Tropical Dermatopathology Manoj Singh
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1Tropical Dermatopathology2
3Tropical Dermatopathology
Manoj Singh MD, MNAMS, FICP, FIAMS Additional Professor Department of Pathology All India Institute of Medical Sciences New Delhi
4
This book has been subsidised by the Government of India through the National Book Trust, India for the benefit of students and was developed under the Scheme for Core Books on Medical Sciences Project.
Price: Rs. 388.00
Published by
Jitendar P Vij
Jaypee Brothers Medical Publishers (P) Ltd
EMCA House, 23/23B Ansari Road, Daryaganj
New Delhi 110 002, India
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Tropical Dermatopathology
© 2003, Manoj Singh
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author and the publisher.
This book has been published in good faith that the material provided by author is original. Every effort is made to ensure accuracy of material, but the publisher, printer and author will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters to be settled under Delhi jurisdiction only.
First Edition : 2003
Publishing Director : RK Yadav
9788180611483
Typeset at JPBMP typesetting unit
Printed at Gopsons Papers Ltd, A-14, Sector 60, Noida 201 301, India
5
This book is fondly dedicated to
Hema
Anuradha
&
Maria
6
7Contributors
Principal Contributor
:
  • M Ramam
  • md
  • Additional Professor
  • Department of Dermatology and Venereology
  • All India Institute of Medical Sciences
  • New Delhi
Contributor
:
  • Paschal D'Souza
  • md
  • Assistant Professor
  • Department of Dermatology
  • Jawahar Lal Nehru College of Medical Sciences
  • Ajmer
8
9Foreword
The climatic and demographic environments of tropical and subtropical hospitals provide conditions conducive to high prevalence of several forms of skin diseases, particularly those with infective basis. The general histopathologist is not well-acquainted with many of these lesions, while the treating dermatologist needs a proper histological diagnosis before initiating specific therapy. An optimal meeting place for these two specialties, which would ultimately benefit the patient, is the field of Dermatopathology, with its twin perspectives of clinical morphology of a condition, and its corresponding diagnostic histological features. This treatise brought out by Dr Manoj Singh, with excellent contributions by his clinical colleagues Dr M Ramam and Dr Paschal D'Souza, is a timely and well brought out compendium of diagnostic criteria for the common and important dermatopathies, and is particularly relevant to tropical and subtropical geographic regions.
In any area of specialty in medical sciences, a good liaison between the clinician and the histopathologist is crucial to accurate diagnosis of the disease. Nowhere is this more important than in the field of dermatology. Thus, the compilation and presentation of this treatise jointly by an expert dermatopathologist and two dermatologists has resulted in combining their experiences to bring into sharp focus the salient points for arriving at a precise diagnosis of skin diseases.
The book highlights the practical and assessable aspects of cutaneous diagnostic problems, and details its subject matter in a simple, understandable and assimilable manner, and is excellently illustrated. The explanation of terms commonly used in dermatopathology, which are conventionally considered the most jaw breaking ones in medicine, have been clarified at the very beginning of the book. Detailed procedures of skin biopsy have been outlined so that the subsequent processing of tissues for proper microscopic interpretation can become easy. The reaction patterns for categories of dermatological lesions and general diagnostic features have also been highlighted to guide the histopathologist in the correct direction to establishing a specific diagnosis. Immunofluorescence, which is of vital importance in the identification of several skin diseases has been emphasized from time to time with very good color illustrations. The text matter and the illustrations amply demonstrate the large body of experience and superb communicative ability of the author and his colleagues.
This book is a handy and useful reference manual for practicing histopathologists, and an excellent knowledge base for resident trainees in pathology and dermatology.
NC Nayak
md, frcpath, fna, fasc, fams
Professor Emeritus of Pathology
All India Institute of Medical Sciences, New Delhi
10
11Preface
Depending on the number of dermatologists at an institution and their interest in dermatopathology, 5-30 percent of the biopsies coming to a department of pathology are skin biopsies. Alongwith the evolution of various subspecialties and super-specialties, dermatopathology has also emerged as an independent specialty and its votaries have evolved from being simple pathologists or dermatologists into dedicated and committed clinicopathological diagnosticians. As in the other fields, the tremendous quantum of knowledge in dermatopathology is exemplified by the emergence of dedicated societies, journals and textbooks in the specialty. This proliferation of knowledge and interest the world over has also seen its off shoot in our country in the form of the Dermatopathology Society of India. This tremendous proliferation of knowledge and information has, however, led to an increasing complexity of the texts available, adding to the confusion and bewilderment of general diagnostic pathologists and dermatologists both at student and faculty levels. Unfortunately the availability of simple and understandable books helpful in diagnosis is rather limited. This book has been designed to meet this need, especially in our country where there is a profusion of skin diseases is seen, and are increasingly being biopsied.
In this book, as the title implies, I have attempted to focus on diseases seen in the tropical and subtropical regions, which, of course, implies a predominance of infectious disorders. Special emphasis has been laid on leprosy, tuberculosis, fungal infections of the skin, etc. Tumors of the skin, not being as common for us as in the West, have been relatively de-emphasized.
Both the clinical and histopathological aspects of dermatopathology lend themselves to illustration. Short of actually seeing a patient or a slide, a color picture provides information that is qualitatively superior to the most detailed description. I have, therefore, focused attention on illustrating both those aspects, as well as correlative aspects, which have been highlighted to promote a conceptual understanding.
I have also attempted to simplify the ‘jargon’ of dermatopathology, so that a novice may manage to successfully steer his way through this sea. Brief mention has also been made of laboratory and OPD procedures, which are used by, and useful to, dermatopathologists.
I hope that this book, like our earlier book (Understanding Dermatopathology, BI Churchill Livingstone), will fill a gap in the current literature on dermatopathology, and will be found useful as a ready reference by all students of this subject, whether postgraduate students of pathology or dermatology, or practicing diagnostic pathologists and dermatologists.
New Delhi
March, 2003
Manoj Singh
12
13Acknowledgements
For once in my life, words almost fail me in describing my gratitude to my friend, Dr M Ramam, whose many meritorious qualities are only offset by a misplaced sense of fairplay, which has led to his being a mere contributor, though he has written all the clinical descriptions, provided all the clinical photos, and, de facto, is as much an author of this book as I have been.
Dr Paschal D'Souza has contributed the treatment aspects of all the diseases, and also contributed to the text.
I acknowledge a deep gratitude to the National Book Trust for commissioning and funding the publication of this book, and Prof PK Dave, Director, All India Institute of Medical Sciences and Chairman of the ACCBMS, NBT for encouraging the development of the book.
I am grateful to M/s Jaypee Brothers Medical Publishers (P) Ltd especially to Mr JP Vij, Mr RK Yadav, Mr Tarun Duneja and Mr RK Majumdar for the processing and publishing of this book, with its various components which had to be laboriously fitted together.
I would like to express my heartfelt gratitude and sincere thanks to many friends and colleagues who helped in the preparation of this book, some materially, and others by giving encouragement and creating an atmosphere conducive for such a task, this particularly includes the members of the Delhi Dermatopathology Forum, and the Dermatopathology Society of India.
Dr Binod Khaitan contributed several transparencies and also helped in writing some sections.
Several colleagues in the department graciously permitted us to photograph their patients.
Mr KK Arora and Ms Pankaj showed exemplary patience and fortitude in converting scribbled pieces of writing into a readable text.
Mr BD Ghosh helped with the scanning of slides and the illustrations.
Mr BK Dash, Mr KB Kapoor and Mr Arun Jain were instrumental in stimulating me whenever they felt that the pace of this book was flagging.
In various tasks of preparing this book, I was helped, physically, mentally and morally by many colleagues. These include Prof Kusum Verma, Prof Prem Chopra, Prof Kusum Kapila, Dr S Datta Gupta, Dr Ashok Mukharjee, Dr Asha Kubba, Dr HK Prasad, Prof KB Logani, Dr V Ramesh, Prof Harsh Mohan, Prof VK Sharma, Prof Neena Khanna, and Dr Manju Aron.
Above all, I am deeply grateful to patients, not only this book is largely based on photographs of their diseases; the very foundation of much of our knowledge of pathology and dermatology stems from them.
New Delhi
Manoj Singh
14
15The Skin Biopsy
March, 2003
The skin biopsy is the most important aid to a dermatologist in making a diagnosis. This relatively simple sounding technique is beset with hidden pitfalls for the unwary. Some amount of thought is necessary on the need for, technique of, and type of skin biopsy.
 
 
Types of Biopsy
The usual types of biopsy are punch biopsy, scalpel biopsy, and shave biopsy.
Punch biopsies result in the excision of cylinders of tissue of uniform diameter, and are adequate in most situations. However, it must be recognized that the depth of a punch biopsy is limited by the depth of the cylindrical metal blade. In situations such as scleroderma, panniculitis, tuberculosis verrucosa cutis or mycetoma where there is gross thickening of the tissue and/or the characteristic pathology is deep seated, a punch biopsy may be inadequate and a scalpel biopsy is recommended.
Most often scalpel biopsies are elliptical. Because the blade is held vertically only around the equator of elliptical biopsies, the biopsy is thickest at the center and tapers off towards the edges. A hexagonal or a diamond shaped biopsy allows the scalpel blade to be kept vertical along most of the edges and produces biopsies of uniform thickness.
Shave or curette biopsies are not recommended in dermatology, though they may have some diagnostic and/or therapeutic role in strictly epidermal lesions like viral warts, seborrheic keratoses, etc.
 
Lesions
It is important to pick the correct lesion to biopsy. Lesions that are evolving or resolving may not show the characteristic changes. Similarly, lesions that have been modified by scratching, infection or local applications are best avoided. As a general rule, it is best to take the biopsy from the most active, or most recent part of the lesion. The inclusion of normal skin in the biopsy is controversial. This practice is probably a carry over from instructions in the surgery department where malignancies need to be excised with an adequate margin of normal tissue. However, the inclusion of normal skin in small skin biopsies, specially punch biopsies, often reduces the amount of lesional tissue available to the pathologist. In lesions where normal skin is necessary for comparison, as in morphea, collagen degeneration, etc. a large scalpel biopsy to include both should be taken, or two punch biopsies may be taken from lesion and normal skin.
When the biopsies taken are deep enough, the tissue pops up when the subcutaneous fat is excised. It can then be gently eased out with non-toothed forceps after incising any remaining attachments at the base of the biopsy. Toothed forceps have no place in a skin biopsy set and must never be used to hold the tissue.
 
Fixation
The biopsy must then be transferred immediately into the appropriate transport medium-buffered formalin for conventional histopathological examination, glutaraldehyde for electron microscopic examination, Stuart's transport medium for immunofluorescence studies and normal saline for microbiological investigations. There is no need to refrigerate formalin fixed tissue. The only time we have seen freezing artifacts (usually described in skin biopsies transmitted by post in extremely cold climates) was when the ward nurse put, a skin biopsy vial in the freezer to preserve it over the weekend!
 
Other Data/Clinical Information
One of the most important components of clinicohistological correlation, which forms the bedrock of diagnostic derma-topathology, is adequate communication between the clinical evaluator and the histopathologist. This is because, in our country, as indeed in most places around the world, the person who examines the skin biopsy has usually not examined 16the patient. It is therefore, essential that a detailed and unbiased clinical description be provided to the pathologist. This necessitates an adequate clinical description and the nearly universal temptation to include only those features which support the made clinical diagnosis, and gloss over the rest, must be firmly resisted. There is a similar case for offering a substantial list of differential diagnoses when the diagnosis is uncertain, and perhaps, even when the clinical diagnosis appears to be quite firm. The description provided should be not only of the patient, his disease, and the spectrum of lesions, but, most importantly, of the specific lesion to be biopsied (due to chronological progression of most lesions, confusion frequently arises because one type of lesion is described, and a different form of lesion biopsied).
 
Purpose of Biopsy
Skin biopsy may be taken for several different reasons; these may be:
  1. To confirm a reasonably certain clinical diagnosis
  2. To rule out a particular condition though it seems rather unlikely, the commonest example being macular Hansen's disease,
  3. To document or authenticate a diagnosis, for publication, research or record.
  4. To seek diagnostic assistance from the pathologist in situations of clinical perplexity and
  5. For other reasons such as therapeutic excision biopsies, those taken for teaching purposes and so on.
It is useful to let the pathologist known what motivated the biopsy in a particular case.
17Patterns in Clinical and Pathological Dermatology
The majority of surgical pathologist employ, by training, chance, or by natural aptitude, the technique of pattern recognition for analyzing a given slide. This technique is a highly desirable one to cultivate as it channelizes one's thought processes, from the first viewing of the slide under the scanner, to a detailed examination of the architectural and cytological features and a consideration of these in the light of the clinical and investigative features, to reach a diagnosis or a group of possible diagnoses.
This training of the mind, and developing ability to channelize one's thought processes in a controlled fashion, form the bedrock of all diagnostic histopathology and especially of dermatopathology.
There are several similarities in the diagnostic approach to a dermatology patient and a pathology slide. The crux of diagnosis is morphological appearance.
For this the method most experts use is to scan their memory banks for a similar pattern recognized/studied in the past (If you have seen it once, you can recognize it a second time, if you have seen it a dozen times, you can identify it with your eyes shut!). There are several caveats to this approach, but, most of the time, it works very well indeed. The major limitations of this approach are also obvious. Skin lesions and biopsies of the same disease do not look identical in all patients. Different diseases may be morphologically similar. Many diseases show a morphological evolution in their lesions with time. Finally, one may be looking at a new disease altogether! In such situations, another, more systematic approach may be more appropriate. Such situations, will, understandably, be more common to the novice, and get fewer with experience.
In clinical dermatology, the alternate approach consists of noting type, size and shape of the lesions, their color, feel and consistency, and their distribution and groupings on the body's surface, associated lesions, etc. Special terms are used to describe these findings (see Dictionary) and certain combinations of these elements are suggestive of particular disease groups, though overlap is considerable. A useful method of dividing different clinical terms may be decided by the level of the lesion compared with the surrounding, normal looking skin.
Flat
Elevated
Depressed
Macule
Infarct
Sclerosis
Telangiectasia
Papule
Plaque
Nodule
Wheal
Vesicle/Bulla
Pustule
Abscess
Cyst
Scale
Scar
Lichenification
Atrophy
Sclerosis
Erosion
Excoriation
Scar
Ulcer
Sinus
Gangrene
Similarly, histological appearances can be categorized by the level of skin primarily involved (epidermis, dermis, appendages, vessels, nerves); the nature of change (inflammation, proliferation, degeneration) the type of inflammatory cells, etc. Descriptive terms and groupings are also used. Various classifications of reaction patterns, using criteria like level of involvement, type of change, etc have been described.
Recognition of morphological patterns in dermatopathology is gradually gaining importance. The most important 18starting point is to first view the slide under a 4 × scanner (we prefer a 2 × objective). Many important architectural points may be missed if one starts looking at a slide under a higher power. In fact, some conditions may be diagnosed just by naked eye examination of a microscopic slide. Examples are seborrheic keratosis, keratoacanthoma, and molluscum contagiosum. Important diagnostic clues may be obtained even by naked eye examination in conditions like viral wart, lichen planus and psoriasis (A reversed microscope eyepiece will work as 2-4 × magnifying glass, and may be an important adjunct to naked eye examination).
It is worthwhile to go through this exercise periodically to improve one's diagnostic acumen and recognize and keep up with the numerous subtle variations that nature plays on every theme.
Diagnostic dermatopathology tends to be clinical diagnosis driven. Slides are examined in the light of the given clinical diagnosis, which is confirmed or refuted. This leaves a largish area, where the histopathologist may be left groping in the dark. Certain specific features may be present, though not consistent with the clinical impression. In our experience, the best results are obtained from a synthesis of clinical and histological features, highlighting the importance of detailed clinical and histological descriptions on requisition forms and reports, and better still, good, personal communication between the dermatologist and the pathologist. Jointly reviewing the clinical lesion and its slide is of course, the ideal.
 
 
Reaction Patterns Helpful in Diagnosis
Ichthyosiform (hyperkeratotic)
:
Ichthyosis, Lichen simplex chronicus
Acanthotic
:
Wart, Molluscum, Seborrheic keratosis, Prurigo nodularis, Psoriasis, Epidermal nevus
Vesiculobullous
:
Epidermal – Pemphigoid
Dermoepidermal – Pemphigoid
Superficial inflammation
:
Psoriasis, Eczema, Lichenoid reaction, Light reaction
Deep inflammation
:
Lupus, Panniculitides, Folliculitis, Perifolliculitis and vasculitides
Granulomatous
:
Epithelioid – TB, leprosy, syphilis, PKDL
Palisading – Parasites, Granuloma annulare
Mixed – Syphilis, PKDL
Degenerative
:
Actinic, PXE, Atrophodermas
Deposits
:
Amyloid, Iron, Melanin
Vascular
:
Hemangioma, Angiokeratoma
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20
21Dictionary of Dermatopathology
  1. Acantholysis: Loss of attachment between epithelial cells. It may be primary, as in pemphigus, or secondary, as in viral blisters.
  2. Acanthosis: Increase in thickness of epidermis.
  3. Apoptosis: Currently used for pre-programmed (genetically determined) cell death. In our field, the term is also used for falling down into the dermis of dead or dying keratinocytes, to form civatte bodies, as in LP, DLE, etc. (this usage by far predates the current meaning of the word!)
  4. Argentaffin: A substance with the ability to reduce silver salts to metallic silver, e.g. melanin in the Fontana-Mason stain, carcinoids arising from appendix.
  5. Argyrophil: A substance ability to reduce silver salts in the presence of an external reducing agent, i.e. melanin, reticulin, carcinoids arising from lung.
  6. Asteroid body: A star shaped inclusion inside a giant cell in granulomas like sarcoidosis.
  7. Atrophy: Thinning of the skin or of the epidermis.
  8. Auspitz sign: Silvery scales of psoriasis scrape off easily with a slide, leaving behind pin point bleeding spots.
  9. Basement membrane: Junction between epidermis and dermis consisting of a dense lamina, hemidesmosomes attaching the basal cells, and anchoring fibrils.
  10. Birefringence: Under polarized light, doubly refractile substances turn light through 45o and appear bright against a dark background as in silica, cholesterol, uric acid, and amyloid.
  11. Blister: See bulla.
  12. Bulla: A fluid filled separation in the skin. It may be intraepidermal, as in pemphigus or viral infections, or dermo-epidermal, as in bullous pemphigoid.
  13. Caseation necrosis: Necrosis where tissue outlines are obscured, as in tuberculosis.
  14. Civatte or colloid bodies: Round eosinophilic bodies in the upper dermis, usually seen with inflammation and basement membrane damage, as in lichen planus.
  15. Coat sleeve: A large lymphocytic infiltrate surrounding a blood vessel, giving this characteristic appearance.
  16. Crust: Clotted plasma with inflammation and keratin flakes, present above the stratum corneum in conditions like eczema.
  17. Dermatopathic lymphadenopathy: Lymph nodes draining inflamed skin with melanin present free and in histiocytes.
  18. Desmosome: Structure attaching adjoining keratinocytes.
  19. Dyskeratosis: Premature keratinization of epidermal cells usually seen as a keratinized cell in between non-keratinized cells.
  20. Eczema: (syn. Dermatitis) a clinical reaction pattern characterized by erythema, edema and crusting in the acute stage, and thickening and hyperpigmentation in the chronic stages.
  21. Elastotic degeneration: Light induced damage to elastic and collagen fibers in the upper dermis, leading to masses of thick, tangled fibers.
  22. Epidermotropism: Presence of lymphocytes in the epidermis without spongiosis, as in mycosis fungoides.
  23. Excoriation: Scratch mark.
  24. Exocytosis: Lymphocytes in the epidermis with spongiosis and microvesicle formation as in psoriasis or eczema.
  25. Follicular plug: Hyperkeratosis distending a hair follicle.
    22
  26. Giant cell: A cell with more than one nucleus, different morphological types are described in different scenarios, e.g.
    Langhans’ type: A peripheral ring of nuclei, as in tuberculosis.
    Foreign body type: With nuclei all over the cytoplasm.
    Touton type: With a central ring of nuclei and peripheral foamy cytoplasm as in xanthomas.
    Tumor type: With nuclei of different sizes and shapes as in malignancies.
  27. Grain: A dyskeratotic cell with a pyknotic nucleus as in Darier's disease.
  28. Granulation tissue: A healing response consisting of capillaries, fibroblasts, and plasma cells.
  29. Granuloma: An organized collection of activated macrophages (epithelioid cells).
  30. Grenz zone: A narrow zone of papillary dermis which is described as being involved in TT leprosy and not in other types.
  31. Horn pearl: A ball of keratinocytes with keratin in centers.
  32. Indian file: Single file of cells infiltrating between collagen bundles as in breast carcinoma.
  33. Keratin: Horny outer covering of the skin, above the epidermis.
  34. Keratinocyte: Mature epidermal cell which contains keratin, and is present in the upper layer of the epidermis.
  35. Keratohyaline: Deeply basophilic granules in the cytoplasm of cells in the granular layer of the epidermis.
  36. Koebner (isomorphic) phenomenon: Lesion of primary disease occurring at sites of trauma, usually linearly in scratch marks.
  37. Langerhans’ cell: A clear cell in the epidermis. It belongs to the monocyte phagocyte series, and plays a role in antigen presentation.
  38. Leucocytoclasia: Leukocyte destruction, especially in acute vasculitis, resulting in scattered nuclear dust.
  39. Macule: A flat lesion not elevated above the surrounding skin.
  40. Max-Joseph space: A dermo-epidermal cleft seen in lichen planus.
  41. Melanocyte: Cell in the basal epidermis which produces melanin.
  42. Melanophage: Histiocyte in the dermis which scavenges incontinent melanin.
  43. Metachromasia: The property of staining a different color from the dye used, as in amyloid staining red with crystal violet or mast cell granules staining purple with toluidine blue.
  44. Mucin, dermal: Ground substance of the dermis consisting of acid mucopolysaccharides (AMPS), mainly hyaluronic acid.
  45. Mucin, epithelial: The secretion of epithelial gland cells, as in salivary glands, mucoid metaplasia or carcinoma of sweat ducts.
  46. Nodule: A large deep-seated, globular lesion.
  47. Papule: A small lesion raised above the level of the surrounding skin.
  48. Parakeratosis: Incomplete maturation, resulting in persistence of epidermal cell nuclei into the horny layer, usually associated with a thin granular layer, and usually due to rapid transit of keratinocytes, as in psoriasis.
  49. Pigment incontinence: Melanin in the dermis, usually as a result of inflammation. It may be present free or inside macrophages.
  50. Plaque: Thickened or indurated area of skin, usually more than 2 cm in diameter.
  51. Poikiloderma: Atrophy of skin with telangiectasia and mottled pigmentation.
  52. Pustule: A pus filled vesicle.
  53. Rupia: Oyster shell like scales, as seen in psoriasis and ulcerosquamous syphilis. Heavy keratinization in lesions which periodically enlarge in area, giving obtuse cone like piles of scales.
    23
  54. Scale: Easily peeled off keratin flake. Types:
    • Branny (pityriasiform)
    • Psoriasiform
    • Ichthyosiform
    • Lamellar/cuticular
    • Membranous, collarettes
    • Seborrheic desquamation
    • Crusted scales
    • Macerated scales.
  55. Spongiosis: Epidermal cells pushed apart by intracellular edema.
  56. Squamous eddy: Concentric ball of squamous cells like horn pearl, but without keratin, as in irritated seborrheic keratosis.
  57. Storiform pattern: In fibrohistiocytic tumors, interweaving bundles of spindle cells (storia: doormat in Latin).
  58. Tombstones: Individual basal cells sticking out in the bulla as pemphigus.
  59. Ulcer: Epidermal loss.
  60. Vesicle: A small bulla, less than 0.5 cm. in diameter.
  61. Villi: Elongated dermal papillae, usually with a few layers of basal cells, protruding into the base of a bulla, as in pemphigus.
  62. Wheal: Transient, erythematous, edematous, lesion lasting a few minutes to a few hours.