Clinical and Pathologic Findings with Differential Diagnostic Lists

1

Epidermal changes

• • Acantholysis (1.2)

  • Atrophy of epidermis (1.9)

  • Dyskeratosis (1.27)

  • Follicular plugging (1.47)

  • Horn cysts (1.59)

  • Hypergranulosis (1.60)

  • Hyperplasia of epidermis (1.61)

  • Hypogranulosis (1.63)

  • Liquefaction degeneration of basal layer (1.64)

  • Necrotic keratinocytes (1.87)

  • Papillomatosis (1.102)

  • Parakeratosis (1.104)

  • Pseudoepitheliomatous (pseudocarcinomatous) hyperplasia (1.116)

  • Spongiosis (1.132)

  • Squamous eddies, keratin pearls, and squamatization (1.134)

  • Transepidermal elimination (1.140)

  • Vacuolization of keratinocytes (1.144)

2

Dermal changes

• • Atrophy of dermis (1.8)

  • Black deposits (1.12)

  • Blue amorphous material (1.15)

  • Brown deposits (1.17)

  • Calcification (1.19)

  • Edema of dermis (1.30)

  • Elastic tissue changes (1.31)

  • Eosinophilic pink amorphous material (1.35)

  • Hemosiderin (1.58)

  • Melanin incontinence (1.79)

  • Mucin and myxomatous changes (1.83)

  • Scars, sclerosis, fibrosis (1.125)

  • Thrombi (1.137)

3

Cell types

• • Basaloid cells (1.11)

  • Clear or pale cells (1.22)

  • Eosinophils (1.36)

  • Epithelioid cells (1.38)

  • Extravasated erythrocytes (1.40)

  • Foam cells (1.46)

  • Granulomas (1.51)

  • Lymphocytes and histiocytes (1.76)

  • Mast cells (1.78)

  • Multinucleated giant cells (1.84)

  • Neutrophils (1.89)

  • Plasma cells (1.111)

  • Small cells (“oat cells”) (1.130)

  • Spindle cells (1.131)

4

Patterns of inflammation and neoplastic proliferation

• • Epidermotropism and pagetoid proliferation (1.37)

  • Folliculitis (1.47)

  • Grenz zone (1.53)

  • Interface dermatitis (1.64)

  • Interstitial dermatitis (1.65)

  • Lichenoid dermatitis (1.72)

  • Nodular and diffuse dermatitis (1.91)

  • Panniculitis (1.101)

  • Perivascular dermatitis, superficial (1.109)

  • Perivascular dermatitis, superficial and deep (1.109)

  • Single filing of cells (1.128)

  • Vasculitis (1.145)

1.1

Abdomen lesions

(see also Trunk lesions 1.141, Umbilicus lesions 1.143)

• • Accessory nipple (29.12)

  • Cutaneous endometriosis (29.9)

  • Dysplastic nevus (20.5)

  • Melanocytic nevus (20.5)

  • Omphalomesenteric duct remnant (29.11)

  • Pemphigoid gestationis (6.3)

  • Pruritic urticarial plaques of pregnancy (3.6)

  • Seborrheic keratosis (18.2)

  • Striae (27.2)

1.2

Acantholysis

Acantholysis is the loss of cohesion between keratinocytes as a result of dissolution of intercellular connections, sometimes resulting in an intraepidermal vesicle. Acanthocyte is an old name for keratinocyte, and means “prickle cell,” referring to the desmosomal spines that normally connect the cells. The process differs from spongiosis (1.9) in that acantholytic keratinocytes tend to be rounded rather than elongated, the desmosomal spines appear destroyed rather than stretched, and exocytosis of lymphocytes into the epidermis is usually absent. Dyscohesive melanocytes in melanoma (20.11) may resemble acantholysis (20.11), but in this situation the term acantholysis is not used (call it “dyscohesion”).

• • Actinic keratosis (sometimes) (18.8)

  • Darter’s disease (11.3)

  • Familial dyskeratotic comedones (10.1)

  • Galli-Galli disease (17.10, rare)

  • Hailey–Hailey disease (5.5)

  • Herpes virus infection (14.2)

  • Impetigo (occasionally) (12.2)

  • Incidental finding or artifact

  • Pemphigus (all varieties, 5.4)

  • Pityriasis rubra pilaris (2.10, rarely)

  • Squamous cell carcinoma (sometimes) (18.11)

  • Acantholytic acanthoma (benign horn-like growth with acantholysis)

  • Staphylococcal scalded skin syndrome (12.2)

  • Transient acantholytic dermatosis (Grover’s disease) (5.6)

  • Warty dyskeratoma (18.7)

1.3

Acneiform lesions

This is a clinical group of conditions characterized by erythematous papules, pustules, and/or comedones, resembling acne (pilosebaceous unit inflammation). See also Follicular eruptions (1.47), Neutrophil eruptions (1.89), and Comedones (1.24).

• • Acne variants (10.1)

  • Arthropod bites (15.7)

  • Bowel bypass syndrome (4.1)

  • Candidiasis (13.4)

  • Dermatitis herpetiformis (6.5)

  • Drug-induced acneiform eruptions (3.5)

  • Folliculitis (10.2)

  • Grover’s disease (5.6)

  • Impetigo (12.1)

  • Miliaria (10.6)

  • Perioral dermatitis (10.1)

  • Pustular vasculitis (4.1)

  • Pyoderma faciale (10.1)

  • Varicella (14.2)

1.4

Alopecia

Alopecia is hair loss. It is commonly subdivided into scarring and non-scarring. Some pathology laboratories prefer to section punch biopsies of alopecia both horizontally and vertically, to maximize the view of more follicles. This author is not a fan of horizontal scalp biopsy sections, but nevertheless they are popular. Vertical scalp biopsies perform comparably to horizontal ones, but some laboratories prefer to receive two biopsies, one for vertical sectioning and one for horizontal, or to subdivide and section a single biopsy both ways.

1.5

Annular lesions

These lesions form clinical rings. Similar terms are gyrate and circinate. See also Serpiginous (1.127), Linear (1.73), and Reticulated (1.123).

1.6

Arm lesions (includes forearms)

(see also Hand lesions 1.56, Leg lesions 1.67)

1.7

Arthritis and skin disease

• • Drug eruption (3.5)

  • Gonococcemia (12.18)

  • Gout (8.5)

  • Loefgren’s syndrome (7.5)

  • Lupus erythematosus (17.6)

  • Lyme disease (12.14)

  • Multicentric reticulohistiocytosis (7.8)

  • Psoriasis (2.8)

  • Pyoderma gangrenosum (4.12)

  • Reiter’s disease (2.8)

  • Relapsing polychondritis (17.8)

  • Rheumatic fever (12.2)

  • Rheumatoid arthritis (3.7, 4.1, 7.3)

  • Schmid’s triad (16.8)

  • Schnitzler syndrome (3.1)

  • Sepsis and subacute bacterial endocarditis (4.1)

  • Sweet’s syndrome (3.7)

  • Vasculitis (4.1)

  • Viral infections ( Chapter 14 )

  • Yersiniosis (1.7)

1.8

Atrophy of the dermis

Dermal atrophy is a decreased thickness of the dermis. In most of these diseases, the epidermis is also atrophic (1.9). In some of them, the dermis is not actually thin, but adipose tissue is deposited higher up in the dermis than usual, or the fat clinically appears herniated, due to lack of dermal support, even though the dermis is not actually thin. Panniculitis ( Chapter 16 ) can also produce the appearance of dermal atrophy, although the atrophy is primarily in the adipose.

• • Acrodermatitis chronica atrophicans (12.14)

  • Aging skin (9.1)

  • Anetoderma (9.11)

  • Aplasia cutis congenita

  • Atrophoderma of Pasini and Pierini (9.4)

  • Corticosteroids (especially injected)

  • Focal dermal hypoplasia (Goltz syndrome, 11.8)

  • Morphea (9.4)

  • Nevus lipomatosus (29.1)

  • Piezogenic pedal papules (29.1)

  • Scars (27.2)

1.9

Atrophy of the epidermis

Epidermal atrophy is a decreased thickness of the epidermis, particularly the spinous layer.

• • Acrodermatitis chronica atrophicans (12.14)

  • Actinic keratosis , atrophic (18.8)

  • Aging , sun-damaged , or radiation-damaged skin (9.1, 9.2)

  • Anetoderma (9.11)

  • Aplasia cutis congenita (17.4)

  • Atrophie blanche (4.13)

  • Atrophoderma (9.4)

  • Corticosteroids (especially topical)

  • Degos disease (4.10)

  • Dermatomyositis (17.7)

  • Graft-versus-host disease, chronic (17.3)

  • Lichen planus, atrophic (usually acanthotic, 2.11)

  • Lichen sclerosus (9.5)

  • Lupus erythematosus (17.6, always consider when extreme atrophy)

  • Necrobiosis lipoidica (7.2)

  • Neoplasms in the dermis will often cause epidermal atrophy

  • Poikiloderma atrophicans vasculare (24.1)

  • Poikiloderma congenitale (11.5)

  • Porokeratosis (18.4, central portion sometimes)

  • Progeria (Werner’s syndrome, 9.6)

  • Scar (27.2)

  • Striae (27.2)

1.10

Axilla lesions

• • Acanthosis nigricans (18.5)

  • Acrochordons (27.4)

  • Axillary granular parakeratosis (1.27)

  • Candidiasis (13.4)

  • Chromhidrosis

  • Contact dermatitis (2.2)

  • Cystic hygroma (25.10)

  • Erythrasma (12.5)

  • Fibrous hamartoma of infancy (27.9)

  • Fox–Fordyce disease (10.7)

  • Hailey–Hailey disease (5.5)

  • Hidradenitis suppurativa (10.1)

  • Hyperhidrosis

  • Intertrigo (2.2)

  • Inverse psoriasis (2.8)

  • Neurofibromatosis (axillary freckling)

  • Pemphigus vegetans (5.4)

  • Pseudoxanthoma elasticum (9.8)

  • Scabies (15.9)

  • Seborrheic dermatitis (2.1)

  • Trichomycosis axillaris (12.5)

1.11

Basaloid cells

Basaloid cells are tumor cells that resemble basal cells of the epidermis (compare with small cells, 1.130). They have a dark oval nucleus and very little cytoplasm.

• • Basal cell carcinoma (18.14)

  • Seborrheic keratosis (18.2)

  • Ameloblastoma (18.14)

  • Cloacogenic carcinoma (18.14)

  • Sebaceous tumors (especially sebaceous adenoma, sebaceous epithelioma, and sebaceous carcinoma, Chapter 21 )

  • Follicular tumors (especially trichoepithelioma and pilomatricoma, Chapter 22 )

  • Sweat gland tumors ( Chapter 23 )

1.12

Black deposits (histologic)

(compare with Brown deposits 1.17)

• • Amalgam tattoo (7.6)

  • Argyria (8.18)

  • Foreign bodies (7.6)

  • Mercury (7.6)

  • Tattoos (7.6)

1.13

Black clinical lesions

(see also Blue clinical lesions 1.14 , Brown clinical lesions 1.18)

• • Angiokeratoma (25.2)

  • Angiosarcoma (25.7)

  • Black dermatographism (7.6)

  • Blue nevus (20.8)

  • Calciphylaxis (8.15)

  • Comedo, open (1.24)

  • Coumarin necrosis (4.18)

  • Deep fungus infection ( Chapter 13 )

  • Disseminated intravascular coagulation (4.14)

  • Ecthyma gangrenosum (12.17)

  • Eschar

  • Foreign body or exogenous substance (7.6)

  • Gangrene

  • Lentigo simplex (20.3), solar lentigo (20.4)

  • Melanoma (20.11)

  • Meningococcemia (12.19)

  • Purpura (1.120)

  • Terra firma dermatosis (dirt on the skin)

  • Vascular neoplasms ( Chapter 25 )

  • Venous lake (25.2)

  • Blister (see Vesicles, 1.147)

1.14

Blue clinical lesions

(see also Brown clinical lesions 1.18, Gray clinical lesions 1.54, and Black clinical lesions 1.13)

1.15

Blue material (H&E stain)

• • Bacteria and some fungi ( 12 , 13 )

  • Calcium (1.19)

  • Foreign materials (7.6)

  • Hematoxylin precipitate

  • Keratohyaline granules (1.63)

  • Mucin (light blue, 1.83)

  • Nuclei and nuclear dust (4.1)

  • Solar elastosis (light blue, 9.1) or radiodermatitis (light blue to pink, 9.2)

1.16

Bone changes and skin lesions

• • Buschke–Ollendorff syndrome (27.6, osteopoikilosis)

  • Conradi–Hunerman syndrome (11.1, chondrodysplasia punctata)

  • Ehlers–Danlos syndrome (9.9, hypermobile joints)

  • Epidermal nevus syndrome (18.1)

  • Epidermolysis bullosa dystrophica (6.6)

  • Goltz syndrome (11.8, osteopathia striata)

  • Incontinentia pigmenti (11.6)

  • Klippel–Trenaunay–Weber syndrome (25.1, bony hypertrophy)

  • Langerhans cell histiocytosis (24.18, osteolytic lesions)

  • Leishmaniasis (15.1, bony erosion)

  • Linear scleroderma (9.3, bony involvement)

  • Maffucci syndrome (25.1, dyschondroplasia)

  • Marfan syndrome (9.9, tall, pectus excavatum, arachnodactyly)

  • McCune–Albright’s syndrome (20.2, polyostotic fibrous dysplasia)

  • Mycetoma (13.14, erosion and deformity)

  • Nail–patella syndrome (triangular lunulae, iliac horns, renal failure)

  • Neoplasms (osteolytic lesions)

  • Neurofibromatosis (26.1, many bony changes)

  • Nevoid basal cell carcinoma syndrome (18.14, cysts, hypertelorism, frontal bossing, bifid ribs)

  • Nevus sebaceus syndrome (21.2)

  • North American blastomycosis (13.8, infection)

  • Osteogenesis imperfecta (9.9, brittle bones)

  • Pachydermoperiostosis (9.7, periosteal proliferation)

  • Rhinoscleroma (12.9)

  • Rhinosporidiosis (13.15)

  • Scrofuloderma (abscess, 12.10)

  • Syphilis, congenital (12.13, dactylitis, epiphysitis, osteoperiostitis, saddle nose, Higoumenakis sign, saber shins)

  • T-cell leukemia-lymphoma (24.3, osteolytic lesions)

  • Xanthoma disseminatum (7.13, osteolytic lesions)

1.17

Brown deposits (histologic)

• • Dematiacious fungi (13.3, 13.10, 13.16)

  • Foreign bodies (7.6)

  • Formalin pigment (acid formaldehyde hematin). This is a brown precipitate resulting from hemoglobin in formalin with a pH below 6. It is a common artifact, especially in areas of red blood cells

  • Gout (8.5)

  • Hemosiderin (1.58)

  • Melanin (1.79)

  • Monsel’s solution (7.6, ferrous subsulfate, used for hemostasis)

  • Ochronosis (8.16)

  • Oxalosis (yellow–brown, 8.15)

1.18

Brown clinical lesions (hyperpigmentation)

(see also Black clinical lesions 1.13, Blue clinical lesions 1.14)

• • Acanthosis nigricans (18.5)

  • Accessory nipple (29.12)

  • Albright’s syndrome (20.2)

  • Cronkhite–Canada syndrome (1.49)

  • Dermatofibroma (27.1)

  • Dermatosis papulosa nigra (18.2)

  • Dowling–Degos disease (17.10)

  • Drugs (3.5, phenothiazines, meclorethamine, psoralen, arsenic, etc.)

  • Dyskeratosis congenita (11.4)

  • Endocrinopathies (17.10, Addison’s disease, Cushing’s disease, etc.)

  • Erythema ab igne (3.9)

  • Erythema dyschromicum perstans (2.15)

  • Fixed drug eruption (3.5)

  • Goltz syndrome (11.8)

  • Granuloma faciale (4.2)

  • Hemochromatosis (8.17)

  • Incontinentia pigmenti (11.6)

  • Laugier–Hunziker syndrome (17.10)

  • Leopard syndrome (20.3)

  • Liver and kidney disease (1.75, 1.66)

  • Macular amyloidosis (8.40)

  • Melanocytic neoplasms ( Chapter 20 )

  • Melasma (17.10)

  • Ochronosis (8.16)

  • Pellagra (2.1)

  • Phytophotodermatitis (1.110)

  • Pigmented adnexal neoplasms ( 22 , 23 )

  • Pigmented basal cell carcinoma (18.14)

  • POEMS syndrome (24.12)

  • Post-inflammatory hyperpigmentation (17.10)

  • Riehl’s melanosis (17.10)

  • Seborrheic keratosis (18.2)

  • Stasis dermatitis (2.1)

  • Terra firma dermatosis (dirt on the skin)

  • Tinea nigra (13.3)

  • Tinea versicolor (13.2)

  • Transient neonatal pustular melanosis (5.2)

  • Urticaria pigmentosa (24.17)

1.19

Calcification

Calcium salts appear as dark blue to purple, brittle deposits on H&E stain (shatter into shards like peanut brittle candy that has been cut by a butter knife). Sometimes instead it has the appearance of bluish granular material. Calcium salts can be stained with alizarin red (more specific) or von Kossa stains (black). Eosinophilic laminated psammoma bodies (1.35) will sometimes calcify, and are seen in meningioma, papillary thyroid carcinoma, and ovarian carcinoma. Schauman bodies are round, blue, calcified, laminated inclusions in multinucleated macrophages, usually seen with sarcoidosis (7.5), but also seen with other granulomas (1.51). Calcareous bodies (purplish oval calcified concretions) are seen with cysticercosis (15.3) and other parasites.

• • Acrodermatitis chronica atrophicans (12.14)

  • Basal cell carcinoma (18.14)

  • Calcifying aponeurotic fibroma (27.16)

  • Calciphylaxis (8.15)

  • Cysts (especially pilar, 19.2)

  • Dermatomyositis (17.7)

  • “Dystrophic” calcification (8.15)

  • Foreign bodies, trauma, and injection sites (7.6)

  • Gout (8.5)

  • “Metastatic” calcification (8.15)

  • Osteoma cutis (29.8)

  • Panniculitis ( Chapter 16 , especially pancreatic fat necrosis, lupus profundus, and subcutaneous fat necrosis of the newborn)

  • Perforating calcific elastosis (9.8)

  • Peyronie’s disease (27.15)

  • Pilomatricoma (22.3)

  • Proliferating trichilemmal cyst (22.4)

  • Pseudoxanthoma elasticum (9.8)

  • Subepidermal calcified nodule (8.15)

  • Scleroderma (9.3, especially CREST syndrome)

  • Trichoepithelioma (22.2)

1.20

Cheilitis (inflammation of the lip)

(see also Lip lesions 1.74)

• • Acrodermatitis enteropathica (17.1)

  • Actinic cheilitis (18.8)

  • Candidiasis (13.4)

  • Cheilitis granulomatosis (7.7)

  • Contact dermatitis (2.2)

  • Drugs (retinoids, etc., 3.5)

  • Erythema multiforme (3.2)

  • Herpes simplex (14.2)

  • Lip licking (2.2)

  • Sarcoidosis (7.5)

  • Squamous cell carcinoma (18.11)

  • Verruca plana (14.1)

  • Xerotic eczema (2.1)

1.21

Chord-like lesions

(see also Linear lesions 1.73)

• • Mondor’s disease (4.16)

  • Sclerosing lymphangitis of penis (4.16)

  • Superficial thrombophlebitis (16.7)

  • Trauma

  • Trousseau’s syndrome (4.16)

1.22

Clear or pale cell neoplasms

(see also Vacuolization of keratinocytes 1.144, Pale epidermis 1.99)

The cells of these neoplasms appear similar to foam cells (1.46), but the cytoplasm is more uniformly pale or clear rather than bubbly. The paleness is usually due to the removal of a substance from the cytoplasm during processing, generally glycogen, mucin, or lipid.

• • Adipose tumors ( Chapter 29 )

  • Balloon cell nevus and balloon cell melanoma (20.5 and 20.11)

  • Clear cell acanthoma (18.6)

  • Clear cell basal cell carcinoma (18.14)

  • Clear cell hidradenoma (23.9)

  • Clear cell sarcoma (20.11)

  • Clear cell syringoma (23.7)

  • Eccrine carcinoma (23.13)

  • Hidroacanthoma simplex (23.10)

  • Metastatic renal cell carcinoma (28.4)

  • Pagetoid diseases (1.37)

  • PEComa (27.21)

  • Pilomatricoma (shadow cells, 22.3)

  • Sebaceous gland tumors ( Chapter 21 )

  • Squamous cell carcinoma (18.11)

  • Trichilemmoma (22.5)

1.23

Clefts (histologic)

“Cleft” is used here to mean an empty space. It may have previously contained fluid, crystals, lipid, or some other material that was removed during processing of the tissue, but in some cases it is simply an artifact. We have excluded vesicles and bullae, vascular spaces, and spaces in which there is some evidence of materials within them.

• • Actinic keratosis (18.8): occasional separation at dermal/epidermal junction (“Freudenthal’s lacunae”)

  • Amyloidosis (8.4) and Colloid milium (8.2): fissured clefts within hyalinized material

  • Basal cell carcinoma (18.14): prominent retraction of tumor from surrounding stroma (“stromal retraction”)

  • Cholesterol clefts: oblong-shaped clefts

  • Cysts (19.1): clefts around loose keratin flakes

  • Darier’s disease (11.3) and warty dyskeratoma (18.7): suprabasal lacunae

  • Gout (8.5): needle-shaped clefts within gouty deposits

  • Lichen planus (2.11): occasional cleft between dermal/epidermal junction due to liquefaction degeneration (“Max Josef space”)

  • Paraffinoma (7.6): Swiss cheese holes in dermis

  • Scleredema (8.12) and sclerotic fibroma (27.1): clefts between collagen bundles

  • Spitz nevus (20.6): prominent clefts around melanocytic nests

  • Subcutaneous fat necrosis and sclerema neonatorum (16.4 and 16.5): small needle-shaped clefts in the subcutaneous fat

1.24

Comedones (singular is comedo)

• • Acne variants (10.1)

  • Dilated pore of Winer (22.1)

  • Familial dyskeratotic comedones (10.1)

  • Favre–Racouchot syndrome and actinic damage (9.1)

  • Nevus comedonicus (18.1)

  • Trichofolliculoma (22.1)

  • Trichostasis spinulosa (22.1)

1.25

Cystic lesions

A cyst is a closed cavity or localized sac containing fluid or some fluctuant material, often lined by epithelium. Unlined cysts are sometimes called pseudocysts. The horn pseudocysts of seborrheic keratosis are called pseudocysts because they are really invaginations of a papillomatous epidermis. Most of the “ true “ lined cysts are in Chapter 19 . Others are listed here.

• • Abscess (12.1)

  • Auricular pseudocyst (19.13)

  • Conventional cysts ( Chapter 19 )

  • Digital mucous cyst (8.9)

  • Focal mucinosis (8.11)

  • Follicular neoplasms (especially pilomatricoma, Chapter 22 )

  • Ganglion cyst (8.9)

  • Hemangioma (25.1)

  • Lymphangioma (25.10)

  • Mucocele (8.10)

  • Pilonidal cyst (10.1)

  • Sweat gland neoplasms (especially solid-cystic hidradenoma, Chapter 23 )

1.26

Diabetes mellitus and skin disease

• • Acanthosis nigricans (18.5)

  • Bullosis diabeticorum (6.9)

  • Candidiasis (13.4)

  • Diabetic dermopathy (pigmented macules of shins, 17.10)

  • Granuloma annulare, disseminated (7.1)

  • Hemachromatosis (8.17)

  • Leg ulcers (1.142)

  • Lipodystrophy (16.11)

  • Necrobiosis lipoidica diabeticorum (7.2)

  • Perforating dermatosis, acquired (9.12)

  • Progeria (9.6)

  • Scleredema diabeticorum (8.12)

  • Xanthomas (7.9)

1.27

Dyskeratosis

(see Fig. 1.27A–C )

Dyskeratotic cells are abnormally or prematurely cornified individual keratinocytes in the epidermis that stain intensely pink with the H&E stain. A small remnant of a basophilic nucleus may be present. Similar pink blobs have been called colloid bodies , cytoid bodies , hyaline bodies , Kamino bodies (in Spitz nevus), or Civatte bodies when they are present in the deep epidermis or superficial dermis. Colloid bodies generally occur in diseases in which there is interface dermatitis and liquefaction degeneration of the basal layer (1.64), and may actually represent altered collagen or basement membrane, fibrin, and immunoglobulin, as well as degenerated keratinocytes. Caterpillar bodies are linear dyskeratotic cells, colloid bodies or degenerated basement membrane material found on the roof of a blister of porphyria cutanea tarda (8.1), resembling a caterpillar. Corps ronds and grains are acantholytic dyskeratotic cells. Corps ronds have a round nucleus, often with a perinuclear halo, while grains have a more oval, grain-like nucleus. There has been considerable confusion regarding the distinction between dyskeratotic, apoptotic , and necrotic keratinocytes. All appear intensely pink with the H&E stain. They may be impossible to distinguish with routine staining, or they may all represent the same thing. For example, in graft-versus-host disease, some authors refer to these cells as dyskeratotic, while others say that they are necrotic. Hence, there is some duplication between these two lists of diseases (see Necrotic keratinocytes, 1.87).

• • Acrodermatitis enteropathica (17.1)

  • Arthropod bites (15.7)

  • Darter’s disease (11.3)

  • Familial dyskeratotic comedones (10.1)

  • Graft-versus-host disease (17.3)

  • Grover’s disease (5.6)

  • Hailey–Hailey disease (5.5)

  • Herpes virus infections (14.2)

  • Incontinentia pigmenti (verrucous second stage, 11.6)

  • Lichen planus (2.11)

  • Lichen sclerosus (9.5)

  • Lichen striatus (2.5)

  • Lupus erythematosus (17.6)

  • Many epithelial neoplasms, especially malignant and irritated benign epidermal tumors ( Chapter 18 ) and irritated benign and malignant adnexal tumors ( 21 , 23 )

  • Orf and milker’s nodules (14.5)

  • Pagetoid dyskeratosis: a peculiar incidental finding of dyskeratosis in pale keratinocytes with orthokeratosis, of uncertain significance (1.37)

  • Porokeratosis (18.4)

  • Spitz nevus (Kamino bodies, 20.6)

  • Viral warts (14.1)

  • Warty dyskeratoma (18.7)

1.28

Ear lesions

• • Acanthoma fissuratum (2.3)

  • Accessory tragus (29.10)

  • Actinic keratosis (18.8)

  • Atypical fibroxanthoma (27.12)

  • Auricular pseudocyst (19.13)

  • Basal cell carcinoma (18.14)

  • Calcinosis (8.15)

  • Chondrodermatitis nodularis helicis (17.9)

  • Epidermoid cyst (19.1)

  • Keloid (27.2)

  • Lentigo maligna (20.11)

  • Lupus erythematosus (17.6)

  • Lupus pernio (7.5)

  • Ochronosis (8.16)

  • Relapsing polychondritis (17.8)

  • Seborrheic dermatitis (2.1)

  • Solar lentigo (20.4)

  • Squamous cell carcinoma (18.11)

  • Venous lake (25.2)

  • Weathering nodules (9.1)

1.29

Eczematous diseases

(see also Papulosquamous 1.103)

Eczematous diseases are those characterized by scaling and erythema, and often spongiosis and parakeratosis, suggesting epidermal changes. Papulosquamous diseases are often lumped together with eczematous diseases, but the “splitters” consider papulosquamous lesions to be more hyperkeratotic, thicker and more heaped-up, and more sharply demarcated than eczematous lesions. Further discussion of eczema appears in Section 2.1. Most of the diseases that might be called eczematous appear in Chapter 2 , but others that may exhibit similar clinical morphology are listed here.

• • Acrodermatitis enteropathica (17.1)

  • Darier’s disease (11.3)

  • Desquamation post-erythema in viral exanthems, Kawasaki’s disease, sunburn, scarlet fever, and drug eruptions

  • Drug eruptions (most are not eczematous, 3.5)

  • Eczematous and papulosquamous diseases ( Chapter 2 )

  • Exfoliative erythroderma (1.39)

  • Follicular mucinosis (10.8)

  • Ichthyosis (11.1)

  • Immunodeficiencies (especially Wiscott–Aldrich syndrome, X-linked agammaglobulinemia, 2.1)

  • Inborn errors of metabolism (especially phenylketonuria, Hurler’s syndrome, Hunter’s syndrome, 2.1, 8.14)

  • Langerhans cell histiocytosis (purpuric, seborrheic dermatitis-like, 24.18)

  • Mycosis fungoides (24.1)

  • Onchocerciasis (15.5)

  • Scabies (15.9)

  • Tinea (13.1)

1.30

Edema of the dermis

Dermal edema produces paleness in the dermis by the accumulation of interstitial fluid. Paleness in the dermis can also be due to mucin accumulation (1.83). Edema in the epidermis is called spongiosis (1.132).

• • Acute eczema (2.1)

  • Arthropod bites (15.7)

  • Burns (6.7)

  • Cellulitis and erysipelas (12.3)

  • Contact dermatitis (2.2)

  • Erythema multiforme (3.2)

  • Fixed drug eruption (3.5)

  • Lichen sclerosus (9.5)

  • Lymphedema

  • Polymorphous light eruption (17.5)

  • Sweet’s syndrome (3.7)

  • Urticaria (3.1)

  • Vasculitis (4.1)

  • Vesiculobullous diseases (1.147, especially pemphigoid, herpes gestationis, bullous mastocytosis, bullous lupus erythematosus, dermatitis herpetiformis)

1.31

Elastic tissue changes

Elastic tissue changes may not be apparent with the H&E stain. An index of suspicion is necessary so that special stains, such as the Verhoeff–van Gieson stain may be done.

• • Acrokeratoelastoidosis (2.15)

  • Actinic granuloma (7.1)

  • Anetoderma (macular atrophy) (9.11)

  • Blepharochalasis (9.10)

  • Connective tissue nevus (27.6)

  • Cutis laxa (9.10)

  • Elastofibroma (27.6)

  • Elastosis perforans serpiginosa (9.13)

  • Erythema ab igne (3.9)

  • Mid-dermal elastolysis (9.15)

  • Pseudoxanthoma elasticum (9.8)

  • Perforating calcific elastosis (9.8)

  • Scars and keloids (27.2)

  • Solar elastosis (9.1)

  • Striae distensae (27.2)

1.32

Elbow lesions

• • Calcinosis cutis (8.15)

  • Dermatitis herpetiformis (6.5)

  • Epidermolysis bullosa (6.6)

  • Frictional lichenoid dermatosis (2.3)

  • Granuloma annulare (7.1)

  • Lichen simplex chronicus and prurigo nodularis (2.3)

  • Lipoid proteinosis (8.3)

  • Psoriasis (2.8)

  • Rheumatoid nodule (7.3)

  • Tuberous xanthoma (7.9)

1.33

Encapsulated or sharply circumscribed neoplasms

The following neoplasms have a tendency to be sharply circumscribed or encapsulated in the dermis or the subcutaneous fat, without an obvious connection to the epidermis.

• • Angioleiomyoma (29.6)

  • Giant cell tumor of tendon sheath (27.9)

  • Lipomas (29.2)

  • Neurilemmoma (26.2)

  • Neurofibroma (26.1)

  • Pilomatricoma (22.3)

  • Solitary glomus tumors (25.5)

  • Sweat gland tumors ( Chapter 23 ): hidradenoma papilliferum, cylindroma, nodular hidradenoma, eccrine spiradenoma

1.34

Eosinophilia in blood with skin disease

• • Angiolymphoid hyperplasia with eosinophilia (25.4)

  • Atopic dermatitis (2.1)

  • Churg–Strauss syndrome (4.5)

  • Coccidioidomycosis (13.6)

  • Drug eruptions (3.5)

  • Eosinophilia–myalgia syndrome (3.5)

  • Eosinophilic fasciitis (9.3)

  • Hypereosinophilic syndrome (24.16)

  • Internal malignancy

  • Mycosis fungoides (24.1)

  • Parasitosis (internal or in skin, Chapter 15 )

  • Pemphigoid (6.1)

  • Schmid’s triad (16.8)

  • Urticaria (3.1)

1.35

Eosinophilic pink amorphous material (H&E stain)

Eosinophilic material appears in these diseases (usually in the dermis). The terms hyaline or hyalinized are often used to refer to homogenized pink material in general. Hyaline is generally periodic acid-Schiff (PAS)–positive and diastase resistant. The term sclerosis (1.125) is used for hyalinized collagen with decreased fibroblasts. Psammoma bodies are laminated, hyalinized, or calcified structures that may be found with meningioma (26.6), melanocytic nevus (20.5), thyroid carcinoma, or psammomatous melanotic Schwannoma (26.2).

• • Amyloidosis (8.4)

  • Ancient melanocytic nevus (20.5)

  • Colloid (hyaline) bodies (1.27)

  • Colloid milium (8.2)

  • Corticosteroid material

  • Eosinophilic cellulitis (flame figures, 3.8)

  • Fibrin and thrombi (1.137)

  • Fibrous proliferations (scar, keloid, fibromatosis) (1.125, Chapter 27 )

  • Gout (see Section 8.5)

  • Granuloma with caseation (1.51)

  • Juvenile hyaline fibromatosis (8.3)

  • Kamino bodies (1.27)

  • Lichen sclerosus (9.5)

  • Lipoid proteinosis (8.3)

  • Necrobiosis lipoidica (7.2)

  • Necrosis (1.86, 1.87)

  • Porphyria (especially erythropoietic protoporphyria, 8.1)

  • Radiodermatitis , chronic (9.2)

  • Rheumatoid nodule (7.3)

  • Russell bodies (1.111)

  • Scleroderma (9.3)

  • Sweat gland tumors (especially cylindroma, eccrine spiradenoma, and nodular hidradenoma, Chapter 23 )

  • Vasculitis (especially hyalinizing segmental vasculitis, in which vessel walls become hyalinized, Chapter 4 )

1.36

Eosinophils in skin

(see Fig. 1.36A , B )

Eosinophils have a bilobed nucleus (fewer lobes than neutrophils), and prominent eosinophilic granules in the cytoplasm. The presence of eosinophils in the skin can be non-specific, but the following conditions should be considered if eosinophils are easy to find. Some diseases, such as lupus erythematosus, usually do not have eosinophils at all.

1.37

Epidermotropism and pagetoid cells

(see also Clear cell neoplasms 1.22)

Epidermotropism refers to migration of malignant cells into the epidermis, usually without significant spongiosis. Exocytosis refers to the migration of cells (usually lymphocytes, neutrophils, or eosinophils) into the epidermis, usually in association with spongiosis (1.132), and usually used for benign conditions. Pagetoid cells are cells in the epidermis, often pale or atypical, resembling Paget’s disease. Pagetoid cells may or may not arrive in the epidermis by means of epidermotropism. Pagetoid melanocytes ( Chapter 20 ) are best known in melanoma, but are also seen in benign melanocytic neoplasms such as Spitz nevus, pigmented spindle cell nevus, congenital nevus in neonates, recurrent nevus, and acral nevus. Care must be taken not to mistake melanocytes in tangentially sectioned epidermis for pagetoid cells, nor to mistake common artifactual vacuoles around keratinocytes for pagetoid cells (1.144).

• • Paget’s disease : pale cells with adenocarcinoma staining features. Carcinoembryonic antigen (CEA), EMA, CK-7, CK-8, usually positive. Mucin in cytoplasm is often positive with mucicarmine, Alcian blue, colloidal iron, and PAS with and without diastase. Basal cells are often compressed and uninvolved. No dyskeratosis

  • Bowen’s disease (squamous cell carcinoma in situ, 18.10): pale keratinocytes may be present which contain glycogen (PAS positive, diastase labile) with frequent dyskeratosis (1.27). Full-thickness atypia often involves basal cells also. High molecular weight keratin positive. Mucin stains, CEA, EMA, CK-7, CK-8, and low molecular weight keratin negative. However, cases have been published with exceptions, such as positive staining for CK-7 and EMA. Usually no pagetoid cells in the stratum corneum, which sometimes occurs with Paget’s disease and melanoma

  • Borst–Jadassohn phenomenon: discrete clones of basaloid, squamatized, or pale keratinocytes in the epidermis that appear different than their neighbors. This can be benign or malignant. It is mainly seen with irritated seborrheic keratosis (18.2) or Bowen’s disease (18.10), and rarely with hidroacanthoma simplex (a form of eccrine poroma limited to the epidermis, 23.10).

  • Melanoma (20.11): S-100 (very sensitive, but not specific), HMB-45 and MART-1 (both very specific, but not sensitive) stains positive. Fontana melanin stain is also positive, but is less useful because keratinocytes may contain melanin transferred from melanocytes. Melanosomes by electron microscopy

  • Mycosis fungoides (24.1): malignant T-lymphocytes (sometimes cerebriform) in spaces called Pautrier microabscesses. Stains such as CD45 (leukocyte common antigen, used for screening), CD4 (T-helper cells), and CD3 (pan-T cells) usually positive

  • Lymphomatoid papulosis (24.5): CD30 positive large atypical lymphocytes, and most smaller ones in the epidermis stain with T-cell markers

  • Langerhans cell histiocytosis (24.18): malignant Langerhans cells, often kidney-shaped nuclei, CDla or S-100 positive

  • Sebaceous carcinoma (21.5): oil red-O stain positive (need frozen section). Sometimes Bowenoid changes (oil red-O negative carcinoma) in the epidermis coexist with sebaceous carcinoma in the dermis. Adipophilin and EMA positivity is useful if frozen section not available

  • Merkel cell tumor (26.7): small cell tumor (1.130) is almost always present also in the dermis, in addition to the epidermotropic cells. Sometimes Bowen’s disease can coexist, or the small cells enter the epidermis. Merkel cell carcinoma cells are usually positive for CK20 (perinuclear dot pattern) and neuron-specific enolase

  • Clear cell acanthoma (18.6): discrete clone of pale keratinocytes in a psoriasiform epidermis, positive for glycogen and keratin

  • Hidroacanthoma simplex (23.10): this is an eccrine poroma with Borst–Jadassohn features, and sweat ducts are present

  • Pagetoid dyskeratosis (1.27)

  • Epidermotropic adnexal carcinoma (23.13): rare

  • Epidermotropic metastatic carcinoma or melanoma: very rare. Usually carcinoma or melanoma cells within the epidermis imply that a neoplasm is primary, but in this case metastatic melanocytes or epithelial cells actually infiltrate the epidermis. This usually can only be diagnosed with certainty when more than one lesion is present, making it more apparent that the lesions are metastatic.

1.38

Epithelioid cells

Epithelioid cells are defined as cells that resemble (-oid) epithelial cells (keratinocytes). They have large oval, pale, vesicular nuclei and abundant eosinophilic cytoplasm. The term “epithelioid cell” confuses neophytes because it is most often used to describe large monocyte-derived macrophages (histiocytes, 1.76) that often form granulomas, but is also used to describe many tumor cells that have a similar appearance. Sometimes immunostaining may be needed to identify the type of epithelioid cell. Vimentin will stain all of these (all mesenchymal lesions) except most examples of squamous cell carcinoma (an epithelial neoplasm). SCC stains with cytokeratin cocktail, while epithelioid sarcoma stains with both vimentin and cytokeratin. True histiocytes found in granulomas, atypical fibroxanthoma, and malignant fibrous histiocytoma usually stain with CD68 or alpha-1 antitrypsin. S-100 protein stains melanocytic neoplasms and Langerhans cell histiocytosis. CD la stains only the Langerhans cell histiocytosis. CD31, CD34, and Ulex stain most vascular neoplasms with proliferating endothelial cells (see Chapter 30 ).

1.39

Exfoliative erythroderma

This is a term used by clinicians for generalized scaling and erythema over an extensive part of the body. It is important to try to determine one of the causes in the following list. The histology depends on which of these is the underlying etiology.

• • Contact dermatitis (2.2)

  • Crusted “Norwegian” scabies (15.9)

  • Darier’s disease (11.3)

  • Dermatomyositis (17.7)

  • Drug eruption (3.5)

  • Eczema (2.1)

  • Graft-versus-host disease (17.3)

  • Ichthyosis variants (11.1)

  • Idiopathic erythroderma (common)

  • Immunodeficiencies, especially Wiskott–Aldrich syndrome (2.1), Omenn syndrome (2.1)

  • Mycosis fungoides (especially Sezary syndrome) (24.1)

  • Onchocerciasis (15.5)

  • Pemphigus foliaceus (5.4)

  • Pityriasis rubra pilaris (2.10)

  • Post-erythema stage of viral exanthems ( Chapter 14 )

  • Psoriasis (2.8)

  • Scarlet fever (12.2)

  • Staphylococcal scalded skin syndrome (12.2)

1.40

Extravasated erythrocytes (red blood cells)

(see also Purpura 1.120)

1.41

Eye and skin lesions

(see also Eyebrow lesions 1.42, Eyelid lesions 1.43, Blue clinical lesions 1.14)

• • Albinism (11.9, nystagmus)

  • Ataxia telangiectasia (11.2, bulbar telangiectasia)

  • Atopic dermatitis (2.1, cataracts)

  • Behçet’s syndrome (4.11, uveitis)

  • Cat scratch disease (12.15, Parinaud’s oculoglandular syndrome)

  • Congenital syphilis (12.13, interstitial keratitis)

  • Cytomegalovirus (14.9, retinitis)

  • Hansen’s disease (12.12, iritis)

  • Herpes virus infections (14.2, keratitis, iritis)

  • Ichthyosis (11.1, mostly corneal changes)

  • Incontinentia pigmenti (11.6, rarely blindness, strabismus)

  • Juvenile xanthogranuloma (7.10, xanthogranulomas, glaucoma, iritis)

  • Kawasaki’s disease (14.10, conjunctivitis)

  • Loefgren’s syndrome (7.5, iritis)

  • Neurofibromatosis (26.1, Lisch nodules of iris)

  • Pretibial myxedema (8.7, exophthalmos)

  • Pseudoxanthoma elasticum (9.8, angioid streaks, retinal hemorrhages, blindness)

  • Reiter’s disease (2.8, conjunctivitis, iritis)

  • Relapsing polychondritis (17.8, ocular inflammation)

  • Rothmund–Thompson syndrome (11.5, cataracts)

  • Sarcoidosis (7.5, iritis)

  • Sturge–Weber syndrome (25.1, glaucoma)

  • Toxoplasmosis (15.15, chorioretinitis)

  • Tuberous sclerosis (27.3, several complications)

  • Vogt–Koyanagi–Harada syndrome (17.2, uveitis)

1.42

Eyebrow lesions

(see also Madarosis 1.77)

• • Alopecia areata (10.9)

  • Dermoid cyst (1.42)

  • Porphyria (especially EP and PCT, 8.1): hypertrichosis

  • Seborrheic dermatitis (2.1): scale and erythema

  • Ulerythema ophryogenes (10.5): follicular plugging and scale

1.43

Eyelid lesions

(see also Madarosis 1.77)

• • Acne rosacea (10.1)

  • Acrochordon (27.4)

  • Amyloidosis (8.4)

  • Angioedema (3.1)

  • Anthrax (12.4)

  • Ascher’s syndrome (7.7)

  • Atopic dermatitis (2.1)

  • Basal cell carcinoma (18.14)

  • Cat scratch disease (12.15)

  • Cellulitis, orbital (12.3)

  • Chagas disease (Romana’s sign, 15.14)

  • Chalazion and sty (10.1)

  • Cicatricial pemphigoid (6.1)

  • Contact dermatitis (2.2)

  • Dacryocystitis

  • Dermatomyositis (heliotrope, 17.6)

  • Herpes simplex (14.2)

  • Hidrocystoma (19.11)

  • Kawasaki syndrome (conjunctivitis, 14.10)

  • Lipoid proteinosis (8.3)

  • Measles (conjunctivitis, 14.7)

  • Milia (19.1)

  • Molluscum contagiosum (14.4)

  • Myxedema (8.6)

  • Necrobiotic xanthogranuloma (7.11)

  • Pediculosis (phthirus pubis on eyelashes, 15.7)

  • Reiter’s syndrome (conjunctivitis, 2.8)

  • Sebaceous carcinoma (4.5)

  • Seborrheic dermatitis (2.1)

  • Seborrheic keratosis (18.2)

  • Stevens–Johnson syndrome (3.2)

  • Syringoma (23.7)

  • Thyroid disease

  • Trichinosis

  • Vitiligo (17.2)

  • Xanthelasma (7.9)

1.44

Face lesions

(see also Nose lesions 1.95, Eyelid lesions 1.43, Eyebrow lesions 1.42)

1.45

Fever with rash

(see also Morbilliform 1.81)

Fibrosis (see Scars)

1.47

Follicular plugging and follicular eruptions

Follicular plugging is hyperkeratosis within hair follicles (usually in the infundibulum). In some of these conditions, there is adnexocentric inflammation around follicles or other adnexal structures such as sweat glands. A few of these just appear to be follicular on a clinical basis, such as some of the transepidermal elimination diseases.

• • Acne variants (10.1)

  • Atopic dermatitis (2.1)

  • Darier’s disease (keratosis follicularis) (11.3)

  • Eczema with follicular accentuation (2.1)

  • Follicular mucinosis (10.8)

  • Folliculitis variants (10.2)

  • Fox–Fordyce disease (10.7)

  • Graft-versus-host disease (follicular type) (17.3)

  • Hidradenitis suppurativa (10.2)

  • Ichthyosis vulgaris (11.1)

  • Keratosis pilaris (10.5)

  • Kyrle’s disease (9.12)

  • Lichen planopilaris (2.11)

  • Lichen sclerosus (9.5)

  • Lichen simplex chronicus (2.3)

  • Lichen spinulosus (10.5)

  • Lupus erythematosus (17.6)

  • Miliaria (actually is sweat duct occlusion, 10.6)

  • Mycosis fungoides, follicular variant (24.1)

  • Perforating folliculitis (10.3)

  • Pityriasis rubra pilaris (2.10)

  • Prurigo nodularis (2.3)

  • Scurvy and phrynoderma (4.17)

  • Seborrheic dermatitis (2.1)

  • Transepidermal elimination diseases (1.140)

  • Trichostasis spinulosa (10.4)

1.48

Foot lesions

(see also Hands 1.56, and also Palm and sole 1.100)

• • Acral lentiginous melanoma (20.11)

  • Acral pseudolymphomatous angiokeratoma (24.14)

  • Atherosclerotic ulcers

  • Buerger’s disease (4.19)

  • Chilblains (3.12)

  • Clear cell sarcoma (20.11)

  • Contact dermatitis (2.2)

  • Eczema (2.1)

  • Epidermolysis bullosa (6.6)

  • Foreign body granuloma (7.6)

  • Kaposi sarcoma (25.9)

  • Larval migrans (15.6)

  • Lichen planus (2.11)

  • Mycetoma (13.14)

  • Purpuric glove and sock syndrome (14.7)

  • Stasis dermatitis and ulcers (2.1, 16.9)

  • Tinea pedis (13.1)

  • Tungiasis (15.11)

1.49

Gastrointestinal tract and skin

1.50

Gingival lesions

(see also Mouth lesions 1.82)

• • Addison’s disease (melanosis, 17.10)

  • Amalgam tattoo (pigment, 7.6)

  • Ameloblastoma (tumor, 18.14)

  • Cowden’s disease (22.5)

  • Drug-induced hyperplasia (phenytoin, nifedipine, cyclosporine, etc., 3.5)

  • Gingivitis due to infection or irritation

  • Juvenile hyaline fibromatosis (hyperplasia, 8.3)

  • Kaposi sarcoma (tumor, 25.9)

  • Leukemia, lymphoma (bleeding, Chapter 24 )

  • Leukoplakia , traumatic or premalignant (1.71)

  • Lipoid proteinosis (hyperplasia, 8.3)

  • Melanoma (tumor, 20.11)

  • Mucosal pemphigoid (ulcers, 6.2)

  • Papillon–Lefevre syndrome (periodontitis, 2.15)

  • Paraneoplastic pemphigus (ulcers, 5.4)

  • Pemphigus vulgaris (ulcers, 5.4)

  • Racial pigmentation

  • Scurvy (bleeding, 4.17)