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    Basal Cell Carcinoma

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    Feb.12.2024

    Basal Cell Carcinoma

    Synopsis

    Key Points

    • Basal cell carcinoma is an extremely common malignant neoplasm 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; biopsy should include deep reticular dermis because infiltrative histology may only be present at deep margin of tumor 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 malignant neoplasm of the epidermis that usually occurs on the head or neck and rarely metastasizes
    • Named for similarity of tumor cell appearance to cells from basal layer of epidermis; currently thought to arise from stem cells of the hair follicle r5

    Classification

    • Clinical and histological subtypes r6
      • 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 r7r8
        • 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)
      • Because of the very low incidence of regional and distant metastasis with basal cell carcinoma, staging with TNM system and American Joint Committee on Cancer stage grouping is not used; instead, stratified by risk of recurrence based on tumor characteristics, as per National Comprehensive Cancer Network guidelines r9
      • Low-risk basal cell carcinoma r1
        • On trunk or limbs (excluding hands, feet, and pretibial and anogenital area) AND size smaller than 2 cm
        • Well-defined borders
        • Primary
        • No immunosuppression
        • Not at site of prior radiation therapy
        • Pathology
          • Nodular, superficial, and other subtypes with nonaggressive growth patterns such as keratotic, infundibulocystic, and fibroepithelioma of Pinkus
          • No perineural involvement
      • High-risk basal cell carcinoma (presence of any high-risk feature places patient in high-risk category) r1
        • On trunk or limbs AND size larger than 2 cm
        • Lesion of any size on head, neck, hands, feet, or pretibial and anogenital region
        • Poorly defined borders
        • Recurrent
        • Patient immunosuppressed
        • Lesion at site of prior radiation therapy
        • Pathology
          • Aggressive growth pattern (having infiltrative, micronodular, basosquamous, morpheaform, sclerosing, or carcinosarcomatous differentiation features)
          • Perineural involvement
      • Locally advanced disease r1
        • Primary or recurrent extensive disease in which surgery or radiation therapy may not result in a cure or is not feasible
      • Initial presentation with regional or distant metastatic disease (rare) r1

    Diagnosis

    Clinical Presentation

    History

    • Skin lesion presenting with any of the following characteristics: r5r10c1
      • Nonhealing within 4 weeks c2
      • Dimpled at midpoint c3
      • Occurs on sun-exposed skin c4
      • Slowly enlarging c5
      • Bleeds occasionally or with minor trauma c6c7
      • Pruritic c8
    • May be asymptomatic r6c9
    • 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 but may appear as a flat patch, plaque, scar, or ulcer; some of the more common characteristics (best appreciated with magnification) include: r11c13c14
      • Arborizing vessels most common feature (59%); telangiectasias (32%) and corkscrew vessels (33%) also common
      • Shiny white structures (49%)
      • Multiple small erosions (20%)
      • Ulceration (8%)
      • Rosettes (13%)
      • Pigmented leaflike (15%) and spoke-wheel (8%) areas
      • Large blue-gray nests, dots, or globules (34%)
      • Lesions may sometimes exhibit crusting, oozing, and easy bleeding
    • 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 r6
    • Solar UV radiation is the main risk factor r12r13r14c15c16
      • UV-B (290-320 nm) rays are more powerful than UV-A in causing basal cell carcinoma c17
      • 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 c18
      • Effect of radiation is related to skin phenotype: fair skin, red or blond hair, light eye color, tendency to freckle, and inability to tan increase risk of basal cell carcinoma r6

    Risk factors and/or associations

    Age
    • Average age at diagnosis is 60 years; incidence increases with age, peaking at around 80 years r5r15c19
    Sex
    • More frequent in males than females r16c20c21
    Genetics
    • Certain genetic conditions increase susceptibility to UV-induced mutagenesis and are associated with elevated risk of basal cell carcinoma c22
      • Basal cell nevus syndrome (Gorlin-Goltz syndrome or basal cell carcinoma syndrome) r6r17r18c23
        • PTCH1, PTCH2, or SUFU
        • Autosomal dominant inheritance
      • Xeroderma pigmentosum r19c24c25
        • XPA through XPG and XPV
        • Autosomal recessive inheritance
      • Bazex-Dupré-Christol syndrome r6c26
        • Unknown gene
        • X-linked dominant inheritance
      • Rombo syndrome r6c27
        • Unknown gene
        • Autosomal dominant inheritance
      • Rothmund-Thomson syndrome r6c28
        • RECQL4 and USB1
        • Autosomal recessive inheritance
      • Werner syndrome r6c29
        • WRN/RECQL2
        • Autosomal recessive inheritance c30
      • Bloom syndrome r6c31
        • BLM/RECQL3
        • Autosomal recessive inheritance
      • Muir-Torre syndrome r6c32
        • 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 r7c33c34c35c36
    • In the US, lifetime risk of developing basal cell carcinoma is 30% or greater in White people r20c37
    • Also occurs in people of color; most common form of skin cancer in Asian and Hispanic people, and second most common in Black people (lesion may be pigmented and is often misdiagnosed) r4r21c38c39c40
    Other risk factors/associations
    • Albinism r2c41
    • High exposure to sunlight, especially during childhood and young adulthood r2r16r22c42c43c44
    • Geography of patient residence, especially during childhood r22
      • Lower latitudes, high altitude, southern hemisphere c51c52c53
    • Non-UV radiation to the skin
      • Ionizing: generally, this refers to radiographic therapy for acne (used before approximately 1950) c54c55
      • Nonionizing
        • Psoralen and UV-A therapy for psoriasis c56
    • Arsenic exposure c57
    • Immunosuppression
      • HIV infection, immunosuppressive drugs c58c59
      • Solid organ transplantr26, especially heart and kidney r24r25c60
        • More than one-half of solid organ transplant recipients will develop nonmelanoma skin cancer, usually basal cell carcinoma or squamous cell carcinoma r27
    • Some data suggest smoking increases risk, especially in females, whereas other studies show no relation r28r29c61c62
    • Alcohol use may increase risk of aggressive histologic subtypes (eg, morpheaform, infiltrative, micronodular) r30c63

    Diagnostic Procedures

    Primary diagnostic tools

    • Initial workup includes history, physical examination including complete skin examination, and biopsy of suspicious lesion r1c64c65
      • Evaluation of suspected basal cell carcinoma with dermoscopy can help rule out other conditions in the differential diagnosis and assist in diagnosis r31c66
        • Dermoscopy has a sensitivity of 91.2% and specificity of 95% for the diagnosis of basal cell carcinoma r31
        • Dermoscopy may allow diagnosis of shallow, nodular basal cell carcinoma; however, not a substitute for definitive biopsy c67
        • Refer patients to a dermatologist for dermoscopy unless the primary care physician has received dermoscopy training relevant to basal cell carcinoma r32
      • Optical coherence tomography and reflectance confocal microscopy may aid in diagnosis, particularly in conjunction with dermoscopy r18r33c68c69
      • Skin biopsy with histopathologic analysis of tissue sample confirms diagnosis c70c71
        • Biopsy should include deep reticular dermis because infiltrative histology may only be present at deep margin of tumor 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 r18c72
      • CT with contrast enhancement is preferred if bone involvement is suspected r1c73
    • Consider genetic testing to exclude genetic syndrome in patients who develop basal cell carcinoma before age 20 years r18c74

    Imaging

    • MRI or CT r1c75c76
      • 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 c77
    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 r34
    • Refer patients to a dermatologist for dermoscopy unless the primary care physician has received dermoscopy training relevant to basal cell carcinoma r32
    Indication
    • Skin lesion with clinical suspicion of malignant neoplasm; 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 c78
    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) r1c79c80c81c82
      • Low-risk subtypes
        • Nodular
        • Superficial
        • Infundibulocystic
        • Fibroepithelial
      • High-risk subtypes
        • Morpheaform
        • Infiltrative
        • Micronodular
        • Basosquamous
        • Sclerosing
        • Carcinosarcomatous

    Differential Diagnosis

    Most common

    • Seborrheic keratosis c83
      • Macules or papules made by epidermal cell proliferation
      • Shave biopsy identifies epithelial proliferation with horn cysts and no sign of malignant neoplasm
    • Keratoacanthoma c84
      • 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 c85
      • 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 c86d1
      • 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 r5r7

    • 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 r35
      • 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 r36
      • 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 r36

    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, and 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 r5
      • 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
      • Laser ablation may be used for low-risk disease in patients unable or unwilling to undergo surgery or other therapies r5r37
      • 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 r1r36r38
        • Cure rates are at least 10% lower than surgical approaches r1
        • Imiquimod has greatest efficacy over a 5-year follow-up, and cosmetic results are best with photodynamic therapy r39r40
        • 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 poorr20r41

    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 5-year recurrence rate:r330% to 2.5% r42
      • Standard excision using wider margins with linear repair, second intention healing, or skin graft is an alternative option
      • If margins are positive after excision
        • Multidisciplinary tumor board consultation to discuss options
          • Repeat resection
          • Radiation therapy
          • If surgery and/or radiation therapy are not curative, treat as for advanced disease
      • If margins are negative after excision
        • If extensive perineural or large-nerve involvement, consider adjuvant radiation therapy
    • For nonsurgical candidates consider multidisciplinary consultation and discussion of definitive radiation therapy r1

    With locally advanced disease or presence of nodal or distant metastases, consult a multidisciplinary tumor board to discuss options r1

    • Locally advanced disease r1
      • Surgery with or without prior (neoadjuvant) systemic therapy with the hedgehog pathway inhibitor vismodegib, or the monoclonal antibody cemiplimab-rwlc r43
        • Cemiplimab-rwlc is approved for patients with locally advanced or metastatic disease previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate r1r37r44
        • Vismodegib is approved for patients with locally advanced or metastatic disease
      • Radiation therapy
      • Systemic therapy (vismodegib, sonidegib, cemiplimab-rwlc) if neither surgery nor radiation therapy feasible
        • Sonidegib is approved for patients with locally advanced disease
    • Nodal disease r1
      • Surgery
      • Radiation therapy or systemic therapy (vismodegib, sonidegib, cemiplimab-rwlc) if surgery not feasible
      • Treatment in a clinical trial
    • Distant metastatic disease r1
      • Systemic therapy (vismodegib, cemiplimab-rwlc)
      • Radiation or surgery for limited metastatic disease
      • Palliative care

    Drug therapy

    • Drug Therapy: Basal Cell CarcinomaCPK, creatine phosphokinase.Efudex (Fluorouracil). Package insert. Bausch Health US, LLC; 2021. Odomzo (Sonidegib). Package insert. Sun Pharmaceutical Industries, Inc.; 2023. Erivedge (Vismodegib). Package insert. Genentech, Inc; 2023. Aldara (Imiquimod). Package insert. Valeant Pharmaceuticals International, Inc; 2018. Libtayo (Cemiplimab). Package insert. Regeneron Pharmaceuticals, Inc.; 2023.
      MedicationCommon regimensLife-threatening or dose-limiting adverse reactionsNotable or nonemergent adverse reactionsSpecial considerations
      Antimetabolite - nucleoside metabolic inhibitor
      Fluorouracil (topical)• Fluorouracil 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
      Hedgehog pathway inhibitor
      Sonidegib• Sonidegib monotherapy• Increased CPK
      • Muscle cramps
      • Musculoskeletal pain
      • Premature epiphyseal fusion
      • Myalgia      		• Abdominal pain
      • Alopecia
      • Anorexia
      • Diarrhea
      • Dysgeusia
      • Fatigue
      • Headache
      • Nausea or vomiting
      • Pain
      • Pruritus
      • Weight loss      		• Advise patients not to donate blood or blood products during treatment and for at least 20 months after last dose
      • Advise males not to donate semen during and after therapy for at least 8
      months after 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 CPK
      • Premature epiphyseal fusion      		• Ageusia
      • Alopecia
      • Anorexia
      • Constipation
      • Diarrhea
      • Dysgeusia
      • Fatigue
      • Nausea or vomiting
      • Weight loss      		• Advise patients not to donate blood or blood products during treatment and for at least 24 months after last dose
      • Advise males not to donate semen during and after therapy for 3 months
      after 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 or erosion
      • Photosensitivity
      • Influenza-like symptoms      		• Edema
      • Erythema
      • Excoriation
      • Flaking, scaling, or dryness
      • Induration
      • Pruritus
      • Scabbing or crusting
      • Skin burning
      • Ulceration
      Programmed death receptor-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      		• Anemia
      • 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 c87
    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 c88
    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 c89c90
    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 c91
    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 c92
    General explanation
    • Basal cell carcinoma is burned off with a laser
    Indication
    • Small, superficial basal cell carcinoma
    Radiation therapy r45c93
    General explanation
    • Tumor is destroyed using high-energy radiation (electron beam, high-energy photons, or proton beam) or orthovoltage radiation
    • Isotope-based brachytherapyr46 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 to whom the following apply: r36
      • Have a tumor that is inoperable because of size or location r1r45
      • Are not eligible for or decline surgery, or express preference for radiation therapy r45
      • Have a tumor for which incomplete surgical excision and reexcision are not possible r45
    Contraindications
    • Genetic diseases that predispose patient to increased radiation sensitivity r45
      • 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 r36
    • Lesion is in area of poor blood supply (eg, lower limbs) r36
    • Patients younger than 60 years in whom late effects of radiation therapy could be problematic r36
    • Lesion is invading bone or cartilage r36
    Photodynamic therapy c94
    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 c95

    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 r1c96

    Complications and Prognosis

    Complications

    • Destruction of adjacent tissue in cases of advanced, aggressive basal cell carcinoma c97
    • Recurrence at original tumor site c98
    • Metastatic basal cell carcinoma (very rare) r47c99

    Prognosis

    • Overall prognosis is excellent because 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 r48
    • Median overall survival for metastatic basal cell carcinoma ranges from 8 months to 7.3 years r4
    • Recurrence rate is low
      • 12.2% recurrence rate within 10 years after standard surgical excision r7
      • 4.4% recurrence rate within 10 years after Mohs surgery r7
    • 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 r49
      • 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 r37

    Screening and Prevention

    Screening

    At-risk populations

    • Anyone with elevated levels of sun exposure (eg, occupational or recreational exposures) c100c101

    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 r50
    • Skin Cancer Foundation recommends the following: r51
      • Self-examination of skin from head to toe every month c102
      • Formal skin examination each year by a dermatologist if earlier history of basal cell carcinoma c103

    Prevention

    • General skin cancer prevention
      • US Preventive Services Task Force recommendations are as follows: r52
        • 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 c104
          • Avoid sunburns c105
          • Cover up; wear a broad-brimmed hat and sun-protective clothing c106
          • Wear sunscreen of at least sun protection factor 15 c107
            • Benefit is most evident and clear regarding prevention of squamous cell carcinoma but less so regarding basal cell carcinoma r14
            • Benefit/risk of sunscreen and sun protection factor level in preventing basal cell carcinoma is controversial r14r53
            • Not a substitute for use of hats and sun-protective clothing
          • Wear sunglasses c108
          • Do not use tanning beds or sunlamp c109
    • Nicotinamide has been shown to decrease the incidence of nonmelanoma skin cancers, including basal cell carcinomas r1
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