title: Tumor budding is an independent risk factor for lymph node metastasis in cutaneous squamous cell carcinoma: a single center retrospective study.
abstract: BACKGROUND
  Although tumor budding is acknowledged as a risk factor for lymph node metastasis in certain types of carcinoma, it is not well investigated in cutaneous squamous cell carcinomas (SCCs). In this study, we analyzed the correlation between tumor budding and nodal metastasis in cutaneous SCC.
  
  
  METHODS
  Histopathologic specimens of 15 metastasizing and 144 non-metastasizing cutaneous SCC were retrospectively reviewed. Cut-off point for tumor budding was determined at five or more foci of an isolated cancer cell or a cluster comprising <5 cells /1.23 mm(2) in the invasive front of the tumor under hematoxylin and eosin sections.
  
  
  RESULTS
  Tumor budding was positive in 93.3% of metastasizing cutaneous SCC and 25.7% of non-metastasizing cutaneous SCC, respectively (p < 0.0001). In multivariate analysis, tumor budding was an independent risk factor for nodal metastasis among the other risk factors (tumor size, tumor thickness, Clark level and poor differentiation) (p = 0.0021). In combination with tumor thickness >4 mm, tumor budding became a better marker for predicting nodal metastasis (sensitivity 93.3%, specificity 84.7%).
  
  
  CONCLUSIONS
  In our cohort, tumor budding was an independent risk factor for nodal metastasis. Our data suggests the promising role of tumor budding in risk evaluation of cutaneous SCC.
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Ibu
authors.initials: I
authors.lastname: Matsuzaki
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Warigaya
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Iwahashi
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Kojima
authors.affiliation: Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Fukumi
authors.initials: F
authors.lastname: Furukawa
authors.affiliation: Department of Diagnostic Pathology, Wakayama Medical University, Wakayama, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Murata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000473:pathology*
keywords: TNM staging; cutaneous squamous cell carcinoma; lymph node metastasis; tumor budding