cutaneous squamous cell carcinomas ( cscc ) comprise about one fifth of all non - melanoma skin cancers , the incidence rate is steadily increasing in the usa and europe . while those tumours that arise secondary to inflammatory and degenerative processes have a much higher metastasis rate . the mortality rate in patients with metastasis is about 75% [ 1 , 2 ] . a malignant transformation is known to occur in many nevi such as a sebaceous nevus , a basal cell nevus or a dysplastic nevus , while a verrucous epidermal nevus has only rarely been associated with neoplastic changes . keratoacanthoma , multifocal papillary apocrine adenoma , multiple malignant eccrine poroma , basal cell carcinoma and cscc have all been reported to develop from a verrucous epidermal nevus [ 3 , 4 , 5 , 6 , 7 ] . in addition , cscc have been reported to arise from other nevoid lesions like a nevus comedonicus , porokeratosis , a sebaceous nevus , an oral sponge nevus and an ichthyosiform nevus with child syndrome [ 8 , 9 , 10 , 11 ] . a 50-year - old asian male presented with a partially pigmented 2-year - old lesion on the upper left side of his back . the lesion measured 3 cm in diameter , was round and had an irregular contour and surface . it had a verrucous pigmented rim on its medial side that measured 68 mm , while the prominent exophytic erythematous part measured 2.1  2.2 cm ( fig . it was friable , bled easily , was though but not indurated and it was not attached to the underlying structures . the trunk also showed few post - pubertal lentigines , but no other nevi or seborrheic keratosis . the patient had no other co - morbidities and he was not immune - compromised . the pathological examination confirmed an epidermal nevus at the periphery of the lesion ( fig . the epidermis showed bowenoid features with irregularly sized nuclei , a loss of polarity , dyskeratosis and mitotic figures ( fig . some sections from the periphery of the specimen showed multiple intraepidermal eddies of atypical cells or the borst - jadassohn phenomenon ( fig . sheets of poorly differentiated , atypical , pleomorphic keratinocytes migrated from the epidermis into the whole dermis , hair follicles ( fig . 4 ) and eccrine glands , including a perivascular and perineural invasion ( fig . 5a atypical cells showed positive staining with cytokeratin markers and other squamous cell carcinoma markers , but they were negative for mart1 and s100 . focal , mild and sparse , subepidermal , lymphocytic infiltrates were found on some sections but were absent in many areas of the lesion . the results were : only mildly increased liver enzymes , an elevated c - reactive protein level and a mild impairment in the pulmonary function tests . the patient was immediately referred to the surgical department for the removal of sentinel lymph nodes . however , the surgeon decided not to excise any lymph nodes as long as the tumour could be totally removed in the absence of enlarged adjacent lymph nodes , demonstrated by clinical and ultrasound examination . six weeks later ( 8 weeks after his first visit ) , the patient had a follow - up . unfortunately , the regional lymph nodes were palpable , while the scar of the primary lesion and the surrounding area remained clear . the swelling was so extensive that it also infiltrated the surrounding subcutaneous tissue , measuring 12  17 cm ( fig . an excision biopsy was taken from the lymph nodes and the surrounding subcutaneous tissues confirming the diagnosis of metastatic cscc . the patient was again operated on for a wide removal of the axillary lymph nodes and adjacent tissues . he was transferred to the al amal cancer hospital for chemotherapeutic and/or radiotherapeutic options ; however ; he was not eligible for either option and plans for intervention were postponed . the patient 's general condition continued to decline with additional refractory anaemia , lymphocytopenia and hypoalbuminaemia . after another 4 weeks , a bone scan , ct and mri images showed metastasis in both lungs ( fig . 8a ) and then 3 weeks later in the spinal cord ( fig . 8b ) and brain ( fig . the patient received only palliative care during his entire stay , mainly to treat his anaemia and to control the pain . the prevalence of verrucous epidermal nevi is about 0.10.5% with an equal male - to - female distribution . to the best of our knowledge , only 12 cases of cscc arising from verrucous epidermal nevi have been reported so far in the literature . nine cases are displayed in table 1 [ 7 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] , while the data in the remaining 3 cases were inadequate : 2/3 cases were described in poster abstracts [ 20 , 21 ] , and the third case was not available as a full text . comparing the cases in table 1 , cscc evolving from verrucous epidermal nevi showed an equal sex distribution among males and females . cscc was more common in caucasians ( 4/10 cases ) followed by asians ( 3/10 cases ) and blacks ( 2/10 cases ) . 3/10 were younger than 30 years , and 7/10 were above the age of 40 years ( mean age 53.4 years ) . the 3 younger cases [ 14 , 17 , 19 ] were all females , caucasian and 2/3 had a good prognosis , including followed - up [ 14 , 19 ] . in half of the cases , the cscc was on the trunk ( including the present case ) ; in the other half , it was on the limbs : 2 on the right upper limb and 3 on the left lower limb . the type and distribution of the verrucous epidermal nevi were quite variable : 5/10 nevi were localized , 3/10 nevi were linear and 2/10 nevi were systematized . we also observed that the left upper limbs and the right lower limbs were spared , too . it is also remarkable that 4/10 cscc erupted on the upper trunk and from localized verrucous epidermal nevi [ 7 , 14 , 15 , and the present case ] . nonetheless , the case of ichikawa et al .   was unique and different , as it developed on the mid - back and from a systematized verrucous epidermal nevus . paradoxically , the largest 3 tumours were associated with good prognosis [ 16 , 18 , 19 ] , while distant metastasis was associated with relatively small tumours [ 15 , and the present case ] . in general , the prognosis of cscc evolving from a localized verrucous epidermal nevus was favourable . 5/6 cases had a good prognosis , with variable lengths of follow - up , ranging from 1 to 5 years ( table 1 ) . distant metastasis , possibly by haematogenous spread , to remote areas happened in 2/8 cases . the reason for distant metastasis in these cases may be inferred to the delay in dissection of sentinel lymph nodes . unfortunately , our case was the only one to show poorly differentiated squamous cell carcinoma . in the epidermis they were also present in some biopsies of the other reported cases [ 12 , 15 , 21 , 22 ] . metastasis to the central nervous system remains a major cause of morbidity and mortality in patients with systemic cancers . brain metastases are the most frequently diagnosed intracranial tumours in adults , with an annual incidence rate estimated at 200,000 cases in the usa alone . a variety of systemic malignancies can metastasize to the central nervous system , although the majority of metastases stem from lung cancer ( 4050% ) , followed by breast cancer ( 2030% ) , melanoma ( 510% ) , lymphoma and various other primary sites , like the gastrointestinal tract ( 46% ) and the prostate . brain metastasis from distant cscc , and not as a direct extension from head and neck tumours , is extremely rare . only one case has been reported from a cscc on the dorsum by an italian group . it was a moderately differentiated squamous cell carcinoma measuring 5 cm in diameter and 8.5 mm in depth . the para - aortic lymph nodes were involved , while the lungs and liver were spared . ours can be considered the second case of brain metastasis from a distant area and not as a direct extension as in cases of head and neck cscc . the report was on a 73-year - old asian male , and the excised tumour was located on his right fourth toe . three years later , he developed metastasis in the thoracic region of the spinal cord . there have been no previous reports on metastasis from cscc from a remote site to the spinal cord . again the current report can be considered the second case of spinal cord metastasis from a distant cscc and not as a direct extension of the tumour . in the present case , apart from the delay in presentation for more than 2 years and the presence of the tumour in a hidden area ( on his back ) , other risk factors contributed to the bad prognosis . factors for high - risk squamous cell carcinomas have been summarized by tufaro et al . . a tumour exceeding 2 cm in size , pathologically determined bowenoid features , poor differentiation , perineural invasion and invasion of the surrounding structure are all high - risk factors for tumour spread . an invasion depth of > 4 mm or a clark level iv has been associated with a 5-fold increase in metastatic risk . there is no consensus on elective sentinel biopsy or lymph node dissection in cscc which does not involve the head and neck regions , especially if there are no clinical or radiological signs of node involvement . in most studies on high - risk cscc , intervention for n0 moreover , the usefulness of lymph node dissection is arguable , as 52% of the patients who underwent lymph node dissection for nodal involvement had disease recurrence and 75% of these patients developed distant metastasis . in conclusion , cscc evolving from a localized verrucous epidermal nevus is rare , but it might be underreported . the depths of the lesions , perineural and perivascular infiltration are factors that favour metastasis . two recently published studies [ 7 , 19 ] showed a good prognosis after the excision of sentinel lymph nodes , which may be an advice for clinicians to excise suspected sentinel lymph nodes immediately . delayed excision of sentinel lymph nodes may carry a bad prognosis as in our case and the case described by levin et al . .
a malignant transformation is known to occur in many nevi such as a sebaceous nevus or a basal cell nevus , but a verrucous epidermal nevus has only rarely been associated with neoplastic changes . 
 keratoacanthoma , multifocal papillary apocrine adenoma , multiple malignant eccrine poroma , basal cell carcinoma and cutaneous squamous cell carcinoma ( cscc ) have all been reported to develop from a verrucous epidermal nevus . 
 cscc has also been reported to arise from other nevoid lesions like a nevus comedonicus , porokeratosis , a sebaceous nevus , an oral sponge nevus and an ichthyosiform nevus with child syndrome . here 
 we report a case of progressive poorly differentiated cscc arising from a localized verrucous epidermal nevus , which caused both spinal cord and brain metastasis .