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Risk factors for lymph node metastasis in cutaneous squamous cell carcinoma: a long-term retrospective study of Japanese patients

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Abstract

Background

Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers. Prognosis is favorable following surgical resection of early-stage disease, but the management of the metastatic disease is challenging. Several prognostic risk factors have been described in the American Joint Committee on Cancer/the Union for International Cancer Control (UICC) 8th edition staging and the Brigham and Women’s Hospital T classification system. However, their clinical validity in Asian populations is unclear because of racial differences in the clinical characteristics of CSCC. This study aimed to identify factors that could predict lymph node metastasis in Asian patients.

Methods

This retrospective single-center study evaluated 540 patients with primary CSCC between 1989 and 2013. Five factors were evaluated for their ability to predict lymph node metastasis: maximum tumor diameter, tumor thickness, depth of invasion, degree of differentiation, and infiltrative growth pattern (INF).

Results

Tumor diameter > 2 cm (p < 0.0001), tumor thickness > 6 mm (p < 0.0001), invasion beyond the subcutaneous fat (p < 0.0001), poor differentiation (p = 0.042), and INFc infiltration (p < 0.0001) were associated with lymph node metastasis in the univariate analyses. In the multivariate analysis, lymph node metastasis was independently associated with tumor size > 2 cm [hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.4–6.2; p = 0.006], tumor thickness > 6.0 mm (HR 2.9, 95% CI 1.3–6.4; p = 0.007), and invasion beyond the subcutaneous fat (HR 2.3, 95% CI 1.0–5.1; p = 0.045).

Conclusion

Larger tumor diameter, greater tumor thickness, and deeper invasion included in the UICC T classification system are associated with increased risks of lymph node metastasis from CSCC in Japanese patients.

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References

  1. Karia PS, Han J, Schmults CD (2013) Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol 68:957–966

    Article  Google Scholar 

  2. Brantsch KD, Meisner C, Schönfisch B et al (2008) Analysis of risk factors determining prognosis of cutaneous squamous cell carcinoma: a prospective study. Lancet Oncol 9:713–720

    Article  Google Scholar 

  3. Hillen U, Leiter U, Haase S et al (2018) Advanced cutaneous squamous cell carcinoma: a retrospective analysis of patient profiles and treatment patterns-results of a non-interventional study of the DeCOG. Eur J Cancer 96:34–43

    Article  Google Scholar 

  4. Haisma MS, Plaat BEC, Bijl HP et al (2016) Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J Am Acad Dermatol 75:722–730

    Article  Google Scholar 

  5. Mullen JT, Feng L, Xing Y et al (2006) Invasive squamous cell carcinoma of the skin: defining a high-risk group. Ann Surg Oncol 13:902–909

    Article  Google Scholar 

  6. Schmults CD, Karia PS, Carter JB et al (2013) Factors predictive of recurrence and death from cutaneous squamous cell carcinoma. JAMA Dermatol 149:541–547

    Article  Google Scholar 

  7. Eigentler TK, Leiter U, Hafner HM et al (2017) Survival of patients with cutaneous squamous cell carcinoma: results of a prospective cohort study. J Invest Dermatol 137:2309–2315

    Article  CAS  Google Scholar 

  8. Brougham ND, Dennett ER, Cameron R et al (2012) The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 106:811–815

    Article  Google Scholar 

  9. Rowe DE, Carroll RJ, Day CL (1992) Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 26:976–990

    Article  CAS  Google Scholar 

  10. Ishihara K, Saida T, Otsuka F et al (2008) Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update. Int J Clin Oncol 13:33–41

    Article  Google Scholar 

  11. Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902–908

    Article  CAS  Google Scholar 

  12. Breuninger H, Schaumburg-Lever G, Holzschuh J et al (1997) Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly malignant subtype of skin cancer. Cancer 79:915–919

    Article  CAS  Google Scholar 

  13. Saito H, Miyatani K, Takaya S et al (2015) Tumor infiltration pattern into the surrounding tissue has prognostic significance in advanced gastric cancer. Virchows Arch 467:519–523

    Article  CAS  Google Scholar 

  14. Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458

    Article  CAS  Google Scholar 

  15. Veness MJ, Palme CE, Smith M et al (2003) Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope 113:1827–1833

    Article  Google Scholar 

  16. Bander TS, Nehal KS, Lee EH (2019) Cutaneous squamous cell carcinoma: updates in staging and management. Dermatol Clin 37:241–251

    Article  CAS  Google Scholar 

  17. Schmitt AR, Brewer JD, Bordeaux JS et al (2014) Staging for cutaneous squamous cell carcinoma as a predictor of sentinel lymph node biopsy results: meta-analysis of American Joint Committee on Cancer criteria and a proposed alternative system. JAMA Dermatol 150:19–24

    Article  Google Scholar 

  18. Karia PS, Jambusaria-Pahlajani A, Harrington DP et al (2014) Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma. J Clin Oncol 32:327–334

    Article  Google Scholar 

  19. Feinstein S, Higgins S, Ahadiat O et al (2019) A retrospective cohort study of cutaneous squamous cell carcinoma with lymph node metastasis: risk factors and clinical course. Dermatol Surg 45:772–781

    Article  CAS  Google Scholar 

  20. Manyam BV, Gastman B, Zhang AY et al (2015) Inferior outcomes in immunosuppressed patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with surgery and radiation therapy. J Am Acad Dermatol 73:221–227

    Article  Google Scholar 

  21. Imao T, Ichimaru N, Takahara S et al (2007) Risk factors for malignancy in Japanese renal transplant recipients. Cancer 109:2109–2115

    Article  Google Scholar 

  22. Morton DL, Thompson JF, Cochran AJ et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370:599–609

    Article  CAS  Google Scholar 

  23. Reynolds C, Mick R, Donohue JH et al (1999) Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer? J Clin Oncol 17:1720–1726

    Article  CAS  Google Scholar 

  24. Gunaratne DA, Howle JR, Veness MJ (2016) Sentinel lymph node biopsy in Merkel cell carcinoma: a 15 year institutional experience and statistical analysis of 721 reported cases. Br J Dermatol 174:273–281

    Article  CAS  Google Scholar 

  25. Tejera-Vaquerizo A, García-Doval I, Llombart B et al (2018) Systematic review of the prevalence of nodal metastases and the prognostic utility of sentinel lymph node biopsy in cutaneous squamous cell carcinoma. J Dermatol 45:781–790

    Article  Google Scholar 

  26. Krediet JT, Beyer M, Lenz K et al (2015) Sentinel lymph node biopsy and risk factors for predicting metastasis in cutaneous squamous cell carcinoma. Br J Dermatol 172:1029–1036

    Article  CAS  Google Scholar 

  27. Ahmed MM, Moore BA, Schmalbach CE (2014) Utility of head and neck cutaneous squamous cell carcinoma sentinel node biopsy: a systematic review. Otolaryngol Head Neck Surg 150:180–187

    Article  Google Scholar 

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Acknowledgements

This work was supported in part by the National Cancer Center Research and Development Fund (2020-J-3). We thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, 951-8566, Japan

    Yuki Saito, Sumiko Takatsuka & Tatsuya Takenouchi

  2. Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Yuki Saito, Hiroki Fujikawa & Riichiro Abe

Authors
  1. Yuki Saito
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  2. Hiroki Fujikawa
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  3. Sumiko Takatsuka
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  4. Riichiro Abe
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  5. Tatsuya Takenouchi
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Contributions

YS: Designed and performed experiments, analysed data and co-wrote the paper. HF: Designed and performed experiments, analysed data. ST, RA: Performed experiments. TT: Designed experiments and co-wrote the paper.

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Correspondence to Yuki Saito.

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Saito, Y., Fujikawa, H., Takatsuka, S. et al. Risk factors for lymph node metastasis in cutaneous squamous cell carcinoma: a long-term retrospective study of Japanese patients. Int J Clin Oncol 26, 606–612 (2021). https://doi.org/10.1007/s10147-020-01830-7

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  • DOI: https://doi.org/10.1007/s10147-020-01830-7

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