(BQ) Part 1 book Histopathology of the skin presents the following contents: Histology of normal skin, techniques of skin biopsy, dermoepidermal junction, the cells of the skin and their identification, common terminologies used in dermatopathology, staining techniques in dermatopathology,... Invite you to consult.
Histopathology of the Skin System requirement: • Windows XP or above • Power DVD player (Software) • Windows media player 10.0 version or above (Software) • Accompanying CD ROM is playable only in Computer and not in CD player Histopathology of the Skin Ashok Aggarwal MBBS, MD Dean and Senior Consultant Skin Institute and School of Dermatology New Delhi-110048 JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD New Delhi Disclaimer: This eBook does not include ancillary media that was packaged with the printed version of the book Published by Jitendar P Vij Jaypee Brothers Medical Publishers (P) Ltd B-3 EMCA House, 23/23B Ansari Road, Daryaganj, New Delhi 110 002, India Phones: +91-11-23272143, +91-11-23272703, +91-11-23282021, +91-11-23245672, Rel: 32558559 Fax: +91-11-23276490, +91-11-23245683 e-mail: jaypee@jaypeebrothers.com Visit our website: www.jaypeebrothers.com Branches • 2/B, Akruti Society, Jodhpur Gam Road Satellite, Ahmedabad 380 015 Phones: +91-079-26926233, Rel: +91-079-32988717, Fax: +91-079-26927094 e-mail: jpamdvd@rediffmail.com • 202 Batavia Chambers, Kumara Krupa Road, Kumara Park East, Bangalore 560 001 Phones: +91-80-22285971, +91-80-22382956, Rel: +91-80-32714073, Fax: +91-80-22281761 e-mail: jaypeemedpubbgl@eth.net • 282 IIIrd Floor, Khaleel Shirazi Estate, Fountain Plaza, Pantheon Road, Chennai 600 008 Phones: +91-44-28193265, +91-44-28194897, Rel: +91-44-32972089, Fax: +91-44-28193231 e-mail: jpchen@eth.net • 4-2-1067/1-3, 1st Floor, Balaji Building, Ramkote Cross Road, Hyderabad 500 095 Phones: +91-40-66610020, +91-40-24758498, Rel:+91-40-32940929, Fax:+91-40-24758499, e-mail: jpmedpub@rediffmail.com • No 41/3098, B & B1, Kuruvi Building, St Vincent Road, Kochi 682 018, Kerala, Phones: 0484-4036109 • 1-A Indian Mirror Street, Wellington Square, Kolkata 700 013 Phones: +91-33-22451926, +91-33-22276404, +91-33-22276415, Rel: +91-33-32901926 Fax: +91-33-22456075, e-mail: jpbcal@dataone.in • 106 Amit Industrial Estate, 61 Dr SS Rao Road, Near MGM Hospital, Parel, Mumbai 400 012 Phones: +91-22-24124863, +91-22-24104532, Rel: +91-22-32926896 Fax: +91-22-24160828, e-mail: jpmedpub@bom7.vsnl.net.in • “KAMALPUSHPA” 38, Reshimbag, Opp Mohota Science College, Umred Road, Nagpur 440 009 (MS) Phones: Rel: 3245220, Fax: 0712-2704275 e-mail: jaypeenagpur@dataone.in Histopathology of the Skin © 2007, Ashok Aggarwal All rights reserved No part of this publication and Photo CD ROM 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 are to be settled under Delhi jurisdiction only First Edition: 2007 ISBN 81-8061-951-6 Typeset at JPBMP typesetting unit Printed at Ajanta Offset Dedicated to Late Prof Pran Nath Behl Foreword Indeed it is intriguing to have a title on Histopathology of the Skin in the Indian context It is unique for it embraces the various relevant facets which need to be appraised to the native students The endeavor to write a book on the title has been made by Dr Ashok Aggarwal who had done his postgraduate degree in Dermatology and Venereology in the year 1978 from Maulana Azad Medical College, New Delhi He had the privilege of working under Dr Pran Nath Behl in Skin Institute and School of Dermatology Over the years his interest in histopathology of skin was recognized and he went for short training to Edinbur gh under Prof Hunter and his group After his return he had a privileged opportunity of streamlining the services in dermatopathology in the Institute He has now utilized his acumen in preparing a dissertation in the form of a booklet hugging various dermatoses attempting to bring about a correlation for the purposes of ultimate diagnosis of the disease It’s a worthwhile endeavor and should help all those who are interested in clinical histopathological and treatment aspect of various dermatoses The illustrations contain therein are of good quality , and may serve as a ready reckoner or accomplishing for the diagnosis of dermatoses in question The sincere attempt therefore is worth applauding and augurs well for the future of the specialty Virendra N Sehgal MD, FNASc, FAMS, FRAS (Lond.) Former Professor/Head Department of Dermatology and Venereology, Goa Medical College, Panji • Professor/Head Department of Dermatology and Venereology, UCMS, Safdarjung Hospital • Professor/Head (Acting Dean), Director-Professor, Department of Dermatology and Venereology, Maulana Azad Medical College/LNJP Hospital, New Delhi • Principal/Medical Superintendent/Director-Professor Dermatology and Venereology, Lady Hardings Medical College, New Delhi • Director -Professor Dermatology/Venereology/Medical Superintendent, UCMS-GTB Hospital, Delhi Sehgal Nursing Home Dermato-Venereology (Skin/VD) Centre A-6 Panchwati, Delhi-110033 (India) Preface The book “Histopathology of the Skin” is a much awaited book in the Indian context on dermatopathology designed for postgraduate students of dermatology It is also meant for general pathologist dealing with the cutaneous morbid conditions The chapters on Normal Histology of Skin and Recognition of Inflammatory Cells will enable beginners to identify common skin structures and inflammatory cells in tissue sections The chapter on Special Stains has been included to give insight into the role of these stain in diagnoses of different skin conditions The histopathological findings of different skin diseases are described in detail but in a simple and straightforward fashion A lar ge number of microphotographs included in this book will further help the readers to assess their histopathological tissue sections Ashok Aggarwal Disorders of Hypopigmentation 111 Fig 16.1: Vitiligo Masson-Fontana stain shows uniform reduction in the number of melanocytes and melanin pigment at the dermo-epidermal junction NEVUS DEPIGMENTOSUS: (ACHROMIC NEVUS) Nevus depigmentosus is characterized by the presence of well circumscribed and usually uniformly hypomelanotic (not amelanotic) macules present at birth The lesion is usually single (circular or rectangular) or distributed as long bands or streaks confined to one side of the body Dermatomal distribution has also been reported The hypopigmentation is the result of defect in transfer of melanosomes from melanocytes to keratinocytes Histopathology (Fig 16.2) • • Normal or slightly reduced number of melanocytes Reduced dopa activity Fig 16.2: Nevus depigmentosus Masson-Fontana stain showing normal number of melanocytes 112 Histopathology of the Skin NEVUS ANEMICUS Nevus anemicus is a congenital disorder characterized by well-defined round macules with irregular edges that are paler than the surrounding skin It may appear at birth or may appear in early childhood Lesions may be single or multiple The condition resembles vitiligo but melanocytes are normally present with normal amount of melanin The hypopigmentation in nevus anemicus is attributed to increased sensitivity of blood vessels to catecholamines Histopathology No histopathologic abnormalities are seen by light or electron microscopy Idiopathic Guttate Hypomelanosis It is a disorder of elderly individuals The lesions are small 2-5 mm in diameter hypopigmented or depigmented macules present mainly on sun exposed areas of extremities Few lesions may also occur on trunk Histopathology (Figs 16.3A and B) • • • • Basket weave hyperkeratosis Some atrophy of epidermis with flattening of rete ridges Reduction but not complete absence of dopa positive melanocytes Decrease in melanin pigment in the basal layer of epidermis Hypomelanosis of Ito: (Incontinentia Pigmenti Achromians) This is seen at birth or in infancy The lesions are sharply demarcated hypo- pigmented macules with a characteristic linear or whorled pattern distributed along the lines of Blaschko Trunk and extremities are the common sites of involvement There may be associated abnormalities of central nervous system, eyes, hair, teeth and musculo- skeletal system Fig 16.3A: Idiopathic guttate hypomelanosis There is basket weave hyperkeratosis and atrophy of the epidermis Fig 16.3B: Idiopathic guttate hypomelanosis Masson-Fontana stain showing decrease in melanin pigment in the basal cell layer Disorders of Hypopigmentation 113 Histopathology • • Dopa stain shows fewer and smaller melanocytes than normal Decrease in the amount of melanin in the basal cell layer with complete absence in some areas Pityriasis Alba Pityriasis alba is a common, asymptomatic disorder usually seen in children and young adults, often with a personal or family history of atopy Characteristically,lesions are ill-defined, hypopigmented macules with slight scaling and a variable amount of mild erythema at the border Lesions may be 0.5-5 cm in size and are distributed commonly on the face, neck, shoulders and extensor aspect of the arms Histopathology • • • • • • • • Mild hyperkeratosis Slight focal parakeratosis Mild focal spongiosis Sparse superficial perivascular infiltrate of lymphocytes Melanocytes normal in number No melanin incontinence Melanin pigmentation of the basal layer may be reduced Some exocytosis of lymphocytes may be seen Ash-leaf Spot White macules are found in 79 to 98 percent cases of tuberous sclerosis at birth Hypopigmented macules as the earliest manifestation of the disease are most helpful in the diagnosis of tuberous sclerosus complex Four types of hypopigmented macules described: • Lanceolate macules to cm in diameter (Ash-leaf spot which has the shape of mountain Ash-leaf) most typical of tuberous sclerosis • Polygonal macules • Confetti spots 2-3 mm in size that occur symmetrically from wrist to elbow and from ankle to knee • Hypomelanosis in dermatomal distribution The margins of the lesions are usually well-defined and the color is white but not the pure white of vitiligo macules Histopathology Normal number of melanocytes with reduction of epidermal melanin Piebaldism It is a rare autosomal dominant condition characterized by a white forelock and depigmented macules The lesions are present at birth and thereafter remain stable It has to be dif ferentiated from vitiligo (Table 16.1) Table 16.1: Difference between piebaldism and vitiligo Piebaldism Vitiligo Birth Course is chronic and stable White forelock with depigmentation of center forehead is characteristic and seen in 80-90 percent of cases Islands of hyperpigmented macules seen either within the hypomelanotic areas or in the normally pigmented skin Histopathology shows absence of melanocytes Uncommon at birth, late onset Usually chronic and progressive White forelock is not a characteristic feature No islands of hypopigmentation seen in normally pigmented skin Histopathology shows absence of melanocytes, Lymphocytic infiltrate is seen in active lesions 17 CHAPTER Erythema Multiforme Erythema multiforme (EM) is an acute, self limiting dermatosis characterized by pleomorphic eruption consisting of macules, papules, vesicles and bullae EM is now described in terms of EM (skin lesions only) and bullous EM s(kin and mucous membrane involvement of variable severity) EM is almost always induced by recurrent herpes simplex virus (HSV) infection The hallmark of this condition are the classic “iris” or “target” lesions which are defined as a round raised plaques with two concentric rings of erythema and edema and a central zone of epidermal necrosis Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN) are the severe variants of EM which at times may be fatal They are characterized by flat atypical target lesions or purpuric macules that are widespread, and associated with high fever, more severe mucosal involvement and systemic symptoms Drugs are a major precipitating cause of SJS and TEN SJS and TEN can be classified as: SJS: Mucosal erosions with widespread purpuric macules and epidermal detachment involving less than 10 percent of body surface area Overlap SJS-TEN : Widespread purpuric macules and epidermal detachment between 10-30 percent of body surface area TEN: Widespread purpuric macules and epidermal detachment above 30 percent of body surface area Histopathology (Fig 17.1) • • • • • • • • • • • • Orthokeratotic stratum corneum Lichenoid (interface) reaction pattern with a mild to moderate lymphocytic infiltrate obscuring the dermo-epidermal interface Vacuolization of the basal cell layer Necrosis of individual keratinocytes in the basal unit is the hallmark of EM Satellite cell necrosis characterized by intraepidermal lymphocytes in close association with necrotic keratinocytes is commonly seen Mild spongiosis and exocytosis are seen An acrosyringeal concentration of apoptotic keratinocytes is regarded as a clue to a drug etiology which may also show eosinophils in the inflammatory infiltrate Vesicular lesions are characterized by subepidermal cleft with prominent epidermal cell death in the overlying roof Dermal infiltrate is composed of lymphocytes and a few macrophages involving the superficial and mid-dermal vessels Toxic epidermal necrolysis shows subepidermal bulla with overlying confluent necrosis of the epidermis and sparse perivascular infiltrate of lymphocytes Extravasated erythrocytes are commonly found within the blister cavity Eosinophils are not usually prominent in EM Drug induced and herpes simplex - associated EM show certain dif ferent histopathologic features (Table 17.1) 115 Erythema Multiforme Fig 17.1: Erythema multiforme showing lichenoid reaction pattern, necrosis of indivi-dual keratinocytes and exocytosis of inflam-matory cells There is vacuolization of the basal cells Table 17.1: Different histological features of HSV associated EM and drug induced EM HSV associated EM Drug induced EM More exocytosis Pronounced liquefactive degeneration of basal cell layer Marked papillary dermal edema, Nuclear dust may be identified in the papillary dermis More widespread keratinocyte necrosis Microscopic blister formation More pigmentary incontinence Friction Blisters Vesiculo-bullous lesions can develop as a result of repeated and prolonged friction of the skin They are commonly seen on soles following a long walk or on palmar surface of fingers as a result of repeated friction produced in certain occupations or sports Histopathology • • • • Intraepidermal blister The roof of the blister is formed by stratum corneum, stratum granulosum and amorphous cellular debris The floor of the blister is composed of pale looking degenerated keratino-cytes Normal undamaged keratinocytes are seen in the rest of lower part of the epidermis Thermal Burns Depending upon the depth of damage, thermal burns are classified into first degree, second degree and third degree burns Histopathology (Table 17.2) Table 17.2: Classification of thermal burns First degree burn Second degree burn Third degree burn Lower epidermis particularly the basal cell layer is intact Only upper epidermis is affected which shows signs of heat coagulation: nuclei may appear pyknotic with perinuclear halo or stain faintly eosinophilic or not at all (“architectural-ghosts”) Necrosis of the surface epidermis with occasional subepidermal blisters Partial thickness dermal necrosis Necrosis of the surface epidermis Full thickness dermal necrosis Destruction of all cutaneous appendages Lower portion of the cutaneous appendages not damaged Coagulation necrosis may extend to the subcutaneous tissue and to the underlying muscle 18 CHAPTER Lichen Sclerosus et Atrophicus (LSA) Lichen sclerosus et atrophicus is an inflammatory disorder of unknown etiology characterized by white polygonal papules that coalesce to form smooth, porcelain-white plaques at times simulating vitiligo The term balanitis xerotica obliterans is used when there is involvement of the male glans and prepuce which often leads to phimosis and kraurosis vulvae refers to involvement of the female labia majora, labia minora, perineum and perianal region which may cause narrowing of the vaginal orifice LSA may coexist with morphea.Although neoplasms have been reported in association with LSA, the current consensus is that LSA is not in itself a premalignant condition Histopathology (Fig 18.1) • • • Hyperkeratosis with follicular plugging The hyperkeratosis is so pronounced that the horny layer is often thicker than the atrophic stratum malpighii that may be reduced to a few layers of flattened cells Marked thinning of stratum malpighii with complete absence of rete ridges The rete ridges may be present in few areas and show irregular downward proliferation In such proliferations, hydropic degeneration of the basal cell is usually more severe The cells of the basal cell layer show hydropic degeneration Fig 18.1: Lichen sclerosus et atrophicus There is follicular plugging, marked thinning of stratum malpighii with vacuolar degeneration of basal cell layer Pronounced lymphedema is seen beneath the epidermis Lichen Sclerosus et Atrophicus (LSA) 117 Fig 18.2: Well established lesion of lichen sclerosus et atrophicus showing inflammatory infiltrate in the mid dermis • Follicular plugging is often associated with atrophy and disappearance of appendageal structures Keratotic plugging is not seen in mucosal lesions • Broad zone of pronounced lymphedema is seen beneath the epidermis In this zone the collagen fibers appear swollen and homogenous, and contains only few nuclei • The blood vessels are dilated and there may be areas of hemorrhage • Elastic fibers are sparse and in older lesions they are absent within the area of lymphedema • In well-established lesions an inflammatory infiltrate is present in the mid dermis (Fig 18.2) In early lesions, the inflammatory infiltrate is quite heavy and is superficial and band-like mimicking lichen planus (interface dermatitis) Features favoring a diagnosis of LSA over lichen planus include: • Basement membrane thickening • Epidermal atrophy • Loss of papillary dermal elastic fibers • Paucity of colloid bodies • Lack of wedge shaped hypergranulosis Lichen sclerosus et atrophicus has to be dif ferentiated from morphea histo-pathologically (Table 18.1) Table 18.1: Histologically difference between Lichen sclerosus et atrophicus and Morphea Lichen sclerosus et atrophicus Epidermis Dermo-epidermal junction Dermis Subcutis Thinning of epidermis follicular plugging Hydropic degeneration of basal cell layer Often subepidermal bulla Marked edema, Elastic fibers absent No inflammation or fibrosis Morphea Relatively normal epidermis No follicular plugging No hydropic degeneration Subepidermal separation not seen Appears homogenized Elastic fibers normal or increased Inflammation and fibrosis 19 CHAPTER Scleroderma Scleroderma literally means hard skin (Gr skleros, hard and derma, skin) It is characterized by deposition of collagen in the skin and sometimes in other or gans of the body It is classified into the following main groups • Localized scleroderma with its variants • Systemic scleroderma with its variants • Mixed connective tissue disease • Eosinophilic fasciitis In localized form of scleroderma skin is thickened and indurated without involvement of internal organs In systemic form there is diffuse involvement of skin accompanied by Raynaud’s phenomenon and a variable degree of involvement of internal organs (lungs, gastrointestinal tract, kidneys and heart) Localized Scleroderma (Morphea) Localized scleroderma is clinically characterized by well-defined ivory colored sclerotic plaques with a distinct violaceous border (the “lilac ring”) There may be a decreased sweat response and loss of hair in the lesions The lesions are indurated but not bound down to the deeper structures Usually the lesions are single or few in number Many clinical variants of localized scleroderma (morphea) are described • Generalized morphea (symmetrical and bilateral lesions seen without any systemic involvement) It differs from systemic sclerosis in several aspects (T able 19.1) • Guttate morphea (which may be a variant of lichen sclerosus et atrophicus) • Nodular (keloidal morphea) • Subcutaneous morphea (morphea profundus) • Linear scleroderma Table 19.1: Difference between generalized morphea and systemic sclerosis Raynaud’s phenomenon Acrosclerosis Organ involvement Prognosis Generalized morphea Systemic sclerosis Not Not Not Not Present Present Present Life-threatening seen seen seen life-threatening Systemic Scleroderma Two distinct subsets are recognized: • Limited systemic scleroderma • Diffuse systemic scleroderma The main differentiating features between limited and diffuse systemic scleroderma are summarized in Table 19.2 Scleroderma 119 Table 19.2: Difference between limited and diffuse systemic scleroderma Limited systemic scleroderma Diffuse systemic scleroderma Constitute about 60 percent cases of systemic scleroderma Patients are relatively young Long history (10 to 15 years) of Raynaud’s phenomenon Skin involvement limited to the digits or hands, face, feet and forearms Nail fold capillary dilatation and early onset of facial and digital telangiectasias Systemic involvement (notably pulmonary hypertension) may not appear for years Joint symptoms uncommon Constitute about 40% cases of systemic scleroderma Patients are relatively old Acute onset of Raynaud’s phenomenon with nonpitting edema of hands and feet Diffuse involvement of skin often sparing only buttocks and back Nail fold capillaries dilatation and destruction common Anticentromere antibodies (ACA) are predective for limited systemic sclerosis including CREST syndrome (sensitivity 60% and specifity 98% present) Early involvement of internal organs Polyarticular symmetrical synovitis, tenosynovitis and tendon friction rubs often present Scl-70 (Antitopoisomerase-1) are predictive for diffuse systemic sclerosis (Sensitivity 38% and specifity 100%) CREST (Calcinosis cutis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly andTelangiectasia) syndrome is a part of limited systemic scleroderma Biopsy Specimen It is important that a deep skin biopsy is taken which should include subcutis as most of the diagnostic histopathological findings are seen in the lower dermis and subcutaneous tissue LOCALIZED SCLERODERMA (MORPHEA) Histopathology • • The histopathological features of morphea and systemic scleroderma are determined by stage of the disease and the site of biopsy (Table 19.3) Biopsy from active peripheral violaceous border of the lesion of morphea shows more pronounced inflammatory reaction (inflammatory stage) The inflammatory cells comprises of lymphocytes, histiocytes and plasma cells present among collagen bundles of the lower two-thirds of the reticular dermis.A more pronounced inflammatory infiltrate is often present in the subcutaneous fat extending upward towards the eccrine glands Trabeculae subdividing the subcutaneous fat appear thickened because of the presence of inflammatory infiltrate and deposition of new collagen Table 19.3: Histopathological features of localized scleroderma and systemic scleroderma Localized scleroderma (Morphea) Inflammatory infiltrate is a prominent histologic feature in early morphea Vascular changes are not significant and occlusive vascular changes not found in morphea Sclerosis of the papillary dermis can be seen in morphea Calcification is uncommon in localized scleroderma • Systemic scleroderma Inflammatory infiltrate is mild both in early and late stage of systemic scleroderma Significant vascular changes are seen in late stage systemic scleroderma comprising of intimal proliferation and complete occlusion of vessels Sclerosis of the papillary dermis is absent in systemic scleroderma Calcification is seen more commonly in systemic scleroderma Collagen changes are seen initially in the lower third of the dermis and in the fibrous trabuculae of the subcutaneous fat Later in the course of the disease the changes extend to the upper portion of the dermis Collagen changes consist of markedly increased eosinophilia of collagen, thickening of collagen bundles and reduction of space between collagen bundles (Fig 19.1) Large areas of subcutaneous fat are replaced by newly formed collagen which is seen as fine wavy fibers rather than bundles and stain faintly with hematoxylin-eosin (Fig 19.2).V ascular changes are mild comprising of endothelial swelling and edema of the wall of the vessels 120 Histopathology of the Skin Fig 19.1: Morphea Collagen bundles are thickened with reduction of spaces within them There is paucity of inflammatory infiltrate No skin appendages seen Fig 19.2: Subcutaneous fat is replaced by newly formed collagen which shows only faint staining Biopsy from the central region of well established lesion of morphea may show only collagen changes and no inflammation The collagen bundles in the reticular dermis are thickened, closely packed and hypocellular They stain more deeply as compared to that in a normal skin In the papillary dermis collagen may appear homogenous in place of loosely arranged fibers The inflammatory infiltrate is almost absent in central area of subcutis The eccrine glands appear markedly atrophic and they seem to lie higher in the dermis instead of lying near the dermal subcutaneous junction as in normal skin because of the replacement of most of the subcutaneous fat by newly formed collagen Vascular changes comprise of paucity of blood vessels, narrowing of the lumen and fibrosis of their walls.VVG stain shows thick elastic fibers in the dermis Histopathology of late lesion of morphea is quite similar to that of systemic scleroderma SYSTEMIC SCLEROSIS (FIG 19.3) Histopathology In early lesions inflammatory infiltrate and vascular changes are mild and comprises of only dilatation of capillaries and lymphatics In well established cases the histopathological changes are: • Sclerosis in the lower two-third of the dermis and the subcutaneous fibrous trabuculae Hyalinized connective tissue replaces subcutaneous fat particularly around sweat glands There may be conspicuous absence of pilosebaceous units, eccrine ducts and glands Intimal proliferation and complete occlusion of the vessels occur in late stages Calcium aggregates can be seen in sclerotic homogenous, collagen of the subcutaneous tissue Histopathology of Morphea Profundus (Fig 19.4) Dense mononuclear cell infiltrate admixed with many plasma cells are present in subcutaneous tissue Extensive sclerosis and hyalinization of connective tissue is seen Bullous lesions are uncommon but may complicate both localized and systemic scleroderma The bullae are subepidermal in location and develop as a result of lymphatic obstruction and subepidermal edema The fascia and striated muscles are involved in the linear , segmental subcutaneous and generalized type of scleroderma The fascia shows fibrosis and sclerosis The muscle fibers show vacuolization and are separated from one another by edema and focal collections of inflammatory cells Scleroderma Fig 19.3: Systemic sclerosis Sclerosis is seen in the lower dermis and the subcutaneous fat Intimal proliferation of vessels is also seen No cutaneous appendages are seen 121 Fig 19.4: Morphea profundus Extensive sclerosis and hyalinization of connective tissue seen with dense mononuclear cell infiltrate in the subcutaneous fatty tissue Eosinophilic Fasciitis (Shulman’ s Syndrome) Eosinophilic fasciitis is a variant of scleroderma characterized by rapid onset of pain, swelling and symmetric induration of the skin and subcutaneous tissues of the limbs Face and fingers are usually spared Visceral involvement and Raynaund's phenomenon are usually absent There is pheripheral eosinophilia and hypergammaglobulinemia The condition sometimes starts following strenuous physical activity Eosinophilia-myalgia syndrome is a condition which is clinically and histopathologically similar to eosinophilic fasciitis It occurred in epidemic form in the USA and Japan in 1989, following ingestion of products containing L-tryptophan There was some defect in the manufacturing technique of L-tryptophan Histopathology: Early Histopathologic Features are: • Edema and inflammatory infiltrate comprising of lymphocytes, histiocytes, plasma cells and a conspicuous number of eosinophils that involve the deep fascia and the interlobular fibrous septa of subcutaneous fat Late Histopathologic Features are: • • Fibrosis of the deep fascia and septa of the subcutaneous tissue Hyalinization of the collagen which also involves the deeper dermis associated with atrophy of the appendages and sclerosis of the lower dermis Differential Diagnosis: Scleroderma In scleroderma there may be fibrosis of the facia but inflammatory cell infiltrate is usually absent in the fascia In eosinophilic fasciitis inflammatory infiltrate in the fascia is a prominent features MIXED CONNECTIVE TISSUE DISEASE Mixed connective tissue disease (MCTD) is a distinct clinical syndrome with combined features of scleroderma, systemic lupus erythematosus and polymyositis The patients have high titers of antibody to a ribonucloprotein, the extractable 122 Histopathology of the Skin nuclear antigen The patients with systemic scleroderma not have this antibody MCTD usually has a benign and chronic course Histopathology When cutaneous tissue of lupus erythematosus are present, the histopathology of skin lesions will show features consistent with the histopathology of lupus erythematosus Other histopathological features depend upon the site, stage and type of cutaneous lesions biopsied and include: • Marked dermal edema with separation of the collagen bundles • Dermal sclerosis • Thickening and narrowing of vessels in the subcutis Direct immunofluorescence of uninvolved skin shows a characteristic pattern of speckled epidermal nuclear staining with specifically for IgG 20 CHAPTER Lichen Simplex Chronicus (Circumscribed Neurodermatitis) Clinically the patient presents as dry scaly, thickened plaques because of persistent itching and rubbing.The plaques often show evidence of excoriation and the normal skin markings are markedly accentuated, the latter finding referred to as lichenification Histopathology (Fig 20.1) • • • • • • Marked compact orthokeratosis Hypergranulosis Focal parakeratosis may be seen occasionally Minimal papillomatosis in certain areas of the section Epidermis shows irregular elongation and thickening of the rete ridges Marked thickening of papillary dermis with bundles of collagen arranged in vertical streaks Scattered inflammatory cells and some fibroblasts are usually present in this region of the dermis Differential Diagnosis • • Prurigo nodularis Psoriasis Fig 20.1: Lichen simplex chronicus showing hyperkeratosis, hypergranulosis, irregular elongation of rete ridges and bundles of collagen in vertical streaks in the papillary dermis 124 Histopathology of the Skin Fig 20.2: Prurigo nodularis showing pronounced hyperkeratosis, papillomatosis and marked irregular acanthosis Papillary dermis shows vertically oriented collagen bundles and inflammatory infiltrate Fig 20.3: Prurigo simplex There is mild acanthosis, mild spongiosis and perivascular lymphocytic infiltration in the upper dermis Prurigo Nodularis Prurigo nodularis is characterized clinically by intensely pruritic nodular lesions 1-3 cm in diameter with a raised warty surface The lesions tend to occur in groups and vary greatly in number The lesions usually are seen on the distal and extensor surface of the extremities The condition has a very protracted course Histopathology (Fig 20.2) • • Pronounced hyperkeratosis Papillomatosis and irregular acanthosis with downward proliferation of the epidermal and adnexal epithelium approaching pseudoepitheliomatous hyperplasia • Papillary dermis shows predominantly lymphocytic inflammatory infiltrate and vertically oriented collagen bundles • Prominent neural hyperplasia is not now considered as an essential feature of prurigo nodularis; increased number of cutaneous nerves can be demonstrated by silver stain or cholinesterase stain in few cases Presence of enlarged dendritic mast cells containing fewer cytoplasmic granules in the dermis has recentlty been reported Prurigo Simplex Clinically prurigo simplex presents as markedly itchy erythematous urticarial papules especially on the trunk and extensor surface of the extremities in a bilaterally symmetrical fashion It is common in middle -aged persons with atopic dermatitis It has to be differentiated from dermatitis herpetiformis (DH) and papular urticaria In prurigo simples there is no grouping of lesions as seen in DH Histopathology (Fig 20.3) Early papules show: • Parakeratosis • Mild acanthosis Lichen Simplex Chronicus • • 125 Spongiosis with an occasional small vesicle Mild perivascular lymphocytic inflammatory infiltrate with few eosinophils is seen in upper dermis Excoriated papules show: • Partial absence of epidermis with crust containing degenerated nuclei of inflammatory cells • Serial sections may show spongiosis and exocytosis of lymphocytes in the follicular infundibulum and a perifollicular infiltrate ... Daryaganj, New Delhi 11 0 002, India Phones: + 91- 11- 2327 214 3, + 91- 11- 23272703, + 91- 11- 232820 21, + 91- 11- 23245672, Rel: 32558559 Fax: + 91- 11- 23276490, + 91- 11- 23245683 e-mail: jaypee@jaypeebrothers.com Visit... epithelium of the normal oral mucosa with the exception of the dorsum of the tongue and hard palate (Fig 1. 21) In the absence of granular and horny layer, the epithelial cells migrate from the. .. 92 14 Hansen’s Disease (Leprosy) 98 15 Leishmaniasis 10 6 16 Disorders of Hypopigmentation 11 0 17 Erythema Multiforme 11 4 18