Basal Cell Carcinoma (BCC)

Basal Cell Carcinoma (BCC)

Basal cell carcinomas are the most common skin cancer. This article details their aetiology, diagnosis and treatment options

Summary Card


Definition
An epidermal keratinocyte neoplasm arising from the epidermis and hair follicles of the dermis.

Aetiology
Medical issues compound genetic and environmental factors.

Types
Nodular is the most common. Others include superficial, micronodular, infiltrative, pigmented and morpheaform.

Low-Risk vs High-Risk
Influenced by the lesion (size, location), histological features and patient medical conditions.

Management
Surgical excision is recommended. Other options include topical therapy, radiotherapy, cryotherapy and Hedge-hog medication.

Follow-up
Low-risk excised lesions in low-risk patients don't require follow-up.

Flashcards
Evidence-based flashcards based on active recall and spaced repetition.


Definition of Basal Cell Carcinoma

A basal cell carcinoma (BCC) is an epidermal keratinocyte neoplasm originating from pluripotential cells in the interfollicular epidermis and infundibulum of the hair follicle distributed along the basal layer and dermo-epidermal junction1,2.

Definition of BCC


Aetiology of BCC


Key Point

Basal cell carcinomas arise from a combination of genetic, environmental and patient causes.

Risk Factors

Basal cell carcinomas are caused by several compounding factrs3-4. These include:

  • Environmental: Exposure to ultraviolet radiation (UVR), prior radiotherapy
  • Immunosuppressed: transplant, HIV, hematologic malignancy
  • Pre-existing lesions:  naevus sebaceous.

Genetics

There has been a number of genetic conditions associated with basal cell carcinomas. These include:

  • Xeroderma Pigmentosum: autosomal recessive deficiency in thiamine dimerase that results in skin cancers and freckle-like hyperpigmentation. BCCs can present quite early (<10 years of age) in these patients.
  • Bazex-Dupré-Christol syndrome is a triad of congenital hypotrichosis,  follicular-atrophoderma of the dorsum hands, and basal cell carcinomas. It occurs in patients <20 years of age.
  • Rombo Syndrome: multiple BCCs (in the middle ages) and follicular-atrophoderma of the elbows and cheeks.
  • Albinism: congenital absence of melanin with ocular pathology due to mutations in the OCA gene.

Gorlin syndrome is discussed in more detail below.  

Gorlin Syndrome

Gorlin syndrome (Basal Cell Naevus Syndrome) is an autosomal dominant condition associated with PTCH gene mutations on chromosome 9. It can also be a sporadic mutation in ~50% of patients.

Features of this systemic condition include:

  • Skin: Multiple early BCCs (before the age of 20)
  • Limbs: Palmar and planter pitting
  • Brain: Falx cerebri calcification, low IQ, blind, paediatric medulloblastoma
  • Craniofacial: odontogenic keratocysts, supraorbital ridging, hypertelorism.
  • Torso: bifid ribs, ovarian fibromas, hypogonadism

Interestingly, the odontogenic keratocysts are most commonly found in the posterior mandible.

These clinical features of Gorlin syndrome are illustrated below.

Gorlin Syndrome

Hedgehog Pathway

The development of BCC is associated with the loss of inhibition of the Hedgehog signalling pathway, which regulates cell growth and differentiation. This is the result of:

  • Inactivating mutations in tumour-suppressor protein patched homologue 1 (PTCH1) gene
  • Activating mutations in smoothened (SMO) transmembrane protein gene
  • Suppressor of fused (SUFU) gene in Gorlin syndrome

💡
Tip: The importance of this Hedgehog pathway is highlighted by the successful use in advanced BCC of hedgehog pathway inhibitors (e.g. vismodegib).


Types of BCCs


Key Point

Basal cell carcinomas can be classified based on their histological subtype. The most common is nodular. There are 26 other variants.


There are 26 histological basal cell carcinoma subtypes6.  Nodular is the most common; other commonly encountered subtypes in clinical practice are:

  • Nodular: well-defined, flesh-coloured, pearly nodule with telangiectasia ± central ulceration. These are the most common.
  • Superficial: flat, pink, keratotic lesions usually in sun-damaged skin. These are the second most common.
  • Infiltrative: poorly-defined yellow-white opacity. These are the third most common.
  • Micronodular: small rounded nodules
  • Pigmented: a dark lesion that can be confused for melanoma
  • Morpheaform:  indurated plaque with a sclerotic or fibrotic appearance.

As mentioned above, there is significant variation in basal cell subtypes. Generally speaking, these are the following required histopathological features

  • Basophilic cells: small, round and found in sheets or nests
  • Nuclei: Peripherial palisading at the margin of the cell nests
  • Ulceration and inflammation, depending the subtype.

😎
Fun Fact: A superficial BCC does not invade the dermis, which enables it to be managed with topical treatments. 


Low-Risk vs High-Risk BCC


Key Point

Risk stratification of basal cell carcinomas is influenced by the lesion (size, location, recurrence), histological features (depth, invasion, PNI) and the patient (immunosuppression, genetic conditions, radiation)


Management of BCC depends on several factors, including the size, site and histological subtype of the tumour, patient comorbidities, previous treatment history and patient preference.

The low-risk and high-risk profiles of BCCs are described below24.


Management of BCCs


Key Point

Basal cell carcinomas are treated primarily through surgical excision. Other treatment options include topical therapy, radiation, Hedgehog inhibitors, cryotherapy.


Basal cell carcinomas are a clinical diagnosis that can be confirmed with a biopsy in patients with diagnostic uncertainty.  Surgery is the recommended treatment modality. Other treatment options, such as radiotherapy, topical therapies, photodynamic therapy (PDT), and hedgehog pathway inhibitors, do exist.

Surgery

Standard surgical excision is suitable for the majority of primary BCCs. Current guidelines (British Association of Dermatology Guidelines 2021) recommend the following indications24:

  • Standard surgical excision as a first-line treatment in low-risk BCC.
  • Immediate reconstruction of lesions with well-defined clinical margins
  • Delayed definitive reconstruction, or Mohs micrographic surgery (MMS) in high-risk BCC with poorly defined clinical margins.

Here are some statistics regarding the 5-year recurrence rate7-9:

  • Completely excised in primary BCCs: 0.5%10
  • Completely excised in recurrent BCCs is 2.9%10
  • Mohs surgery for primary BCCs is 0.3-6.5%11,12.

Deep margins should be into the subcutaneous fat or other deeper structures if needed. The peripheral margins should be excised as follows:

  • Low-risk: 4 mm peripheral clinical surgical margin24.
  • High risk: 5 mm peripheral clinical surgical margin24.
  • Recurrent BCC: 5 mm peripheral clinical surgical margin24.

💡
Tip: Mohs micrographic surgery can be considered for high-risk primary or recurrent BCCs24.

Topical Therapy

Two topical agents are licensed for BCC: imiquimod and 5-fluorouracil (5-FU).

Imiquimod

  • Toll-like receptor 7 agonist induces a tumour-directed cellular response to produce interferon-alpha, TNF-alpha, and interleukins, and decreases expression of Bcl-2 (leading to tumour apoptosis).
  • It is licensed for superficial BCC with a regimen of 5 days per week over 6 weeks.
  • Results in local skin reactions, and some patients develop flu-like illness.
  • 5-year cure rate >80%19
  • Non-inferior cosmetic outcomes compared to surgical excision20.

5-Fluorouracil cream (Efudix)

  • Topical chemotherapeutic agent
  • Thymine analogue inhibits thymidylate synthetase disrupting DNA synthesis and causing apoptosis.
  • It is licensed for superficial BCCs once or twice daily for 3-4 weeks.
  • Rates of local reactions are similar to imiquimod but less flu-like symptoms.

Radiotherapy

Radiotherapy can be considered individually, particularly for patients with poorer performance status or medical comorbidities that may not be suitable for surgery.

It may be an adjuvant treatment to surgery in patients with

  • Involved histological margins for which further surgery is inappropriate
  • Involved histological margins with PNI

The evidence for the role of adjuvant radiotherapy in a completely excised BCC with PNI is weak14. It should not be offered to patients who

  • Have previously received radiotherapy at the site of lesion
  • Have underlying medical conditions, such as Gorlin Syndrome.  

Hedgehog pathway inhibition

Vismodegib and Sonidegib are Hedgehog pathway inhibitors targeting oncogenic smoothened receptors.

  • Both are approved by the EMA and FDS  for the treatment of adults with locally advanced diseases who are not candidates for surgery or radiotherapy24.
  • Vismodegib is also approved for patients with metastatic BCC
  • Consider in patients with Gorlin Syndrome

Vismodegib has demonstrated efficacy in the pivotal ERIVANCE and STEVIE clinical trials21-22.  Sonidegib was assessed in the BOLT trial23

Other Options

Curettage

Curettage, in combination with cautery or electrodesiccation, up to three cycles has been used as a treatment modality.

  • Expedient and cost-effective technique for low-risk superficial lesions
  • Does not allow histological margin assessment
  • Recurrence rate is 4-8% for low-risk15 and 20% for high-risk BCCs16
  • If subcutaneous fat is exposed, curettage should be abandoned, and the wound excised surgically.

Cryosurgery

Cryosurgery with liquid nitrogen spray in freeze-thaw cycles is an effective treatment for selected low-risk, well-defined BCCs17

  • 5-year recurrence rates range from 7.5- 20%18
  • Not necessarily a better cosmetic outcome16

Laser Therapy

  • Laser therapy can be considered for low-risk superficial or thin nodular BCCs
  • Pulsed dye and CO2 laser.
  • Current evidence and the long-term efficacy of this treatment option are weak.

Photodynamic Therapy

  • Topical PDT can be considered in low-risk, superficial BCC.


Follow-up of BCCs


Key Point

Routine follow-up is generally not recommended for low-risk, completely excised basal cell carcinomas in low-risk patients.


There is no evidence that follow-up is required for patients with a single, adequately treated low-risk BCC.

Routine follow-up can be considered for patients with

  • Inadequately treated BCC at high risk for recurrence
  • Patients with a history of multiple primary or recurrent BCCs
  • Increased risk of developing multiple BCC (e.g. in the setting of Gorlin syndrome or immunosuppression)

There is no evidence to support how often this should be, but a 6-monthly follow-up for the first year, then annually for at least 5 and possibly up to 10 years or longer, maybe appropriate24.

Close Margins (<1mm)

If a basal cell carcinoma has been narrowly excised, consider the following:

  • Refer to MDT if a high-risk narrowly BCC
  • Consider surgical re-excision, Mohs, radiotherapy, or monitoring.
  • The patient's choice should be factored into the decision-making process


Flashcards

Evidence-based flashcards are designed for active recall & spaced repetition using the Feynman Technique.

This deck is continually updated for thePlasticsPro users.


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