Basal cell carcinoma

Abstract

Basal cell carcinomas are the most common of all skin cancers, but are often overlooked, perhaps in the wake of increased public awareness of the dangers posed by malignant melanoma. The incidence has been increasing rapidly, adding to the workload of an already stretched primary and secondary care service. A better understanding of how these slow-growing lesions present and behave may help GPs to feel more comfortable managing patients in primary care.

Clinical case scenario

A 60-year-old retired oil rig diver attends for a well-man check. At the end of the consultation he asks you to look at a lump he has on his cheek close to his nose. He first noticed it around 18 months ago when washing his face. It has not changed noticeably in that time and has never caused him any bother; he just thought to ask about it in passing. On closer inspection you note he has fair skin and a raised, flesh-coloured lesion with rolled edges about 5 mm in diameter with surrounding telangiectasia. You decide to inspect the rest of his skin and find a similar lesion on the right side of his neck. Lymph node examination is normal.

Epidemiology

Basal cell carcinomas (BCCs) are an extremely common form of non-melanoma skin cancer (NMSC), accounting for around 80% of all skin cancers worldwide (Primary Care Dermatology Society (PCDS), 2011). With nearly 2% of all GP appointments being booked to review skin lesions, they are a common finding in primary care (National Institute for Health and Care Excellence (NICE), 2010).

Primary care will have to deal with an increased demand for skin cancer services. Incidence rates for NMSC have risen by at least 166% since the 1990s, and are expected to continue to increase until the year 2030 (Cancer Research UK, 2020a). A number of lifestyle factors have contributed to this increase, and an increase in the presentation of BCCs in a younger population. Such factors include more frequent travel to sunnier climates and the pursuit of a tan (Cancer Research UK, 2020a; NICE, 2010).

BCCs are more common in men and in the elderly (NICE, 2010). However, anyone can develop a BCC and the lifetime risk is between 23 and 39% (PCDS, 2011). However, there are difficulties obtaining reliable data on NMSCs and the actual numbers are likely to be much higher. The reasons for this observation are varied, for example, when multiple lesions in the same patient are recorded as a single lesion (NICE, 2010).

Each year 880 000 referrals are made to secondary care in the UK, many related to skin cancer (Elective Care Transformation Programme, 2019). There is an opportunity for GPs with an interest to work with their dermatology colleagues to offer a more comprehensive ‘skin’ service within the community. This could reduce hospital waiting times, remove the inconvenience for patients of a hospital visit and free up hospital appointments for more complex skin conditions.

History

BCCs are often referred to as ‘rodent ulcers’. This was first used as early as 1827 by an ophthalmologist in his article ‘Observations respecting an ulcer of peculiar character which attacks the eyelids and other parts of the face’ (Jacob, 1827).

Anatomy and physiology of the skin

The skin (integumentary system) is a massive organ with a large surface area from which BCCs can develop. It provides a physical barrier to the outside world, protects from the effects of ultra-violet (UV) radiation, helps in the production of vitamin D and plays a significant part in our interaction with the outside world, including in how the world perceives us. It is made up of the epidermis, dermis, and hypodermis, each with its own characteristics and function. The epidermal layer, which is the most superficial layer has the biggest role in the origin of these skin cancers and is worth further consideration.

Epidermis

The epidermis is largely made up of keratinocytes at different levels of maturation; it can be divided into four different layers based on levels of maturation: Stratum basale (basal cell layer), stratum spinosum, stratum granulosum and stratum cornicum.

The basal cells begin their journey in the stratum basale as small cuboidal cells with large nuclei. These cells move through the layers as they mature, with newer cells pushing them towards the more superficial stratum cornicum. As this happens the cells change, becoming flattened and devoid of a nucleus and other organelles, with lots of aggregated keratin taking up the space that is left (National Cancer Institute, 2020).

Pathogenesis

The term BCC derives from a histological similarity to the basal cell. The exact origin, of BCCs, however, is unknown, but thought to be somewhere within the epidermis and associated appendages.

There is no single genetic mutation identified as the cause of BCCs. The ‘hedgehog’ cellular signalling pathway has, however, been shown to be involved in the majority of cases (Tanese, 2019).

BCCs rarely metastasise, a feature which differentiates them from other forms of skin cancer. Metastases occur in less than 0.55% of BCCs, with the most common sites being lymph nodes, lungs, bone and other locations in the skin (Piva de Freitas et al., 2017). Although BCCs rarely metastasise, left untreated they can spread through soft tissue planes, becoming locally invasive and destroying local tissues and the underlying skeleton (PCDS, 2011).

Risks and associations

UV radiation exposure

UV radiation is thought to be the main causative agent for the cellular mutation leading to the development of BCCs. The mutation of a PATCH gene (tumour suppression receptor protein) and mutation of the p53 gene lead to loss of function of their associated proteins and ultimately their tumour suppression activity (Bakshi et al., 2017; Tanese, 2019).

UV radiation is also the strongest risk factor for the development of a BCC, being the cause in up to 90% of fair-skinned people. Up to one third of people actively seek to exploit the effects of UV radiation, through natural and artificial means, to obtain a tan (Cancer Research UK, 2020b). The proportion in the young is even larger, helping to explain the rising incidence in this age group. Exposure to artificial UV light at a young age has a profound effect on risk. The increase in risk with first use of a sun bed before the age of 25 is as high as 40%, and use at any age when compared with those who have never used a sun bed has shown to increase risk by 29%. A side effect of sun bed use is increased episodes of sunburn; people who burn and never tan are twice as likely to develop a BCC (Cancer Research UK, 2020b). The risk of developing a BCC is 43% higher in those exposed to UV radiation with an outdoor occupation and higher still in those living closer to the equator (Cancer Research UK, 2020b).

Age and sex

In general, BCCs are more common in an elderly population and in males. However, growth has been seen over time in the incident rates of younger age groups, particularly in females. This is thought to be due to the increase in travel to sunnier climates, an increase in outdoor activities and an increase in the proportion of individuals wishing to acquire a tan (Flohil et al., 2013).

Phenotypical factors

Features such as hair and eye colour, skin type and moles/freckles have marked effects on risk. Those with skin type 1 and 2 who have lighter hair and eye colour, fairer skin and more moles and freckles have a 70% greater risk of developing a BCC in comparison with those with skin type 3 and 4 who have darker features. This is most probably as a result of the susceptibility to damage from UV radiation in those who hold these characteristics (Cancer Research UK, 2020b).

Inherited conditions

A number of inherited syndromes are associated with an increased number of BCCs such as Gorlin–Gaultz syndrome and Xeroderma Pigmentosum that cause increased sensitivity to UV light (Joshi et al., 2012; Lehmann et al., 2011)

Gorlin–Gaultz syndrome (basal cell naevus syndrome) is an autosomal dominant condition linked with the development of a large number of early onset BCCs. It is also associated with a number of other abnormalities involving the skeletal, ophthalmic and neurological systems. It occurs as a result of a mutation in the PATCH gene (see above). Fortunately, it is rare, affecting up to 1 in 50 000 to 1 in 150 000 people worldwide (Joshi el al., 2012).

Past medical history

Psoriasis doubles the risk of BCC. It is strongly associated with the use of P (Psoralen) UVA treatment, increasing with cumulative dose (Pouplard et al., 2013). A solid organ transplant and the subsequent use of immunosuppressants increases the risk of developing a BCC, especially with older age, male sex and a past history of skin cancer (Stasko and Hanlon, 2020).

Family history

A family history of skin cancer of any type increases risk. It also increases the risk of developing a BCC at a younger age, especially if the relative was under the age of 50 at the time of diagnosis and/or there is a family history of both malignant melanoma (MM) and NMSC (Berlin et al., 2015). In those with a family history of MM the increase in risk can be as great as 27% (Wei et al., 2019).

Presentation

Lesions typically develop on areas that receive exposure to UV radiation. The face, chest and back are the most common sites. Typically, BCCs grow very slowly and may have even been present for many years before presentation.

The physical appearance can vary depending on subtype, but typically a skin-coloured nodule that occasionally bleeds, does not heal and has grown slowly should raise suspicion. The spontaneous bleeding can lead to a bloody crust, which can help to differentiate it from actinic keratoses and squamous cell carcinomas that more typically develop a characteristic keratinised crust (PCDS, 2011). There are a number of histological variants of BCC; however, it can be broadly grouped into four subtypes based on shared characteristics.

Nodular

Nodular BCCs are the most common variant, accounting for 60 to 80% of cases and are most commonly found on the skin of the head and neck. These are nodular and flesh-coloured with pearly rolled edges. There may be peripheral and/or superficial telangiectasia. The central portion can appear depressed and ulcerated, features that lead to the term rodent ulcer. An example of a classic BCC can be seen in Fig. 1. A cystic pattern can develop, in which multiple nodules can be found at the periphery of a central lesion filled with mucinous material and are soft to touch. As it grows it can become more irregular and if pigmented, lesions can resemble melanoma (known as nodular-pigmented BCC) (Dourmishev et al., 2013).

Figure 1.

Nodular BCC.

Superficial

Superficial BCCs account for between 10 and 30% of BCCs and occur not only on the skin of the trunk, but also on the face. These are well-defined, erythematous and scaly patches that can have slightly raised borders, and are easily confused with dermatitis. A superficial BCC can be seen in Fig. 2. Erosions on the surface can occur as it grows, as well as areas of regression which present as pale fibrotic areas within the lesion (Dourmishev et al., 2013).

Figure 2.

Superficial BCC.

Superficial BCCs can often spread to form skip lesions. When resected, due to these lesions a large amount of tissue has to be removed, leading to large defects. Combined with a high recurrence rate these BCCs need more urgent attention, especially if on the face or neck. They are more common in women and a younger age group (Mina et al., 2013).

Morphoeic

Morphoeic BCCs are an uncommon, but aggressive, subtype that accounts for up to 6% of BCCs. Morphoeic BCCs demonstrate infiltrative spread, both deeply and laterally, and can cause significant damage, especially on the face where they most commonly occur (Marsh et al., 2008).

Presenting as a subtle, depressed, flesh-coloured, ill-defined plaque these can easily be mistaken for scar tissue, seen in Fig. 3. Ulceration and bleeding are uncommon with this subtype, but this can happen as lesions get larger (Mackiewicz-Wysocka et al., 2013).

Figure 3.

Morphoeic BCC.

Basosquamous

Basosquamous BCCs are a concerning, but fortunately rare, subtype displaying features of both BCC and squamous cell carcinoma (SCC). Basosquamous BCCs commonly affect the head and neck, with the nose, the ear and the area around the ear being the sites most often affected. They presents non-specifically (seen in Fig. 4) and infiltrate more deeply than other subtypes. A higher metastatic potential and a higher local recurrence rate prompt referral and diagnosis through biopsy is necessary (Lima et al., 2012).

Figure 4.

Basosquamous BCC.

Assessment

Patients are often concerned about the possibility of MM when they notice a lesion on their skin. It is through history and examination that the clinician can identify features that make either BCC or MM a more likely diagnosis.

First, identifiable from the history, BCCs typically grow more slowly than MM or SCC. There may have been little change in the lesion since it was first noticed.

When examining the lesion, it is important to look for the individual characteristics of both BCC and MM. Stretching the skin, known as the stretch test, can highlight the pearly rolled edges of a BCC. Any irregularities or asymmetry in shape, colour or outline should raise suspicion of MM. Following examination of the lesion in question or if the patient is considered to be at high risk then a full body examination is recommended so that further BCCs and other skin cancers can be detected. It is important to examine patients in a room with good lighting looking first in the areas of high risk before moving on to the rest of the body in a systematic way, ensuring full coverage. Any suspicious lesion with features of BCC or MM warrants closer inspection with a dermoscope. Use of a dermoscope requires adequate training and familiarity with use (Schwarz, 2018).

Dermoscopy

Dermoscopes are capable of impressive magnification of up to x100. This magnification enables the user to see more detail; in addition oil immersion can be used to get a clearer view. The devices of today often have attachments that enable photographs to be taken.

Through pattern recognition, characteristics of different lesions can be identified, helping to differentiate BCC from MM. Features that can help to identify MM have been found and are based on pigmentation networks, for example, irregular distribution of colour into blotches and globules and vascular patterns. For the identification of BCC to be made, an absence of these features is needed. Positive features of BCC include arborising (branch-like) blood vessels; blue-grey dots, globules and ovoid nests; spoke wheel structures; maple-leaf like areas; erosions and ulceration, amongst others. These features are shown below in Fig. 5.

Figure 5.

Dermoscopic features of BCC.

A Cochrane review of the subject looked at 11 studies with data on over 11 500 lesions and found dermoscopy to be more accurate for both identification and exclusion of other diagnoses. Through training and wider use in primary care, more people may be referred appropriately and others (Dinnes et al., 2018).

Management in primary care

There is the potential for GPs to manage some BCCs in primary care. Low-risk BCCs (detailed in Box 1) can be managed by GPs with a specialist interest in skin lesion management, now known as GPs with an extended role (GPwER). These GPs must participate in local multi-disciplinary teams, audit and continue to show evidence of continued professional development in this area.

Box 1.

Low-risk BCC.

Patient Not: • 24 years or younger in age • Immunosuppressed/gorlins Lesion is: • Above clavicle • Less than 1-cm diameter with clear margins • Not recurrent following incomplete excision • Not persistent following excision • Not morphoeic, infiltrative, basosquamous • Not over important structures • Not in an area where closure may be difficult • Not in an area where difficult excision may lead to poor cosmesis • Not in a site where cosmesis important Adapted from NICE (2010)

For the majority of BCCs, appropriate referral is needed to secondary care. Low-risk lesions do not need to be referred under a 2-week cancer pathway and can be referred routinely. However, if lesions are close to important facial structures then a referral to be seen within 6 weeks is appropriate. For lesions with any characteristics that make the diagnosis of a BCC difficult, such as concerning pigmentation or signs of SCC then a 2-week referral should be considered (NICE, 2010).

Confirming diagnosis

Histological examination is needed to confirm diagnosis. There are a number of options available to obtain a tissue sample. Punch biopsies are a simple procedure that can offer both diagnosis and treatment for lesions 10 mm in diameter or under. As a defect is left, closure is needed, and therefore, scarring is left, which is less than ideal in cosmetically sensitive areas. Shave biopsies are an alternative in these areas, but do not give the potential for cure in the way that punch biopsies can offer (Schwarz, 2018).

There are a number of techniques in development that may enable diagnosis without removal of tissue. Improvements in imaging technologies raise the possibilities of using light and the way it interacts with skin tissue to show characteristics consistent with BCC. This has the potential to speed up the time between presentation and treatment and avoid the need for biopsy (Balu et al., 2015).

Treatment

Excision

Excision is the most appropriate initial treatment for most types of BCC. The excision should include margins of normal tissue. A 4-mm margin is usually sufficient for lesions less than 20 mm in diameter and will result in cure in 95% of cases without the need for re-excision (Schwarz, 2018).

Depending on the size of the lesion this can leave a large defect that can be difficult to close with primary closure. Flaps or grafts require the skills of a plastic surgeon or with advice from an experienced dermatologist and this explains why not all can be removed in primary care.

Curettage and cautery

Curettage and cautery (C&C) is an option for small, low-risk lesions. Lesions go through three cycles of C&C in one session (Schwarz, 2018). Treatment using this method is not suitable for larger, more aggressive BCCs, as recurrence rate in these is up to 27% (Blixt et al., 2013).

Cryotherapy

Cryotherapy is another option for low-risk lesions, using liquid nitrogen directly applied to lesions. This results in the cells of the lesion necrosing, the formation of a blister underneath and then subsequent healing of the area in a number of weeks. It can result in scarring or hypopigmentation, and therefore, may not be suitable for those concerned with cosmesis. Recurrence rates when used effectively are typically quite good, with recurrence rates as low as 8% at 5 years (Asai, 2020; Telfer et al., 2008).

Topical therapies

Imiquimod is an immune response modulator that results in an inflammatory reaction, and as such local skin irritation should be expected. It can be used for low-risk superficial lesions and when there are concerns about surgical intervention. It is applied once a day for at least 6 weeks. When used in this way for superficial lesions, it can result in a good cure rate of 84% (Asai, 2020). Recurrence rates have been shown to be much lower with lesions <0.4 mm in depth in comparison with those >0.4 mm, highlighting its suitability for superficial lesions only (Asai, 2020).

Fluouracil is a topical antimetabolite that results in the necrosis of tumour cells when applied. It can cause a significant inflammatory reaction that can be difficult to tolerate, and exposure to the sun must be limited during use. It is applied twice daily for about 6 weeks. Care must be taken when applying to lesions near the eyes and mouth, due to increased sensitivity of the skin and risk of scarring. It can be used for small superficial BCCs, however, it does have a high recurrence rate and there are some concerns that recurrences may be more aggressive (Asai, 2020).

Photodynamic therapy

Photodynamic therapy is a technique where a photosensitising agent, such as methyl aminolevulinate cream, is applied to a lesion before it is exposed to light, causing an inflammatory reaction. It is not as good as surgical excision or imiquimod in treating the lesions, and when used for nodular BCC can have poor outcomes, with cure rates reported as low as 10%. For this reason, it is best used for the treatment of superficial, low-risk BCCs. It does, however, result in good cosmetic outcomes (Asai, 2020).

Mohs microsurgery

A technique first developed in the 1930s by Frederick Mohs, uses slices of tissue examined under a microscope to identify where further resection is required.

It is used when lesions are high risk or when they have been incompletely excised, with the aim of preserving as much healthy tissue as possible. It also enables high cure rates with only a 0–2.5% rate of recurrence. Unnecessary tissue excision is prevented, resulting in easier closure and better cosmetic results (Asai, 2020).

Radiotherapy

Radiotherapy can be used as primary treatment or as an adjunct. When used as a primary treatment it is often because the patient is not a suitable candidate for surgery, due to age or other comorbidities, and the lesion has a high risk of recurrence (Asai, 2020). It is effective in treating primary lesions with cure rates up to 96% quoted for the lowest risk lesions. It also has the benefit of relative sparing of normal tissue, and as a result may preserve important structures and provide good cosmetic outcomes. It does, however, have side effects such as erythema, skin damage, pain and infection. In the long term, permanent alopecia in the area occurs, radiation-associated dermatitis may result, and there is a risk of more aggressive recurrence or development of new malignancy, particularly in areas that are already exposed to UV radiation. Patients have to attend on multiple occasions, which can be a barrier for some patients, for example, those with mobility or transport difficulties (Asai, 2020).

Prevention

Reduction of UV radiation exposure is the best way to reduce the risk of BCC, with an aim to limit lifetime cumulative damage. This can be done through the use of sunscreen with a high sun protection factor (SPF) and protection from the sun with clothing including glasses and hats. Use of broad-spectrum high SPF sunscreen is particularly beneficial; use in children can reduce UV damage and subsequent neoplasm by around 80% (Asai, 2020). Other ways to reduce risk of UV damage are to avoid prolonged exposure to the sun, exposure to high-intensity sunlight and sunbed use. Oral nicotinamide (vitamin B3), obtainable over the counter, may help to reduce the incidence of BCCs in those at high risk, with one study showing the rate of new NMSC being reduced by 23% compared with placebo at 1 year (Starr, 2015).

Summary

The number of cases is rising and new BCCs are going to be seen more frequently in primary care. Through knowledge, experience, examination and dermoscopy, GPs are in a prime position to tackle this rise in cases head on. Unfortunately, the study of dermatology is often neglected in medical school and few trainees are lucky enough to spend time in the speciality during their training. Consequently, few are afforded the opportunity to develop an interest in dermatology at trainee level. How to use a dermoscope is not therefore learned, and the knowledge and experience needed to treat these lesions is equally missed. Courses from a number of providers are available to learn about the management of skin lesions and use of the dermoscope. However, continued practice and experience is needed and dermoscopes are unfortunately expensive, posing a large financial commitment on the individual clinician. Practices may wish to consider the purchase of a dermoscope for shared use. This will enable continued development of skills and confidence in the management of BCCs. Also, the ease of access may spark an interest in those who have not used one before.

BCC is a slow growing cancer that, more often than not, can be completely treated without long term harm to patients. The measures discussed above provide the opportunity to reduce referral to secondary care and provide complete treatment in primary care. This has the potential to improve patient satisfaction and reduce strain on the wider health economy.

KEY POINTS

BCCs (‘rodent ulcers’) are slow growing skin cancers

BCCs are less aggressive than other skin cancers, but can cause significant local damage if left untreated

Dermoscopy can be used to identify BCCs and differentiate them from other benign and cancerous lesions

Different treatment options are available depending on the type of BCC, the site of the lesion, the age of the patient and patient choice

Surgical management is usually the best treatment option

With appropriate training, low-risk lesions can be managed or removed in primary care without the need for onward referral

Footnotes

Acknowledgement

Acknowledgement to Dr John Forgie for the support given and interest in dermatology gained.

ORCID iD

Dr Luke Alexander Paterson

References

Aasi SZ (2020) Treatment of basal cell carcinomas at low risk for recurrence. Available at: www.uptodate.com/contents/treatment-and-prognosis-of-basal-cell-carcinoma-at-low-risk-of-recurrence (accessed 25 June 2020).

Bakshi

Chaudhary

Rana

, et al.(2017) Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond. Molecular Carcinogenesis 56(12): 2543–2557. DOI: 10.1002/mc.22690.

Balu

Zachary

Harris

, et al.(2015) In vivo multiphoton microscopy of basal cell carcinoma. JAMA Dermatology 151(10): 1068–1074. DOI: 10.1001/jamadermatol.2015.0453.

Berlin

Cartmel

Leffell

, et al.(2015) Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype. Cancer Epidemiology 39(6): 1078–1083. DOI: 10.1016/j.canep.2015.09.005.

Blixt

Nelsen

Stratman

(2013) Recurrence rates of aggressive histologic types of basal cell carcinoma after treatment with electrodesiccation and curettage alone. Dermatologic Surgery 39(5): 719–725. DOI: 10.1111/dsu.12122.

Cancer Research UK (2020a) Non-melanoma skin cancer incidence statistics. Available at: www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-melanoma-skin-cancer/incidence#headin https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-melanoma-skin-cancer/incidence#heading-Twog-Two (accessed 10 June 2020).

Cancer Research UK (2020b) Non-melanoma skin cancer risk factors. Available at: www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-melanoma-skin-cancer/risk-factors (accessed 13 June 2020).

Ciążyńska

Narbutt

Woźniacka

, et al.(2018) Trends in basal cell carcinoma incidence rates: A 16-year retrospective study of a population in central Poland. Advances in Dermatology and Allergology. 35(1): 47–52. DOI: 10.5114/ada.2018.73164.

Dinnes J, Deeks JJ, Chuchu N, et al. (2018) Visual inspection and dermoscopy, alone or in combination, for diagnosing keratinocyte skin cancers in adults. Cochrane Database of Systematic Reviews 12: art. no.: CD011901. DOI: 10.1002/14651858.CD011901.pub2.

10.

Dourmishev

Rusinova

Botev

(2013) Clinical variants, stages, and management of basal cell carcinoma. Indian Dermatology Online Journal 4(1): 12–17. DOI: 10.4103/2229-5178.105456.

11.

Elective Care Transformation Programme (2019) Transforming elective care service: Dermatology. Available at: www.england.nhs.uk/wp-content/uploads/2019/01/dermatology-elective-care-handbook-v1.pdf (accessed 23 August 2020).

12.

Flohil

Seubring

van Rossum

, et al.(2013) Trends in basal cell carcinoma incidence rates: A 37-year Dutch observational study. Journal of Investigative Dermatology 133(4): 913–918. DOI: https://doi.org/10.1038/jid.2012.431.

13.

Jacob

(1827) Observations respecting an ulcer of peculiar character which attacks the eyelids and other parts of the face. Dublin Hospital Report 4: 231–239.

14.

Joshi

Deshmukh

Golgire

(2012) Gorlin-Goltz syndrome. Dental Research Journal (Isfahan) 9(1): 100–106. DOI: 10.4103/1735-3327.92963.

15.

Lehmann

McGibbon

Stefanini

(2011) Xeroderma pigmentosum. Orphanet Journal of Rare Diseases 6: 70-Available at: https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-6-70.

16.

Lima

Verli

de Miranda

, et al.(2012) Basosquamous carcinoma: Histopathological features. Indian Journal of Dermatology 57(5): 382–383. DOI: 10.4103/0019-5154.100489.

17.

Mackiewicz-Wysocka

Bowszyc-Dmochowska

Strzelecka-Weklar

, et al.(2013) Basal cell carcinoma – diagnosis. Contemporary Oncology (Pozn) 17(4): 337–342. DOI: 10.5114/wo.2013.35684.

18.

Marsh

Dickinson

Neill

, et al.(2008) αvβ6 integrin promotes the invasion of morphoeic basal cell carcinoma through stromal modulation. Cancer Research 68(9): 3295–3303. DOI: 10.1158/0008-5472.CAN-08-0174.

19.

Mina

Picariello

Fewkes

(2013) Superficial basal cell carcinomas of the head and neck. Dermatologic Surgery 39(7): 1003–1008. DOI: 10.1111/dsu.12178.

20.

National Cancer Institute (2020) Layers of the ski: SEER training modules, U. S. National Institutes of Health, National Cancer Institute. Available at: https://training.seer.cancer.gov/melanoma/anatomy/layers.html (accessed 13 June 2020).

21.

NICE (2010) Improving outcomes for people with skin tumors including melanoma (update). Available at: www.nice.org.uk/guidance/csg8/resources/improving-outcomes-for-people-with-skin-tumours-including-melanoma-2010-partial-update-pdf-773380189 (accessed 10 June 2020).

22.

PCDS (2011) Basal cell carcinoma – an overview. Available at: www.pcds.org.uk/clinical-guidance/basal-cell-carcinoma-an-overview (accessed 10 June 2020).

23.

Piva de Freitas

Senna

, et al.(2017) Metastatic basal cell carcinoma: A rare manifestation of a common disease. Case Reports in Medicine 2017: 8929745-DOI: 10.1155/2017/8929745.

24.

Pouplard

Brenaut

Horreau

, et al.(2013) Risk of cancer in psoriasis: A systematic review and meta-analysis of epidemiological studies. Journal of the European Academy of Dermatology and Venerology 27(S3): 36–46. DOI: 10.1111/jdv.12165.

25.

RCGP. Clinical topic guide: Dermatology. Available at: www.rcgp.org.uk/training-exams/training/gp-curriculum-new/clinical-topic-guides/dermatology.aspx (accessed 08 December 2020).

26.

Saàdani

Baybay

ElMahi

, et al.(2018) Basosquamous carcinoma: Report of two cases and review of literature. International Journal of Cancer and Clinical Research 5(1): 093-DOI: 10.23937/2378-3419/1410093.

27.

Schwartz RA (2018) Basal cell carcinoma. Available at: https://bestpractice.bmj.com/topics/en-gb/269 (accessed 25 June 2020) DOI: 10.1016/j.jaad.2017.10.007.

28.

Starr

(2015) Oral nicotinamide prevents common skin cancers in high-risk patients, reduces costs. American Health and Drug Benefits 8(Spec Issue): 13–14. DOI: 10.1016/j.jaad.2017.10.007.

29.

Stasko T and Hanlon AM (2020) Epidemiology and risk factors for skin cancer in solid organ transplant recipients. Available at: www.uptodate.com/contents/epidemiology-and-risk-factors-for-skin-cancer-in-solid-organ-transplant-recipients (accessed 25 June 2020).

30.

Tanese

(2019) Diagnosis and management of basal cell carcinoma. Current Treatment Options in Oncology 20(2): 13-DOI: 10.1007/s11864-019-0610-0.

31.

Telfer

Colver

Morton

, et al.(2008) Guidelines for the management of basal cell carcinoma. British Journal of Dermatology 159(1): 35–48. DOI: 10.1111/j.1365-2133.2008.08666.x.

32.

Wei

Nan

(2019) Having a first-degree relative with melanoma increases lifetime risk of melanoma, SCC and BCC. Journal of the American Academy of Dermatology 81(2): 489–499. DOI: 10.1016/j.jaad.2019.04.044.