Basal cell and squamous cell cancer

Skin cancer can be divided into melanoma (see separate text and examples) and non-melanoma skin cancer (NMSC). The two most frequent subtypes of NMSC are basal cell carcinoma and squamous cell carcinoma. Both these types of cancer are one of the most common cancer types in humans. Currently, between 2 and 3 million NMSC occur globally each year. The incidence of NMSC is rising across the world and it is believed to be tripled by 2050. Ultraviolet radiation from the sun is considered the main etiological factor with some additional factors listed below. The primary treatment is the surgical removal of the tumor, which in most cases is sufficient for cure.

Basal cell carcinoma is the most common form of cancer in Caucasians and is rare in populations with more pigmented types of skin. Its incidence outnumbers all other forms of skin cancer taken together as it represents around two-thirds of all cancers diagnosed in the skin. Excessive sun exposure, especially in young adulthood, is considered as an important risk factor. Rare cases are associated with inherited genetic syndromes such as Gorlin-Goltz syndrome. Basal cell carcinomas grow in hair-bearing skin and the most common location is the facial skin. Alike other epithelial malignancies, they exhibit invasive growth, but only in exceptional and rare cases does this type of tumor appear to develop metastases and thus prognosis is excellent.

Basal cell carcinoma develops without any known precursor stages and such stepwise tumor progression is not a feature. The progenitor cell for this cancer is believed to reside within the niche of hair follicle stem cells. Classification of Basal cell carcinoma is descriptive and major subtypes can be identified based on the microscopic growth pattern as superficial, nodular, pigmented, basal cell carcinoma with adnexal differentiation, micronodular, infiltrating, basosquamous, sclerosing, and basal cell carcinoma with sarcomatoid differentiation. The first four subtypes bear low risk for locally aggressive behavior and metastasis, while others are considered as high-risk subtypes.

The common histopathological features of basal cell cancer include undifferentiated tumor cells (basal cell-like) with a palisading arrangement of nuclei in the periphery of tumor nests. The tumor is often seen as connected to the epidermis and surrounding the tumor there is often a specialized loose connective tissue stroma rich in fibroblasts and collagen. The sclerosing type shows diffuse invasive growth of small strands of tumor cells immersed in abundant fibroblastic tumor stroma. Rarely, the tumor has areas similar to squamous cells carcinoma (basosquamous type) or various sarcomas (basal cell carcinoma with sarcomatoid differentiation).

Squamous cell carcinoma of the skin is a common form of human cancer, mainly in Caucasian populations, and is most frequently located in facial skin and skin subjected to chronic sun exposure. The main risk factor for cutaneous squamous cell cancer is accumulated exposure to ultraviolet radiation from the sun. It is also more frequent in immunosuppressed individuals (mainly associated with solid organ transplantation). In such patients, infection with human papillomaviruses (HPV) is a contributing factor for tumor development. Rare cases are associated with inherited genetic syndromes such as Xeroderma pigmentosum.

Squamous cell carcinoma in the skin typically develops through precursor stages. A common precursor lesion is an actinic keratosis, which is defined as epidermal dysplasia without invasive growth in combination with signs of ultraviolet damage in the dermis (solar elastosis). Squamous cell carcinoma in the skin can progress to poorly differentiated cancer and eventually develop metastases. The development of metastases is uncommon for squamous cell cancer of ordinary skin. However, Squamous cell carcinoma in immunosuppressed patients and in skin areas adjacent to mucosal surfaces, e.g. lips and peri-genital/anal skin can often be more aggressive and metastasize to regional lymph nodes.

Typical histopathological features of cutaneous squamous cell carcinoma include the growth of atypical cells with squamous differentiation into the dermis and deeper-lying structures. The tumors can vary in degree of differentiation from well-differentiated tumors with extensive keratinization to poorly differentiated tumors with severe cellular atypia and only hinted signs of squamous differentiation. Less common morphological variants are keratoacanthoma, acantholytic, spindle- and clear-cell squamous cell carcinoma.

Histological diagnosis of both basal and squamous cell carcinoma is usually straightforward. Basal cell carcinoma shows immunoreactivity toward antibodies against epithelial cell adhesion molecule (clone BerEP4), bcl2, and CD10, which is useful for differentiation of this tumor from tumors originating in skin adnexal elements. Cutaneous squamous cell cancer expresses cytokeratins (e.g. KRT5) and in poorly differentiated and spindle-cell variants, expression of p63 and p40 can be useful in the diagnosis.