Tumours of the Skin

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Keratinocyte-derived tumours of the epidermis are of two main types: basal-cell carcinoma and squamous-cell carcinoma

Both basal-cell carcinoma and squamous-cell carcinoma are predisposed to by exposure to light and ionizing radiations, and are therefore most commonly seen in exposed areas such as the head and neck, and the dorsum of the hands. Both types of tumour arise most frequently in the elderly, and multiple lesions are not uncommon.
Basal-cell carcinoma, which occurs in three main patterns, is a locally invasive tumour that does not metastasize
The three main patterns are nodular basal-cell carcinoma, morphoeic basal-cell carcinoma, and superficial basal-cell carcinoma.

Nodular basal-cell carcinoma is the most common pattern, occurring most frequently in those over the age of 50 years. Arising on areas exposed to light, such as the face and forehead, it is relatively rare on the trunk and limbs. It presents as a firm, raised nodule, often showing central ulceration, with a raised, pearly edge, which may show numerous telangiectatic vessels. It is composed of clusters of small, dark cells resembling those of the basal layer of the epidermis. The edge of each cluster often shows a regular palisaded pattern. In the larger more protuberant lesions, cystic change is frequently seen.
Morphoeic basal-cell carcinoma appears as a flat, thickened, whitish or yellowish plaque, which may be sunken and firm, with focal areas of ulceration. In contrast to nodular basal-cell carcinoma, it has indistinct edges and the tumour may extend in the dermis or some way beyond the visible or palpable borders. Histologically, small clumps and cords of basal cells are separated by a dense fibrous stroma.

Superficial basal-cell carcinoma usually appears as a flat, red plaque, often with an irregular edge. It is most common on the face, but this variant can occur on the trunk. Sometimes there are raised areas within the tumour, representing the development of a nodular basal-cell carcinoma within the pre-existing superficial lesion. Histologically, there are usually many small buds or nodular downgrowths of basal cells from the overlying epidermis. This superficial pattern may be multifocal, e.g. occurring in the irradiation field over the vertebrae in patients previously given radiotherapy for ankylosing spondylitis.

Invasive squamous carcinoma of the skin may arise in pre-existing epidermal dysplastic lesions

Two patterns of intraepidermal dysplasia are recognized. One is actinic keratosis (also known as solar keratosis), which occurs most commonly on the face, scalp and backs of the hands (i.e. light-exposed skin). It arises as irregular plaques or patches (frequently multiple), up to 1 cm in diameter, with a rough, hard hyperkeratotic surface. Histologically the cells in the lower half of the epidermis show marked dysplasia and atypia.

The other pattern shows epidermal atypia, with pleomorphism and mitoses, throughout all layers of the epidermis to the surface. This is regarded as squamous carcinoma in situ (intraepidermal carcinoma) and, like actinic keratoses, occurs on light-exposed skin, but may also occur on skin that is normally covered, e.g. on the trunk.

Clinically, lesions appear as flat or raised reddish brown plaques, sometimes with surface keratinous scale, and occasionally with focal ulceration. 

The incidence of malignant invasive change supervening in intraepidermal carcinoma is very much greater than that in actinic keratoses. Most squamous carcinomas of the skin are locally invasive and well-differentiated, with the formation of keratin nests; occasionally, poorly differentiated non-keratinizing squamous carcinoma can develop in an area of pre-existing intraepidermal carcinoma. Invasive squamous carcinoma. unlike basal-cell carcinoma, has the potential for metastasis, usually metastasizing to regional lymph nodes initially. 

One variant of invasive squamous carcinoma, verrucous carcinoma, is particularly common on the vulva in elderly women, presenting as a well-differentiated, exophytic, cauliflower-like lesion. This tumour grows locally, rarely metastasizing.

Melanocytes in the basal layer of the epidermis are an important source of tumour-like hamartomas (naevi) and invasive malignant tumours (malignant melanoma)

Melanocytic naevi (commonly known as 'moles') are extremely common and most individuals have a few somewhere on the skin, some people having very large numbers. They are regarded as hamartomatous malformations, and five main patterns are recognized.
In junctional naevus, the abnormal clumps of melanocytes are confined to the epidermis and are located in the basal layer. Clinically the lesions are flat (macular) and uniformly and deeply pigmented. They usually develop in childhood and adolescence.

Compound naevi are raised, pale brown, slightly nodular lesions with an irregular surface, but the pigmentation is uniform. They are most common in adolescents and young adults. Histologically, there are clumps of melanocytes in both the epidermis (similar to those seen in junctional naevus) and the upper dermis. 
Those intradermal naevus cells that are closest to the junctional nests are histologically similar to the intraepidermal naevus cells. However, in the deeper levels they are smaller and more compact, a feature that is said to indicate maturation of the naevus cells. It is believed that the natural history of intraepidermal junctional naevus cells is for them to drop into the dermis and to become smaller and more compact the longer they have been in the dermis. It is not uncommon for coarse hairs to emerge from compound naevi (hairy mole).

Intradermal naevi are also raised, but are normally smoothly domed, and may be flesh-coloured or slightly brown. They are usually seen in adults and are rare in adolescents and children. They appear to be entirely composed of naevus cells within the dermis, and there is no nested junctional component, although there may be a slight increase in melanocytes in the basal layer.

Lentigo maligna is a pattern of junctional melanocyte proliferation affecting the faces of the elderly

Clinically the lesions appear as flat, variegated, brown-black areas of pigmentation on the faces of elderly men and women. They gradually increase in size and have an irregular outline. Histologically the basal layer of the epidermis is largely replaced by an almost continuous line of large atypical melanocytes, which sometimes partially extend down skin appendages such as hair follicles. Occasionally a solid, raised nodule arises within such an area, often indicating the development of a supervening early nodular malignant melanoma (lentigo maligna melanoma). 

Malignant melanomas of the skin present as irregular pigmented lesions

Compared to benign pigmented melanocytic lesions, malignant melanomas are often larger (with a history of recent increase in size), with an irregular border leading to asymmetry, and variable pigmentation. Ulceration may be present. Some forms are flat, others manifesting as raised nodular lesions.
Malignant melanomas can be classified into three main groups:

1 Lentigo malignant melanoma. A nodular lesion arising in a pre-existing facial lentigo maligna.

2 Superficial spreading malignant melanoma. Usually a flat lesion with variable pigmentation and irregular edges. This is the most common type, accounting for about 75% of all malignant melanomas; it is in this group that the recent increase in incidence has 
been most marked.

 3 Nodular malignant melanoma. Presents as a raised brown-black nodule, usually without preceding benign melanocytic lesion. These account for about 5% of all malignant melanomas.

A further group that is worth recognizing is the so-called acral lentiginous malignant melanoma. This is confined to the hands and feet, the sole of the foot being an important site, and some occur beneath the fingernails and toenails (sub-ungual melanoma). Although it is most common in elderly Caucasians, it is particularly common in Orientals. Histologically it resembles superficial spreading malignant melanoma.
Superficial spreading malignant melanoma may either be in situ or invasive

In superficial spreading malignant melanoma in situ, the atypical melanocytes are confined to the epidermis. In contrast, with invasive superficial spreading malignant melanoma, in addition to the in situ change, clusters of malignant melanocytes invade the dermis. In the invasive type, the prognosis largely depends on the depth of dermal invasion (see blue box). In most cases, at the time of excision biopsy to establish the diagnosis, the invasion is very superficial; the prognosis is good for these tumours if they are adequately excised.
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