Argon–Helium Cryoablation for Cutaneous Squamous Cell Carcinoma in the Elderly

Cutaneous squamous cell carcinoma (cSCC) is a common type of malignant neoplasm in non-melanoma skin cancer (NMSC). Most cases of simple cSCC are considered curable by surgical removal of the lesion. However, clinical treatments for cSCC with medium- or large-sized lesions are difficult. Meanwhile, the effectiveness of the treatments is not guaranteed, especially for elderly patients, because of an intolerance to surgical resection or other adjuvant modalities. In such cases, safe and effective treatments with excellent aesthetic outcomes are urgently needed. In this study, we reported 6 elderly cSCC patients with medium- or large-sized lesions treated with argon–helium cryoablation. The average age of all 6 patients was 78 years (range 72–85 years). They were all diagnosed with cSCC with a median tumor size of 5.8 cm (range 2.5–15.5 cm) and dermal invasion. Complete ablation was achieved in all cases after a single ablation session (2 freeze–thaw cycles). Patients experienced mild pain and hemorrhage after ablation, but the symptoms were manageable. One patient developed infection and fever because of extensive necrosis of the tumor, which was eventually cured after treatment. All patients obtained good cosmetic outcomes, and their quality of life improved significantly. In the 5-year follow-up study, 4 patients were alive while 2 patients died of unrelated diseases 3 years after cryotherapy. None of the 6 patients had a recurrence. These results suggested the feasibility of argon–helium cryoablation as a novel therapeutic strategy for elderly cSCC with medium- or large-sized lesions.

Whole genome analysis reveals the genomic complexity in metastatic cutaneous squamous cell carcinoma

Metastatic cutaneous squamous cell carcinoma (cSCC) is associated with a high risk of recurrence and poor prognosis. There is limited published data exploring whole genome sequencing (WGS). The aim of this project was to provide the first comprehensive genomic understanding of the state of metastatic cSCC. In this study, we used WGS on matched tumor and blood DNA to detect somatic genetic alterations from 25 patients with regional metastases of head and neck cSCC. Our computational analyses interrogate clinical impacts of these genetic alterations on metastatic cSCC across the cohort for both the coding and non-coding genome. In the non-coding genome, 3UTR regions of EVC (48%), PPP1R1A (48%) and LUM (16%) were significantly functionally altered (Q-value < 0.05). Further, significant functional alterations are observed in the tumor suppressing lncRNA LINC01003 ( 68% of specimens, Q-value: 0.0158). In addition, significant recurrent copy number loss in tumor suppressor genes KANSL1 and PTPRD and gain in CALR, CCND1 and FGF3 was observed for coding regions. SNVs driver analyses predicted TP53, CDKN2A, as potential drivers of the metastasis cSCC (using 3 different tools). Indel signature analysis highlight dominance of ID signature 13 followed by ID8 & ID9. Interestingly, ID 9 has previously been shown to have no association with skin melanoma, unlike ID 13 and 8, suggesting some point of difference between these two skin-based diseases. The overall landscape of variation in metastatic cSCC is dominated by cell cycle and DNA repair disruption.

Complement Factor D Is a Novel Biomarker and Putative Therapeutic Target in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-γ and interleukin-1β. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression.

Prognostic value of 18F-FDG PET/CT and MRI features in patients with high-risk and very-high-risk cutaneous squamous cell carcinoma

Objectives: This study aimed to evaluate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) features in patients with high-risk and very-high-risk cutaneous squamous cell carcinoma (cSCC). Methods: This study included 54 consecutive patients with surgically resected primary high-risk and very-high-risk cSCC who underwent preoperative FDG-PET/CT and/or MRI. Among them, 14 patients (26%) had recurrences. We retrospectively reviewed the FDG-PET/CT (n = 34) and MRI (n = 48) and investigated the clinical significance and prognostic value of imaging features in cSCC. Results: On FDG-PET/CT, the maximum standardized uptake value (SUVmax) of the primary tumor (13.0 ± 6.4 vs. 6.9 ± 5.3, p < 0.05) was higher in cSCC with recurrence than in cSCC without recurrence. On MRI, the maximum diameter of the lesion (46.8 ± 24.1 mm vs 30.4 ± 17.0 mm, p < 0.05) and the frequency of muscle/tendon/bone invasion (42% vs 11%, p < 0.05) were significantly greater in cSCC with recurrence than in cSCC without recurrence. In the univariate analysis, prognostic factors for recurrence were SUVmax of the primary tumor (p < 0.01), the maximum diameter of the lesion (p < 0.05), and depth of invasion (p < 0.05). The areas under the receiver operating characteristic curves of the SUVmax (0.78) were superior to those of the maximum diameter (0.71) and depth of invasion (0.60). Conclusions: SUVmax, maximum diameter, and depth of invasion were useful parameters for prognostic factors predicting recurrence in patients with high-risk and very-high-risk cSCC. Advances in knowledge: SUVmax represents a prognostic factor.