basal cell carcinoma (BCC)

Etiology

(risk factors):

• white-skinned persons with poor capacity to tan
• previous therapy with X-rays for facial acne
• sun exposure in both childhood & adult life increases risk
  • heavy sun exposure during youth
• ingestion of arsenic (development of BCC 30-40 years later)

Epidemiology

• most common form of skin cancer
• 500-1000/100,000 in the USA, higher in the sunbelt
• age: > 40 years, males > females
• incidence 21-26/100,000 age < 40
• rare in brown & black skinned individuals
• 40% development of 2nd BCC within 3 years of 1st

Pathology

• locally invasive & destructive skin cancer with limited capacity to metastasize
  • BCC depends on stromal growth factors in the epidermis/dermis.
  • when invasion of vessels occurs & tumor cells lodge at distal sites, the absence of growth factors precludes metastatic growth
  • occasionally when sufficiently dedifferentiated, BCC may acquire the ability to metastasize
• BCC generally arises from epidermis with the capacity to develop hair follicles, thus rarely occurs on the lips or mucous membranes
• proliferating atypical epidermal basal cells
  • large, oval, deep-blue staining on H&E
  • little anaplasia
  • infrequent mitoses
• variable amounts of mucinous stroma
• nodular basal cell carcinoma is the most common histologic subtype
• lesions tend to enlarge radially rather than invade deeper structures

* histopathology images

Immunophenotype

(keratinocytes in basal layer contain CK5,14,15)

• Ber-EP4: strongly + (squamous cell carcinoma -)
• bcl-2: diffusely + (trichoepithelioma periphery + only)

Genetics

• PTCH1 mutations in patients with Gorlin syndrome
• PTCH2 mutations in sporadic BCC
• SMO mutations in sporadic BCCs
• other implicated genes: rasGAP

Clinical manifestations

• papule or nodules often ulcerated with crust
  • described as friable papule with telangiectasias
  • described as slow growing perly-pink papule
• variant forms may appear as scar or thin plaque
• color is generally pink or red, but variant forms may contain blue, brown or black pigment
• translucent lesions with fine telangiectasia may be seen within the lesion
• generally firm to hard; however cystic lesion may occur
• a central erosion may develop
  • surface generally smooth unless eroded
• generally isolated single lesion on sun-exposed surface (exception is superficial BCC)
• multiple lesions may occur
• raised border of lesion is highly characteristic of BCC

* images

Laboratory

• biospy of clinically suspicious lesions (see pathology)

Diagnostic procedures

• combined reflectance confocal microscopy with optical coherence tomography may facilitate noninvasive, real-time diagnosis & simultaneous depth assessment

Complications

• lesions around the eyes, in the nasolabial folds, around the ear canal & posterior auricular sulcus may invade deeply
• destruction of muscle & bone may occur
• invasion of the dura mater & meningitis can occur
• hemorrhage from large eroded vessels may occur

Differential diagnosis

• intradermal nevus
• sebaceous hyperplasia
• fibrous papule of the face
• trichoepithelioma
• squamous cell carcinoma

Management

• superficial lesions may be treated topically
  • cryotherapy with liquid nitrogen except in the danger sites (see complications)
  • imiquimod (Aldara) 5% topical
    • lesions of the trunk & extremities
    • 80% histological cure rate
    • does NOT leave scar
  • 5-fluorouracil may also be used for trunk & extremities
  • not indicated for nodular BCC
• surgical excision
  • microscopically-controlled surgery (Mohs surgery) reserved for head & neck lesions, large or recurrent lesions, or when cosmetic outcome is crucial
  • primary closure, skin-flaps or grafts
  • appears to be treatment of choice
  • high-risk primary BCC may require > 3 mm margins
• electrosurgery (electrodessication & curettage) except in the danger sites (see complications)
• radiation therapy is an alternative to surgery when disfigurement may accompany surgical excision
• vismodegib may be an option for locally advanced BCC or metastasis when surgery or radiation is not an option
  • GDC-0449 holds promise for invasive BCC
• DNAzyme Dz13, designed to bind specifically to Jun mRNA, injected into nodular BCC (100 ug) results in
  • tumor cell apoptosis,
  • inhibition of angiogenesis
  • stimulation of adaptive immune responses
• watchful waiting may be appropriate in patients with asymptomatic nodular or superficial BCC & a limited life expectancy
• prevention:
  • sunscreen, protective clothing
  • celecoxib may reduce incidence of both cutaneous SCC & basal cell carcinoma (BCC)

See National Cancer Institute - Skin Cancer Treatment

More general terms

• carcinoma
• skin cancer

More specific terms

• morpheaform or sclerosing basal cell carcinoma
• nodular basal cell carcinoma
• pigmented basal cell carcinoma
• rodent-type basal cell carcinoma
• superficial basal cell carcinoma
• ulcerative basal cell carcinoma

Additional terms

• dermatoheliosis (photoaging, skin aging)
• Mohs surgery

Patient information

basal cell carcinoma (skin cancer) patient information

Database

• OMIM: https://mirror.omim.org/entry/605462