Eczema is a common inflammatory skin disease presenting clinically with red papules or plaques containing small vesicles, which may itch, ooze and crust. There are several clinical subtypes. The characteristic histological feature is intercellular oedema in the epidermis (spongiosis), which separates the keratinocytes and can cause vesicle formation. Chronic inflammation with lymphocytic infiltration of the epidermis and dermis is often seen. Pathogenesis is variable and includes:

Psoriasis is a common chronic relapsing dermatitis that classically manifests as circumscribed red skin plaques often several centimetres in diameter, with silvery surface scale. Extensor surfaces of knees and elbows, the sacral region and the scalp are common sites. Nail changes are common and arthritis develops in a small percentage of patients. Onset is usually in early adult life. The pathogenesis is unclear but there is hyperproliferation of keratinocytes, with the epidermal turnover time reduced from the normal 13days to 3–4days. The histological features of classical psoriasis are:

• regular epidermal hyperplasia (thickening)

• parakeratosis (retained nuclei within the surface keratin layer)

• thinning of the granular layer

• neutrophil microabscesses

• increased mitotic activity (cell turnover).

Lichen planus presents clinically as multiple small itchy violet papules, around the wrist and elbows. Oral and genital lesions also occur. Skin lesions often resolve after several months or years. Histological features include:

Erythema multiforme (EM) is an uncommon but potentially serious hypersensitivity response to certain infections (herpes simplex and Mycoplasma) and drugs (including sulphonamides, penicillin and aspirin). Clinical lesions include red macules, papules and vesicles. The characteristic ‘target’ lesion has a pale, raised or eroded centre and erythematous (red) rim. Symmetrical involvement of the limbs is most commonly seen. Stevens–Johnson syndrome is severe erythema multiforme with oral mucosal lesions. Toxic epidermal necrosis is the most serious manifestation of EM, with a high risk of systemic sepsis and fluid imbalance due to extensive loss of skin and mucosal epithelium; mortality is 35%. Histological examination shows a lichenoid inflammatory infiltrate with epidermal cell apoptosis.

Vesico-bullous diseases are classified according to the site of the vesicle formation, which may be within the epidermis or at the dermo-epidermal junction. The pathogenesis in many cases involves immune complex formation with autoantibodies. Examples are shown in Table 61. Many of these diseases are described further below.

Burns can be caused by hot liquids (scalds), gases or solids, as well as fire. Burn injuries are classified as:

In first degree burns there is endothelial injury and leakage of intravascular fluid into the surrounding tissue. There is vascular congestion with pain and erythema, but no skin necrosis. Second degree burns show epidermal necrosis with blistering as the epidermis separates from the dermis. Regeneration of the skin surface cells can occur from adjacent viable epidermis or from surviving skin adnexal structures. More severe damage occurs in third degree burns, with necrosis of the epidermis and dermis. As the extent of severe burn injuries increases, so does the risk of serious or fatal complications, including:

Skin grafting is often required for healing of third degree burns.

Skin infections are common, with a wide variety of potential pathogens, including:

Lichenoid inflammatory pattern skin lesions may be part of systemic lupus erythematosus or more commonly isolated cutaneous disease, called discoid lupus erythematosus. Immunoglobulins and complement are deposited along the dermo-epidermal junction.

Recipients of immunocompetent bone marrow transplants often develop lesions in the skin, gastrointestinal tract and liver, when grafted lymphocytes attack host tissue. Cutaneous graft-versus-host disease has a lichenoid pattern.

Bullous pemphigoid is a blistering skin disease that occurs in the elderly. Up to 90% have IgG autoantibodies against the bullous pemphigoid major antigen located in the epidermal basement membrane. The vesicles and bullae usually contain eosinophils.

Pemphigus is an intraepidermal blistering disease with autoantibodies to various structural proteins involved in intercellular adhesion.

Dermatitis herpetiformis is a subepidermal blistering disease characterised by IgA antibody deposition, although the exact pathogenesis is unclear. There is a strong association with coeliac disease.

Epidermolysis bullosa is a rare, blistering, skin disease with several subtypes that have dominant or recessive inheritance. Some variants are lethal in early life, others cause disfiguring scars with increased risk of developing squamous cell carcinoma. Blisters develop at sites of skin trauma or rubbing.

Xeroderma pigmentosum is a rare, autosomal-recessive disease with defective DNA repair. There is extremely high incidence of epidermal and melanocytic malignancies.

Basal cell papilloma is also known as seborrhoeic keratosis or seborrhoeic wart. It is a common benign warty tumour, arising in adults. It occurs almost anywhere on the body and is often pigmented. Microscopically the tumour consists of papillary projections of uniform cells resembling normal basal epidermal keratinocytes. There is hyperkeratosis and frequent formation of keratin nodules (horn cysts).

Basal cell carcinoma is the commonest human malignant neoplasm. It typically arises in chronically sun-exposed skin of older adults; 80% develop on the head or neck. Metastasis is rare but, if untreated, basal cell carcinoma may cause extensive local tissue erosion, hence the historical name of ‘rodent ulcer’. Basal cell carcinoma has several microscopic growth patterns:

The tumour cells resemble those of the normal basal epidermis and are recognised histologically by their small hyperchromatic nuclei, mitotic figures and palisading (regular arrangement) of cells at the periphery of the tumour nests.

Squamous cell carcinoma is also a common tumour arising on sun-exposed skin of older adults. The tumour cells resemble those of the suprabasal epidermis in normal skin. Well-differentiated squamous cell carcinomas produce keratin and microscopically show thin cytoplasmic extensions or ‘prickles’, which represent desmosomal cell junctions, between the tumour cells. Squamous cell carcinomas have a low incidence of metastasis to local lymph nodes and distant sites (approximately 1%).

Squamous cell carcinoma often develops within a pre-existing dysplastic epidermal lesion, such as actinic keratosis or Bowen’s disease (epidermal carcinoma in situ). Rarely, squamous cell carcinoma can arise in a chronic ulcer (Marjolin’s ulcer), burn or scar. Immunosuppressed patients (e.g. following renal transplantation) have an increased incidence of squamous cell carcinoma.

Is a rapidly growing keratotic nodule that resembles well-differentiated squamous cell carcinoma, both clinically and microscopically, and the distinction between the two lesions can be very difficult. Keratoacanthomas tend to involute spontaneously, but can leave marked scarring.

Pigmented skin lesions can be due to:

Clinical features that raise suspicion of melanoma in a pigmented lesion include:

The incidence of melanoma in the UK is rising more rapidly than that of any other malignancy. The pathogenesis is clearly linked to UV-induced cell damage. Individuals with fair skin and hair, a history of sunburn and repeated high-intensity sun exposure are at particular risk. A strong family history is also significant.

Traditionally, classification of melanoma has been by architectural type:

Lentigo maligna arises mainly on the chronically sun-exposed skin of the head and neck in the elderly. Atypical melanocytes replace the normal basal epidermis. The tumour may be present as an irregular pigmented macule for several years before invasive dermal malignancy with metastatic potential develops.

Superficial spreading melanoma is characterised by atypical melanocytes scattered irregularly at all levels of the epidermis; this pattern is also known as ‘pagetoid spread’. It can develop at any age, and is commonest on the back in males and lower leg in females.

More recently, melanomas have been classified according to their growth pattern into radial growth phase or vertical growth phase. It is proposed that only tumours showing evidence of proliferation in the dermis (vertical growth phase) have the capacity to metastasise (Table 63).

Classical melanoma cells are ‘epithelioid’ – large polygonal or cuboidal cells with copious cytoplasm and a large single eosinophilic nucleolus. Pigmentation is often found in a percentage of cells, but amelanotic lesions do occur and may be misdiagnosed clinically. Melanoma cells can also be spindle shaped. The histological diagnosis can be confirmed with immunocytochemistry with antibodies to S100 (a marker of neural crest origin) and HMB45 (see Box 32).

The most important prognostic factor in melanoma is the depth of invasion (Breslow thickness), measured from the top of the granular epidermal layer to the deepest dermal melanoma cell. The anatomical depth of invasion is also expressed as the Clark level (Figure 71). More recently, the prognostic importance of sentinel lymph node status in melanoma has been realised. The sentinel node is the specific node (or sometimes nodes) draining the area of a tumour. It can be identified by injecting coloured dye and radioactive tracer into the region of the primary tumour, and then locating the specific draining lymph nodes which take up the dye and radioactivity. The sentinel node status is a powerful prognostic indicator in melanoma and is included within the most recent staging system for the tumour. The sentinel node technique is also being utilised in the management of other tumours, particularly breast cancer, in order to reduce the morbidity associated with total axillary lymph node removal. Other adverse prognostic factors include:

Survival in malignant melanoma is improving as a result of greater public and medical awareness with earlier clinical presentation. Radial growth phase lesions have virtually 100% 5-year survival. When the Breslow thickness exceeds 1.5mm, 5-year survival drops to 34%.

Deposits in the skin most frequently arise from:

Cutaneous infiltration by lymphoma and leukaemia can also occur.