PPD is usually associated with an underlying malignant anorectal tumor and has a relatively poor prognosis  with a high risk of local recurrence . The rate of malignancy associated with PPD ranges from 33% to 86% . Immunohistological examination alone is not sufficient to differentiate whether or not PPD is associated with underlying anorectal cancer in half of the cases, and endoscopic and radiologic evaluation is mandatory to confirm the presence or absence of underlying malignancy.
In the present study, primary anorectal carcinoma could not be identified preoperatively in half of the patients, and APR was performed in only 1 case. There was 1 death in the WLE group. However, only half of the patients with anorectal cancer underwent APR + WLE to preserve the anus, although there were cases of recurrence-free survival of more than 5 years after WLE. Further investigations are needed to identify cases in which APR should be pursued aggressively and those in which WLE (with or without transanal local excision) can be considered.
The 2 deaths occurred in a patient without an identified primary tumor who underwent WLE alone as the initial treatment (case 1) and in a patient with a primary tumor identified preoperatively who underwent APR + WLE (case 7).
Case 1 was found to have a dermal invasion in a WLE specimen and suspected to have underlying anorectal cancer based on histological and immunohistological findings. Five years after surgery, the patient was found to have multiple distant metastases (inguinal lymph nodes, liver, and bone) and died 1 year later. Patient 7 had a mucinous (muc/sig) adenocarcinoma of the anal gland with the invasion of the external anal sphincter and a positive surgical margin. This patient received postoperative chemoradiotherapy (FOLFOX + radiotherapy at 50.9 Gy/33 Fr) but had the first relapse in the inguinal lymph nodes about 6 months later and underwent inguinal lymph node dissection. Three months later, he had a second relapse in the pararenal lymph nodes and underwent further chemotherapy (FOLFIRI + panitumumab). After an additional 3 months, he had another relapse in the pararenal aortic lymph nodes and received another course of chemotherapy (FOLFIRI + panitumumab). However, he developed multiple liver, lung, and bone metastases and died 2 years after surgery.
Both these fatal cases had immunohistological findings in a preoperative skin biopsy suggestive of underlying anorectal carcinoma, inguinal lymph node metastasis as the first relapse, and distant metastasis several months later. If WLE is performed to preserve the anus, a careful search for distant metastasis and regular follow-up are essential, even if recurrence occurs after a long period.
In terms of initial treatment, there were 4 recurrences after WLE (with or without transanal local excision), 2 after APR, and 1 after radiotherapy. There were 2 recurrences in lymph nodes (with or without distant metastasis) after initial APR + WLE and 2 local recurrences plus 2 lymph node recurrences in the initial WLE group. All 6 cases of recurrence after surgical resection had positive resection margins at the initial surgery. Chemoradiotherapy or radiotherapy was performed in 2 cases after APR and in all 4 cases after WLE. WLE was performed for local recurrence in 3 patients, 2 of whom (cases 6 and 12) developed distant metastasis as a second recurrence and are alive and under treatment more than 4 years after their initial diagnosis. One of the patients with local recurrence (case 3) had a third recurrence and survived for more than 5 years. Lymph node dissection was performed in 4 patients with recurrence limited to the inguinal or lateral lymph nodes. Two patients (cases 1 and 7) died of distant metastasis after a second recurrence, and 2 patients were alive without recurrence (cases 2 and 9). Local resection was performed in patients with locoregional (local or lymph node) recurrence. Long-term survival may be possible if distant recurrence does not occur within a short interval.
Of the 5 patients in this study who underwent mapping biopsy, 4 had positive margins, 1 had local recurrence, 3 had lymph node recurrence, and 2 had a recurrence of distant metastasis. Accurate histological examination by four-quadrant biopsy or multiple sharp punch biopsies of the lesion’s periphery has been recommended as a prerequisite for mapping the lesion preoperatively. Intraoperative frozen section analysis of the resection margin has been proposed to reduce the possibility of borderline invasion and minimize the local recurrence rate . However, frozen section analysis of surgical margins in PPD can be misleading and dangerous because it may appear negative intraoperatively but become permanently positive on subsequent histological analysis. It is believed that permanent margin status is not a predictor of local recurrence and that a minimally invasive carcinoma measuring <1 mm probably does not have an adverse prognosis, whereas a deeply invasive carcinoma behaves as a fully malignant adenocarcinoma .
In this study, 1 patient (case 3) received radiotherapy, and another (case 13) received preoperative chemoradiotherapy. It is difficult to identify the extent of excision in EMPD because of skip lesions . It may be necessary to devise a method such as mapping biopsy, which is similar to surgical excision, for areas in which a skin lesion has been irradiated. Although there are no definite opinions on the treatment of adenocarcinoma of the anal canal with PS at present, there are some case reports of radiotherapy for PPD [32, 33], and it may become an option in the future.