Chapter 5

Non-melanoma skin cancer (NMSC)

Skin cancer can be divided into two principal types on the basis of clinical and biological differences:

Non-Melanoma Skin Cancer (NMSC)

These types of cancer are derived from keratinocytes and are far more common than melanoma, but have a much lower case-fatality (<0.1%). The principal types of NMSC are:

There are in addition a number of other lesions that are pre-malignant or related to skin cancer.

So, at least initially, you have to think about 5 conditions, 2 are cancer proper and the other 3
are premalignant or related in some other way to either BCC or SCC.

Actinic keratoses —premalignant lesions

Actinic keratoses are focal areas of dysplasia characterised by erythema and scale that usually feel rough when the fingers are rubbed over them [1]. They are a marker of UVR exposure occurring at those sites that have received the most cumulative sun exposure such as the scalps of bald-headed men, the backs of the hands and the nose and ears. They are most common in those with sun sensitive skin and in those with high UVR exposure (and hence increase with age). They can be considered precursors of squamous cell carcinoma in that a very small proportion of actinic keratoses progress to squamous cell carcinoma. AKs vary in size from 1mm to over 1cm in diameter. They are frequently multiple with some patients having over 20 lesions or more.

The distinction between sun damaged skin and early AKs may be not be straightforward, as in many patients with multiple AKs, you can see or feel small areas of erythema and scale that if biopsied would show dysplasia. There is considerable clinical variation in what experienced clinicians will describe as an AK. Exact figures for AK incidence are therefore not surprisingly not known, but clinically they are the most common dysplastic or neoplastic lesion of skin. The author can rarely sit on a bus in Edinburgh without spotting many AKs on other elderly passengers.

Click image to enlarge

Should all AKs be treated?

The exact proportion of AKs that progress to SCC is still debated and this influences views on how aggressively they should be sought out and treated. For instance one estimate is that the chance of an AK progressing to an SCC is around 1:1000/year. It is also thought that many regress (at least over the short term)—perhaps around 25% in one year. It is therefore possible to argue that (some) AKs may not need treatment, but rather that effort should be focussed on early detection of SCC. There is however little or no systematic evidence on which to base strong recommendations. In practice the default option is to treat AKs with the following arguments being used to justify this course of action.

My own view is that there may be considerable heterogeneity in AK behaviour related to their size with larger lesions being more worthy of attention. Similarly, I doubt there is a clear distinction between small AKs and the histological abnormalities frequently seen in sun damaged skin without clinical evidence of an AK.

Treatment of actinic keratoses

AKs are superficial lesions and the abnormal clones of cells are close to the skin’s surface (within the epidermis). Excision is not therefore usually required. THe most consistent and traditionally widely used treatments are:

Given the frequent occurrence of a large number of lesions cryotherapy is often used as the first line treatment. Further details of these treatments and others such as topical chemotherapy that may be used to treat AKs are described in the next chapter on treatment of NMSC. Finally, if the clinical diagnosis is assured then histological confirmation is not normally required [2]. However if samples are taken (as in curettage and cautery) it is advised that such samples are sent for histopathological confirmation. Inevitably some AKS will be excised because they were thought to be SCCs clinically.

Intraepithelial carcinoma (IEC, Bowen’s disease)—premalignant lesions

Intraepithelial carcinoma is in situ carcinoma of the skin. That is, the clone of cells is confined to the epidermis and has not breached the basement membrane. By contrast with actinic keratoses, in IEC the dysplasia involves the full thickness of the epidermis. One can envisage IEC as further along the pathway of carcinogenesis than an AK, and the rate of progression to SCC from IEC is judged to be much higher at around 5-10%than for AKs [1].

IEC is the result of sun exposure and therefore follows the usual risk factors. However some IEC may be the result of other carcinogenic agents such as arsenic. Histopathological confirmation of the diagnosis may be required with an incisional biopsy (that is you do not excise all the lesion, but just take a sample for histology) to assay for any invasion (and hence the presence of an SCC). All surgical samples of presumed IEC must be sent for histopathological examination. We do not have accurate incidence figures for IEC but they would appear to be less common than AKs but more common than BCCs.

The use of the term IEC and Bowen’s disease is confusing. Some AKs show full thickness dysplasia and therefore are by the definition given above are IEC (‘Bowenoid actinic keratosis’). However the term Bowen’s disease is often clinically used to refer to an area of dysplasia that has a characteristic clinical picture that resembles a plaque of psoriasis and is found on sites such as the trunk or the lower legs, most commonly in elderly women. These lesions may be quite large, up to 6cm or more, and are often well defined plaques. Although these plaques are much more common in those with greater sun exposure, it is likely that some other cofactor must play a role in their pathogenesis as their appearance and focus on the lower limbs is distinct.

Click image to enlarge

Treatment of Bowen’s disease

The usual therapeutic options are either

In the UK this is probably the order of preference of therapy. More advice on management of Bowen’s disease is given in the next chapter.

Basal cell carcinoma (BCC)

Basal cell carcinomas are keratinocyte tumours that histologically resemble basal cells but the exact keratinocyte subset that gives rise to them is not known [1]. There are no known precursors of BCC. AKs and IEC are not precursors of BCC, but of course people who have had AKs or IEC are at increased risk of BCC because all these diseases relate to prior UVR exposure.

Vignette

The typical BCC measures less than 1 cm across, has a pearly edge surrounding a small ulcer and shows prominent telangiectasia, and is located on the middle third of the face. They often present as lesions that start off very small and are noticed by the patient to be a cut that doesn’t heal before steadily growing larger. They may appear over a matter of months or be present for many years growing only very slowly.

Click image to enlarge

Epidemiology

BCCs are the commonest human cancers in those with pale skin with an incidence of approximately 100/100,000 in Northern Europe. The median age of cases is 67, and the sex incidence is equal. BCC incidence increases with age, and they are much more common in those with pale skin who have lived in areas with high ambient UVR.

BCC are most common on the middle third of the face, but are found on other sun exposed sites too such as the scalp, back, legs and arms. Very (very) rarely they occur on sun protected sites such as the genitalia or buttocks. BCCs on less frequently affected sites are often harder to diagnose as they tend to look atypical.

The majority of patients who present with BCC will have no risk factors beyond being relatively pale skinned and exposure to UVR. There are however certain additional risk groups.

BCC Behaviour: invade but ‘never’ metastasise

Basal cell carcinomas are unique in the sense that whereas they are invasive they virtually never metastasise [3]. Although metastasis is so rare, that they are invasive still means that not only can they invade the dermis but they can grow down and (for instance) invade cartilage, or the orbit, and track down nerves such as the supraorbital nerve. Their familiarity to doctors should not hide the fact that in a minority of cases cause significant morbidity and, very rarely, even death.

Not all BCC look the same

Dermatology would be much easier to learn if all instances of a particular diagnosis looked the same, but this is not the case. Remember not all patients with ischaemic heart disease present the same way either. For BCC whilst there may be a continuum of appearances there are various clinical pathological subtypes that are clinically useful, and influence management. Some examples include:

Click image to enlarge

Treatment of BCC

Confirmatory histopathology is required in virtually all cases. BCC cannot always be reliably distinguished from a number of related tumours (especially appendageal tumours [4]). The treatment of choice is excision with a 4mm margin. There are however some caveats to add to this simple statement, as some may be treated with curettage or even cryotherapy. Therapy is discussed in detail in the following chapter.

Squamous cell carcinoma (SCC)

Squamous cell carcinomas are keratinocyte tumours that appear on histological grounds to be more differentiated than BCC in they appear histologically nearer to terminally differentiated keratinocytes than basal cells. It is a frequent mistake to believe that this means that they are derived from the terminally differentiated cells above the proliferative compartment in the epidermis—this cannot be the case, as these cells being terminally differentiated, have lost the ability to divide and therefore cannot give rise to malignant clone. As with so much dermatology, nomenclature reflects morphology rather than ontogeny.

Clinical Vignette

The typical SCC is a keratinising nodule that may be ulcerated or show excess keratin formation. They are often referred to as ‘ugly’ and ‘untidy’ looking. Given their relation with high levels of cumulative UVR exposure the surrounding skin may show many features of photodamage including dermal atrophy, dyspigmentation, and an increased variations in skin vasculature. They vary in size from ~5mm up to 6cm or greater. Some poorly differentiated SCCs appear to have lost their ‘keratinising’ appearance and resemble a piece of raw steak or jam on the skin’s surface.

Click image to enlarge

Epidemiology

SCC are less common than BCC with an incidence of around 20:100,00 in Northern Europe, with a median age of 75. They are more common in men than women (3:2). SCC are most common on the sites that receive the largest amount of cumulative UVR such as the tops of the ears, face and back of hands. Their body site distribution therefore is identical to that of AKs, which are precursors of SCC, but different from BCCs and, as we shall learn, different from melanomas.

Most patients will have no risk factors except relatively pale skin and sun exposure. There are however a number of other risk factors:

Clinical behaviour

SCC are both invasive and capable of metastasising and therefore of causing death. As a general rule SCCs of sun exposed skin are less aggressive than SCCs of other keratinocyte derived tumours such as the SCC of the cervix or mouth or oesophagus. The reason for this is unclear. Actinic keratoses and Bowen’s disease are precursors of SCC.

Treatment of SCC

SCC should be excised with a margin of normal tissue of 4-6 mm. This might mean that flaps or grafts are required (discussed in the next chapter)

Keratoacanthomas

Keratoacanthomas are biologically fascinating lesions in that they look like SCC both clinically and histologically, but their behaviour is radically different — after a period of rapid growth they regress leaving an unsightly scar [1]. Their clinical importance is therefore that they are easily confused with a fast growing SCC, so much so, that many of us believe they cannot be reliably distinguished on clinical appearance alone, and instead should be treated as SCCs until proved otherwise.

Clinical Vignette

Keratoacanthomas tend to grow very quickly over a period of 6-8 weeks attaining a size of 2-6cm or even larger. They resemble a volcano with the central plug comprising keratin within a symmetrical and smooth cylindrical shoulder. They are most common on sun exposed sites. However, unlike SCC they involute without any treatment. They do not metastasise. When they do disappear they tend to leave an unsightly scar.

Click image to enlarge

We do not have accurate incidence figures for KAs but they are less common than SCCs and are more common in the usual high risk groups (sun sensitive skin and high UVR exposure).From a clinical (rather than biological) perspective the main issue is distinguishing keratoacanthomas from SCCs. The short rapid growth is a clue as is the typical ‘volcano’ morphology. However, both these features can be seen in SCC which are more common than keratoacanthomas; the problem is that not treating a SCC is a worse offence that overtreating a keratoacanthoma. In practice the fact that keratoacanthoma heal leaving an unsightly scar suggests that keratoacanthoma should be excised as though they were SCC. This approach is bolstered by the fact that for a histopathologist to diagnose a keratoacanthoma with confidence, an incisional biopsy needs to be across the whole lesion (rather than say an incisional punch biopsy). In the majority of instances the appropriate management is therefore to manage as for SCC with excision.