Summary
Basal cell carcinoma (BCC) is a keratinocyte cancer and the most common type of skin cancer overall. BCC is caused by genetic mutations within the sonic hedgehog signaling (SHH) pathway affecting the basal keratinocytes, hair follicles, and eccrine sweat glands. Important risk factors include UV exposure and a history of organ transplantation. Some individuals have a genetic predisposition to BCC. BCC typically occurs in individuals > 40 years of age and lesions are commonly seen on sun-exposed areas (e.g., head and neck). Typical characteristics include a nonhealing, slow-growing nodule or plaque that may bleed easily or ulcerate. Dermoscopy can be used to support clinical findings, but a skin biopsy is necessary for diagnostic confirmation. Nodular BCC and superficial BCC are the most common histologic subtypes. Risk stratification of BCC is used to classify the lesions as low-risk or high-risk for recurrence after excision and thereby guide management. Tumor resection (Mohs micrographic surgery or surgical excision) is the preferred treatment modality; radiotherapy can be considered if resection is not feasible. Other treatment modalities (e.g., cryotherapy, topical pharmacotherapy, photodynamic therapy) may be considered in selected situations but are associated with higher recurrence rates than resection. Metastatic BCC is rare but has a poor prognosis; multidisciplinary care is recommended. All patients should be screened for recurrence and the development of new skin cancers after treatment. Photoprotective measures should be recommended to all individuals for primary prevention and the prevention of recurrent or subsequent skin cancers.
Risk factors
- Intermittent UV exposure is the most significant risk factor, especially for individuals with: [1][2][3]
- Previous history of basal cell carcinoma [4]
- Presence of any nevus on an extremity [2]
- Autoimmune conditions (e.g., rheumatoid arthritis) [1]
- Immunocompromised state (e.g., solid organ transplant recipient)
- Age > 40 years [1][2]
- Male sex [1]
- Exposure to any of the following:
- Chemicals (e.g., arsenic)
- Ionizing radiation
- Phototherapy (e.g., PUVA) [5]
- Genetic predisposition [1][3]
The use of a tanning bed before 24 years of age doubles the risk of developing BCC. [2]
Epidemiology
Clinical features
- Nonhealing well-circumscribed pearly papule, nodule, or plaque with rolled borders, telangiectasia, and/or central umbilication (see “Common subtypes of BCC” for further detail)
- Typically located in areas with sun exposure; most commonly on the face and neck
- Advanced lesions often have central ulceration
- Often painless; may be associated with bleeding or pruritus
- Lesions gradually increase in size (indolent growth)
- Perineural invasion can occur in high-risk BCC lesions and manifests as neuropathy.
- Metastasizes rarely (< 1%); can spread to lymph nodes, soft tissue, lungs, and bone
Most basal cell carcinomas occur on areas of sun-exposed skin. [1][2]
Subtypes and variants
There are several clinical and histological BCC variants; the most common are described here.
BCC lesions may have more than one clinical and histopathological subtype. [1][2]
Low-risk BCC subtypes [1][2]
Nodular basal cell carcinoma
The most frequently occurring subtype of BCC (accounts for 50–80% of BCC) [1][2]
-
Papule or nodule with the following: [1][2]
- Shiny with a pearl-like appearance
- Rolled borders
- Central depression, erosion, or ulceration (rodent ulcer) [6]
- Superficial telangiectasias with arborizing pattern (tree-like branching)
- Most commonly located on the face, especially the nose [6]
Superficial basal cell carcinoma
The second most frequent subtype of BCC (accounts for 10–30% of BCC) [1][2]
-
Plaque with the following:
- Thin and scaly
- Raised border with a pearl-like appearance
- Central atrophy
- Most commonly located on the trunk and legs
Superficial BCC is the least invasive BCC subtype. [2]
Pigmented basal cell carcinoma [1][2]
- Nodular or superficial BCC lesion that contain melanin
- Manifests as a blue, brown, or black lesion
- See “Pigmented features of BCC” for further details.
Features of pigmented basal cell carcinoma can resemble those of melanoma. [1][2]
High-risk BCC subtypes [1][2][3]
These lesions account for < 20% of all BCCs.
- Micronodular: erythematous macule, thin papule, or plaque
- Infiltrative
- Poorly defined flat or depressed light-colored papule or plaque with the following:
- Other features include induration, ulceration, and crust formation
- Morpheaform
- Other: basosquamous (metatypical), sclerosing
Micronodular and infiltrative BCC may be clinically indistinguishable from superficial or nodular BCC. Histopathological examination is needed to confirm the diagnosis. [2]
Nevoid basal-cell carcinoma syndrome (Gorlin syndrome) [1][7]
- Rare, autosomal-dominant inherited syndrome
- Manifests with multiple BCC lesions during childhood or adolescence
- Associated with:
- Malformations (e.g., macrocephaly, hypertelorism)
- Other tumors (e.g., medulloblastoma, ovarian fibroma)
Diagnostics
General principles [3][4]
- All patients with suspected BCC should undergo a full-body skin examination.
- Dermoscopy can support visual inspection of lesions. [8][9]
- A skin biopsy is required for diagnostic confirmation and risk stratification.
- Biopsy all lesions suspicious for BCC.
- The biopsy specimen should include the deep reticular dermis.
- Further evaluation for regional, nodal, or distant metastasis is may be requiredy in patients with high-risk BCC; see “Staging of BCC” for details.
Dermoscopy findings of BCC [9][10]
- Arborizing (branching) blood vessels
- Ulceration
- Crystalline structures (i.e., shiny white areas or streaks)
-
Pigmented features of BCC
- Large blue-gray ovoid nests
- Leaf-like structures
- Multiple blue-gray nonaggregated globules
- Spoke wheel-like concentric structures
Skin biopsy [2][4]
Select a biopsy technique based on the clinical features of the lesion and procedural risks ; use shared-decision making.
- Techniques:
- Shave biopsy for a raised lesion
- Punch biopsy of the most abnormal area of a large lesion
- Full-thickness excisional biopsy is preferred for lesions with pigmented features of BCC to rule out melanoma.
- Consider complete excision (with appropriate margins) as a diagnostic and therapeutic procedure for small lesions.
- Ensure adequate sample size and depth (including the deep reticular dermis) for histopathological examination; if not, a repeat biopsy may be required. [3][4]
- To optimize the quality of the pathology report, biopsy samples should include the following: [4]
- Patient demographics
- Presence of risk factors for BCC
- Size and morphology of the lesion
- Initial sample or repeat
Perform a full-thickness excisional biopsy if there is any concern for malignant melanoma (e.g., pigmentation, ABCDE criteria). [2]
Pathology
- Palisading nuclei: Nuclei appear aligned.
- Tumor cells appear similar to epidermal basal cells.
References:[11]
Differential diagnoses
Other common skin cancers or precancerous lesions [2]
- Precancerous skin lesions (e.g., actinic keratosis, Bowen disease, lentigo maligna)
- Keratoacanthoma
- Cutaneous squamous cell carcinoma
- Melanoma
Benign skin conditions [2]
Trichoepithelioma [12]
- Definition: a rare, benign tumor of the hair follicle that usually occurs in younger individuals [12]
-
Clinical features
- Small annular papule with central depression
- Typically located on the face (e.g., cheek)
-
Diagnostics
- Perform a full-thickness skin biopsy.
- Histology findings may be similar to those of morpheaform basal cell carcinoma or other skin tumors.
- Treatment: Mohs micrographic surgery (especially if on the face) or surgical excision
The differential diagnoses listed here are not exhaustive.
Staging
Assessment of disease extent [3]
Refer patients with high-risk features of BCC to a specialist (e.g., oncologist) for diagnostic evaluation for locoregional, nodal, and distant metastases, which may include:
- CT with IV contrast: for suspected spread to bone or lymph nodes
- PET-CT or ultrasound: for lymph node metastasis [13]
- MRI: for suspected perineural or deep soft tissue involvement
Imaging for staging is rarely required because metastasis is uncommon. If perineural metastasis is suspected, MRI is the preferred imaging modality. [3]
Staging [2][4]
- BCC is a locally invasive tumor that rarely metastasizes.
- Staging using the AJCC TNM staging system has limited clinical utility; can be used to stage metastatic disease.
- Stratifying BCC based on the risk of recurrence after excision is recommended to guide clinical decision-making.
Risk stratification of BCC [2][3][4]
Risk stratification is based on clinical and histopathological features.
- High-risk BCC: lesions with any high-risk feature of BCC
- Low-risk BCC: lesions with no high-risk features of BCC
| High-risk features of BCC [1][3][4] | |
|---|---|
| Tumor characteristics |
|
| Histopathology features |
|
| Patient factors |
|
Treatment
General principles [2][3][4]
- Definitive treatment of BCC is recommended.
- The choice of therapy is based on:
- Risk of recurrence (see “Risk stratification of BCC”)
- Need for conservation of tissue and function
- Patient expectations (use shared decision-making)
- Treatment options include:
- Resection : generally preferred as it is associated with the lowest recurrence rates
- Radiotherapy: when resection is not feasible
- Superficial therapies : for superficial low-risk BCC
- Systemic therapies : for locally advanced or metastatic BCC
- Consults and referrals
- Consider referral to a dermatologist for management.
- Multidisciplinary care is necessary for patients with high-risk BCC lesions or metastatic BCC and those who cannot undergo surgery or radiation.
- Ensure appropriate follow-up for BCC to assess for new or recurrent skin cancers.
Overview of treatment options [2][3][4]
| Overview of treatment options for BCC [2][3][4] | ||
|---|---|---|
| Indications | Special considerations | |
| Mohs micrographic surgery (MMS) |
|
|
| Surgical excision |
|
|
| Curettage and electrodessiccation (C&E) | ||
| Shave removal |
|
|
| Radiotherapy (RT) |
| |
| Cryotherapy, topical pharmacotherapy, and/or photodynamic therapy |
| |
| Systemic therapies |
|
|
MMS is considered superior to surgical excision, as the entire tumor margin is intraoperatively assessed to ensure R0 resection, which reduces the risk of recurrence, and the conservation of healthy tissue is maximized. [3][4]
BCC typically extends beyond the clinically visible margins. Incompletely excised tumors have a recurrence rate of ∼ 26% compared to ∼ 6% after R0 resection. [4]
Localized BCC [2][3][4]
High-risk BCC
- Preferred: MMS
- Alternatives
- Surgical excision with wide margins
- RT for patients who cannot undergo resection
- Consider adjuvant RT if there is evidence of perineural or large nerve invasion.
Low-risk BCC
- Preferred: resection
- Shave removal for superficial BCC on trunk or extremities
- C&E for superficial BCC in non-hair-bearing areas
- Standard surgical excision (4 mm margins)
- RT is preferred for patients who cannot undergo resection.
- Alternatives for small, low-risk BCC lesions with no dermal extension in patients who cannot undergo resection or RT
- Cryotherapy
- Topical pharmacotherapy (i.e., imiquimod or 5-fluorouracil)
- Photodynamic therapy
Avoid electrodesiccation and curettage in lesions in cosmetically sensitive areas (e.g., face) and hair-bearing areas. [3][4]
Locally advanced or metastatic BCC [2][3][4]
Specialist referral and multidisciplinary care are recommended to consider the following options:
- Surgery with or without RT (preferred if feasible)
- Hedgehog pathway inhibitors (e.g., vismodegib, sonidegib)
- Immunotherapy with cemiplimab
- Palliative care
- Enrollment into clinical trials
Follow-up for BCC [3][4]
Regular follow-up is essential as patients are at an increased of developing subsequent skin cancers. [3]
- Screen for skin cancers every 6–12 months for 5 years; then annually for life.
- Encourage adherence to photoprotective measures.
- Educate patients and/or caregivers on self-examination to detect recurrence or new lesions.
Follow-up with a dermatologist is strongly recommended for immunosuppressed individuals and those with ≥ 4 nonmelanoma skin cancers and/or ≥ 1 melanoma in the past 5 years. [3]
Prognosis
- Excellent prognosis with a low rate of metastasis (< 0.1%) [3]
- If metastasis occurs, the prognosis is poor. [4]
- Individuals with a history of BCC are at an increased risk of developing subsequent BCC and other skin cancers (SCC, melanoma). [2][3]
Prevention
- Screening: Consider recommending regular skin self-examination (e.g., monthly). [14][15]
- Prevention: Recommend photoprotective measures to all individuals regardless of skin type. [14][16]
Related One-Minute Telegram
- One-Minute Telegram 74-2023-1/3: Unclear benefit of skin cancer screening
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