verrucous carcinoma ( vc ) was defined by ackerman in 1948   as a diagnostically problematic squamous cell neoplasia involving lip , oropharyngeal , and laryngeal mucosa . as a result ackerman 's tumor .  vc is strongly associated with the chronic use of tobacco or with the practice of chewing betel nuts . according to recent studies , human papillomavirus could have a potential role in the tumoral development and progression , although this topic is still under discussion . this uncommon lesion , in its pure form , can be considered a disease of later life , typically occurring in the seventh - eighth decades , with a strong male predominance . in the south - eastern usa women were particularly affected because of their historically common practice of snuff dipping . in the head and neck district , vc most frequently involves the oral cavity , where it commonly arises from buccal mucosa and lip . it is considered a slowly growing neoplasm that can reach considerable size before being brought to medical attention . it appears as a papillary nonulcerated gray - white or red mass with a very broad base of attachment . this heavily keratinized , well differentiated variant of squamous cell carcinoma shows warty - like aspects and lacks conventional cytologic findings of atypia , exhibiting only locally invasiveness and no metastatic potential . we report a case of oral vc , referring all the diagnostic difficulties occurring in the clinicopathological examination . during an oral examination a 77-year - man showed a whitish verrucous , exophytic mass , about 1 centimetre in diameter , localized in the hard palate at the upper right premolars and extending also to the vestibular side of the gingiva . he quit smoking since 50 years , and he is currently affected by arterial hypertension in pharmacological treatment . the lesion was first stained by toluidine blue and lugol stainings , and then incisional biopsies were performed at the observation time and 15 days later . in two weeks the lesion grew larger and triplicated its size ( figure 1 ) . nevertheless , the lesion has continued to grow , and a total excision with an osseous box and  en bloc  avulsion of involved teeth ( 1.3 - 1.4 - 1.5 ) were done . according to the clinical behaviour of the lesion , the correct diagnosis was of vc , as confirmed by some histopathological features showed by the second biopsy . actually , 2 weeks after the surgical treatment , the patient showed a similar lesion close to the distal excision margin , on the palatal side . the first incisional biopsy was histopathologically assessed as verrucous hyperplasia , showing ( 1 ) proliferation of cutaneous epithelium , resulting in variable epithelial thickness , ( 2 ) verrucous exophytic component , ( 3 ) smoothly contoured , though irregular / asymmetrical and not pushing , ( 4 ) no evidence of frank invasion , and ( 5 ) mild dysplasia of deep keratinocytic layers ( figure 1 ) . the definitive surgical specimen shows a tan mass , with a papillary wart - like surface and sharp borders . histologically , pathologists confirmed the clinic diagnosis of vc , on the base of these features : dense superficial keratinisation , dyskeratosis , minimal cytological atypia , pushing margins without a frank infiltration ( figure 2 ) , nor vascular or perineural invasion , and prominent lymphoplasmacytic infiltrate at the base of the lesion . the clinico - histo - pathological diagnosis of vc is often exclusionary and extremely difficult . the precise histological categorisation of mucosal lesions that include an exophytic growth component is a difficult and often encountered experience . it has been reported that multiple biopsies over several years are often required before diagnostic histological features supporting an appropriate interpretation are identified . the term  verrucous  was applied for lesions showing a keratotic exophytic surface composed of sharp or blunt epithelial projections with keratin - filled invaginations ( plugging ) , but without obvious fibrovascular cores . the histological features of vc , for example , verrucous surface and  elephant feet-  like downgrowth seeming to compress the underlying connective tissue and typically showing minimal or absent cytological atypia , are widely known . often the invasion can be lacking in incisional biopsies , and it is not possible to exclude an underlying conventional carcinoma . distinction from classical squamous cell carcinoma is a frequent problem also for clinicians because of the extensive nature of the lesion mimicking an invasive cancer . vc shows the characteristics of cell kinetics that are similar to those of normal epithelium and not to conventional squamous carcinoma . s - phase is confined to basal layer , unlike the invasive cancer . by flow cytometry , vc is a diploid lesion ; on the contrary , the conventional squamous cancer often shows aneuploidy and genomic instability .   in superficial biopsies without an obvious invasive growth , the bland benign appearing cytology may , also , induce to an erroneous diagnosis of benign squamous proliferation . an anecdote that he related during his extensive travels dealt with his early experience at the ellis fischel cancer center and a patient who had multiple biopsies of an oral cavity lesion which dr . he personally examined the patient and confronted him with an obviously invasive lesion extending through the oral cavity and involving the skin of the cheek . the pathologist , when a surgeon asked him the specific  nature  of a problematic lesion arisen on the oral cavity , replied as  the bad kind !  to confirm the difficulty in the diagnosis of a vc on incisional biopsies . because it is cytologically benign , besides the focal basal cell nuclear hyperchromatism , distinction from vc and verrucous hyperplasia ( vh ) the final diagnosis of vc can eventually depend on identifying , as in our case , the characteristic peripheral buttressing and shouldering . it should be also noted that some authors considered vh as a continuum of lesions simultaneously occurring with or metachronously evolving into vc and/or conventional scc [ 8 , 10 ] . anyway , it is essential that the pathologist alerts the clinician to the progressive nature of the lesion and recommends complete excision or close followup and rebiopsy [ 8 , 10 ] . in sum differential diagnosis , vc should be analysed regarding ( a ) conventional scc , especially with those scc showing  verrucoid  features , ( b ) proliferative verrucous leukoplakia ( pvl ) , ( c ) reactive keratosis and epithelial hyperplasia , ( d ) pseudoepitheliomatous hyperplasia , ( e ) verruca vulgaris , and ( f ) keratoacanthoma when verrucous carcinoma affects cutaneous sites . in particular it is mandatory to rule out hybrid carcinoma including vc and conventional scc . hybrid carcinomas should be staged and managed as conventional scc because their metastatic potential , contrary to classical vc , shows excellent prognosis following complete surgical removal in the early stages . finally we report the controversy regarding the role and the effect of radiation therapy on vc . neck dissection is not indicated for any pure vc , given the absence of nodal metastases ; cervical adenopathy may be associated with vc , representing reactive changes and not metastatic disease . the literature supports the concept that radiotherapy is contraindicated in the treatment of vc for the occurrence of radiation - induced anaplastic transformation , manifesting 2 to 8 months following the therapeutic cycle . as the literature is confusing , we retain that radiotherapy could be used only in selected clinical settings , when surgery is not possible . this paper has identified the common pitfalls during routine assessment of surgical or bioptical material : the pathologically underdiagnosed cases ( diagnosis of keratosis or vh , with synchronous or metachronous aggressive pattern of growth ) , the clinically undertreated   ( pvl and vc , without a histological diagnosis of dysplasia ) , and the surgically overtreated cases ( vc treated as a conventional invasive scc , with demolitive surgical resection and useless lymphadenectomy ) . we realize that a correct diagnosis is founded on the precise comparison and integration of all the   results and not on the isolated valuation of the different findings . in this context