brief s2k guidelines basal cell carcinoma of the skin · 2018-06-30 · basal cell carcinoma...

10 Basal cell carcinoma DOI: 10.1111/ddg.12015

JDDG | Supplement 3˙2013 (Band 11) © 2013 The Authors • DDG © Blackwell Verlag GmbH, Berlin • JDDG • 11 (Suppl. 3): 10–15

Basal cell carcinoma

Brief S2k guidelines – Basal cell carcinoma of the skin Axel Hauschild1*, Helmut Breuninger2*, Roland Kaufmann3, Rolf-Dieter Kortmann4, Martin Klein5, Jochen Werner6, Julia Reifenberger7, Thomas Dirschka8, Claus Garbe9

(1) Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Germany (2) Department of Dermatology, Tübingen University Hospital, Germany(3) Department of Dermatology, Frankfurt University Hospital, Germany(4) Department of Radiation Therapy and Radio-oncology, Leipzig, Germany(5) Fachklinik Hornheide, Division of Oral and Maxillofacial Surgery, Plastic and Aesthetic Surgery, Münster, Germany(6) Department of Otolaryngology, Marburg University Hospital, Germany(7) Department of Dermatology, Düsseldorf University Hospital, Germany(8) Dermatology Practice, Düsseldorf, Germany (9) Department of Dermatology, Tübingen University Hospital, Germany

The present guidelines were commissioned by the Dermatologic Cooperative Oncology Group (DECOG) of the GermanCancer Society (DKG) and the German Society of Dermatology (DDG).

ADO Guidelines Coordinator: Prof. Dr. Stephan Grabbe, MainzVersion 03/2012

Australia [1, 2]. In Central Europe basalcell carcinoma is also among the mostcommon malignant tumors. InGermany the incidence is about 1701new reports per 100 000 inhabitantsannually. The average age is 60 years.Both sexes are affected, but the diseaseoccurs more frequently in men. Approx. 80 % of basal cell carcinomas occur inthe head and neck region.The most important etiological factorsare a genetic pre-disposition with lightskin pigmentation and cumulative UVexposure. Basal cell carcinomas can alsooccur in conjunction with hereditary dis-eases such as (nevoid) basal cell carcino-ma syndrome (Gorlin-Goltz syndrome),xeroderma pigmentosum, and albinism.Additional risk factors include exposureto arsenic and long-term immunosup-pression. Tight scar tissue and nevi sebacei are also predisposing factors [3].

Diagnosis and histology

Recommendations• A biopsy with histological evalua-

tion should be performed on any cutaneous lesion of uncertainbenign/malignant nature.

• The diagnosis of basal cell carcino-ma is generally made clinically andconfirmed by histology. Exceptionsare multiple superficial basal cellcarcinomas and Gorlin-Goltz syn-drome. Light microscopy can helpto increase the certainty of a clinicaldiagnosis.

• In addition to inspecting the tumor,the initial clinical examinationshould include an inspection of theentire skin surface.

• Along with the diagnosis, histologi-cal findings should contain the following information:

− Histological type− Histological depth (maximal verti-

cal tumor diameter in mm)− Microscopic examination of resec-

tion margins showing no tumorcells / virtually no tumor cells, pos-sibly with minimum distance of thetumor from the resection margin /incomplete resection.

• Imaging studies to rule out metasta-sis are not generally recommended.They should only be performed ifthere is clinical suspicion of metas-tasis or for very advanced primarytumors.

BackgroundEpidemiology and clinical appearance

Basal cell carcinoma (formerly alsoknown as “basalioma”) is a locallydestructive epithelial neoplasm withbasaloid differentiation. It is the mostcommon cancer in the United States and

Statements• Basal cell carcinoma (BCC) of the

skin is the most commonly occur-ring non-benign tumor in humanbeings. The aggressive tumorexhibits local infiltration anddestructive growth. Metastasis isextremely rare.

• In Germany, the incidence of BCCis approx. 170 new reports per 100 000 inhabitants per year.

• Basal cell carcinoma arises de novowithout a precancerous lesion.

• Predilection sites are chronicallysun-exposed areas of the skin (face,head, neck, upper chest).

• Pre-disposing genetic factors play arole in disease.

• Patients often have multiple tumorssimultaneously or over a span ofyears or decades.

Basal cell carcinoma 11

© 2013 The Authors • DDG © Blackwell Verlag GmbH, Berlin • JDDG • 11 (Suppl. 3): 10–15 JDDG | Supplement 3˙2013 (Band 11)

The diagnosis is generally made on thebasis of clinical findings. Dermatoscopymay be helpful for differential diagnosis[4]. To confirm the diagnosis, it is neces-sary to obtain a histological analysis;depending on tumor size and treatmentapproach, this may be with an incisionbiopsy, excision biopsy, or therapeuticexcision [5]. An exception may be madefor multiple, superficial tumors or basalcell carcinoma syndrome. Subclinicalspread of disease often evades certaindetection, and even with modern non-invasive diagnostic techniques can onlybe detected with microscopy. For pig-mented lesions, basal cell carcinoma aswell as melanoma must be differentiated.Rather than a biopsy, a complete resec-tion should be performed. For destruc-tive basal cell carcinomas and/or clinicalsuspicion of infiltration of deep struc-tures, additional imaging studies may beneeded for diagnosis.Basal cell carcinomas are characterizedby a large clinical spectrum. Tumorstend to arise on sun-exposed areas of theskin, without any pre-cancerous lesions.The most common subtype, a solid(syn.: nodular) basal cell carcinoma,begins as a flat elevated, circumscribed,yellow-red papule with a string-of-pearl-like margin and typical dilated bloodvessels extending from the border intothe center of the tumor. There are alsoother variants such as basal cell carcino-ma of the trunk (superficial type) whichpresents with erythematous plaques andcicatricial basal cell carcinomas whichresemble scars. Later erosions and ulcer-ations can occur. A typical clinical signof basal cell carcinoma is recurrent, usu-ally punctate bleeding.Histogenetically, basal cell carcinomasarise from cells in the basal cell layerand/or the outer root sheath of the hairfollicles. Sometimes they exhibit differentiation resembling certain fea-tures of the adnexa (follicles, sebaceousglands, eccrine, or apocrine sweat

• In basal cell carcinoma syndrome(Gorlin-Goltz syndrome), diagnosismust often be confirmed with imag-ing studies (radiographs) of osseousanomalies (e. g., panoramic radi-ograph of jaw). Patients with basalcell carcinoma syndrome should beexposed to as little ionizing radiationas possible during examinations.

glands). The histological subtypes ofbasal cell carcinoma are based on the dif-ferent patterns of differentiation whichare also found in the current WHO his-tological classification. The followingclassification has proven useful in clinicalpractice: Basal cell carcinoma of the skin developsover months or years. The lesions laterbecome ulcerative (rodent ulcer) and canalso destroy deep tissue structures (ulcusterebrans). If uninhibited growth reachesvital structures (frontal skull base,carotid artery, etc.) the disease can befatal. Metastasis of basal cell carcinoma isextremely rare. Similar to squamous celland other carcinomas of the skin, thecurrent staging of basal cell carcinoma isbased on the UICC classification. It isuseless for clinical practice, however. TheT classification is too unspecific and theN and M categories rarely apply to thistype of tumor. To ensure the quality oftreatment, the following information isuseful: • Clinical tumor size (horizontal tumor

diameter)• Localization• Histological type• Histological spread in depth (vertical

tumor diameter in mm)• Therapeutic safety margin (for resec-

tion or radiation treatment orcryotherapy)

• Resection margins microscopicallywithout tumor cells/nearly withouttumor cells/incomplete resection. Thisinformation assumes that thehistopathological preparation methodof the tumor specimen is also documented.

Therapy

Recommendations• Surgical treatment with histological

control of the complete removal ofthe tumor with no remaining cells atthe resection margins should beoffered as the first-line therapy.Surgery may be done with systemat-ic control of the margins (micro-scopically controlled surgery) orwith a tumor-adapted safety marginand conventional histologic exami-nation. For superficial basal cell car-cinomas, horizontal excision (shaveexcision) with conventional histol-ogy is also possible (Table 1).

Surgical treatment with histological con-firmation is the standard procedure fortreatment of basal cell carcinoma. Iftumor removal is incomplete, all surgicalpossibilities for re-excision should beexhausted as long as they are feasiblegiven the patient’s overall condition andthe tumor spread. This applies in partic-ular to all infiltrative and cicatricial basalcell carcinomas and for infiltration ofdeeper structures that are not limited tothe skin. There is a vast array of treat-ments, including radiation therapy aswell as curettage, cryotherapy, laser ther-apy, and photodynamic therapy andlocal drug treatments such as imiquimodand 5-fluorouracil. The disadvantage ofthese procedures is lacking histologicalcontrol of the treatment result and ahigher rate of recurrence compared tosurgery [3]. An overview of risk-associat-ed treatment recommendations is pre-sented in Tables 1 and 2. In very elderly or multimorbid patientswith asymptomatic or low-risk basal cellcarcinoma, aggressive treatment approach-es no longer seem warranted. Theapproach should be palliative without acurative intention. Local tumor removalor radiation therapy may be performedto ensure local tumor control and/orimprove quality of life in the short-term.

• For local tumors that cannot beremoved in sano, as well as for inop-erable patients, an interdisciplinarytreatment concept is warranted.Usually radiation treatment is per-formed in such situations (Table 2).

• Patients with basal cell carcinomasyndrome should not be treatedwith ionizing radiation.

• Alternative treatment procedures –for multiple or superficial basal cellcarcinomas, and in inoperablepatients – as well as locally destruc-tive procedures (electrodesiccation,curettage, cryotherapy, laser therapy,and photodynamic therapy as wellas local drug treatments withimiquimod or 5-fluorouracil) maybe considered (Table 2).

• Until approved, systemic treatmentwith Hedgehog inhibitors(Vismodegib, LDE225) should beconsidered in the framework of clin-ical trials for selected patients withinoperable or metastatic basal cellcarcinoma.

12 Basal cell carcinoma


Microscopically controlled surgeryMicroscopically controlled surgery is theconservative surgical excision of a tumor(2–4 mm safety margin) with markingsfollowed by a complete histopathologicalevaluation of lateral and basal margins ofthe excised material [6]. This allows fortopographical classification of subclinicalresidual tumor and targeted re- excisions ifneeded, until the outer surface of theexcised material is negative for residualtumor. Even for small unproblematictumors, the procedure may have advan-tages. Given the high diagnostic certainty,healthy skin can be spared and only histo-logically confirmed tumor cells areexcised. Processing may be done with

cryostat or paraffin sections. Paraffin sec-tions are superior to cryostat sections interms of the information they can provide.

Radiation treatmentRadiation treatment is indicated for pri-mary inoperability, as well as followingincomplete surgical resection (R1, R2) ifre-excision is not possible. Radiotherapyis contraindicated in patients with basalcell carcinoma syndrome (Gorlin-Goltzsyndrome).In 84–96 % of patients the sole use ofradiation therapy to treat basal cell carci-noma can lead to a long-term cure, butit is a more time-consuming method.Radiotherapy of R1 and R2 resections

can significantly decrease the rate of localrecurrences. Indications also includelacking willingness to undergo surgery,general or local inoperability, R1 or R2situations and recurrences. In moderntreatment concepts, radiation treatmentof basal cell carcinoma is mainly donewith electrons of adequate energy inindividual dosages ranging from 2.0 to3.0 Gy. For definitive radiation therapy,total dosages of 60 to 70 Gy are used.Postoperatively, total doses of 50 to 60Gy (R1) or 60 to 70 Gy (R2) may beused. Radiation treatment methodsusing orthovolt therapy with higherindividual doses (e. g., 5 Gy) with alower total dose can also achieve highrates of tumor control [7–10].

Other treatment methodsGiven the local infiltration of basal cellcarcinomas, conventional surgery withless precise histological control leavesmore residual tumor – depending on thesafety margin 5–34 % (Table 3). To pre-vent recurrences with conventional sur-gery, larger safety margins must be used,even for small tumors (0.3–1 cm), whichputs a greater burden on the patient.Cryotherapy is performed using liquidnitrogen with either a contact or open

Table 1: Recommendations for surgical treatment of basal cell carcinoma (with histological control) by tumor type,localization, and risk of recurrence.

Surgical and histological procedures Recommended indications

Surgery with systematic control of margins (histographic/micrographic surgery)

“Problem localizations” on the face (e. g., lids, lip, nose, and ear) in conjunction with size and histological type as well as recurrentlesions

Surgery with tumor-adapted safety margin andconventional histology

Small tumors at any localizationLarger tumors on the trunk and extremities,

Horizontal excision with conventional histology Multifocal, superficial BCC, especially on the trunk and extremities

Table 2: Therapy alternatives for surgical treatment (without histological control).

Type of treatment and indication • Radiation therapy for primary inoperability, as well as after incomplete surgical removal (R1, R2), if re-excision is not

possible.Contraindicated in basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

• Cryotherapy: smaller superficial tumors, e. g., on the eyelids. Especially in elderly patients in whom surgery would be asignificant burden.

• Immunological treatment with imiquimod, photodynamic therapy (PDT) and local chemotherapy with 5-fluorouracil,especially for superficial BCC and basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

• Hedgehog inhibitors (Vismodegib; LDE225) should only be used in clinical studies on patients with inoperable basalcell carcinoma or metastatic BCC until the drug is approved

Table 3: Percentage of residual tumor components that may be expectedfor a given safety margin and tumor type.

Tumor type Safety marginProbability of residual

tumor components

Basal cell carcinoma with diameter < 20 mm

3 mm 4–5 mm

15 % 5 %

Infiltrative BCC3 mm 5 mm

13–15 mm

34 % 18 % 5 %



spray procedure at –196 °C; there is nohistological control, but for small andsuperficial tumors, especially in elderlypatients, it may be an alternative to sur-gery [11]. In certain situations, especiallyin patients with multiple superficial basalcell carcinomas, it may be appropriate,especially for tumors on the trunk orextremities. With thermal destructiontechniques, the healing and aestheticresults are poorer than with conventionalexcision. Other methods, such as curet-tage with electrodesiccation and tangen-tial removal (shave excision) of basal cellcarcinomas, should be reserved for use inonly a limited number of patients due tolacking histological control.

Superficial basal cell carcinomasThere are also other treatment optionsfor superficial basal cell carcinomas.Photodynamic therapy may be used fortopical treatment. First, a specific sub-stance (e. g., delta aminolevulinic acidsand its esters) is applied to the tumorwhich causes synthesis of a photosensi-tizer in the tumor tissue (protoporphyrinIX). Next the patient is exposed tointense light with a wavelength in theabsorption spectrum of the photosensi-tizer. This treatment acts largely selec-tively on tumor tissue and must be per-formed twice per treatment cycle [12]. Local treatment with imiquimod 5 %cream may also be used to treat superfi-cial basal cell carcinomas [13, 14], pri-marily for multiple BCC. In the drugapproval study, imiquimod was appliedonce daily 5 �/weekly for 6 weeks; therate of histologically controlled, completehealing of superficial basal cell carcinomawas ca. 80 % [15]. The cytostatic agent5-fluorouracil (5 % in cream) may alsobe used. 5-fluorouracil is given topicallydaily for 4–6 weeks. Prospective random-ized studies on treatment results are stillbeing awaited, however.

Hedgehog inhibitorsFor basal cell carcinoma syndrome(Gorlin-Goltz syndrome) as well as vari-ous sporadically occurring basal cell car-cinomas, mutations have been shown inthe Sonic hedgehog signal transductionpathway which are relevant for the devel-opment of basal cell carcinoma.

In 2009 the results were published froman early clinical study with 33 patientswho were given a Hedgehog inhibitor(GDC-0449), an inhibitor of SMO(smoothened). Eighteen out of 33patients in the dose-escalation study hadcomplete or partial remission of theirnon-resectable and previously irradiated,and sometimes metastatic, basal cell carci-nomas [16]. A worldwide phase II studywith Vismodegib (GDC-0449) was com-pleted in 2011. The manufacturer(Roche) has applied for approval to theEuropean Medicines Agency (EMA) andis offering patients with inoperable ormetastatic basal cell carcinoma treatmentwith Vismodegib (as of January 2012) inthe framework of an Early AccessProgram (EAP). Another inhibitor of theSonic hedgehog signal transduction path-way (LDE225; Novartis) is currentlybeing tested in clinical studies on patientswith basal cell carcinoma.

Follow-up care, primary andsecondary prevention

Recommendations• Patients with basal cell carcinoma

should undergo follow-up at leastonce a year for three years, giventhat the majority of local recur-rences occur within two years.

• Given the frequency of secondtumors, patients with basal cell car-cinoma should undergo regularscreening.

• Patients who have local recurrencesor non in toto resectable tumors, aswell as patients with a higher risk ofnew tumors (immunosuppression,genetic pre-disposition, prior multi-ple basal cell carcinomas), should bemore closely monitored and possi-bly undergo lifelong follow-up.

• Patients should be instructed in reg-ular self-inspection techniques inorder to detect basal cell carcinomaas early as possible.

• Patients with basal cell carcinoma –especially basal cell carcinoma syn-drome or chronically immunosup-pressed patients – should protectthemselves against excessive expo-sure to sunlight.

After micrographic surgery, despite thelow rate of recurrence, primary tumorsshould be followed-up given that newtumors can occur in ca. 30 %. Withother procedures, recurrences after unde-tected subtotal excision are usually clini-cally apparent within three years (ca. 70 %), but may be identified even afterten years [3]. Annual follow-up withclinical inspection of the entire skin sur-face is advisable for at least three years.Patients with local recurrences or incom-plete resection, as well as those with ahigher risk of new tumors (immunosup-pression, genetic pre-disposition) shouldbe more closely monitored and possiblyundergo lifelong follow-up. It is impor-tant to thoroughly inform the patientand carefully instruct him or her in per-formed regular self-inspections. There is insufficient evidence on a directrelationship with chronic exposure toultraviolet light. Yet the increased inci-dence of tumors on areas of the skin withchronic sun-exposure suggests that UVlight is indeed a co-factor in the patho-genesis of disease. Thus, patients withmultiple basal cell carcinomas andimmunosuppressed patients in particularshould protect themselves against exces-sive exposure to the sun.

Psycho-oncologyThe effects of basal cell carcinoma onvarious psychosocial dimensions andquality of life, as well as the related needfor support, have not yet been systemat-ically studied.A comparative study on patients withbasal cell carcinoma and a matchedsample from the general populationfailed to find any difference in regardto psychosocial problems [17]. Onestudy focusing on basal cell carcinomasyndrome in particular reportedmarked symptoms of depression in 50 % [18].Based on the S3 guidelines on malignantmelanoma and the S3 guidelines (workin progress) for patients with varioustumors entitled “Psycho-oncologicaldiagnosis, counseling and treatment ofcancer patients”, for basal cell carcino-ma as well, an assessment of the individ-ual burden and health-related quality oflife are advisable.

14 Basal cell carcinoma


Declaration of conflicts of interests

Prof. Dr.Axel Hauschild

Prof. Dr.HelmutBreuninger

Prof. Dr.RolandKaufmann

Prof. Dr.Rolf-DieterKortmann

Prof.Dr.MartinKlein

Prof.Dr.JochenWerner

PD Dr.Julia Reifenberger

Prof. Dr.ThomasDirschka

Prof. Dr.ClausGarbe

Honoraria forconsulting activityor participation inadvisory boards

Almirall Hermal, BMS,Boehringer Ingelheim,Celgene, Eisai, GSK,IGEA, La Roche-Posay,MEDA Pharma, MELASciences, MSD, Novartis, Roche, SciBase, SOBI, Spirig

none Roche, No-vartis, LEO

none notdeclared

notdeclared

none not declared

not declared

Honoraria foreducational activities

Almirall Hermal, BMS,Boehringer Ingelheim,Celgene, Eisai, GSK,IGEA, La Roche-Posay,MEDA Pharma, MELASciences, MSD,Novartis, Roche, SciBase, SOBI, Spirig

none Merck-Serono,Merz, Pfizer,Basilea

none notdeclared

notdeclared

nein not declared

not declared

Research grants Almirall Hermal, BMS,Boehringer Ingelheim,Celgene, Eisai, GSK,IGEA, La Roche-Posay,MEDA Pharma, ME-LASciences, MSD, Novartis, Roche, SciBase, SOBI, Spirig

none LEO, Roche,Novartis, ABScience, Abbott Almirall, Amgene, Basilea,BMS, Cell-gene, GSK, Regenerone,Jansen-Cilag,Lefi, Meda,Merz,Sciderm, Pfizer

none notdeclared

notdeclared

none not declared

not declared

Royalties none none none none notdeclared

notdeclared

none not declared

not declared

Stock/stock options

none none none none notdeclared

notdeclared

none not declared

not declared

Personal relationsto a representativeof a company inthe health caresector

nein none none none notdeclared

notdeclared

none not declared

not declared

Member of socie-ties relevant to theguideline’s topic

ADO none ADO, DDG none notdeclared

notdeclared

none not declared

not declared

Political, academicor scientific interests that maylead to a conflictof interests

none “surgicalschool”

none none notdeclared

notdeclared

none not declared

not declared

Employee duringthe last 3 years

UniversitätsklinikumSchleswig-Holstein,Campus Kiel

Universitäts-HautklinikTübingen

Universitäts-klinikumFrankfurt

Universitäts-klinikumAöR

notdeclared

notdeclared

Universitätsk-linik Düsseldorf

not declared

not declared

Conflicts of interest



Correspondence toProf. Dr. med. Axel HauschildDepartment of DermatologyUniversity Hospital Schleswig-Holstein(UKSH)Campus KielSchittenhelmstrasse 724105 Kiel, GermanyE-mail: [email protected]

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brief s2k guidelines basal cell carcinoma of the skin · 2018-06-30 · basal cell carcinoma...

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