1988). lichenoides and mycosis fungoides: A clin-
Comparative clinicopathological study on icopathological, immunohistochemical, and
pityriasis lichenoides chronica and small molecular study. Am J Dermatopathol, 40(6),
plaque parapsoriasis. Am J Dermatopathol, 409–415.
10(3), 189–196.
C H APT ER 4
Parasitoses
CHAPTER MENU
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
159
160 CHAPTER 4: Parasitoses
Nodular ulcerated
lesions on the arm
(left)
Histiocyte-rich
granulomatous
infiltrate (right)
Plasma-cell-rich
granulomatous
infiltrate (left) with
interspersed
histiocytes replete
with amastigotes
(right)
Amastigotes in
histiocytic giant cell
(left, arrow).
Immunohistochemical
stain with polyclonal
anti-Leishmania
antibody (right)
Ulcerated lesion on
the cheek (left)
Plasma-cell-rich
granulomatous
infiltrate (right)
Granulomatous
infiltrate (left). Large
mononuclear
histiocytes containing
amastigotes
(right, arrow)
Amastigotes in
mononuclear
phagocytes
(left, arrows), anti
Leishmania
immunostain
(polyclonal antibody)
(right)
Leishmania mexicana, like all Leishmania spp., and histopathology in C3H mice. Exp
is an obligate intracellular protozoan para Parasitol, 50(1), 45–56.
site which is endemic to Mexico and Central Andrade‐Narvaez, F. J., Medina‐Peralta, S.,
America. Clinical and histologic features are Vargas‐Gonzalez, A., Canto‐Lara, S. B., &
Estrada‐Parra, S. (2005). The histopathol
identical with other forms of cutaneous
ogy of cutaneous leishmaniasis due to
leishmaniasis. Differentiation is feasible by
Leishmania (Leishmania) mexicana in the
molecular methods (PCR/sequencing).
Yucatan peninsula, Mexico. Rev Inst Med
Reference Trop Sao Paulo, 47(4), 191–194.
Trophozoites with
eccentric nuclei (top
and bottom)
Amebiasis primarily occurs in tropical and vulva, or via liver abscess perforating to
and subtropical areas; rarely in Europe. the abdominal wall. Acanthamebiasis (e.g.
Gastrointestinal infection is caused by via contaminated contact lenses) may cause
Entamoeba histolytica. The skin may get keratitis, followed by CNS involvement.
affected via primary infection or more fre CF: Nodular and cystic lesions, which
quently by per continuitatem extension of evolve into deep ulcers with undermined
rectal amebiasis to the anus, perianal skin, and elevated borders.
164 CHAPTER 4: Parasitoses
4.1.4 Rhinosporidiosis
Hyperplastic nasal
mucosa
(left and right)
Large spherules,
containing
endospores
PAS stain
Grocott
(methenamine silver)
stain
Rhinosporidium seeberi, the causative agent DD: Lethal midline granuloma (NK/T‐cell
of rhinosporidiosis, is an aquatic proto lymphoma); cryptococcosis.
zoon, morphologically mimicking a fun
gus. Preferential sites of infection are the Reference
nasal or ocular mucosa. Males in tropical
de Silva, N. R., Huegel, H., Atapattu, D. N.,
areas are more often infected than females.
Arseculeratne, S. N., Kumarasiri, R.,
CF: The cornified skin is only rarely
Gunawardena, S., . . . Fernando, R. (2001).
affected. Mucosal surfaces are primarily Cell‐mediated immune responses (CMIR)
involved. Papules and large strawberry‐ in human rhinosporidiosis. Mycopathologia,
like polyps occur on the nasal, ocular, and 152(2), 59–68.
nasopharyngeal mucosa. Sudarshan, V., Gahine, R., Daharwal, A.,
HF: Kujur, P., Hussain, N., Krishnani, C., &
• Polypoid exophytic mass Tiwari, S. K. (2012). Rhinosporidiosis of the
• Presence of sporangia (large spherules, parotid duct presenting as a parotid duct
cyst – a report of three cases. Indian J Med
replete with small round “endospores”)
Microbiol, 30(1), 108–111.
in the submucosal propria (Grocott and
PAS)
• Mixed accompanying round cell 4.2 Arthropod: Arachnids
infiltrate with histiocytes, neutrophils,
lymphocytes and plasma cells, and few 4.2.1 Mites
giant cells in the adjacent propria There is a large variety of different mites,
• No cellular atypia (versus lethal midline and apart from scabies and harvest mites,
granuloma [NK/T‐cell lymphoma] with include Cheyletiella mites, poultry mites,
marked pleomorphism) house dust mites, and other species.
166 CHAPTER 4: Parasitoses
Touch preparation of
a mite (left)
Drawings of mites
(right) (from Simon,
1848)
4.2.1.2 Scabies
Eczematous lesions
(left)
Nodular lesions on
the arm of a child
(middle)
Nodular lesions on
the penis shaft (right)
Feces (scybala)
(middle)
Crusted scabies is a rare variant of scabies, on the face and capillitium. The crusts are
occurring preferentially in immunocom highly contagious, as they are replete with
promised people. The suffix “Norwegica,” myriads of mites.
which traditionally has been used, is a HF: Massive hyperkeratotic scales with a
misnomer: this variant of scabies does not plethora of scabies mites, ovula, and scybala.
have any Scandinavian ties at all. DD: Other hyperkeratotic disorders, pso
CF: Massive hyperkeratotic crusts are riasis vulgaris, tylotic eczema.
found preferentially on the extremities,
4.2: Arthropod: Arachnids 169
Papulovesicles on
the back (left) and
groin (top right).
Detail (bottom right)
In the fall (in Europe), the larva of occur. Spider bites also may be a possible
Trombicula autumnalis, which may tem trigger for acute generalized exanthema
porarily attach to the skin and suck tous pustulosis (AGEP).
blood, causes pruritic allergic reactions HF:
mostly in people who have been in the • Necrosis at the site of spider bite
outdoors. • Hemorrhage and accompanying vascu
CF: Small itchy macules appear preferen lopathy (thrombi)
tially at the rims of tight clothing (socks, • Polymorphous dermal infiltrate, con
underwear, belt), which evolve into tiny sisting of lymphocytes, neutrophils,
papulovesicles. Excoriation and bacterial eosinophils
superinfection may result from vigorous
DD: Pyoderma gangrenosum; pyogenic
scratching.
granuloma; vasculitis; trauma; thrombotic
HF:
or embolic infarction.
• Slight superficial erosion or spongiosis
only Reference
• Moderate lymphocytic infiltrate in the
Davidovici, B. B., Pavel, D., Cagnano, E.,
dermis with eosinophils
Rozenman, D., Halevy, S., EuroScar, & Regi, S.
• Mites not present
s. g. (2006). Acute generalized exanthematous
DD: All other arthropod bite reactions. pustulosis following a spider bite: Report of 3
cases. J Am Acad Dermatol, 55(3), 525–529.
4.2.2 Spiders° Elston, D. M., Eggers, J. S., Schmidt, W. E.,
CF: Painful erythema followed by urticarial Storrow, A. B., Doe, R. H., McGlasson, D., &
or papular induration and central hemor Fischer, J. R. (2000). Histological findings
rhagic necrosis at the site of previous spider after brown recluse spider envenomation.
bite. Systemic symptoms (pain, fever) may Am J Dermatopathol, 22(3), 242–246.
170 CHAPTER 4: Parasitoses
4.2.4 Insects
“Dirty” irregular
eczematous lesions
on the neck (right).
Inset: Pediculus
capitis
Figure 4.2.4 Arthropods: Insects Cimex Lectularius; Bedbugs (left). Pediculosis Capitis (right).
associated with mantle cell lymphoma: Exaggerated insect bite reactions in patients
Clinicopathological, immunopathological, positive for HIV. Military Medical Consortium
and molecular studies. Am J Dermatopathol, for the Advancement of Retroviral Research.
27(4), 290–295. J Am Acad Dermatol, 29(2 Pt 1), 269–272.
Smith, K. J., Skelton, H. G., 3rd, Vogel, P.,
Yeager, J., Baxter, D., & Wagner, K. F. (1993).
The female sand flea (Tunga penetrans) DD: Subungual warts; pyogenic granuloma.
thrives in the skin, where it produces sev
eral hundred eggs. Reference
CF: In tropical climates, small pruritic
Coates, S. J., Thomas, C., Chosidow, O.,
centrally ulcerated papules or nodules Engelman, D., & Chang, A. Y. (2020). Part
preferentially occur on the toes, under the II – Ectoparasites: Pediculosis and tungiasis.
toenails, and at interdigital sites. J Am Acad Dermatol, 82(3), 551–569.
HF: Intradermally located female flea, Nazzaro, G., Genovese, G., & Veraldi, S. (2019).
bearing hundreds of eggs within its body. Clinical and histopathologic study of 39
Accompanying polymorphous round cell patients with imported tungiasis. J Cutan
infiltrate. Pathol, 46(4), 251–255.
C H APT ER 5
CHAPTER MENU
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
173
174 CHAPTER 5: Helminthic Infections (Parasitic Worms)
Helminths are macroparasites, usually by direct penetration into the skin. There is
affecting the intestinal tract, the lymph, or no consistent taxonomy of helminths. The
blood vessels, and occasionally the skin. main groups comprise roundworms (nem
Humans are infected by eggs or larvae, atodes), tapeworms (cestodes), and flukes
which are either ingested, transmitted by (trematodes).
bite of an insect, which serves as vector – or
Winding superficial
tunnel on the back of
one foot (left)
Intraepidermal
spongiotic vesicles,
filled with fluid and
inflammatory cells
(right)
5.2 Filariasis
Dirofilariasis: nodular
suppurative
subcutaneous
infiltrate containing
roundworm with
signature crenelated
surface (left, arrow
and right)
Filariasis: inflammatory
infiltrate in the upper
dermis (left) and
microfilariae (right,
arrow)
Subcutaneous
nodule (left, long
arrow) and
hypopigmented spots
(left short arrows)
Nodular fibrotic
infiltrate (middle) with
onchocercaria
(right)
5.4 Cysticercosis
Cysticercus larva of
Taenia solium with
typical scolex that is
“watching you”
(as signature
histology)
Infection occurs via fecal‐oral spread: the limbs. There often are characteristic
ingestion of the tapeworm eggs that are accompanying neurological symptoms
shed with the feces of humans harboring (seizures).
adult Taenia solium. Humans are the inter HF: Larva with typical scolex.
mediate host for the larvae, which may DD: Lipoma; subcutaneous cyst;
migrate to the brain and cause neurologi pseudotumor.
cal symptoms (seizures). Infiltration into
other organs (heart, eyes), including the Reference
skin, is not uncommon. Ponnighaus, J. M., Nkhosa, P., & Baum, H. P.
CF: Swelling and subcutaneous painful (2001). [Cutaneous manifestation of cyst
lumps with cysts, mostly on the trunk and icercosis]. Hautarzt, 52(12), 1098–1100.
5.5 Sparganosis
Sparganum
with central excretory
canal (left, arrow)
Tegument of the
larva with adjacent
calcareous
bodies (right, arrows)
and vertically
oriented muscle
5.6 Schistosomiasis (Bilharziasis)
Schistosoma
(left, arrows) within a
dense inflammatory
infiltrate. Overlying
pseudocarcinomatous
hyperplasia
Multiple ova of
Schistosoma
(right: detail)
to the splanchnic and urogenital venous are dense infiltrates mainly composed of
plexus, where they mature into adult neutrophils and eosinophils. In routine
worms. sections, cercariae can be found in excep
Migration of parasites to the skin into tionally rare cases.
preexisting pathologic conditions may DD: Arthropod bites; urticaria; other
occur (bilharziasis cutanea tarda). worm infections.
CF: Pruritic papular dermatitis, preferen
tially on the legs (early), followed by aller Reference
gic febrile reaction with accompanying Davis‐Reed, L., & Theis, J. H. (2000). Cutaneous
urticaria, edema, arthritis, eosinophilia schistosomiasis: Report of a case and review
(intermediate stage). Chronic stage with of the literature. J Am Acad Dermatol, 42(4),
involvement of internal organs (lungs, 678–680.
liver, bladder, CNS). In the skin, often Eulderink, F., Gryseels, B., van Kampen, W. J.,
intensive inflammation with verrucous & de Regt, J. (1994). Haematobium schisto
papules and nodules, preferentially at per somiasis presenting in the Netherlands as a
skin disease. Am J Dermatopathol, 16(4),
ineal and gluteal sites. These inflamed
434–438.
skin lesions may contain Schistosoma eggs,
Matz, H., Berger, S., Gat, A., & Brenner, S.
albeit in very low numbers. (2003). Bilharziasis cutanea tarda: A rare
HF: Eggs are rarely found in chronic skin presentation of schistosomiasis. J Am Acad
lesions. Leading histopathological changes Dermatol, 49(5), 961–962.
Papular eruptions
(left) (Courtesy of
H.C. Korting, M.D., †)
Dermal neutrophilic
and eosinophilic
infiltrate around
cercaria (middle and
right, arrow)
Fresh water fowl (ducks) are the primary human skin (incomplete life cycle). At the
hosts of schistosomes of the Trichobilharzia site of infection, intensely pruritic urticar
genus. Infected ducks release cercariae ial erythema develop (swimmer’s itch).
into the water, where they usually infect CF: Macular and papular intensely pru
snails (complete life cycle). Instead, bath ritic and urticarial lesions, preferentially at
ing humans may get infected per chance, water‐exposed body sites.
albeit only very superficially, with cercar HF: Only in exceptional cases, cercariae
iae not being able to pass through the may be encountered in the subepidermal
180 CHAPTER 5: Helminthic Infections (Parasitic Worms)
Papular lesions as a
sequela to treatment
with leeches
Pseudolymphomatous
infiltrate in the
dermis
Sepsis
CHAPTER MENU
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
181
182 CHAPTER 6: Sepsis
Necrotic (left),
pustular (middle),
and hemorrhagic
(right)
lesions of advanced
septic vasculitis
Subepidermal
blistering and
hemorrhage
Neutrophilic
perivascular and
interstitial infiltrate
Papulonecrotic
lesions on the hands
(top left and bottom)
Schematic
differences between
leukocytoclastic
vasculitis (top right)
and septic vasculitis Septic vasculitis with signature
(bottom right): the thrombosed vascular lumen
latter showing
signature thrombi –
the former with
distinctly patent
vessel lumen.
Neutrophils (black
dots) and karyorrhexis
(tiny black dots) are
present in either
condition (red dots:
erythrocytes)
Meningococcemia:
signature fibrinoid
thrombi within vessel
lumina of
postcapillary venules.
Note paucity of
inflammatory infiltrate
with extremely scarce
neutrophils
Signature thrombi
with secondary
hemorrhage. Paucity
of adjacent
leukocytoclastic
infiltrate
Papulopustular
lesions (left and
middle)
Occlusive vasculitis
with neutrophils
(right)
Intra- and
extravascular
accumulation of
Penicillium
organisms and
cellular debris
PAS-positive spores
(arrows) adjacent to
hyphae
Necrotic lesion on
the lower arm (left)
Massive
subepidermal
edema. Dense
infiltrate in the dermis
(right) and
vasculopathy (arrow)
Septic thrombotic
vasculitis with
hyphae (left, arrows).
Aspergillus hyphae
within vessel lumina,
walls, and in adjacent
dermis. Anti-BCG
staining (right) cross-
reacting with fungal
epitopes
abscess 10–11 bartonellae 25–29
acanthamebiasis 163 Bazin’s disease (erythema induratum) 38–39
acantholysis BCG vaccination granuloma 30–31
bacterial infections 3, 67 bedbugs 170
viral infections 110, 112, 113, 115 bilharziasis 178–179
acne agminata 32 bird’s‐eye cells see koilocytes
acne inversa 17–18 black flies 176
acne papulopustulosa 7 Blastomyces dermatitidis 97
acnitis 32 blastomycoid granuloma 98
acrodermatitis chronica atrophicans 49, 56–59 blastomycosis 96–98
juxta‐articular fibrous nodules 58–59 European 94–95
acrodermatitis continua suppurativa keloidal 98
(Hallopeau) 72, 73 North American 96–97
acrokeratosis verruciformis Hopf 134 South American 101–102
acropustulosis, infantile 70 blisters
actinic reticuloid 59 cytomegalovirus 119
actinomycosis 48–49 ecthyma contagiosum 149, 150
acute generalized exanthematous pustulosis erysipelas 14
(AGEP) 71–72 hand‐foot‐and‐mouth disease 141
Aeromonas hydrophila 180 herpes simplex 110
AIDS, Kaposi sarcoma 122–127 impetigo contagiosa 3
algae 107 phlegmon 16
Alternaria 103–104 septic vasculitis 182
amastigotes 160, 161, 162 staphylococcal scalded skin syndrome 66, 67
amebiasis 163–164 toxic epidermal necrolysis 67
Ancylostoma braziliense 174 varicella zoster virus infections 112
Annelida 180 blue cells, basophilic 136, 137
anthrax 22–23 Bockhardt’s ostiofolliculitis 4–5
aphthoid Pospischill–Feyrter 110 Borrelia infections (Lyme disease) 49–59
arachnids 165–170 differential diagnosis 59
arthropods 160, 165–172 stage I 50–54
aspergillosis 103–104 stage II 55–56
Aspergillus sepsis 187 stage III 56–59
asymmetric periflexural exanthema of botryomycosis 28–29
childhood 152–153 bowenoid papulosis 128, 135
atypical mycobacterioses 29, 39–40 bubo 64
Azzopardi phenomenon 145 bullous lesions see blisters
Burkitt lymphoma 117–118
bacillary angiomatosis 25–26 Buruli ulcer 29, 47
Bacillus anthracis 22
bacterial infections 1–75 calcified bodies 161
dermatoses associated with 66–67 Calymmatobacterium granulomatis 63, 64
dermatoses mimicking 68–75 Candida albicans 84
bacterial sepsis 185–186 Candida lipolytica 85
Atlas of Clinical Dermatopathology: Infectious and Parasitic Dermatoses, First Edition. Günter Burg,
Heinz Kutzner, Werner Kempf, Josef Feit, and Omar Sangueza.
© 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd.
189
190 Index