Journal of Clinical and Aesthetic Dermatology • Hot Topics in Squamous Cell Carcinoma July 2024 • Meeting Highlights

The American College of Mohs Surgery (ACMS) held its 56th Annual Meeting on May 2–5, 2024, in Phoenix, Arizona. The conference gave researchers, physicians, and members of industry the opportunity to share and learn about the latest research in skin cancer, including cutaneous squamous cell carcinoma (cSCC). The event included speaker presentations on various clinical topics in skin cancer, as well as posters reporting the latest data assessing surgical interventions and outcomes in cSCC. Summaries of key abstracts from the meeting are included here.

Outcomes of high-risk cutaneous squamous cell carcinoma – does clinical or histologic size matter more? – a prospective study. Among patients with cutaneous squamous cell carcinoma (cSCC), researchers compared clinical outcomes of those with preoperative size of 2cm or greater (clinical size ≥2cm; n=140) to those with a preoperative size less than 2cm but a postoperative defect size of 2cm or greater (histological size ≥2cm; n=192). Patients with a clinical size of 2cm or greater were significantly older than those with a histological size of 2cm or greater. Preoperative tumor size and postoperative defect size were significantly larger in cSCC clinically 2cm or greater. Cases with a histological size of 2cm or greater required wider margins for clearance and increased MMS stages to achieve negative margins. Postoperative wound infections were significantly more frequent in cSCC clinically 2cm or greater, compared to cSCC histologically 2cm or greater. Patients with a clinical size of 2cm or greater did not experience heightened rates of active bleeding, wound dehiscence, or scarring abnormalities. There were no differences in local recurrence, metastasis, additional surgical intervention, adjuvant radiation therapy (ART), or mortality.

Patient and primary tumor characteristics associated with cutaneous squamous cell carcinomas with satellitosis or in transit metastases and associated mortality. Here, Pahalyants et al observed a 0.5-percent incidence (n=108) of satellitosis or in-transit metastasis (S-ITM) among 23,166 cases of cSCC. A total of 77.8 percent of S-ITM cases were located at the head and neck, compared to 47.8 percent of non-S-ITM cases. Poor differentiation occurred in 43.5 and 6.5 percent of S-ITM and non- S-ITM cases, respectively. In addition, male sex, history of immunosuppression, lymphovascular invasion, perineural invasion (PNI), tumor diameter of 20mm3, and depth of invasion were significantly more frequent in tumors with S-ITM, compared to tumors without S-ITM. Recurrent/metastatic tumors at initial presentation were associated with S-ITM. The rate of local recurrence was significantly higher in tumors with S-ITM, compared to tumors without S-ITM (39.8% vs. 3.0%). Nodal and distant metastases occurred in 40.7 and 17.6 percent of S-ITM cases, respectively, compared to 1.9 and 0.6 percent of non-S-ITM cases, respectively; this difference was significant. Additionally, diseasespecific mortality was significantly higher in cases with S-ITM (46.3%), compared to cases without S-ITM (1.1%). At one-year follow-up, there was a 77.8 percent survival rate for patients with S-ITM after receiving primary treatment; the threeyear survival rate was 37 percent. Characteristics independently associated with S-ITM included history of immunosuppression, head and neck tumors, moderate/poor differentiation, large caliber PNI, tumor diameter greater than 20mm3, and invasion beyond the dermis.

Significant practice variation in the use of adjuvant radiation for high T-stage cutaneous squamous cell carcinoma following resection with negative surgical margins. In this retrospective study, Ran et al evaluated the use of ART for patients with resected Brigham and Women’s Hospital (BWH) Stage T2b/T3 and/or American Joint Committee on Cancer 8th Edition (AJCC) Stage T3/T4 cSCC. Data were collected from 12 healthcare centers, 10 located in the United States (US) and two located internationally. In total, 258 (13.5%) of 1,908 patients received ART. Younger age at diagnosis and immunocompromised status were more frequent among patients who underwent ART than those who did not receive ART. Compared to the non-ART group, a greater proportion of patients in the ART group had head and neck tumors (74.4% vs. 85.3%), invasion beyond subcutaneous fat (29.2% vs. 54.3%), poor differentiation (35.9% vs. 42.6%), and lymphovascular invasion (3.1% vs. 7.0%). A greater percentage of patients in the non-ART group underwent Mohs micrographic surgery (MMS) only, whereas excision only was more common in the ART group. Researchers identified nine factors that influenced ART use, including age, head and neck location, invasion beyond subcutaneous fat, and tumor size of 2cm or greater. Use of ART ranged from 0 to 30.7 percent across the 12 centers. Considering the risk factors PNI, invasion beyond subcutaneous fat, tumor diameter of 2cm or greater, and poor differentiation, researchers found that the overall rate of ART increased with an increasing number of risk factors.

Clinical outcomes of cutaneous squamous cell carcinomas treated with Mohs micrographic surgery using cytokeratin immunostains. Here, Handfield et al compared outcomes among patients with cSCC who underwent MMS and hematoxylin and eosin (H&E) staining with (n=152) and without (n=84; controls) intraoperative multicytokeratin (MCK) staining. Median age was significantly higher in the control group, at 77.5 years, compared to the MCK group, at 72.5 years. Significantly more patients in the MCK cohort had tumors of the head and neck, compared to controls. Rates of moderate and poor differentiation were 36.8 and 46.1 percent, respectively, in the MCK cohort; comparatively, 27.4 and 32.1 percent of controls had moderate and poor differentiation, respectively. BWH tumor stage was significantly higher in the MCK cohort. Controls had a significantly higher rate of adjuvant therapy use, compared to patients in the MCK group (56.2% vs. 10.5%). Compared to controls, patients in the MCK cohort largely experienced significantly decreased adverse outcomes; the exception was distant metastasis, which occurred in a nonsignificantly higher percentage of the MCK cohort (10.5%), compared to the control cohort (8.3%). In-transit metastasis occurred in 22.6 percent of controls, compared to 7.2 percent of patients in the MCK group. Local recurrence was reported in 20.2 and 10.5 percent of patients in the control and MCK cohorts, respectively. The rate of cSCC-specific mortality was 7.9 percent in the MCK cohort, compared to 21.4 percent in the control cohort.

Cutaneous squamous cell carcinoma of the ear compared to other H-zone sites. In this study, researchers analyzed clinical and demographic characteristics of cSCC of the ear and compared it to cSCC of other H-zone locations. A total of 222 tumors of the ear and 772 tumors of other H-zone sites were analyzed. Male sex, smoking history, and older age were more frequent among patients with cSCC of the ear, compared to those with other H-zone tumors. According to unweighted analysis, 13.4 percent of tumors of the ear had poor differentiation or were undifferentiated, compared to seven percent of other tumors. Additionally, PNI and BWH T2b/ T3 were more frequent in tumors of the ear, compared to other H-zone tumors (11.3% vs. 6.5% and 18.9% vs. 12.7%, respectively). Both nodal and distant metastases trended toward significantly increased incidence in tumors of the ear, compared to other locations.

A comparative analysis of keratoacanthomas and cutaneous squamous cell carcinoma treated with Mohs micrographic surgery. Here, Gao et al compared the clinical features and outcomes of 127 keratoacanthoma (KA) and 562 invasive cSCC cases treated with MMS. Significantly more patients with cSCC were male. The majority of cSCC tumors were located at the head and neck (73.1%), while the majority of KAs were located at the extremities (66.9%). The mean diameter of KAs was larger than that of cSCC tumors. The mean number of required MMS stages was 1.28 for KAs, compared to 1.52 for cSCC tumors, which was a significant difference. Significantly more KAs achieved clearance with one stage of MMS compared to cSCC tumors (77.2% vs. 58.9%). The number of MMS stages needed to achieve clearance was positively associated with cSCC tumor diameter, but not KA diameter. The mean number of MMS stages needed for clearance was also significantly lower for KAs compared to well-differentiated invasive cSCC cases. At a mean 1.5-year follow-up, recurrence was observed in six cases of cSCC (3 of which were well differentiated) and zero cases of KA.

Addition of the 40-gene expression profile (40-GEP) test in risk assessment improves prognostic accuracy and risk stratification for high-risk cutaneous squamous cell carcinoma (HR-cSCC) of the head and neck successfully treated with Mohs micrographic surgery (MMS). Fitzgerald et al studied the use of 40-gene expression profile (GEP) to stratify metastatic risk in patients with high-risk cSCC of the head and neck who achieved negative margins with MMS and did not undergo postoperative radiation therapy. Data from 417 tumors were analyzed. The 40-GEP test led to significant risk stratification at three years, with metastasis-free survival rates of 93.5, 84.2, and 46.7 percent for Class 1 (low risk), Class 2A (higher risk), and Class 2B (highest risk) results, respectively. According to multivariate analysis, use of the 40-GEP test significantly increased metastatic risk prediction. The combination of 40- GEP testing with BWH or AJCC8 staging resulted in significantly improved risk prediction over either method alone.

RESEARCH BITE—Aberrant expression of B7-H4 and B7-H5 contributes to the development of cutaneous SCC

Sample analysis showed that B7 homolog 4 (B7-H4) and B7-H5 gene expression was reduced in primary cutaneous squamous cell carcinoma (cSCC) and metastatic cSCC tissue, compared to normal and primary cSCC tissue, respectively. Enrichment analysis showed that B7-H4 and B7-H5 were involved in T cell, lymphocyte, and monocyte proliferation and activation, as well as cytokine expression. Among 45 cSCC samples, B7-H4 had higher expression than B7-H5. Expression of B7-H4 was significantly associated with tumor size, and there was a significant association between B7-H5 expression and disease stage.

Source: Chen L, Zhou B, Tang M, et al. Aberrant expression of B7-H4 and B7-H5 contributes to the development of cutaneous squamous cell carcinoma. Arch Dermatol Res. 2024;316(7):382.