Objective: To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of atypical forms of microglandular hyperplasia of the cervix (AMGH). Methods: A total of 29 cases of AMGH diagnosed at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from January 2010 to December 2024 were analyzed. Relevant clinical and pathological data of the patients were collected using the electronic medical record system and medical records copied from the outside hospitals. The patients were followed up. Results: Among the 29 cases, 28 were consultation cases, 22 (79%) of the 28 cases were considered as glandular neoplastic lesions by the original institutions. The nature of the lesion was uncertain in 1 case, the diagnosis was suspicious for AMGH in another 1 case, and only 4 cases were clearly diagnosed as AMGH. The median age of the 29 patients was 44 (43, 48) years. Eighteen (62%) of the 29 cases presented as cervical polyp. Twelve of the 16 tested cases were negative for human papillomavirus. The pathological presentation was complex and diverse, including solid, trabecular, cribriform, and papillary patterns, forming pseudo-invasive structures. The glandular epithelium and proliferating reserve cells had diverse morphologies, which presented with abundant eosinophilic cytoplasm or clear cytoplasm. Signet-ring or hobnail cells were also seen. The nuclear atypia was mild, with 0-7 mitotic figures per 10 HPF. Immature squamous metaplasia was noted. The stroma showed edema, myxoid change and hyaline degeneration, accompanied by infiltration of acute and chronic inflammatory cells. Immunohistochemistry demonstrated that p16 was negative in 8/16 of the cases or patchy positive in the other 8/16, Ki-67 positive rate was less than 10% in all 16 cases, p53 was wild phenotype (9/9), and carcinoembryonic antigen was negative in 4/5 cases and focally positive in 1/5 cases, while p63 was positive in 6/9 of the tested cases. Conclusions: AMGH is a benign non-neoplastic lesion of the cervical glands. Half of the cases occur in perimenopausal or postmenopausal women, often presenting as polypoid hyperplasia or localized cervical thickening/elevation with a friable, fragile texture. Microscopically, it may show a pseudoinvasive pattern, making it prone to misdiagnosis as a malignant lesion. Thus, differentiation from cervical adenocarcinoma, clear cell carcinoma and microglandular endometrioid carcinoma is required. Integration of clinical history, immunohistochemistry and molecular testing may aid in the differential diagnosis.

Objective: To investigate the clinicopathological and molecular genetic characteristics of pediatric tumors with DICER1 mutations. Methods: A total of 90 patients diagnosed with various types of pediatric tumors at Beijing Children's Hospital, Capital Medical University, Beijing, China from July 2023 to September 2025 were included in this study. PCR amplification and Sanger sequencing were performed to detect the coding-region mutations of the DICER1 gene. The clinical, histopathological, and molecular genetic features of the cases with DICER1 mutation were then analyzed. Results: Among the 90 patients, 39 were male and 51 were female, with an age of onset ranging from 1 month to 17 years [median 7.13 (2.77, 10.37) years]. DICER1 mutations were detected in 37 patients (37/90, 41.1%). Among them, 9 cases harbored one mutation [6 pleuropulmonary blastomas (PPBs), 2 sex cord stromal tumors (SCSTs), and 1 cystic nephroma (CN)], 27 cases carried two mutations [10 PPBs, 3 anaplastic sarcomas of the kidney (ASKs), 3 SCSTs, 3 thyroid adenoma, 2 nodular thyroid goiters, 2 thyroid follicular lesions, 2 CN, 1 embryonal rhabdomyosarcoma, and 1 case with multiple primary tumors], and 1 case exhibited three mutations (bilateral ASKs). Despite variations in the site of origin, DICER1-mutant tumors shared several morphological features. Grossly, they presented as multilocular cystic, cystic-solid to solid masses. Microscopically, they exhibited a subepithelial layer of mesenchymal cells, with focal rhabdomyoblastic/chondroid/chondrosarcomatous differentiation, as well as cellular anaplasia. Germline testing using peripheral blood in the 31 patients with DICER1 mutation confirmed germline origin in 61.3% (19/31) of them. Parental analysis (n=12) demonstrated genetic inheritance in 8 cases, predominantly from families with tumor history. Germline variants scattered throughout DICER1 and consisted of loss-of-function mutations (nonsense, frameshift, and splice-site). Somatic mutations showed distinct clustering in exons 24 and 25 hotspots (codons 1705, 1709, 1809, 1810 and 1813), primarily missense variants. Notably, one multiple primary tumor case harbored a somatic mosaic p.E1705K mutation. Conclusions: DICER1 mutations are frequently detected in pediatric PPB, CN, SCST, ASK, nodular thyroid goiter, thyroid adenoma, and genitourinary rhabdomyosarcoma, which often represent as the index case of DICER1 syndrome. Performing DICER1 mutation testing in these patients not only facilitates tumor diagnosis and secondary cancer surveillance, but also enables the comprehensive genetic risk assessment and management for patient's family members.

Objective: To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT). Methods: Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review. Results: Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis. Conclusions: SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.

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 investigate the clinicopathological features, immunophenotype and prognosis of SWI/SNF complex-deficient sinonasal carcinomas. Methods: The clinicopathological, immunohistochemical profiles of 13 SWI/SNF complex-deficient sinonasal carcinomas diagnosed at Xuanwu Hospital, Beijing, China between Januay 2019 and December 2024 were reviewed and followed up. Results: The patients' ages ranged from 33-81 years, median 59.0 (41.5, 64.5) years, including 10 males and 3 females. Imaging findings showed space-occupying lesions in the nasal cavity and sinuses. Microscopically, tumors predominantly exhibited invasive growth in medium-to-large nests or sheets, with relatively uniform morphology, mainly basaloid and/or small cells, while one recurrent case displayed epithelioid morphology. Focal necrosis was observed in 7 cases. Immunohistochemical results showed loss of SMARCA4/BRG1 in 7 cases, loss of SMARCB1/INI1 in 6 cases, and concurrent loss of SMARCA2 in 5 cases. CKpan was expressed to varying extent in all cases, 10 cases were EMA positive, and 5 cases were partially positive for p63/p40. Among neuroendocrine markers, 10 cases showed focal expression of syn or CgA. The Ki-67 proliferation index ranged from 40% to 90%. PD-L1 staining showed combined positive score (CPS) was ≥1 in 3 SMARCB1-deficient cases (CPS ranging from 2 to 3) and CPS <1 in the other 10 cases. Among the 13 patients, 2 were lost to follow-up, 6 died (postoperative survival: 1-25 months), and 5 remained alive, with the longest survival time of 130 months (follow-up range, 8-130 months). Conclusions: SWI/SNF complex-deficient sinonasal carcinoma is a rare undifferentiated malignancy in the head and neck, characterized by distinct pathological and molecular genetic features. SMARCA4-deficient and SMARCB1-deficient carcinomas both exhibit basaloid or small cell-like morphology. Compared to SMARCB1-deficient carcinomas, SMARCA4-deficient carcinomas show reduced expression of squamous cell markers but increased expression of neuroendocrine markers. The positive PD-L1 staining is more likely present in SMARCB1-deficient carcinomas than SMARCB4-dificient ones. Co-loss of SWI/SNF and SMARCA2 correlates with poorer prognosis. Comprehensive evaluation of histopathology, immunohistochemistry, and molecular genetics is critical for accurately diagnosing this rare entity.

To identify the cell types that are infected with KSHV and the immune interactions in Kaposi sarcoma (KS) lesions, we performed spatial transcriptomics with seven KS skin tumors. We used a single-cell RNA-sequencing reference data set from healthy skin donors with a method to conduct spatially informed cell-type deconvolution for spatial transcriptomics. This allowed us to predict the relative amounts of each cell type within the patient sample sections. We included custom probes for five KSHV genes that allowed us to measure human and KSHV expression patterns at the same time. We then compared the spatial gene expression data of KS skin samples with six normal skin samples and found higher expression of marker genes corresponding to macrophages/dendritic cells, lymphatic endothelial cells, and vascular endothelial cells in the KS skin lesions when compared to normal skin samples. Our spatial transcriptomic results from thousands of spots across multiple KS tumors indicated a correlation between high levels of STC1 and decreased expression of macrophage markers. Together, these analyses offer potential mechanisms by which KSHV infection may remodel skin tissue, inhibit immune responses against KSHV infection, and confer resistance to anticancer therapies.

N6-methyladenosine (m6A) RNA methylation, dynamically regulated by methyltransferases, determines RNA fate and impacts tumorigenesis, yet the linkage between FDX1 gene expression and m6A modification in breast cancer (BC) remains unclear. Through bioinformatics analysis of The Cancer Genome Atlas (TCGA) database and experimental validation by qRT-PCR, we found that FDX1 is downregulated in BC tissues and cells. Functional assays including colony formation, Transwell, and apoptosis detection demonstrated that FDX1 upregulation inhibited proliferation, migration, invasion, and promoted apoptosis. Mechanistically, the m6A methyltransferase METTL3 was highly expressed in BC and suppressed FDX1 expression via m6A methylation, as confirmed by MeRIP-qPCR and RNA stability analysis. This METTL3-mediated m6A modification of FDX1 accelerated BC malignant progression. Our study elucidates that the METTL3-FDX1 axis plays an instrumental role in BC progression, revealing a novel epigenetic regulatory mechanism.

To prepare for future crises, providers who serve people experiencing homelessness may benefit from reviewing and incorporating lessons learned from responses to the COVID-19 pandemic. We present results of a rapid qualitative analysis of data from three focus groups with permanent supportive housing staff and four focus groups with clients in four large U.S. cities from July-August 2022. Clients and staff described how the pandemic challenged organizational practices and client-provider interactions, affected mental health and substance use, and produced mixed effects on housing and homelessness. Both clients and staff emphasized the importance of relationships and agreed that effective practices included providing vaccination at supportive housing sites and incorporating virtual options for therapy and support groups. Client and staff perspectives are synthesized to provide lessons learned and recommendations for responding to future public health events, like the COVID-19 pandemic; the analysis is framed using the socioecological model.

There are limited data on the risk factors associated with pulmonary exacerbation (PEx) in very young people with CF (VY-PwCF). The goal of our study was to examine the risk factors associated with PEx in the first 3 years of life and the relationship between PEx in early life and subsequent nutritional and pulmonary outcomes.

Using the CF Foundation Patient Registry (CFFPR), we analyzed demographic, clinical and PEx data on PwCF born between 2003 and 2017. Multivariable logistic regression analyzed the probability of a PEx between ages 1 and 3, and later-life forced expiratory volume in 1 s (FEV1) and body mass index (BMI) z-scores were modelled using negative binomial and linear regressions, respectively.

A total of 7,342 patients were included in our analysis. Medicaid insurance status, pancreatic insufficiency, asthma diagnosis before age 3, hypertonic saline use before age 1 and a positive respiratory culture for methicillin-resistant Staphylococcus Aureus and Stenotrophomonas maltophilia respectively before age 1 were associated with an increased odds of PEx diagnosis. FEV1 at age 6 and BMI z-scores at age 3 were lower in those who experienced early PEx.

We identified several risk factors that are associated with PEx diagnosis in the first 3 years of life and found that PEx in the first 3 years negatively impacted ppFEV1 at age 6 and BMI z-score at age 3. These data will be helpful for clinicians in counselling caregivers of VY-PwCF on PEx risk factors and identifying patients at higher risk of PEx in the first 3 years of life.

Objective: COVID-19 has heavily burdened healthcare systems worldwide, underscoring the need for accurate treatment decision-making to optimize patient recovery. This study leverages machine learning (ML) to evaluate how treatments affect the length of stay (LOS) for hospitalized COVID-19 patients in Iran. Method: We analyzed clinical data from 1793 patients with 106 features, identifying key variables through detailed profiles. Support Vector Machine (SVM), k-Nearest Neighbors (kNN), and Artificial Neural Network (ANN) models were then used to predict LOS based on personalized COVID-19 treatment regimens. Results: Actemra and Bromhexine exhibited the strongest correlation with LOS. In the first experiment, the models achieved average predictive accuracies of 90.0% (SVM), 89.53% (k-NN), and 86.30% (ANN); in the second experiment, the accuracies were 96.8% (SVM), 89.53% (k-NN), and 94.56% (ANN), demonstrating their effectiveness in forecasting hospital stay durations. Conclusion: Our study showed that medications such as Actemra and Bromhexine were associated with the affected factors for predicting LOS, especially when administered early to patients without major comorbidities. Those with conditions such as cardiovascular disease or diabetes had longer stays. The ML models predicted LOS with high accuracy, demonstrating their potential to assist clinical decisions. Overall, early treatment and predictive modeling can enhance patient outcomes and optimize hospital resource use.