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Squamous Cell Carcinoma of the Skin

Cutaneous Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) of the skin is one of the three most frequent skin cancers with about 250,000 new cases diagnosed each year in the United States. Although most patients with the condition are cured, more than a tenth of them will eventually develop metastases. Treatment for small, superficial lesions is by electrodesiccation and curettage, while surgical excision or Mohs micrographic surgery are used for invasive disease.


Presentation

A significant lifetime ultraviolet radiation exposure is the principal determinant of squamous cell carcinoma (SCC) and the disease appears most frequently in the older, fair-skinned population [1]. Increased use of natural or artificial sunlight by the younger generation may be one of the reasons for the rising incidence of cutaneous squamous cell carcinoma (cSCC) [2] [3]. Chronic skin ulceration and an immunosuppressed state are also predisposing factors for this malignant disease.

The carcinoma appears most commonly on sun-exposed areas, mainly on the head and neck. Changes are often present on the forehead, scalp, lip, and ears. The presentation is variable and the tumor could arise in the form of a plaque, nodule, or non-healing ulcer with scaling and crusting. The size is an important indicator for the risk of metastasis, as is the rate of growth and the state of differentiation of the cells. Growths larger than 2 cm metastasize more frequently than smaller ones [4] [5]. Another factor influencing the rate of metastases is the location with the lips and ears among the most dangerous areas.

There are several forms of cSCC, which may range from in situ neoplasm to metastatic disease. Cutaneous SCC often develops from actinic keratoses which are very common, scaly and small precancerous lesions found on sun-exposed areas [6]. Different studies report varying rates for actinic keratoses turning into invasive cSCC, while about a quarter of them will regress within a year [7]. Actinic cheilitis, another precancerous lesion, appears on a lip as a fissure or dry patch, and sometimes develops into SCC. Squamous cell carcinoma in situ, in some cases called Bowen disease, is a precursor of fully developed cSCC. Invasive cSCC could spread locally and metastasize [4]. The variant of SCC, Marjolin ulcer, can develop at the sites of chronic inflammation and has an over 30% metastasis and mortality rate [8] [9] [10].

Conjunctival squamous cell carcinoma has a variable appearance. An unusual pterygium may indicate the presence of a tumor, hence all resected pterygia should undergo histologic examination [11].

Fatigue
  • (b) Number of adverse events by the end of treatment The most frequently encountered adverse effects associated with the combined adjuvant therapy regimen were dry skin, fatigue, and generalised eye and lip reactions ( Brewster 2007 ).[doi.org]
  • In both cohorts, the median duration of response was 7.6 months.[ 50 ][ Level of evidence: 3iiiDiv ] The most common adverse events were muscle spasms, alopecia, dysgeusia, weight loss, and fatigue.[cancer.gov]
Severe Pain
  • At our first observation, the patient was asthenic, with severe pain and functional limitations. There was also a superinfection due to Pseudomonas Aeruginosa resistant to antibiotics, and a G3 anemia secondary to the bleeding lesion.[ncbi.nlm.nih.gov]
Otalgia
  • Additionally, local symptoms such as dysphagia or otalgia (for a progressive squamous cell carcinoma on the face) are prominent. In the United States an estimated 3932 to 8791 patients died from invasive cutaneous squamous cell carcinoma in 2012.[dermatologyadvisor.com]
Ulcer
  • Univariate analysis identified previous skin lesions (ulcers and scars) as risk factor for lymph node metastasis (p 0.047). Better survival was demonstrated for T3 (p 0.018) classification.[ncbi.nlm.nih.gov]
  • The primary tumor of both patients showed complete regression, leaving ulceration. In patient 1, the ulceration completely resolved after 3 months. Patient 2 underwent surgical resection and full-thickness skin grafting.[ncbi.nlm.nih.gov]
  • The presentation is variable and the tumor could arise in the form of a plaque, nodule, or non-healing ulcer with scaling and crusting.[symptoma.com]
  • Forty-one of these patients had a clear history of a preexisting thermal burn or irradiation dermatitis (Marjolin's ulcer). The average lesion was over 2 cm in diameter, and the average Marjolin's ulcer was over 5 cm.[ncbi.nlm.nih.gov]
  • […] desmoplastic histological SCC subtype; ear, lip, hand, feet or genital tumor site; presence of perineural or lymphovascular invasion; nodal metastasis at presentation; recurrent SCC; SCC arising from scars or chronic skin disease, for example, chronic ulcers[ncbi.nlm.nih.gov]
Fair Complexion
  • Causes Those at greatest risk are: Those who have fair complexions and poor tanning capacity (burn easily Over 55 years of age Male (two to three times more common in men than in women) Have worked outdoors most of their lives Have been exposed to chemical[healthcentral.com]
  • Fair complexion Persons with a fair complexion; hazel, blue, or gray eyes; and light-colored hair (blond or red), as well as those who burn easily when exposed to the sun, are at higher risk for cSCC than are persons with other physical characteristics[emedicine.medscape.com]
  • complexion, 3 blue eyes, 11 male sex, 11,12 and older age at transplant.[skintherapyletter.com]
  • People with a fair complexion, light coloured hair and burn easily are particularly prone.[skincheckwa.com.au]
Blonde Hair
  • People at the highest risk for developing basal cell carcinoma have fair skin, red or blond hair, and green, blue, or gray eyes.[nyulangone.org]
  • Individuals with light-colored skin, freckled skin, blond hair, red hair, and light eyes have a greater risk for skin cancer.[innerbody.com]
  • Red or blond hair. Although having a fair complexion is a risk factor for skin cancer and actinic keratosis, people of all skin colors can get skin cancer and actinic keratosis.[web.archive.org]
  • Individuals with fair complexions, red or blonde hair, and a propensity to sunburn rather than tan are at increased risk of developing SCC ( Gallagher 1995 ).[doi.org]
Skin Plaque
  • Slow-growing ulcer or reddish skin plaque. Bleeding may occur from the tumour. SCC may give rise to local metastases or spread to local lymph nodes [ 1 ].[patient.info]
  • The lesion caused by SCC is often asymptomatic Ulcer or reddish skin plaque that is slow growing Intermittent bleeding from the tumor, especially on the lip The clinical appearance is highly variable Usually the tumor presents as an ulcerated lesion with[en.wikipedia.org]
Mechanically Fragile Skin
  • People with the inherited condition recessive dystrophic epidermolysis bullosa (RDEB), in which there is a defect in the type VII collagen gene whereby either no collagen VII or very low levels are produced resulting in a mechanically fragile skin, have[doi.org]

Workup

A careful description of the appearance, location, and size of the tumor is essential. The gold standard for diagnosis is the histological evaluation. This method efficiently distinguishes cSCC from other skin conditions [12]. Nevertheless, problems do arise, especially when the bioptic sample is too small [13]. The biopsy must contain the full thickness of the diseased tissue, as well as adjacent normal skin for comparison. Excisional biopsy may be well suited for small lesions, but for larger lesions and those in esthetically and functionally important areas, incisional biopsy is performed as a base for a decision of definitive treatment.

Actinic keratosis contains atypical keratinocytes. It is classified according to the distribution of the atypical cells. In the first category (KIN I), the dysplastic keratinocytes are restricted to the lower third of the epidermis, whereas in higher categories they occupy an increasing thickness. In the KIN III category – which is the same as cSCC in situ - the atypical keratinocytes occupy all layers of the epidermis [14].

The classification of cSCC is according to the tumor-node-metastasis (TNM) staging system. This scheme incorporates the size of the tumor, the involvement of regional lymph nodes, and the absence or presence of metastases. An alternative scheme for nodal staging has been developed recently with good predictive power [15].

New methods for a noninvasive examination of skin lesions (dermoscopy, reflectance confocal microscopy, optical coherence tomography) have been developed [16]. Computerized tomography (CT) and magnetic resonance imaging (MRI) are used to examine the extent of the disease.

Treatment

  • Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up).[ncbi.nlm.nih.gov]
  • This study investigated whether patients found the treatment acceptable and assessed the outcome of treatment in terms of local control, cosmesis and hand function.[ncbi.nlm.nih.gov]
  • The first-line treatment is surgery, which has a high cure rate. In advanced cases, however, the established treatment is often not curative and shows a high rate of side effects. Improved treatment modalities are necessary.[ncbi.nlm.nih.gov]
  • RESULTS: 3 patients (2 females, 1 male, ages 86 to 93) received cetuximab for the treatment of unresectable SCC. In 2 patients partial remissions were achieved and maintained with continuous treatment for 17 and 18 months.[ncbi.nlm.nih.gov]

Prognosis

  • With early recognition and treatment, most of these tumors have a favorable prognosis. If the lesions are left untreated, however, the results may prove fatal.[ncbi.nlm.nih.gov]
  • Some authors regard the sarcoid reaction to be a sign of a good prognosis on the basis of studies of a few patients with solid tumors. In our case, however, the patient died of pulmonary metastasis with pleuritis carcinomatosa shortly after surgery.[ncbi.nlm.nih.gov]
  • BACKGROUND: Parotid metastases from cutaneous squamous cell carcinoma (CSCC) are associated with poor prognosis. However, the incidence of occult parotid lymph node metastases in high-risk CSCC is unclear.[ncbi.nlm.nih.gov]
  • We also review novel classification schemes proposed during the last decade which attempt to stratify SCC lesions based on prognosis. Biopsy leads to definitive diagnosis.[ncbi.nlm.nih.gov]
  • Despite the histologic dissimilarity, the long-term prognosis of the reported cases was similar to conventional SCC.[ncbi.nlm.nih.gov]

Etiology

  • The majority arise on the head and neck skin, and cumulative UV exposure is thought to be the most likely etiological factor. The majority of deaths from SCC occur in a high-risk subgroup of patients.[ncbi.nlm.nih.gov]
  • The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from[ncbi.nlm.nih.gov]
  • To shed light on the etiology, we estimated the relative contributions of genetic and environmental factors on the occurrence of each disease, in addition to their influence on coaggregation of the two diseases.[ncbi.nlm.nih.gov]
  • Etiology Pathophysiology While cumulative ultraviolet exposure and skin type are the most important etiologic factors in the development of squamous celll carcinomas, other risk factors include: immunosuppression, older age, certain chemical exposures[dermatologyadvisor.com]
  • Etiology Exposure to cancer-promoting stressors and the response of the body to those exposures (host response) promote the development of cSCC.[web.archive.org]

Epidemiology

  • Chan School of Public Health, Boston, MA 02115, USA. 6 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Richard M.[ncbi.nlm.nih.gov]
  • Author information 1 Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands. 2 Clinical Research Program, Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. 3 Department of Epidemiology[ncbi.nlm.nih.gov]
  • Abstract Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC).[ncbi.nlm.nih.gov]
  • Introduction Invasive primary skin malignancy arising from keratinocytes of skin or mucosa Epidemiology common in f air-skinned individuals common in elderly patients 2 nd most common form of skin cancer (first is basal cell carcinoma ) risk factors sun[medbullets.com]
  • To provide an update regarding the epidemiology and management of NMSC in SOTR. Ten-year incidence rates range from 10% in Italy to 20% in Northern Europe to 70% in Australia.[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • It also presents new coverage of pathophysiology, diagnostic reasoning, evidence-based practice, geriatrics, and pediatrics.[books.google.com]
  • Sites Face, ears, scalp, dorsal hands Pathophysiology Often induced by ionizing radiation Tends to affect sun damaged, fair skin of older individuals and skin of solid organ transplant recipients HPV / human papillomavirus has major role in development[pathologyoutlines.com]
  • Etiology Pathophysiology While cumulative ultraviolet exposure and skin type are the most important etiologic factors in the development of squamous celll carcinomas, other risk factors include: immunosuppression, older age, certain chemical exposures[dermatologyadvisor.com]
  • Pathophysiology Malignant transformation of normal epidermal keratinocytes is the hallmark of cSCC. One critical pathogenic event is the development of apoptotic resistance through functional loss of TP53, a well-studied tumor suppressor gene.[emedicine.medscape.com]

Prevention

  • IMPACT: Our results indicate that controlling allergy and IgE levels may be a new avenue of skin cancer prevention in susceptible populations, and implicate immune mechanisms in skin carcinogenesis. 2011 AACR.[ncbi.nlm.nih.gov]
  • Understanding the determinants of patient delay could help prevent advanced presentation. The purpose of the present study was to examine patient- and healthcare-related factors associated with delay before the detection and treatment of SCC.[ncbi.nlm.nih.gov]
  • The differential diagnosis and possible histogenesis of PSCC is discussed and the importance of extensive pathologic examination to prevent misdiagnosis is emphasized.[ncbi.nlm.nih.gov]
  • CONCLUSION: Cetuximab is suitable for palliation in elderly patients, able to maintain remissions and prevent disease progression over extended periods of continuing treatment without significant toxicity.[ncbi.nlm.nih.gov]

References

Article

  1. Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol. 2002;146(Suppl):61:1-6.
  2. Voiculescu V, Calenic B, Ghita M, et al. From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers. Dis Markers. 2016;2016:4517492.
  3. Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B. 2001;63(1-3):8-18.
  4. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med. 2001;344(13):975-983.
  5. 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. 1992;26(6):976-990.
  6. Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42:4-7.
  7. Ratushny V, Gober MD, Hick R, Ridky TW, Seykora JT. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J Clin Invest. 2012;122(2):464-472.
  8. Kowal-Vern A, Criswell BK. Burn scar neoplasms: a literature review and statistical analysis. Burns. 2005;31(4):403-413.
  9. Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. 2009;60(2):203-211.
  10. Fleming MD, Hunt JL, Purdue GF, Sandstad J. Marjolin's ulcer: a review and reevaluation of a difficult problem. J Burn Care Rehabil. 1990;11(5):460-469.
  11. Hirst LW, Axelsen RA, Schwab I. Pterygium and associated ocular surface squamous neoplasia. Arch Ophthalmol. 2009;127(1):31-32.
  12. Tan KB, Tan SH, Aw DC, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation. J Skin Cancer. 2013;2013:752864.
  13. Swanson PE, Fitzpatrick MM, Ritter JH, Glusac EJ, Wick MR. Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens. J Cutan Pathol. 1998;25(3):153-159.
  14. Cockerell CJ. Histopathology of incipient intraepi- dermal squamous cell carcinoma (“actinic kerato- sis”). J Am Acad Dermatol. 2000;42:11–17.
  15. Forest VI, Clark JJ, Veness MJ, Milross C. N1S3: a revised staging system for head and neck cutaneous squamous cell carcinoma with lymph node metastases: results of 2 Australian Cancer Centers. Cancer. 2010;116(5):1298-1304.
  16. Warszawik-Hendzel O, Olszewska M, Maj M, Rakowska A, Czuwara J, Rudnicka L. Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma. J Dermatol Case Rep.2015;31;9(4):89-97.

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Last updated: 2019-07-11 20:02