4
Top-Down

  • Hyperkeratosis/parakeratosis, 221
  • Upper epidermal change, 228
  • Acantholysis, 238
  • Subepidermal space/cleft, 248
  • Granular “material” in cells, 255
  • “Busy” dermis, 260
  • Dermal material, 263
  • Fat necrosis, 276

    Flegel disease

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  • Hyperkeratosis and variable lymphocytic infiltrate
  • Scattered “dyskeratotic” keratinocytes may be present
  • Atrophic or acanthotic epidermis

    Porokeratosis

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  • Hyperkeratosis/parakeratosis (cornoid lamellae) and lymphocytic infiltrate
  • Cornoid lamellae (tiered parakeratosis above altered granular layer) (arrow)
  • A lichenoid infiltrate may be present

    Inflammatory linear verrucous epidermal nevus

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  • Hyperkeratosis alternating with parakeratosis
  • Acanthotic epidermis

    Actinic keratosis

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  • Hyperkeratosis alternating with parakeratosis (alternating pink and blue stratum corneum)
  • Beneath parakeratosis, atypical keratinocytes in lower epidermis
  • Orthokeratosis above banal keratinocytes in adnexal structures

    Axillary granular parakeratosis

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  • Parakeratosis with granules
  • Granules retained in the stratum corneum (arrows)

    Dermatophytosis

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  • Parakeratosis with organisms
  • Slightly refractile organisms (spheres and tubules) in stratum corneum
  • Parakeratosis may be seen above orthokeratosis (“sandwich sign”)
  • Obvious organisms on PAS (arrows)

    Key differences

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    (a)

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    (b)

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    (c)

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    (d)

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    (e)

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    (f)

    1. Actinic keratosis: alternating pink and blue stratum corneum above buds of atypical keratinocytes and banal keratinocytes in spared adnexal structures
    2. Inflammatory linear verrucous epidermal nevus: hyperkeratosis alternating with parakeratosis over acanthosis without atypia
    3. Pityriasis rubra pilaris: checkerboard parakeratosis and hyperkeratosis, irregular acanthosis (see page 108)
    4. Axillary granular parakeratosis: retained granules in stratum corneum
    5. Dermatophytosis: circles and linear hyphae in stratum corneum

    6. Nutritional deficiency: upper epidermal parakeratosis/necrosis with pallor (see page 321)

      Note Tinea versicolor (has yeast and hyphal forms) is in the differential; dermatophytosis and tinear versicolor may be subtle and appear like “normal” skin on low power.

      Clonal seborrheic keratosis

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  • Upper epidermal change of nests of keratinocytes that may be slightly paler than surrounding keratinocytes
  • Nests are composed of monomorphous, typical keratinocytes

    Epidermodysplasia verruciformis

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  • Upper epidermal change of keratinocytes with blue-gray expanded cytoplasm and haloes around nuclei

    Epidermolytic hyperkeratosis

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  • Upper epidermal change of prominent keratohyaline granules and chicken-wire cell membranes – granular-vacuolar change (arrows)

    Myrmecium

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  • Upper epidermal change of koilocytes with very prominent keratohyaline granules

    Orf

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  • Upper epidermal change of reticular degeneration (edema of the cells with retention of cell membranes) and pink intracytoplasmic globules (arrows)
  • Usually acral skin

    Paget disease

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  • Upper epidermal change of scattered large cells singly and in nests
  • May be able to see a compressed basal layer beneath nests (eye-liner)
  • Large cells have expanded cytoplasm and nuclei at periphery

    Verruca plana

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  • Upper epidermal change of koilocytes – cells with haloes around nuclei
  • Epidermal surface is flat to only slightly papillated
  • Hypergranulosis

    Verruca vulgaris

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  • Upper epidermal change of koilocytes
  • Epidermal surface papillated
  • Hypergranulosis
  • Toeing-in (arborization) of rete ridges

    Key differences

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    (a)

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    (b)

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    (c)

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    (d)

    1. Hailey-Hailey disease: acantholysis (rounding up and separation of individual keratinocytes); (see page 240)
    2. Clonal seborrheic keratosis: nests of typical, monomorphous keratinocytes
    3. Epidermodysplasia verruciformis: expanded blue-gray cytoplasm, some perinuclear haloes
    4. Epidermolytic hyperkeratosis: strung-out cell membranes, loss of nuclei, granular-vacuolar change

      Key differences, continued

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      (e)

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      (f)

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      (g)

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      (h)

    5. Myrmecium: very prominent keratohyaline granules and intracytoplasmic, angular inclusions
    6. Orf: reticular degeneration (pink cell membranes with loss of nuclei) with scattered inclusions
    7. Paget’s disease: scattered cells that lack intercellular bridges with prominent grayish cytoplasm
    8. Verruca: Koilocytes

      Darier disease

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  • Benign acantholytic dyskeratosis with corp ronds (long arrow) and grains (short arrow)
  • Parakeratosis/crust above the acantholytic dyskeratosis
  • Villi (projections of dermis lined by basal cells) may be present at the base

    Grover disease

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  • Benign acantholytic dyskeratosis in small foci
  • Also foci of spongiosis, acantholysis without dyskeratosis (Hailey-Hailey pattern and pemphigus patterns)

    Hailey-Hailey disease

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  • Benign acantholysis (sometimes with dyskeratosis) involving at least 2/3 or the full thickness of the epidermis
  • Resembles a “dilapidated brick wall”

    Herpes virus infection

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  • Benign non-dyskeratotic acantholysis with ballooning degeneration
  • Multinucleated cells with rimming of chromatin
  • Follicular necrosis/acantholysis is a clue
  • Often involves and destroys basal cells, which are spared in pemphigus vulgaris

    Pemphigus foliaceus

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  • Benign acantholysis in the upper stratum spinosum, making the granular layer appear altered
  • May see “cling-ons” (acantholytic cells on roof of split)

    Pemphigus vulgaris

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  • Benign acantholysis above the basal layer
  • Basal layer intact and appears like “tombstones”

    Squamous cell carcinoma (adenoid or pseudoglandular or acantholytic)

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  • Malignant dyskeratotic acantholysis in a large, infiltrative tumor
  • Prominent atypical cells (arrows) and mitoses

    Warty dyskeratoma

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  • Histologically like Darier disease with corp ronds (long arrow) and grains (short arrow) but may have more prominent cup-shape and/or follicular involvement
  • Clinically a solitary lesion

    Key differences

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    (a)

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    (b)

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    (c)

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    (d)

    1. Darier disease: prominent parakeratosis/crust above corp ronds and grains (“benign dyskeratotic acantholysis”); villi may be evident
    2. Grover disease: multiple patterns of acantholysis (Darier like, Hailey-Hailey-like, pemphigus-like) and spongiosis in small foci
    3. Hailey-Hailey disease: majority of epidermis involved by acantholysis (usually non-dyskeratotic acantholysis)
    4. Herpes virus infection: ballooning degeneration, multinucleated cells with chromatin rimming

      Key differences, continued

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      (e)

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      (f)

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      (g)

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      (h)

    5. Pemphigus foliaceus: granular layer prominent with acantholysis
    6. Pemphigus vulgaris: non-dyskeratotic acantholysis above tombstoned basal layer; follicles may be involved
    7. Squamous cell carcinoma: acantholysis and squamous pearls, atypical keratinocytes and mitoses (malignant dyskeratotic acantholysis)
    8. Warty dyskeratoma: cup-shaped area of acantholysis and dyskeratosis (“benign dyskeratotic acantholysis”), villi (arrows) at base

      Angiokeratoma

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  • Subepidermal space (can appear intraepidermal)
  • Thin “grenz zone” (arrow)
  • Filled with erythrocytes

    Bullous pemphigoid/Pemphigoid (herpes) gestationis

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  • Subepidermal space
  • Eosinophils (arrows) are prominent at the base
  • May see festooning (papillated bulla base)

    Dermatitis herpetiformis

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  • Subepidermal space
  • Neutrophils (arrows) are prominent at the base
  • May see clusters of neutrophils in papillae adjacent to blister
  • Note that this same histologic pattern can be seen with linear IgA disease, neutrophil-rich bullous pemphigoid, bullous lupus erythematosus, and epidermolysis bullosa acquisita
  • May see reverse festooning (papillated inferior surface of bulla roof)

    Lymphangioma

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  • Subepidermal space with internal papillations
  • Thin “grenz zone” (long arrow)
  • Spaces lined by endothelial cells (short arrow) and may contain a few erythrocytes

    Polymorphous light eruption

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  • Subepidermal space (edema)
  • Superficial and deep vessels surrounded by lymphocytes

    Porphyria cutanea tarda

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  • Subepidermal space
  • Non-inflammatory base
  • Festooning of papillary dermis
  • Thickened vessel walls (long arrow)

  • Caterpillar bodies in epidermis (short arrow)

    Note  Differential diagnosis of a non-inflammatory subepidermal bulla includes non-inflammatory bullous pemphigoid, epidermolysis bullosa acquisita, diabetic bullae, and epidermolysis bullosa subtypes.

    Key differences

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    (d)

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    (e)

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    (f)

    1. Angiokeratoma: erythrocytes fill the spaces
    2. Bullous pemphigoid: eosinophils at base, festooning
    3. Dermatitis herpetiformis: neutrophils at base, reverse festooning
    4. Lymphangioma: empty spaces lined by endothelial cells
    5. Polymorphous light eruption: perivascular lymphocytes
    6. Porphyria cutanea tarda: non-inflammatory base, festooning, caterpillar bodies

      Aluminum chloride (Drysol solution)

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  • Granular “material” in histiocytes
  • Fine, bluish granules of similar size
  • Large blue-purple collagen “concretions” (arrow)
  • An adjacent scar is often evident

    Ferric subsulfate (Monsel solution)

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  • Granular “material” in histiocytes and extracellularly
  • Similar in staining quality to hemosiderin
  • Larger collagen “concretions” of brown-yellow to black material may be present
  • An adjacent scar is often evident

    Hemosiderin

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  • Granular “material” in histiocytes (hemosiderophages)
  • Yellow-brown, refractile globules and granules of varying sizes
  • Appears green-yellow with microscope condenser lowered
  • Extravasated erythrocytes may be present

    Melanin (in an intradermal melanocytic nevus)

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  • Granular “material” in melanocytes and melanophages
  • Brown, fine granules of similar size within nested (clustered) melanocytes with smaller cells toward base with individual cells splaying through collagen
  • Appears darker brown to black with microscope condenser lowered

    Key differences

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    (b)

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    (c)

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    (d)

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    (e)

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    (f)

    1. Aluminum chloride (Drysol solution): presence of a scar with adjacent histiocytes containing fine, bluish granules; blue-purple collagen “concretions”
    2. Ferric subsulfate (Monsel solution): presence of a scar with adjacent histiocytes containing brown-yellow pigment; brown-yellow to black collagen “concretions”
    3. Hemosiderin: variably-sized, refractile globules and granules of yellow-brown pigment
    4. Melanin: non-refractile, similarly-sized circles of brown pigment
    5. Leishmaniasis: dot-like bluish organisms within sheets of histiocytes; scattered plasma cells (see page 206)
    6. Tattoo: black particles free in dermis and within macrophages (see page 273)

      Blue nevus, hypopigmented

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  • “Busy” dermis
  • Spindle cells with oval to round nuclei in clusters and splaying through sclerotic collagen
  • Occasional cells with melanin pigment (arrows)

    Metastatic breast carcinoma, interstitial pattern (carcinoma en cuirasse)

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  • “Busy” dermis
  • Dense collagen with hyperchromatic cells interstitially
  • Hyperchromatic cells display nuclear molding

    Key differences

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    (b)

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    (c)

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    (d)

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    (e)

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    (f)

    1. Blue nevus, hypopigmented: occasional cells with melanin pigment
    2. Dermatofibroma: collagen entrapment (see page 166)
    3. Granuloma annulare: subtle hints of palisading, increased mucin (see page 89)
    4. Kaposi sarcoma: increased vessels (see page 186)
    5. Leukemia cutis: atypical cells with granular cytoplasm (see page 139)
    6. Metastatic breast carcinoma, interstitial pattern: hyperchromatic nuclei with molding

      Amyloidosis, nodular

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  • Dermal material that is pink and amorphous, diffuse and perivascular
  • Plasma cells (arrows) are often present around vessels

    Calcinosis cutis

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  • Dermal material that is blue-purple and chunky
  • Calcium deposits can be seen in adnexal tumors (trichoepithelioma, pilomatricoma)
  • Calcium may be deposited on the altered elastic fibers in pseudoxanthoma elasticum

    Erythropoietic protoporphyria

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  • Dermal material that is pink and amorphous and fills the upper half of the dermis
  • Early lesions have pink material around vessels

    Gel foam

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  • Dermal material that is bluish, curvy and ribbon-like

    Lipoid proteinosis

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  • Dermal material that is pink and amorphous, often filling the dermis full-thickness
  • May be perpendicular to epidermis and around adnexae and vessels

    Ochronosis

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  • Dermal material that is banana-shaped and brown-orange (altered collagen; arrows)

    Osteoma cutis

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  • Dermal material – bone, which has bright, dense pink trabeculae with nuclei with haloes around them (osteocytes)
  • Differential diagnosis includes an ossified pilomatricoma, identifiable if keratin with shadow cells is present

    Paraffinoma

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  • Dermal material that is lost during processing and is “seen” as irregularly shaped circular spaces (arrows)
  • Dark pink sclerotic stroma
  • Swiss-cheese appearance

    Pseudoxanthoma elasticum

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  • Dermal material (altered elastic fibers) that is blue and squiggly (arrows)
  • Sometimes the corkscrew fibers are calcified

    Hyaluronic acid (dermal filler)

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  • Dermal material
  • Material is light blue and in pools
  • May have a surrounding foreign body giant cell reaction

    Tattoo

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  • Dermal material that is black (most commonly) and is free in the dermis as well as within macrophages

    Key differences

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    (b)

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    (c)

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    (d)

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    (e)

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    (f)

    1. Amyloidosis, nodular: amorphous pink material with plasma cells
    2. Calcinosis cutis: blue-purple chunks
    3. Erythropoietic protoporphyria: amorphous pink material around vessels and in upper dermis
    4. Gel foam: blue interconnected ribbons
    5. Hyaluronic acid: bluish material
    6. Lipoid proteinosis: amorphous pink material filling the entire dermis; often around adnexae

      Key differences, continued

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      (g)

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      (h)

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      (i)

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      (j)

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      (k)

    7. Ochronosis: brown-orange banana-shapes
    8. Osteoma cutis: well-defined pink shapes with nuclei
    9. Paraffinoma: irregular circular spaces like Swiss cheese
    10. Pseudoxanthoma elasticum: squiggly blue lines
    11. Tattoo: black particles within macrophages and free in dermis

      Lipodermatosclerosis

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  • Fat necrosis
  • Individual adipocytes are lost and replaced by arabesques of pink, ruffled membranes (lipomembranous fat necrosis) (arrows)

    Pancreatic fat necrosis

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  • Fat necrosis
  • Necrosis of the fat with “ghost-like” shadows of fat cells remaining
  • Calcification/neutrophils/eosinophils may be present
  • Septal vessels are inflamed

    Key differences

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    (b)

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    (c)

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    (d)

    1. Lipodermatosclerosis: pink arabesques of membranes replacing adipocytes
    2. Lupus profundus: hyaline fat necrosis, lymphocytic lobular infiltrate (see page 146)
    3. Pancreatic fat necrosis: ghost-like necrosis of fat, +/−calcification
    4. Subcutaneous fat necrosis of the newborn: crystalline shapes and inflammation within fat lobules (see page 148)