DERMATOPATHOLOGY

CHAPTER 11 DERMATOPATHOLOGY



Approach to pediatric skin biopsy interpretation

Aplasia cutis congenita
Cutis laxa

Focal dermal hypoplasia (Goltz syndrome)

Ichthyoses
Non-syndromic ichthyoses
Ichthyosis vulgaris

X-linked recessive ichthyosis

Lamellar ichthyosis / congenital ichthyosiform erythroderma (non-bullous ichthyosiform erythroderma)

Bullous ichthyosiform erythroderma / epidermolytic hyperkeratosis

Ichthyosis hystrix of Curth-Macklin

Syndromic ichthyoses
Sjögren-Larsson syndrome

Neutral lipid storage disease

Netherton’s syndrome

Omenn syndrome

KID syndrome (keratitis, ichthyosis and deafness)

Conradi-Hunermann-Happle syndrome

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

Trichothiodystrophy

Hereditary Palmoplantar Keratodermas (PPKs)
Epidermolytic palmoplantar keratoderma (Vorner type)

Pachonychia congenita

Epidermolysis bullosa (EB)
Epidermolysis bullosa simplex (EBS)
Weber-Cockayne EBS

Dowling-Meara EBS

EBS with muscular dystrophy

Plectin mutations

Plakophilin mutations

Junctional epidermolysis bullosa (JEB)
Lethal junctional EB (“Herlitz” JEB)

Non-lethal JEB

JEB with pyloric atresia

Dystrophic Epidermolysis Bullosa
Transient bullous dermolyis of the newborn

Incontinentia Pigmenti

Acrodermatiis enteropathica

Porokeratosis
Porokeratosis of Mibelli

Linear porokeratosis

Acantholytic diseases
Darier’s disease

Hailey-Hailey disease

Pemphigus vulgaris

Pemphigus foliaceus

Other blistering and bullous diseases
Bullous impetigo

Staphylococcal scalded skin syndrome

IgA pemphigus

Infantile acropustulosis

Erythema toxicum neonatorum

Herpes simplex

Erythema multiforme

Fixed drug eruption

Polymorphous light eruption

Bullous pemphigoid

Insect and mite bites

Dermatitis herpetiformis

Bullous dermatosis of childhood (Linear IgA disease)

Bullous lupus erythematosus

Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

Bullous urticaria pigmentosa and bullous mastocytosis

Atopic dermatitis/eczema

Seborrheic dermatitis

Psoriasis

Pityriasis lichenoides

Pityriasis rubra pilaris

Cutaneous infection-related diseases
Molluscum contagiosum

Varicella zoster virus (VZV) infection

Gianotti-Crosti syndrome

Fish tank granuloma

Cutaneous candidiasis

Scabies

Necrotizing fasciitis (echthyma gangrenosum)

Cutaneous lupus erythematosus (LE)

Morphea

Systemic sclerosis / scleroderma

Lichen sclerosus et atrophicus

Sweet’s syndrome (acute febrile neutrophilic dermatosis)

Pyoderma gangrenosum

Cutaneous graft versus host disease (GVHD)

Granuloma annulare

Rheumatoid nodule

Necrobiosis lipoidica (NL)

Panniculitis
Septal panniculitis
Erythema nodosum

Lobular panniculitis
Idiopathic nodular panniculitis

Alpha 1 antitrypsin deficiency

Lipoatrophy (lipodystrophy)
Familial lipodystrophy
Congenital generalized lipodystrophy

Familial partial lipodystrophy, Dunnigan type

Acquired lipodystrophy
Generalised

Partial

Cytophagic histiocytic panniculitis

Lupus panniculitis (lupus profundus)

Subcutaneous fat necrosis of the newborn

Vasculopathy including vasculitis
Vascular occlusive diseases
Purpura fulminans

Urticaria
Cryopyrinopathies
Familial cold autoinflammatory syndrome

Muckle-Wells syndrome

Neutrophilic (leukocytoclastic) vasculitis
Acute hemorrhagic edema of the skin of the newborn (Finkelstein’s disease)

Henoch-Schonlein purpura

Microscopic polyarteritis

Polyarteritis nodosa (PAN)

Behçet’s disease

Wegener’s granulomatosis

Churg-Strauss syndrome

Vascular malformations and vascular tumors
Vascular malformations
Arteriovenous malformation

Venous malformation

Glomangioma or glomulovenous malformation

Blue rubber bleb nevus syndrome

Lymphatic malformation
Lymphangioma circuscriptum

Cystic hygroma / lymphangioma

Capillary malformation (‘port wine stain’)

Complex combined vascular malformations with limb overgrowth

Angiokeratoma

Vascular tumors
Infantile hemangioma (hemangioma of infancy)

Congenital hemangioma (rapidly involuting and non involuting- ‘RICH’ and ‘NICH’)

Tufted angioma

Pyogenic granuloma

Glomus tumor

Kaposiform hemangioendothelioma

Kaposi sarcoma

Cutaneous infiltrations
Leukemia

Lymphoma

Rhabdomyosarcoma

Neuroblastoma

Langerhans cell histiocytosis

Mastocytosis

Tumors and hamartomas
Pilomatrixoma

Trichoepithelioma

Trichofolliculoma

Follicular poroma

Nevus sebaceus

Syringocystadenoma papilliferum

Epidermal nevus

Connective tissue nevus

Collagenoma

Buschke-Ollendorff syndrome (BOS)

Dermatofibroma

Smooth muscle hamartoma and Becker’s nevus

Juvenile xanthogranuloma

Malignant skin tumors in childhood
Basal cell carcinoma

Squamous cell carcinoma

Dermatofibrosarcoma protuberans (DFSP)

Melanocytic lesions
Congenital melanocytic nevus (CMN)

Acquired melanocytic nevi

Spitz nevus

Spindle cell nevus of Reed

Blue nevus

Malignant melanoma

Hypertrophic scar/keloid

Cutaneous calcification
Subepidermal calcified nodule

Tumoral calcinosis

Cysts
Epidermoid cyst

Dermoid cyst

Mucinous cyst

Median raphe cyst

Lip cleft cyst / lip pits


APPROACH TO PEDIATRIC SKIN BIOPSY INTERPRETATION



• Close clinicopathological correlation and frequent multidisciplinary team meetings with joint discussion of clinical photographs and histopathological material is essential in pathological interpretation of skin biopsies
image similar histological features may require different interpretations according to the circumstances

• Interpretation of vascular lesions is assisted by attendance of the pathologist at meetings where discussion of radiological findings including Doppler flow studies takes place

• Punch biopsies need to be examined at several levels for assessment of subtle findings

• Beware the biopsy which looks ‘normal’ on routine histology
image clinical discussion may direct attention to subtle changes compatible with a particular clinical diagnosis

• Timing of the biopsy in relation to the evolutionary stage of the disease may affect histological features
image eg in vasculitic disease, the stage of infiltration of vessel walls by inflammatory cells may have passed and only perivascular inflammation remains

• Prior consultation with the pathologist is important to ensure optimal handling of tissue

• A good maxim in investigation of a skin condition is ‘If in doubt, biopsy’
image punch biopsy is minimally invasive

• Beware the traumatic biopsy taken with forceps which may induce artefactual separation of the epidermis from the underlying dermis (Fig 11.1)

image

Fig 11.1 Photomicrograph of incisional skin biopsy taken while holding the skin with a forceps demonstrating artefactual separation of the epidermis from the dermis.



SPECIFIC ENTITIES IN PEDIATRIC DERMATOPATHOLOGY



• Almost any pathological process can potentially affect children

• Many conditions common in adult practice almost never occur

• Many conditions are unique to pediatric practice

• This section concentrates on entities common or specific to pediatric practice
image for details on conditions more usually seen in adults see standard dermatopathology texts

• Due to the importance of clinicopathological correlation of clinical, genetic and histopathological findings for correct interpretation of skin biopsies, for many conditions relevant diagnostic clinical and genetic findings are provided in this chapter


APLASIA CUTIS CONGENITA



• Estimated incidence 3 in 10,000 births

• Familial cases reported
image compatible with autosomal dominant transmission
– no gene locus identified

• May be associated with a large number of other anomalies (Frieden 1986)


Clinical features



• 80% located on scalp
image most in midline
– at or in close proximity to parietal hair whorl

• Any skin site may be involved

• Commonly presents at birth with a well-circumscribed ulcer

• Lesions single in 70–75% of cases
image double in 20%

image triple in 8%

• Typically 1–3 cm in diameter, round or oval, sharply marginated and hairless

• Involvement of underlying bone, dura or meninges may occur if lesion large and in one of the cranial suture lines


Histopathological features



• Flattened epidermis

• Total absence of adnexal structures

• Dermal fibrosis

• Variable reduction of elastic fibers


Differential diagnosis and diagnostic pitfalls



• Clinically, iatrogenic injuries caused by forceps or scalp electrodes

• Histopathologically, an ulcer or scar due to trauma cannot be differentiated from aplasia cutis congenita


CUTIS LAXA



• Group of extremely rare disorders of elastic tissue characterized by loose inelastic skin


Genetics



• Congenital or acquired forms
image one autosomal dominant

image two major autosomal recessive (type I and type II)
– AR cutis laxa type I is the most severe form
· associated in some cases with mutations in fibulin-5 (Mégarbané et al 2009)

image X-linked recessive form

• Some forms are caused by mutations in the elastin gene

• Acquired form has an immunological basis
image reported following febrile illness or surgery or as an apparent hypersensitivity reaction to penicillin

• May also occur in a localized or generalized form following an inflammatory skin disorder such as erythema multiforme, dermatitis herpetiformis or Sweet’s syndrome


Clinical features



• Skin hangs in loose folds
image impression of being too large for the body

• Cutis laxa type I
image involves nearly the entire body surface
– worsens over time

image hoarse low-pitched voice (redundant vocal cords)

image associated with emphysema
– may develop in first few months

image diaphragmatic hernia, diverticula of the gastrointestinal tract and bladder

• Cutis laxa type II
image pre- and post-natal growth restriction

image joint laxity

image intellectual and motor development is unpredictable


Histopathological features



• Loss of fine elastic fibers in papillary dermis (Fig 11.2)
image remaining fibers shortened and vary in diameter
– may be fragmented

• In acquired form may be associated inflammatory component
image neutrophils, eosinophils and lymphocytes in superficial and deep dermis

• Electron microscopy shows abnormal elastic fibers
image tangled microfibrils

image reduced elastin

image fragmentation of fibers

image

Fig 11.2 Photomicrograph of skin biopsy from a patient with cutis laxa. Elastic van Gieson stain demonstrates epidermal atrophy and absence of elastic fibers in the superficial dermis.



Differential diagnosis and diagnostic pitfalls



• Histological features may be subtle
image special stain for elastin (Elastic Van Gieson) required

image compare with age-matched control


FOCAL DERMAL HYPOPLASIA (GOLTZ SYNDROME)



• Rare
image minimally affected individuals may remain unrecognized


Genetics



• X-linked dominant
image deletion in Xp11.23P, X-linked PORCN

• History of miscarriages of male fetuses and stillbirths suggests male lethality

• Linear pattern of skin lesions following Blaschko’s lines as well as streaking of long bones indicate X chromosome mosaicism


Clinical features



• Typically linear cutaneous atrophy with telangiectasia and pigmentation
image usually present from birth

image any part of the body

• Lesions may be striate, atrophic, lipomatous and papillomatous

• Hair can be sparse and brittle

• Nail abnormalities also described

• Eye involvement in 20%
image usually coloboma

• Hands and feet involved in 60–70%
image syndactyly, polydactyly, absence or hypoplasia of digits

image lobster claw deformity

• Scoliosis in 15–20%

• Osteopathia striata
image longitudinal linear striations in metaphyses of long bones
– 20% of gene carriers

– characteristic but not diagnostic

• Dental anomalies in 40%
image enamel defects, hypoplastic or dysplastic teeth, delayed eruption, irregular spacing and notched incisors

• 15% have variable mental deficiency

• Abnormalities also described in respiratory, digestive, genitourinary tract and cardiovascular system


Histopathological features (Fig 11.3)



• Depending on timing of biopsy

• Early lesions
image thinning of the dermis

image few collections of fat around dermal blood vessels

• Later lesions
image marked thinning of dermis and fat deposits in the papillary dermis

• Late lesions
image fat nodules separated from the epidermis by only a few collagen fibers

image

Fig 11.3 Photomicrograph of skin biopsy from a patient with focal dermal hypoplasia (Goltz syndrome) demonstrating focal thinning of the dermis and clusters of fat cells in the reticular dermis. Clinically the lesion was linear and striate.



Differential diagnosis and diagnostic pitfalls



• No adipocytes are present in the dermis of young infants with focal dermal hypoplasia
image appear over time

• Biopsies of very early lesions may show only an increase in numbers of small venules and capillaries in the upper dermis
image occasional small cluster of adipocytes in the reticular dermis


RESTRICTIVE DERMOPATHY



Clinical features



• Rare lethal genodermatosis
image lamin A deficiency
– autosomal recessive

• Premature birth

• Fixed facial expression

• Thin, slightly adherent shiny skin

• Significant restriction of limb movements and respiratory effort

• Characteristic dysmorphic facies

• Arthygryposis with limbs in fixed flexion deformity tightly encased by skin

• Death within hours or within a few weeks


Histopathological features (Fig 11.4)



• Marked thinning of dermis compared with age-matched controls

• Decrease or absence of elastin

• Collagen fibers in bundles parallel to skin surface

• Decreased numbers of adnexal structures

• Electron microscopy
image disorganized collagen bundles

image abnormally thin collagen fibrils

image decrease in elastic fibers

image

Fig 11.4 Photomicrograph of skin biopsy from a patient with restrictive dermopathy demonstrating thinning of the epidermis, decreased elastin, and a reduction in numbers of adnexal structures which are poorly differentiated.



POIKILODERMA CONGENITA (ROTHMUND–THOMSON SYNDROME)



Clinical features



• Rare

• Autosomal recessive
image helicase gene mutations

• Poikiloderma affecting cheeks and backs of hands

• Short stature

• Sparse hair

• Cataracts

• Hypogonadism

• Midface hypoplasia

• Increased incidence of squamous carcinoma and osteogenic sarcoma


Histopathological features (Fig 11.5)



• Hyperkeratosis

• Epidermal atrophy

• Vasodilatation

• Pigment incontinence

• Fragmentation of elastic tissue

• Loss of appendages

image

Fig 11.5 Photomicrograph of skin biopsy from a patient with poikiloderma demonstrating epidermal atrophy. The dermis shows numerous small telangiectatic vessels associated with some melanophages and loss of skin appendages.



ICHTHYOSES




Introduction



• Group of mainly hereditary disorders characterized clinically by visible scaling

• Inflammatory scaling disorders, such as psoriasis and eczema, and disorders such as pityriasis rubra pilaris are usually categorized separately

• Pathology may be confined to the skin or part of a generalized syndrome

• Genetic testing is becoming increasingly available
image many genes implicated

image algorithmic approach to direct testing

• Skin biopsy is a screening procedure
image often not diagnostic although there are a few notable exceptions

• Most characterized histologically by thickened stratum corneum

• Epidermal hyperplasia and dermal inflammatory response are variable
image result of disordered epidermal homeostasis and barrier dysfunction


Handling of the specimen



• Prior consultation between dermatologist and pathologist is advised to narrow the differential diagnosis

• Consideration of need for frozen sections
image Oil red O staining in neutral lipid storage disease

image alcohol dehydrogenase staining for Sjögren–Larsson syndrome

• Fixation in glutaraldehyde if electron microscopy is likely to be required
image to confirm ichthyosis vulgaris, Netherton syndrome, epidermolytic hyperkeratosis, harlequin ichthyosis, ichthyosis hystrix of Curth–Macklin

• Hair sample examined if differential diagnosis includes Netherton syndrome or trichothiodystrophy


NON-SYNDROMIC ICHTHYOSES




ICHTHYOSIS VULGARIS



• Most common and often mildest form of generalized ichthyosis

• Prevalence difficult to measure
image clinical overlap with other conditions associated with dry skin

image variable expression in response to temperature and humidity


Genetics



• Likely autosomal dominant with variable expression

• Linkage to 1q21 (Compton et al 2002)
image contains several genes vital to epidermal function including profilaggrin

• Recently described mutations in filaggrin gene (Oji et al 2009, Nomura et al 2009)


Clinical features



• Not present at birth
image manifests within first year of life

• Fine white scales most prominent on the trunk and extensor surfaces of the limbs

• Flexural areas almost always spared

• Improves in warm humid environments

• Keratosis pilaris (keratotic plugging of hair follicles) in 75%

• Hyperlinear palms and soles in 80%

• Increased incidence of atopic dermatitis


Histological features (Fig 11.6)



• Compact hyperkeratosis of stratum corneum

• Reduced or absent granular layer
image useful diagnostic feature

• Epidermis of average thickness

• Hair follicles and sweat ducts may show keratotic plugs

• Electron microscopy
image reduced or absent keratohyaline granules

image

Fig 11.6 Photomicrograph of skin biopsy from a patient with ichthyosis vulgaris demonstrating compact orthokeratosis and reduced granular layer.



X-LINKED RECESSIVE ICHTHYOSIS



• Relatively common

• 1 in 2000–10,000

• Heterozygous females clinically unaffected
image rare reports of affected homozygous females


Genetics



• Steroid sulfatase (STS) gene
image Xp22.3
– > 90% due to complete deletion

– minority due to partial gene deletions or point mutations


Clinical features


Related posts:

  1. METABOLIC DISEASE PATHOLOGY
  2. BONE PATHOLOGY
  3. RENAL PATHOLOGY
  4. TUMORS AND TUMOR-LIKE LESIONS

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Jun 18, 2016 | Posted by in PEDIATRICS | Comments Off on DERMATOPATHOLOGY

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