Differentiation and risk stratification of basal cell carcinoma with deep learning on histopathologic images and measuring nuclei and tumor microenvironment features.

BACKGROUND: Nuclear pleomorphism and tumor microenvironment (TME) play a critical role in cancer development and progression. Identifying most predictive nuclei and TME features of basal cell carcinoma (BCC) may provide insights into which characteristics pathologists can use to distinguish and stratify this entity. OBJECTIVES: To develop an automated workflow based on nuclei and TME features from basaloid cell tumor regions to differentiate BCC from trichoepithelioma (TE) and stratify BCC into high-risk (HR) and low-risk (LR) subtypes, and to identify the nuclear and TME characteristics profile of different basaloid cell tumors. METHODS: The deep learning systems were trained on 161 H&E -stained sections which contained 51 sections of HR-BCC, 50 sections of LR-BCC and 60 sections of TE from one institution (D1), and externally and independently validated on D2 (46 sections) and D3 (76 sections), from 2015 to 2022. 60%, 20% and 20% of D1 data were randomly splitted for training, validation and testing, respectively. The framework comprised four stages: tumor regions identification by multi-head self-attention (MSA) U-Net, nuclei segmentation by HoVer-Net, quantitative feature by handcrafted extraction, and differentiation and risk stratification classifier construction. Pixel accuracy, precision, recall, dice score, intersection over union (IoU) and area under the curve (AUC) were used to evaluate the performance of tumor segmentation model and classifiers. RESULTS: MSA-U-Net model detected tumor regions with 0.910 precision, 0.869 recall, 0.889 dice score and 0.800 IoU. The differentiation classifier achieved 0.977 ± 0.0159, 0.955 ± 0.0181, 0.885 ± 0.0237 AUC in D1, D2 and D3, respectively. The most discriminative features between BCC and TE contained Homogeneity, Elongation, T-T_meanEdgeLength, T-T_Nsubgraph, S-T_HarmonicCentrality, S-S_Degrees. The risk stratification model can well predict HR-BCC and LR-BCC with 0.920 ± 0.0579, 0.839 ± 0.0176, 0.825 ± 0.0153 AUC in D1, D2 and D3, respectively. The most discriminative features between HR-BCC and LR-BCC comprised IntensityMin, Solidity, T-T_minEdgeLength, T-T_Coreness, T-T_Degrees, T-T_Betweenness, S-T_Degrees. CONCLUSIONS: This framework hold potential for future use as a second opinion helping inform diagnosis of BCC, and identify nuclei and TME features related with malignancy and tumor risk stratification.

Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment: A Systematic Review and Meta-Analysis.

Importance: Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment. Objective: To identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis. Data Sources: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023. Study Selection: Two reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis. Data Extraction and Synthesis: The search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023. Main Outcomes and Measures: The major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted. Results: This systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P < .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P < .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US. Conclusions and Relevance: In this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.

Efficacy of adalimumab in pediatric generalized pustular psoriasis: case series and literature review.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, severe, and sometimes fatal form of childhood psoriasis. The first line therapies include acitretin, cyclosporin A, and methotrexate which take effect slowly and have varying long-term side effects for children. Recently, the anti-tumor necrosis factor-alpha (TNF-α), adalimumab has shown efficacy in adult patients with pustular psoriasis; however, there is lack of evidence of its usage in the pediatric population. METHODS: Data on efficacy of adalimumab in treating pediatric GPP along with a literature review are presented. RESULTS: A total of seven patients had marked clearance and reduction in PGA and systemic/laboratory score within the first week of first injection and achieved almost complete clearance of skin lesions by 1-month follow up. In literature, adalimumab treating pustular psoriasis in pediatric has been described in six children who failed in prior treatment. All six patients showed a satisfactory therapeutic effect. CONCLUSIONS: Subcutaneous injection of adalimumab every other week in the treatment of children with GPP has significant clinical efficacy with rapid clearance of skin lesions, providing a novel alternative for children with pustular psoriasis who responded poorly to traditional treatment or are not suitable for traditional treatment.

A prospective study on the treatment of immediate post-operative scar with narrowband intense pulsed light under polarized dermoscopy.

(a) To evaluate the efficacy and safety of narrow-band intense-pulsed light (DPL) in immediate post-operative scar. (b) To observe the process of scar formation under dermoscopy in the first 6 months. Nine patients with postoperative scars were enrolled in the randomized, prospective, split-scar study. Patients were treated in one half of the scar with DPL for cosmetic improvement at a wavelength of 500-600 nm and the other half was not treated as control. The laser treatments were initiated 2 weeks after the surgery and were given 3 times over a 4-week period. All patients were followed-up for 3 months from the last treatment. Photographs and dermoscopy digital images were collected each time. (a) Neither DPL or control produce statistically significant improvements in Vancouver Scar Scale. Moreover, comparatively, there was no statistical difference in Vancouver Scar Scale between DPL or control. However, 6 out of 9 patients treated with DPL had reduced scores in vascularity sooner compared with control. (b) Under dermoscopy, redness, and swelling were obvious from 2 weeks after surgery, but were gradually alleviated. The surface of the scar gradually became uneven and rough. DPL might be beneficial in early recovery of immediate post-operative scar.

IFN­Î³ induces apoptosis in human melanocytes by activating the JAK1/STAT1 signaling pathway.

The present study aimed to investigate the role of janus kinase (JAK)1/STAT1 in interferon (IFN)­Î³­induced apoptosis in human melanocytes. Following IFN­Î³ treatment, the viability of human melanocytes were analyzed using a Cell Counting Kit­8 assay and the apoptotic rate was determined using flow cytometry. Western blotting was also performed to analyze the phosphorylation levels of JAK1, JAK2 and the transcriptional factor STAT1, as well as the expression levels of Bcl­2, Bax, Bcl­2 homologous antagonist killer (Bak) and cleaved caspase­3. Finally, following the pretreatment with the STAT1 inhibitor fludarabine, human melanocytes were treated with IFN­Î³ and flow cytometry was used to detect the apoptotic rate. The results revealed that IFN­Î³ reduced the proliferation and induced the apoptosis of human melanocytes. In addition, IFN­Î³ treatment led to decreased expression levels of Bcl­2 and increased expression levels of Bax, Bak and cleaved caspase­3, alongside the activation of the JAK1/STAT1 signaling pathway. Conversely, the pretreatment with the STAT1 inhibitor fludarabine decreased the apoptotic rate of human melanocytes following IFN­Î³ induction. In conclusion, the findings of the present study suggested that IFN­Î³ may induce the apoptosis of human melanocytes by activating the JAK1/STAT1 signaling pathway, alongside increasing the expression levels of Bax, Bak and cleaved caspase­3, and decreasing the expression levels of Bcl­2.

Integrative Analysis of Long Noncoding RNA (lncRNA), microRNA (miRNA) and mRNA Expression and Construction of a Competing Endogenous RNA (ceRNA) Network in Metastatic Melanoma.

Worldwide, metastatic melanoma of the skin has an aggressive course with high morbidity and mortality. Therefore, an increased understanding of the pathogenesis of metastatic melanoma has gained increasing attention, including the role of epigenetic modification and competing endogenous RNA (ceRNA). This study aimed to used bioinformatics data to undertake an integrative analysis of long noncoding RNA (lncRNA), microRNA (miRNA) and mRNA expression to construct a ceRNA network in metastatic melanoma. Data from the Cancer Genome Atlas (TCGA), the Gene Ontology (GO) database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were analyzed. There were 471 cases that included 103 primary solid tumors and 368 cases of metastatic melanoma that included transcriptome sequencing data (including lncRNA and mRNA); 452 cases had miRNA sequencing data. Analysis of chip data identified 85 6 mRNAs, 67 miRNAs, and 250 lncRNAs that were differentially expressed in cases of metastatic melanoma, of which 25 miRNAs, 18 lncRNAs, and 18 mRNAs participated in the formation of ceRNAs. Survival analysis identified seven differentially expressed mRNAs, five differentially expressed miRNAs (miRNA-29c, miRNA-100, miR-142-3p, miR-150, miR-516a-2), and six differentially expressed lncRNAs (AC068594.1, C7orf71, FAM41C, GPC5-AS1, MUC19, LINC00402) that were correlated with survival time in patients with metastatic melanoma. Bioinformatics data and integrative analysis identified lncRNA, miRNA, and mRNA expression to construct a ceRNA and patient survival network in metastatic melanoma. These findings support the need for further studies on the mechanisms involved in the regulation of metastatic melanoma by ceRNAs.

Oncogenomic analysis identifies novel biomarkers for tumor stage mycosis fungoides.

Patients with mycosis fungoides (MF) developing tumors or extracutaneous lesions usually have a poor prognosis with no cure has so far been available. To identify potential novel biomarkers for MF at the tumor stage, a genomic mapping of 41 cutaneous lymphoma biopsies was used to explore for significant genes.The gene expression profiling datasets of MF were obtained from Gene Expression Omnibus database (GEO). Gene modules were simulated using Weighted Gene Co-expression Network Analysis (WGCNA) and the top soft-connected genes (hub genes) were filtrated with a threshold (0.5). Subsequently, module eigengenes were calculated and significant biological pathways were enriched based on the KEGG database.Four genetic modules were simulated with 3263 genes collected from the whole genomic profile based on cutoff values. Significant diseases genetic terminologies associated with tumor stage MF were found in black module. Subsequently, 13 hub genes including CFLAR, GCNT2, IFNG, IL17A, IL22, MIP, PLCG1, PTH, PTPN6, REG1A, SNAP25, SUPT7L, and TP63 were shown to be related to cutaneous T-cell lymphoma (CTCL) and adult T-cell lymphoma/leukemia (ATLL).In summary, in addition to the reported genes (IL17F, PLCG1, IFNG, and PTH) in CTCL/ATLL, the other high instable genes may serve as novel biomarkers for the regulation of the biological processes and molecular mechanisms of CTLT (MF/SS).

Cutaneous phaeohyphomycosis caused by Exophiala dermatitidis: A case report and literature review.

We report a case of cutaneous phaeohyphomycosis caused by Exophiala dermatitidis. An adult male presented with a 1 month history of erythematous swelling and ulcer on the right forearm. E. dermatitidis was identified from the lesion through microscopic examination, in vitro culture, cutaneous biopsy and molecular analysis. He was treated with oral itraconazole (400 mg/day) and showed improvement.

Penile metastasis of sigmoid colon carcinoma: a rare case report.

BACKGROUND: Metastasis to penis usually arises from genitourinary organs, but in rare cases, metastasis comes from the sigmoid colon. Furthermore, very few cases of penile metastasis of primary sigmoid colon carcinoma have been reported. CASE PRESENTATION: We described a case of a 53-year-old man with penile metastasis of sigmoid colon carcinoma along with a review of the literature. Physical examination revealed two subcutaneous nodules on the glans penis. Biopsy of the nodules showed that penile metastasis of sigmoid colon carcinoma. CONCLUSION: Metastasis of sigmoid colon carcinoma to the penis is extremely rare, which presents an advanced form of sigmoid colon carcinoma, therefore survival is extremely shortened. Although treatment of penile metastasis is almost always palliative, it is important to recognize this unusual manifestation so that timely appropriate treatment can be initiated. Early recognition may enhance survival rate of these patients.