eMedicine Specialties > Dermatology > Malignant Neoplasms

Squamous Cell Carcinoma

Author: Debjani Sahni, MBBS, MRCP, Cutaneous Oncology Fellow, Brigham and Women's Hospital, Dana Farber Cancer Institute
Coauthor(s): Chrysalyne D Schmults, MD, Instructor in Dermatology, Harvard Medical School; Director, Mohs Micrographic Surgery Center, Department of Dermatology, Brigham and Women's Hospital
Contributor Information and Disclosures

Updated: Mar 18, 2009

Introduction

Background

Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer and accounts for 20% of cutaneous malignancies.1 Squamous cell carcinoma frequently arises on the sun-exposed skin of middle-aged and elderly individuals. Most squamous cell carcinomas are readily identified and removed in the physician's office as a minor surgical procedure. Larger and more invasive lesions may require aggressive surgical management, radiation therapy, or both. High-risk squamous cell carcinoma carries a significant risk of metastasis and, as such, requires careful evaluation and treatment.

General risk factors associated with the development of squamous cell carcinoma are as follows2,3,4,5,6,7,8 :

  • Age older than 50 years
  • Male sex
  • Light skin; blonde or light brown hair; green, blue, or gray eyes
  • Skin that sunburns easily (Fitzpatrick skin types I and II)
  • Geography (closer to the equator)
  • History of prior nonmelanoma skin cancer
  • Exposure to UV light (high cumulative dose of sunshine, tanning beds, or medical UV treatments)
  • Exposure to chemical carcinogens (eg, arsenic, tar)
  • Exposure to ionizing radiation (medical treatments, occupational or accidental radiation exposure)
  • Chronic immunosuppression
  • Chronic scarring conditions
  • Certain genodermatoses
  • Human papillomavirus (HPV) infection (specific subtypes)

Pathophysiology

Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes. Some cases of squamous cell carcinoma occur de novo (ie, in the absence of a precursor lesion); however, some squamous cell carcinomas arise from sun-induced precancerous lesions known as actinic keratoses (AKs). Patients with multiple AKs are at increased risk for developing squamous cell carcinoma.9 Squamous cell carcinoma is capable of locally infiltrative growth, spread to regional lymph nodes, and distant metastasis, most often to the lungs.

Frequency

United States

Determining the true incidence of squamous cell carcinoma is difficult because health registries exclude nonmelanoma skin cancer (including squamous cell carcinoma) from their databases because of the high number of cases and limited resources to collect data and because the rate of squamous cell carcinoma varies based on geographic locale. In 1994, the annual incidence in the United States ranged from 81-136 cases per 100,000 population for men and 26-59 cases per 100,000 population for women.10

Studies also confirm a dramatic increase in the incidence of cutaneous squamous cell carcinoma over the past several decades. For example, in Rochester, Minnesota, the annual age-adjusted incidence rates of squamous cell carcinoma per 100,000 women rose from 47 cases from 1984-1986 to 100 cases from 1990-1992. The corresponding rates for men increased from 126 cases to 191 cases per 100,000 population.11

One reason for the rising incidence of squamous cell carcinoma may be an increase in sun exposure in the general population. Some postulate that ozone depletion may be intensifying UV exposure. Other factors that may contribute to the increased incidence of squamous cell carcinoma include the advancing age of the US population, earlier and more frequent diagnosis of squamous cell carcinoma due to enhanced public awareness of skin cancer, and more frequent skin examinations by physicians.

Additionally, the number of patients on immunosuppressive therapy, used in solid organ transplantation and various rheumatologic and dermatologic conditions, is increasing. Squamous cell carcinoma formation has been associated with immunosuppressive drug therapy in solid organ transplantation patients, who have a markedly elevated risk of squamous cell carcinoma formation. Metastasis also may be more common in this group.12

International

Prevalence rates of squamous cell carcinoma vary in different countries. The highest incidence occurs in Australia, where the age-adjusted incidence has been calculated to be 1332 cases per 100,000 population for men and 755 cases per 100,000 population for women. Again, this is likely due to large numbers of light-skinned people in this region who have had extensive sun exposure.13

Mortality/Morbidity

Most squamous cell carcinomas are readily treated and produce few sequelae. A subset of high-risk lesions causes most of the morbidity and the mortality associated with squamous cell carcinoma. Such lesions may cause extensive destruction of tissue, and their removal may entail substantial cosmetic deformity. The overall risk of metastasis for squamous cell carcinoma is in the range of 2-6%; however, rates as high as 47% have been reported for cases with extensive perineural invasion. Lymph node metastasis is associated with significant morbidity; however, 5-year survival rates as high as 73% have been achieved with the combination of surgical lymphadenectomy and radiation therapy.14 Once lung metastasis occurs, the disease is currently incurable.

Race

Squamous cell carcinoma is the second leading cause of skin cancer in whites.1 Persons of Irish or Scottish ancestry have the highest prevalence in the United States. Squamous cell carcinoma is relatively rare in people of African and Asian descent, although it is the most common form of skin cancer in these groups. Squamous cell carcinoma in blacks carries a higher mortality rate, perhaps due to delayed diagnosis because tumors are more likely to occur in sun-protected areas, including the scalp and sites of previous injury and scarring.15

Sex

Squamous cell carcinoma occurs in men 2-3 times more frequently than it does in women, most likely as a result of greater cumulative lifetime UV exposure.

Age

The typical age at presentation is approximately 70 years; however, this varies widely, and, in certain high-risk groups (eg, organ transplant recipients [OTRs], patients with epidermolysis bullosa), squamous cell carcinoma often manifests at a much younger age.

Clinical

History

A detailed patient history often reveals the presence of one or more risk factors for squamous cell carcinoma (SCC) (see general risk factors in Background). Most squamous cell carcinomas are discovered by patients and are brought to a physician's attention by the patient or a relative. The typical squamous cell carcinoma manifests as a new or enlarging lesion that concerns the patient. Squamous cell carcinoma is typically a slow-growing malignancy, but some lesions enlarge rapidly. Although most squamous cell carcinoma patients are asymptomatic, symptoms such as bleeding, weeping, pain, or tenderness may be noted, especially with larger tumors. Numbness, tingling, or muscle weakness may reflect underlying perineural involvement, and this history finding is important to elicit because it adversely impacts prognosis.16

  • Actinically derived squamous cell carcinoma: The most common type of squamous cell carcinoma is the sun-induced type. As such, a history of long-term sun exposure dating back to childhood is frequently elicited. Many patients report having experienced multiple blistering sunburns during their lifetime, while others may have used indoor tanning beds or received UV light therapy (eg, psoralen plus UVA [PUVA] for psoriasis). Patients may have been treated in the past for sun-induced lesions such as AKs, basal cell carcinoma (BCC), melanoma, or squamous cell carcinoma.
  • Immune suppression: Patients should always be questioned about possible sources of immunosuppression. A history of solid-organ transplantation, hematologic malignancy (particularly chronic lymphocytic leukemia [CLL]), HIV infection or AIDS, or long-term use of immunosuppressive medications (eg, as treatment for an autoimmune condition) may be elicited.
  • Marjolin ulcer: This eponym refers to a squamous cell carcinoma that arises from chronically scarred or inflamed skin. Patients may report a change in the skin (eg, induration, elevation, ulceration, weeping) at the site of a preexisting scar or ulcer. The latency period is often 20-30 years; therefore, the diagnosis requires a high index of clinical suspicion.
  • HPV-associated squamous cell carcinoma: Virally induced squamous cell carcinoma most commonly manifests as a new or enlarging warty growth on the penis, vulva, perianal area, or periungual region. Patients often present with a history of "warts" that have been refractory to various treatment modalities in the past. A history of previously documented genital HPV infection may be elicited.

Physical

Squamous cell carcinoma (SCC) may manifest as a variety of primary morphologies with or without associated symptoms.

  • Squamous cell carcinoma in situ (SCCis): Squamous cell carcinoma in situ is defined histologically by atypia involving the full thickness of the epidermis but without invasion into the dermis. Clinically, lesions of squamous cell carcinoma in situ range from a scaly pink patch to a thin keratotic papule or plaque similar to an AK. Bowen disease is a subtype of squamous cell carcinoma in situ characterized by a sharply demarcated pink plaque arising on non–sun-exposed skin. Erythroplasia of Queyrat refers to Bowen disease of the glans penis, which manifests as one or more velvety red plaques.

    <BR><BR>Squamous cell carcinoma in situ, Bowen di...



    Squamous cell carcinoma in situ, Bowen disease. Courtesy of Hon Pak, MD.

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    <BR><BR>Squamous cell carcinoma in situ, Bowen di...



    Squamous cell carcinoma in situ, Bowen disease. Courtesy of Hon Pak, MD.


    <BR>Squamous cell carcinoma. Courtesy of Hon Pak,...


    Squamous cell carcinoma. Courtesy of Hon Pak, MD.

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    <BR>Squamous cell carcinoma. Courtesy of Hon Pak,...


    Squamous cell carcinoma. Courtesy of Hon Pak, MD.

  • Typical squamous cell carcinoma: The characteristic invasive squamous cell carcinoma is a raised, firm, pink-to-flesh–colored keratotic papule or plaque arising on sun-exposed skin. Approximately 70% of all squamous cell carcinomas occur on the head and neck, with an additional 15% found on the upper extremities. Surface changes may include scaling, ulceration, crusting, or the presence of a cutaneous horn. Less commonly, squamous cell carcinoma may manifest as a pink cutaneous nodule without overlying surface changes. The absence of surface changes should raise suspicion of a metastatic focus from another skin or nonskin primary site or a different and potentially more lethal tumor such as Merkel cell carcinoma. A background of severely sun-damaged skin, including solar elastosis, mottled dyspigmentation, telangiectasia, and multiple AKs, is often noted.

    <BR>Large sun-induced squamous cell carcinoma on ...


    Large sun-induced squamous cell carcinoma on the forehead/temple.

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    <BR>Large sun-induced squamous cell carcinoma on ...


    Large sun-induced squamous cell carcinoma on the forehead/temple.


    <BR>Squamous cell carcinoma. Courtesy of Hon Pak,...


    Squamous cell carcinoma. Courtesy of Hon Pak, MD.

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    <BR>Squamous cell carcinoma. Courtesy of Hon Pak,...


    Squamous cell carcinoma. Courtesy of Hon Pak, MD.

  • Periungual squamous cell carcinoma: Periungual squamous cell carcinoma typically mimics a verruca and is frequently misdiagnosed for years as a wart prior to biopsy. Less commonly, lesions may resemble chronic paronychia with swelling, erythema, and tenderness of the nail fold; onychodystrophy also may be noted.
  • Marjolin ulcer: This subtype of squamous cell carcinoma appears as a new area of induration, elevation, or ulceration at the site of a preexisting scar or ulcer. Patients with this form of squamous cell carcinoma can have a poor prognosis. The diagnosis of Marjolin ulcer should be considered in any ulcer that fails to heal with standard therapy.
  • Perioral squamous cell carcinoma: Squamous cell carcinoma of the lip usually arises on the vermillion border of the lower lip. It is sometimes predated by a precursor lesion, actinic cheilitis, which manifests as xerosis, fissuring, atrophy, and dyspigmentation. Actinic cheilitis is analogous to AK of the skin. Squamous cell carcinoma on the lip manifests as a new papule, erosion, or focus of erythema/induration. Intraoral squamous cell carcinoma typically manifests as a white plaque (leukoplakia) with or without reddish reticulation (erythroplakia). Common locations include the anterior floor of the mouth, the lateral tongue, and the buccal vestibule.
  • Anogenital squamous cell carcinoma: Squamous cell carcinoma in the anogenital region may manifest as a moist, red plaque on the glans penis; indurated or ulcerated lesions may be seen on the vulva, external anus, or scrotum. Associated symptoms include pain, pruritus, and intermittent bleeding.
  • Verrucous carcinoma: Verrucous carcinoma is a subtype of squamous cell carcinoma that can be locally destructive but rarely metastasizes. Lesions appear as exophytic, fungating, verrucous nodules or plaques, which may be described as "cauliflowerlike." Verrucous carcinoma is further subdivided based on its location in the anogenital region (Buschke-Löwenstein tumor), the oral cavity (oral florid papillomatosis), and the plantar foot (epithelioma cuniculatum).
  • Lymphadenopathy: With any invasive (not in situ) squamous cell carcinoma, regional lymph nodes should be examined. Lymph node enlargement must be further evaluated by fine-needle aspiration (FNA) or nodal biopsy.

Causes

The primary cause of most squamous cell carcinoma (SCC) is cumulative lifetime sun exposure. The frequency of squamous cell carcinoma is increased at lower latitudes, correlating with an increased intensity of ambient light. Other causes of squamous cell carcinoma are discussed below.

  • UV sunlight exposure
    • The component of sunlight believed to be most important in cutaneous carcinogenesis is UVB (290-320 nm), which is both an initiator and a promoter of carcinogenesis. In animal models, UV-induced photocarcinogenesis appears to involve the UVB and UVA-2 spectral ranges.17
    • UVB-induced photocarcinogenesis appears to work by suppressing the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage, specifically the generation of pyrimidine dimers in keratinocyte DNA that is a molecular trigger of UV-mediated immunosuppression.18
    • Inactivation of the tumor suppressor gene TP53 occurs in up to 90% of all cutaneous squamous cell carcinoma lesions.19 Other tumor suppressor genes found to be mutated in squamous cell carcinoma include P16 (INK4a) and P14 (ARF).20
  • Therapeutic UV exposure: UV light treatments used for psoriasis (and other recalcitrant dermatoses) also predispose to the development of squamous cell carcinoma. PUVA is particularly phototoxic and mutations in both TP53 and the oncogene Ha-Ras are present in a large proportion of PUVA-associated squamous cell carcinoma.21 In addition to being mutagenic, UVA in conjunction with UVB is a potent suppressor of the cutaneous immune system, which likely contributes to its role in cutaneous carcinogenesis.
  • Fair complexion: Individuals with skin types I and II account for most of the patients who develop squamous cell carcinoma; patients with oculocutaneous albinism are also at risk, and squamous cell carcinomas account for the most common type of cutaneous malignancy in this group. Such individuals lack natural protection from UV-induced carcinogenesis, owing to reduced levels of the photoprotective pigment, melanin.22
  • Ionizing radiation: Therapeutic ionizing radiation is typically associated with the later development of BCCs, but the risk of developing squamous cell carcinomas is also increased.23 Most patients with radiation-induced tumors have a remote history of x-ray therapy for acne vulgaris, although patients developing squamous cell carcinoma in radiation ports for Hodgkin disease or thyroid cancer treatment is not uncommon.
  • Chemical carcinogens: Exposure to arsenic is a well-established cause of cutaneous squamous cell carcinoma and internal cancers.4 Today, the main source of arsenic is contaminated well water, although arsenic may also be found in traditional Chinese medicines. Other carcinogens associated with squamous cell carcinoma include polycyclic aromatic hydrocarbons such as tar, soot, and pitch.
  • DNA repair failure: Healthy human skin is constantly repairing UV-induced damage through DNA repair mechanisms. Patients with xeroderma pigmentosum have a deficiency in an enzyme essential for normal DNA repair and are thus prone to the development of innumerable squamous cell carcinomas, and, less commonly, other cutaneous tumors.24
  • Iatrogenic immunosuppression: The use of immunosuppressive medications to prevent rejection in OTRs is associated with a 65- to 250-fold increased risk of developing squamous cell carcinoma compared with the general population.25
    • The primary risk factor in these patients is cumulative lifetime UV exposure in combination with having skin type I or II. This risk also increases with the number of years posttransplantation, presumably because of the cumulative effects of prolonged immunosuppressive therapy.
    • The greatest risk occurs in heart transplant patients, with diminishing risk seen in recipients of kidney and liver transplants, which correlates with the degree of immunosuppression (ie, number and/or dosage of medications) typically required to prevent rejection in these patient populations.
    • Pretransplantation end-organ disease may also impact the development of posttransplant squamous cell carcinoma. For example, among renal transplant recipients, the highest prevalence of skin cancer was observed in patients with polycystic kidney disease, while the lowest incidence was seen in those with diabetic nephropathy. Similarly, cholestatic liver disease was associated with a greater posttransplantation risk of skin cancer compared with other causes of liver failure.
  • Noniatrogenic immunosuppression: In addition to iatrogenic immunosuppression, defects in cell-mediated immunity related to lymphoproliferative disorders (eg, CLL) predispose to the development of aggressive squamous cell carcinoma. The specific mechanisms by which immunosuppression leads to squamous cell carcinoma development are poorly understood, but diminished immunosurveillance is thought to be critical. CD8+ T cells specific for the tumor suppressor gene TP53 have been observed in patients with squamous cell carcinoma, suggesting that a functional immune system may target keratinocytes expressing mutated TP53.26 Suppression of the immune system would presumably abrogate this response and might be expected to facilitate the development of squamous cell carcinoma.
  • HPV: Infection with specific subtypes of HPV is believed to play a role in the development of anogenital and periungual squamous cell carcinoma. HPV types 6 and 11 are associated with Buschke-Löwenstein tumors, whereas HPV type 16 has been frequently identified in both genital and periungual squamous cell carcinoma, suggesting the possibility of genital-digital spread.27,28 HPV types 5 and 8 are associated with cutaneous squamous cell carcinoma in transplantation patients.29
  • Chronic inflammation
    • Chronic inflammation, irrespective of the underlying etiology, may lead to the development of squamous cell carcinoma. Both noninfectious inflammatory diseases and chronic infections have been associated with squamous cell carcinoma.
    • Likewise, the Marjolin ulcer variant of squamous cell carcinoma may develop in patients with a chronic scarring condition such as dystrophic epidermolysis bullosa. In fact, the leading cause of death in patients with dystrophic epidermolysis bullosa is metastatic cutaneous squamous cell carcinoma.8 More recently, evidence suggests that patients with junctional epidermolysis bullosa may also be at increased risk for developing squamous cell carcinoma.30 The underlying pathogenesis of such lesions is not understood, but mutations in the TP53 and P16 tumor suppressor genes have been described in dystrophic epidermolysis bullosa–associated squamous cell carcinoma.31
  • Some of the conditions that predispose to the development of squamous cell carcinoma are highlighted as follows:
    • Chronic inflammatory and scarring conditions 
      • Burn scar or thermal injury
      • Venous ulcer
      • Lymphedema
      • Discoid lupus erythematosus
      • Erosive oral lichen planus
      • Lichen sclerosis et atrophicus
      • Mutilating keratoderma
      • Necrobiotic lipoidica
    • Chronic infections
      • Osteomyelitis
      • Acne conglobata
      • Hidradenitis suppurativa
      • Dissecting cellulitis of scalp
      • Lupus vulgaris
      • Lymphogranuloma venereum
      • Granuloma inguinale
      • Chronic deep fungal infection
    • Genetic syndromes and dermatoses
      • Dystrophic epidermolysis bullosa
      • Epidermodysplasia verruciformis
      • Xeroderma pigmentosum
      • Oculocutaneous albinism
      • Dyskeratosis congenita
      • Porokeratosis (Mibelli type, disseminated superficial actinic type, linear type)
      • Nevus sebaceous
      • KID (keratitis, ichthyosis, deafness) syndrome

More on Squamous Cell Carcinoma

Overview: Squamous Cell Carcinoma
Differential Diagnoses & Workup: Squamous Cell Carcinoma
Treatment & Medication: Squamous Cell Carcinoma
Follow-up: Squamous Cell Carcinoma
Multimedia: Squamous Cell Carcinoma
References
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References

  1. Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol. Mar 1992;26(3 Pt 2):467-84. [Medline].

  2. Leiter U, Garbe C. Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight. Adv Exp Med Biol. 2008;624:89-103. [Medline].

  3. Masini C, Fuchs PG, Gabrielli F, et al. Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals. Arch Dermatol. Jul 2003;139(7):890-4. [Medline].

  4. Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic arsenicism: review of seventeen cases. J Am Acad Dermatol. Feb 1998;38(2 Pt 1):179-85. [Medline].

  5. Herman S, Rogers HD, Ratner D. Immunosuppression and squamous cell carcinoma: a focus on solid organ transplant recipients. Skinmed. Sep-Oct 2007;6(5):234-8. [Medline].

  6. Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia. Dermatol Surg. Jan 2005;31(1):38-42; discussion 42. [Medline].

  7. Nguyen P, Vin-Christian K, Ming ME, Berger T. Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus. Arch Dermatol. Jun 2002;138(6):758-63. [Medline].

  8. Mallipeddi R. Epidermolysis bullosa and cancer. Clin Exp Dermatol. Nov 2002;27(8):616-23. [Medline].

  9. Newman MD, Weinberg JM. Topical therapy in the treatment of actinic keratosis and basal cell carcinoma. Cutis. Apr 2007;79(4 Suppl):18-28. [Medline].

  10. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. May 1994;30(5 Pt 1):774-8. [Medline].

  11. Gray DT, Suman VJ, Su WP, Clay RP, Harmsen WS, Roenigk RK. Trends in the population-based incidence of squamous cell carcinoma of the skin first diagnosed between 1984 and 1992. Arch Dermatol. Jun 1997;133(6):735-40. [Medline].

  12. Hampton T. Skin cancer's ranks rise: immunosuppression to blame. JAMA. Sep 28 2005;294(12):1476-80. [Medline].

  13. Buettner PG, Raasch BA. Incidence rates of skin cancer in Townsville, Australia. Int J Cancer. Nov 23 1998;78(5):587-93. [Medline].

  14. Veness MJ, Morgan GJ, Palme CE, Gebski V. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope. May 2005;115(5):870-5. [Medline].

  15. McCall CO, Chen SC. Squamous cell carcinoma of the legs in African Americans. J Am Acad Dermatol. Oct 2002;47(4):524-9. [Medline].

  16. Williams LS, Mancuso AA, Mendenhall WM. Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR detection and its impact on patient management and prognosis. Int J Radiat Oncol Biol Phys. Mar 15 2001;49(4):1061-9. [Medline].

  17. de Gruijl FR, Rebel H. Early events in UV carcinogenesis--DNA damage, target cells and mutant p53 foci. Photochem Photobiol. Mar-Apr 2008;84(2):382-7. [Medline].

  18. Katiyar SK. UV-induced immune suppression and photocarcinogenesis: chemoprevention by dietary botanical agents. Cancer Lett. 2007;255:1-11. [Medline].

  19. Ziegler A, Jonason AS, Leffell DJ, et al. Sunburn and p53 in the onset of skin cancer. Nature. Dec 22-29 1994;372(6508):773-6. [Medline].

  20. Brown VL, Harwood CA, Crook T, Cronin JG, Kelsell DP, Proby CM. p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma. J Invest Dermatol. May 2004;122(5):1284-92. [Medline].

  21. Ziegler A, Jonason AS, Leffell DJ, et al. Sunburn and p53 in the onset of skin cancer. Nature. Dec 22-29 1994;372(6508):773-6. [Medline].

  22. Perry PK, Silverberg NB. Cutaneous malignancy in albinism. Cutis. May 2001;67(5):427-30. [Medline].

  23. Karagas MR, Nelson HH, Zens MS, et al. Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure. Epidemiology. Nov 2007;18(6):776-84. [Medline].

  24. Zghal M, El-Fekih N, Fazaa B, et al. [Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 49 Tunisian cases]. Tunis Med. Dec 2005;83(12):760-3. [Medline].

  25. Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. J Am Acad Dermatol. Jul 2002;47(1):1-17; quiz 18-20. [Medline].

  26. Black AP, Bailey A, Jones L, Turner RJ, Hollowood K, Ogg GS. p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma. Br J Dermatol. Nov 2005;153(5):987-91. [Medline].

  27. Alam M, Caldwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases. J Am Acad Dermatol. Mar 2003;48(3):385-93. [Medline].

  28. Della Torre G, Donghi R, Longoni A, et al. HPV DNA in intraepithelial neoplasia and carcinoma of the vulva and penis. Diagn Mol Pathol. Mar 1992;1(1):25-30. [Medline].

  29. Stockfleth E, Nindl I, Sterry W, Ulrich C, Schmook T, Meyer T. Human papillomaviruses in transplant-associated skin cancers. Dermatol Surg. Apr 2004;30(4 Pt 2):604-9. [Medline].

  30. Mallipeddi R, Keane FM, McGrath JA, Mayou BJ, Eady RA. Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa. J Eur Acad Dermatol Venereol. Sep 2004;18(5):521-6. [Medline].

  31. Arbiser JL, Fan CY, Su X, et al. Involvement of p53 and p16 tumor suppressor genes in recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. J Invest Dermatol. Oct 2004;123(4):788-90. [Medline].

  32. Jambusaria-Pahlajani A, Hess S, Berg D, Schmults CD. Equipoise exists in the peri-operative management of cutaneous squamous cell carcinoma with perineural invasion: A survey study of American College of Mohs Surgery surgeons. Manuscript under review.

  33. Hess SD, Jambusaria A, Katz K, Schmults CD. Clinical equipoise exists in the peri-operative management of high-risk cutaneous squamous cell carcinoma: A survey study of American College of Mohs Surgery surgeons. Manuscript under review.

  34. Williams LS, Mancuso AA, Mendenhall WM. Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR detection and its impact on patient management and prognosis. Int J Radiat Oncol Biol Phys. Mar 15 2001;49(4):1061-9. [Medline].

  35. Land R, Herod J, Moskovic E, et al. Routine computerized tomography scanning, groin ultrasound with or without fine needle aspiration cytology in the surgical management of primary squamous cell carcinoma of the vulva. Int J Gynecol Cancer. Jan-Feb 2006;16(1):312-7. [Medline].

  36. Cho SB, Chung WG, Yun M, Lee JD, Lee MG, Chung KY. Fluorodeoxyglucose positron emission tomography in cutaneous squamous cell carcinoma: retrospective analysis of 12 patients. Dermatol Surg. Apr 2005;31(4):442-6; discussion 446-7. [Medline].

  37. Brantsch KD, Meisner C, Schonfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. Aug 2008;9(8):713-20. [Medline].

  38. Ross AS, Schmults CD. Sentinel lymph node biopsy in cutaneous squamous cell carcinoma: a systematic review of the English literature. Dermatol Surg. Nov 2006;32(11):1309-21. [Medline].

  39. Bargman H, Hochman J. Topical treatment of Bowen's disease with 5-Fluorouracil. J Cutan Med Surg. Mar-Apr 2003;7(2):101-5. [Medline].

  40. Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens ML. Imiquimod 5% cream in the treatment of Bowen's disease. J Am Acad Dermatol. Mar 2001;44(3):462-70. [Medline].

  41. Smith KJ, Hamza S, Skelton H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clin Exp Dermatol. Sep 2004;29(5):505-12. [Medline].

  42. Marmur ES, Schmults CD, Goldberg DJ. A review of laser and photodynamic therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg. Feb 2004;30(2 Pt 2):264-71. [Medline].

  43. Jambusaria-Pahlajani A, Miller C, Quon H. Surgical monotherapy versus surgery plus radiotherapy in high risk cutaneous squamous cell carcinoma: A systematic review of outcomes. Dermatol Surg. In press.

  44. Wollina U, Hansel G, Koch A, Kostler E. Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin. J Cancer Res Clin Oncol. May 2005;131(5):300-4. [Medline].

  45. Otley CC, Cherikh WS, Salasche SJ, McBride MA, Christenson LJ, Kauffman HM. Skin cancer in organ transplant recipients: effect of pretransplant end-organ disease. J Am Acad Dermatol. Nov 2005;53(5):783-90. [Medline].

  46. Kuflik EG, Gage AA. The five-year cure rate achieved by cryosurgery for skin cancer. J Am Acad Dermatol. Jun 1991;24(6 Pt 1):1002-4. [Medline].

  47. Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol. Aug 1992;27(2 Pt 1):241-8. [Medline].

  48. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. Jun 1992;26(6):976-90. [Medline].

  49. Holmkvist KA, Roenigk RK. Squamous cell carcinoma of the lip treated with Mohs micrographic surgery: outcome at 5 years. J Am Acad Dermatol. Jun 1998;38(6 Pt 1):960-6. [Medline].

  50. Robins P, Dzubow LM, Rigel DS. Squamous-cell carcinoma treated by Mohs' surgery: an experience with 414 cases in a period of 15 years. J Dermatol Surg Oncol. Oct 1981;7(10):800-1. [Medline].

  51. Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol. Apr 2005;141(4):456-64. [Medline].

  52. Tan PY, Ek E, Su S, Giorlando F, Dieu T. Incomplete excision of squamous cell carcinoma of the skin: a prospective observational study. Plast Reconstr Surg. Sep 15 2007;120(4):910-6. [Medline].

  53. Chen K, Craig JC, Shumack S. Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol. Mar 2005;152(3):518-23. [Medline].

  54. Mrass P, Rendl M, Mildner M, et al. Retinoic acid increases the expression of p53 and proapoptotic caspases and sensitizes keratinocytes to apoptosis: a possible explanation for tumor preventive action of retinoids. Cancer Res. Sep 15 2004;64(18):6542-8. [Medline].

  55. Papoutsaki M, Lanza M, Marinari B, et al. The p73 gene is an anti-tumoral target of the RARbeta/gamma-selective retinoid tazarotene. J Invest Dermatol. Dec 2004;123(6):1162-8. [Medline].

  56. Clayman GL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. Feb 1 2005;23(4):759-65. [Medline].

  57. Brantsch KD, Meisner C, Schonfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. Aug 2008;9(8):713-20. [Medline].

  58. Ross AS , Miller F, Elenitsas R, Xu X, Troxel AB, Schmults CD. Diameter of involved nerves predicts outcome in cutaneous squamous cell carcinoma with perineural invasion: an investigative-blinded retrospective cohort study. Under review.

  59. Jensen P, Hansen S, Moller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. Feb 1999;40(2 Pt 1):177-86. [Medline].

  60. Euvrard S, Kanitakis J, Decullier E, et al. Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma. Transplantation. Apr 27 2006;81(8):1093-100. [Medline].

  61. Veness MJ, Quinn DI, Ong CS, et al. Aggressive cutaneous malignancies following cardiothoracic transplantation: the Australian experience. Cancer. Apr 15 1999;85(8):1758-64. [Medline].

  62. Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia. Dermatol Surg. Jan 2005;31(1):38-42; discussion 42. [Medline].

  63. Frierson HF Jr, Deutsch BD, Levine PA. Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Hum Pathol. Dec 1988;19(12):1397-402. [Medline].

  64. Lobo DV, Chu P, Grekin RC, Berger TG. Nonmelanoma skin cancers and infection with the human immunodeficiency virus. Arch Dermatol. May 1992;128(5):623-7. [Medline].

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Further Reading

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Keywords

squamous cell carcinoma, skin cancer, SCC, actinic keratoses, SCC in situ, Bowen disease, Bowen's disease, keratotic invasive SCC, leukoplakia, erythroplasia of Queyrat, nodular SCC, periungual SCC, Marjolin ulcer, actinically derived SCC, adenoid squamous cell carcinoma, ASCC, adenosquamous cell carcinoma, verrucous carcinoma,  keratoacanthoma,  oral florid papillomatosis, epithelioma cuniculatum, giant condyloma of Buschke and Löwenstein, malignant tumor of keratinocytes, sun-induced cancerous lesions

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Contributor Information and Disclosures

Author

Debjani Sahni, MBBS, MRCP, Cutaneous Oncology Fellow, Brigham and Women's Hospital, Dana Farber Cancer Institute
Debjani Sahni, MBBS, MRCP is a member of the following medical societies: British Association of Dermatologists, Royal College of Physicians, and St John's Dermatological Society
Disclosure: Nothing to disclose.

Coauthor(s)

Chrysalyne D Schmults, MD, Instructor in Dermatology, Harvard Medical School; Director, Mohs Micrographic Surgery Center, Department of Dermatology, Brigham and Women's Hospital
Chrysalyne D Schmults, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Society for Dermatologic Surgery, and International Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Medical Editor

R Stan Taylor, MD, Professor of Dermatology, University of Texas Southwestern Medical School; Director of Skin Surgery and Oncology Clinic, Department of Dermatology, University of Texas Southwestern Medical Center
R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Mary Farley, MD, Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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