Introduction to dermatopathology

Author: Dr Nick Love, PhD, medical student, Stanford University School of Medicine, Stanford, California, USA. Editor in Chief DermNet NZ: Adjunct A/Prof. Amanda Oakley, Hamilton, New Zealand. April 2019.


Introduction

This introductory course on dermatopathology is intended for medical students and registrars/residents.

The H&E stain

Hematoxylin (H) is a dark blue/violet histology stain that is positively charged, binding to negatively charged basophilic substances such as DNA and RNA. It can be considered a mostly nuclear stain. Conversely, eosin (E) is a negatively charged red, pink, orange stain that highlights acidophilic, positively charged substances such as amino acid side chains (lysine, arginine) that are relatively plentiful in the cytoplasm.

The H&E stain

Normal skin

The illustrations of normal skin show comparatively thin skin from the wrist (bottom) and thicker skin from the bottom of the foot (left, an acral site). Note, only acral sites have a stratum lucidum. Fine, spiny intercellular desmosomes in the stratum spinosum are also visible. Within the epidermis, non-keratinocytes have comparatively hyperchromatic nuclei.

Histopathology of normal skin

Seborrhoeic keratoses

Seborrhoeic keratoses are well-demarcated proliferations of monotonous, sometimes cuboidal epidermal keratinocytes. They are characterised by keratin-filled 'horn cysts' within the epidermis.

Histopathology of seborrhoeic keratosis

Psoriasis

Psoriasis show acanthosis (epidermal hyperplasia) with flattened retes and parakeratosis (retention of keratinocyte nuclei in the stratum corneum). Neutrophils in the stratum corneum (Munro microabscesses) or upper epidermis (pustule of Kogoj) are pathognomonicThe epidermis is thinned above elongated dermal papillae.

Histopathology of psoriasis

Lichen planus

Lichen planus classically exhibits a lichenoid inflammatory pattern in which there are prominent mononuclear cells at the dermal-epidermal junction that cause damage, often described as a 'sawtooth' appearance. Basal keratinocytes may show vacuolar degeneration due to immune-mediated apoptosis. Other features are hypergranulosis (thickening of stratum granulosum), acanthosis, epidermal thinning, pigment incontinence (pigment within melanophages in the upper dermis) and spongiosis (oedema within the epidermis). See lichen planus pathology.

Histopathology of lichen planus

Basal cell carcinoma

There are several subtypes of basal cell carcinoma (BCC) in which there is a peripheral palisade of basal keratinocytes with hyperchromatic nuclei. The left lesion is a superficial BCC, and the right one is an infiltrative BCC. Following histological slide processing, retraction artefact results in clefts. See basal cell carcinoma pathology.

Histopathology of basal cell carcinoma

Dermatitis herpetiformis

Dermatitis herpetiformis is a blistering disorder characterised by neutrophils at the tips of dermal papillae and subepidermal vesicles filled with neutrophils. Eosinophils, spongiosis and perivascular inflammation are also typical. Direct immunofluorescence reveals granular IgA in the papillary dermis. See dermatitis herpetiformis pathology.

Histopathology of dermatitis herpetiformis

Drug eruption

The pathological findings in drug eruptions are diverse and include many of the features seen in other types of lesions including spongiosis, interface activity and variable lichenoid inflammation.

Histopathology of drug eruption

Mycosis fungoides

Mycosis fungoides is a type of T-cell lymphoma characterised by epidermal T-lymphocytes with hyperchromatic nuclei which may form pathognomonic and Pautrier micro-abscesses. Other features are perivascular lymphocytes, spongiosis, and surface serum crust. See mycosis fungoides pathology.

Histopathology of mycosis fungoides

Actinic keratosis

An actinic keratosis classically shows atypical basal keratinocytes and the 'flag sign' (alternating parakeratosis and orthokeratosis) that usually spares adnexal structures. Prominent epidermal hyperkeratosis, acanthosis and solar elastosis are often present. The hypertrophic variant is notable for a thick stratum corneum.

Histopathology of actinic keratosis

Squamous cell carcinoma in situ

Squamous cell carcinoma in situ results in full-thickness atypia of keratinocytes. Typically there are parakeratosismitotic figures, acanthosis, and solar elastosis. Atypical squamous cells do not extend into the dermis. See squamous cell carcinoma in situ pathology.

Histopathology of squamous cell carcinoma in situ

Cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma results in dyskeratosis and invades beyond the basement membrane into the dermis. Cellular atypia may be described as glassy. Other features include ulceration (serum crust) and keratin pearls. See squamous cell carcinoma pathology

Histopathology of squamous cell carcinoma

Melanocytic naevus

Melanocytic naevi can be intradermal, where there is a proliferation of melanocytes within the dermis, compound, in which there are also junctional nests of melanocytes at the bottom of papillary retes, or junctional, where there are no dermal melanocytes. A blue naevus is characterised by deeply pigmented spindle cell melanocytes and lies underneath a relatively acellular dermal stroma.

Naevi with varying levels of atypical features may be called atypical or dysplastic due to architectural asymmetry, bridging of retes, wider junctional than dermal component, cellular atypia, fibroplasia and lymphocytic infiltration. The images are from an acral site, showing a thick stratum corneum. See melanocytic naevus pathology and blue naevus pathology.

Histopathology of melanocytic naevus

Melanoma

Melanoma is a malignant proliferation of atypical melanocytes. Histological features include a dusky cytoplasm, pagetoid scatter (abnormal cells within the higher levels of the epidermis) and irregular cellular nests. Melanoma in situ is confined to the epidermis whereas invasive melanoma extends past the basement membrane into the dermis. Reactive, perilesional lymphocytic inflammation is common. See melanoma pathology.

Histopathology of melanoma

Molluscum contagiosum

The classical histology of molluscum contagiosum is epidermal hyperplasia with a crater containing molluscum bodies (Henderson-Patterson bodies). These are large keratinocytes with eosinophilic intracytoplasmic inclusions that push aside the nucleus. See molluscum contagiosum pathology.

Histopathology of molluscum contagiosum

Viral wart

Two distinct subtypes of viral warts are shown: verruca vulgaris (the common wart, left) and verruca plana (the flat wart, right). Verruca vulgaris is characterised by hyperkeratosis, hypergranulosis, parakeratosis, blood in the stratum corneum and prominent acanthosis. The rete ridges point inwards. Large warts are highly vascularised with enlarged capillaries in the periphery and dermal papilla. Flat warts lack hypertrophic features. Typically, there are koilocytes with a perinuclear halo in the upper epidermis

Histopathology of viral wart

Herpes simplex

Herpes simplex infection results in widespread keratinocyte necrosis and balloon cells with the '3 M’s' — multinucleation, moulding of nuclei (closely juxtaposed nuclei that conform to each other’s shape), and margination of chromatin.

Histopathology of herpes simplex virus

Bullous pemphigoid

Bullous pemphigoid is recognised by a subepidermal split, which generates tense bullae (the left image). The right-sided images show pre-cleft formation with a brisk eosinophilic infiltrate. Direct immunofluorescence shows deposition of IgG or C3 along the basement membrane. See bullous pemphigoid pathology.

Histopathology of bullous pemphigoid

Pemphigus vulgaris

Pemphigus vulgaris is a blistering disease in which there is acantholysis of keratinocytes above the basal layer (the 'tombstone' pattern). There is usually a superficial perivascular inflammatory infiltrate. Direct immunofluorescence shows deposition of IgG between the epidermal keratinocytes creating a fishnet pattern. See pemphigus vulgaris pathology.

Histopathology of pemphigus vulgaris

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