Implications of Satellitosis or In-transit Metastasis in Cutaneous Squamous Cell Carcinoma

Abstract

cell carcinoma and melanoma, satellitosis or in-transit metastasis (S-ITM) is not incorporated into the current cutaneous squamous cell carcinoma (CSCC) staging systems. It is important to determine if the clinical outcomes of S-ITM are relevant to prognosis for patients with CSCC.OBJECTIVES To evaluate the association of S-ITM with clinical outcomes in patients with CSCC and to determine its prognostic implications. DESIGN, SETTINGS, AND PARTICIPANTSA dual-institution (Cleveland Clinic and Brigham and Women's Hospital) database was queried for patients who were treated for CSCC in 2010 to 2020. Patients who were node-negative and had S-ITM-the presence of dermal lesions between the primary tumor and first-echelon lymphatic nodal basins at any point in the disease course-were identified. Subcohorts of patients with T3N0 tumors, T4N0 tumors (bone invasive), N1 to 3, and M1 disease were identified for comparison. The American Joint Committee on Cancer staging system was used to define cancer stages. Data were analyzed from January 15 to March 31, 2021. MAIN OUTCOMES AND MEASURESPairwise comparison of CSCC recurrence and disease-specific survival in patients with and without S-ITM was performed using Cox proportional hazard modeling. Kaplan-Meier and Fine-Gray competing risk methods were used to estimate disease-specific survival and CSCC recurrence, respectively. RESULTSIn a total of 518 patients with CSCC, S-ITM was present in 72 (13.9 %) patients (median age [range], 73.9 [31.6-95.8] years; 59 [82%] men; 69 [96%] White non-Hispanic individuals; 25 [35%] patients with immunosuppression) who were node-negative. The subcohorts were composed of 341 patients with T3N0 cancer, 36 with T4N0, 70 with N1 to 3, and 19 with M1 disease. Pairwise comparisons between disease levels using Cox proportional hazard model demonstrated lower cumulative incidence of CSCC recurrence rates in the T3N0 (HR, 0.21; 95% CI, 0.14-0.30; P < .001) and T4N0 (HR, 0.36; 95% CI, 0.19-0.68; P = .001) cohorts compared with the S-ITM cohort. No significant difference was observed between patients who were node-positive and those with S-ITM (HR, 0.74; 95% CI, 0.48-1.14; P = .16). The 5-year disease-specific survival rates were 76% for T3N0, 64% for T4N0, 41% for S-ITM, and 39% for N1 to 3. Compared with the S-ITM cohort, DSS was significantly higher in the T3N0 (HR, 0.23; 95% CI, 0.15-0.35; P < .0001) and T4N0 (HR, 0.37; 95% CI, 0.19-0.76; P = .01) cohorts, and not significantly different in the node-positive (HR, 0.77; 95% CI, 0.84-3.93; P = .30) and metastatic cohorts (HR, 1.81; 95% CI, 0.84-3.93; P = .13).CONCLUSIONS AND RELEVANCE This multi-institutional cohort study found that patients with CSCC and S-ITM appear to have clinical outcomes comparable to those of patients who are node-positive, and an increased risk of recurrence and worse survival compared with patients who have T3 and T4 disease. These outcomes are similar to those observed for Merkel cell carcinoma and melanoma. Given that S-ITM may be a powerful prognostic factor, it should be ...

Porocarcinoma of the Ear Found to Have Cutaneous In-Transit and Regional Nodal Metastasis: Implications for Management and Importance of Clinical Examination

“…Recent studies have demonstrated that cSCC patients with in-transit metastases have clinical outcomes similar to those who are node-positive, and may be useful for prognostication. 5 Given the similar or greater aggressiveness and poor outcomes of EPC compared with cSCC, identification of in-transit metastases may warrant prognostic and management approaches similar to those for nodal metastases. The potential for EPC satellite lesions to affect management highlights the importance of thorough skin examination, as in this case, and suggests that their presence or absence should be reflected in future staging systems or consensus guidelines.…”

The role of micrometastasis in high‐risk skin cancers

“…For skin cancers, predictive risk estimates remain poor and staging systems remain inadequate 19,62,71 . In consequence, aggressive biologic behaviour often goes unrecognised.…”

“…For skin, these include all intradermal or subdermal metastasis between the primary scar and the tumour-draining nodal basin. 26,[61][62][63] Macrometastatic ITM present as papulo-nodules and are described for SCC, 40,62,64 MCC 26,27 and melanoma. 58,61,[65][66][67][68] As external assay techniques improve in sensitivity, it is expected that smaller mass cancer cell clusters will be identified in lymphatic channels.…”

Validation of the 2022 National Comprehensive Cancer Network Risk Stratification for Cutaneous Squamous Cell Carcinoma

“…Cutaneous squamous cell carcinoma (CSCC) is the second most common keratinocyte carcinoma in the US, with an estimated 700 000 to 1 000 000 cases reported annually . While most patients with CSCC are cured with Mohs micrographic surgery (Mohs) or wide local excision (WLE) alone, a subset of patients go on to develop poor outcomes, including local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD) .…”

“…utaneous squamous cell carcinoma (CSCC) is the second most common keratinocyte carcinoma in the US, with an estimated 700 000 to 1 000 000 cases reported annually. 1,2 While most patients with CSCC are cured with Mohs micrographic surgery (Mohs) or wide local excision (WLE) alone, a subset of patients go on to develop poor outcomes, including local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). [3][4][5][6][7] Current staging systems such as the American Joint Committee on Cancer's AJCC Cancer Staging Manual, 8th edition (AJCC-8) and the Brigham and Women's Hospital (BWH) staging system are based on tumor characteristics that have been shown to impact prognosis.…”