Weedon's Skin Pathology: Expert Consult - Online and Print, third Edition

1044 Pages·2009·168.95 MB·English

by  David Weedon AO MD FRCPA FCAP(Hon)

© 2010, Elsevier Limited All rights reserved.
First Edition 1997
Second Edition 2002
The right of David Weedon to be identified as author of this work has been asserted by
him in accordance with the Copyright, Designs and Patents Act 1988.
No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage
and retrieval system, without permission in writing from the publisher. Permissions may
be sought directly from Elsevier's Rights Department: phone: [phone] (US) or
([phone] (UK); fax: [phone]; e-mail: healthpermissions@elsevier.
com. You may also complete your request on-line via the Elsevier website at http://www.
elsevier.com/permissions.
ISBN: 978-0-7020-3485-5
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging in Publication Data
A catalog record for this book is available from the Library of Congress
Notice
Medical knowledge is constantly changing. Standard safety precautions must be followed,
but as new research and clinical experience broaden our knowledge, changes in treatment
and drug therapy may become necessary or appropriate. Readers are advised to check the
most current product information provided by the manufacturer of each drug to be
administered to verify the recommended dose, the method and duration of administration,
and contraindications. It is the responsibility of the practitioner, relying on experience and
knowledge of the patient, to determine dosages and the best treatment for each individual
patient. Neither the Publisher nor the author assumes any liability for any injury and/or
damage to persons or property arising from this publication.
The Publisher
Working together to grow
libraries in developing countries
www.elsevier.com | www.bookaid.org | www.sabre.org
The
publisher’s
policy is to use
paper manufactured
Printed in China from sustainable forests
Last digit is the print number: 9 8 7 6 5 4 3 2 1
P r e f a c e
Completing the third edition of this book has been a Herculean task, of the word ‘prominent’ to describe the magnitude of an inflammatory
not made any easier by a high reporting load, another myocardial infiltrate. Hopefully not too many ‘prominents’ have crept into this
infarct in July 2008, and my computer illiteracy in an era when com- edition. The recent death of A. Bernard (Bernie) Ackerman has been
petency in this skill is almost essential for proper functioning as a described as the ‘end of an era’. Few others contributed so much to
dermatopathologist and author. I must thank my colleagues, particu- dermatopathology. Other mentors of mine have now retired, some
larly Dr Richard Williamson and Dr Nick Mellick who commenced more fully than others, such as John Sullivan, John Kerr, Robin Cooke,
work at midnight during my absences. They also did some reference and Alistair Burry. Hopefully I am wiser for their counsel, and for their
and OMIM hunting for me. interest in my career. The work of Professor Kerr in establishing apop-
This new era is not without its shortcomings. Some of the medical tosis as a concept was monumental, as evidenced by its basic role in
graduates seem to lack the breadth and depth of knowledge that char- many aspects of carcinogenesis. As a consequence of my interest in
acterized earlier generations, but this reduced knowledge does not this concept since the 1970s, I still cringe when I hear the term
seem to interfere with the ability of recent graduates to practice medi- ‘necrotic keratinocytes’ used for apoptotic cells.
cine. One recent graduate proudly told me that she had ‘Googled her Medical writing style has also changed enormously in the last 20
way through medical school’, something that I could never achieve. years. No longer are the titles of articles short and succinct. Some are
Many pathologists are now ‘PubMed-ing’ their way through the daily mini-abstracts. Everyone seems to be a co-author these days; 17
sign-out. As a consequence, the need for a comprehensive textbook in authors for a letter to the Editor seems somewhat excessive, but I have
any field has probably lessened. Notwithstanding this view, the last heard many times the justification for this event. Also, the possessive
edition of this book contained a valuable collection of references, and apostrophe is going the way of the dodo. There seems little point in
as this is likely to be the last edition of this book by the current author, retaining eponymous designations without one, although I appreciate
it seemed appropriate to build on, rather than purge, this bank of the reasoning that the person does not own the disease. The possessive
references. PubMed-ing one's way to a diagnosis is seemingly not apostrophe has been with us since the 17th century, so it will be
without its problems. To use an analogy from the old days of warfare: retained here for syndromes that have traditionally been named in this
‘if one feeds in the wrong coordinates, one hits the wrong target’. style. This edition has sections on treatment. As I am not a dermatolo-
Hopefully, this comment does not sound like ‘sour grapes’ from an gist, doses of drugs have not been given. These sections are intended
acknowledged troglodyte, unable to do the same. In a similar vein, the to highlight recent treatment trials and guidelines as well as some suc-
undersigned marvels at the reliance placed on immunoperoxidase cessful treatments of an anecdotal nature.
markers to reach a presumptively-correct diagnosis. Automation of I would like to thank and acknowledge the assistance once again of
these tests appears to have lessened rather than strengthened their Dr Geoffrey Strutton, and for this edition, the help of Dr Adam Rubin
specificity. It is often forgotten that the specificity of an antibody for for some of the photomicrographs. I also thank Alyson Coxon and Cleo
a particular tumor is only as specific as the last paper to be published. Wilkinson for their assistance. Michael Houston, Executive Publisher
I watch with interest as D2-40, one of the newer markers, goes the at Elsevier Ltd, and Ben Davie, the Development Editor, provided
same way as vimentin, CD34, and CD10 before it. sound advice. Their patience during the long gestation period of this
Since the last edition of this book, Professor W. St C. (Bill) volume was amazing. Finally, once again my secretary and friend Pam
Symmers, who was instrumental in getting me to write the precursor Kent typed every word of the text and all the references and tables,
volume to this book, has ‘passed on’. He was truly inspirational, and not to mention her role as my proxy computer operator.
from the old school of language perfection. I still recall vividly his David Weedon
hand-written comments on some proofs admonishing me for my use Brisbane, Australia

1
An approach to the
interpretation of skin biopsies
Introduction 4 Combined reaction patterns 12 Transepithelial elimination 15
Major tissue reaction patterns 4 Minor tissue reaction patterns 12 Patterns of inflammation 16
The lichenoid reaction pattern Epidermolytic hyperkeratosis 12 Superficial perivascular inflammation 16
(‘interface dermatitis’) 4
Acantholytic dyskeratosis 12 Superficial and deep dermal inflammation 17
The psoriasiform reaction pattern 5
Cornoid lamellation 12 Folliculitis and perifolliculitis 18
The spongiotic reaction pattern 6
Papillomatosis (‘church-spiring’) 15 Panniculitis 18
The vesiculobullous reaction pattern 7
Acral angiofibromas 15
The granulomatous reaction pattern 7
Eosinophilic cellulitis with ‘flame figures’ 15
The vasculopathic reaction pattern 11
4 SECTION 1 • INTRODUCTION
Patterns of inflammation
INTRODUCTION
There are four patterns of cutaneous inflammation characterized on
Dermatopathology requires years of training and practice to attain an the basis of distribution of inflammatory cells within the skin:
acceptable level of diagnostic skill. Many have found this process an 1. superficial perivascular inflammation
exciting and challenging one, well worth the expenditure of time and 2. superficial and deep dermal inflammation
intellectual effort. To the trainee, there seems to be an endless number
3. folliculitis and perifolliculitis
of potential diagnoses in dermatopathology, with many bewildering
4. panniculitis.
names. However, if a logical approach is adopted, the great majority
of skin biopsies can be diagnosed specifically and the remainder can There are numerous dermatoses showing a superficial perivascular
be partly categorized into a particular group of diseases. This learning inflammatory infiltrate in the dermis and a limited number in the other
process can be enhanced under the tutelage of a skilled mentor and categories. Sometimes panniculitis and folliculitis are regarded as
by ‘optical mileage’, a term used for the self-examination and diagnosis major tissue reaction patterns, because of their easily recognizable
of large amounts of day-to-day material; such cases invariably differ pattern.
from ‘classic’ examples of an entity found in teaching sets. It should
not be forgotten that the histopathological features of some dermato-
ses are not diagnostically specific and it may only be possible in these MAJOR TISSUE REACTION PATTERNS
circumstances to state that the histopathological features are ‘consis-
tent with’ the clinical diagnosis.
A significant number of inflammatory dermatoses can be categorized
The interpretation of many skin biopsies requires the identification
into one of the following six major reaction patterns, the key morpho-
and integration of two different, morphological features – the tissue
logical feature of which is included in parentheses:
reaction pattern and the pattern of inflammation. This is a crude algo-
1. lichenoid (basal cell damage; interface dermatitis)
rithmic approach; more sophisticated ones usually hinder rather than
enhance the ability to make a specific diagnosis. 2. psoriasiform (regular epidermal hyperplasia)
Tissue reaction patterns are distinctive morphological patterns 3. spongiotic (intraepidermal intercellular edema)
which categorize a group of cutaneous diseases. Within each of these 4. vesiculobullous (blistering within or beneath the epidermis)
histopathological categories there are diseases which may have similar 5. granulomatous (chronic granulomatous inflammation)
or diverse clinical appearances and etiologies. Some diseases may show 6. vasculopathic (pathological changes in cutaneous blood vessels).
histopathological features of more than one reaction pattern at a par-
Each of these reaction patterns will be discussed in turn, together with
ticular time or during the course of their evolution. Such cases may
a list of the dermatoses found in each category.
be difficult to diagnose. In this edition, an attempt has been made to
list diseases which characteristically express more than one tissue reac-
tion pattern (see below).
THE LICHENOID REACTION PATTERN
The pattern of inflammation refers to the distribution of the inflam-
matory cell infiltrate within the dermis and/or the subcutaneous tissue. (‘INTERFACE DERMATITIS’)
There are several distinctive patterns of inflammation (see below):
their recognition assists in making a specific diagnosis. The lichenoid reaction pattern (‘interface dermatitis’) (see Ch. 3, pp.
Some dermatopathologists base their diagnostic approach on the 35–70) is characterized by epidermal basal cell damage, which may be
inflammatory pattern, while others look first to see if the biopsy can manifested by cell death and/or basal vacuolar change (known in the
be categorized into one of the ‘tissue reactions’ and use the pattern of past as ‘liquefaction degeneration’). The basal cell death usually pres-
inflammation to further categorize the biopsy within each of these ents in the form of shrunken eosinophilic cells, with pyknotic nuclear
reaction patterns. In practice, the experienced dermatopathologist remnants, scattered along the basal layer of the epidermis (Fig. 1.1).
sees these two aspects (tissue reaction pattern and inflammatory These cells are known as Civatte bodies. They are undergoing death
pattern) simultaneously, integrating and interpreting the findings in a by apoptosis, a morphologically distinct type of cell death seen in both
matter of seconds. For trainees in dermatopathology, the use of tissue physiological and pathological circumstances (see p. 36). Sometimes
reaction patterns, combined with the mnemonic for diseases with a the basal cell damage is quite subtle with only an occasional Civatte
superficial and deep inflammatory pattern, appears to be the easiest body and very focal vacuolar change. This is a feature of some drug
method to master. reactions.
The categorization of inflammatory dermatoses by their tissue reac- In the United States, the term ‘interface dermatitis’ is used
tions will be considered first. synonymously with the lichenoid reaction pattern, although it is not
usually applied to the subtle variants. Its use in other countries is by
no means universal. At other times, it is used for the morphological
Tissue reaction patterns subset (see below) in which inflammatory cells extend into the basal
layer or above. The term is widely used despite its lack of precision.
There are many different reaction patterns in the skin, but the majority It is warmly embraced as a diagnosis, but it is nothing more than a
of inflammatory dermatoses can be categorized into six different pat- pattern, encompassing many clinical entities with diverse presenta-
terns. For convenience, these will be called the major tissue reaction tions, etiologies, and treatments.
patterns. Occasionally, diseases express more than one major pattern, A distinctive subgroup of the lichenoid reaction pattern is the poi-
either ab initio or during their evolution. They are dealt with sepa- kilodermatous pattern, characterized by mild basal damage, usually of
rately in the ‘Combined reaction patterns’ section. There are a number vacuolar type, associated with epidermal atrophy, pigment inconti-
of other diagnostic reaction patterns which occur much less commonly nence, and dilatation of vessels in the papillary dermis (Fig. 1.2). It is
than the major group of six, but which are nevertheless specific for a feature of the various types of poikiloderma (see p. 66).
other groups of dermatoses. These patterns will be referred to as minor The specific diagnosis of a disease within the lichenoid tissue reac-
tissue reaction patterns. They will be considered after the major reac- tion requires an assessment of several other morphological features.
tion patterns. These include:
1
AN APPROACH TO THE INTERPRETATION OF SKIN BIOPSIES • CHAPTER 5
Fig. 1.2 The poikilodermatous variant of the lichenoid reaction pattern. It is
characterized by mild vacuolar change of the basal layer of the epidermis, mild
epidermal atrophy, and dilatation of vessels in the papillary dermis. (H & E)
disseminated superficial actinic porokeratosis; it obscures the
dermoepidermal interface (so-called ‘interface dermatitis’) in
erythema multiforme, paraneoplastic pemphigus, fixed drug
eruptions, acute pityriasis lichenoides (PLEVA), acute graft-
versus-host disease (GVHD), one variant of lupus erythematosus,
and reactions to phenytoin (Dilantin) and other drugs; and it
involves the deep as well as the superficial part of the dermis in
lupus erythematosus, syphilis, photolichenoid eruptions, and some
drug reactions);
3. the presence of prominent pigment incontinence (as seen in drug
reactions, the poikilodermas, lichenoid reactions in dark-skinned
people, and some of the sun-exacerbated lichen planus variants,
e.g. lichen planus actinicus); and
4. the presence of satellite cell necrosis (lymphocyte-associated
apoptosis) – defined here as two or more lymphocytes in close
A
proximity to a Civatte body (a feature of graft-versus-host
reaction, regressing plane warts, subacute radiation dermatitis,
erythema multiforme, and some drug reactions).
The diseases showing the lichenoid reaction pattern are listed in
Table 1.1.
THE PSORIASIFORM REACTION PATTERN
From a morphological viewpoint, the psoriasiform tissue reaction (see
Ch. 4, pp. 71–91) is defined as epidermal hyperplasia in which there
is elongation of the rete ridges, usually in a regular manner (Fig. 1.3).
It is acknowledged that this approach has some shortcomings, as
many of the diseases in this category, including psoriasis, show no
significant epidermal hyperplasia in their early stages. Rather, dilated
vessels in the papillary dermis and an overlying suprapapillary scale
may be the dominant features in early lesions of psoriasis. Mitoses are
B increased in basal keratinocytes in this pattern, particularly in active
lesions of psoriasis.
Fig. 1.1 The lichenoid reaction pattern. (A) There are shrunken keratinocytes
with pyknotic nuclear remnants (Civatte bodies) in the basal layer. These cells are The psoriasiform reaction pattern was originally defined as the
undergoing death by apoptosis. (B) There is also focal vacuolar change. (H & E) cyclic formation of a suprapapillary exudate with focal parakeratosis
related to it. The concept of the ‘squirting dermal papilla’ was also put
forward with the suggestion that serum and inflammatory cells escaped
1. the type of basal damage (vacuolar change is sometimes more from the blood vessels in the papillary dermis and passed through the
prominent than cell death in lupus erythematosus, epidermis to form the suprapapillary exudate referred to above. This
dermatomyositis, the poikilodermas, and drug reactions); ‘concept’, though outmoded, is useful in considering early lesions of
2. the distribution of the accompanying inflammatory cell infiltrate psoriasis in which dilated vessels and surface suprapapillary scale are
(the infiltrate touches the undersurface of the basal layer in lichen often the only features. The epidermal hyperplasia which also occurs
planus and its variants, early lichen sclerosus et atrophicus, and in was regarded as a phenomenon secondary to these other processes.
6 SECTION 1 • INTRODUCTION
Table 1.1 Diseases showing the lichenoid reaction pattern
(‘interface dermatitis’)
Lichen planus
Lichen planus variants*
Lichen nitidus
Lichen striatus
Lichen planus-like keratosis
Lichenoid drug eruptions*
Fixed drug eruptions*
Erythema multiforme and variants*
Superantigen ‘id’ reaction*
Graft-versus-host disease*
Subacute radiation dermatitis* Fig. 1.3 The psoriasiform reaction pattern showing epidermal hyperplasia with
regular elongation of the rete processes. There are several layers of scale resulting
Eruption of lymphocyte recovery
from intermittent ‘activity’ of the process. (H & E)
AIDS interface dermatitis
Lupus erythematosus*
Diseases showing the psoriasiform reaction pattern are listed in
Dermatomyositis Table 1.2.
Poikiloderma congenita(le)*
Kindler’s syndrome THE SPONGIOTIC REACTION PATTERN
Congenital telangiectatic erythema (Bloom’s syndrome)
The spongiotic reaction pattern (see Ch. 5, pp. 93–122) is character-
Lichen sclerosus et atrophicus
ized by intraepidermal intercellular edema (spongiosis). It is recognized
Dyskeratosis congenita
by the presence of widened intercellular spaces between keratino-
Poikiloderma of Civatte cytes, with elongation of the intercellular bridges (Fig. 1.4). The spon-
Pityriasis lichenoides* giosis may vary from microscopic foci to grossly visible vesicles. This
reaction pattern has been known in the past as the ‘eczematous tissue
Persistent viral reactions
reaction’. Inflammatory cells are present within the dermis, and their
Perniosis
distribution and type may aid in making a specific diagnosis within this
Polymorphic light eruption (pin-point type) group. This is the most difficult reaction pattern in which to make a
specific clinicopathological diagnosis; often a diagnosis of ‘spongiotic
Paraneoplastic pemphigus
reaction consistent with …’ is all that can be made.
Lichenoid purpura
The major diseases within this tissue reaction pattern (atopic der-
Lichenoid contact dermatitis matitis, allergic and irritant contact dermatitis, nummular dermatitis,
Still’s disease (adult onset) and seborrheic dermatitis) all show progressive psoriasiform hyperpla-
sia of the epidermis with chronicity (Fig. 1.5). This change is usually
Late secondary syphilis
accompanied by diminishing spongiosis, but this will depend on the
Porokeratosis
activity of the disease. Both patterns may be present in the same
Drug eruptions biopsy. The psoriasiform hyperplasia is, in part, a response to chronic
Phototoxic dermatitis rubbing and scratching.
Six patterns of spongiosis can be recognized:
Prurigo pigmentosa
1. neutrophilic spongiosis (where there are neutrophils within foci of
Erythroderma
spongiosis);
Mycosis fungoides
2. eosinophilic spongiosis (where there are numerous eosinophils
Regressing warts and tumors within foci of spongiosis);
Regressing pityriasis rosea 3. miliarial (acrosyringial) spongiosis (where the edema is related to
the acrosyringium);
Lichen amyloidosus
4. follicular spongiosis (where the spongiosis is centered on the
Vitiligo
follicular infundibulum);
Lichenoid tattoo reaction
5. pityriasiform spongiosis (where the spongiosis forms small vesicles
Diseases marked * may have a true interface pattern. containing lymphocytes, histiocytes, and Langerhans cells); and
6. haphazard spongiosis (the other spongiotic disorders in which
there is no particular pattern of spongiosis).
The diseases showing the spongiotic reaction pattern are listed in Table
1.3(a).
A seventh pattern, which is really a variant of haphazard spongiosis,
combines epidermal spongiosis with subepidermal edema (Fig. 1.6),
which can vary from mild to severe, even forming subepidermal blis-
ters. Its causes are listed in Table 1.3(b).
1
AN APPROACH TO THE INTERPRETATION OF SKIN BIOPSIES • CHAPTER 7
Fig. 1.4 The spongiotic reaction pattern. There is mild intercellular edema with Fig. 1.5 The spongiotic reaction pattern in a lesion of some duration.
elongation of the intercellular bridges. (H & E) Psoriasiform hyperplasia coexists with the spongiosis. (H & E)
Table 1.2 Diseases showing the psoriasiform reaction pattern
Psoriasis
Psoriasiform keratosis
AIDS-associated psoriasiform dermatitis
Pustular psoriasis
Reiter’s syndrome
Pityriasis rubra pilaris
Parapsoriasis
Lichen simplex chronicus
Benign alveolar ridge keratosis
Subacute and chronic spongiotic dermatitides
Erythroderma
Fig. 1.6 Epidermal spongiosis combined with subepidermal edema. This
Mycosis fungoides
combination characterizes a certain group of diseases. (H & E)
Chronic candidosis and dermatophytoses
Inflammatory linear verrucous epidermal nevus (ILVEN)
Norwegian scabies The anatomical level of the split may be subcorneal, within the
Bowen’s disease (psoriasiform variant) stratum malpighii, suprabasal or subepidermal. The mechanism respon-
sible for vesiculation may be exaggerated spongiosis, intracellular
Clear cell acanthoma
edema and ballooning (as occurs in viral infections such as herpes
Lamellar ichthyosis simplex), or acantholysis. Acantholysis is the loss of coherence between
Pityriasis rosea (‘herald patch’) epidermal cells. It may be a primary phenomenon or secondary to
inflammation, ballooning degeneration (as in viral infections of the
Pellagra
skin), or epithelial dysplasia. In the case of subepidermal blisters,
Acrodermatitis enteropathica
electron microscopy and immunoelectron microscopy could be used
Glucagonoma syndrome to make a specific diagnosis in most cases. In practice, the subepider-
Secondary syphilis mal blisters are subdivided on the basis of the inflammatory cell infil-
trate within the dermis (Fig. 1.7). Knowledge of the immunofluorescence
findings is often helpful in categorizing the subepidermal blistering
diseases.
Table 1.4 lists the various vesiculobullous diseases, based on the ana-
THE VESICULOBULLOUS REACTION PATTERN
tomical level of the split and, in the case of subepidermal lesions, the
predominant inflammatory cell within the dermis.
In the vesiculobullous reaction pattern, there are vesicles or bullae at
any level within the epidermis or at the dermoepidermal junction (see
Ch. 6, pp. 123–168). A specific diagnosis can usually be made in a THE GRANULOMATOUS REACTION PATTERN
particular case by assessing three features – the anatomical level of the
split, the underlying mechanism responsible for the split and, in the This group of diseases (see Ch. 7, pp. 169–194) is characterized by
case of subepidermal lesions, the nature of the inflammatory infiltrate the presence of chronic granulomatous inflammation; that is, localized
in the dermis. collections of epithelioid cells usually admixed with giant cells,