Identifying the impact of minor risk factors in Brigham and Women's Hospital stage T1 cutaneous squamous cell carcinomas on risk of poor outcomes: A retrospective cohort study

J Am Acad Dermatol. 2025 Jun;92(6):1319-1326. doi: 10.1016/j.jaad.2025.02.052. Epub 2025 Feb 24.

Abstract

Background: While Brigham and Women's Hospital T1 cutaneous squamous cell carcinomas are overall low risk, a small subset develop poor outcomes.

Objective: To evaluate the impact of minor risk factors on poor outcomes in T1 tumors.

Methods: Data were collected retrospectively from 11 centers. Univariable and multivariable regression analyses were performed evaluating the impact of minor risk factors (moderate differentiation, diameter 1-2 centimeters, fat invasion, and small-caliber perineural invasion) on poor outcomes. Cumulative incidence function plots were created for time to poor outcomes by number of minor risk factors.

Results: A total of 15,481 Brigham and Women''s Hospital T1 tumors were included, of which 90 (0.58%) developed major poor outcomes and 332 (2.1%) developed any poor outcome. Minor risk factors that were significant on multivariable analysis included moderate differentiation, diameter, and subcutaneous fat invasion. Cumulative incidence function plots demonstrated an increased risk of poor outcomes with presence of multiple minor risk factors; the risk of metastasis and major poor outcomes exceeded 5% in tumors with 3 minor risk factors.

Limitations: Retrospective design, limited number of major poor outcomes.

Conclusion: T1 tumors with multiple minor risk factors may be eligible for closer surveillance. Future staging systems should consider incorporating both major and minor risk factors.

Keywords: cutaneous squamous cell carcinoma; depth of invasion; differentiation; perineural invasion; poor outcomes; staging; tumor diameter.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell* / epidemiology
  • Carcinoma, Squamous Cell* / mortality
  • Carcinoma, Squamous Cell* / pathology
  • Carcinoma, Squamous Cell* / therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • Skin Neoplasms* / therapy
  • Subcutaneous Fat / pathology