title: The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients.
abstract: BACKGROUND
  Although extramammary Paget's disease (EMPD) mostly presents as intraepithelial carcinoma, we sometimes encounter patients with invasive EMPD (iEMPD) who have lymph node metastasis and may develop distant metastasis. Although sentinel lymph node biopsy (SLNB) is widely accepted for various cancers, there is no large study that has assessed its role in iEMPD.
  
  
  OBJECTIVE
  The main objective of this study is to assess the role of SLNB in patients with iEMPD.
  
  
  METHODS
  We retrospectively collected data on 151 iEMPD patients treated from 1998 to 2012 in 11 institutes in Japan. All 151 patients received curative surgery for their primary tumor and none of them had distant metastasis. SLNB was performed on the 107 patients without lymphadenopathy to determine their LN status. The 44 other patients with lymphadenopathy underwent one of the following procedures to determine their LN status: SLNB in 22 cases, immediate LN dissection in 21, and LN biopsy in 1.
  
  
  RESULTS
  Compared to those without lymphadenopathy, patients with lymphadenopathy had advanced primary tumors (nodule in the primary tumor, thicker tumor, deeper invasion level, and lymphovascular invasion). The rate of LN metastasis in patients with lymphadenopathy was 80%, compared to 15% in patients without lymphadenopathy who underwent SLNB. Compared to those with negative SLN, patients with positive SLN had advanced primary tumors (nodule in the primary tumor, deeper invasion level, and lymphovascular invasion). Multivariate analysis revealed that dermal invasion (odds ratio 5.8, p=0.04) and lymphovascular invasion (odds ratio 18.0, p=0.0023) were independent factors associated with SLN positivity. Notably, there was no difference in survival between patients with or without SLN metastasis (p=0.71). On the other hand, patients with lymphadenopathy showed worse survival than those with positive SLN (p=0.045).
  
  
  CONCLUSIONS
  Clinical lymphadenopathy was strongly correlated with pathological LN metastasis and also associated with worse survival than absence of lymphadenopathy. The rate of occult LN metastasis detected by SLNB was 15%. Survival was not affected by SLN status even when an advanced primary tumor was present in patients with positive SLN. Our results raise the possibility that SLNB and subsequent LN dissection improved the survival of patients with early stage lymphatic spread. Our study indicates that SLNB should be considered for iEMPD if lymphadenopathy is not apparent.
authors.affiliation: University of Tsukuba, Japan. fujisan@md.tsukuba.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kiyohara
authors.affiliation: University of Tokyo, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.affiliation: Hyogo Cancer Center, Akashi, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Murata
authors.affiliation: University of Shinshu, Nagano, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Uhara
authors.affiliation: Toyama Prefectural Central Hospital, Toyama-shi, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Hatta
authors.affiliation: University of Kyushu, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: University of Hokkaido, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: University of Tsukuba, Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital, Tokyo, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ohara
mesh_terms: D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008206:Lymphatic Diseases / Q000473:pathology; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D010145:Paget Disease, Extramammary / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D012189:Retrospective Studies; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate
keywords: Extramammary Paget's disease; Lymphadenopathy; Sentinel lymph node