Clinical recognition confirmed by biopsy and histopathologic exam
Etiology
- Primarily UV (especially 290–320 nm ultraviolet B) and sun exposure
- Ultraviolet spectrum is divided into three regions: UVA (320–400 nm), UVB (280–320 nm), and UVC (200–280 nm).
- UVB is primary cause of erythema after sun exposure and sunburn.
- UVB most closely associated with BCC and is also the primary cause of skin aging changes.
- UVA is associated with skin sensitivity from sulfonamides, phenothiazines, psoralens (PUVA therapy).
- UVC is absorbed by the atmosphere ozone layer.
- Intense intermittent (sporadic, particularly by indoor workers) recreational sun exposure is associated with melanoma and BCC, chronic occupational sun exposure associated with SCC (Zanetti 2006).
- Relative sun exposure at different sites was compared with the relative incidence of periocular BCC — correlation was poor suggesting alternative etiologic factors (Paolo 1998).
- Sun sensitive skin — BCC patients report being more prone to sunburn (pain and/or blistering lasting 2 or more days) after first hour of sun exposure.
- Early age UV exposure — meta-analysis of 9,328 nonmelanoma skin cancers, showed indoor tanning a risk when exposure is before age 25 (Wehner 2012).
- Red hair is risk factor and for multiple BCCs (Kiiski 2010).
- Blond hair, freckles and extremity moles (Wu 2013)
- Lightly pigmented iris, correlates with light pigmentation
- Family history of melanoma is a risk factor for BCC (Wu 2013).
- Cumulative UV exposure might not be a risk factor — time spent outdoors, in summer, not consistently significant in case control studies (Karagas 2014).
- Cigarette smoking is not associated with eyelid BCC (Wojno 1999), but does increase risk of cutaneous squamous cell carcinoma (Leonardi-Bee 2012).
- Chronic human papillomavirus infection not associated with BCC, does increase the risk of cutaneous squamous cell carcinoma (Karagas 2010).
Epidemiology
- According to the American Cancer Society BCC accounts for half of all cancers in the US (Rubin 2005).
- More than one million cases annually in the US (Cancer Facts and Figures, American Cancer Society).
- Australia has the highest incidence of BCC in the world.
- Men and women are equally affected (Cook 1999).
- Correlation with latitude is stronger for SCC than BCC.
- Reported increase in incidence of BCC might be due to improved surveillance.
- Among malignant eyelid tumors in Olmstead County from 1976 to 1990, BCCs accounted for 90% (Cook 1999).
- Age and gender adjusted incidence was 14.4 BCC per 100,000 individuals per year.
- Most national registries in the US do not collect information on BCC, so epidemiologic data on BCC in general is limited (Wu 2013).
History
- Nodule
- Ulceration
- Growth
- Erythema
- Bleeding
- Persistence
- Progression
- Prior skin lesions
Clinical features
- Nodular lesion is a pearly papule, often with central ulceration (noduloulcerative BCC) with overlying telangiectasia and rolled border (Figure 1).

Figure 1. Nodular basal cell.
- Morpheaform lesion is an indurated scar-like plaque with indistinct margins.
- At lid margin, mostly arise in anterior lamella, BCC is rarely seen on nonhair-bearing surfaces such as palms and soles.
- At clinical margins, tumor can be circumscribed or infiltrative
- Morpheaform spreads beneath epithelium, nodular spread is more superficial.
- Pigmented BCCs (Figure 2) are rare, and behavior is similar to other BCC (Kirzhner 2012).

Figure 2. Pigmented basal cell carcinoma.
- Metastasis from BCC is possible, though very rare, with a median interval from presentation to metastasis of 9 years.
- Metastasis is to regional lymph nodes, followed by bone, liver, and lung.
- Prognosis with metastatic disease is poor with mean survival ranging from 8 months to 3.6 years (Walling 2004).
- Primary BCC on the caruncle (Mejer 1998) has been reported in 9 cases (Ugurlu 2014).
- Intraocular invasion by periocular BCC has been reported in a patient with lepromatous leprosy (Aldred 1980).
- Orbital invasion especially with recurrent medial canthal lesions (Figure 3)

Figure 3. Deep medial canthal basal cell carcinoma.
- Recurrent tumor can be evident beneath the conjunctiva without recurrent skin involvement (Lee 2010).
- Vigilant histopathologic evaluation of all lesions removed from the eyelid is important.
- A 28-year-old man underwent excision of a presumed upper lid margin wart, without histopathologic evaluation, which actually harbored a BCC.
- He developed and died of intracranial extension 7 years later (Moro 1998).
Testing
- Biopsy — histopathology
- Oval nuclei
- Scant cytoplasm
- Cells resemble basal cells of epidermis
- Rarely display anaplasia
- First project into upper dermis
- Palisading = tumor cells at periphery arranged in radial pattern
- Abundant collagen in stroma is typical of morpheaform
- Lacunae = islands of tumor cells retract from stroma
- Desmosomal and hemidesmosomal attachments are present, but reduced in number
- Necrosis is common
- Morpheaform BCC has elongated strands of infiltrating tumor, several cell layers thick
- Superficial spreading tumors can have deeper tumor buds extending into the dermis.
- Palisading cells push their way into surrounding and infiltrate less
- Basosquamous tumors have squamous differentiation — might be more likely to recur