since crocker first described extramammary paget disease ( empd ) of the scrotum and penis , empd has been reported as a rare malignancy . the disease is seen most frequently in caucasians and more commonly in women than in men . the most common sites of empd include the female genitalia and perianal regions ; the penoscrotal area has been less commonly reported , with most cases described in asia . penoscrotal empd usually presents grossly as a well - demarcated erythematous lesion and symptoms like pruritus may precede the appearance of clinically visible lesions . because of its rare incidence ( 1/3.7 million males annually ) , the pathophysiology , staging , prognosis , and treatment of empd have not been clarified . the present study reports the clinical characteristics of empd of the penis and scrotum and the outcome of wide local excision of empd . a single - institution retrospective review identified 44 male patients who had visited seoul national university hospital ( seoul , korea ) for empd of the external genitalia between january 2000 and december 2012 . of these 44 patients , the analysis was performed for 19 patients who had undergone wide local excision . excluded patients had undergone radiotherapy and chemotherapy without surgical excision or had undergone surgical excision in other hospitals . the mean age of the patients at diagnosis was 68 years ( range , 57 to 82 years ) . most patients underwent computed tomography of the abdomen / pelvis , chest x - ray , and tumor marker evaluation ( carbohydrate antigen 19 - 9 , carcinoembryonic antigen [ cea ] , prostate - specific antigen , and alpha - fetoprotein ) . wide local excision was performed with or without preoperative mapping biopsy ( fig . 1 ) and intraoperative frozen biopsy , except in one patient who underwent wide local excision with grossly uninvolved lateral margins of 1 cm . in patients who did not undergo preoperative mapping biopsy , the initial excision margin was decided as 2 cm away from the grossly demarcated margin . prophylactic lymph node dissection was not performed , except in one patient who was already known to have locoregional lymph node invasion without distant metastasis . reconstruction was performed by split - thickness skin graft , full - thickness skin graft , local scrotal flap , or by primary closure . all participants were followed up for a mean duration of 22.5 months ( range , 1 to 60 months ) . routine surveillance biopsies were not performed in asymptomatic patients . however , if any new suspicious lesions were found on physical examination , further punch biopsies were considered , and most patients underwent computed tomography or ultrasonography to evaluate for recurrence or progression . the fisher exact test was used for statistical analyses of factors described by p - value . all patients had presented with pruritus and erythematous lesions , which were the most common exam findings . in some patients , the empd lesions had been misdiagnosed as eczema or some other benign skin lesion at outside clinics and were thus managed with supportive treatment . this misdiagnosis delayed proper management by 43.5 months on average , ranging from 1 month to 198 months . to see whether this delay in treatment predicted worse outcomes , the patients were divided into two groups by a 30-month duration from onset of symptoms to treatment . this comparison did not reveal statistical differences in depth of invasion ( p=0.108 ) or disease progression ( p=0.263 ) between the early ( < 30 months ) and delayed treatment ( 30 months ) groups . the lesions were located at the penoscrotal junction in 10 patients ( 52.6% ) , at the penoscrotal junction with spread to the pubic area in 4 ( 21.1% ) , at the scrotum in 4 ( 21.1% ) , and at the penis in 4 ( 4.8% ) . of the 19 patients , 6 patients had presented to our institution with recurrent empd . of these six , three patients had undergone the initial surgical excision at an outside institution . among the remaining three patients , one had cryotherapy at an outside hospital , and two were treated with applications of imiquimod at the department of dermatology in our hospital . of the whole , one patient had a locoregional invasive disease and another had metastatic disease at diagnosis , respectively . three patients had underlying malignancies that were diagnosed and treated before the management of empd . the details of treatment and outcomes in this cohort are summarized in table 2 . except for one patient ( no . 6 ) , all of the patients had undergone preoperative mapping biopsy or intraoperative frozen biopsy ( fig . seven patients underwent preoperative mapping biopsy without intraoperative frozen biopsy . in seven patients , intraoperative frozen biopsy was positive and thus additional excisions were performed until a negative margin was obtained , except in one patient ( no . 2 ) for whom margin - free resection would have created too large of a soft tissue defect . tumor cells were detected in resected margins in 10 patients ( 52.6% ) in final pathologic reports . additional excision was not performed for these patients , who were closely followed up instead . there were four recurrent cases ( 21.1% ) , and two of these patients ( 10.5% ) died from the disease . the performance of preoperative mapping biopsy was not correlated with the resection margin ( p=0.628 ) or local recurrence ( p=0.071 ) . the lesion invaded the dermis in 14 patients ( 73.7% ) and invaded the subcutaneous fat layer in 1 patient ( 5.3% ) . the resection margin ( p=0.279 ) and invasion depth ( p=0.235 ) did not correlate with local recurrence . two of nine patients with a positive resection margin underwent additional excision of the positive lesion and there were no recurrences in these patients . patients 2 and 3 , in whom local recurrence was observed at 2 years and 8 months postoperatively , respectively , underwent secondary operations and have been followed up with no evidence of disease at 5 years . patient 6 had undergone palliative chemotherapy with 5-fluorouracil and cisplatin but died from disease progression . patient 18 had imiquimod treatment before the operation , but complete surgical excision of the large lesion could not be obtained owing to morbidity , including vessel injury , lymph edema , and large skin defect . mostly , empd arises as a primary cutaneous malignancy and rarely occurs in association with adnexal carcinoma of a nearby sweat gland or in association with a malignancy of an adjacent organ . wide local excision has been thought to be the treatment of choice for penoscrotal empd . yang et al .   reported that intraoperative frozen biopsy examination reduces rates of positive resection margins and recurrence . our institute has performed intraoperative frozen biopsy or preoperative mapping biopsy since 2000 . in the present study , we report the outcomes of penoscrotal empd patients who underwent surgical excision and review the clinical factors influencing outcomes . preoperative mapping biopsy can help surgeons to define excision margins for lesions and to decide on the reconstructive method . in contrast with previous studies   that reported that frozen biopsy improves the chance of obtaining negative margins , the resection margin was positive in 10 of 19 patients in the present study . this may be because empd has multicentric origins with satellite lesions besides the gross lesion . a positive resection margin was reported to be a risk factor for local recurrence , and depth of invasion and lymphovascular involvement were reported to be important pathological predictors of metastatic potential . however , our findings did not show statistical significance , possibly because of the small sample size , and lymphovascular involvement was not included in the pathologic report , although two progressive cases had occurred among the 14 dermis - invasive diseases . the high proportion of dermis - invasive cases ( 14/19 , 73.7% ) is a salient point . this may reflect the health care trend in south korea , by which most difficult cases are managed at tertiary university hospitals . in contrast with invasive disease , intraepidermal empd had a good prognosis in the present study , and no disease progression was observed despite two cases of local recurrence . therefore , because empd is frequently mistaken for eczema or contact dermatitis , a biopsy should be performed on any uncontrolled inflammatory lesion of the external genitalia to prevent delayed diagnosis . the pathogenesis of empd has not been elucidated , but the discussions of this have involved tumor cells spreading from apocrine or eccrine gland tumors , epidermotropic spreading from a regional malignancy , malignant transformation of epithelial cells , and malignant transformation of stem cells in the epidermis . internal malignancy was found to be a poor prognostic factor in a study of empd cohorts   in which 3 cases of internal malignancy were observed to have no local recurrence at follow - up . the incidence of internal malignancy related to empd is lower in asians than in caucasians . thus , routine colonoscopy to screen for empd - associated colon cancer may not be indicated among asian patients . instead , routine immunoperoxidase study for cea and low - molecular - weight cytokeratin ( ck ) could be recommended if internal malignancy is suspected . most cases of empd revealed strong immunoreactivity for cea and ck-7 with androgen receptor , in contrast with negative reactivity for ck-20 and p53 . for instance , ck-20-positive empd may represent secondary paget disease due to associated colorectal cancer , and c - erbb-2 was found to have a strong association with dermal invasion . in the present study , cases treated by nonsurgical methods were not included . in the present study , a positive resection margin and local recurrence in intraepidermal cases had a relatively good prognosis . among dermis - invasive cases , however , two patients with recurrence died of disease progression . in intraepidermal cases with local recurrence , wide excision of the lesion appears to be the most effective modality of treatment , as li et al . however , dermis - invasive lesions with local recurrence should be managed by wide excision with adjuvant management such as radiation therapy . kim et al .   reported that radiotherapy can be effective for local control in unresectable cases , and hata et al a retrospective review of the surgical management of empd from the mayo clinic   showed that mohs surgery appears to be effective for paget disease because the tumor has indistinct margins . there are some studies on chemotherapy in the management of empd [ 21 - 25 ] , but the efficacy has not been clarified . we plan to further investigate and report on the multimodality treatment of empd in a future publication . although penoscrotal empd is a rare malignancy , its diagnosis should not be delayed to allow for prompt treatment . wide local excision is recommended with preoperative mapping biopsy and intraoperative frozen biopsy in nonmetastatic disease . our findings suggest that intraoperative frozen biopsy or preoperative mapping biopsy can not guarantee negative margins on final pathology . however , preoperative mapping biopsy and wide local excision with intraoperative frozen biopsy results in good prognosis in the treatment of empd , especially in those cases without dermal invasion . in recurrent cases , wide local excision is the treatment of choice , but adjuvant management like radiotherapy should be recommended in the presence of dermal invasion or regional invasion .
purposethere are only a few reports of extramammary paget disease ( empd ) of the external genitalia because it is a rare malignancy . 
 we investigated patients with empd of the penis and scrotum and report the outcome of surgical management.materials and methodsfrom 2000 to 2012 , a total of 19 patients diagnosed as having penile and scrotal empd underwent wide local excision with or without intraoperative frozen biopsy or preoperative mapping biopsy . 
 the medical charts of these patients were reviewed and analyzed retrospectively . 
 mean follow - up was 22.5 months ( range , 1 to 60 months).resultsthe mean age of the patients was 68 years ( range , 57 to 82 years ) . in some patients , the lesions were misdiagnosed as either eczema or some other benign skin lesion at outside institutions , with a mean delay in diagnosis of 43.5 months ( range , 1 to 198 months ) . 
 intraoperative frozen biopsy or preoperative mapping biopsy was performed in 18 patients . 
 the resection margin was negative in 9 patients ( 47.4% ) and positive in 10 patients ( 57.6% ) . 
 intraepithelial empd without dermis invasion was observed in 5 patients ( 26.3% ) , whereas diseases with dermis invasion were noted in 14 patients ( 73.7% ) . during the follow - up period , 
 recurrences occurred in four patients , and two patients with dermis invasion and recurrence died from the disease.conclusionsdiagnosis of empd should not be delayed to allow for prompt management . 
 our findings suggest that intraoperative frozen biopsy or preoperative mapping biopsy can not guarantee negative margins on final pathology . 
 however , preoperative mapping biopsy and wide local excision with intraoperative frozen biopsy demonstrates good prognosis of empd , especially in those cases without dermal invasion .