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(BQ) Part 1 book Histopathology of the skin presents the following contents: Pigmented purpuric dermatosis, dermatitis herpetiformis, sarcoidosis, lupus erythematosus, pyoderma gangrenosum, urticaria pigmentosa, gyrate and annular erythemas, seborrheic keratosis, basal cell carcinoma,... Invite you to consult.
21 CHAPTER Pigmented Purpuric Dermatosis (Schamberg’s Disease) Progressive pigmentary dermatosis (PPD) includes a group of conditions characterized clinically by the presence of petechial and pigmentary macules on lower legs The disease has a chronic and relapsing course There is extravasation of erythrocytes in the skin and or marked hemosiderin deposits which produces reddish brown lesions on skin Following clinical entities are included under the heading of pigmented purpuric dermatosis • Schamberg's disease (progresseive pigmented purpuric dermatosis) • Purpura annularis telangiectodes (Majocchis disease) • Lichen aureus • Pigmented purpuric lichenoid dermatosis of Gougerot and Blum • Eczematoid like purpura of Doucas and Kapetanakis Other rare conditions included in the group are: • Itching purpura of Löwenthal • Linear PPD • Granulomatous variant • Transitory PPD • Familial forms There are a number of drugs reported to induce PPD They are: • Acetaminophen • Aspirin • Adalin • Carbamol • Chlordiazepoxide • Glipizide • Glybuzole • Hydralazine • Meprobamate • Persentin • Reserpine • Thiamine • Interferon alfa • Injection Medroxy progesterone acetate Schamberg's Disease (Progressive Pigmented Purpuric Dermatosis) Schamberg's disease is characterized by asymptomatic closely set pinhead-sized reddish brown macules resembling groups of cayenne-pepper present mainly on the lower limbs Pigmented Purpuric Dermatosis 127 Purpura Annularis Telangiectodes (Majocchis Disease) The lesions are annular , bluish-red in color which initially show central red telangiectatic puncta and later on there is atrophy The lesions are variable in number and may involve upper extremities also Pigmented Purpuric Lichenoid Dermatosis (Gougerot-Blum Syndrome) Clinically the condition presents as plaques of various hues comprising of tiny lichenoid paplues Lichen Aureus (Lichen Purpuricus) This is characterized by sudden onset of intensely itchy, localized eruption consisting of lichenoid papules in association with purpuric lesions with a characteristic golden-brown color The lesions are mainly present on the lower legs but trunk and face may also be involved on rare occasions Itching and Eczematoid Purpura of Doucas and Kapentanakis The lesions in this condition are more extensive and severely pruritic Histopathology (Fig 21.1) All the clinical variants of PPD have a common histopathology showing only minor differences • Epidermis shows mild spongiosis and exocytosis of lymphocytes (except in lichen aureus) • Dermis shows perivascular infiltrate of lymphocytes and macrophages around superficial small blood vessels of the skin with endothelial cell swelling and narrowing of the lumina • Extravasation of red blood cells with marked hemosiderin deposition in macrophages is a characteristic feature (Fig 21.2) The degree of hemosiderin deposit is variable Fig 21.1: Schamberg’s disease Dermis shows perivascular lymphohistiocytic infiltration and macrophages around super-ficial and small blood vessels Fig 21.2: Perl’s stain demonstrating hemosiderin deposition in the upper dermis 128 Histopathology of the Skin Figs 21.3A and B: Lichen aureus Band like infiltrate is seen in the upper dermis associated with increased dermal capillaries Perl’s stain is positive for hemosiderin deposit (Fig 21.3B) Special Stains Perl's stain is used to demonstrate iron (hemosiderin) deposition in the superficial dermis which are seen as dark blue deposits Histopathological Variations Include • • • Band like infiltrate separated from the epidermis by a thin rim of uninvolved collagen and associated with increased dermal capillaries in cases of lichen aureus (Figs 21.3A and B) In lichen aureus absence or a near absence of civatte bodies or basal layer vacuolopathy helps in differentiating it from lichen planus Spongiosis and prominent neutrophils in the dermal infiltrate are seen in itching purpura Granulomatous infiltrate is a feature of granulomatous variant Differential Diagnosis Stasis Dermatitis In stasis dermatitis there is deposition of hemosiderin even in the deeper dermis in comparison to PPD where the hemosiderin deposition is confined to superficial part of dermis only Epidermal changes are more pronounced and fibrin deposits and changes of intravascular red blood cell sludge are also features of stasis dermatitis Leukocytoclastic Vasculitis/Cutaneous V asculitis Clinically the lesions in cutaneous vasculitis are erythematous papules that are palpable and not blanch on diascopy Histopathology of established lesions show infiltrates of neutrophils and nuclear dust in and around venules along with deposition of fibrin in vessel walls and occasionally in its lumen 22 CHAPTER Dermatitis Herpetiformis Dermatitis herpetiformis (DH) is a condition characterized by extremely pruritic eruption comprising of symmetrical papulovesicles, vesicles or crusts on inflamed skin, mainly involving the extensor surfaces, i.e elbows, knees, buttocks, scapula and scalp The papulovesicular lesions show a characteristic herpetiform grouping There is no involvement of the oral mucosa Young to middle aged individuals are usually affected with a slight male predominance In the majority of cases (90%) there is an associated gluten-sensitive enteropathy Histopathology The characteristic histopathological findings are seen in erythematous skin adjacent to early blisters Hence, while taking a biopsy the inclusion of perilesional skin is important Sequence of histopathologic changes that occurs in evolution of a lesion of dermatitis herpetiformis are: • Accumulation of neutrophils at the tips of dermal papillae (Fig 22.1A) • Gradually eosinophils appear amongst neutrophils which, however, remain predominant in number • Formation of multiloculated blisters because of separation of tips of the dermal papillae from the overlying epidermis (Fig 22.1B) • Fibrin is seen in the papillae which imparts a bluish coloration Fig 22.1A: Dermatitis herpetiformis Accumulation of neutrophils at the tips of the dermal papilla Fig 22.1B: Dermatitis herpetiformis Multilobulated blister which is subepidermal in location 130 • • • • • Histopathology of the Skin Blisters become unilocular as the rete ridges loose their attachment to the dermis as seen in clinically apparent blisters (Fig 22.2) When the unilocular subepidermal blister is formed, the characteristic papillary microabscess can be observed at the periphery of the blister Prominent inflammatory infiltrate of neutrophils and some eosinophils is seen in the dermis beneath the papillae Leukocytoclasis of several neutrophils can be seen Apoptotic keratinocytes may be a chance finding seen above the papillary microabscesses Immunofluorescence Testing Direct immunofluorescence (DIF) test shows granular deposits of IgA in the dermal papillae of perilesional and uninvolved skin, although the deposition is not uniform The deposition is maximum in normal skin adjacent to an active lesion Fibrillar IgA deposits may also be present Other immunoglobulins particularly IgM can be seen in 30 percent and C3 in approximately 50 percent of cases Early in the course of the disease IgA deposits may be absent and a repeat DIF should then be performed Epidermolysis Bullosa Acquisita Epidermolysis bullosa acquisita (Dermolytic pemphigoid, EBA) is a rare, non- hereditary subepidermal bullous disorder characterized by acquired fragility of skin In the classical form bullae develop on non-inflammatory bases in areas prone to minor trauma such as acral areas.The bullae heal with scarring and milia formation.A characteristic nail dystrophy and alopecia are other features present This form is associated with malignant lymphoma, amyloidosis and colitis or enteritis Some patients have marked involvement of oral and conjunctival mucosa in addition to acral lesions and nail dystrophy These cases resemble cicatricial pemphigoid (cicatricial pemphigoid-like) In other cases the bullae may arise on pruritic, erythematous macules and papules, the lesions being more generalized and not entirely acral in location (bullous pemphigoid-like) Histopathology Shows (Fig 22.3) • • Subepidermal bulla with fibrin and only a few inflammatory cells in the bullous cavity The roof of the blister is well preserved with few dermal fragments attached to the epidermis Fig 22.2: Dermatitis herpetiformis Unilocular subepidermal bulla containing predominantly neutrophils Fig 22.3: Epidermolysis bullosa acquisita Subepidermal bulla with fibrin and only a few inflammatory cells in the bullous cavity Dermatitis Herpetiformis • • • 131 Dermal changes depend upon whether the bullae are inflammatory (arising on inflamed skin) or non-inflammatory (arising on normal skin) In non-inflammatory lesions sparse lymphocytic infiltrate is seen around the vessels of the superficial vascular plexus In inflammatory lesions dense inflammatory infiltrate comprising predomi-nantly of neutrophils is present in the upper dermis Few eosinophils may also be seen Immunofluorescence Testing DIF (Direct immunofluorescence test): Perilesional skin shows linear deposition of immunoglobulins particularly IgG and of complement at the basement membrane zone in the vast majority of cases IgM and IgA may also be present as well A deposition of only linear C3 at the dermoepidermal junction favors the diagnosis of bullous pemphigoid and when multiple immunoglobulin subclasses (IgG, IgM and IgA) are present at the dermoepidermal junction, then the diagnosis is more likely of EBA DIF may not reliably help to differentiate bullous pemphigoid from EBA Indirect immunofluorescence (IIF) test: Circulating anti-basement membrane zone antibodies are seen in upto 50 percent cases of EBA Salt-split technique is a more reliable test and exact diagnosis can be made in majority of cases The antibodies in EBA are directed against type VII collagen antigen a major component of anchoring fibrils and hence on salt-split skin studies IgG is demonstrated on the floor and not on the roof of the split In bullous pemphigoid, localization of antibodies only to the floor of the blister is not a feature They are demonstrated either only on the roof of the blister or both on the roof and floor of the subepidermal blister Cicatricial Pemphigoid (Benign Mucous Membrane Pemphigoid) Cicatricial pemphigoid (benign mucous membrane pemphigoid) is an uncommon, chronic, vesiculo-bullous disease characterized by its chronic course, its scarring nature and its predilection for the mucosal surfaces Cutaneous lesions occur in about 25 percent of cases but only in 10 percent it is the initial clinical presentation There is a tendency for blister to recur in the same area The most commonly involved mucosal surfaces in the order of frequency , are the oral mucosa, the conjunctiva, the larynx, the genitalia and the esophagus Two types of cutaneous lesions are seen In one type there are scattered tense bullae that heal without scarring In the other type recurring blisters develop on one or several areas of erythema and heal with scarring Localized Cicatricial Pemphigoid (Brunsting-Perry T ype) In this type of cicatricial pemphigoid there are no mucosal lesions but there are one or several circumscribed erythematous patches on which recurrent crops of blisters appear Ultimately atrophic scarring results Usually patches are confined to the head and neck Histopathology Subepidermal bulla is seen Dermal infiltrate depends upon the age of the lesion Very early lesions show predominance of neutrophils and neutrophilic abscess As the lesions age, number of eosinophils increases and in older lesions there are more of lymphocytes and less number of neutrophils • Eosinophils are always fewer in number in comparison to that seen in bullous pemphigoid • Newly formed collagen bundles are seen in areas of scarring These are arranged parallel to the surface instead of normal haphazard arrangement • The presence of a sebaceous gland within the blister is regarded as an important feature in the diagnosis of cicatricial pemphigoid This results from extension of the bulla along the edge of the pilosebaceous unit Occasionally it may be impossible to differentiate cicatricial pemphigoid from bullous pemphigoid and dermatitis herpetiformis on histopathologic examination • • 132 Histopathology of the Skin Direct Immunofluorescence (DIF) T est Linear deposits of IgG and C3 are seen along the basement membrane zone in approximately 80 percent of cases IgA and other immunoglobulins may be detected in approximately 20 percent of cases but only rarely is IgA the only immunoglobulin present Herpes Gestationis (Pemphigoid Gestationis) Herpes gestationis is a rare pruritic, vesiculo-bullous dermatosis that usually develops during the second to third trimester of pregnancy Initial lesions are pruritic urticarial plaques that usually develop in the periumblical area The lesions gradually involve the extremities, hands and feet and progress to form tense vesicles, bullae and few herpetiform lesions The disease tends to recur with subsequent pregnancies and the lesions get exacerbated during menstrual period and by oral contraceptives Histopathology Early urticarial plaques show: • Marked edema of the papillary dermis • Superficial and mid-dermal perivascular infiltrate of lymphocytes, histiocytes and eosinophils • Spongiosis which may be eosinophilic in nature is often seen overlying the tips of the dermal papillae • Focal necrosis of the basal keratinocytes which lead to subepidermal blister is evident in clinically vesiculo-bullous lesions • Subepidermal bulla contains eosinophils, lymphocytes and histiocytes DIF (Direct Immunofluorescence) test: Linear deposition of C3 and sometimes IgG along the basement membrane zone is seen in perilesional skin Bullous Systemic Lupus Erythematosus Vesiculo-bullous lesions in patients with systemic lupus erythematosus are non-itchy, widespread and occasionally show predilection for sun exposed areas of the body Histopathology Three different histopathologic patterns are described: • Dermatitis herpetiformis like with subepidermal splitting and papillary micro abscesses The neutrophils and nuclear dust are present deeper in the papillary dermis around vessels which is usually not seen in dermatitis herpetiformis • Histopathologic pattern showing marked basal layer vacuolization that leads to subepidermal blister • There may be vasculitis with subepidermal blister and pustule formation DIF (Direct immunofluorescence) test: IgG and C3 deposition at the epidermal basement membrane zone IgM and IgA are seen in 50 percent and 60 percent of cases respectively The linear pattern of deposition is more common (50%) as compared to granular “band like pattern” (25%) Epidermolysis Bullosa Epidermolysis bullosa (EB) comprises a group of genetically determined skin fragility disorders characterized by blistering of the skin and mucosa following mild mechanical trauma Mechanobullous disease is an alternative term used for these disorders These mechanobullous diseases are classified on the basis of the level of the split • Epidermolytic (Epidermolysis bullosa simplex and its subtypes) • Junctional (Junctional epidermolysis bullosa and its subtypes) • Dermolytic (Dystrophic epidermolysis bullosa and its subtypes) Dermatitis Herpetiformis 133 Histopathology A definitive diagnosis of various types and subtypes of epidermolysis bullosa cannot be made on routine light microscopy Routine histopathology in majority of variants of EB shows: • Subepidermal blister • Scanty inflammatory infiltrate Histochemical staining is required for the diagnosis of various types of epidermolysis bullosa Darier-White Disease (Keratosis Follicularis) and Acral Darier- White Disease (Acrokeratosis verruciformis of Hopf) Darier White disease (DWD) is an autosomal dominant disorder characterized by abnormal keratinization of the epidermis, nail and mucous membranes.The cutaneous lesions are discrete, scaly, waxy, crusted papules that are usually malodorous, and are commonly seen on the face, forehead, scalp, chest and back The lesions are more severe in summer Punctate keratosis on the palms and soles occur in most patients The nails are fragile and there is a characteristic V-shaped scalloping of the free edge and subunqual thickening.White centrally depressed papules are often seen on the mucosa of the cheeks, palate and gums and may involve the rectum and vulva Multiple plane keratosis on the dorsa of hands (acrokeratosis verruciformis) are a common finding Histopathology Shows (Fig 22.4) • • • • • • Acanthosis, hyperkeratosis and papillomatosis Lacunae, which are small, slit like intraepidermal vesicles present directly above the basal cell layer They contain acantholytic cells There is irregular upward proliferation into the lacunae of papillae lined by a single layer of basal cells or so-called villi The most characteristic feature is the presence of corps ronds and grains The corps ronds and grains are seen in the upper startum malpighii specially in the granular and horny layer They possess a central homogenous, basophilic pyknotic nucleus that is surrounded by a clear halo Peripheral to the halo lies basophilic dyskeratotic material as a shell Grains are seen in the horny layer and as acantholytic cells within the lacunae They resemble parakeratotic cells but are somewhat lar ger Dermis shows a chronic inflammatory infiltrate Fig 22.4: Darier’s-White disease showing suprabasal lacunae, corps ronds and grains 134 Histopathology of the Skin Fig 22.5: Hailey-Hailey disease showing suprabasal bulla with villi formation and acantholytic cells Hailey-Hailey Disease (Benign Familial Pemphigus) Hailey-Hailey disease (HHD) is an autosomal dominant condition characterized by late onset (aged 20-30 years) of painful erosions, vesiculopustules and scaly erythematous plaques at the sites of friction such as the neck, axillae, groins and perineum Mucosal involvement is not common Histopathology (Fig 22.5) The histopathologic findings in HHD are similar to Darier-White disease (DWD) in that there is acantholysis with epidermal clefting and vesiculation but the acantholysis is more pronounced in DWD Diabetic Bulla Cutaneous disorders associated with diabetes mellitus are thought to occur in about one-third of patients during the course of their disease Three cutaneous disorders usually considered diagnostic of diabetes are : • The syndrome of limited joint mobility and waxy skin • Diabetic dermopathy • Diabetic bulla Diabetic bullous lesions are usually recurrent in nature and most commonly affect the acral areas especially the feet Histopathology • • • Intraepidermal cleavage without acantholysis situated in the superficial part of the epidermis is the most commonly seen histopathological finding Subepidermal bulla may be seen in some cases Dermal papillary blood vessels may show slight thickening Differential Diagnosis Includes • • • • • Bullous pemphigoid Epidermolysis bullosa acquisita Porphyria cutanea tarda Erythema multiforme Drug eruption 23 CHAPTER Sarcoidosis Sarcoidosis is a systemic disease with involvement of multiple organs including skin In many cases cutaneous lesions may be the only presenting manifestation Between 10 to 35 percent of patients with systemic sarcoidosis exhibit cutaneous lesions The skin lesions in sarcoidosis can be categorized as: • Specific : Showing a granulomatous histology and • Non-specific Specific Lesions The specific lesions are varied in morphology comprising of papules, nodules, plaques, subcutaneous tumors and scaly erythematous and atrophic flat lesions The skin lesions because of their characteristic varying color hues and a waxy translucent appearance usually prompts the diagnosis of sarcoidosis They are almost never pruritic or painful Maculopapular sarcoidosis is a term used for flat-topped translucent reddish to brownish papules seen around eyes and nasolabial folds Papules when present in annular configuration simulate, granuloma annulare Annular lesions are also produced by plaque type lesions that undergo central atrophy simulating necrobiosis lipoidica Subcutaneous sarcoidosis (Darier-Roussy) usually presents as nodules which are usually not translucent, have a violaceous hue and are commonly seen on extremities and trunk Plaques of sarcoidosis may show large telangiectatic vessels on the surface– angiolupoid lesions and the term lupus pernio is used for plaque lesions present on the ear lobes, nose, fingers and toes Tumor like lesions may be confused with cutaneous T cell lymphomas (CTCL) Scarring alopecia, widespread erythema and hypopigmented macules are infrequent manifestations Non-specific Lesions Erythema nodosum is a non-specific skin lesion of sarcoidosis which when present is an indicator of the benign selflimiting course of the disease Histopathology (Specific Lesions) • • • Epidermis is usually normal or atrophic Verrucous lesions show acanthosis Prominent hyperkeratosis is seen in ichthyosiform variant Sarcoidal granulomas are discrete, round or oval localized either in the superficial dermis or they may extend through the whole thickness of the dermis or subcutis depending on the type of cutaneous lesion biopsied Sarcoidal granulomas are composed predominantly of epithelioid histiocytes and multinucleate giant cells which may be either Langhan's or foreign body type They are referred to as naked granulomas because of lack of notable mantle of lymphocytes around the granulomas and absence of caseous necrosis They may, however, be surrounded by a sparse rim of lymphocytes and plasma cells and only on rare occasions lymphocytes are present within them (Fig 23.1) 62 CHAPTER Arthropod Bite Reactions (Papular Urticaria) Arthropod bites and stings cause intense pruritus with the development of localized or widespread papules and papulovesicles often with a central punctum Papular urticaria or lichen urticatus is caused by hypersensitivity to insect bites (fleas, gnats, mosquitoes or bedbugs) It is characterized by grouped urticarial papules and papulovesicles with a tendency to spread Intensely pruritic localized or widespread grouped papules and papulovesicles often with a central punctum are manifestations of arthropod bites and stings Histopathology Histopathological findings in arthropod bite reaction and papular urticaria are quite similar and include: • Wedge shaped superficial and deep perivascular and interstitial inflammatory dermal infiltrate composed of lymphocytes and eosinophils (Fig 62.1) • Epidermis shows foci of spongiosis, vesicle formation or even epidermal necrosis depending upon the extent of damage (Fig 62.2) • Mosquito bite reaction in early stage shows many neutrophils as inflam-matory infiltrate mostly vasculocentric and later a predominantly mono-nuclear infiltrate of lymphocytes and plasma cells Eosinophils are few or absent Fig 62.1: Arthropod bite reaction showing wedge shaped perivascular and interstitial inflammatory infiltrate comprising of lymphocytes and eosinophils Fig 62.2: Arthropod bite reaction showing epidermal necrosis with subepidermal bulla Arthropod Bite Reactions (Papular Urticaria) 267 Persistent arthropod assault reaction shows: • Dense lymphoid infiltrate often with formation of lymphoid follicles resembling a lymphoma When parts of the sting apparatus are retained within the dermis then there is: • Chronic inflammatory response with eosinophils and • Pseudocarcinomatous epidermal hyperplasia Most arthropod sting reactions produce similar histological changes: • Epidermal findings include focal spongiosis, hyperplasia and dyskeratosis Necrosis and ulceration can be seen in the epidermis at punctum site • A superficial and deep perivascular infiltrate composed of lymphocytes and eosinophils and extending into the deep reticular dermis is typical of sting reactions Histology may also reveal prominent endothelial cell swelling and extravasation of erythrocytes Although these changes are most common, variations can be seen in the histology of insect stings • Neutrophils and plasma cells may be seen in some instances and may be the predominant cell type present The reaction may present with a complete absence of eosinophils • Occasionally arthropod parts such as the stinging apparatus of the honey bee may remain in the skin These remnants can induce the formation of foreign body granuloma or rarely epidermal cyst 63 CHAPTER Keratosis Pilaris Keratosis pilaris is characterized by keratotic follicular papules which mainly affects lateral aspects of the upper arms, thighs and buttocks There is no itching and the condition may occur in association with ichthyosis vulgaris Histopathology Shows (Fig 63.1) • An orthokeratotic plug that fills the orifice and upper part of the follicular infundibula • Mild perivascular mononuclear cell infiltrate in the dermis adjacent to the involved hair follicle Histopathologically and clinically keratosis pilaris has to be differentiated from: Lichen spinulosus: In this condition the keratin plug protrudes much more above the follicular orifice and it usually contains one or more hair shafts Phrynoderma: The follicular keratin plug in this condition is parakeratotic Fig 63.1: Keratosis pilaris An orthokeratotic plug fills the orifice and the upper part of the infundibulum Perivascular mononuclear cell infiltration is seen adjacent to the involved hair follicle 64 CHAPTER Lichen Amyloidosis and Macular Amyloidosis Lichen amyloidosis and macular amyloidosis are forms of primary localized cutaneous amyloidosis Lichen amyloidosis is characterized by severely pruritic closely set, discrete, verrucous papules commonly seen on the legs, especially the shins These papules may coalesce to form plaques simulating lichen simplex chronicus or hypertrophic lichen planus Macular amyloidosis is characterized by pruritic pigmented macules showing reticulated or rippled pattern The common site of involvement is interscapular area of the upper back Clinically macular amyloidosis is often misinterpreted as mere postinflammatory hyper-pigmentation Special stains By light microscopy, amyloid appears amorphous, eosinophilic and hyalinized Special stains are employed to distinguish it from other glassy pink substances Congo-red stain is commonly employed to demonstrate amyloid deposits which appear brick-red in color Amyloid stains, metachromatically with crystal violet and methyl violet stains Histopathology • Both lichen and macular amyloidosis show globules of dull pink material (amyloid) that are limited to the widened dermal papillae (Figs 64.1 and 64.2) The deposits are usually smaller in macular amyloidosis than in lichen amyloidosis Fig 64.1: Lichen amyloidosis showing amyloid in the dermal papilla Fig 64.2: Macular amyloidosis There is deposition of dull pink material in the widened dermal papillae Epidermis shows atrophy 270 Histopathology of the Skin Occasionally the amount of amyloid in macular amyloidosis is so small that it may not be detected even when special stains are used In such cases a second biopsy is advised to confirm the diagnosis • There is often marked pigmentary incontinence in the form of melanophages in the papillary dermis • The inflammatory infiltrate is usually insignificant The presence of broadened dermal papillae in the apparent absence of an infiltrate of inflammatory cells is a clue to macular or lichen amyloidosis 65 CHAPTER Malignant Melanoma Malignant melanoma in majority of cases arises invariably from melanocytes at the epidermal-dermal junction The lesions are commonly associated with a pre-existing nevus They may be localized entirely within the epidermis (in situ melanoma) or may extend from the epidermis into the dermis (invasive malignant melanoma) Occasionally invasive melanoma may be entirely dermal at presentation Invasive melanoma may be: non-tumorigenic (“radial or horizontal growth phase”) and tumorigenic (“vertical growth phase”) In the non-tumorigenic radial or horizontal growth phase, the melanoma cells are confined to the epidermis (melanoma in situ) or the epidermis and papillary dermis without formation of an expansile tumor mass (microinvasive melanoma) In the tumorigenic vertical growth phase there is invasion of the dermis with expansile tumor formation Melanoma cells have abundant cytoplasm containing varying amounts of melanin that often consists of small “dusty” particles They are almost entirely devoid of readily visible dendrites The nuclei tend to be large and hyper-chromatic with irregular nuclear membrane and irregularly clumped chromatin (Fig 65.1) Histopathologically melanomas can be described as non-tumorigenic or tumorigenic (T able 65.1) The non-tumorigenic radial or horizontal growth phase is the beginning stage of melanoma in which the neoplastic melanocytes (melanoma cells) are confined to the epidermis (melanoma in situ) or to the epidermis and papillary dermis without formation of an expansile tumor mass (micro-invasive melanoma) The vertical growth phase or a phase of dermal invasion with expansile tumor formation usually follows the initial non-tumorigenic radial or horizontal growth phase after a varying period of time Fig 65.1: Melanoma cells containing varying amount of melanin 272 Histopathology of the Skin Table 65.1: Features differentiating tumorigenic and non-tumorigenic melanoma Non-tumorigenic melanoma (Fig 65.2) Tumorigenic melanoma (Figs 65.3 and 65.4) Expand more or less along the radii of a imperfect circle Appears as an expanding papule within a previously indolent plaque as viewed clinically ABCD criteria has been described lesion and grows in three dimensions in a balloon like fashion to for clinical diagnosis form a nodule ABCD criteria is not applicable A Lesional Asymmetry (one half of a lesion does not Tumor nodule is commonly symmetrical with smooth borders match the other half in shape or in color distribution B Lesional Border irregularity (the lesion tends to have an indented coastline like the map of a small island) C Lesional Color variegation (the surface is multicolored The color is quite uniform and may be pink rather than blue-black and may include shades of tan, brown, blue-black, grey-white and other variations) D Lesional Diameter ( generally greater than mm, but Diameter is often less than mm may be smaller) Histopathologically most of the lesional cells are Histopathologically a mass of melanoma cells is present in the located in the epidermis In microinvasive lesions dermis, defined as at least one cluster (nest) in the dermis that is few lesional cells are seen in the papillary dermis larger than the largest intraepidermal cluster (indicative of a tumor No mass of melanoma cells is seen in the dermis (no with capacity for expansile growth in the dermis) Any mitosis in cluster larger than the largest intraepidermal cluster) the dermal component of the melanoma is strong indication of a No mitoses in the dermal component of the melanoma tumor with the capacity of expansile growth in the dermis and defines a typical vertical growth phase Fig 65.2: Non-tumorigenic melanoma Most of the melanoma cells are located in the epidermis Fig 65.3: Tumorigenic melanoma Mass of melanoma cells is seen in the dermis Malignant Melanoma 273 Fig 65.4: Nests of melanoma cells in the dermis Melanoma in situ and non-tumorigenic invasive melanoma are classified into the following types: • Lentigo maligna • Superficial spreading • Acral lentiginous • Mucosal lentiginous Tumorigenic melanoma may arise “dero novo” (nodular melanoma) or originate in relation to a preexisting nontumorigenic types of melanoma mentioned above and are thus named accordingly 66 CHAPTER Cutaneous Neurofibroma Cutaneous neurofibromas occur as multiple, variously sized soft tumors on skin The associated skin lesions seen are cafe au lait spots and bilateral axillary freckling Plexiform neurofibroma is a form of cutaneous neurofibroma which has the flabby texture of a “bag of worms” Histopathology Shows • • • • • • • Non-encapsulated, loosely textured tumors present in the dermis They may extend into the subcutis, often in a diffuse infiltrative fashion (Fig 66.1) A free Grenz zone separates the tumor from the epidermis Tumor mass is formed of delicate fascicles, usually only a single cell thick The cells have an oval or spindle shaped nuclei and scant indefinite cytoplasm Nuclear pleomorphism may sometimes be seen but there is no mitosis Matrix is formed of wavy collagen Increased blood vessels are seen in the stroma In plexiform neurofibroma, numerous large nerve fascicles are seen embedded in a cellular matrix containing abundant mucin, as well as fibroblasts and Schwann cells Fig 66.1: Neurofibroma Non-encapsulated loosely textured tumor comprising of delicate fascicles usually a single cell thick seen in the dermis Cutaneous Neurofibroma 275 Fig 66.2: Lipoma consisting of normal fat cells Lipomas Lipomas occur as single or multiple subcutaneous lumps that are soft and movable against the overlying skin Some lipomas show characteristic clinical presentation and location Histopathology Shows (Fig 66.2) • • Normal fat cells that are indistinguishable from fat cells in the subcutaneous tissue Thin connective tissue capsule surrounds the tumor mass Index A C Acanthosis nigricans 245 Acne vulgaris 211 Actinic keratosis 172 acantholytic type 173 atrophic type 173 bowenoid type 173 hypertrophic type 172 pigmented type 173 Actinic prurigo (Hutchinson’s summer prurigo, hereditary polymorphous light eruption) 217 Actinic reticuloid 219 Alopecias 180 areata 180 androgenetic 183 scalp biopsy 180 traction 183 trichotillomania 182 Arthropod bite reactions 266 Cells of the skin and their identification 20 Chronic actinic dermatitis 218 Common terminologies used in dermatopathology 26 acantholysis 26 acanthosis 26 anaplasia 26 apoptosis 26 argentaffin 26 argyrophilic 26 atrophy 26 ballooning degeneration 27 cleft 27 cornoid lamella 27 corps and ronds 27 degeneration 27 delling 27 desmoplasia 27 dyskeratosis 27 elastorrhexis 27 elastosis 27 epidermal hyperkeratosis 28 epidermotropism 28 exocytosis 28 festooning 28 fibrosis 28 fibrous tissue 28 flame figures 28 follicular plugging/poral hyperkeratosis 28 grains 28 granuloma 28 grenz zone 28 horn cyst 29 horn pearls 29 Congo red stain methodology 42 staining technique 42 Cutaneous neurofibroma 274 B Basal cell carcinoma 156 basosquamous carcinoma 159 clinical subtypes 156 fibroepithelioma of Pinkus 157 morpheaform 157 nodular 156 pigmented 156 superficial 156 fibroepithelioma 159 histopathological subtypes 158 adenoid type 158 cystic type 158 infiltrating type 159 infundibulocystic type 159 keratotic type 159 metatypical type 159 micronodular type 158 multifocal superficial type 158 pigmented type 158 sclerosing (morphea) type 159 Borderline lepromatous 101 Borderline tuberculoid 100 Bowen’s disease 174 Bullous pemphigoid 70 D Demodicidosis 213 Dermal muscle cells smooth muscle 13 striated muscle 13 Dermatitis and eczema 46 Dermatitis herpetiformis 129 bullous systemic lupus 132 Darier-White disease 133 diabetic bulla 134 epidermolysis bullosa 132 epidermolysis bullosa acquisita 130 Hailey-Hailey disease 134 herpes gestationis 132 localized cicatricial pemphigoid 131 Dermatofibroma 220 Dermatophytosis 74 classification 75 histopathology 77 Majocchi’s granuloma 78 histopathology 78 special stains 74 tinea capitis 77 histopathology 77 tinea corporis 75 histopathology 76 tinea barbae 76 tinea incognito 78 tinea nigra 78 histopathology 78 tinea unguium 77 histopathology 78 Dermis blood vessels 11 collagen elastic fibers 10 extracellular matrix ground substance 10 lymphatic vessels 11 mucosal epithelium 12 nerves 11 subcutaneous fat 10 Dermoepidermal junction 4,18 Disorders of hyperpigmentation skin biopsy and special stains 200 Becker’s melanosis 202 freckles (ephelides) 200 lentigines 202 melanotic macules of Albright’s syndrome 201 mucosal melanotic macules 201 solar lentigo 203 Disorders of hypopigmentation 110 ash-leaf spot 113 hypomelanosis of Ito 112 idiopathic guttate hypomelanosis 112 nervus anemicus 112 278 nevus depigmentosus 111 piebaldism 113 pityriasis alba 113 vitiligo 110 Dopa oxidase methodology 44 staining technique 44 E Eosinophilic fasciitis 121 Epidermal or infundibular cyst 163 Epidermis basal cell layer granular cell layer horny layer squamous cell layer Erythema annulare centrifugum 150 erythema chronicum migrans 151 erythema gyratum repens 151 erythema marginatum 151 Erythema elevatum diutinum 241 Erythema induratum-nodular vasculitis 237 Erythema multiforme 114 friction blisters 115 thermal burns 115 Erythema nodosum 235 F Fite-Faracco stain methodology 41 solutions required 41 Fixed drug eruption 247 G Giemsa stain methodology 43 staining technique 43 Glomus tumor 256 Gram’s stain for bacteria 43 methodology 44 staining technique 44 Granuloma annulare 249 Histopathology of the Skin lymphangioma 254 superficial lymphangioma 254 verrucous hemangioma 253 Histoid leprosy 104 Lucio phenomenon 105 histopathology 105 Histology of normal skin Histopathology of morphea profundus 120 Histopathology of pustular psoriasis 191 Hydropic degeneration of basal cells hyperchromasia 29 hypergranulosis 29 hyperkeratosis 29 hyperplasia 29 hypogranulosis 29 incontinence of pigment 29 Indian filing of cells 30 infiltrate 29 interface dermatitis 30 karyolysis 30 karyorrhexis 30 keratotic plugging 30 leukocytoclasis 30 lobular panniculitis 31 metachromasia 30 metaplasia 30 necrosis 30 nesting or theques of cells 30 panniculitis 31 papillomatosis 30 parakeratosis 31 pigmentation or pigment deposition 30 pleomorphism 31 polymorphism 31 pseudocarcinomatous hyperplasia 31 reticular degeneration 31 sclerosis 31 septal panniculitis 31 spongiosis 31 squamous eddies 32 storiform pattern 31 stratum malpighii 32 vasculitis 32 H I Hair follicle apocrine glands eccrine glands (sweat glands) sebaceous glands Hansen’s disease 98 Hemangiomas lymphangiomas 251 angiokeratomas 253 cavernous hemangioma 252 cherry hemangioma 251 Ichthyosis vulgaris 229 Immunofluorescence testing 65, 69 acropustulosis of infancy 67 histopathology 67 direct 65 indirect 66 pemphigus vegetans 66 transient acantholytic dermatosis 66 histopathology 67 Indeterminate lesions-unclassified lesions 103 Inflammatory skin 20 dermis 21 basophils 23 eosinophils 21 epithelioid cells 24 giant cells 24 histiocytes 21 lymphocytes 21 mast cells 23 neutrophils 21 plasms cells 22 epidermis 20 balloon cells 20 dyskeratotic cells 20 malignant dyskeratosis 21 Paget’s cells 21 Tzanck cells 21 K Keloid and hypertrophic scar 223 Keratoacanthoma 167 multiple 168 solitary 167 Keratosis pilaris 268 Knuckle pads 225 L Late lesions of pustular psoriasis 192 Leiomyoma 261 Leishmaniasis 106 diffuse (acute) cutaneous 107 localized (acute) cutaneous 106 mucocutaneous 108 post kala-azar dermal 108 visceral l09 viscerotropic 109 Lentigo simplex 204 lentiginosis profusa/multiple lentiginosis syndrome 205 Peutz-Jegher’s syndrome 205 speckled lentiginous nevus (nevus spilus) 205 Lepra reaction 103 histology of delayed hypersensitivity reaction 104 histology of erythema nodosum leprosum 104 Lepromatous 102 Leukocytoclastic (hypersensitivity) vasculitis 239 Lichen amyloidosis and macular amyloidosis 269 279 Index Lichen nitidus 60 lichen striatus 61 histopathology 62 Lichen planus 53 atrophic 55 histopathology 56 bullous 56 histopathology 56 drug-induced 57 histopathology 57 hypertrophic 55 histopathology 55 lichen planopilaris 54 histopathology 55 actinicus 58 histopathology 58 pemphigoides 56 histopathology 57 pigmentosus 57 histopathology 57 oral 58 histopathology 59 ulcerative (erosive) 58 histopathology 58 Lichen sclerosus et atrophicus 116 Lichen scrofulosorum 96 Lichen simplex chronicus 123 prurigo nodularis 124 prurigo simplex 124 Localized scleroderma 119 Lupus erythematosus 138 chilblain LE/Perniotic 142 chronic cutaneous 139 rare subtypes of LE specific skin disease 141 verrucous 141 Lupus miliaris disseminatus faciei (LMDF) 214 Lymphocytoma cutis 198 M Malignant melanoma 271 Masson’s trichrome stain methodology 39 solutions required 39 staining technique 40 Masson-Fontana stain 45 methodology 45 solutions required 45 staining technique 45 Melanocytes Langerhans’ cells Merkel cells Melanocytic nevi 205 cafe au lait spots 207 compound nevus 206 intradermal nevus 206 junctional nevus 206 lentiginous junctional nevi 206 nevus of Ota 207 notalgia paraesthetica 207 Milia 165 Mixed connective tissue disease 121 Mycosis fungoides 226 adnexotropic 227 granulomatous slack skin 228 pagetoid reticulosis 227 poikiloderma vasculare atrophicans 228 psoriasiform mycosis fungoides 228 sezary syndrome 228 N Nevus flammeus 255 O Oral leukoplakia 176 P Paget’s disease 178 Paraneoplastic pemphigus 68 Parapsoriasis 193 PAS (Periodic acid-Schiff’s) methodology 38 solutions required 38 staining technique 39 Pemphigus foliaceous 69 Pemphigus group 64 Perioral dermatitis 213 Perl’s stain solutions required 38 staining technique 38 Photosensitive eczema 219 Pigmented purpuric dermatosis (Schamberg’s disease) 126 itching and eczematoid purpura of doucas and kapentanakis 127 leukocytoclastic vasculitis/cutaneous vasculitis 128 lichen aureus 127 pigmented purpuric lichenoid dermatosis 127 progressive pigmented purpuric dermatosis 126 purpura annularis telanglectodes 127 special stains 128 stasis dermatitis 128 Pityriasis lichenoides 243 Pityriasis rubra pilaris 196 Polar lepromatous 103 Polymorphous light eruption 216 Porokeratosis 231 Procedure for staining paraffin sections methodology 33 solutions required 33 staining technique 33 Psoriasis 188 Pyoderma gangrenosum 146 Pyogenic granuloma 257 R Rosacea 212 S Salt-split skin immunofluorescence studies 70 differential diagnosis 71 direct immunofluorescence test 72 pemphigus erythematosus 72 lupus band test 72 endemic pemphigus foliaceous 72 histopatholgoy 72 IgA pemphigus 72 Sarcoidosis non-specific lesions 135 special stains 137 specific lesions 135 subcutaneous sarcoidosis 136 Scleroderma 118 biopsy specimen 119 localized 118 systemic 118 Seborrheic keratosis 152 acanthotic type 153 adenoid (reticulated) type 153 clonal type 155 hyperkeratotic type 154 irritated type and inverted follicular keratosis 152 melanoacanthoma 155 Secondary syphilis 264 Special staining procedures methodology 35 result 35 solutions required 35 staining technique 35 Specific types of spongiotic dermatitis 46 allergic contact dermatitis 46 histopathology 46 atopic dermatitis 52 chronic superficial dermatitis 51 dyshidrotic dermatitis 49 erythroderma and generalized exfoliative dermatitis 50 280 irritant contact dermatitis 48 nummular dermatitis 48 photo-allergic dermatitis 49 seborrheic dermatitis 50 stasis dermatitis 51 Sporotrichosis 78 disseminated form 79 histopathology79 fixed cutaneous 79 lymphocutaneous form 79 Squamous cell carcinoma 169 Staining techniques in dermatopathology 33 Steatocystoma multiplex 165 Steroid acne 211 Striae distensae 224 Subacute cutaneous lupus erythematosus 142 Subpolar lepromatous 102 Superficial granulomatous (vegetative) pyoderma gangrenosum 147 Sweet’s syndrome acute febrile neutrophilic dermatosis 263 Syringocystadenoma papilliferum 259 Syringoma/trichoepithelioma cylindroma 208 cylindroma 210 trichoepithelioma 208 Systemic sclerosis 120 T Techniques of skin biopsy 14 Trichilemmal or pilar cyst 164 Tuberculoid 99 Tuberculosis of the skin 92 lupus vulgaris 93 histopathology 93 miliary tuberculosis 94 histopathology 95 papulonecrotic tuberculid 95 histopathology 95 primary cutaneous tuberculosis 92 histopathology 92 Histopathology of the Skin scrofulodenna 94 histopathology 94 tuberculosis cutis orificialis 95 histopathology 95 tuberculosis verrucosa cutis 93 histopathology 93 tuberculous gumma 95 histopathology 95 Tuberous sclerosis 222 Tubular apocrine adenoma 260 U Urticaria 238 Urticaria pigmentosa 148 histopathology of urticarial vasculitis 239 V van Gieson’s stain 35 methodology 36 solutions required 36 staining technique 36 Verhoeff’s stain 37 methodology 37 solutions required 37 staining technique 37 Verrucous carcinoma 171 Verrucous epidermal nevus 160 Vesiculobullous disorders 63 Viral infections of skin 83 condyloma acuminata 90 histopathology 90 eczema herpeticum 84 epidermodysplasia verruciformis 90 histopathology 90 giant condyloma acuminatum of Buschke and Lowenstein 91 histopathology 91 herpes simplex 83 herpetic folliculitis 84 herpetic whitlow 84 histopathology 84 infection with HSV-2 84 methodology 43 molluscum contagiosum 86 histopathology 86 palmoplantar warts 88 primary HSV-1 infection 83 recurrent HSV-1 infection 83 special variants of cutaneous herpes simplex 84 uncommon clinical variants 88 histopathology 88 varicella and herpes-zoster 85 hsitopathology 85 verruca plana 89 histopathology 89 verruca vulgaris 87 histopathology 87 histopathology of filliform wart 88 verrucae 86 von Kossa stain 42 X Xeroderma pigmentosum 233 Y Yeast infections candidiasis 80 histopathology 80 pityriasis versicolor 81 histopathology 81 pityrosporum folliculitis 82 histopathology 82 Z Ziehl-Neelsen (ZN) stain 40 methodology 41 staining technique 41 ... of antibodies only to the floor of the blister is not a feature They are demonstrated either only on the roof of the blister or both on the roof and floor of the subepidermal blister Cicatricial... ring-like border of the lesions show collarette of scales on their inner aspect The lesions mostly involve the trunk and proximal parts of the limbs and may be pruritic Histopathology In the superficial... number • Formation of multiloculated blisters because of separation of tips of the dermal papillae from the overlying epidermis (Fig 22 .1B) • Fibrin is seen in the papillae which imparts a bluish