A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors
Introduction
The incidence of extramammary Paget disease (EMPD) is reported to be rare, ranging from 0.1 to 2.4 patients per 1,000,000 person-years [1], [2]. It typically appears as carcinoma in situ and has a favorable prognosis because of the slow development of the disease [3], [4]. However, once it progresses to an invasive tumor, invasive EMPD (iEMPD), it metastasizes mainly through the lymphatic channels and becomes fatal [5], [6], [7]. The proportion of EMPD patients with iEMPD is reported to be low: the invasive form has been reported in only 20% of all EMPD cases [1], [8]. Although the exact numbers are unknown, occurrence of lymph node (LN) and distant metastasis in iEMPD have been reported to be 34% to 61% [6], [7], [9], [10]. In cancer treatment, a TNM staging system is crucial not only for estimating the survival of each patient but also for determining the population at high risk and for discovering new treatment methods. However, owing to the rarity of the disease, accumulation of data on a sufficient number of patients to create a disease-specific TNM staging system for EMPD has thus far not been achieved. In our study, we collected and analyzed data on 301 iEMPD patient from 12 institutes in Japan and propose a new EMPD-specific TNM staging system based on the prognostic analyses.
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Patients
We retrospectively collected 350 iEMPD patients treated from 1998 to 2012 at 12 institutes in Japan. We excluded patients with intraepithelial tumors because intraepithelial tumors theoretically have no chance of metastasis or of becoming fatal. The following patient data were collected: demographic features (age and gender at presentation); clinical presentation (presence of nodule, size of the whole lesion, and presence of lymphadenopathy); histopathological findings of the surgical specimen
Results
The summary of this cohort is shown in Table 1. The average age was 72.2 years and the male/female ratio was 3.37, male dominant. The average tumor thickness was 3.7 mm with a median thickness of 1.5 mm. One hundred sixty-five patients (55%) had tumors ≦2 mm in thickness according to Breslow’s classification for melanoma. One hundred sixty-four patients (54%) had level II or III tumors according to Clark’s classification. Lymphovascular invasion, a factor reported to be associated with poor
Discussion
Currently, the staging systems for penile, vaginal, and skin appendage cancers are adopted when reporting iEMPD with stage classifications because no staging classification system for EMPD has been established [10], [13], [14]. However, using another staging system is inappropriate because each such staging system has been established on the basis of data specific to a particular kind of cancer. Although a large number of patient data is required to establish a staging classification system for
Conclusions
We collected and analyzed 301 patients with iEMPD. The factors associated with survival were tumor thickness, lymphovascular invasion, number of LN metastases, and distant metastasis. On the basis of our results, we propose a TNM staging system for iEMPD. In addition, most of the distant metastases occurred after or synchronously with LN metastasis, which raises the possibility that lymphatic spread is the primary event of tumor dissemination. We should continue to accumulate data and revise
Funding source
None.
Conflict of interest
None.
Acknowledgements
We are grateful to Brian K. Purdue and Flaminia Miyamasu for their English revision.
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