title: The Effect of Differentiation Grade of Cutaneous Squamous Cell Carcinoma on Excision Margins, Local Recurrence, Metastasis, and Patient Survival: A Retrospective Follow-Up Study.
abstract: BACKGROUND
  The incidence of cutaneous squamous cell carcinoma (SCC) is increasing worldwide. Despite a growing body of literature on prognostic factors, it remains unclear how tumor differentiation grade influences patient survival. The aim of this study was to investigate a possible correlation between cutaneous SCC differentiation, local recurrence, metastasis, and patient survival.
  
  
  METHODS
  All consecutive patients treated for cutaneous SCC between 2001 and 2008 were retrospectively analyzed. Univariate survival analysis was used to assess the association of different tumor characteristics with survival.
  
  
  RESULTS
  One hundred thirty-one patients with 155 SCCs were included (median follow-up, 81 months; range, 27-125 months). Although no significant correlation between tumor differentiation grade and local recurrence could be found, it was an independent prognostic factor for metastatic disease and overall survival (OS). Metastasis-free survival at 5 years was significantly higher in well-differentiated tumors (70%) compared to moderately (51%) and poorly differentiated SCCs (26%; P = 0.012); identical percentages were found for OS (P = 0.005). Furthermore, patients with incomplete excision of the first tumor showed an increased relative risk of dying of SCC of 4.0 (95% confidence interval, 2.4-6.6; P < 0.001) compared to excision with clear margins.
  
  
  CONCLUSIONS
  Studies that investigated the relationship between SCC differentiation grade and patient survival are scarce and inconsistent. The present study indicates tumor differentiation grade is an independent prognostic factor for OS. This finding suggests poor differentiation of cutaneous SCC alone is sufficient to upstage the primary tumor in the TNM classification system.
authors.affiliation: From the Departments of *Plastic and Reconstructive Surgery, †Trials and Statistics, and ‡Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Jacobus Nick
authors.initials: JN
authors.lastname: Brinkman
authors.forename: Edin
authors.initials: E
authors.lastname: Hajder
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Den Bakker
authors.forename: Steven E R
authors.initials: SE
authors.lastname: Hovius
authors.forename: Marc A M
authors.initials: MA
authors.lastname: Mureau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D016019:Survival Analysis; D016896:Treatment Outcome