A brief refresher with useful tables, figures, and research summaries

Keratinocyte carcinomas (KCs) include cutaneous squamous-cell carcinomas (SCCs) and basal-cell carcinomas (BCCs). Keratinocyte carcinomas are the most common cancers in the United States — more common than all other cancers combined. The term “nonmelanoma skin cancer” (NMSC) is still frequently used to refer to BCCs and SCCs, although this nonspecific terminology encompasses other cancers, such as Merkel cell carcinoma, dermatofibrosarcoma protuberans (DFSP), angiosarcoma, and various appendageal cancers. Therefore, when referring specifically to SCCs and BCCs, the term “keratinocyte carcinoma” is preferred.

The incidence of KC increases with the following factors:

• age

• cumulative sun exposure

• sun-sensitive skin: light hair, blue eyes, easily sunburned

• immunosuppression (e.g., after solid organ transplantation, immunosuppressive therapy of autoimmune disease, chronic lymphocytic leukemia): chronic immunosuppression significantly increases risk for developing cutaneous malignancies, particularly SCC (up to 65 times the risk in the general population)
  
  

The following table lists risk factors for development of BCCs: 

Actinic keratoses (AKs) are precursor lesions to SCCs and found in the same phenotypic patient populations. AKs are precancerous and treated with more conservative approaches; an estimated 1 in 100 AKs will progress to SCCs. 

Basal-cell carcinomas (BCCs) can have many different appearances. The most common forms are superficial and nodular BCCs.

Key features of nodular BCC include a translucent, pink, smooth papule with slight shine, scale, and prominent vessels. The following images show the appearance of various nodular BCCs:

The following images of BCC are from a 1992 NEJM review article Nonmelanoma Cancers of the Skin:

Note the prominent telangiectasia in this translucent papule.

Note the pink macular areas with irregular borders, telangiectasia, loss of skin markings, and small erosions.

The tumor measured 16 mm in diameter. Note the rolled border and the low level of telangiectasia relative to that in the surrounding photodamaged skin. Characterized by scar-like depression and typically more aggressive.

The lesion resembles a malignant melanoma but has rolled, translucent borders. Pigmented BCC ae commonly mistaken for melanoma or benign seborrheic keratoses.

Seemingly Limited Basal-Cell Carinoma in a 45-Year-Old Woman (Panel A) and the Defect (Measuring 30 by 38mm) Resulting from Surgical Efforts to Obtain a Tumor-free Tissue Margin (Panel B). BCC with significant subclinical extension after Mohs surgery. BCC with significant subclinical extension after Mohs surgery.
(Source: Nonmelanoma Cancers of the Skin. N Engl J Med 1992.)

Additional images of BCCs can be found here.

Squamous-cell carcinomas (SCCs) can also have variable clinical presentations. Cutaneous SCCs are most commonly found on chronically sun-exposed skin, as hyperkeratotic ovoid plaques or papules. The following images show some examples of SCCs:

Multiple hyperkeratotic papules and plaques on the scalp and an ulcerated nodule with hemorrhagic crust on the left scalp.
(Source: VisualDx)

The following images are from a 1992 NEJM review article Nonmelanoma Cancers of the Skin:

Squamous-Cell Carcinoma Measuring 20 mm in Diameter with Elevated Red Borders and Central Erosion.

Well-Differentiated Squamous-Cell Carcinoma Measuring 10 mm in Diameter. The lesion is clinically indistinguishable from keratoacanthoma (see image below).

Squamous-Cell Carcinoma and Arsenical Keratoses of the Palms and Soles

Keratoacanthoma Measuring 10 mm in Diameter with Central Keratin Plug. The lesion is clinically indistinguishable from well-differentiated squamous-cell carcinoma (see image above). Keratoacanthoma are typically fast-growing but less invasive.

An eroded and crusted plaque on the shin.
(Source: VisualDx)

An eroded and crusted plaque on the shin.
(Source: VisualDx)

A diagnosis of BCC or SCC should be confirmed via skin biopsy, using either punch or shave technique. See this NEJM video of the punch biopsy procedure.

Staging of SCCs should be performed in high-risk cases. The Brigham and Women’s Hospital Tumor Staging for Cutaneous Squamous-Cell Carcinoma has been found to have better prognostic value than other criteria and includes upstaging for poorly differentiated tumors, depth of tumor invasion ≥2 cm, perineural invasion, and invasion beyond subcutaneous fat.

The approach to treatment of BCCs and SCCs is similar; in both cases the goal is cure. Patients who are immunosuppressed (e.g., solid-organ–transplant recipients or patients with chronic lymphocytic leukemia) should be managed aggressively, ideally in dedicated high-risk skin cancer clinics.

Surgery

Surgery is associated with the highest cure rate (95%–99% at 5 years). Surgical treatment includes:

• wide local excision

• Mohs micrographic surgery
  
  

Nonsurgical Options

Nonsurgical treatment is associated with lower long-term cure rates than surgery in some cases, although it is appropriate for many cases of low-risk keratinocyte carcinomas. Nonsurgical treatment options include:

• electrodesiccation and curettage

• topical creams (e.g., 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac)

• cryotherapy

• localized radiation therapy

• laser therapy

• intralesional methotrexate, 5-fluorouracil

• photodynamic therapy

• oral chemotherapy
  
  

Metastatic keratinocyte carcinomas require systemic chemotherapeutics, immunotherapies, or novel small-molecule–targeted inhibitors. In the case of metastatic BCCs, vismodegib (hedgehog pathway inhibitor) is FDA approved for this indication. Metastatic or locally advanced cutaneous SCC management can involve adjuvant radiation therapy, sentinel lymph node biopsy, chemotherapy (e.g., cisplatin, 5-fluorouracil), epidermal growth factor–receptor inhibitors (e.g., cetuximab), and immunotherapy (e.g., nivolumab, ipilimumab). For more details see the National Comprehensive Cancer Network (NCCN) guidelines.