Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.
Ferroptosis/physiology* ; Macrophages/metabolism* ; Humans ; Animals ; Iron/metabolism* ; Reactive Oxygen Species/metabolism* ; Lipid Peroxidation/physiology* ; Inflammation/metabolism*

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective:Glioblastoma (GBM) is a primary malignant tumor in the central nervous system, whose tissue heterogeneity and invasive growth characteristics lead to a very poor prognosis for patients. Hub genes in GBM are screened by bioinformatics analysis; expressions of Hub genes in human GBM tissue, and their effects on GBM biological behaviors and Notch signaling pathway proteins are explored, and their regulatory roles in GBM proliferation in xenograft tumor model mice are evaluated.Methods:(1) The gene expression profiles of GBM tissue and normal brain tissue from the Gene Expression Omnibus (GEO) database were obtained; differentially expressed genes (DEGs) were screened, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted on DEGs. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify modules significantly related to GBM. Gene set enrichment analysis (GSEA) on the related module genes was performed; STRING database (version 12.0) was used to construct protein-protein interaction (PPI) network and screen the hub genes. (2) Normal brain tissue samples from 8 patients with epilepsy and GBM tissue samples from 10 patients with GBM who underwent surgical resection in Department of Neurosurgery, He'nan Provincial People's Hospital from January 1, 2022 to December 1, 2023 were collected; expressions of synaptosomal-associated protein 25 (SNAP25) and vesicle-associated membrane protein 2 (VAMP2) were detected by immunohistochemical staining and Western blotting. (3) LN229 and U87 cells were routinely cultured in vitro and divided into shRNA-SNAP25/shRNA-VAMP2 group and empty vector group, and then, cells in each group were transfected with shRNA-SNAP25/shRNA-VAMP2 lentivirus or empty vector lentivirus, respectively; 24 hours after transfection, SNAP25 and VAMP2 mRNA and protein expressions in the 2 groups were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blotting. LN229 and U87 cells were routinely cultured in vitro and divided into shRNA-SNAP25 group, shRNA-VAMP2 group and empty vector group; cells in each group were transfected with shRNA-SNAP25 lentivirus, shRNA-VAMP2 lentivirus or empty vector lentivirus, respectively; 48 hours after transfection, proliferation was detected by clone formation assay, proliferating cell nuclear antigen Ki-67 expression was detected by immunofluorescent staining, invasion was detected by Transwell invasion assay, and Notch1, HEY1 and HES1 protein expressions in Notch signaling pathway of LN229 cells were detected by Western blotting. (4) LN229 cells transfected with shRNA-SNAP25 lentivirus, shRNA-VAMP2 lentivirus or empty vector lentivirus for 48 hours were subcutaneously injected into the right axilla of 4-week-old BALB/c nude mice, respectively, as shRNA-SNAP25 transplantation group, shRNA-VAMP2 transplantation group and empty vector transplantation group (5 mice in each group); on 28 th day of injection, immunohistochemical staining was used to detect the Ki-67 expression in the LN229 cell-transplanted tumor tissues. Results:(1) A total of 1,473 DEGs were screened, of which 880 were upregulated and 593 were downregulated. WGCNA indicated that DEGs were divided into 5 modules (greenish-blue, blue, black, brown and gray ones), among which the greenish-blue module was significantly negatively correlated with GBM ( r=-0.700, P<0.001); GSEA analysis showed that the greenish-blue module mainly involved Notch signaling pathway, and PPI network analysis identified SNAP25 and VAMP2 as hub genes. (2) Immunohistochemical staining results showed that expressions of SNAP25 and VAMP2 in GBM tissue were significantly lower than those in normal brain tissue ( P<0.05). (3) Compared with those in the empty vector group, the SNAP25 mRNA and protein expressions in LN229 and U87 cells of the shRNA-SNAP25 group were statistically decreased ( P<0.05). Compared with those in the empty vector group, the VAMP2 mRNA and protein expressions in LN229 and U87 cells of the shRNA-VAMP2 group were significantly decreased ( P<0.05). Compared with the empty vector group, the LN229 and U87 cells in the shRNA-SNAP25 group and shRNA-VAMP2 group had significantly increased colony formation number, Ki-67 expression and invasive cell number ( P<0.05). Compared with the empty vector group, LN229 cells in the shRNA-SNAP25 group and shRNA-VAMP2 group had statistically increased Notch1, HEY1, and HES1 protein expressions ( P<0.05). Immunohistochemical staining results showed that compared with that in the empty vector group (1.00±0.00), the Ki-67 expression in LN229 cell-transplanted tumor tissues of the shRNA-SNAP25 group and shRNA-VAMP2 group was statistically increased (1.41±0.05, 1.40±0.09, P<0.05). Conclusion:Hub genes SNAP25 and VAMP2 may negatively regulate the malignant biological behavior of GBM through Notch pathway, which might be the new candidate targets for GBM precise treatment.

Objective:To investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:Glioblastoma (GBM) is a primary malignant tumor in the central nervous system, whose tissue heterogeneity and invasive growth characteristics lead to a very poor prognosis for patients. Hub genes in GBM are screened by bioinformatics analysis; expressions of Hub genes in human GBM tissue, and their effects on GBM biological behaviors and Notch signaling pathway proteins are explored, and their regulatory roles in GBM proliferation in xenograft tumor model mice are evaluated.Methods:(1) The gene expression profiles of GBM tissue and normal brain tissue from the Gene Expression Omnibus (GEO) database were obtained; differentially expressed genes (DEGs) were screened, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted on DEGs. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to identify modules significantly related to GBM. Gene set enrichment analysis (GSEA) on the related module genes was performed; STRING database (version 12.0) was used to construct protein-protein interaction (PPI) network and screen the hub genes. (2) Normal brain tissue samples from 8 patients with epilepsy and GBM tissue samples from 10 patients with GBM who underwent surgical resection in Department of Neurosurgery, He'nan Provincial People's Hospital from January 1, 2022 to December 1, 2023 were collected; expressions of synaptosomal-associated protein 25 (SNAP25) and vesicle-associated membrane protein 2 (VAMP2) were detected by immunohistochemical staining and Western blotting. (3) LN229 and U87 cells were routinely cultured in vitro and divided into shRNA-SNAP25/shRNA-VAMP2 group and empty vector group, and then, cells in each group were transfected with shRNA-SNAP25/shRNA-VAMP2 lentivirus or empty vector lentivirus, respectively; 24 hours after transfection, SNAP25 and VAMP2 mRNA and protein expressions in the 2 groups were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western blotting. LN229 and U87 cells were routinely cultured in vitro and divided into shRNA-SNAP25 group, shRNA-VAMP2 group and empty vector group; cells in each group were transfected with shRNA-SNAP25 lentivirus, shRNA-VAMP2 lentivirus or empty vector lentivirus, respectively; 48 hours after transfection, proliferation was detected by clone formation assay, proliferating cell nuclear antigen Ki-67 expression was detected by immunofluorescent staining, invasion was detected by Transwell invasion assay, and Notch1, HEY1 and HES1 protein expressions in Notch signaling pathway of LN229 cells were detected by Western blotting. (4) LN229 cells transfected with shRNA-SNAP25 lentivirus, shRNA-VAMP2 lentivirus or empty vector lentivirus for 48 hours were subcutaneously injected into the right axilla of 4-week-old BALB/c nude mice, respectively, as shRNA-SNAP25 transplantation group, shRNA-VAMP2 transplantation group and empty vector transplantation group (5 mice in each group); on 28 th day of injection, immunohistochemical staining was used to detect the Ki-67 expression in the LN229 cell-transplanted tumor tissues. Results:(1) A total of 1,473 DEGs were screened, of which 880 were upregulated and 593 were downregulated. WGCNA indicated that DEGs were divided into 5 modules (greenish-blue, blue, black, brown and gray ones), among which the greenish-blue module was significantly negatively correlated with GBM ( r=-0.700, P<0.001); GSEA analysis showed that the greenish-blue module mainly involved Notch signaling pathway, and PPI network analysis identified SNAP25 and VAMP2 as hub genes. (2) Immunohistochemical staining results showed that expressions of SNAP25 and VAMP2 in GBM tissue were significantly lower than those in normal brain tissue ( P<0.05). (3) Compared with those in the empty vector group, the SNAP25 mRNA and protein expressions in LN229 and U87 cells of the shRNA-SNAP25 group were statistically decreased ( P<0.05). Compared with those in the empty vector group, the VAMP2 mRNA and protein expressions in LN229 and U87 cells of the shRNA-VAMP2 group were significantly decreased ( P<0.05). Compared with the empty vector group, the LN229 and U87 cells in the shRNA-SNAP25 group and shRNA-VAMP2 group had significantly increased colony formation number, Ki-67 expression and invasive cell number ( P<0.05). Compared with the empty vector group, LN229 cells in the shRNA-SNAP25 group and shRNA-VAMP2 group had statistically increased Notch1, HEY1, and HES1 protein expressions ( P<0.05). Immunohistochemical staining results showed that compared with that in the empty vector group (1.00±0.00), the Ki-67 expression in LN229 cell-transplanted tumor tissues of the shRNA-SNAP25 group and shRNA-VAMP2 group was statistically increased (1.41±0.05, 1.40±0.09, P<0.05). Conclusion:Hub genes SNAP25 and VAMP2 may negatively regulate the malignant biological behavior of GBM through Notch pathway, which might be the new candidate targets for GBM precise treatment.

Objective:To investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.