The Nonmelanoma Skin Cancer Biology Essay


Skin cancers mainly arise from the epidermis in the form of basal cell carcinoma or Squamous cell carcinoma (SCC) both can be categorised as non-melanoma skin cancer (NMSC). NMSC is the most common skin cancer diagnosed in the white population worldwide. Skin cancer may also arise from the melanocyes causing malignant melanoma (MM). Malignant melanoma has a high metastatic potential and its incidence is increasing more than any other cancer. (Ogden and Telfer 2009).

Nonmelanoma Skin Cancer

There is a 30% risk for Caucasians to develop BCC in their lifetime, with BCC being four times more frequent than SCC. (Ridky 2007). The incidence of NMSC has increased over the past 20 years in the USA and many European countries. This increase may be related to increased exposure to UV light, the fact that the population is living longer and enhanced cancer detection from improved education and screening. (Marks 1995) . "Whilst metastasis from BCC is extremely rare, metastasis from high-risk SCC may be fatal". (Samarasinghe and Vishal 2012)

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The skin of the head and neck is then most common site of presentation, accounting for more than 80% of all diagnosed cases. BCC normally presents itself as a pearly nodule with rolled edges; the lesion can ulcerate and become crusted. SCC tends to present as rapidly growing pink or red nodules. SCC usually produces keratin and can produce a keratin horn; this horn is a way or identifying a SCC. (Samarasinghe and Vishal 2012)

A biopsy is the only way to determine if the abnormal cells are cancerous. The histopathology report should confirm the type of skin cancer and how differentiated the cells are from the original tissue i.e. the grade. Once the diagnosis has been confirmed the cancer needs to be staged. In the UK the TNM system is used please refer to figure1 in the appendix for a full explanation of the TNM system for NMSC.

The chances of a BCC to metastasize are slim, so assessment of lymph nodes is only needed in extreme cases. Regional lymph nodes should be examined in all cases of SCC. Particular attention should be given to SCC of the lips, ears and genital areas. Furthermore lymph nodes should be given a thorough assessment in cases arising in sites of chronic ulceration/inflammation or areas of previous radiotherapy treatment.

Magnetic resonance or CT imaging may be helpful in the planning of treatment, especially in tumours involving major nerves, Lymph nodes, bones or parotid glands as damage to these structures could lead to debilitating conditions. (Jennings and Schmults 2010)

Management of NMSC

A randomised control trial conducted by (Smeets et al. 2004) compared the treatment of primary and recurrent BCC's with Moh's Micrographic Surgery (MMS) and surgical excision (SE). Fewer recurrences were seen when treated with MMS than SE; however the results were not statically significant, nevertheless treatment of recurrent BCC's with MMS showed to be significantly more effective than SE.

For aggressive tumours MMS seems to be the gold standard. A comprehensive study by (Paoili et al. 2011) looks at the treatment of 587 BCCs with MMS, 56% were primary aggressive BCCs and the remaining 44% were recurrent BCCs. The 5-year recurrence rates were 2.1% form primary tumours and 5.2 for recurrent BCCs.

Cryosurgery is capable of destroying NMSCs, (Emanuel and Kufilk 2004) looked at the treatment of 3937 BCCs and 446 SCCs with cryosurgery. The majority of the lesions were small T1-T2. Kufilk reported a 5year cure rate of 99% for BCC and 100% for SCC and a combined 30-year cure rate of 98.6%. For advanced / aggressive SCC cryosurgery is not recommended for SCC. (Samarasinghe and Vishal 2012)

Occasionally surgery is not a reasonable treatment for the patient; the patient may be too ill to undertake a general anaesthetic or for cosmetic reasons a non invasive procedure is preferred.

Photodynamic therapy (PDT) is an emerging treatment that uses light sensitive compounds that when become exposed to light become toxic to target malignant cells resulting in cell death. A study by (Ikram et al. 2011) examined the effect of PDT on superficial NMSC's. Regarding BCC's a complete response was seen in 86.2% of cases with 3.5% reoccurring in the first year. SCC's had similar positive results with 81.9% showing a complete response to treatment and 11% recurring in the first year.

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Another nonsurgical treatment options is 5-Fluorouracil

There is not much information on treatment of 5-FU for the treatment of SCC but a study by (Morse et al. 2003)

This paper highlights the use of 5-FU as a possible treatment on cosmetically important locations.

However very small study size and very few studies in this area, Makes 5-FU not really sutable for SCC.

Sometimes adjuvant treatment offers a distinct advantage when treating NMSC. A study by (Marmur, Nolan and Henry 2012) suggest using Photodynamic Therapy (PDT) during MMS surgery. The tumour is excised using MMS then the light source is applied to the lesion.

Using PDT intra-operatively allows the photo sensitizer to bypass the epidermal barrier for increased absorption thus overcoming the main limitation with conventional PDT. Another advantage highlighted in this study is that PDT applied this way may destroy the microscopic undetected disease around the excised area. Patients used in the study had no reoccurrence after 18months. However there was no indication on how many patients were used therefore no statistical analysis; rendering the findings insignificant.

Radiotherapy can be used in both Adjuvant and Definitive settings for the treatment of NMSC. In a study by (Kwan, Wilson and Moravan 2004) 121 patients with SCC and 61 patients with BCC were treated with radiotherapy, only 13% of the BCC patience had reoccurrence of disease compared with 38% of SCC. This study suggests BCC's are well controlled with radiotherapy, SCC seem to have a high recurrence rate when treated with radiotherapy compared with MMS.

Due to SCC's risk of metastatic involvement to regional lymph nodes bigger margins need to be used during surgical excision; this may have significant cosmetic and functionality issues especially around the lower lip. Radiotherapy is a good choice in this instance as it maintains excellent oral function. (Kwan, Wilson and Moravan 2004)

Patients presenting with neglected T4 NMSC are an uncommon occurrence. There are some studies that show Radiotherapy can be used to help treat T4 nonmelanoma skin cancer. A study by (Matthiesen et al. 2011) looked at the use of intensity-modulated radiation therapy (IMRT) as a radical treatment for NMSC of the head and neck. Six Patients received IMRT, 4 of which had no-reoccurrence of disease. A limitation to these findings is the sample size mainly down to the atypical presentation of T4 NMSC.

If radical treatment is not suitable for the patient involved and the tumour has grown and spread to lymph regional lymph nodes. Palliative treatment is normally the suitable option. Large NMSC lesions can cause a lot of painful and troubling symptoms. Discharge and bleeding can be difficult to control and the odour from a necrotic tumour can be unpleasant. The aim of a study by (Barnes et al. 2010) was to look at the efficacy of radiotherapy as a palliative treatment for NMSC. 82% of symptomatic lesions were palliated in those patients who were available for follow up.

Organ transplant patients are estimated 65 times more susceptible to develop skin cancer compared to the general population (Jensen et al. 1999). Management of these types of patients require close attention as tumours can spread very quickly. If a patient has received an organ transplant and is facing life threatening skin cancer, decreasing immonosupprestion drugs should be considered.


Immunosupressed patients often develop multiple aggressive tumours.

A study by (McKenna and Murphy 1999) looked at the use of Acitretin to reduce the number of new tumours in renal transplant patients. Patients received low-dose Acitretin(0·3 mg/kg daily) over a 5 year period. There was a significant reduction in the number of new tumours in patients from years 1-4. However no significant results were found in year 5 due to the small sample size. Pleases refer to figure 2 in the appendix

Malignant Melanoma

Since 1999 the amount of men developing MM has increased by 43% and women by 26%. (Ogden and Telfer 2009)


Fig 1 - TNM staging for NMSC

Available from:

Figure 2

(McKenna and Murphy 1999)