Clinical Reference / Therapeutic Strategies / Non-Melanoma Skin Cancers (NMSC): Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC)

Non-Melanoma Skin Cancers (NMSC): Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC)


Key Points

  • Accurate and timely diagnosis is essential to guide the appropriate management of any skin cancer.
  • A skin biopsy is strongly recommended if there is any question regarding the diagnosis.
  • Surgical excision is almost always the first line treatment for most non-melanoma skin cancers.
  • Mohs micrographic surgery is a tissue-sparing surgical excision technique that may be used to remove clinically indistinct skin cancers or lesions on the face or other body sites.
  • Patients who are immunocompromised (HIV/AIDS, solid organ transplant or bone marrow transplant patients, patients with lymphoma and leukemia, or iatrogenically-immunosuppressed patients) have an increased risk of non-melanoma skin cancers, especially squamous cell carcinoma, and should be monitored very closely for the evolution of NMSCs.
  • UV (ultraviolet) light plays significant role in the pathogenesis of NMSC.
  • Vismodegib is a new medical therapeutic option for the treatment of advanced local or metastatic basal cell carcinoma.

Initial Evaluation: Basal Cell Carcinoma

Basal cell carcinomas (BCCs) have several key clinical features:

  • BCC is the most common cancer in humans.
  • It commonly presents as a pearly papule or plaque or nodule (i.e., nodular BCC) sometimes with exaggerated telangiectasias or central ulceration.
  • Some forms are hyperkeratotic (i.e., superficial BCC), pigmented (i.e., pigmented BCC), or scar-like (i.e., morpheaform BCC).
  • In general, BCCs are relatively slow-growing tumors and may develop over months to years and invade locally rather than metastasize. If left untreated, the tumor will progress to invade subcutaneous tissue, muscle, or even bone.

BCCs are best managed by physicians expert in their recognition, natural history, and treatment. Failure to correctly manage tumors initially may lead to significant cosmetic deformity. A biopsy to confirm the diagnosis should be performed before treating any lesion.

Classic basal cell carcinomas present as a pearly papule with exaggerated telangiectasia and central ulceration within

Superficial basal cell carcinomas: erythematous scaly plaques with sharply-demarginated borders

Pigmented basal cell carcinomas: pearly plaques with pigmentation

Morpheaform basal cell carcinomas: indurated flesh-colored or hypopigmented plaques with dermal infiltration, telangiectasias

Differential Diagnosis

Actinic keratoses

Bowen’s disease (squamous cell carcinoma in situ): erythematous hyperkeratotic plaques with slight induration and crusting

Principles of Basal Cell Carcinoma Management

The histologic subtype and anatomic location are important considerations in the management of BCCs, thus a biopsy is necessary to guide optimal treatment choice. Although most subtypes are amenable to standard surgical excision, some (such as morpheaform or micronodular) are best treated with Mohs micrographic surgery. Superficial BCCs can be treated with cryosurgery, curettage and electrodesiccation, topical imiquimod or 5-fluorouracil therapy, or photodynamic therapy (PDT).

Initial therapy

First-line therapy: Surgical excision

  • Surgical excision with a 3 to 5 mm margin of normal tissue is usually optimal. Send the specimen for pathologic evaluation to assure adequacy of excision.
  • In cases when surgery is not possible (i.e., elderly persons and/or in the debilitated, clinically indistinct borders or extensive area) or contraindicated, radiation therapy provides excellent results. It is also excellent for surgically complex lesions.
  • For superficial or small (under 1 cm) lesions of the trunk, cryosurgery or curettage and electrodesiccation (C & E) provide an acceptable cure rate and good cosmetic outcome. C & E scars may be unsightly, and so this is not the preferred treatment for facial lesions, and is not recommended for large primary BCC, morpheiform or recurrent BCC. Complications of cryosurgery include scarring and postinflammatory pigmentary changes.
  • Indications for Mohs micrographic surgery: refer to a dermatologist
    • Facial lesions over 1 cm in diameter that have been present for more than 2 years and lesions located on the temple, eyelid, medial canthus, nose, and nasolabial fold, as they are more likely to recur
    • Recurrent BCCs
    • Lesions with clinically indistinct margins
    • Histopathology is morpheaform or micronodular pattern
    • Tumors greater than 2 cm in diameter on the body
    • Tumors that will require extensive reconstruction to repair the surgical defect

Alternative therapy

  • Topical imiquimod 5% cream (such as Aldara)
  • 5-fluorouracil
  • Photodynamic therapy (PDT). Referral to dermatologist is strongly recommended

Subsequent therapy

  • Patient education with respect to pathogenesis and natural history of basal cell carcinomas is essential. Sun protection must be stressed.
  • Perform a complete examination of all sun exposed skin on the initial visit and then quarterly following definitive treatment for the first year. Annual full-body skin examination thereafter is indicated to identify future development of tumor recurrence and new skin cancers.

Initial Evaluation: Squamous Cell Carcinoma

Predisposing factors for squamous cell carcinoma (SCC) include precursor lesions (actinic keratosis [AK], Bowen’s disease), UV exposure, ionizing radiation, environmental carcinogens (arsenic), immunosuppression, scars, burns, human papillomavirus (HPV), genodermatoses (xeroderma pigmentosum, albinism).

Squamous cell carcinomas of the skin have several key clinical features:

  • Hyperkeratotic, erythematous papules and plaques
  • Have superficial ulceration
  • Typically occur on sun-exposed areas
  • Carry a higher risk for metastasis than BCC

Principles of Squamous Cell Carcinoma Management

The diagnosis of SCC is based on biopsy; a superficial biopsy may reveal only an in situ (epidermal) component and may miss the invasive component that is underlying or adjacent to the area of biopsy. Close clinical follow-up is necessary.

Initial therapy

First-line therapy: Surgical excision

  • Surgical excision with 3 to 5 mm margins. Pathologic evaluation of the margins should be performed for adequacy of resection.
  • Careful palpation of regional lymph nodes before surgery is required.

Alternative therapy

  • Destructive measures (curettage and electrodesiccation or cryotherapy) may also be curative, but do not provide margins for pathologic confirmation of adequacy of resection.
  • For lesions not easily excised, or in patients who are not good surgical candidates, radiation therapy may be used.
  • Patients with multiple and/or clinically aggressive lesions may require systemic retinoid therapy (acitretin, such as Soriatane) for chemoprophylaxis of future recurrence or development of primary lesions. Referral to a dermatologist or oncologist is recommended.

Subsequent therapy

  • Close clinical follow-up, with careful examination of the surgery site, draining lymph nodes, and the rest of the patient’s exposed skin should be performed.
  • As these lesions are usually found on sun exposed areas, and because photodamage is likely an important factor in the pathogenesis of SCC, photoprotection should be emphasized.

Initial Evaluation: Keratoacanthoma

Keratoacanthomas are rapidly-growing (within few weeks) nodular proliferations of keratinocytes that may represent a variant of squamous cell carcinoma. In some cases, lesions are self-involuting over a period of few months. They should be closely monitored for complete involution, or alternatively, managed with complete surgical excision. Intralesional chemotherapy, such as with bleomycin, is also an alternative therapy for lesions that do not completely self-involute.

Dome-shaped, crateriform hyperkeratotic nodule on sun exposed skin

Initial Evaluation: Bowen’s Disease (Squamous Cell Carcinoma in Situ)

The eponym Bowen’’s disease is used to describe squamous cell carcinoma in situ on any cutaneous surface except the glans penis. It bears several clinical features:

  • Untreated, Bowen’’s disease may progress to invasive squamous cell carcinoma.
  • Bowen’’s disease may occur on sun exposed sites, on extragenital sites where actinic lesions are rare (palms, trunks of persons with no history of sun exposure), in the genital region, and on the glans penis (erythroplasia of Queyrat or penile intraepithelial neoplasia [PIN]).
  • Actinically induced lesions are considered a step in the progression of actinic keratoses to squamous cell carcinoma.

Erythematous, hyperkeratotic plaques with slight induration and crusting

Differential Diagnosis

Actinic Keratosis

Superficial basal cell carcinoma: an erythematous scaly plaque with a sharply demarginated border.

Principles of Squamous Cell Carcinoma In Situ Management

The diagnosis of SCC in situ requires biopsy; clinically, these lesions may clinically resemble actinic keratoses or squamous cell carcinoma. Partial biopsy is sometimes the most feasible but carries the risk of missing underlying or adjacent invasive component.

Initial therapy

First-line therapy: Surgical excision

  • Complete surgical excision is the preferred therapy when feasible. This may require staged excision.
  • For smaller lesions of SCC in situ on the trunk (under 1 cm), curettage and electrodessication (C&E) with close clinical follow-up is appropriate.
  • Lesions with indistinct clinical margins, or on the face, especially adjacent to the eyelids, nose, or lips, should strongly be considered for Mohs micrographic surgery as both a tissue-sparing treatment and for complete excision.
  • Imiquimod 5% cream applied once daily (5 days a week) for a 6-week treatment period may be attempted. The area will become erythematous and may erode.
  • Photodynamic therapy (as above).

Alternative therapy

  • For lesions not easily excised, or in patients who are not good surgical candidates, radiation therapy may be used.
  • Cryotherapy with thermocouple control, as done for other cutaneous carcinomas, may be curative.

When to refer to a dermatologist

  • Clinical cases requiring Mohs micrographic surgery or photodynamic therapy.
  • For management of patients with large, clinically-aggressive, metastatic, or multiple lesions.
  • For management of multiple NMSC diagnosed in the setting of immunosuppression.

Clinical Cases

Case 1

  • 42-year-old man with a slowly-enlarging lesion on the right infraorbital cheek
  • No prior history of skin malignancy
  • Patient is otherwise healthy
  • Skin exam: 5 x 7 mm pearly plaque with central dell and prominent telangiectasias; a full-body skin examination does not identify any other suspicious lesions
  • Biopsy reveals nodular and micronodular BCC

Initial therapy

Referral for Mohs surgery with repair (indications: histopathology, proximity to eye)

Follow-up

  • 3 months for full-body skin examination
  • Photoprotection recommended

Case 2

  • 50-year-old woman with a scaly lesion on the back of unknown duration
  • No prior history of skin malignancy
  • Patient is otherwise healthy
  • Skin exam: 8 x 8 mm sharply-demarcated pink plaque with minimal scale; a full-body skin examination does not identify any other suspicious lesions
  • Biopsy reveals superficial BCC

Initial therapy

  • The patient is offered surgical excision, photodynamic therapy, and imiquimod cream treatment and opts for imiquimod
  • Imiquimod 5% cream is applied daily to the lesion for 6 weeks
  • Follow-up evaluation at 8-10 weeks

Follow-up

  • The patient reports significant erythema, crusting, and inflammation at the site of imiquimod application, which has now subsided; there is no evidence of persistent skin cancer at the treatment site
  • A full-body skin examination is performed and does not identify any other suspicious lesions
  • Follow-up evaluation at 3 months for full-body skin examination
  • Photoprotection recommended

Case 3

  • 47-year-old man presents for evaluation of a new lesion on the arm that has been growing over 3 months
  • No prior history of skin cancer
  • Patient is otherwise healthy
  • Skin exam: 1.2 x 0.8 cm pearly plaque with telangiectasias on the right arm; a full-body skin examination does not reveal additional suspicious lesions
  • Biopsy reveals: nodular BCC

Initial therapy

  • Surgical excision with 3mm margins with complex linear closure; the excisional specimen is sent to pathology to determine adequacy of surgical margins
  • Follow-up in 2 weeks for suture removal, and again at 3 months for full-body skin examination

Follow-up evaluation at 3 months

  • A full-body skin examination is performed, and no suspicious lesions are identified; the surgical excision is well-healed without evidence of recurrence
  • Photoprotection recommended
  • Follow-up evaluation at 3 months for full-body skin examination

References

Brunner M et al (2014) Assessment of the new nodal classification for cutaneous SCC and its effect on patient stratification, Head Neck, Epub ahead of print.

Cox NH, Eedy DJ, Morton CA (2007) Guidelines for management of Bowen’s disease: 2006 update, BJD, 156:11-21.

Karia PS, Jambusaria-Pahlajani A, Harrington DP, Murphy GF, Qureshi AA, Schmults CD. (2014) Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital Tumor Staging for Cutaneous Squamous Cell Carcinoma. J Clin Onc, 32(4):327-34.

Morton CA et al (2008) Guidelines for topical photodynamic therapy: update, BJD, 159:1245-66.

Sekulic A et al (2012) Efficacy and safety of vismodegib in advanced basal cell carcinoma, NEJM, 366:2171-9.