S2 Guidelines DOI: 10.111/j.1610-0387.2008.06708.x

JDDG | Supplement 12008 (Volume 6) Journal compilation Blackwell Verlag, Berlin JDDG 1860-6024/2008/Suppl 1 S2-S4

DefinitionBasal cell carcinoma (BCC; also knownas basal cell epithelioma) is a locallydestructive epithelial tumor which gen-erally does not metastasize. BCC is themost common type of cancer in the USAand Australia, and one of the most com-mon tumors in central Europe. InGermany the incidence is around 100 /100,000 yearly. The average age at presen-tation is 60 years, with a tendencytowards appearing at younger ages. Menand women are equally affected. About80 % of BCC occur in the head andneck region. In rare cases, BCC can belocally aggressive, infiltrating cartilagi-nous and bony structures and invadingthe skull to cause disability or death. Thetumor almost never metastasizes. Etiologic factors are genetic predisposi-tion, fair skin and UV exposure. In con-trast to squamous cell carcinoma, pre-cancerous or in situ lesions are not seen.BCC may develop in scars and rarely innevus sebaceus. Chronic arsenic inges-tion and long-term immunosuppressionare other risk factors. BCC are also com-mon in syndromes such as xerodermapigmentosum, nevoid basal cell carcino-ma syndrome and albinism.BCC usually start as flat or slightlyraised circumscribed red-yellow papuleswith a pearly border. There are otherclinically different variants such as super-ficial BCC which mimics dermatitis orsclerosing BCC which presents as a scar.More advanced BCC typically are erod-ed or ulcerated. They may destroy the underlying muscle, cartilage or bone, making orbital exenteration orresection of the external ear or nose nec-essary.The histogenetic origin of BCC is eitherthe cells of the basal cell layer or those ofthe outer root sheath of the hair follicle.They may show differentiation resem-bling the adnexal structures, such as hairfollicles, sebaceous glands, or eccrine and

apocrine sweat glands. The histologicclassification of BCC is based on thesedifferent patterns of differentiation, asreflected in the WHO standards, andhas proven useful in clinical practice. BCC develop over months to years andslowly may ulcerate (ulcus rodens) andlater destroy deeper tissues (ulcus tere-brans). There is a risk of death when vitalunderlying structures are involved, suchas a major artery. Metastases occur inwell under 1:1000 cases. BCC arestaged, just as are squamous cell carcino-ma and other cutaneous carcinomas, following the UICC classification.Unfortunately this scheme is not refinedenough for regular clinical use, as the Tcategory is too broad, while the N and M categories are almost never seen. The following information is help-ful in planning and evaluating therapy: Clinical tumor size (maximum hori-

zontal diameter) Location Histologic type Histologic depth (maximum vertical

thickness) Therapeutic margin (with excision,

cryotherapy or radiation therapy) Resection margins free of tumor /

not free of tumor. This informationcan only be incorporated when it isstated how the histological evalua-tion was performed.

Diagnostic ApproachMost BCC are diagnosed clinically.Histologic confirmation is necessary;depending on the size and planned ther-apy, the biopsy can be incisional, exci-sional, or part of the definitive treat-ment. The clinically inapparent tumormargins cannot be identified with any ofthe modern imaging techniques but onlyconfirmed with histologic study.Additional imaging studies with CT orMRI may be needed for destructiveBCC.

TherapyOperative therapy with histologic con-trol is the standard treatment of BCC.When the excision is incomplete, everyeffort should be made to perform a com-plete re-excision, keeping in mind thepatients general status and the type oftumor. This level of care is especiallyimportant for BCC with infiltrative orsclerodermiform patterns of growth andwhen deeper infiltration of subcuta-neous structures has occurred. The list ofadditional therapeutic modalities islengthy and includes radiation therapyas well as locally destructive measuressuch as curettage, cryotherapy, laserdestruction and photodynamic therapy(PDT). In addition, topical medicationssuch as imiquimod and 5-fluorouracilcan be employed. The disadvantage of allthese methods is the lack of histologiccontrol and the higher recurrence ratethan surgery. An overview of risk-adjust-ed therapeutic recommendations is givenin Tables 1 and 2. In very old patients or those with multi-ple other medical problems who haveasymptomatic or low-risk BCC, anaggressive approach may not be appro-priate; in such cases a palliative approachwithout intent of cure is acceptable.Tumor debulking or radiation therapycan delay the local spread and greatlyimprove the quality of life.

Micrographic SurgeryMicrographic surgery involves the exci-sion of the tumor with a small margincoupled with topographic marking andfollowed by complete histological con-trol of the entire periphery and base ofthe excision. This makes it possible toidentify clinical inapparent tumor exten-sions, which can then be included in re-excisions until the excision borders aretumor-free. Even with smaller tumors,micrographic surgery has a tissue-spar-ing effect insuring that the tumor is

Guidelines

Short German guidelines: Basal cell carcinoma Axel Hauschild, Helmut Breuninger, Roland Kaufmann, Rolf-Dieter Kortmann, Volker Schwipper, JochenWerner, Julia Reifenberger,Thomas Dirschka, Claus Garbe

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entirely removed but as much normalskin as possible is saved- Both frozen sec-tions and paraffin-embedded sectionscan be used, but paraffin sections areconsidered to be more accurate andinformative.

Other MethodsExcision with conventional histologicprocessing cannot identify as many of

the irregular tumor processes as micro-graphic surgery and thus is coupled witha higher recurrence rate, which rangesfrom 5-35% depending on excision mar-gin (Table 3). In order to minimize therecurrence rate, even smaller tumorsmust be excised with larger margins(0.3-1.0 cm).Cryotherapy with liquid nitrogen (-196C) using either the spray or con-

tact method is performed without histo-logical control, but offers an alternativefor small or superficial tumors especiallyin eldery patients. In selected cases, espe-cially with multiple superficial BCC;curettage with electrodesiccation or tan-gential (shave) excision may be appropri-ate, especially on the trunk and extremi-ties. Thermal destructive measures healworse and produce poorer cosmeticresults than conventional excision. Thesemethods are used infrequently todaybecause of the lack of histologicalcontrol.There are additional therapeutic optionsfor superficial BCC. Photodynamictherapy (PDT) is a procedure in which aphotosensitizer (usually tropical -aminolevulinic acid or its esters) is applied tothe tumor which is then irradiated withan energy-rich, usually narrow wavelength light source. This treatment selec-tively destroys the tumor tissue. Efficacyresults are comparable to cryotherapy, sothat the indications overlap. Topicaltreatment with imiquimod 5 % creamcan be used for superficial BCC, espe-cially when multiple. Treatment fivetimes weekly for 6 weeks produces 80%cures as monitored with post-treatmenthistologic studies. This regimen is theone currently officially recommended inEurope. The cytostatic agent 5-fluo-rouracil (5% cream) can be applied top-ically daily for 4-6 weeks, although thereare no prospective randomized studiesdocumenting its effectiveness.

Radiation Therapy Radiation therapy alone achieves curerates comparable to conventional sur-gery, especially with small tumors.Adjuvant radiation therapy followingR1 and R2 resections greatly reducesthe local recurrence rate. The mainindications for radiation therapy arepatients refusal of surgery, inoperabilitybecause of local or systemic factors,incomplete (R1 or R2) resections andrecurrence. Depending on the site andextent of involvement, individual dosesof 2.0-5.0 Gy are used. Postoperativelytotal dosages of 40.0 Gy (R1) and 60Gy (R2) are used. For primary radiationtherapy, 70 Gy with an adequate mar-gin of treatment are required. Thechose of what type of radiation, espe-cially afterloading, depends on the bodyregion, tumor size and condition ofpatient.

Table 1: Therapeutic recommendations surgical treatment of basal cellcarcinoma (with histologic control) with regard to tumor type, locationand risk of recurrence.

Table 2: Alternative therapeutic approaches (without histologic control).

Table 3: Likelihood of residual tumor based on tumor type and excisionmargin.

Surgical and histologic procedure Indications

Micrographic surgery (procedureswith systematic control of histologic margins)

Problematic locations on face (eyelids,lips, nose and ears) depending onsize and histologic type Recurrent tumors

Standard excision with tumor-adjusted margins and conven-tional histology

Small tumors at any site. Larger tumors on the trunk and extremities

Shave excision with conventional histology

Superficial BCC especially on thetrunk and extremities

Type of Therapy and Indications

Radiation therapy: Alternative to conventional excision. Also for inoperabletumors and following incomplete excision (R1, R2). Contraindicated innevoid basal cell carcinoma syndrome

Cryotherapy: Small superficial tumors, especially on the eyelids. Also suitedfor elderly patients who might not tolerate a more invasive procedure

Immunological therapy with imiquimod only for superficial BCC and innevoid basal cell carcinoma syndrome

Photodynamic therapy only for superficial BCC and in nevoid basal cellcarcinoma syndrome

Topical chemotherapy with 5-fluorouracil only for superficial BCC and innevoid basal cell carcinoma syndrome

Type of BCC MarginLikelihood of residual tumor

BCC with diameter

Follow-upFollow-up is essential, even in patientstreated with micrographic surgery withits extremely low recurrence rate. Over30% will develop a second BCC in a 10 year period. No matter what treat-ment is employed, about 70% of recur-rences are identified within 3 years, butthe rest can appear much later, even after10 years. The patient should be exam-ined yearly for at least 3 years. Patientswith recurrent or incompletely excisedtumors as well as those with increasedrisk for new tumors, such as immuno-suppression or genetic predispositionshould be examined require an individ-ualized follow-up regimen with morefrequent examinations. All patientsshould be instructed on self-examina-tion looking for both recurrences andnew tumors.

Consensus-building Process andParticipantsThis current short guideline waswritten between July and September2007 in interdisciplinary cooperationbetween the German Cancer Societyand the German Dermatologic Society, based on the full-length guide-lines published asInterdisziplinrenLeitlinien zur Diagnostik undBehandlung von Hauttumoren (C. Garbe, ed.), Kapitel DeutscheLeitlinie: Basalzellkarzinom with theauthors Helmut Breuninger, Tbingen;Gnter Sebastian, Dresden; Rolf-Dieter Kortmann, Leipzig; Volker

Schwipper, Mnster; Jochen Werner,Marburg und Claus Garbe, Tbingen. Guideline coordinator: Prof. Dr. C.Garbe, Universitts-Hautklinik Tbingen.Authors: Axel Hauschild*, Universitts-Hautklinik Kiel; Helmut Breuninger*,Universitts-Hautklinik Tbingen;Roland Kaufmann, Universitts-Hautklinik Frankfurt; Rolf-DieterKortmann, Universitts-Klinik frStrahlentherapie und RadioonkologieLeipzig; Volker Schwipper, FachklinikHornheide, Mnster; Jochen Werner,Universitts-Klinik fr Hals-, Nasen-und Ohrenheilkunde Marburg; JuliaReifenberger, Universitts-HautklinikDsseldorf; Thomas Dirschka,Hautarztpraxis Wuppertal; Claus Garbe,Universitts-Hautklinik Tbingen.Next update planned: Spring 2010.The guideline coordinator is queriedyearly by ISTO (Information Center forStandards in Oncology) about requiredupdates. In case these are needed, the updated version of the guidelineswill be published at www.krebsgesellschaft.de, www.ado-homepage.de and www.awmf.org.

Conflict of interestAxel Hauschild declares the followingconflict of interest: In the past 2 years hehas acted as a consultant for or acceptedlecture fees from: MEDA Pharma (Germany) Abraxis Oncology (USA) BayerSchering (Germany/USA) BMS (USA, Europe)

Celgene (Europe) essex pharma/Schering-Plough

(Germany, USA) Galderma Deutschland Genta (USA) GSK (USA, Europe) Hermal (Germany) La Roche-Posay (Germany) Merck (Germany) Onyx (USA) Pfizer (USA, Germany) Roche Pharma (Germany) Synta (USA)All remaining authors have not declaredany conflict of interests.

correspondence toProf. Dr. med. Axel HauschildKlinik fr Dermatologie, Venerologieund AllergologieUniversittsklinikum Schleswig-Holstein Campus KielSchittenhelmstrae 7D-24105 KielTel.: +49-43 1-59 7-18 52Fax: +49-43 1-59 7-18 53E-Mail: ahauschild@dermatology.uni-kiel.de

References1 Breuninger H, Sebastian G,

Kortmann RD, Schwipper V, WernerJ, Garbe C (2005) Deutsche Leitlinie:Basalzellkarzinom. In: Garbe C (Ed.)Interdisziplinre Leitlinien zurDiagnostik und Behandlung vonHauttumoren. Georg Thieme Verlag,Stuttgart, New York S. 111.

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*Equally contributing, H. Breuninger was first author of these guidelines from 19962006 and created the original draft. A. Hauschild took over the firstauthorship in 2007 and is responsible for the changes made since then.