nevertheless , it is commonly misdiagnosed , which leads to a poor prognosis and more aggressive treatments . subungual squamous cell carcinoma ( sscc ) is a rare entity with an extremely varied clinical presentation . the lack of awareness among physicians , its indolent natural history , and the higher prevalence of other benign conditions on the ungual apparatus are responsible for delay in its diagnosis . we have reported here four cases of sscc with a previous mistaken diagnosis of a benign process unsuccessfully treated for years . figure 1 shows the different clinical presentation of cases herein reported . the first patient presented with involvement of two digits . radiological studies did not reveal alterations , except for an incidental osteochondroma in the fourth patient . histological examination revealed sscc in all cases , but immunostaining for human papillomavirus ( hpv ) was only positive in the first patient , who presented with deeper tissue involvement [ figure 2 ] . all surgical procedures resulted in free - margin tumoral excisions , without recurrences or nodal involvement during follow - up between 5 and 30 months . clinical and histological data of the four study patients a ) keratotic and verrucous lesion below the nail plate mimicking a viral wart ( case 1 ) , ( b ) crusted subungual lesion ( case 2 ) , ( c ) erythematous and eroded lesion covered by crusts and keratotic material ( case 3 ) , ( d ) prominent onycholysis and fleshy nodular lesion ( case 4 ) ( a ) positive immunostaining for hpv in case 1 ( arrows)hpv immunostaining , 200 ) , ( b ) moderately differentiated subungual squamous cell carcinoma in the second patient . ( h and e , 100 ) , ( c and d ) well - differentiated squamous cell carcinoma in third and fourth patients . lobular aggregations of slightly atypical keratinocytes and incipient horn pearl formation ( arrows)(h and e , 100 ) tumors located in subungual tissues include squamous cell carcinoma ( scc ) , bowen 's disease , melanoma , basal cell carcinoma , and keratoacanthoma among others . usually , sscc affects a single digit , the thumb and the great toe being the most frequently involved . multiple fingers involvement has also been described . the incidence is higher in men between the fifth and seventh decades of life . the proposed aetiologies of the disease include chronic infection , chemical or physical microtrauma , genetic disorders such as congenital ectodermal dysplasia , radiation , tar , arsenic or exposure to minerals , sun exposure , immunosuppression , and previous hpv infection . hpv involvement has gained importance , as hpv dna was recovered from 60% to 90% of cases of sscc and > 60% were related to hpv 16 . genital - digital transmission has been suggested as a plausible pathogenetic factor in sscc , as hpv 16 is the most frequent serotype found in genital warts . however , there are probably other factors implicated in malignancy , as viral warts in hands are very common and the development of sscc remains rare . in the cases herein reported , all potential causative factors of sscc were excluded with the clinical history data and the physical examination . the clinical features may be variable and include chronic pain and swelling , onycholysis , or nail plate dyschromia . the most frequent presentation consists of wart - like appearance involving the nail bed and periungual areas in association with nail dystrophy . viral warts , onychomycosis , or chronic paronychia remain the most commonly mistaken entities . besides , the tumor masked by the nail plate , lack of awareness , and overlying secondary infections lead to misdiagnosis for an average of 4 - 40 years . therefore , exploratory nail plate removal and subsequent biopsy are advised in all patients with chronic nail conditions that fail to respond to conventional treatment . in patients with recurrent nail infections or chronic ulcerations , tissue culture is also needed . imaging studies may be done to assess possible bone involvement . as a result of delayed diagnosis , most patients with sscc present with invasive disease , with bony involvement ranging from 16% to 66% . sscc is considered a low - grade malignancy and less aggressive than scc arising elsewhere . the tendency to recurrence is higher on the nail unit than in other anatomic areas . this fact can probably be due to residual hpv in surrounding areas or , more frequently , due to incomplete tumor removal . wide local excision and simple excision have also been proven effective , the former being preferred because of the lower recurrence rate . amputation of the distal phalanx is usually the recommended treatment for patients with bone infiltration . radiation therapy has also been reported to be effective . in conclusion , a high index of suspicion for sscc is required . therefore , an early biopsy in chronic persistent or recurrent nail lesions , and subsequent early sscc diagnosis may prevent more aggressive treatments and assures a favourable prognosis . human papillomavirus infection probably has an important role in the development of subungual squamous cell carcinoma.subungual squamous cell carcinoma has a high recurrence rate . human papillomavirus infection probably has an important role in the development of subungual squamous cell carcinoma .
subungual tumors are rare in general . of all tumors , subungual squamous cell carcinoma ( sscc ) 
 is the most frequent one . 
 protean clinical presentations and the lack of awareness of the disease are responsible for an incorrect or delayed diagnosis and subsequent delayed treatment . we have reported here four patients with sscc who were previously wrongly diagnosed with a benign process and treated unsuccessfully for years . 
 we would like to highlight the need of a biopsy in chronic or recurrent nail lesions that fail to respond to a previous conservative treatment in order to rule out sscc .