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CASE REPORT – OPEN ACCESSInternational Journal of Surgery Case Reports 4 (2013) 731– 734

Contents lists available at SciVerse ScienceDirect

International Journal of Surgery Case Reports

journa l h om epage: www.elsev ier .com/ locate / i j scr

irst report of squamous cell carcinoma arising within an intraoraladial forearm free flap

ames A. Cymermana,∗, Raghav Kulkarnia, David Gouldesbroughb, James A. McCaulc

Head & Neck Research, Bradford Institute for Health Research, Temple Bank House, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, UKDepartment of Pathology, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, UKBradford Institute for Health Research, Temple Bank House, Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, UK

a r t i c l e i n f o

rticle history:eceived 7 May 2013ccepted 8 May 2013vailable online 6 June 2013

eywords:CCntraoralree-flapecurrence

a b s t r a c t

INTRODUCTION: Oral epithelial dysplasia within free tissue reconstructions of the oral cavity has beenreported. We report a case where squamous carcinoma arose within radial forearm skin transferred tothe oral cavity 23 years previously. After a thorough literature search we believe this is the first report ofsuch a phenomenon.PRESENTATION OF CASE: A 62-year-old man presented to our service with pain and a new mass in the leftfloor of mouth. The floor of mouth had been reconstructed with a radial forearm free flap (RFFF) 23 yearsearlier following resection of a mucosal squamous cancer. This new mass was within the reconstructiontissue. Biopsy showed multiple areas of dysplasia and a single new focus of invasive carcinoma. This newtumour was excised and reconstructed with a contralateral nasolabial flap. Formal histology showed anarrector pili muscle adjacent to invasive cancer. Some years earlier dysplasia had been noted in the freeflap skin component.DISCUSSION: The skin component of free tissue transfer reconstruction flaps has been shown to developepithelial dysplastic change. This has been found to be associated with similar levels of p53 mutation and

increased Ki-67 expression within this intraoral skin and adjacent dysplastic mucosa. Our case demon-strates similar levels of expression of mutated p53 and Ki-67 in in situ epithelium and in invasive tissueperhaps supporting the idea of expansion of premalignant cells into the skin flap epidermis.CONCLUSION: We have shown for the first time that a new SCCa has developed within the cutaneouscomponent of a free tissue transfer flap. With improved longevity of patients treated with primary surgery

is negical

for oral cavity SCCa there© 2013 Sur

. Introduction

Oral squamous cell carcinoma (OSCC) has a five-year survivalf less than 50% [1]. Alcohol and tobacco are known to be mainausative agents and underlying genetic susceptibility may alsoe an important aetiological factor [2]. Viral agents may also be

nvolved [3]. Reasons for poor survival are: late clinical presenta-ion, 3–4% annual second primary tumour development, and a highecurrence rate at the site of the original tumour. Recurrence ratesave been reported as 10–30% in patients with advanced tumoursespite complete and adequate primary resection [4]. The defini-ion of a local recurrence is any tumour occurring in three yearsf the primary tumour within a 2 cm distance from the originalesion [5]. Recurrence is thought to often occur due to undetected

icro-invasion of nearby tissues not eliminated during primaryreatment [6]. The initial presence of a precursor lesion that sub-equently develops into invasive carcinoma is recognized and this

∗ Corresponding author. Tel.: +44 01274 383920.E-mail addresses: james.cymerman@bthft.nhs.co.uk, jacymerman@me.com,

acscotdoc@aol.com (J.A. Cymerman).

210-2612 © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. ttp://dx.doi.org/10.1016/j.ijscr.2013.05.011

Open access under CC BY

ed for vigilance in monitoring for this cancer recurrence site.Associates Ltd. Published by Elsevier Ltd.

conceptualizes the multi-step process of cancer development in theoral mucosa. It is possible therefore that invasive cancer recurrencecould occur due to the persistence of undetected dysplasia adjacentto the resected tumour.

Following surgical excision of an OSCC, the surgical defect iscommonly reconstructed using free tissue transfer [2]. Microvas-cular surgery has been carried out in the UK since the 1970s andthe radial forearm free flap is the workhorse used to reconstructoro-facial tissues following cancer resection [6].

There is little published describing the behaviour of these cuta-neous flaps within the oral cavity following engraftment despitetheir widespread use [7]. Although most authors report that theskin maintains its architecture and maturation, an inflammatoryreaction can be seen [8]. The skin flap can undergo morphologi-cal changes in this new environment and eventually may resembleoral mucosa at the gross level. This process is described as mucos-alization [9]. It is not clear whether this represents alteration of thenative epidermis of the flap, or replacement of this cell population

Open access under CC BY-NC-ND license.

with oral mucosal epithelial cells from the adjacent mucosa, thoughboth mechanisms have been suggested. Changes in the flap appearto be reactive and associated with an inflammatory process. Thereis a degree of reversibility of these changes evident in some cases.

-NC-ND license.

CASE REPORT – OPEN ACCESS732 J.A. Cymerman et al. / International Journal of Surgery Case Reports 4 (2013) 731– 734

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tion with a RFFF. Previous reports of SCCa in skin graft and dysplasiain fasciocutaneous flaps have speculated that these lesions mayhave developed from adjacent oral mucosa or minor salivary glandslocated below the transplanted skin. In this report the location

Fig. 1. Original clinical photo of RFFF from the 1980s.

egardless of these clinically evident changes, the structure of theermis persists and is not replaced by oral mucosal lamina pro-ria. The inflammatory reaction observed is considered by someuthors to be related to continued alcohol consumption, tobaccose and poor oral hygiene. In some cases these habits continue afterurgery and maintain risk of further carcinoma development [9].

There have been reports of other diseases presenting on intra-ral skin flaps, including: focal acantholytic dyskeratosis on the skinf a myocutaneous pectoralis major flap [10], and an OSCC devel-ping on a skin graft in the buccal mucosa [6]. We present the firsteported case of OSCC arising within the skin of a microvascularadial forearm free flap.

. Presentation of case

This man was first referred to our department in 1984 (aged9) with a floor of mouth SCCa. The tumour was excised with a

cm margin and the defect was reconstructed with a radial forearmree flap (RFFF) (Fig. 1). Histology confirmed invasive OSCC withevere dysplasia extending to the resected mucosal margin. Furtheresection was performed at the time to ensure adequate marginsnd this was reported as clear. Adjuvant therapy was not given.

In 1997 he developed a further lesion at the edge of the recon-truction flap that was treated by laser excision. Histology showedarcinoma-in situ with a focal invasive component that was com-letely excised.

In 2000 he presented with clinically suspicious floor of mouthucosal change. This was biopsied and this showed mild atypia

menable to further laser excision, which was planned. Unfor-unately he repeatedly deferred treatment so this was nevererformed.

In 2007 he again presented to our service with pain and a newass in the left floor of mouth. At that time he was smoking 20

igarettes per day and consuming up to 84 units of alcohol per week.Examination revealed a raised, indurated, erythematous lesion

Fig. 2) within the previously reconstructed RFFF skin and lefteck lymphadenopathy at level 1b. MRI showed a mass in the leftnterior floor of mouth breaching mylohyoid with two enlargedubmandibular nodes with appearances suggestive of centralecrosis. This new tumour was excised (Fig. 3) and the defect recon-tructed with a contralateral nasolabial flap. Histology revealedultiple areas of dysplasia and a single new focus of invasive car-

inoma with an infiltrative front within the graft tissue adjacent ton arrector pili muscle (Figs. 4 and 5). There was no perineural orymphovascular spread. There was however metastatic SCC in two

Fig. 2. Clinical photograph of SCCa arising within the RFF. Note hyperplastic nodules.Indurated, biopsy proven SCCa is indicated by arrow.

level 1 nodes with extracapsular spread. Adjuvant radiotherapywas administered.

This patient has been closely followed up and remains diseasefree at the time of writing.

3. Discussion

The skin component of free tissue transfer reconstruction flapshas been shown to develop epithelial dysplastic change. This hasbeen shown recently to be associated with similar levels of p53mutation and increased Ki-67 expression within this intraoralskin and adjacent dysplastic mucosa [7]. We used immunohis-tochemical (IHC) analysis with MIB-1 antibody to assess Ki-67antigen expression as an indicator of cellular proliferation withinthe tumour and adjacent dysplastic epithelium (Fig. 3). We alsoused IHC to stain for mutated, stabilized p53 in normal appearingmucosa, dysplastic mucosa and tumour tissue from this patient. Wewere able to demonstrate that the changes reported by Robinsonet al. [7] with regard to these IHC markers were present in this caseof cancer within the free flap.

In this patient carcinoma developed 23 years after reconstruc-

Fig. 3. Intra-operative photo detailing resected specimen.

CASE REPORT – OPEN ACCESSJ.A. Cymerman et al. / International Journal of Surgery Case Reports 4 (2013) 731– 734 733

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f the tumour within the epidermal component of the free flapuggests that this was the epithelium of tumour origin. Macro-copically the invasive cancer was seen in the middle of the flapFig. 3), and microscopically flap epithelium differed from that ofuccal mucosa or salivary glands. Histopathological examination ofhe excised tissue showed an arrector pili muscle adjacent to thenvasive cancer (Fig. 4), confirming that the new cancer had risen

ithin the radial forearm skin.A further possibility for the cell of origin for the invasive

omponent in this free flap epithelial component is adjacent dys-lastic mucosal epithelium. Lateral expansion of an altered clonef dysplastic keratinocytes has been suggested to displace normalpithelial cells in free flap skin [11]. Robinson et al. [7] demon-trated severe epithelial dysplasia of engrafted free flaps in theresence of field cancerisation. Our case demonstrates similar lev-ls of expression of mutated p53 and Ki-67 in in situ epitheliumnd in invasive tissue perhaps supporting the idea of expansionf premalignant cells into the skin flap epidermis. The develop-

ent of locally recurrent cancer and second primary tumours has

een described as occurring in this way [11]. Thus proliferation ofersisting dysplastic epithelium into flap epidermis and continu-us exposure to alcohol, tobacco and other risk factors may allow

Fig. 5. Arector pili (single arrow) with adjacent cancer (double arrows).

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acquisition of the further genetic damage required for invasivetumour cells to develop within the field of genetically alteredmucosal cells [7].

Conclusion

We have shown for the first time that a new SCCa has developedwithin the cutaneous component of a free tissue transfer flap. Withimproved longevity of patients treated with primary surgery fororal cavity SCCa there is need for vigilance in monitoring for thiscancer recurrence site.

Conflict of interest statement

None.

Funding

None.

Ethical approval

Written informed consent was obtained from the patient forpublication of this case report and accompanying images. A copyof the written consent is available for review by the Editor-in-Chiefof this journal on request.

Author contributions

Mr. James Cymerman – main author and literature reviewer;Mr. Raghav Kulkarni – secondary author and literature reviewer;Dr. David Gouldesbrough – Head & Neck pathologist – diagnosedlesion, advised on pathology and supplied histology for report; Pro-fessor James McCaul – secondary author, literature reviewer andoverseer of report.

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