squamous cell carcinoma of the skin (SCCS)
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Introduction
Malignant tumor of epithelial keratinocytes in skin & mucous membrane.
Etiology
- ultraviolet radiation
- ionizing radiation
- sun exposure in both childhood & adult life increases risk[7]
- trivalent arsenic*
- Fowler's solution used as a tonic & in the treatment of psoriasis
- ingestion of arsenic
- may be present in the drinking water
- betel nut?
- human papilloma virus (anogenital area & periungual skin)
- HPV- 16, 18, 31, 33, 35, 45
- immunosuppression
- pharmaceuticals
- topical nitrogen mustard for treatment of mycosis fungoides
- tyrosine kinase inhibitors[2]
- hydroxyurea
- voriconazole
- HCTZ[15]
- oral PUVA photochemotherapy
- discoid lupus erythematosus (rare)
- industrial carcinogens*
- chronic inflammation*[4]
* the atypical chemokine receptor D6 suppresses development of chemically-induced skin tumors
Epidemiology
- 12/100,000 white males, 7/100,000 white females, 1/100,000 blacks in continental USA
- 62/100,000 whites in Hawaii
- white with poor tanning capacity at risk
- age > 55 years in USA, 20s & 30s in Australia
- incidence 4/100,000 USA age < 40[3]
- males > females, but more frequently on legs of females
- more common in sunbelt
- penile SCC accounts for 20% of SCC in developing countries, but only 1% in USA
- oral mucosa SCC high in India, southeast Asia, & Puerto Rico, & low in Japan, Israel & Scandinavia
- more common in persons working outdoors
- industrial workers exposed to carcinogens
- most common type of skin cancer in immunosupressed patients after solid organ transplant[2]
- incidence of SCCS is 25 times higher in organ transplant patients taking long-term immunosuppressive agents
Pathology
- squamous cell carcinoma generally develops from a precancerous lesion or carcinoma in situ
- precursors to SCC
- highly differentiated SCC
- keratinization within or on the surface of the tumor
- various grades of anaplasia
- poorly differentiated SCC
- no sign of keratinization
- anaplasia with multiple mitoses
- squamous cell carcinoma of the lips
- develops from leukoplakia or actinic cheilitis
- found on lower lip in 90 of cases
- SCCS tend to retain their surface scale
- as SCCS accumulates a large amount of scale, it is called a cutaneous horn
Invasive squamous cell carcinoma: (also see Bowen's disease & erythroplasia of Queyrat)
* histopathology images[12]
Immunophenotype
Genetics
- associated with defects in PTCH1
- overexpression of kallikrein-8
Clinical manifestations
- slowly evolving, isolated keratotic or eroded papule or plaque that persists for months
- highly differentiated SCC
- firm or hard on palpation
- may be tender to palpation
- indurated papule, plaque or nodule
- hyperkeratosis
- erosion or ulceration may crust in center
- margins may be elevated
- erythematous, yellow or flesh-colored
- lesions generally isolated, but may be multiple
- distribution: sun-exposed areas
- evidence of chronic sun exposure
- generally does not itch
- firm or hard on palpation
regional lymphadenopathy may accompany metastases
- poorly differentiated SCC
- fleshy & granulomatous erosive papules & nodules & papillomatous vegetations
- ulceration with a necrotic base & soft, fleshy margin
- hemorrhagic, crusting
- generally isolated, but may be multiple especially on genitalia
- lymphadenopathy due to metastases more common than with differentiated SCC
- soft on palpation
- squamous cell carcinoma of the lip
Diagnostic procedures
- skin biopsy (shave biopsy of lesion)
Complications
- risk of metastasis 2-5%
Differential diagnosis
- nummular eczema
- psoriasis
- Paget's disease of the breast
- basal cell carcinoma: does not present as hyperkeratotic lesion
- keratoacanthoma
Management
- surgery
- excision with primary closure, skin flaps or grafting
- microscopically controlled surgery on face or in difficult sites (Mohs surgery)
- small lesions may be treated with electrodessication & curettage[4]
- most lesions require surgical excision[4]
- radiation therapy if surgery is not feasible
- pembrolizumab (Keytruda) monotherapy for locally advanced SCCS not amenable to surgery or radiation therapy (images)[16]
- prognosis
- 90% remission after therapy
- tumors induced by ionizing radiation or arsenic, occurring in the bed of a burn scar or on the genitalia are more likely to metastasize (up to 20%)
- patients with SCC secondary to arsenic ingestion may also have SCC of the lung & bladder
- lesions arising from solar (actinic) keratosis have lowest metastatic potential
- SCC of the skin has an overall metastatic rate of 3-4%
- prevention:
- sunscreen, protective clothing
- cryotherapy of actinic keratoses
- celecoxib may reduce incidence of both cutaneous SCC & basal cell carcinoma (BCC)[5]
- nicotinamide 500 mg BID lowers risk of cutaneous SCC in high-risk patients by 25%[8]
- benefit lost when nicotinamide discontinued
- topical fluorouracil 5% BID for 2-4 weeks in high-risk patients reduces need for surgery by 75% over the year after treatment[13]
More general terms
More specific terms
- erythroplasia of Queyrat
- Marjolin's ulcer
- squamous cell carcinoma (SCC) of the anus
- squamous cell carcinoma in situ (Bowen's disease)
- squamous cell carcinoma of the nail bed
Additional terms
References
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 222-227
- ↑ 2.0 2.1 2.2 2.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2022
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 3.0 3.1 Christenson LJ, Borrowman TA, Vachon CM, Tollefson MM, Otley CC, Weaver AL, Roenigk RK. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005 Aug 10;294(6):681-90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16091570
- ↑ 4.0 4.1 4.2 4.3 Nibbs RJ, Gilchrist DS, King V, Ferra A, Forrow S, Hunter KD, Graham GJ. The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors. J Clin Invest. 2007 Jul 2;117(7):1884-1892. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17607362
- ↑ 5.0 5.1 Elmets CA et al Chemoprevention of nonmelanoma skin cancer with celecoxib: A randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010 Dec 15;102(24):1835-44. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21115882 <Internet> http://dx.doi.org/10.1093/jnci/djq442
Meyskens FL Jr and McLaren CE. Chemoprevention, risk reduction, therapeutic prevention, or preventive therapy? J Natl Cancer Inst. 2010 Dec 15;102(24):1815-7. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21115881 <Internet> http://dx.doi.org/10.1093/jnci/djq466 - ↑ 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 Jun;26(6):976-90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1607418
- ↑ 7.0 7.1 Wu S et al. Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: A cohort study. Cancer Epidemiol Biomarkers Prev 2014 Jun; 23:1080 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24876226 <Internet> http://cebp.aacrjournals.org/content/23/6/1080
- ↑ 8.0 8.1 Chen AC, Martin AJ, Choy B et al A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med 2015; 373:1618-1626. October 22, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26488693 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1506197
- ↑ 9.0 9.1 Squamous cell carcinoma (image) American Academy of Dermatology https://www.aad.org/public/diseases/skin-cancer/squamous-cell-carcinoma
Squamous cell carcinoma (SCC) (image) Skin Cancer Foundation http://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma - ↑ 10.0 10.1 Alam M, Ratner D. (images) Cutaneous squamous-cell carcinoma. N Engl J Med. 2001 Mar 29;344(13):975-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274625
- ↑ 11.0 11.1 DermNet NZ (images) Squamous cell carcinoma of the skin http://www.dermnetnz.org/lesions/squamous-cell-carcinoma.html
- ↑ 12.0 12.1 12.2 Monroe MM, Meyers AD (images) Medscape: Cutaneous Squamous Cell Carcinoma http://emedicine.medscape.com/article/1965430-overview
- ↑ 13.0 13.1 Harrison P 5-FU Cream Reduces Surgery in High-Risk SCC Patients Medscape. Jan 08, 2018. https://www.medscape.com/viewarticle/891047
- ↑ Bowser A MedPage Today. Dermatology Times. January 28, 2018 https://www.medpagetoday.com/dermatology/generaldermatology/70798
Karia PS, Morgan FC, Califano JA, Schmults CD. Comparison of tumor classifications for cutaneous squamous cell carcinoma of the head and neck in the 7th vs 8th edition of the AJCC cancer staging manual. JAMA Dermatol 2017. Dec 20 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29261835
Karia PS, Morgan FC, Ruiz ES, Schmults CD. Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data. JAMA Dermatol. 2017 Aug 1;153(8):781-788. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28678985 Free PMC Article
Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013 Jun;68(6):957-66. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23375456
Jambusaria-Pahlajani A, Kanetsky PA, Karia PS et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. 2013 Apr;149(4):402-10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23325457 - ↑ 15.0 15.1 Pedersen SA, Gaist D, Schmidt SAJ et al Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol. 2018 Apr;78(4):673-681.e9. Epub 2017 Dec 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29217346 Free Article
- ↑ 16.0 16.1 Worcester S Latest FDA Pembrolizumab Approval Expands Label to Cutaneous SCCs. Medscape - Jul 13, 2021 https://www.medscape.com/viewarticle/954715
Thakker S, Al-Mondhiry J Complete Resolution of Bulky Cutaneous Squamous Cell Carcinoma by Programmed Death-1 Inhibitor. Ann Intern Med Clinical cases. 2024. March 5. https://www.acpjournals.org/doi/10.7326/aimcc.2023.0570 - ↑ Kim JY, Kozlow JH, Mittal B, et al; Work Group. Guidelines of care for the management of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2018;78:560-78. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29331386
- ↑ 18.0 18.1 NEJM Knowledge+
Wysong A. Squamous-Cell Carcinoma of the Skin. N Engl J Med. 2023 Jun 15;388(24):2262-2273. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37314707 Review. No abstract available. https://www.nejm.org/doi/pdf/10.1056/NEJMra2206348