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Basal Cell Carcinoma

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Synopsis
Terminology
Diagnosis
Treatment
Complications and Prognosis
Screening and Prevention

Apr.26.2023

Basal Cell Carcinoma

Synopsis

Key Points

Basal cell carcinoma is an extremely common malignancy of the epidermis that usually occurs on the head or neck and rarely metastasizes
Most common basal cell carcinoma subtype is nodular basal cell carcinoma, which generally appears as a pearly white, dome-shaped papule with notable telangiectatic surface vessels
Excisional biopsy with histopathology is gold standard for diagnosis; include deep reticular dermis if lesion is suspected to be more than a superficial process ^r1
Surgical excision is gold standard for treatment
Radiation therapy is a good alternative for patients who are not surgical candidates or who refuse surgery ^r1
Topical medications such as 5-fluorouracil or imiquimod may be used for superficial basal cell carcinoma in patients who are unable or unwilling to undergo surgery or radiation therapy ^r1
Systemic medications such as hedgehog pathway inhibitors (vismodegib and sonidegib) and immunotherapy (cemiplimab) may be used in advanced disease
Complications may include destruction of adjacent tissue in cases of advanced, aggressive disease and rarely metastasis
100% survival with nonmetastatic, noninvasive basal cell carcinoma ^r2
Continued long-term surveillance is essential; 30% to 50% of patients will develop another basal cell carcinoma within 5 years ^r1

Urgent Action

In immunosuppressed patients, early skin biopsy (as soon as skin lesion is noticed) and treatment of premalignant and malignant lesions are paramount ^r3

Pitfalls

A conservative approach to treatment based on the knowledge that basal cell carcinoma is rarely fatal can put patient at risk of serious morbidity (eg, destruction of adjacent tissue in cases of advanced, aggressive basal cell carcinoma)
May be difficult to diagnose basal cell carcinoma in skin of color owing to pigmentation and rarity ^r4

Terminology

Clinical Clarification

Basal cell carcinoma is an extremely common malignancy of the epidermis that usually occurs on the head or neck and rarely metastasizes

Classification

Clinical and histological subtypes ^r5
- Nodular
  - Most common subtype, representing 50% to 80% of lesions
  - Primarily involves head and neck
  - Generally appears as a pearly white, dome-shaped papule with notable telangiectatic surface vessels and rolled borders ^r6^r7
  - Sometimes pigmented with melanin
- Superficial
  - Second most common subtype; 10% to 30% of lesions
  - Appears as well-defined erythematous scaly plaque with central clearing
  - Sometimes pigmented with melanin
  - Most common on trunk
- Infundibulocystic
  - Well-defined pearly papule
  - Commonly on head and neck in older adults
- Fibroepithelial (fibroepithelioma of Pinkus)
  - Uncommon
  - Indolent form
  - Often on trunk
- Morpheaform
  - Less than 10% of lesions
  - Infiltrated plaque with slightly shiny surface and ill-defined borders; may resemble a scar
  - Commonly on head or neck
  - Tends to be more aggressive and has higher rate of recurrence
- Infiltrative
  - Poorly defined, indurated or indented plaque; white, yellow, or pink color
  - May have overlying crusts, erosion, or ulceration
- Micronodular
  - May be erythematous macules or thin papules or plaques
  - Micronodular changes may be present alongside other histological subtypes
- Basosquamous
  - Rare: less than 2% of cases
  - Well-defined nodular or superficial squamous cell carcinoma—appearance with underlying histological features of both basal cell and squamous cell carcinomas
  - Mostly found on head and neck
  - Aggressive and associated with high rates of recurrence and metastasis
Risk stratification (risk of recurrence)
- Formal staging with TNM system and American Joint Committee on Cancer stage grouping is not used; instead, stratified by risk of recurrence per National Comprehensive Cancer Network guidelines ^r8
  - Low-risk basal cell carcinoma ^r1
    - Area less than 20 mm on trunk and extremities (excluding pretibia)
    - Well-defined borders
    - Primary
    - No immunosuppression
    - Not at site of prior radiation therapy
    - Pathology
      - Nodular, superficial, and other nonaggressive subtypes
      - No perineural involvement
  - High-risk basal cell carcinoma ^r1
    - Area 20 mm or larger on trunk and extremities (excluding pretibia)
    - Lesion of any size on head, neck, pretibia, hands, feet, and anogenital region
    - Poorly defined borders
    - Recurrent
    - Patient immunosuppressed
    - Lesion at site of prior radiation therapy
    - Pathology
      - Aggressive growth pattern (infiltrative, micronodular, basosquamous, morpheaform, sclerosing, or carcinosarcomatous features)
      - Perineural involvement

Diagnosis

Clinical Presentation

History

Skin lesion presenting with any of the following characteristics: ^r9^r10^c1
- Nonhealing within 4 weeks ^c2
- Dimpled at midpoint ^c3
- Occurs on sun-exposed skin ^c4
- Slowly enlarging ^c5
- Bleeds occasionally or only when poked or knocked ^c6^c7
- Pruritic ^c8
May be asymptomatic ^r5^c9
History of risk factors may include the following:
- Previous basal cell carcinoma or other nonmelanomatous skin cancer
- Family history of basal cell carcinoma ^c10
- Chronic sun exposure, especially during childhood and young adulthood ^c11
- Use of tanning booths ^c12

Physical examination

Typical lesions resemble a papule or nodule and may have the following characteristics: ^c13^c14
- Central ulceration, erosion, or depression ^c15^c16^c17
- Waxy appearance ^c18
- Raised or crusty border ^c19^c20
- Tendency to bleed when knocked or pulled ^c21
- Translucent or pearly color ^c22^c23
- Pigmentation ^c24
Commonly occur in head and neck area, and within treatment field of prior radiation therapy; some subtypes occur on trunk or legs ^r1

Causes and Risk Factors

Causes

Arise in sun-damaged skin because of mutagenic effects of UV light on keratinocyte progenitor cells ^r5
Solar UV radiation is the main risk factor ^r11^r12^r13^c25^c26
- UV-B (290-320 nm) rays are more powerful than UV-A in causing basal cell carcinoma ^c27
- UV-A (320-400 nm) rays are less powerful than UV-B in causing basal cell carcinoma, but exposure to UV-A rays is usually much greater because UV-A is more prevalent than UV-B at the Earth's surface and many sunscreens do not block UV-A as well as they block UV-B ^c28
- Effect is exacerbated by skin phenotype: fair skin, red or blond hair, light eye color, tendency to freckle, and inability to tan ^r5

Risk factors and/or associations

Age

Average age at diagnosis is 60 years; risk increases with advancing age ^r14^c29

Sex

More frequent in males than females ^r15^c30^c31

Genetics

Certain genetic conditions increase susceptibility to UV-induced mutagenesis and are associated with elevated risk of basal cell carcinoma ^c32
- Basal cell nevus syndrome (Gorlin-Goltz syndrome or basal cell carcinoma syndrome) ^r5^r16^r17^c33
  - PTCH1, PTCH2, or SUFU
  - Autosomal dominant inheritance
- Xeroderma pigmentosum ^r18^c34^c35
  - XPA through XPG and XPV
  - Autosomal recessive inheritance
- Bazex-Dupré-Christol syndrome ^r5^c36
  - Unknown gene
  - X-linked dominant inheritance
- Rombo syndrome ^r5^c37
  - Unknown gene
  - Autosomal dominant inheritance
- Rothmund-Thomson syndrome ^r5^c38
  - RECQL4 and USB1
  - Autosomal recessive inheritance
- Werner syndrome ^r5^c39
  - WRN/RECQL2
  - Autosomal recessive inheritance ^c40
- Bloom syndrome ^r5^c41
  - BLM/RECQL3
  - Autosomal recessive inheritance
- Muir-Torre syndrome ^r5^c42
  - MLH1, MSH2, MSH6, or PMS2
  - Autosomal dominant inheritance

Ethnicity/race

More common in people with fair skin, red or blond hair, and light eye color ^r1^c43^c44^c45^c46
In the US, lifetime risk of developing basal cell carcinoma is 30% or greater in White people ^r19^c47
Also occurs in people of color; most common form of skin cancer in Asian and Hispanic people, second most common in Black people (may be pigmented and often misdiagnosed) ^r4^r20^c48^c49^c50

Other risk factors/associations

Albinism ^r2^c51
High exposure to sunlight, especially during childhood and young adulthood ^r2^r15^r21^c52^c53^c54
- Occupational, such as farming, lifeguarding, and construction work ^r2^r12^r15^c55^c56^c57^c58
- Recreational ^r2^r22^c59^c60
Geography of patient residence, especially during childhood: ^r21
- Lower latitudes, high altitude, southern hemisphere ^c61^c62^c63
Non-UV radiation to the skin
- Ionizing: generally, this refers to x-ray therapy for acne (used before approximately 1950) ^c64^c65
- Nonionizing
  - Psoralen and UV-A therapy for psoriasis ^c66
Arsenic exposure ^c67
Immunosuppression
- HIV infection, immunosuppressive drugs ^c68^c69
- Smoking^r23^r24, especially in females^r23^c70^c71
- Solid organ transplant^r27, especially heart and kidney ^r25^r26^c72
  - Over half of solid organ transplant recipients will develop nonmelanoma skin cancer, usually basal cell carcinoma or squamous cell carcinoma ^r28
Alcohol use may increase risk of aggressive histologic subtypes (eg, morpheaform, infiltrative, micronodular) ^r29^c73

Diagnostic Procedures

Primary diagnostic tools

Initial workup includes history, physical examination including complete skin examination, and biopsy of suspicious lesion ^r1^c74^c75
- Evaluation of suspected basal cell carcinoma with dermoscopy can help rule out other conditions in the differential diagnosis and assist in diagnosis ^r30^c76
  - Dermoscopy may allow diagnosis of shallow, nodular basal cell carcinoma; however, not a substitute for definitive biopsy ^c77
  - Refer patients to a dermatologist for dermoscopy, unless the primary care physician has received dermoscopy training relevant to basal cell carcinoma ^r31
- Optical coherence tomography and reflectance confocal microscopy may aid in diagnosis, particularly in conjunction with dermoscopy ^r16^r32^c78^c79
- Skin biopsy with histopathologic analysis of tissue sample confirms diagnosis ^c80^c81
  - Include deep reticular dermis in biopsy if lesion is suspected to be more than a superficial process ^r1
  - In immunosuppressed patients, early skin biopsy (as soon as skin lesion is noticed) and treatment of premalignant and malignant lesions are paramount
3-Dimensional imaging studies are recommended if there is suspicion for extensive disease (eg, invasion of deep soft tissue or bone, perineural disease) ^r1
- MRI with contrast enhancement is preferred for evaluation of perineural invasion or periorbital spread ^r16^c82
- CT with contrast enhancement is preferred if bone involvement is suspected ^c83
Consider genetic testing to exclude genetic syndrome in patients who develop basal cell carcinoma before age 20 years ^r16^c84

Imaging

MRI or CT ^r1^c85^c86
- Perform when extensive disease such as bone involvement, perineural invasion, or deep soft tissue involvement is suspected
- MRI preferred over CT for suspected perineural disease

Procedures

Dermoscopy ^c87

General explanation

Noninvasive optical procedure for evaluation and differentiation of skin lesions
Generally provides enough information to determine histopathologic subtype and tumor extension of a basal cell carcinoma ^r33
Refer patients to a dermatologist for dermoscopy, unless the primary care physician has received dermoscopy training relevant to basal cell carcinoma ^r31

Indication

Skin lesion with clinical suspicion of malignancy; applicable for shallow, nodular basal cell carcinoma
May help rule out other conditions in the differential diagnosis and assist in diagnosis; however, not a substitute for definitive biopsy

Skin biopsy ^c88

General explanation

Selection of biopsy technique
- Factors to consider include tumor morphology, expected histologic subtype, expected depth, and anatomic location, as well as patient-specific factors such as bleeding diatheses and abnormal wound healing
  - Obtain more extensive biopsy tissue (eg, excisional biopsy, multiple scouting biopsies) if tumor appears to be deeply invasive or has other aggressive features
  - Perineural invasion may not be identified with incomplete biopsy
- Excisional biopsy with histopathology is gold standard for diagnosis
- Shave biopsy (removing only epidermis and outer dermis with a tangential technique) is most commonly done and adequate for superficial basal cell carcinoma
- Punch biopsy (removing all layers of skin into subcutaneous fat with a small tool resembling a cookie cutter) provides a thicker specimen
Terminology: distinguish excisional biopsy from an excision with margins; the latter is performed as treatment to completely remove the tumor

Indication

All suspected basal cell carcinoma cases

Interpretation of results

Documents histopathologic subtype and presence of features that increase risk of local recurrence (eg, perineural invasion, invasion beyond reticular dermis) ^r1^c89^c90^c91^c92
- Low-risk subtypes
  - Nodular
  - Superficial
  - Infundibulocystic
  - Fibroepithelial
- High-risk subtypes
  - Morpheaform
  - Infiltrative
  - Micronodular
  - Basosquamous
  - Sclerosing
  - Carcinosarcomatous

Differential Diagnosis

Most common

Seborrheic keratosis ^c93
- Macules/papules made by epidermal cell proliferation
- Shave biopsy identifies epithelial proliferation with horn cysts and no sign of malignancy
Keratoacanthoma ^c94
- Low-grade skin tumor that resembles squamous cell carcinoma and rarely metastasizes
- Excisional biopsy results show well-differentiated squamous epithelium with a central mass of keratin
  - Deep incisional biopsy may be adequate
  - Shave biopsy is not enough to distinguish histology from that of basal cell carcinoma
Actinic keratosis ^c95
- Scaly, rough skin lesions (usually smaller than 1 cm) that typically begin as small macules
- In basal layer of skin, biopsy shows abnormal keratinocytes varying in shape and size with atypical nuclei
Squamous cell carcinoma ^c96^d1
- Malignant proliferation of epidermal keratinocytes that occurs most commonly on chronically sun-exposed skin in older patients
- Presents as more invasive lesion than basal cell carcinoma
  - Even early (in situ) squamous cell carcinoma shows full-thickness epidermal involvement with atypical keratinocytes
  - Dermal invasion is common
- Biopsy covering full thickness of skin shows cancerous squamous cells
  - Shave biopsy is not sufficient for diagnosis

Treatment

Goals

Complete removal of tumor with clear histologic margins and minimal functional and cosmetic compromise
In settings of metastatic basal cell carcinoma (very rare): remission with extension of survival time

Disposition

Recommendations for specialist referral

Referral to a dermatologist for confirmation of diagnosis and appropriate treatment
Histopathologic analysis is often done by a dermatopathologist
Plastic/cosmetic/reconstructive surgeon to do excision or excisional biopsy involving cosmetically challenging sites or reconstruction after excision
- Refer patients requiring Mohs surgery to a surgeon specifically trained in this technique
Multidisciplinary tumor board consultation, including a radiation oncologist and medical oncologist, is recommended in situations where either radiation therapy, chemotherapy, or both are under consideration

Treatment Options

Surgical excision is first line treatment of all types of basal cell carcinoma ^r9

If required, reconstruction after surgical resection can be performed immediately or delayed for days to weeks, depending on type of repair, patient characteristics, and logistics ^r34
- Immediate reconstruction is preferred in patients with basal cell carcinoma with high-risk factors if clinical margins are well defined under bright lighting and magnification or dermoscopy ^r35
- Delayed reconstruction, or Mohs micrographic surgery, is first line approach for patients when lesion is in a high-risk anatomic area and has poorly defined margins under bright lighting and magnification or dermoscopy ^r35

Local low-risk basal cell carcinoma ^r1

Standard excision with 4-mm clinical margins and with closure techniques such as linear closure, second intention healing, or skin graft
- If margins are positive after excision, recommend 1 of the following:
  - Mohs micrographic surgery or other forms of peripheral and deep en face margin assessment
  - Standard reexcision for trunk and extremities (excluding pretibia, hands, feet, nail units, ankles)
  - Radiation therapy for nonsurgical candidates
Destructive techniques are an alternative when there is low risk of local extension or recurrence; disadvantage is that these do not allow histologic examination of tissue ^r9
- Electrodesiccation and curettage may be performed in areas without hair growth (ie, not scalp, pubic and axillary regions, or beard area in males), provided that treatment be changed to excision if tumor appears to extend beyond the dermis ^r1
- Radiation therapy for nonsurgical candidates or those with advanced age and poor performance status
  - Usually reserved for patients aged 60 years or older ^r1
- Laser ablation may be used for low-risk disease in patients unable or unwilling to undergo surgery or other therapies ^r9^r36
- Topical medications (5-fluorouracil or imiquimod), cryotherapy, or photodynamic therapy may be used for superficial basal cell carcinoma in patients who are unable or unwilling to undergo surgery or radiation therapy ^r1^r35^r37
  - Cure rates are at least 10% lower than surgical approaches ^r1
  - Imiquimod has greatest efficacy over a 5-year follow-up, while cosmetic results are best with photodynamic therapy ^r38^r39
  - Cryosurgery resulted in a clearance rate of 100% at 1 year in one randomized trial of treatment of nonfacial, superficial basal cell carcinoma (228 tumors in 97 patients); however, wound healing times are longer compared to curettage, and cosmetic result may be poor^r19^r40

Local high-risk basal cell carcinoma ^r1

Mohs micrographic surgery or other forms of peripheral and deep en face margin assessment
- Mohs is the most reliable strategy with lowest recurrence rate:^r320% to 2.5% ^r41
- If margins are positive after excision:
  - Multidisciplinary tumor board consultation to discuss options
    - Repeat resection
    - Radiation therapy
    - Systemic therapy (vismodegib or sonidegib) if curative radiation therapy or surgery not feasible
- If margins are negative after excision:
  - If extensive perineural or large-nerve involvement, consider adjuvant radiation therapy
Standard excision, using wider margins with linear or delayed repair
- If margins are positive after excision:
  - Recommend Mohs micrographic surgery or resection with complete margin assessment
    - If residual disease is present, consider multidisciplinary tumor board consultation regarding options (radiation therapy or systemic therapy)
- If margins are negative after excision:
  - If extensive perineural or large-nerve involvement, consider adjuvant radiation therapy
Radiation therapy for nonsurgical candidates ^r1
Systemic therapy (vismodegib or sonidegib) if neither radiation therapy nor surgery is feasible ^r1
- Vismodegib may also have a role as neoadjuvant therapy to reduce tumor burden before surgical excision of locally advanced tumors in functionally sensitive locations ^r42

Nodal or distant metastatic disease ^r1

Multidisciplinary tumor board consultation to discuss options
- Surgery
- Systemic therapy with hedgehog pathway inhibitor (vismodegib or sonidegib) ^r43
  - Anti-PD1 antibody cemiplimab-rwlc may be used to treat patients with metastatic or locally advanced basal cell carcinoma who have previously been treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate ^r1^r36^r43
- Treatment in a clinical trial
- Radiation therapy

Drug therapy

Topical therapies
- Appropriate in cases of superficial basal cell carcinoma in patients who are unable or unwilling to undergo surgery or radiation therapy ^r1
  - 5-Fluorouracil ^c97
  - Imiquimod ^c98
Intralesional chemotherapies ^r32
- Interferon alfa-2b ^c99
- 5-Fluorouracil ^c100
- Bleomycin ^c101
Systemic agents
- Indicated with advanced or metastatic disease ^r1^r37^r43
  - Hedgehog pathway inhibitors
    - Vismodegib ^c102
    - Sonidegib ^c103
  - PD-1 inhibitor
    - Cemiplimab-rwlc ^c104

Drug Therapy: Basal Cell Carcinoma
Medication	Common regimens	Life-threatening or dose-limiting adverse reactions	Notable or nonemergent adverse reactions	Special considerations
Antimetabolite - nucleoside metabolic inhibitor
Fluorouracil (topical)	• Fluorouracil (topical) monotherapy	• Photosensitivity	• Allergic contact dermatitis • Skin burning • Crusting • Leukocytosis • Pruritus • Rash • Scarring • Soreness • Ulceration	• Increased risk of serious or fatal adverse reactions in patients with low or absent dihydropyrimidine dehydrogenase activity
Epidermal growth factor receptor (EGFR) antagonist
Cetuximab	• Cetuximab monotherapy	• Cardiopulmonary arrest • Dermatologic toxicity • Infusion-related reactions • Interstitial lung disease (ILD) • Radiation recall	• Diarrhea • Electrolyte abnormalities • Headache • Infection	• Effective contraception required during and after therapy for 2 months for females of reproductive potential
Hedgehog pathway inhibitor
Sonidegib	• Sonidegib monotherapy	• Increased creatine phosphokinase (CPK) • Muscle cramps • Musculoskeletal pain • Premature epiphyseal fusion • Myalgia	• Abdominal pain • Alopecia • Anorexia • Diarrhea • Dysgeusia • Fatigue • Headache • Nausea/vomiting • Pain • Pruritus • Weight loss	• Advise patients not to donate blood or blood products during treatment and for at least 20 months after the last dose • Advise males not to donate semen during and after therapy for at least 8 months after the last dose • Effective contraception required during and after therapy for at least 20 months for females of reproductive potential and for at least 8 months for males with female partners of reproductive potential
Vismodegib	• Vismodegib monotherapy	• Arthralgia • Dermatologic toxicity • Muscle spasms • Increased creatine phosphokinase (CPK) • Premature epiphyseal fusion	• Ageusia • Alopecia • Anorexia • Constipation • Diarrhea • Dysgeusia • Fatigue • Nausea/vomiting • Weight loss	• Advise patients not to donate blood or blood products during treatment and for at least 24 months after the last dose • Advise males not to donate semen during and after therapy for 3 months after the last dose • Effective contraception required during and after therapy for 24 months for females of reproductive potential and for 3 months for males with female partners of reproductive potential
Immune response modifier
Imiquimod	• Imiquimod monotherapy	• Skin weeping/erosion • Photosensitivity • Flu-like symptoms	• Edema • Erythema • Excoriation • Flaking/scaling/dryness • Induration • Pruritus • Scabbing/crusting • Skin burning • Ulceration
Programmed death receptor-1 (PD-1) blocking antibody
Cemiplimab	• Cemiplimab monotherapy	• Adrenal insufficiency • Colitis • Diabetic ketoacidosis • Exfoliative dermatitis • Hepatitis • Hyperthyroidism • Hypophysitis • Hypothyroidism • Infusion-related reactions • Myocarditis • Nephritis • Neurotoxicity • Pneumonitis • Thyroiditis	• Diarrhea • Fatigue • Musculoskeletal pain • Rash	• Effective contraception required during and after therapy for at least 4 months for females of reproductive potential

Nondrug and supportive care

Procedures

Excisional surgery ^c105

General explanation

Tumor is excised with surrounding normal tissue margins
Followed by any of the skin reconstruction techniques: linear closure, secondary intention healing, or skin graft

Indication

Low-risk basal cell carcinoma if lesion can be excised with 4-mm clinical margins ^r1
High-risk basal cell carcinoma, using wider margins ^r1

Mohs surgery ^c106

General explanation

During a single procedure under local anesthesia, tumor is removed in multiple stages; patient remains on site between stages
Excision margin is inspected repeatedly so that additional excision can be done as necessary to attain negative margins

Indication

High-risk basal cell carcinoma ^r1
Basal cell carcinoma with aggressive histology
Basal cell carcinoma at anatomic location requiring tissue conservation (eg, eyelid) ^r1
Low-risk basal cell carcinoma, if margins are positive after excision ^r1

Contraindications

Procedure may be too long and tedious for patient to tolerate
Patient does not tolerate repeated injections of local anesthetic
Very large or unresectable tumor

Electrodesiccation and curettage ^c107^c108

General explanation

Procedure in which tumor is scraped away down to the dermal layer with a curette, followed by denaturation of area by electrodesiccation ^r1
Up to 3 cycles of the procedure are completed in 1 session ^r1

Indication

Low-risk basal cell carcinoma ^r1
Superficial, noninfiltrative lesion ^r1

Contraindications

Areas of terminal hair growth such as scalp, pubic and axillary regions, and beard area in males ^r1
Tumor reaching subcutaneous adipose layer ^r1

Cryosurgery ^c109

General explanation

Lesion is destroyed with very cold temperature using a cryoprobe (instrument with tip cooled by liquid nitrogen) ^r1

Indication

Superficial, noninfiltrative lesion ^r1
May be used for superficial basal cell carcinoma in patients who are unable or unwilling to undergo surgery or radiation therapy ^r1

Laser ablative therapy ^c110

General explanation

Basal cell carcinoma is burned off with a laser

Indication

Small, superficial basal cell carcinoma

Radiation therapy ^r44^c111

General explanation

Tumor is destroyed using high-energy radiation (electron beam, high energy photons, or proton beam) or orthovoltage radiation
Isotope-based brachytherapy^r45 may be useful for sites on head and neck ^r1

Indication

Patients aged 60 years or older with low-risk and high-risk basal cell carcinomas of nodular or infiltrative subtypes and who: ^r35
- Have a tumor that is inoperable because of size or location ^r1^r44
- Are not eligible for or decline surgery, or express preference for radiation therapy ^r44
- Have a tumor for which incomplete surgical excision and reexcision are not possible ^r44

Contraindications

Genetic diseases that predispose patient to increased radiation sensitivity ^r44
- Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)
- Xeroderma pigmentosum
- Basal cell nevus syndrome
- Bazex syndrome
- Epidermodysplasia verruciformis
Recurrent basal cell carcinoma after previous radiation therapy ^r35
Lesion is in area of poor blood supply (eg, lower limbs) ^r35
Patients younger than 60 years in whom late effects of radiation therapy could be problematic ^r35
Lesion is invading bone or cartilage ^r35

Photodynamic therapy ^c112

General explanation

Photosensitizers are delivered topically to lesions in prodrug form (eg, aminolevulinic acid)
Prodrug is metabolized in situ and generates a photoactive substance
A light source applied to this area energizes the photosensitizer, which generates highly reactive singlet oxygen locally resulting in necrosis, apoptosis, and possibly increased local immune effects

Indication

May be used for superficial basal cell carcinoma in patients who are unable or unwilling to undergo surgery or radiation therapy ^r1

Contraindications

Skin sensitivity to light at 400 to 450 nm
Porphyria
Porphyrin allergy

Comorbidities ^c113

Special populations

Patients with diabetes may present late with basal cell carcinoma, particularly when it occurs on lower extremities
- Increases the need for excisional surgery and Mohs surgery, because the basal cell carcinoma tends to be deeper

Monitoring

Continued long-term surveillance is essential; 30% to 50% will develop another basal cell carcinoma within 5 years ^r1
During first 5 years, examine patient at least every 6 to 12 months; then at least annually for life ^r1^c114

Complications and Prognosis

Complications

Destruction of adjacent tissue in cases of advanced, aggressive basal cell carcinoma ^c115
Recurrence at original tumor site ^c116
Metastatic basal cell carcinoma (very rare) ^r46^c117

Prognosis

Overall prognosis is excellent, as most cases are curable when detected and treated early
100% survival with nonmetastatic, noninvasive basal cell carcinoma ^r2
5-year survival rate is only 10% in cases of recurrent and invasive basal cell carcinomas, because these do not respond well to chemotherapy ^r47
Median overall survival for metastatic basal cell carcinoma ranges from 8 months to 7.3 years ^r4
Recurrence rate is low
- 5% recurrence rate within 5 years after standard surgical excision ^r6
- 1% recurrence rate after Mohs surgery ^r6
Risk of recurrence is directly related to the adequacy of excision; 1% of recurrence rate for lesions excised with clear margins compared with 31% to 41% recurrence rate when margins are positive ^r48
- Overall, approximately 11% of cases are incompletely excised
30% to 50% of patients will develop another basal cell carcinoma within 5 years ^r1
Patients are also at increased risk of developing other forms of skin cancer ^r36

Screening and Prevention

Screening

At-risk populations

Anyone with elevated levels of sun exposure (eg, occupational or recreational exposures) ^c118^c119

Screening tests

US Preventive Services Task Force concluded that evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults ^r49
Skin Cancer Foundation recommends the following: ^r50
- Self-examination of skin from head to toe every month ^c120
- Formal skin examination each year by a dermatologist if earlier history of basal cell carcinoma ^c121

Prevention

General skin cancer prevention
- US Preventive Services Task Force recommendations are as follows: ^r51
  - Counsel young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin types to reduce their risk of skin cancer
  - Selectively offer counseling to adults older than 24 years with fair skin types about minimizing their exposure to UV radiation to reduce skin cancer risk
  - Evidence indicates that the net benefit of counseling all adults older than 24 years is small
  - In determining whether counseling is appropriate in individual cases, patients and clinicians should consider the presence of risk factors for skin cancer
  - Methods of minimizing UV light exposure include the following:
    - Avoid midday sun ^c122
    - Avoid sunburns ^c123
    - Cover up; wear a broad-brimmed hat and sun-protective clothing ^c124
    - Wear sunscreen of at least sun protection factor 15 ^c125
      - Benefit is most evident and clear regarding prevention of squamous cell carcinoma, but less so regarding basal cell carcinoma ^r12
      - Benefit/risk of sunscreen and sun protection factor level in preventing basal cell carcinoma is controversial ^r12^r52
      - Not a substitute for use of hats and sun-protective clothing
    - Wear sunglasses ^c126
    - Do not use tanning beds or sunlamp ^c127
Nicotinamide has been shown to decrease the incidence of nonmelanoma skin cancers, including basal cell carcinomas ^r1

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Basal Cell Carcinoma

Synopsis

Key Points

Urgent Action

Pitfalls

Terminology

Clinical Clarification

Classification

Diagnosis

Clinical Presentation

History

Physical examination

Causes and Risk Factors

Causes

Risk factors and/or associations

Age

Sex

Genetics

Ethnicity/race

Other risk factors/associations

Diagnostic Procedures

Primary diagnostic tools

Imaging

Procedures

Dermoscopy c87

General explanation

Indication

Skin biopsy c88

General explanation

Indication

Interpretation of results

Differential Diagnosis

Most common

Treatment

Goals

Disposition

Recommendations for specialist referral

Treatment Options

Drug therapy

Nondrug and supportive care

Procedures

Excisional surgery c105

Mohs surgery c106

Electrodesiccation and curettage c107c108

Cryosurgery c109

Laser ablative therapy c110

Radiation therapy r44c111

Photodynamic therapy c112

Comorbidities c113

Special populations

Monitoring

Complications and Prognosis

Complications

Prognosis

Screening and Prevention

Screening

At-risk populations

Screening tests

Prevention

Dermoscopy ^c87

Skin biopsy ^c88

Excisional surgery ^c105

Mohs surgery ^c106

Electrodesiccation and curettage ^c107^c108

Cryosurgery ^c109

Laser ablative therapy ^c110

Radiation therapy ^r44^c111

Photodynamic therapy ^c112

Comorbidities ^c113