Basal cell carcinoma (BCC)
Basal cell carcinoma
Definition
Basal cell carcinoma (BCC) is a carcinoma derived from basal cells of the interfollicular epidermis and/or hair follicle. BCCs exhibit morphological variability but they invariably contain islands or nests of peripherally paliaded basaloid cells with hyperchromatic nuclei and scant cytoplasm.
Synonyms
Basal cell epithelioma; basalioma
Epidemiology
BCC is the most common malignancy in humans . Incidence rates are inversely related to geographical latitude and are higher in lighter-skinned populations. Rates are highest in Australia (where one in two residents develops BCC before the age of 70 years) and lowest in parts of Africa . Worldwide, the incidence of BCC is increasing everywhere except for Australia, where it seems to have reached a plateau . In the USA, the incidence rate is approximately 576 cases per 100 000 person-years {108}. The male-to-female ratio is approximately 1.5:1. Patients with two or more BCCs are at high risk of developing subsequent tumours, which are more likely to be of the superficial subtype.
Multiple BCCs disproportionately occur in men . The risk of BCC steadily increases with age. However, incidence rates are increasing faster in younger age groups, particularly among women. Exposure to indoor tanning is a risk factor for early-onset BCC .
Etiology
The finding that ultraviolet (UV) radiation exposure is the most important risk factor for BCC carcinogenesis is supported by abundant evidence , including higher incidence rates of BCC in regions closer to the equator and among individuals with relatively high sun exposure, and the tumours’ predilection for anatomical sites exposed to more sunlight. These tumours harbour many UV radiation signature mutations. Intermittent acute UV
radiation exposure, particularly during childhood, is implicated in the development of BCC. However, unlike in squamous cell carcinoma (SCC), the increase in BCC incidence peaks at approximately 30 000 hours of cumulative sun exposure and then flattens; in contrast, SCC risk increases indefinitely with increasing cumulative sun exposure . Ionizing radiation and systemic arsenic exposure are also known environmental insults
associated with BCC carcinogenesis, and organ transplant recipients may develop a risk of BCC as much as 10 times that in the general population.
Localization
BCC is predominantly found in sun exposed skin; in one review, 64% of cases were found on the head, and 24% on the trunk . However, BCC has also been reported in the perianal and genital region, nail unit, palm, and sole. Different histological subtypes have predilections for different anatomical locations: superficial BCC occurs mainly on the trunk (overall), whereas nodular BCC is the predominant subtype of the head and neck. Superficial BCC is most common in females, in whom it is more often found on the legs than at other sites.
Clinical features
The variety of clinical presentations seen in BCC reflects the variety of the histopathological variants of these tumours. The classic feature is a pearly, telangiectatic papule, which may be eroded or ulcerated. Superficial BCC may present as an annular, mildly scaly plaque resembling tinea corporis. Sclerosing/morphoeic BCC and infiltrating BCC can have a scar-like appearance; pigmented BCC can resemble melanoma.
Genetic profile
BCC has one of the highest prevalence rates of somatic mutations of all cancers, and most of these mutations show the UV radiation signature of cytosine to thymine
substitutions (C>T or CC>TT). Loss of heterozygosity of the PTCHI gene on chromosome 9q22.3 is found in 58-69% of sporadic BCCs, as well as in all BCCs in patients with naevoid BCC syndrome (NBCCS). About of the PTCHI mutations found in sporadic BCCs show the UV radiation signature. Mutations in the TP53 gene on chromosome 17p13.1 are found in 44-65% of BCCs. Loss of function of this gene is implicated in dysregulation of cell-cycle arrest, senescence, apoptosis, and DNA repair. MCIR variants are also implicated in BCC pathogenesis, and the risk is independent of skin and hair colour.
Genetic susceptibility
NBCCS is an autosomal dominant disorder characterized by multiple BCCs, odontogenic keratocysts of the jaws, palmar and/or plantar pits, and skeletal abnormalities. Patients with NBCCS develop one to more than a thousand BCCs, starting in puberty. The risk is increased following UV radiation exposure. Patients with NBCCS typically have germline mutations in the PTCHI gene, which encodes a receptor for the sonic hedgehog (SHH) protein. PTCHI mutation leads to increased release of the transmembrane protein smoothened (SMO), which leads to downstream activation of the GLII transcriptional pathway. Other genetic abnormalities that predispose individuals to BCC include xeroderma pigmentosum, Bazex—Dupré—Christol syndrome, and Rombo syndrome.
Prognosis and predictive factors
There is no formal staging system for risk stratification specific to patients with BCC. In the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, BCC is typically grouped with other cutaneous malignancies, including SCC {68}; however, TNM staging is rarely reported for this tumour, which usually remains localized. The National Comprehensive Cancer Network (NCCN) guidelines stratify the BCC variants by low versus high risk of recurrence, on the basis of clinical and pathological parameters, chiefly histological type (Table 1.01).
Nodular basal cell carcinoma
Definition
Nodular basal cell carcinoma (BCC), the most common BCC variant is characterized by large tumour nodules in the dermis.
ICD-O code 8097/3
Localization
Nodular BCC is most common in the head and neck region.
Clinical features
Nodular BCC presents as a pearly plaque or nodule, often with telangiectasia. On dermoscopy, a pattern of arborizing vessels is seen. The cystic variant may appear as a translucent cystic nodule, and mucin-filled cystic cavities may resemble hidrocystoma. Ulceration is frequent in larger lesions, historically termed “rodent ulcers”.
Prognosis and predictive factors
Nodular BCC is considered to be a low risk variant of BCC. After adequate surgical excision (with the appropriate method determined by location and tumour size), recurrence and metastasis are exceedingly rare.
Superficial basal cell carcinoma
Definition
Superficial basal cell carcinoma (BCC) is a BCC variant with epidermal connection, confined to the papillary dermis.
ICD-O code 8091/3
Synonym
Superficial multifocal basal cell Carcinoma
Clinical features
Superficial BCC is characterized by erythematous patches ranging from a few millimetres to > 10 cm in diameter. It accounts for 10-30% of BCCs and occurs most frequently on the trunk. Areas of regression appear as pale patches or fibrosis. Clinically, this is a low-risk histological subtype.
Micronodular basal cell carcinoma
Definition
Micronodular basal cell carcinoma (BCC) is a high-risk variant of BCC; it is characterized by small nests, which often extend deeply into the dermis.
Clinical features
Micronodular BCC presents as an elevated or flat, poorly defined lesion, and is most common on the head and neck. It is classified as a high-risk tumour, with the potential to recur after surgery.
Infiltrating basal cell carcinoma
Definition
Infiltrating basal cell carcinoma (BCC) is a BCC variant characterized by narrow tumour cords and nests with an irregular, infiltrative growth pattern.
Synonym
Basal cell carcinoma with aggressive growth pattern
Clinical features
These tumours have a scar-like presentation, and are most frequent on the upper trunk, head, and neck. They are more common in patients aged <35 years than older patients. Biopsy should include deep reticular dermis for most accurate diagnosis. Prognosis and predictive factors This subtype has a high risk of recurrence, necessitating surgery with strict margin control. Infiltrating BCC is often admixed with low-risk subtypes (e.g. nodular BCC and superficial BCC), but the presence of infiltrative morphology defines the risk of the tumour.
Sclerosing/morphoeic basal cell carcinoma
Definition
Sclerosing/morphoeic basal cell carcinoma (BCC) is a BCC variant characterized by very thin cords of basaloid cells surrounded by abundant collagenous stroma. ICD-O code 8092/3
Synonym
Morpheaform basal cell carcinoma
Clinical features
This subtype presents as a poorly defined, scar-like plaque that rarely ulcerates or bleeds.
Prognosis and predictive factors like infiltrating BCC, micronodular BCC and basosquamous carcinoma, this variant of BCC is a high-risk subtype, prone to increased frequency of perineural invasion and local recurrence, and necessitating surgical excision with strict margin control.
Basosquamous carcinoma
Definition
Basosquamous carcinoma is considered to be an aggressive variant of basal cell carcinoma (BCC); it has features of both BCC and squamous cell carcinoma (SCC), as well as transition zones between the two.
Synonym
Metatypical basal cell carcinoma
Epidemiology
Basosquamous carcinoma arises most commonly in the sun-exposed skin of older, fair-skinned White men.
Clinical features
The lesion presents as a slowly evolving papule or nodule, which may ulcerate. Dermoscopic features include a keratin mass, surface scaling, ulceration, and white structureless areas. The lesion combines the polymorphous vascular pattern of BCC with white circles, which are also a diagnostic clue to keratoacanthoma and other SCCs (36). Basosquamous carcinoma has a metastatic rate of 5—8.4%, which is comparable to that of SCC and higher than that of conventional BCC (<O.I%). Metastases are most frequent in regional lymph nodes, followed by lung.
Prognosis and predictive factors
This is an aggressive BCC subtype; the local recurrence rate may be as high as 4.5%, and lymph node metastasis occurs in 5% of cases. Patients with metastatic disease have a median survival of 6.5 years and an overall 5-year survival rate of 54%.
Pigmented basal cell carcinoma
Definition
Pigmented basal cell carcinoma (BCC) is a BCC variant that contains melanin pigment.
Epidemiology
Pigmented BCC has a predilection for individuals of African, Hispanic, and Asian descent
Clinical features
Pigmented BCC shows pigmentation, usually superimposed on other classic clinical BCC features (tumours without classic BCC features can be difficult to distinguish from melanoma). The pigmentation can be focal and dot-like or can involve the entire tumour. Dermoscopy can improve diagnostic accuracy. Dermoscopic features include large blue-grey ovoid nests, blue-grey globules, and leaf-like areas.
Basal cell carcinoma with sarcomatoid differentiation
Definition
Basal cell carcinoma (BCC) with sarcomatoid differentiation is a BCC variant that has a basaloid epithelial component and sarcomatous stroma, which can exhibit a variety of histologies.
Synonyms
Metaplastic carcinoma; carcinosarcomatous basal cell carcinoma; sarcomatoid basal cell carcinoma
Clinical features
These carcinomas occur predominantly in elderly men, in sun-exposed areas of the head, neck, chest, and forearms. The tumours tend to be large (averaging 2.8 cm) at presentation.
Histogenesis
A small series showed similar chromosomal changes in epithelial and mesenchymal components, divergent differentiation of the epithelial component.
Prognosis and predictive factors
The rarity of this tumour makes determination of prognosis difficult.
Basal cell carcinoma with adnexal differentiation
Definition
Basal cell carcinoma (BCC) with adnexal differentiation is a BCC variant with differentiation towards follicular, sebaceous, apocrine, or eccrine glands.
ICD-O code 8090/3
Clinical features
Infundibulocystic BCC and BCC with ductal differentiation have a predilection for periocular skin.
Genetic profile
A small series of BCCs with metrical differentiation showed molecular abnormalities in CTNNBI, KIT CDKN2A, TP53, SMAD4, ERBB4, and PTCHI, providing supporting evidence that these tumours may be variants of BCC .
Genetic susceptibility
Multiple infundibulocystic BCCs can occur in the familial setting, and can also occur in naevoid BCC syndrome. BCC with sebaceous differentiation may be seen in Muir—Torre syndrome, and often has significant histological overlap with other sebaceous neoplasms.
Prognosis and predictive factors
Adnexal BCC variants do not have prognostic significance.
Fibroepithelial basal cell carcinoma
Definition
Fibroepithelial basal cell carcinoma (BCC) is a BCC variant composed of delicate, interanastomosing strands of basaloid cells surrounded by abundant fibroblastic stroma.
ICD-O code 8093/3
Synonyms
Fibroepithelioma of Pinkus; Pinkus tumour
Localization
These lesions most commonly involve the trunk, in particular the back. They are rarely multiple.
Clinical features
Fibroepithelial BCC presents as a flesh coloured nodule.
Reference:
WHO classification of skin tumours, 4th edition (2018): 26-34.