Skin

Introduction

The skin is commonly affected by a wide range of pathologies. Some of these are cutaneous manifestations of systemic disease processes whilst others are primary disorders of the skin. Common systemic viral illnesses such as measles and chickenpox are associated with characteristic skin rashes and many autoimmune and vasculitic disorders, such as systemic lupus erythematosus, dermatomyositis, scleroderma and Henoch–Schönlein purpura, present with skin manifestations. Primary disorders of the skin are extremely common and the vast majority of these are inflammatory or neoplastic in type.

Inflammatory disorders

Skin has a limited repertoire of responses to injury. The most common of these are illustrated in Figs 21.1 to 21.4 . Most stimuli result in a combination of these changes, each with varying degrees of severity. As a result, definitive diagnosis of inflammatory dermatological conditions requires careful correlation of clinical and histological findings. Few skin conditions have pathognomonic histological appearances.

Dermatitis is a common clinical term used to describe a wide variety of inflammatory skin conditions with diverse causes. Histologically, there are changes of acute or chronic inflammation ( Figs 21.5 and 21.6 ). Some disorders have additional histological features that may indicate a more specific diagnosis or aetiology. Two relatively common inflammatory dermatoses with characteristic clinical and microscopic features are lichen planus ( Fig. 21.7 ) and psoriasis ( Fig. 21.8 ).

Systemic viral infections frequently cause skin rashes, some of which have typical histological features, e.g. herpes simplex virus (HSV) infection (see Fig. 5.12 ), chickenpox and shingles. The latter two disorders are different clinical manifestations of infection by the herpes zoster virus and the histological changes closely resemble those of HSV infection. Other viruses give rise to apparently localised skin lesions by causing proliferation of the cells of the epidermis. Common examples include viral warts ( Fig. 21.9 ), which are caused by human papillomavirus infection (see also Ch. 17 ), and molluscum contagiosum ( Fig. 21.10 ), which is due to infection by a poxvirus.

Neoplastic disorders

Common primary skin tumours may be divided broadly into those arising from epithelial cells, those arising from melanocytes and those arising within dermal and subcutaneous tissues. Much less commonly, skin can be involved by metastatic tumour from other sites (e.g. lung or renal cancer) or by direct invasion from an underlying neoplasm (most commonly breast cancer). Lymphoma may also affect the skin either primarily (e.g. mycosis fungoides , see Fig. 16.11 ) or in cases of systemic lymphoma.

Epithelial neoplasms

Seborrhoeic keratosis and basal cell papilloma are terms used interchangeably to describe a very common benign skin lesion seen predominantly in elderly patients. Basal cell carcinoma is a low-grade malignant tumour that resembles the basal cells of the epidermis; squamous cell carcinoma is a more aggressive tumour that resembles the cells of the prickle cell layer (stratum spinosum) of the epidermis. Both of these malignant tumours are strongly associated with chronic sun exposure. Chronic sun damage is also associated with premalignant change in the skin in the form of epidermal dysplasia , with disordered maturation of keratinocytes. Severe dysplasia, the skin equivalent of CIN 3 (see Fig. 17.7 ), can be described as carcinoma in situ , intra-epidermal carcinoma or using the eponymous term Bowen’s disease . Lesser degrees of epidermal dysplasia are termed actinic or solar keratosis .

Melanocytic lesions

In normal skin, melanocytes are scattered in the basal layers of the epidermis, their fine cytoplasmic processes ramifying between the keratinocytes towards the skin surface ( E-Fig. 21.10 ). Melanocytes are responsible for the synthesis of the brown pigment melanin, which is then transferred to adjacent keratinocytes. There are significant racial and genetic differences in the melanin synthetic activity of melanocytes, resulting in the varying degrees of normal pigmentation seen in the skin. Exposure to sunlight enhances melanin synthesis and transfer into keratinocytes.

Benign pigmented skin lesions are very common and are known colloquially as ‘moles’. This term encompasses a large group of benign lesions called naevi , which are characterised histologically by aggregates of melanocytic cells at various sites within the skin. The three main subtypes, junctional , compound and intradermal naevi , are shown in Fig. 21.15 .

Malignant melanoma is an important and highly malignant tumour of melanocytic cells. Its main features and histological variants are illustrated in Figs 21.16 to 21.19 . There are also melanocytic lesions with features intermediate between a benign naevus and a malignant melanoma. These are described as atypical or dysplastic naevi and may progress to melanoma in some cases.

Benign melanocytic naevi

These are of three main types, defined according to the location of the melanocytic nests:

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  Junctional melanocytic naevus: Nests of melanocytes are confined to the lower epidermis.

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  Compound melanocytic naevus: Nests are located in both the lower epidermis and upper dermis.

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  Intradermal melanocytic naevus: Nests of melanocytes are present in the dermis only.

Benign naevi ( E-Fig. 21.11 ) have a predictable natural history and are illustrated in Fig. 21.15 . Most begin as flat, pigmented junctional naevi , with nests of pigmented melanocytes confined to the lower levels of the epidermis, sitting on the epidermal basement membrane. Purely junctional naevi are most commonly found in children. As the child grows older, some of these junctional melanocytes migrate across the basement membrane into the upper dermis where they lose most of their pigment and the cells become smaller and tightly packed together. There are some remaining pigmented junctional nests in the epidermis and smaller non-pigmented naevus cells in the dermis. At this stage, the naevus is called a compound naevus and the intradermal nests produce a lesion that is raised above the level of skin to form a brown, raised nodule. In early adulthood, most of the junctional nests of melanocytes migrate into the dermis until no more are present in the epidermis. At this stage, the naevus is a completely intradermal naevus . All of these lesions are completely benign but, rarely, a previously benign naevus will transform into a malignant melanoma. This usually occurs by a well recognised route: the junctional nests do not completely migrate into the dermis but proliferate abnormally and show features of cytological and architectural atypia, producing a dysplastic or atypical naevus . If untreated, a proportion of these eventually become superficial spreading malignant melanoma ( Figs 21.16 and 21.17 )

Malignant melanocytic lesions (malignant melanoma)

Malignant melanoma ( E-Fig. 21.12 G ) is a malignant tumour of melanocytes, the incidence of which is increasing dramatically in white-skinned people around the world. Excessive sun exposure, particularly sunburning, is believed to be the principal cause. Neglected malignant melanomas have frequently metastasised at the time of presentation, but public awareness is leading to patients presenting earlier, such that many malignant melanomas may now be completely cured by primary excision of the lesion. Malignant melanoma spreads initially via lymphatics to regional lymph nodes and subsequently via the blood-stream, by which time control of the disease is extremely difficult.

The risk of metastasis, and therefore the prognosis, depends mainly on the following factors:

Cysts and other skin lesions

Some common skin lesions are difficult to classify because their aetiologies are incompletely understood. Examples include the various cysts commonly referred to as ‘sebaceous cysts’ by clinicians. Common skin cysts fall into two main categories histologically, epidermoid cysts ( Fig. 21.20 ) and pilar cysts ( Fig. 21.21 ). Other lesions such as the pyogenic granuloma ( Fig. 21.22 ) and dermatofibroma ( Fig. 21.23 ) share some features with benign neoplasms, but are considered by others to be reactive proliferations, often occurring after minor injury. Dermatofibrosarcoma protuberans ( Fig. 21.24 ) shows some histological similarities to dermatofibroma, but as the name suggests, this is a malignant soft tissue neoplasm (a sarcoma). Other soft tissue lesions are considered in Ch. 22 .

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