171 squamous cell carcinoma

PART 13DeRmATology

999SQUAMOUS CELL CARCINOMA

171 �SQUAMOUS�CELL�CARCINOMA

Jonathan�B.�Karnes,�MDRichard�P.�Usatine,�MD

PATIeNT SToRy

A 66-year-old farmer presents with new growths on his scalp (Figure 171-1). The patient admits to lots of sun exposure and has already had one squamous cell carcinoma (SCC) excised from the scalp 5 years ago. On close inspection there are many suspicious areas for SCC (Figure 171-1). Figure 171-2 demonstrates a shave biopsy of a SCC on a scalp using a dermablade. The pathology demonstrated that 2 of 3 biopsy sites were positive for SCC (E and G were SCC and F was read as actinic keratoses). The patient was referred for Mohs surgery. The Mohs surgeon recommended field treatment with 5-fluoruracil for 4 weeks before surgery to minimize the amount of cutting that would be needed to clear the SCC from this diffusely sun-damaged scalp.

INTRoDUCTIoN

Cutaneous SCC is the second most common cancer in humans and arises most often as a result of cumulative sun damage. Although the mortality is declining, incidence is increasing in all populations making this cancer a common and significant burden on patients.

ePIDemIology

• Mortality from SCC has been observed as 0.29 per 100,000 population.1

• Metastasis from SCC occurs in 2% to 9.9% of cases.2

• The incidence is increasing in all age groups and populations at a rate of 3% to 10%.2

• In the United States, approximately 2500 people die from SCC every year.3

• SCC is the second most common skin cancer and accounts for up to 25% of nonmelanoma skin cancers.4

• More than 250,000 new cases of invasive SCC are diagnosed annually in the United States.4

PATHoPHySIology

SCC is a malignant tumor of keratinocytes. Most SCCs arise from precursor lesions called actinic keratoses. SCCs usually spread by local extension but are capable of regional lymph node metastasis and distant metastasis. Human papillomavirus (HPV)-related lesions may be found on the penis, labia, and perianal mucosa, or in the periun-gual region or elsewhere associated with immunosuppression.5

FIGURE 171-2 Shave biopsy of a squamous cell carcinoma on the scalp. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-1 Multiple squamous cell carcinomas on the scalp of a farmer with a lot of sun exposure. The pathology demonstrated that 2 of 3 biopsy sites were positive for squamous cell carcinoma (E and G were squamous cell carcinomas and F was read as actinic keratosis). (Courtesy of Richard P. Usatine, MD.)

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DeRmATology1000 SQUAMOUS CELL CARCINOMA

SCCs that metastasize most often start on mucosal surfaces and sites of chronic inflammation.

RISK FACToRS

• Long-term cumulative UV exposure is the greatest risk factor.

• Childhood sunburns.

• Occupational exposure.

• Other UV exposure including PUVA therapy and tanning beds.

• Smoking.

• HPV exposure.

• Exposure to ionizing radiation.

• Arsenic exposure.

• Fair skin.

• Age older than 60 years.

• Male gender.

• Living at lower latitude and higher altitude.

• Nonhealing ulcers.

• Chronic or severe immunosuppression, including posttransplant immunosuppression, HIV, and long-term steroid use.

• Genetic syndromes, including Muir Torre, xeroderma pigmento-sum, dystrophic epidermolysis bullosa, epidermodysplasia verruci-formis, and oculocutaneous albinism.4

DIAgNoSIS

• The only sure method of making the diagnosis is a biopsy. Biopsy suspicious lesions (thickened, tender, indurated, ulcerated, or crusting) especially in sun-exposed areas.

CLINICAL FEATURES

SCC often presents as areas of persistent ulceration, crusting, hyperkeratosis, and erythema, especially on sun-damaged skin.

Less common types of SCC:

• Marjolin ulcer—SCC of the extremities found in chronic skin ulcers or burn scars. This is a more common risk in darker pig-mented individuals (Figure 171-3).

• Erythroplasia of Queyrat—SCC in situ on the penis or vulva related to HPV infection (Figure 171-4). This can progress to invasive SCC of the penis (Figure 171-5).

TYPICAL DISTRIBUTION

SCC is found in all sun-exposed areas and on mucus membranes. The most common sites are:

• Face (Figures 171-6 and 171-7).

• Lower lip (Figures 171-8 and 171-9).

• Ears (Figure 171-10).

• Scalp (Figures 171-1 and 171-11).

• Extremities—arm—(Figures 171-12 and 171-13).

FIGURE 171-4 Erythroplasia of Queyrat (squamous cell carcinoma in situ) under the foreskin of an uncircumcised man. This is related to human papil-lomavirus infection as is cervical cancer. (Courtesy of John Pfenninger, MD.)

FIGURE 171-5 Squamous cell carcinoma of the glans penis. (Courtesy of Jeff Meffert, MD.)

FIGURE 171-3 Marjolin ulcer (squamous cell carcinoma) arising in a burn that occurred years before on the face. (Courtesy of Richard P Usatine, MD.)

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• Hands (Figure 171-14).

• Fingers (Figure 171-15).

• Mucus membranes (Figure 171-16) (see Chapter 43, Oral Cancer).

BIOPSY

• Deep shave biopsy is adequate to make the diagnosis of most SCCs.

• Punch biopsy or incisional biopsy is an alternative for lesions that are pigmented or appear to be deeper.

FACTORS AFFECTING METASTATIC POTENTIAL OF CUTANEOUS SQUAMOUS CELL CARCINOMA6

The following factors are taken from “Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma.”6

Site.Tumor location influences prognosis: sites are listed in order of in-

creasing metastatic potential.2

1. SCC arising at sun-exposed sites excluding lip and ear.

2. SCC of the lip (Figures 171-8 and 171-9).

3. SCC of the ear (Figure 171-10).

4. Tumors arising in non–sun-exposed sites (e.g., perineum, sacrum, sole of foot) (Figures 171-4, 171-5, and 171-16).

5. SCC arising in areas of radiation or thermal injury, chronic drain-ing sinuses, chronic ulcers, chronic inflammation, or Bowen dis-ease, such as the SCC arising in a burn site (Figure 171-3).

Size: diameter.

Tumors larger than 2 cm in diameter are twice as likely to recur locally (15.2% vs. 7.4%), and 3 times as likely to metastasize (30.3% vs. 9.1%) as smaller tumors (Figure 171-17).

Size: depth.

Tumors greater than 4 mm in depth (excluding surface layers of keratin) or extending down to the subcutaneous tissue (Clark level V) are more likely to recur and metastasize (metastatic rate 45.7%) com-pared with thinner tumors. Recurrence and metastases are less likely in tumors confined to the upper half of the dermis and less than 4 mm in depth (metastatic rate 6.7%).

hiStologic diFFerentiation.

Poorly differentiated tumors have a poorer prognosis, with more than double the local recurrence rate and triple the metastatic rate of better differentiated SCC. Tumors with perineural involvement are more likely to recur and to metastasize.

hoSt immunoSuppreSSion.

Tumors arising in patients who are immunosuppressed have a poorer prognosis. Host cellular immune response may be important both in determining the local invasiveness of SCC and the host’s response to metastases. Figures 171-16, 171-17, and 171-18 are SCCs in patients who are HIV-positive.

previouS treatment and treatment modality.

The risk of local recurrence depends upon the treatment modality. Locally recurrent disease itself is a risk factor for metastatic disease.

A

B

FIGURE 171-6 A. Squamous cell carcinoma on the nose of an 88-year-old woman. B. Subtle small squamous cell carcinoma on the nasal alae. Note that any crusting lesion on the face may be a squamous cell carcinoma no matter how small it is. (Courtesy of Richard P. Usatine, MD.)

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A

B

FIGURE 171-7 A. Large cystic appearing squamous cell carcinoma on the face. Although this could have been a basal cell carcinoma, it defi-nitely required a biopsy and excision. B. Small subtle invasive squa-mous cell carcinoma on the face that could have been overlooked or treated as an actinic keratosis. Any scaling lesion on the face that per-sists should be biopsied. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-9 Squamous cell carcinoma showing ulceration on the lower lip of a man that was a smoker. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-8 Squamous cell carcinoma on the lower lip growing rapidly in a patient that was taking an immunosuppressive medication after a renal transplant. (Courtesy of Richard P. Usatine, MD.)

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FIGURE 171-14 Squamous cell carcinoma in situ on the thenar eminence of the hand. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-13 3 Large ulcerating squamous cell carcinoma on arm. (Courtesy of Jonathan B. Karnes, MD.)

FIGURE 171-12 Large squamous cell carcinoma on the leg of a home-less man. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-11 Squamous cell carcinoma on the shaven scalp of a 35-year-old man, which was formerly mistaken for a wart. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-10 Squamous cell carcinoma arising in an actinic keratosis on the helix of a 33-year-old woman. (Courtesy of Richard P. Usatine, MD.)

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A

B

FIGURE 171-15 Two different appearing cases of squamous cell carci-noma on the finger. A. It took 2 shave biopsies to establish the correct diagnosis in this case. B. Squamous cell carcinoma in situ with human papillomavirus changes and pigment incontinence in a 35-year-old woman. The irregular hyperpigmented lesion on the proximal nailfold was originally suspicious for melanoma. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-16 perianal invasive squamous cell carcinoma in an human immunodeficiency virus-positive man who had engaged in anal inter-course and was infected with human papillomavirus. The ulcerations were suspicious for invasive squamous cell carcinoma and not typical of condyloma acuminata.(Courtesy of Richard P. Usatine, MD.)

FIGURE 171-17 Large squamous cell carcinoma on the arm of an human immunodeficiency virus-positive 51-year-old man. It grew to this size in 1 year and took 2 biopsies to get a definitive diagnosis. Differential diagnosis includes mycosis fungoides. (Courtesy of Richard P. Usatine, MD.)

FIGURE 171-18 Squamous cell carcinoma invading the internal nasal structures in an human immunodeficiency virus-positive man who was afraid of having a biopsy done earlier. patient referred to ear, nose, and throat specialist. (Courtesy of Richard P. Usatine, MD.)

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Local recurrence rates are considerably less with Mohs micrographic surgery than with any other treatment modality.

DIFFeReNTIAl DIAgNoSIS

• Actinic keratoses are precancers on sun-exposed areas, which can progress to SCC (see Chapter 166, Actinic Keratosis and Bowen Disease).

• Bowen disease is SCC in situ before it invades the basement membrane (see Chapter 166, Actinic Keratosis and Bowen Disease).

• Keratoacanthoma is a subtype of SCC that may resolve spontane-ously, but is generally treated as a low risk SCC. Figure 171-19 shows an invasive SCC resembling a lower-risk keratoacanthoma subtype (see Chapter 167, Keratoacanthoma).

• Basal cell carcinoma (BCC) cannot always be distinguished from SCC by clinical appearance alone. Figure 171-17A could be a BCC by appearance but was proven to be SCC by biopsy (see Chapter 170, Basal Cell Carcinoma).

• Merkel cell carcinoma (neuroendocrine carcinoma of the skin) is a rare aggressive malignancy. It is most commonly seen on the face of white elderly persons. It can resemble a SCC and the diagnosis is made on biopsy (Figure 171-20).

• Nummular eczema can usually be distinguished by the multiple coin-like shapes, transient nature, and pruritus (Chapter 145, Atopic Dermatitis).

mANAgemeNT

The following recommendations are derived from the “Multiprofes-sional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma.” table 171-1 for a summary of treatment options.

Surgical resection for definitive treatment should include margins as given below:

• 4-mm margin—Should be adequate for well-defined, low-risk tumors less than 2 cm in diameter, such margins are expected to remove the primary tumor mass completely in 95% of cases.5 SoR A

• 6-mm margin—Recommended for larger tumors, high-risk tumors, tumors extending into the subcutaneous tissue and those in high-risk locations (ear, lip, scalp, eyelids, nose).5

MOHS MICROGRAPHIC SURGERY

Frederick Mohs pioneered a technique for excising cutaneous tumors with immediate analysis of a continuous margin mapped to the clini-cal site. Mohs surgery offers superior cure rates compared with stan-dard excision or destructive techniques, spares uninvolved tissue, and allows for reconstruction at the time of excision.

Mohs surgery may be considered for any continuous tumor, but is specifically indicated for lesions larger than 2 cm, lesions with ill- defined clinical borders, lesions with aggressive histologic subtypes, recurrent lesions, and lesions on or near the eye, nose, ear, mouth,

FIGURE 171-20 Merkel cell carcinoma on the lower lip of an elderly woman. This is an aggressive cancer with a high mortality rate. (Courtesy of Jeff Meffert, MD.)

FIGURE 171-19 Squamous cell carcinoma on the shoulder of an human immunodeficiency virus-positive man. Note that the pearly bor-ders and telangiectasias resemble a basal cell carcinoma and the cen-tral crater suggests that this could be a keratoacanthoma. (Courtesy of Richard P. Usatine, MD.)

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TablE 171-1 Summary of Treatment Options for primary Cutaneous Squamous Cell Carcinoma

Treatment Indications Contraindications Notes

Surgical excision All resectable tumors Where surgical morbidity is likely to be unreasonably high

Generally treatment of choice for SCC

high-risk tumors need wide margins or histologic margin control

Mohs’ micrographic surgery/excision with histologic control

high-risk tumors, recurrent tumors

Where surgical morbidity is likely to be unreasonably high

Treatment of choice for high-risk tumors

Radiotherapy Nonresectable tumors Where margins are ill-defined

Curettage and cautery Small, well-defined, low-risk tumors

high-risk tumors Curettage may be helpful prior to surgical excision

Cryotherapy Small, well-defined, low-risk tumors

high-risk tumors, recurrent tumors

Only suitable for experienced practitioners

Reprinted from Motley R, Kersey p, Lawrence C. Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. BrJ Plast Surg. 2003;56:85-91.

hair-bearing scalp, or chronic ulcers. Patients with chronic immuno-suppression or genetic tumor syndromes may also benefit from Mohs surgery compared to standard excision.4

CURETTAGE AND ELECTRODESICCATION

Excellent cure rates have been reported in several series, and experience suggests that small (<1 cm), well-differentiated, primary, slow-growing tumors arising on sun-exposed sites can be removed by experienced physicians with electrodessication and curettage (EDC).5

The experienced clinician undertaking EDC can detect tumor tissue by its soft consistency, which may be of benefit in identifying invisible tumor extension and ensuring adequate treatment. Electro-desiccation is applied to the curetted wound and the curettage-cautery cycle then repeated twice. SoR C

CRYOSURGERY

Good short-term cure rates have been reported for small, histologi-cally confirmed SCC treated by cryosurgery in experienced hands. Prior biopsy is necessary to establish the diagnosis histologically. There is great variability in the use of liquid nitrogen for cryotherapy. Start by drawing a 4- to 6-mm margin around the SCC and then use a total freeze time of 60 seconds. This can be divided up into two 30-second freezes with a thaw in between. Most patients prefer local anesthetic because these long freeze times are quite painful. SoR C

Cryosurgery and curettage and electrodesiccation are not appro-priate for locally recurrent disease.

RADIOTHERAPY

Radiation therapy alone offers short- and long-term cure rates for SCC that are comparable with other treatments. It is recommended for lesions arising on the lip, nasal vestibule (and sometimes the out-side of the nose), and ear. Certain very advanced tumors, where sur-gical morbidity would be unacceptably high, may also be best treated by radiotherapy. SoR C

ELECTIVE PROPHYLACTIC LYMPH NODE DISSECTION

Elective prophylactic lymph node dissection has been proposed for SCC on the lip that is greater than 6 mm in depth and for cutaneous SCC that is greater than 8 mm in depth, but evidence for this is weak. SoR C

PReVeNTIoN AND SCReeNINg

• All skin cancer prevention starts with sun protection.

• There is good evidence from multiple randomized controlled trials (RCTs) that daily sunscreen use decreases the risk of developing sun-related SCCs.7,8 SoR A In the longest RCT, sunscreen was applied regularly to the head, neck, hands, and forearms for 4.5 years with a decrease in SCC during the study period.7 After cessa-tion of the trial, the participants were followed for another 8 years and SCC tumor rates were significantly decreased, by almost 40%, during the entire follow-up period.8

• Sun protection should include sun avoidance, especially during peak hours of UV transmission, protective clothing, and sunscreen use.

• Indoor tanning is not safe and should be avoided.

• United States Preventive Services Task Force has not found suffi-cient evidence to recommend regular screening for any skin cancer in the general population.9

• Most experts believe that persons at high risk for SCC (including previous personal history of any skin cancer, high-risk family his-tory and high-risk skin types with significant sun exposure, on immunosuppression after an organ transplant) should be screened regularly for skin cancer by a physician trained in such screening.

• Evidence for the value of self-screening is lacking but persons at high risk for skin cancer should also be encouraged to observe their own skin and to come in for evaluation if they see any suspicious changes or growths.

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PRogNoSIS

Prognosis is excellent for small, thin lesions less than 2 mm thick that are removed with clear margins in immunocompetent patients. In these patients, the risk of metastasis is near zero. The risk of metastasis increases markedly with thicker lesions and lesions with thicknesses greater than 6 mm metastasize to the regional nodes 16% of the time.10

FolloW-UP

Patients should be seen at least yearly for skin examinations after the diagnosis and treatment of a SCC. The 3-year risk of recurrence of a new SCC after having a single SCC is 18%.11

PATIeNT eDUCATIoN

Includes use of a hat and sunscreen on a regular basis with frequent follow-up for early recognition of new skin cancers.

REFERENCES

1. Lewis KG, Weinstock MA. Nonmelanoma skin cancer mortality (1988-2000): the Rhode Island follow-back study. Arch Dermatol. 2004;140(7):837-842.

2. Weinberg AS, Ogle CA, Shim EK. Metastatic cutaneous squamous cell carcinoma: an update. Dermatol Surg. 2007;33(8):885-899.

3. American Cancer Society. Cancer Facts & Figures 2010, http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-and-figures-2010, accessed June 1, 2012.

4. Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology, 3rd ed. Philadel-phia, PA: Saunders; 2012:2776.

5. Berg D, Otley CC. Skin cancer in organ transplant recipients: epi-demiology, pathogenesis, and management. J Am Acad Dermatol. 2002;47(1):1-17; quiz 18-20.

6. Motley R, Kersey P, Lawrence C. British Association of Dermatol-ogists, British Association of Plastic Surgeons. Multiprofessional guidelines for the management of the patient with primary cutane-ous squamous cell carcinoma. Br J Plast Surg. 2003;56(2):85-91.

7. Green A, Williams G, Neale R, et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet. 1999;354:723-729. Erratum: Lancet. 1999;354:1038.

8. van der Pols JC, Williams GM, Pandeya N, Logan V, Green AC. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev. 2006;15(12):2546-2548.

9. Wolff T, Tai E, Miller T. Screening for Skin Cancer: An Update of the Evidence for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2009, http://www.ncbi.nlm.nih.gov/books/NBK34051/.

10. Brantsch KD, Meisner C, Schönfisch B, et al. Analysis of risk fac-tors determining prognosis of cutaneous squamous-cell carci-noma: a prospective study. Lancet Oncol. 2008;9(8):713-720.

11. Marcil I, Stern RS. Risk of developing a subsequent nonmela-noma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and metaanalysis. Arch Dermatol. 2000;136(12):1524-1530.

PROVIDER RESOURCES

• Medscape. Head and Neck Cutaneous Squamous Cell Carcinoma—http://emedicine.medscape.com/article/1965430-overview.

• Skinsight. INFORMED: Melanoma and Skin Cancer Early Detection—http://www.skinsight.com/info/for_professionals/skin-cancer-detection-informed/skin-cancer-education.

• Chapters and videos on diagnosing and surgically managing SCC can be found in the following book/DVD or electronic app: Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Proce-dures in Office Practice. Philadelphia, PA: Elsevier; 2012.

Information about smartphone and tablet apps of this resource can be viewed at www.usatinemedia.com.

PATIENT RESOURCES

• The Skin Cancer Foundation. Squamous Cell Carcinoma—http://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma.

• PubMed Health. Squamous Cell Carcinoma—http://www.ncbi.nlm.nih.gov/pubmedhealth/pmh0001832/.

• Skinsight. Squamous Cell Carcinoma—http://www.skinsight.com/adult/squamouscellcarcinomaScc.htm.

• MedlinePlus. Squamous Cell Carcinoma—http://www.nlm.nih.gov/medlineplus/ency/article/000829.htm.

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171 squamous cell carcinoma

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