BACKGROUND: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC.
METHODS: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes.
RESULTS: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation.
CONCLUSIONS: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification.

OBJECTIVE: To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK-positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China.
METHODS: This retrospective study analyzed data for 36 advanced-stage patients with ALK-positive LUSC (cohort A) and 13 patients with ALK-positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once-daily ensartinib 225 mg. Outcome analysis included the demographic characteristics, tumor response, progression-free survival (PFS), and treatment-related adverse events (TRAE).
RESULTS: Among the 49 patients, the majority were under 65 years old (73.5%), non-smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0-1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE.
CONCLUSIONS: Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

OBJECTIVE: To elucidate the prognostic implications of mucosal and deep margin distances in oral tongue squamous cell carcinoma (OTSCC), and to assess a different margin cut-off value in T1-T2 versus T3-T4 tumors.
METHODS: This single-center retrospective study included 223 patients who received surgery for a primary OTSCC between January 2017 and December 2021.
RESULTS: Multivariable analysis showed that deep margin distance ≥3 mm in T1-T2 tumors and ≥5 mm in T3-T4 tumors was significantly associated with better RFS and OS. Mucosal and deep margin distances were globally clinically useful for 2-year RFS prediction of T1-T2 tumors, for which deep margins seemed to have more clinical utility than mucosal margins. The influence of margin distances on 2-year RFS seemed greater for T1-T2 tumors than T3-T4 tumors.
CONCLUSIONS: Mucosal and deep margin distances were associated with OS and RFS in OTSCC. Shorter deep margin distances may be aimed for in T1-T2 versus T3-T4 tumors.

BACKGROUND: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China.
METHODS: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index.
RESULTS: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model.
CONCLUSIONS: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

Bronchoesophageal fistula (BEF) is a rare, yet clinically significant, condition characterized by an abnormal connection between the bronchial tree and the esophagus. We present the case of a 25-year-old female who initially presented with symptoms of aspiration pneumonitis and was subsequently diagnosed with BEF, attributed to poorly differentiated squamous cell carcinoma. Despite initial attempts at palliative intervention through esophageal stent placement, persistent symptoms prompted further investigation, revealing the underlying malignancy. This case underscores the diagnostic challenges associated with BEF, particularly when malignancy is involved, and emphasizes the importance of a multidisciplinary approach in optimizing patient outcomes. Early recognition, thorough evaluation, and comprehensive oncological management are essential in addressing the clinical complexities posed by BEF. Further research is warranted to better understand the pathophysiology and optimal management strategies for this rare but clinically significant condition.

OBJECTIVE: This study aims to analyze the clinicopathological characteristics and survival outcomes of tongue cancer in the pediatric population, a topic with limited existing data, using a population-based cohort.
METHODS: Pediatric patients diagnosed with tongue cancer from 1975 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Survival rates were assessed using Kaplan-Meier analysis. Univariate survival analysis was conducted with the log-rank test, while multivariate analysis involved Cox proportional-hazards regression to identify factors influencing overall survival (OS). A predictive nomogram was developed based on Cox regression findings.
RESULTS: In total, 97 pediatric patients with tongue cancer were identified, with a median age at diagnosis of 15 years (range: 1-19 years). Tumors were classified as squamous cell carcinoma (45.4%), rhabdomyosarcoma (RMS) (13.4%), and others (41.2%). Of the patients, squamous cell carcinoma was more common in older children, whereas rhabdomyosarcoma was more common in younger children. The Cox proportional hazard regression revealed that histology and surgery were significant independent predictors of overall survival. The chance of death increased with no surgery. Moreover, patients with squamous cell carcinoma or rhabdomyosarcoma have a poorer survival percentage than patients with other subtypes.
CONCLUSIONS: Tongue cancer in children is rare and associated with poor survival outcomes. This study highlights the significance of tumor histology and surgical intervention in determining overall survival, offering valuable insights for clinical decision-making in pediatric tongue cancer.

Surgical excision is the most effective treatment of skin carcinomas (basal cell carcinoma or squamous cell carcinoma). Preoperative assessment of tumoral margins plays a decisive role for a successful result. The aim of this work was to evaluate the possibility that hyperspectral imaging could become a valuable tool in solving this problem. Hyperspectral images of 11 histologically diagnosed carcinomas (six basal cell carcinomas and five squamous cell carcinomas) were acquired prior clinical evaluation and surgical excision. The hyperspectral data were then analyzed using a newly developed method for delineating skin cancer tumor margins. This proposed method is based on a segmentation process of the hyperspectral images into regions with similar spectral and spatial features, followed by a machine learning-based data classification process resulting in the generation of classification maps illustrating tumor margins. The Spectral Angle Mapper classifier was used in the data classification process using approximately 37% of the segments as the training sample, the rest being used for testing. The receiver operating characteristic was used as the method for evaluating the performance of the proposed method and the area under the curve as a metric. The results revealed that the performance of the method was very good, with median AUC values of 0.8014 for SCCs, 0.8924 for BCCs, and 0.8930 for normal skin. With AUC values above 0.89 for all types of tissue, the method was considered to have performed very well. In conclusion, hyperspectral imaging can become an objective aid in the preoperative evaluation of carcinoma margins.

BACKGROUND: The relationship between tobacco smoking and cutaneous photodamage or malignancies is still unclear. In addition to smoking, both ultraviolet radiation and immunosuppression have an impact on carcinogenesis. The purpose was to study the association of smoking with cutaneous photoaging, actinic keratosis (AK), skin cancers, and pigment cell nevi in adult subjects at risk of any type of skin cancer.
METHODS: In this cross-sectional study at Kuopio University Hospital, Finland, between May 2017 and October 2020, 488 subjects (aged 21-79 years, 246 males and 242 females, 94 with immunosuppression) were examined for a variety of skin lesions, photoaging severity, nevi, tobacco pack-years (TPY), as well as for possible confounding factors.
RESULTS: In logistic regression analyses, no marked association was found between TPY and total skin photoaging, facial photoaging, AK, or nevi, especially when other confounding factors, such as age, were considered. In addition, TPY was not associated with melanoma, basal cell carcinoma, or any type of skin cancer. However, ever smokers produced an elevated crude odds ratio (OR=1.99; 95% CI: 1.02-3.88, p=0.043) for squamous cell carcinoma (SCC) compared to non-smokers. In further analysis, TPY of ≤10 produced an elevated multivariable adjusted odds ratio (AOR=4.90; 95% CI: 1.31-18.26, p=0.018) for SCC, but TPY >10 did not (AOR=1.14; 95% CI: 0.22-6.05, p=0.876).
CONCLUSIONS: Smoking was associated, though not dose-dependently, with an increased likelihood of SCC, but it was not associated with basal cell carcinoma or melanoma. However, the impact of smoking on cutaneous photoaging severity, AK, and nevi, appears to be weak.

OBJECTIVE: The JCOG (Japan Clinical Oncology Group) 0212 study did not confirm the noninferiority of mesorectal excision (ME) alone to ME with LLND for rectal or anal adenocarcinomas. Furthermore, the significance of LLND for SCCs remains unknown. We evaluated the significance of lateral lymph node dissection (LLND) of squamous cell carcinoma (SCC) of the anal canal.
METHODS: This retrospective cohort study was conducted in 435 patients with SCCs among 1,781 patients with anal canal tumors. In 40 patients who underwent LLND, the 5-year relapse-free survival (5y-RFS) and 5-year overall survival (5y-OS) were compared between groups with positive and negative histopathological findings. In 71 patients with negative lateral lymph node metastasis in the preoperative diagnosis, the 5y-RFS, 5y-OS, and 5-year local recurrence-free survival were compared between patients who did and did not undergo LLND.
RESULTS: The clinical and pathological T stages predicted pathological lateral pelvic lymph node metastasis. There was no statistically significant difference in 5y-RFS and 5y-OS between patients who did and did not undergo LLND. Among patients who underwent LLND, 5y-RFS in those with positive histopathological findings (15.0%) was worse than that in those without (59.2%) (p = 0.002).
CONCLUSIONS: In patients who underwent LLND, 5y-RFS in those with positive histopathological findings than in those without LLND did not contribute to prognosis.