Skin

DIRECT IMMUNOFLUORESCENCE (IF)

against IgG, IgA, IgM, C3, C1q, and fibrinogen ●● Evaluated with IF microscope

ELECTRON MICROSCOPY (EM)

●● Used for undifferentiated neoplasms, metabolic disorders, various types of epidermolysis bullosa

CYTOGENETIC TESTING

medium

●● Cutaneous involvement and underlying genetic defect

APLASIA CUTIS CONGENITA

ICHTHYOSIS

●● Epidermal disorders, dryness and scaling of skin

●● Flexor surfaces spared, extensor surfaces involved

●● Moderate hyperkeratosis, reduced/absent granular layer, follicular plugging

●● Ichthyosis vulgaris, lamellar ichthyosis, X-linked ichthyosis

●● CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects)

●● Crust interferes with normal fetal development, can be fatal

Collodion baby

●● Infant encased in keratinous membrane (sheds after 1-2 weeks)

DARIER DISEASE

basal acantholysis ●● Dyskeratotic cells (corps ronds) and para-

keratosis (corps grains) ●● Face, neck, upper trunk, oral mucosa

HAILEY-HAILEY DISEASE

wall appearance

POROKERATOSIS

●● Keratotic papules, plaques, and keratotic ridges

●● Coronoid lamella (column of parakeratosis, overlying dyskeratotic keratinocytes)

●● Most pronounced features noted in porokeratosis of Mibelli

RESTRICTIVE DERMOPATHY

●● Prematurity, rigid and tense skin, perineal abnormalities, fixed facial expression, skin denudations

●● Thick/hyperkeratotic epidermis, flattening of rete ridges, thin dermis, poorly developed adnexal structures

ECTODERMAL DYSPLASIA

●● Dysplasia of all structures derived from ectoderm

●● Hypoplasia of hair, sebaceous glands, apocrine and eccrine glands

FOCAL DERMAL HYPOPLASIA

defects with ocular, dental, and skeletal system abnormalities

●● Thinned out dermis with thin fibrils of collagen admixed with adipocytes

EPIDERMOLYSIS BULLOSA

●● Bullous lesions develop spontaneously or after minor trauma

Simplex

●● Good prognosis, blisters heal without scarring

Junctional

years of age ●● Cleavage plane at lamina lucida of basement

membrane at dermo-epidermal junction ●● Similar changes in mucosa of urinary/

respiratory/gastrointestinal tract

Dystrophic

●● Recessive form has bad prognosis (ulcerations and erosions)

●● Cleavage plane in papillary dermis, below basement membrane

INCONTINENTIA PIGMENTI

keratotic lesions, hyperpigmented lesions ●● Vesicular stage: Eosinophilic spongiosis ●● Hyperpigmented stage: Numerous melano-

phages in dermis

in infancy ●● Similar changes in zinc deficiency states ●● Vesiculobullous lesions (acral/periorofacial)

LINEAR IGA BULLOUS DERMATOSIS

●● Tense bullae lower part of trunk, prepubertal children

●● Subepidermal blisters with neutrophils/ eosinophils

●● Direct IF: Linear IgA at basement membrane zone

●● No association with gluten-sensitive enteropathy

DERMATITIS HERPETIFORMIS

phils, eosinophils, and fibrin ●● Direct IF; IgA granular deposits at the tips of

dermal papillae

HERPES GESTATIONIS

neonate ●● Subepidermal bulla with eosinophils ●● Direct IF: Linear deposits of C3 and IgG at

basement membrane

ERYTHEMA MULTIFORME, STEVENSJOHNSON SYNDROME, AND TOXIC EPIDERMAL NECROLYSIS (TEN)

bullous formations ●● Skin and mucosa ●● May be related to viral infections, drugs ●● Vacuolar alteration of basal cell layer,

necrotic keratinocytes

●● Dermal perivascular infiltrate of lymphocytes

●● TEN: Full-thickness epidermal necrosis, subepidermal bulla formation

ERYTHEMA TOXICUM NEONATORUM

●● Transient macula-pustular rash, selflimiting

TRANSIENT NEONATAL PUSTULAR MELANOSIS

heal with hyperpigmented macules ●● Pustules contain neutrophils

ACROPUSTULOSIS OF INFANCY

●● Pustules on palms, black infants, self-limiting, infancy

●● Erythematous scaling vesicular lesions, serum crust

vesicles ●● Mixed moderate dermal perivascular

inflammation ●● Other types of allergic dermatitis with simi-

alr histology are nummular, atopic, contact, and dyshidrotic dermatitis

PSORIASIS VULGARIS

●● Plaque and guttate types more common in children

bleeding = Auspitz sign

●● Confluent parakeratosis, Munro-microabscesses, regular elongation of rete ridges

●● Thin supra-papillary plates, dilated vessels in rete ridge, mild perivascular infiltrate

SEBORRHEIC DERMATITIS

riasis and spongiform dermatitis

LICHEN PLANUS

aspect extremities, back ●● May be seen in oral mucosa, nails, hair ●● Hyperkeratosis, hypergranulosis, irregu-

lar epidermal hyperplasia, sawtooth rete ridges, vacuolization of basal cell layer and colloid bodies

●● Band-like lymphohistiocytic infiltrate at dermo-epidermal junction

PITYRIASIS ROSEA

plaque) ●● Viral etiology (HHV-7 and parvovirus) ●● Focal parakeratosis, focal epidermal

spongiosis ●● Extravasated erythrocytes in papillary der-

mis, mild perivascular lymphohistiocytic infiltrate in superficial dermis

PITYRIASIS RUBRA PILARIS

parakeratosis and hyperkeratosis ●● Follicular plugging, mild perivascular der-

mal inflammation ●● Keratoderma of palms, cephalic involvement

PITYRIASIS LICHENOIDES

●● PLEVA, also known as Mucha-Habermann disease (pityriasis lichenoides et varioliformis acuta)

extremities ●● Parakeratosis, spongiosis, necrotic kerati-

nocytes, neutrophilic epidermal infiltrate, ulceration

PAPULAR ACRODERMATITIS OF CHILDHOOD

EBV)

LICHEN SCLEROSUS

band below papillary dermis ●● Overlapping features with morphea

BACTERIAL INFECTIONS

Impetigo

●● Most common bacterial infection in children

Non-bullous (impetigo contagiosa)

of body ●● Subcorneal pustule filled with Gram-

positive cocci ●● May be superimposed on other pre-existing

skin conditions

Bullous impetigo

to flaccid bullae

tory cells

●● Superficial dermis contains neutrophilic infiltrate

●● Localized form of staphylococcal scalded skin syndrome (SSSS)

Staphylococcal scalded skin syndrome

SSSS ●● ETA toxin causes bullous impetigo ●● Abrupt onset of fever, erythema, and large

flaccid sterile bullae ●● Bullae rupture with peeling of sheets of epi-

dermis: Scalded appearance ●● Similar to bullous impetigo, but no dermal

inflammation ●● Good prognosis with complete recovery in

2-3 weeks

Toxic shock syndrome

●● TSS toxin-I and enterotoxins produced by S. aureus

●● Acute life-threatening multisystem disorder, fever, generalized rash, hypotension

Ecthyma

infiltrate

Ecthyma gangrenosum

●● Pseudomonas aeruginosa, immunocompromised children

●● Necrotizing vasculitis at base of cutaneous ulcer

Erysipelas

infiltrate

VIRAL INFECTIONS

Human papillomavirus

plantaris, verruca palmaris, condyloma acuminata

●● HPV 6 and 11 cause benign or low-grade lesions

hyperkeratosis, parakeratosis, hypergranulosis, koilocytosis

●● Condyloma acuminata (anogenital warts): Prenatal mode of transmission (maternal history of warts) or due to sexual abuse

Molluscum contagiosum

invagination ●● Intracytoplasmic, large eosinophilic round

inclusion bodies: Molluscum bodies ●● Thin crescentic nuclei ●● Numerous lesions in immunocompromised

hosts

Herpes virus infection

EBV ●● Primary infection by varicella-zoster virus

causes chicken pox ●● Herpes-zoster caused by reactivation of

virus from dorsal root ganglion (immunocompromised hosts)

keratinocytes, intranuclear ground-glass inclusions

FUNGAL INFECTIONS

Superficial infections

●● Dermatophytosis (tinea), Pityrosporum and Candida

●● Fungal diagnosis made by culture/biopsy/ KOH preparation

cosis, and cryptococcosis

●● Suppurative/granulomatous inflammation of dermis/subcutaneous tissue

●● Pseudoepitheliomatous hyperplasia of epidermis

INFESTATIONS

Scabies

eosinophils ●● Mite/eggs identified in parakeratotic layer

of skin

ACUTE FEBRILE NEUTROPHILIC DERMATOSIS

vasculitis

GRANULOMA ANNULARE

●● Asymptomatic ringed papules (dorsum of hands/feet)

●● Upper dermal zones of myxoid collagen degeneration surrounded by palisaded histiocytes

NECROBIOSIS LIPOIDICA

around degenerated collagen, plasma cell infiltrate

●● Involves entire dermis and extends to subcutaneous tissue

JUVENILE RHEUMATOID ARTHRITIS

●● Palisading granulomas around fibrinoid collagen degeneration

SARCOIDOSIS

●● Multisystem disorder, red-yellow cutaneous plaques

septa (septal panniculitis)

ERYTHEMA NODOSUM

●● Symmetric tender erythematous subcutaneous nodules, extensor surface of lower legs

●● Septal pattern of panniculitis, fibrosis, and granulomatous inflammation

●● Associated with inflammatory bowel disease, tuberculosis, streptococcal infection, coccidioidomycosis

SUBCUTANEOUS FAT NECROSIS OF NEONATES

sis, infiltration by macrophages and multinucleated giant cells (contain lipid and calcium deposits)

SCLEROMA NEONATORUM

●● Diffuse involvement of fat cells by radially arranged crystals of lipid

underlying systemic disorder (collagen vascular disease)

●● Damage to vessel wall: Fibrinoid necrosis, perivascular inflammation, extravasation of red cells

LEUKOCYTOCLASTIC VASCULITIS

infection in children ●● Purpuric rash lower extremities, arthralgia,

arthritis, abdominal pain, and hematuria ●● Self-limiting, resolves in a few weeks

LYMPHOCYTIC VASCULITIS

●● Insect bite reaction, PLEVA, lymphomatoid papulosis and collagen vascular diseases

●● Benign pigmented purpuras (lichen aureus, Schamberg-Majocchi purpura)

●● Superficial perivascular lymphocytic infiltrate, extravasated red blood cells, hemosiderin laden macrophages

ACNE

tion, blockage of follicular infundibula, comedones formation

EOSINOPHILIC PUSTULAR FOLLICULITIS

LUPUS ERYTHEMATOSUS

●● Malar rash, oral ulcers, photosensitivity, alopecia, discoid lupus erythematosus

●● Mild hyperkeratosis, epidermal atrophy, vacuolization of basal cell layer

●● Interface dermatitis with extension around blood vessels and adnexa

●● Direct IF: Continuous granular deposit of C3, IgG along dermo-epidermal junction of skin

SCLERODERMA (PROGRESSIVE SYSTEMIC SCLEROSIS)

●● Mild/variable inflammation, thick hyalinized collagen bundles in dermis/subcutaneous fat

●● Response seen in immunocompromised hosts after receiving immunocompetent donor cells

●● After stem cell transplant or after transfusion of non-irradiated blood in immunocompromised children

sis surrounded by lymphocytes (satellite necrosis), epidermal necrosis

●● Subepidermal bullae, dermal hyalinization of collagen

CALCINOSIS CUTIS

●● Localized dystrophic or systemic metastatic type

●● Subepidermal calcific nodules in heals of infants after repeated needle sticks

●● Tumoral calcinosis in soft tissue around joints

MUCOPOLYSACCHARIDOSES

●● Lysosomal enzyme deficiency → abnormal accumulation of mucopolysaccharides in multiple organs including skin

acanthosis ●● Normal adnexal structures ●● In epidermal nevus syndromes; associated

central nervous system, skeletal and renal system defects

EPIDERMAL INCLUSION CYST

●● Dermal nodule lined by keratinizing stratified squamous epithelium

TRICHILEMMAL CYST

●● Lined by keratinized epithelium devoid of granular cell layer

DERMOID CYST

●● Developmental cysts, located along lines of embryonic suture closures

●● Locations: periorbital, midline nose, neck, scalp

●● Cysts lined by keratinizing stratified squamous epithelium and adnexal structures

●● Lumen contains lamellar keratin, sebum, and hair

●● Midline cysts may contain sinus tract; evaluate radiologically before excision

ERUPTIVE VELLUS HAIR CYST

nated keratin ●● Multiple hair in lumen

STEATOCYSTOMA MULTIPLEX

stratified squamous epithelium

●● Covered by thick homogenous eosinophilic cuticle

ADNEXAL TUMORS

Follicular Neoplasms

●● Tumors with follicular differentiation most common

Pilomatrixoma (calcifying epithelioma of Malherbe)

and neck ●● Basaloid cells, ghost cells, calcified/

ossified stroma, foreign body giant cell inflammation

Trichoepithelioma

Trichoblastoma

●● Less well-differentiated form of trichoepithelioma

Eccrine neoplasms

Syringoma

some tadpole shaped ●● Confined to upper half of dermis

Sebaceous and apocrine neoplasms

Nevus sebaceous of Jadassohn

or face ●● Epithelial hyperplasia, mild papillomatosis,

numerous sebaceous lobules, malformed small hair follicles

BASAL CELL NEVUS SYNDROME

MELANOCYTIC NEOPLASMS

Congenital melanocytic nevi

●● Giant (bathing trunk pattern), large and small in size

●● Verrucous epidermal hyperplasia, coarse hair

perivascular ●● Individual melanocytes infiltrate collagen

bundles, deeper dermis, and subcutaneous fat

●● Giant nevi in head/neck; associated with leptomeningeal melanocytosis/melanoma

●● Congenital nevi have higher risk of transformation to melanoma

Acquired melanocytic nevi

show maturation with depth ●● Junctional, intradermal, or compound

Spitz nevus

●● Also known as spindle and epithelioid cell nevus

by clefts, Kamino bodies, mitotic figures, pagetoid epidermal spread

●● Considerable nuclear and cytologic pleomorphism

plasia ●● Difficult to differentiate from melanoma

sometimes

Halo nevi

●● Dense lymphocytic infiltrate destroys the melanocytes and produces depigmented halo around nevus

●● Common in patients with vitiligo; similar immunologic mechanism

Blue nevus

pigment, nests/fascicles, extend into reticular dermis

Clark dysplastic nevus

●● Positive family history of melanomas and dysplastic nevi

●● Broad junctional/compound nevi, bridging of rete ridges by melanocytes, lamellar fibroplasias, cytologic atypia

●● Features mimicked by nevi in very young children, nevi located in genitalia/ conjunctiva/palms/soles

Malignant melanoma

placental metastasis from mother ●● Similar clinical/histologic features as

adults ●● Prognosis depends on maximum thickness

of lesion (Breslow depth)

MESENCHYMAL NEOPLASMS

Neurothekeoma

matrix in dermis ●● Positive staining for CD3, vimentin, CD10 ●● Negative for S100

Solitary/plexiform neurofibroma

Vascular tumors

Hemangiomas

clusters of spindle cells ●● Infantile/juvenile hemangioma; GlUT-1

positive

Pyogenic granuloma

dermal collarette overlying lesion

Tufted hemangioma

●● Well-defined foci of closely set capillaries in dermis/subcutaneous tissue

Myogenic tumors

Congenital infantile myofibromatosis

pericytoma-like proliferation ●● Peripheral fascicular proliferation of

fibroblasts/myofibroblasts

Cutaneous myofibroma

●● Similar features as infantile myofibromatosis, but it is well circumscribed

Infantile digital fibromatosis

●● Dome-shaped papules on fingers/toes of infants

●● Lateral and dorsal aspects of distal/middle interphalangeal joints

(contain actin) resembling erythrocytes ●● Inclusion bodies stain red with Masson tri-

chrome stain ●● Benign tumor, mostly regresses with time

Giant cell fibroblastoma

●● Also known as juvenile dermatofibrosarcoma protuberans

●● Proliferation of infiltrating spindle cells in dermis/subcutaneous tissue, moderate nuclear pleomorphism

●● Pseudovascular spaces lined by multinucleated cells

Hematopoietic neoplasms

Mast cell diseases

●● Solitary mastocytoma; present at birth and regresses spontaneously in a few years

●● Urticaria pigmentosa; diffuse maculopapular rash, 3-9 month infants, regresses by puberty

●● Diffuse mastocytosis; systemic with poor prognosis

mast cells with bland nuclei and abundant pale to amphophilic cytoplasm (fried egg appearance)

●● Stain with CD117, Giemsa (metachromatic granules), toluidine blue, Leder stain

Histiocytoses

Langerhans cell histiocytosis (LCH) ●● Langerhans histiocytes positive for S100

and CD1a ●● Letterer-Siwe disease (acute disseminated

with visceral involvement, infancy) ●● Hand-Schüller-Christian disease (chronic

multisystem disease with osseous involvement but less visceral, early childhood)

●● Focal disease with one or more bone involvement (eosinophilic granuloma, late childhood and adults)

●● Cutaneous manifestation, scalp and anogenital region most common

●● Diffuse infiltrate of Langerhans histiocytes in papillary dermis, abundant pale cytoplasm and reniform nucleus, multinucleated histiocytes and eosinophils

Juvenile xanthogranuloma ●● Yellowish/red papular lesions ●● Diffuse infiltrate of histiocytes, cytoplasmic

lipidization, Touton giant cells, lymphocytes, and eosinophils

Sinus histiocytosis with massive lymphadenopathy ●● Also known as Rosai-Dorfman disease ●● Papules and nodules ●● Histiocytes show emperipolesis of lympho-

cytes ●● Histiocytes are S100 positive

Leukemia and lymphoma

●● Anaplastic large cell leukemia, lymphomatoid papulosis, angiocentric cutaneous T-cell lymphoma

BLUEBERRY MUFFIN BABY

●● Congenital viral infections, dermal extramedullary hematopoiesis, hemolytic disease of newborn, blue bleb rubber nevus syndrome, twin-to-twin transfusion, metastasis from neuroblastoma, leukemia, choriocarcinoma, rhabdomyosarcoma

DERMAL MANIFESTATIONS OF TUBEROUS SCLEROSIS

●● Angiofibroma, fibromas, shagreen patch, leaf-shaped hypopigmentation