CASE REPORT

Successful Treatment of a Keratoacanthomawith Electrochemotherapy: A Case Report

Paola Pasquali . Enrico P. Spugnini . Alfonso Baldi

Received: November 26, 2017 / Published online: January 24, 2018� The Author(s) 2018. This article is an open access publication

ABSTRACT

Introduction: Few studies have evaluated theefficacy of intralesional bleomycin injectioncombined with electroporation for the treat-ment of cutaneous tumors. However, the phe-nomenon that electroporation can enhance thecytotoxicity of bleomycin in vivo by 300–700fold has been intensely investigated.Case Presentation: Keratoacanthoma in an86-year-old patient was treated with intrale-sional bleomycin combined with electropora-tion. Treatment consisted of local application ofshorty and intense electric pulses followed bylocal injection of bleomycin. Electroporationwas always well tolerated by the patient, with

no significant complaints, and the tumor hadcompletely regressed by day 71 of the follow-up.Conclusion: The results suggest that intrale-sional bleomycin injection combined withelectroporation could represent a valid alterna-tive therapeutic approach for the treatment ofkeratoacanthomas.

Keywords: Bleomycin; Electroporation;Keratoacanthoma; Onkodisruptor

INTRODUCTION

Keratoacanthoma (KA) is a pruritic and rapidlygrowing cutaneous neoplasm that appears mostfrequently in sun-exposed regions and intert-riginous areas of elderly people [1]. It bears aclose histopathological similarity to squamouscell carcinoma (SCC) and is essentially classifiedas a low-risk SCC originating from the hair fol-licle [1]. The predilection for sun-exposed sitessupports a pathogenetic role for ultravioletradiation in KA. The National ComprehensiveCancer Network guideline recommends widesurgical excision or Mohs micrographic surgeryfor the treatment of local, low-risk SCC [1].Alternative treatments for patients refusingsurgery or for neoplasms arising in areas wheresurgery is difficult to perform may be required;these include cryosurgery, intralesional appli-cation of 5-fluorouracil, methotrexate, or

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P. PasqualiDermatology Service, Pius Hospital De Valls,Tarragona, Spain

E. P. SpugniniBiopulse Srl, Naples, Italy

A. Baldi (&)Department of Environmental, Biological andPharmaceutical Sciences and Technologies,University of Campania ‘‘Luigi Vanvitelli’’, Caserta,Italye-mail: alfonsobaldi@tiscali.it

Dermatol Ther (Heidelb) (2018) 8:143–146

https://doi.org/10.1007/s13555-018-0222-9

interferon a-2a, radiation therapy, and systemicoral retinoids [2, 3].

Electrochemotherapy (ECT) is a loco-re-gional therapy characterized by the applicationof permeabilizing electric pulses on tumors afterthe systemic or intralesional administration of achemotherapy drug [4]. ECT is presently used asfirst-line therapy in an adjuvant fashion inveterinary oncology, since it has been proved toimprove the efficacy of chemotherapeuticagents and their uptake by the neoplastic cells,especially the anti-cancer chemotherapy drugbleomycin, resulting in enhanced local controlof the neoplasia [5, 6]. In humans, the use ofECT was initially limited to the palliation ofcutaneous metastases of melanoma [7], andseveral phase II trials are ongoing for differenttumor types with promising results [8]. In par-ticular, ECT is emerging as a valid therapeuticand palliative treatment for cutaneous andsubcutaneous malignancies, including SCC. Incomparison to other standard treatments, suchas surgery or radiotherapy, ECT has the addi-tional advantage of rapid action on multiplelesions and with repeated sessions in theabsence of significant side effects and with nofunctional impairment [7]. Recently, ourresearch group has proposed a novel protocolfor ECT involving the adoption of bursts ofrectangular and biphasic pulses with aselectable period of repetition [9]. This protocolhas been shown to decrease the morbidity ofthe treated animals and to improve the clinicaloutcome. It has been already successfully usedin humans for the treatment of large viral warts[10].

CASE REPORT

We report the case of a 86-year-old man with aneruptive, pruriginous KA for 3 months on theshoulder. The lesion size was 11.20 9 12.20 mm(Fig. 1a, c). Clinical and dermoscopic images ofthe lesions were taken using a Canon EOS RebelT6i Twin-Flash RL camera (Canfield ScientificInc., Parsippany, NJ, USA) followed by punchbiopsy to confirm histologically the diagnosis ofKA (Fig. 1a0). The patient refused surgical treat-ment; therefore, an alternative approach

involving ECT was proposed. The patient wasthoroughly informed about the procedure andsigned a consent form. The tumor area wasanesthetized with a subcutaneous injection (1cc) of mepivacaine 2%. The patient was thentreated with trains of eight biphasic pulses at avoltage of 700 V/cm and pulse repetition fre-quency of 1 Hz, which lasted 50 ? 50 ls with a300-ls interpulse (total treatment time per train3.2 ms), generated by an electroporator(Onkodisruptor�; Biopulse S.r.l., Naples, Italy).The pulses were delivered using caliper elec-trodes. Immediately after the pulses, bleomycinat a concentration of 1 mg/cm3 was injectedinto the tumor at a depth of about 1.5 mm to afinal volume of 1 cc. The treatment was welltolerated, and the patient did not report anydiscomfort after the intervention. Localresponse was assessed after 10 weeks from theprocedure, and an objective response wasobserved. The patient reported only scar tissuewithin the total resolution of the pre-existingKA (Fig. 1b, d).

All procedures followed were in accordancewith the ethical standards of the responsiblecommittee on human experimentation (ethicalcode of the Universita degli Studi della Cam-pania ‘‘L. Vanvitelli’’, approved with D.R.992/2012) and with the Helsinki Declaration of1964, as revised in 2013. Informed consent wasobtained from the patient for being included inthe study.

DISCUSSION

Surgical excision is the treatment of choice forthe majority of cases of KA. However, surgicaltreatment can result in functional and aestheticdefects, especially when the lesion is large orlocated in cutaneous areas that are difficult totreat with surgery. In these latter cases, aneffective nonsurgical treatment would be moreappropriate. We report here an alternativetherapeutic approach for KA, namely, the use ofECT combined with intralesional bleomycininjection. The indications for ECT are primitiveor relapsing tumors of the skin or subcutaneoustissue of many different histological types [11].Tumor size strongly influences the response.

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Lesions whose largest diameter does not exceed3 cm show a higher complete response rate thanneoplasms, as previously described [7]. ECT hasbeen shown in clinical trials to have a highresponse rate in the treatment of patients withprimary or metastatic skin cancers [8]. Interest-ingly, ECT has been already successfully used totreat eruptive KAs [12]. In the case presentedhere, the patient showed an excellent responseto the ECT treatment and at the moment ofwriting this report is well. This good result is inaccordance with our previous work on ECTtreatment of cutaneous pathologies whichshowed that the majority of patients had no ormild pain after ECT [10]. This study, togetherwith the work of Ribero et al. [12], suggests thatECT can be considered as an excellent alterna-tive to current therapies in the treatment of KA.Nevertheless, it must be considered that KA can

spontaneously regress; therefore, more cases arenecessary to exactly define the impact of ECTon the clinical history of KA.

CONCLUSIONS

Electrochemotherapy has several advantagesover radiotherapy for the treatment of suchconditions as radio-dermatitis, lymphedema,and secondary cancers, including its simplicityand lack of complications [7]. We suggest that itcould be an effective alternative treatment forKA, especially for patients who refuse surgery orwhose conditions are not suitable for a surgicalprocedure. Larger, controlled clinical studies arerequired to confirm its safety and efficacy forthe treatment of KA as well as for other skinmalignancies.

Fig. 1 a Keratoacanthoma at presentation. Inset (a0)shows the histological appearance of the tumor (hema-toxylin/eosin, 910). b Dermoscopy: crateriform centralhyperkeratosis. c Appearance at 71-day follow-up

dermoscopy. d Appearance at 71-day follow-up der-moscopy: residual erythema and crusts

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ACKNOWLEDGEMENTS

Funding. The study and article processingcharges were funded by Biopulse Srl.

Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thisarticle, take responsibility for the integrity ofthe work as a whole, and have given theirapproval for this version to be published.

Disclosures. EP. Spugnini is a stockholder ofBiopulse Srl. A. Baldi is a stock-holder of Bio-pulse Srl. P. Pasquali has nothing to disclose.

Compliance with Ethics Guidelines. Allprocedures followedwere in accordancewith theethical standards of the responsible committeeon human experimentation (ethical code of theUniversita degli Studi della Campania ‘‘L. Van-vitelli’’, approved with D. R. 992/2012) and withthe Helsinki Declaration of 1964, as revised in2013. Informed consent was obtained from thepatient for being included in the study.

Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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