{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:44:59Z","timestamp":1789659899195,"version":"4.0.1"},"reference-count":50,"publisher":"FapUNIFESP (SciELO)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["An. Bras. Dermatol."],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>The concept of \"field cancerization\" was first introduced by Slaughter in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular studies support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. An important clinical implication is that fields often remain after the surgery for the primary tumor and may lead to new cancers, designated presently as \"a second primary tumor\" or \"local recurrence,\" depending on the exact site and time interval. In conclusion, the development of an expanding pre-neoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed. The most important etiopathogenetic, clinical, histopathological and therapeutic aspects of field cancerization are reviewed in this article.<\/jats:p>","DOI":"10.1590\/abd1806-4841.20132300","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T13:35:34Z","timestamp":1385386534000},"page":"775-786","source":"Crossref","is-referenced-by-count":54,"title":["Cutaneous field cancerization: clinical, histopathological and therapeutic aspects"],"prefix":"10.1590","volume":"88","author":[{"given":"Luis Antonio Ribeiro","family":"Torezan","sequence":"first","affiliation":[{"name":"University of Sao Paulo Medical School, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyro","family":"Festa-Neto","sequence":"additional","affiliation":[{"name":"University of Sao Paulo Medical School, 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patients with head and neck squamous cell carcinoma: an assessment of clonal relationships","volume":"5","author":"Califano J","year":"1999","journal-title":"Clin Cancer Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/gcc.10019","article-title":"Discordance of genetic alterations between primary head and neck tumors and corresponding metastases associated with mutational status of the TP53 gene","volume":"33","author":"Tabor MP","year":"2002","journal-title":"Genes Chromosomes Cancer"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"14025","DOI":"10.1073\/pnas.93.24.14025","article-title":"Frequent clones of P53-mutated keratinocytes in normal human skin","volume":"93","author":"Jonason AS","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1073\/pnas.93.1.274","article-title":"Early p-53 mutations in mouse skin carcinogenesis by UV-B radiation: immunohistochemical detection of mutant p-53 protein clusters of pre-neoplastic epidermal cells","volume":"93","author":"Berg RJ","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"a001008","DOI":"10.1101\/cshperspect.a001008","article-title":"TP53 mutations in human cancers: origins, consequences and clinical use","volume":"2","author":"Olivier M","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1056\/NEJM199503163321104","article-title":"Association between cigarette smoking and mutation of the p-53 gene in squamous cell carcinoma of the head and neck","volume":"332","author":"Brennan JA","year":"1995","journal-title":"N Eng J Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/sj.onc.1200812","article-title":"Field cancerization and polyclonal p53 mutation in the upper acrodigestive tract","volume":"14","author":"Waridel F","year":"1997","journal-title":"Oncogene"},{"key":"ref11","first-page":"335","article-title":"Actinic keratosis: how to differentiate the good from the bad ones?","volume":"16","author":"Quaedvlieg PJ","year":"2006","journal-title":"Eur J Dermatol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1365-2133.2006.07692.x","article-title":"Guidelines for the management of actinic keratoses","volume":"156","author":"de Berker D","year":"2007","journal-title":"Br J Dermatol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/j.1365-2133.2007.07865.x","article-title":"Actinic keratoses: non-invasive diagnosis for field cancerization","volume":"156","author":"Ulrich M","year":"2007","journal-title":"Br J Dermatol"},{"key":"ref14","first-page":"651","article-title":"Development of a treatment algorithm for actinic keratoses: a European Consensus","volume":"18","author":"Stockfleth E","year":"2008","journal-title":"Eur J Dermatol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1111\/j.1468-3083.2010.03625.x","article-title":"Aesthetic effects of topical photodynamic therapy","volume":"24","author":"Kohl E","year":"2010","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2133.2007.07860.x","article-title":"Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification","volume":"156","author":"R\u00f6wert-Huber J","year":"2007","journal-title":"Br J Dermatol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1067\/mjd.2000.103339","article-title":"The risk of progression to invasive disease","volume":"42","author":"Glogau RG","year":"2000","journal-title":"J Am Acad Dermatol"},{"key":"ref18","first-page":"241","article-title":"What is the role of field-directed therapy in the treatment of actinic keratosis? 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management of actinic keratoses in the United States with topical fluorouracil: a pharmacoeconomic evaluation","volume":"70","author":"Gupta AK","year":"2002","journal-title":"Cutis"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1590\/S0365-05962002000600006","article-title":"Imiquimod 5% cream in the treatment of superficial and nodular basal cell carcinomas: study of 10 cases","volume":"77","author":"Festa-Neto C","year":"2002","journal-title":"An Bras Dermatol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1001\/archderm.141.4.467","article-title":"Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials","volume":"141","author":"Korman N","year":"2005","journal-title":"Arch 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A randomized placebo-controlled study","volume":"162","author":"Apalla Z","year":"2010","journal-title":"Br J Dermatol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/j.1365-2133.2011.10209.x","article-title":"A randomized multicentre study of directed daylight exposure times of 11\/2 vs 21\/2 hs daylight- mediated PDT with methyl aminolevulinate in patients with multiple thin actinic keratoses of the face and scalp","volume":"164","author":"Wiegell SR","year":"2011","journal-title":"Br J Dermatol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1468-3083.2011.04432.x","article-title":"Photodynamic therapy for skin field cancerization: an international consensus. 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