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Skin Cancers, Common

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Skin Cancers, Common

Basics

Description

Malignant transformation of normal melanocytes; BRAF, NRAS, C-KIT, CKDN2A mutations implicated

Any of the following is alert of possible cancer:

Biopsy for histological diagnosis, excisional biopsy if possible of any lesion suspicious of melanoma

No baseline or surveillance laboratory test recommended (1)[B]

Not routinely indicated; but obtain if regional lymphadenopathy and/or neurologic symptoms suggestive of perineural involvement (1)[C]

Differentiates between skin cancer types and subtypes, determines high-risk histologic features, and for melanoma, determines stage of disease

Radiation therapy = option for poor surgical candidates (1,2)[B]

Acetretin often used for chemoprevention; associated with lower rates of SCC

View LargeHistologic Tumor ThicknessRecommended Margin of ResectionIn situ5 mm ≤1 mm1 cm1 " 2 mm1 " 2 cm (plus SLN biopsy) ≥2 mm2 cm (plus SLN biopsy)

Indicated for melanomas of >1 mm depth (stage (II) or <1 mm with poor histologic prognostic features; mitoses >1/mm2; ulceration) (6)[A]

View LargePrimaryRecurrentBCCBCCMohs1%6%Surgical excision5 " 10%12 " 17%ED& C8%18 " 40%Cryosurgery8%13%Radiation therapy7 " 9%10%

Modified from: Uptodate.com

View Large5-YearSurvivalStage IA ≤1 mm, no ulceration ≥95%Stage IB ≤1 mm + ulcer 1 " 2 mm89 " 91%Stage IIA1 " 2 mm + ulcer 2 " 4 mm77 " 79%Stage IIB2 " 4 mm + ulcer ≥4 mm63 " 67%Stage IIC>4 mm + ulcer45%Stage IIINodal involvement27 " 70%Stage IVDistant metastases<20%

1 NCCN clinical practice guidelines in oncology: Basal cell and squamous cell skin cancers, 2011;v.1. Available at http://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf [Accessed September 2011].2Kwasniak LA, Garcia-Zuazaga J. Basal cell carcinoma: evidence-based medicine and review of treatment modalities. Int J Dermatol. 2011;50:645 " 658. [View Abstract]3Motley R, Kersey P, Lawrence C. Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. Br J Dermatol. 2002;146:18 " 25. [View Abstract]4Cox NH, Eedy DJ, Morton CA. Guidelines for management of Bowen 's disease: 2006 update. Br Assoc Dermatol. 2006;156:11 " 21.5Shimizu I, Cruz A, Chang KH. Treatment of squamous cell carcinoma in situ. Dermatol Surg. 2011;37:1 " 18. [View Abstract]6Garbe C, Peris K, Hauschild A. Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. European J Cancer. 2010;46:270 " 283. [View Abstract]

  • Skin cancers are the most common types of cancer, accounting for 50% of all cancers.
  • The 3 most common in decreasing order: Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma
  • BCC and SCC are often classified as "non-melanoma skin cancer "  (NMSC).

Epidemiology

  • Most common skin cancer (80% of NMSC)
  • Men > Women (1.5:1)
  • US incidence rate: 150/100,000 women
  • Peak incidence: 50 " “80 years old (>40 years)
  • Second most common (20% of NMSC)
  • Men > Women (3.1:1)
  • US incidence rate: 24/100,000 women
  • Peak incidence: 70 years old
  • <40 years old: Women > Men
  • Incidence in US is 16.7/100,000 women; with increasing incidence in women <40 years old
  • Lifetime risk in US is 1 in 57 (risk increases to 1 in 33 when including melanoma in situ)
  • Peak incidence: 60 years old; but most common cancer in women aged 30 " “34 years

Risk Factors

  • Phenotypic factors: Fair skin that burns/freckles, blond/red hair, blue/green eyes
  • Genetic syndromes: Xeroderma pigmentosum (BCC, SCC), dystrophic nevoid BCC syndrome, bazex syndrome (BCC), rombo syndrome (BCC), epidermo-dysplasia verruciformis (SCC), oculocutaneous albinism (SCC, melanoma), epidermolysis bullosa (SCC#1 cause death)
  • Sun exposure (#1 risk factor), outdoor occupations, residence at high altitudesBCC = intermittent burning; SCC = chronic long-term exposure
  • Tanning bed usage: Odds ration for BCC (1.5), SCC (2.5)
  • Psoralen + UVA (PUVA): >200 sessions (SCC)
  • Radiation therapy (dose dependent)3 ƒ — increased risk NMSC, long latency
  • Chemical exposures (SCC > BCC), exposure to carcinogenic agents, tobacco use (SCC)Pesticides, asphalt, tar, and polycyclic aromatic hydrocarbons, arsenicLong latency period
  • Human papillomavirus infection (SCC)Oncogenic strains 16, 18, especially anogenital, periungual
  • Chronic immunosuppression, solid organ transplantation (SCC > BCC)
  • 64 ƒ — increased risk SCC; usually 10 years outIn darkly pigmented patients, 30 " “40% SCCs develop in scars or nonhealing ulcers.
  • BCC = intermittent burning; SCC = chronic long-term exposure
  • 3 ƒ — increased risk NMSC, long latency
  • Pesticides, asphalt, tar, and polycyclic aromatic hydrocarbons, arsenic
  • Long latency period
  • Oncogenic strains 16, 18, especially anogenital, periungual
  • In darkly pigmented patients, 30 " “40% SCCs develop in scars or nonhealing ulcers.
  • Phenotype: Light skin, tendency to burn, red or blond hair, light eyes
  • Family history of melanoma (1 " “2 in first-degree relative, or multiple in distant relatives)
  • Genetic syndromes: Xeroderma pigmentosum; dysplastic nevus syndrome
  • Sun exposure (intermittent burning); tanning bed usage; PUVA treatment (>200 sessions); residence in equatorial latitudes
  • History of previous melanoma (3 " “5% risk of developing second); >100 benign nevi; atypical nevi; history of NMSCs
  • Chronic immunosuppression, Hodgkin 's lymphoma

General Prevention

  • Sun protection: Clothing, hat, sunglasses, sunscreen applied during time of greatest sun intensity (10 a.m. and 4 p.m.)
  • Sunless tanning lotion if tanned skin desired
  • Monthly self skin exams recommended; call provider with any new or changing lesion (1)[C]

Pathophysiology

  • All skin cancers thought to involve multistep process of progressive genetic mutations
  • UV radiation causes DNA replication/transcription errors and suppresses immune system.
  • Arise from pluripotential keratinocytes in basal layer of epidermis of follicular structures
  • P53 tumor suppressor gene, patched (PTCH)/hedgehog pathway gene mutations implicated
  • Malignant transformation of nl keratinocytes
  • Some cases occur de novo; others arise from sun-induced precursor lesions (actinic keratoses)
  • P53 tumor suppressor gene, epidermal growth factor receptor (EGFR), and cyclooxygenase (COX) gene mutations implicated

Diagnosis

History

  • New or changing (size, shape, color) lesion
  • Lesions that does not heal or bleeds with minimal trauma
  • Pain at site
  • Personal history of skin cancer
  • Personal/family history of melanoma
  • Determine other risk factors for skin cancers

Physical Exam

  • Determine size, location, and whether there is connection to underlying structures
  • Note if borders are well or poorly defined
  • Note scars (Is it a recurrent tumor?)
  • Examine for satellite lesions
  • Examine lymph nodes (LN), and in case of melanoma, full LN exam
  • Full body skin exam to exclude other cutaneous malignancies
  • Typically on sun-exposed skin
  • Multiple subtypes: Clinical appearance varies
  • Nodular variant (60%): Pearly flesh-colored papule or nodule, +/ " “ rolled borders, with magnification, branching telangiectasias
  • Superficial variant: Pink/red, well-circumscribed thin scaly plaque,+/ " “ thready border
  • Typically on chronically sun-exposed skin
  • SCC in situ: Thin scaly pink plaque
  • Invasive squamous cell carcinoma: Indurated erythematous plaque, often with crusting, ulceration, or hyperkeratotic scale resembling a horn
  • Commonly on legs and back; can occur on any skin/mucosal surface (scalp, nail bed, mouth, labia, sclera)
  • May be raised or flat with surface of skin
  • New or changing lesion with >1 of "ABCDs " Asymmetry, Border irregularity, Color variegation (>1 color), Diameter >6 mm
  • Asymmetry, Border irregularity, Color variegation (>1 color), Diameter >6 mm

Tests

Differential Diagnosis

  • Pigmented lesions: Nevus, atypical nevus, seborrheic keratosis
  • Nonpigmented lesions: Angiofibroma, actinic keratosis, molluscum contagiosum, sebaceous hyperplasia intradermal nevus, verruca vulgaris

Treatment

Basal Cell Carcinoma

  • Mohs micrographic surgery (1,2)[B] yields lowest recurrence for primary/recurrent BCC.Indicated for high-risk or recurrent facial BCCs
  • Surgical excision (1,2)[B] for high-risk non-face primary/recurrent BCCs
  • Indicated for high-risk or recurrent facial BCCs
  • Surgical excision: 4 mm margin of normal skin (clears 95% BCCs <2 cm diameter) (1,2)[B]
  • Electrodesiccation and curettage (ED & C): Cost-effective for trunk or extremities (2)[B]
  • Cryotherapy: For superficial BCC or to ensure clear margins of nodular BCC (1)[C]
  • Options for lowest risk BCCs or when patients are unable to tolerate other modalities (2)[C]Topical 5-fluorouracil 5% (1,2)[A] " “ FDA-approved regimen; 2 ƒ — day for 3 " “6 weeks
  • Superficial subtype only (90% cure rate) (2)[C]Topical imiquimod 5% cream (1,2)[A] " “ FDA-approved regimen: 5 ƒ —/week qhs ƒ — 6 weeks; not indicated for use on face, hands, feet
  • Superficial subtype only (low cure rates) (2)[C]Photodynamic therapy (PDT) (1,2)[A]; not yet FDA approved for treatment of BCC
  • Topical 5-fluorouracil 5% (1,2)[A] " “ FDA-approved regimen; 2 ƒ — day for 3 " “6 weeks
  • Topical imiquimod 5% cream (1,2)[A] " “ FDA-approved regimen: 5 ƒ —/week qhs ƒ — 6 weeks; not indicated for use on face, hands, feet
  • Photodynamic therapy (PDT) (1,2)[A]; not yet FDA approved for treatment of BCC

Squamous Cell Carcinoma

  • Remove entire tumor and confirm negative margins as metastasis possible (5 " “10%) and recurrence carries worse prognosis (1)[C]
  • Risk factors for SCC recurrence (% metastasis): Lips (13.7%), ears (11%), temples, genitalia; >2 cm (or 1.5 cm on ear or lip); histology with poor differentiation; history of recurrent tumor; immunosuppression; occurring within a scar or chronic wound (up to 35%)
  • Mohs micrographic surgery (1,3)[B]
  • Surgical excision: 6 mm margins (1,3)[B]
  • Mohs surgery (if high-risk location) (4,5)[B]
  • Surgical excision: 4 " “6 mm margins (4,5)[B]
  • Cryotherapy (4,5)[B]
  • ED & C (4,5)[B]
  • Radiation therapy (1,3)[B]
  • Scoop excision followed by cryotherapy or ED & C
  • Topical 5-fluorouracil (4,5)[B] " “ off-label
  • Topical imiquimod (4,5)[B] " “ off-label

Melanoma

  • Typically within 4 " “6 weeks of diagnosis (6)[C]
  • No impact of margin on survival, may have an effect on local/regional recurrence
  • Surgical margins determined by thickness of tumor (depth of invasion) (6)[A]

Additional Treatment

  • Refer BCCs/SCCs with high-risk features for Mohs surgery
  • Refer melanoma ≥1 mm depth (or with high-risk features) to general surgery for simultaneous re-excision and SLN biopsy
  • Refer metastatic disease to oncology

Ongoing Care

Follow-Up Recommendations

  • Close follow-up to assess post-treatment effects, detect local recurrences and new skin cancers (but no national guidelines exist)
  • During each visit, evaluate and palpate scar for recurrence. Any changes should be biopsied.
  • Full body skin exams 2 " “4 ƒ —/year for 5 " “10 years (6)[C] to detect loco-regional recurrence earlyIf <1 mm: q6 months to 1 year
  • If <1 mm: q6 months to 1 year

Prognosis

  • Age-adjusted mortality rate: 0.12/100,000. Slow growing, rare metastasis (0.028 " “0.55%)
  • Local recurrence: ¢ ˆ ¼50% of recurrences apparent within 2 years post-treatment; 80% within 5 years. Recurrence after 10 years rare.
  • Recurrence rates by treatment modality:
  • SCCIS: Rate of progression to SCC = 3 " “5%. Metastasis (5 " “10%) typically occurs within 5 years.
  • Age-adjusted mortality for invasive SCC: 0.26/100,000 persons
  • Patients with one SCC have 40% risk of developing additional SCCs within next 2 years.
  • If detected early, possible cure with excision. 85% diagnosed as localized skin disease.Most important prognosticators = tumor thickness; ulceration/mitoses on histology
  • Most important prognosticators = tumor thickness; ulceration/mitoses on histology

Complications

  • Local recurrence can occur with all skin cancers and all treatment modalities.
  • Patients with history of skin cancer at increased risk for subsequent skin cancers and for developing and dying from noncutaneous cancers.

References

Codes

ICD9

  • 172.00 Melanoma
  • 173.90 Unspecified malignant neoplasm of skin, site unspecified
  • 173.91 Basal cell carcinoma of skin, site unspecified
  • 173.92 Squamous cell carcinoma of skin, site unspecified
  • 173.99 Other specified malignant neoplasm of skin, site unspecified
  • 172.9 Melanoma of skin, site unspecified

ICD10

  • C44.90 Unspecified malignant neoplasm of skin, unspecified
  • C44.91 Basal cell carcinoma of skin, unspecified
  • C44.92 Squamous cell carcinoma of skin, unspecified
  • C44.99 Other specified malignant neoplasm of skin, unspecified
  • C43.9 Malignant melanoma of skin, unspecified

SNOMED

  • 372130007 malignant neoplasm of skin (disorder)
  • 429114002 malignant basal cell neoplasm of skin (disorder)
  • 254651007 squamous cell carcinoma of skin (disorder)
  • 93655004 malignant melanoma of skin (disorder)

Clinical Pearls

  • Sun exposure is the major risk factor for skin cancer, but skin cancer can occur on any skin surface.
  • Basal cell carcinoma is slow growing, but can produce significant local destruction. Metastasis is rare.
  • Squamous cell carcinoma is often slow growing, but with greater potential to metastasize (5 " “10%). SCC is the #1 cause of skin cancer deaths in the elderly.
  • Melanoma is the #1 cause of skin cancer deaths in young adults. Early detection is key to long-term survival.