Basal cell carcinoma in skin of colour
What is a basal cell carcinoma?
A basal cell carcinoma (BCC) is a keratinocytic or non–melanoma skin cancer formed by uncontrolled growth and replication of basal cells in the lower levels of the epidermis. They are sometimes referred to as rodent ulcers or basaliomas.
What is skin of colour?
Skin of colour is a subjective term referring to natural skin pigmentation ‘darker’ than white (ie, brown or black skin). When compared against a graded assessment of skin colour types such as the Fitzpatrick scale, ‘skin of colour’ may refer to skin classified as type IV or higher . In some contexts, ‘skin of colour’ is also used to describe the skin type of a non–white ethnic group including those of African, Asian, South American, Pacific Island, Maori, Middle Eastern, and Hispanic descent .
Who gets basal cell carcinoma?
BCCs are among the most commonly diagnosed cancers worldwide. BCC accounts for 65–75% of skin cancers . BCC is the most common form of skin cancer seen in Caucasians, Asians, and Hispanics. It is the second most common form of skin cancer seen in African Americans and Asian Indians .
Reported incidence rates of BCC tend to vary across different studies and time periods, although incidence rates per 100,000 across the last 50 years have been:
- 0.32–6.4 in Chinese
- 0.7–1.4 in Asian Indians
- 1–2 in African Americans
- 6 in New Zealand Maori (for non–melanoma skin cancers in general) [2–4].
Global incidence rates of BCC are increasing, and this trend is significantly more prominent in white skinned people, particularly in older age groups and in women [5,7]. Most diagnoses occur at over 50 years of age and peak at around 70–80 years of age in both men and women, regardless of skin colour .
Risk factors for BCC
BCC is more common in individuals with:
- Previous BCC or other skin cancers (squamous cell carcinoma, melanoma)
- Repeated prior episodes of sunburn
- Outdoor occupation or recreation (particularly during childhood)
- Previous cutaneous injury, thermal burn, disease (eg, cutaneous lupus, sebaceous naevus)
- Inherited syndromes: basal cell naevus syndrome (Gorlin syndrome), Bazex–Dupré–Christol syndrome, Rombo syndrome, Oley syndrome, and xeroderma pigmentosum
- Family history of nonmelanoma skin cancer
- Other risk factors include exposure to arsenic or ionising radiation, and immunosuppression due to disease or medicines .
Ultraviolet radiation exposure (sunlight) is a much more significant risk factor for BCC in white–skinned people . However, while sunlight is generally less of a risk factor in skin of colour, susceptibility to BCC varies between individuals with the same skin type depending on their ethnic origins .
What causes basal cell carcinoma?
BCC is thought to begin from an uncontrolled proliferation of basal cells in the skin following an abnormal genetic transformation, usually as a result of sun exposure as UV light damaging and mutating DNA . In addition, UV radiation suppresses the ability of the immune system to detect and destroy tumour cells. In darker skin, a higher content of UV light–absorbing melanin protects the DNA from mutation and damage.
What are the clinical features of basal cell carcinomas?
Regardless of skin colour, BCCs can occur anywhere on the skin. The most common sites are the face and ears, neck, shoulders, and back. There are various subtypes of BCC.
These are small and slow growing translucent lesions with rolled edges.
- Prominent small blood vessels (telangiectasia).
- Nodular BCC is firm with a smooth surface.
- Cystic BCC is soft with jelly–like contents.
- A so–called ‘rodent ulcer’ has central ulceration.
The most common type of BCC found in younger adults.
- Commonly found on upper trunk and shoulders.
- Slightly scaly, irregular plaque.
- Thin, translucent rolled border.
- Multiple microerosions.
Also known as morpheaform or sclerosing BCC.
- Usually found in midfacial sites.
- Waxy, scar–like plaque with indistinct borders.
- Wide and deep subclinical extension.
- May infiltrate cutaneous nerves (perineural spread).
Also known as mixed basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
- Infiltrative growth pattern.
- Potentially more aggressive than other forms of BCC.
A rare histological variant of BCC.
- Lace–like arrangement of malignant cells around connective tissue.
- Nodular or ulcerated lesions.
- Lower grade than nodular and morphoeic BCCs.
- No body site predisposition .
Fibroepithelial tumour of Pinkus
A warty plaque, usually found on the trunk.
What are the clinical features of basal cell carcinoma in skin of colour?
Diagnosis of basal cell carcinoma in skin of colour can be difficult due to their rarity and pigmentation. More than 50% of BCCs found in skin of colour are pigmented with ‘pearly’ brown or black appearance.
Nodular BCCs are the predominate subtype found, while morphoeic BCCs are rare. Adenoid BCC is more common than in Caucasians.
What are the complications of basal cell carcinoma?
Complications of BCCs may include:
- Recurrence or persistence after treatment
- New lesions
- Neglected advanced BCC
- Very rarely, metastatic BCC.
Recurrence of BCC
BCCs have an estimated 3–10% 5–year recurrence rate depending on whether the treated lesion is a primary BCC or itself a recurrence. Most recurrences are evident 4–12 months after treatment. Recurrence is more likely with:
- Incomplete excision or narrow margins at primary excision
- Morphoeic, micronodular, and infiltrative subtypes
- BCCs located on the head and neck .
The type of treatment received on a BCC can also influence recurrence rates. Higher recurrence rates (~7–10%) may be seen with all treatment methods except Mohs micrographic surgery (~1%) .
Development of new BCCs
There is a significantly increased risk of developing new BCCs after a previous one. Estimates from various studies have suggested a 3–year cumulative risk of between 30–77% for new BCC formation. Associated factors for new BCC formation may include:
- Older age
- Male sex
- Multiple non–melanoma skin cancers on initial presentation
- Truncal BCCs .
Advanced BCCs are often a result of neglect as BCCs are very slow growing tumours, often taking months to years to reach this stage. They may be several centimetres in diameter. They may infiltrate tissues below the skin and are very difficult to treat surgically.
Metastatic or invasive BCCs are rare, with an estimated occurrence rate of 0.03–0.55%. The primary BCC is often large, neglected or recurrent, located on the head and neck region. It may arise in sites exposed to ionising radiation or ones that have had multiple prior treatments. Metastatic BCCs can be fatal.
How is basal cell carcinoma diagnosed?
BCCs are diagnosed by their typical appearance clinically and on examination using a dermatoscope . The diagnosis is confirmed by incision or excisional biopsy.
In patients with advanced BCCs, it may be important to determine the depth of tumour invasion and the spread to surrounding tissue. The Union for International Cancer Control (UICC) 8th edition staging system for cutaneous carcinomas (skin cancers) is a commonly used system.
Tumour staging for cutaneous carcinomas
TX: Primary tumour cannot be assessed
T0: No evidence of primary tumour
Tis: Carcinoma in situ
T1: Tumour ≤ 2 cm without high–risk features
T2: Tumour > 2–4 cm
T3: Tumour with invasion of maxilla, mandible, orbit or temporal bone
T4a: Tumour with gross cortical bone/marrow invasion
T4b: Tumor with skull base or axial skeleton invasion including foraminal involvement and/or vertebral foramen involvement to the epidural space
Nodal staging for cutaneous carcinomas (non–head and neck)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in one local lymph node ≤ 3cm
N2: Metastasis in a single ipsilateral lymph node > 3 to ≤ 6 cm or in multiple ipsilateral nodes ≤ 6 cm.
N3: Metastasis in lymph node ≥ 6cm
What is the differential diagnosis of basal cell carcinoma?
There are several lesions that can be mistaken for a basal cell carcinoma, especially:
- Actinic keratosis
- Squamous cell carcinoma (SCC)
- Intraepidermal squamous cell carcinoma
- Seborrhoeic keratosis
- Intradermal naevus (mole)
- Sebaceous hyperplasia
- Melanocytic naevus
- Pyogenic granuloma
- Microcystic adnexal carcinoma
- Cutaneous T–cell lymphoma
- Merkel cell carcinoma
- Atypical fibroxanthoma
- Metastasis to skin.
What is the treatment for basal cell carcinoma?
Treatment options are the same, regardless of skin colour. Excisional biopsy with a 3–5mm margin is the standard and recommended treatment for most BCCs.
Smaller margins increase the risk of recurrence. Deeper incisions and more complex wound closure (flap or skin graft) may be required for larger BCCs. The removed specimen is then examined by a pathologist for a final diagnosis and disease staging .
Potential side effects of this procedure can include infection, scarring and temporary or permanent loss of sensation due to nerve severing.
Cryotherapy is the treatment of a superficial skin lesion by freezing it, usually with liquid nitrogen . It is suitable for small superficial BCCs (≤1cm) on covered areas of trunk and limbs, and not advised to treat BCCs on head, neck and knees.
- Double freeze–thaw application technique.
- Results in a blister that crusts over and heals within several weeks.
- May require wound dressing if the wound is at risk of rubbing.
Complications and side effects of cryotherapy include:
- The procedure leaves a permanent white mark.
- If applied to the back of a hand, there is a risk of damaging the underlying tendons.
- Application over a nerve involved in sensation may result in temporary numbness for weeks or months.
Shave, curettage and electrocautery
- Suitable for small, well–defined nodular or superficial BCCs.
- Lesions are usually located on trunk or limbs.
- Wound is left open to heal by secondary intention.
- Moist wound dressings lead to healing within a few weeks.
- The eventual scar quality is variable.
Mohs margin–controlled micrographic excision
Mohs micrographic controlled surgery involves removing skin tissue in successively deeper horizontal sections under local anaesthetic. Each section is examined with a microscope to identify cancerous tissue. Sections are continually removed until no cancerous tissue is identified .
- Used in high–risk areas of the face around eyes, lips, and nose.
- Suitable for ill–defined, morphoeic, infiltrative and recurrent subtypes.
- Large defects are repaired by flap or skin graft.
Mohs margin–controlled micrographic excision has very high cure rates achieved by trained dermatologists or dermatologic surgeons.
Imiquimod is a topical immune response modifying drug [9,10]. Imiquimod cream is used when surgical removal is inappropriate.
- Best used for superficial BCCs less than 2 cm diameter.
- Applied three to five times each week, for 6–16 weeks.
- Results in a variable inflammatory reaction, maximal at three weeks.
Side effects and complications of imiquimod cream include:
- Minor scarring
- Pain or itching
- Inflammatory reaction, maximal 3–4 days after procedure
5–Fluorouracil cream is a topical cytotoxic agent [9,10]. It is used to treat small superficial basal cell carcinomas.
- Requires prolonged course, eg twice daily for 6–12 weeks.
- Causes inflammatory reaction.
- Has high recurrence rates.
Side effects and complications of 5–Fluorouracil cream include:
- Inflammation and photosensitivity over the applied area is expected
- Significant pain
- Erythema multiforme
- Permanent hyperpigmentation
Photodynamic therapy (PDT) refers to a technique in which BCC is treated with a photosensitising chemical, and exposed to light several hours later [9,10].
- Topical photosensitisers include aminolevulinic acid lotion and methyl aminolevulinate cream.
- Suitable for low–risk small, superficial BCCs and thin nodular BCCs or in patients with multiple BCCs.
- Best avoided if tumour in site at high risk of recurrence.
- Results in inflammatory reaction, maximal 3–4 days after procedure.
- Treatment repeated 7 days after initial treatment.
- Excellent cosmetic results.
Side effects and complications of photodynamic therapy include:
- Pain or itching
- Inflammatory reaction, maximal 3–4 days after procedure.
Radiotherapy or X–ray treatment can be used to treat primary BCCs or as adjunctive treatment if margins are incomplete [9,10]. Radiotherapy is mainly used if surgery is not suitable. It is best avoided in young patients and in people with genetic conditions predisposing to skin cancer. The best cosmetic results are achieved using multiple fractions.
Side effects and complications of radiotherapy include:
- Inflammation and scarring over treated area is expected
- Late development of new BCCs, or BCC recurrence
What is the treatment for advanced or metastatic basal cell carcinoma?
Advanced or metastatic BCCs require multidisciplinary consultation. A combination of treatments may be used including:
- Targeted therapy using hedgehog signaling pathway inhibitors such as vismodegib.
What is the recommended follow-up for basal cell carcinoma?
There are no established guidelines for follow–up to the removal of a basal cell carcinoma. An annual skin check is recommended for anyone who has had a BCC, given an estimated 30–77% cumulative risk of experiencing another one within 3 years. [8–10].
Year–round protection against excessive sun exposure is important in all skin types.
- Stay indoors or under the shade in the middle of the day.
- Wear covering clothing.
- Apply high protection factor SPF50+ broad–spectrum sunscreens generously to exposed skin if outdoors.
- Avoiding indoor tanning (sun beds, solaria).
What is the outcome for basal cell carcinoma in skin of colour?
BCCs are very slow growing tumours and unlikely to reach an advanced stage unless significantly neglected. As long as it has been completely excised, BCC does not recur. However, another may develop elsewhere.
The prognosis is of the rare metastatic BCC is very poor with a median survival time of 8 months following diagnosis [3,10].