Noritaka Oyama

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Clinically established biomarkers such as KL-6 and surfactant protein-D (SP-D) for SSc-associated interstitial lung disease (ILD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for pulmonary arterial hypertension (PAH), are already used as adjunctive tools in routine clinical assessment, whereas many other candidate biomarkers, including interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers remain at varying stages of clinical validation. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and future precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone. However, most candidate biomarkers still require external validation, assay standardization, and demonstration of incremental value over conventional clinical variables before routine clinical implementation.

Basal cell carcinoma rarely coexists with malignant mesenchymal component(s), termed as basal cell carcinosarcoma (BCCS). BCCS often comprises an osteosarcomatous change, which considerably varies in the histological extent among reported cases. Owing to its rarity and morphological heterogeneity, the disease may be underrecognized and pose accurate diagnosis and treatment approaches. In this study, we present a case of BCCS with a focal osteosarcomatous component in a 91-year-old woman with a rapidly enlarging solitary tumor on the left cheek. Histopathological examination revealed a biphasic tumor composed of conventional basal cell carcinoma and a high-grade sarcomatous component, both of which were intermingled gradually in the transitional zone. Limited portions of the sarcomatous component contained atypical spindle-to oval-shaped cells and osteoclast-like multinucleated giant cells surrounded by an osteoid matrix. Immunohistochemically, these cells were positive for an osteoblastic marker SATB2 and an osteoclast-associated marker tartrate-resistant acid phosphatase, respectively, but negative for epithelial markers AE1/AE3 and BerEP4. These findings supported a diagnosis of BCCS with an osteosarcomatous component. To the best of our knowledge, literature review identified only 21 similar cases thus far reported, but no previous reports have used a combined use of SATB2 and tartrate-resistant acid phosphatase immunostaining to substantiate the osteosarcomatous focus in cutaneous carcinosarcoma. Our case may highlight the potential diagnostic value of these 2 markers in distinguishing the true osteosarcomatous components from mimicking elements such as dystrophic calcification or hyalinized collagen deposition, but also in detecting a subtle osteosarcomatous component in carcinosarcoma.

Psoriasis is a chronic, immune‐mediated inflammatory disease with heterogeneous manifestations. Reliable biomarkers reflecting disease severity and treatment response remain limited. Glycans—carbohydrate structures attached to proteins and lipids—play key roles in biological processes, contributing to functional specificity. Abnormal glycosylation has been implicated in the pathogenesis of inflammatory and neoplastic diseases, highlighting their potential as therapeutic targets and biomarkers. This study aimed to evaluate serum N‐glycan profiles as potential biomarkers for psoriasis, focusing on the ratio of sialylated biantennary N‐glycan (S) to fucosylated asialo‐biantennary N‐glycan (FA), termed the S/FA ratio. Serum samples from 45 patients with psoriasis, 12 with atopic dermatitis (AD), and 19 healthy controls were analyzed using high‐performance liquid chromatography. The performance of the S/FA ratio was compared with reported biomarkers (CRP and CCL20), and its associations with Psoriasis Area and Severity Index (PASI) and treatment response were examined. The S/FA ratio was significantly higher in psoriasis than in healthy controls ( p < 0.001) and correlated with PASI ( r = 0.485, p < 0.001) and its components. Receiver operating characteristic analysis showed comparable diagnostic accuracy among the S/FA ratio (AUC = 0.788, sensitivity: 73.7%, specificity: 73.3%), CRP (AUC = 0.780), and CCL20 (AUC = 0.741). Changes in the S/FA ratio were correlated with improvements in PASI after systemic treatment ( r = 0.467, p = 0.002), including a patients subgroup receiving IL‐23 inhibitors. The S/FA ratio was not significantly influenced by demographics, comorbidities, or arthralgia. No significant difference was observed between psoriasis and AD, and the S/FA ratio was not significantly elevated in AD compared with healthy controls. The serum S/FA ratio may serve as a glycan‐based biomarker associated with disease severity and treatment response in psoriasis, although its ability to distinguish psoriasis from other inflammatory diseases requires further validation in larger and treatment‐naïve cohorts.

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Among emerging biomarkers, interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers have shown particular promise. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone.