The PPD is rare and accounts for 5.4–20% of extramammary paget’s disease (EMPD) cases [2, 3, 4], often associated with internal malignancies and a poor prognosis [5]. The number of recorded cases is small, most of which describe the disease manifestations, and a variety of treatment modalities. The most important diagnostic criteria for PPD is Paget's cells, which are characterized by round ceils with a pale vacuolated cytoplasm and a large reticular nucleus [6]. A biopsy of the lesion should be implemented to confirm the diagnosis before surgery. The differential diagnosis should include leukoplakia, Bowen's disease, squamous-cell cancer, eczema, and so on. In a review by Grow, PPD can be divided into three different patterns on the basis of origins, 50% of cases associated with an apocrine or eccrine carcinoma, called "original paget’s disease (PD)", 25% with an underlying anal/rectal adenocarcinoma or squamous cell carcinoma, called "pagetoid extension", and 25% with no underlying malignant lesion [7]. These lesions might locate within the anal canal, perianal area or around the anus, and involve one quadrant to the whole circle. In our case, the patient suffered from PPD around the anal without underlying carcinoma according to CT scans, gastroenteroscopy, PET-CT and any other examination methods. The enlarged inguinal lymph nodes in the left side indicated a high degree of malignancy.
Treatment for PPD varies depending on the different origins and staging of the disease. It is commonly accepted that wide excision could direct toward achieving local control, especially for the “original PD”, and it can be performed repeatedly if recurrence happens. If the skin defect is huge after resection, local rotation flaps, or skin grafting might preserve patients’ anal function. For patients with downward spread of anal/rectal malignant, more aggressive surgery should be considered to cure the disease, including the possibility of an abdominoperineal resection (APR) [8]. For PPD patients with no underlying carcinoma, there is no widely accepted recommendation yet because of the small number of the cases. Wide excision is the first choice just like the one we performed, and a negative margin should be guaranteed. Patients must be closely followed up, to detect not only a possible recurrence, but also delayed underlying malignant tumor. Besides surgery, radiation therapy is an alternative treatment in some circumstances. Though there are no randomized controlled trials to compare surgery with radiation therapy for EMPD, radiation therapy for EMPD may be indicated in patients medically unfit for surgery, for recurrence following surgery, in any patient who wishes to preserve the functional or as an adjuvant to surgery in patients with an underlying adenocarcinoma [9]. However, some literature contained a view that radiotherapy had no place in the management of the condition because of high recurrence rates [10, 11]. We gave the patient radiotherapy covering the bilateral inguinal lymphatic drainage area because of the enlarged inguinal lymph nodes to prevent possible lymph node metastasis. Chemotherapy is another way of adjuvant treatment often combined with radiation, but there is no guideline for the deployment of chemotherapy drugs. Topical chemotherapeutic agents include 5-fluorouracil (5-FU) and mitomycin C, though no survival data has been recorded due to sporadic cases. In general, this is in the setting of invasive or more aggressive recurrent disease, because the response to chemotherapy has been poor. 5-FU may be useful for symptomatic relief, preoperative delineation of disease extent, cytoreduction prior to surgery and postoperative detection of early disease recurrence [12]. Although some authors have reported successful treatment of Paget’s disease with chemo-radiotherapy, the use of adjuvant therapy has not been associated with improved local control or survival [13]. Based on our experience, the patient was treated with XELOX regimen according to pathological findings of adenocarcinoma from hepatic metastasis without any identified underlying carcinoma, and it worked, to a certain extent, from the descending tumor marker and the steady state of metastases.
Shutze et al. gave classification to PPD based on the disease pathology from the cases reported in the literature and correlated with surgical treatment [14]. The survival data varied dramatically from diseases in different stages. Wide local excision was recommended for patients with Paget's cells found in perianal epidermis and adnexae without primary carcinoma (Stage I) and cutaneous Paget's disease with associated adnexal carcinoma (Stage IIA), though the most common morbidity after surgery was local recurrence with the rates of 44–60% [15, 16]. Repeated resection is an effective way when it happens and often obtains a good survival outcome. But tumor stages are not fixed and sometimes require restaging as the disease progresses or the underlying carcinoma is identified. For patients with PPD of more aggressive staging, the prognosis is extremely poor. Distance metastases often occur months after the first treatment, usually involving the liver, the lung, and the bone, and may lead to rapid progress. Among three different patterns of PPD, the pagetoid extension has worse prognosis than original PD [17], while PPD without underlying malignant lesion has the most uncertain outcome. Immunohistochemical stains are helpful in identifying the origins of the disease from raising the suspicion of underlying malignancy with positive CK20 and CEA [18]. Brown et al. found that survival was significantly worse for cases of primary PPD treated with radiotherapy compared to cases treated upon recurrence [19], but this might be because those patients were likely to have poorer general condition or more extensive metastasis so that they could receive radiotherapy at primary stage. This patient had non-invasive PPD at first surgery except enlarged inguinal lymph nodes in the left side, but only seven months since surgery, she was found to have hepatic metastasis, which recurred after HAE and HIFU. When distant metastasis happens, local treatment alone cannot obtain satisfactory effect. So we gave her chemotherapy regimens of XELOX based on the pathologic findings of adenocarcinoma, and fortunately, the patient got a declining tumor marker value and stable metastases.