Bone marrow fibrosis (MF) reflects stromal remodeling and has been associated with treatment resistance and adverse outcomes in hematologic malignancies; however, its clinical significance in acute lymphoblastic leukemia (ALL) remains uncertain. We retrospectively analyzed 103 patients with newly diagnosed ALL and documented MF grades between 2018 and 2023, comparing patients with MF grades 0-1 and those with MF grades 2-3. Higher-grade MF was present in 50 patients (48.5%). B-ALL accounted for a greater proportion of cases in the MF 2-3 group than in the MF 0-1 group (94.0% vs. 69.8%; nominal p = 0.002), and this difference remained statistically significant after false discovery rate correction. No mutation-level difference between the MF groups remained significant after correction for multiple comparisons. In Cox regression, MF 2-3 was associated with a lower observed hazard of death compared with MF 0-1 (adjusted HR, 0.26; 95% CI, 0.12-0.55; p < 0.001). A similar association was observed in a sensitivity analysis restricted to patients with B-ALL (adjusted HR, 0.30; 95% CI, 0.13-0.70; p = 0.005). Given the retrospective design, limited number of deaths, and potential residual confounding, this unexpected inverse association should be considered exploratory and should not be interpreted as evidence of a biologically protective effect of MF. In conclusion, higher-grade MF was common in newly diagnosed ALL and was associated with B-lineage disease. An unexpected inverse association between MF grade and observed mortality was identified in this cohort and persisted in the B-ALL-restricted sensitivity analysis. External validation is required before MF can be considered for prognostic stratification or treatment decision-making.

An octogenarian woman with Merkel cell carcinoma of the right upper arm, staged as Stage IIIA at initial diagnosis, underwent wide local excision with sentinel lymph node biopsy followed by adjuvant radiation therapy. She later developed regional nodal recurrence requiring axillary dissection, which was confirmed by biopsy as metastatic Merkel cell carcinoma, requiring axillary dissection. Despite subsequent treatment with pembrolizumab, she developed progressive metastatic disease one year later, with new hepatic and pulmonary lesions. Biopsy of a hepatic lesion demonstrated a poorly differentiated neuroendocrine carcinoma with a high proliferative index. Notably, immunohistochemistry showed absence of cytokeratin 20 (CK20) expression, raising diagnostic uncertainty regarding lineage confirmation in the setting of CK20-negative metastatic disease. Given the clinical context, the patient was treated with carboplatin and etoposide per established guidelines for high-grade neuroendocrine tumors; however, she exhibited continued disease progression and ultimately transitioned to hospice care, where she died. This case highlights the diagnostic and therapeutic challenges of advanced Merkel cell carcinoma in the setting of immune checkpoint inhibitor exposure, particularly the potential for loss of the canonical Merkel cell carcinoma immunophenotype at metastatic sites following such therapy. It underscores the importance of integrating clinical history, treatment exposure, and morphologic findings when evaluating atypical metastatic neuroendocrine neoplasms, especially when canonical immunohistochemical markers such as CK20 are absent.

Zinner syndrome is a rare congenital malformation of the urogenital system characterized by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction. A variant of Zinner syndrome is present when, instead of a seminal vesicle cyst, there is agenesis of the ipsilateral seminal vesicle. Although Zinner syndrome has been associated with urogenital neoplasms in some cases, to our knowledge, no case of a patient with Zinner syndrome and a contralateral neuroendocrine tumor (NET) has been previously described. The patient is a 26-year-old man who developed urinary retention due to a tumor of the right seminal vesicle infiltrating the prostate and obstructing the prostatic urethra. Abdominal and bladder MRI showed dysgenesis of the left kidney, seminal vesicle, and ejaculatory duct, as well as a mildly contrast-enhancing mass of the right seminal vesicle infiltrating the adjacent prostate. Gallium-68 PET-CT showed increased somatostatin receptor (SSTR) expression in the right seminal vesicle. Histologically, it was a well-differentiated NET with infiltrates of epithelial tumor cells that were positive for chromogranin, synaptophysin, and CD56. Chromogranin was also increased in the serum. The patient underwent radical prostatectomy, and it was decided not to proceed with chemotherapy or radiotherapy. Zinner syndrome may be associated with a contralateral NET of the genitourinary tract. Therefore, patients with Zinner syndrome should be regularly followed up to avoid overlooking a co-occurring malignancy.

Cervical cancer is largely preventable through effective screening and human papillomavirus (HPV) vaccination; however, mortality disparities remain a persistent public health challenge in the United States. This study aimed to examine long-term trends and socio-demographic and geographic inequalities in cervical cancer mortality.

We conducted a population-based study of cervical cancer mortality among U.S. women aged ≥25 years from 1999 to 2023 using national mortality data from the CDC WONDER database. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Temporal trends were evaluated using Joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Analyses were stratified by census region, race/ethnicity, urbanization level, age group, and state. Age restrictions were harmonized across bridged-race and single-race population estimates, and corrected estimates were used for trend analyses.

Overall cervical cancer mortality declined substantially from 1999 to 2023, with the female-specific AAMR decreasing from 4.37 to 2.09 per 100,000 women (AAPC, -3.27%; 95% CI, -3.81 to -2.73). Despite this overall decline, substantial disparities persisted. Mortality rates remained consistently higher in the Southern region and lowest in the Northeast, which showed the greatest reduction over time (AAPC, -4.23%; 95% CI, -5.31 to -3.13). Non-Hispanic Black women experienced persistently higher mortality compared with other racial and ethnic groups, and women residing in nonmetropolitan areas had elevated mortality rates. Considerable geographic variation was observed across states, with mortality rates in higher-burden states approximately two- to four-fold higher than those in lower-burden states. Sensitivity analyses restricted to women aged ≥25 years confirmed consistent long-term mortality trends between bridged-race and corrected single-race estimates. No evidence of an accelerated decline around 2019/2020 was identified, and the previously reported post-2019 acceleration was attributable to inconsistent age restrictions during data extraction rather than a true epidemiological change.

Although cervical cancer mortality has declined significantly in the United States over the past two decades, substantial socio-demographic and geographic disparities persist. These findings highlight the need for targeted public health strategies to improve equitable access to screening, HPV vaccination, and timely treatment, particularly in high-risk populations and underserved regions.

Predictive biomarkers are needed to identify patients with high-grade glioma who benefit from cyclin-dependent kinase 6 (CDK6) inhibition. We hypothesized that an integrated Radiomics-Immune Score (R/I-Score), combining MRI-derived tumor heterogeneity with peripheral immune profiling, would predict progression-free survival (PFS) benefit from CDK6 inhibitor-containing therapy (CDK6i).

We conducted a two-center, retrospective cohort study utilizing longitudinal data from departmental neuro-oncology registries. The final study population comprised 116 adult patients with measurable disease who had undergone baseline contrast-enhanced MRI within 21 days prior to treatment initiation. To ensure methodological rigor and internal consistency, we adopted a two-stage study design. In the first stage (Biological Modeling), the total cohort (N = 116) was partitioned into a training set (n = 81) and an independent testing set (n = 35) to develop and validate the R/I-Score. In the second stage (Clinical Validation), we addressed the selection bias inherent in observational data by performing 1:2 Propensity Score Matching (PSM). This yielded a balanced analytical cohort of 108 patients (36 treated with CDK6i and 72 concurrent contro\ls). The primary endpoint was the treatment-by-biomarker interaction for progression-free survival (PFS), specifically assessing the R/I-Score's ability to stratify therapeutic responders.

In the overall matched cohort (N = 108), patients treated with CDK6i exhibited numerical but statistically non-significant trends toward improved efficacy compared to concurrent controls in terms of median PFS (4.8 vs. 3.5 months; HR 0.72, P = 0.091), objective response rate (19.4% vs. 9.7%; P = 0.180), and disease control rate (44.4% vs. 30.6%; P = 0.165). The Combined R/I-Clinical Model demonstrated exceptional diagnostic performance in the independent testing cohort (N = 108), achieving a Treatment-Effect AUC of 0.97 and excellent calibration. In the PSM efficacy analysis, the R/I-Score successfully identified a distinct responder subpopulation: patients with a High R/I-Score derived significant survival benefit from CDK6i compared to concurrent controls (HR 0.48; 95% CI 0.25-0.91; P = 0.008), whereas those with a Low R/I-Score did not (HR 1.05; 95% CI 0.58-1.92). The interaction between the R/I-Score and treatment was statistically significant (P_interaction = 0.012). Furthermore, High R/I-Score patients achieved superior objective response rates (33.3% vs. 5.6%) and sustained treatment duration (median 6 vs. 3 cycles) without increased toxicity (Grade ≥3 AEs: P>0.05). Biological interpretability analysis revealed that the score was driven by tumor morphological complexity and NK/CD8+ T-cell infiltration.

The multi-modal R/I-Score serves as a robust, non-invasive predictive biomarker for CDK6i therapy in GBM. By selecting patients based on specific radiomic-immune phenotypes, this tool facilitates precision oncology, maximizing therapeutic efficacy while avoiding futile treatment in non-responders.

Accurate preoperative imaging is essential for optimal surgical planning in breast carcinoma. Mammography and ultrasonography are commonly used imaging modalities; however, their relative effectiveness in tumor size estimation and lymph node evaluation varies. This study aimed to compare the diagnostic role of preoperative ultrasonography and mammography in breast carcinoma and to correlate imaging findings with intraoperative and histopathological outcomes.

This prospective comparative observational study included 50 female patients with malignant breast disease undergoing elective surgery at a tertiary care teaching hospital. All patients underwent preoperative mammography and ultrasonography. Imaging findings were correlated with intraoperative observations and histopathological examination. Statistical analysis was performed using SPSS Statistics version 26.0 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY), with p < 0.05 considered statistically significant.

The mean age of patients was 51.38 ± 9.65 years. Ductal carcinoma was the most common histopathological subtype (62%, n = 31). Ultrasonography demonstrated a mean tumor size of 2.97 ± 0.46 cm, which was closer to the intraoperative tumor size (3.49 cm) than the mammographic estimate of 2.53 ± 0.41 cm. Both ultrasonographic and mammographic tumor-size estimates differed significantly from the intraoperative measurements (both p < 0.001). Ultrasonography showed a stronger association with intraoperative lymph node findings than mammography.

Preoperative ultrasonography yielded a mean tumor-size estimate closer to the reference measurement than mammography and showed a stronger association with intraoperative lymph node findings. However, the combined use of both imaging modalities provides optimal diagnostic assessment and should be routinely employed in the preoperative evaluation of breast carcinoma.

Peritoneal metastasis (PM) is the most common form of organ-specific metastasis in advanced gastric cancer (GC), and is driven by the dynamic interplay between cancer cells and the tumor microenvironment (TME). This review elaborates on the mechanisms through which cancer cells utilize metabolic reprogramming, mechanical stress, and neural control to shape the microenvironment conducive to tumor growth. It also describes the metastatic cascade of their active dissemination and colonization processes of cancer cells within the peritoneal cavity. Finally, on the basis of these mechanistic insights, we propose a three-step strategy that dismantle physical barriers, blocks nutrient supply, and reverses immune suppression. The aim of this study to transform PM from a treatment challenge into a manageable disease, further improving disease prognosis.

Juvenile generalized myasthenia gravis (MG) management aims to control symptoms while minimizing corticosteroid-related toxicity. However, large-scale evidence on real-world pediatric treatment patterns remains limited.

We conducted a retrospective cohort study using a large Japanese hospital-based claims database (Medical Data Vision). We identified patients aged 0-17 years with juvenile generalized MG between April 2008 and November 2024. We summarized the use of cholinesterase inhibitors, oral corticosteroids, immunosuppressants, and intensive treatments (plasma exchange, intravenous immunoglobulin [IVIg], or high-dose steroid pulse therapy) during the one-year follow-up period after the first confirmed MG diagnosis recorded in the database. We also compared patient characteristics and treatment patterns by age group (children: 0-9 years vs. adolescents: 10-17 years).

We identified 261 patients with juvenile generalized MG, including 125 children and 136 adolescents cases. Cholinesterase inhibitors were the most frequently used medication (69.3% [181/261]). Oral corticosteroids were commonly used (65.9% [172/261]), whereas immunosuppressant use was limited; only 89/261 (34.1%) received tacrolimus. Among the 217 patients with complete one-year follow-up data, 146 received corticosteroid. The mean daily corticosteroid dose, calculated as the annual cumulative corticosteroid dose divided by 365 days, was 8.7 mg/day (SD 7.1) (children: 6.2 mg/day [SD 4.1]; adolescents: 11.4 mg/day [SD 8.6]). Among 261 generalized MG patients, 52 (19.9%) received intensive treatments, with a higher proportion in adolescents than children (25.7% [35/136] vs. 13.6% [17/125]). IVIg was the most common intensive treatment (13.4% [35/261]), followed by steroid pulse therapy (10.3% [27/261]) and plasma exchange (3.8% [10/261]). Adolescent generalized MG had higher intensive care unit hospitalization rates than child generalized MG (8.8% [12/136] vs. 0.8% [1/125]), and all thymectomies occurred in adolescent patients (8.1% [11/136] vs. 0% [0/125]).

In Japanese real-world practice, about one in five children with generalized MG required intensive treatments, particularly among adolescents, while steroid-sparing immunosuppression was used in only one-third. These findings support close monitoring of adolescent generalized MG and highlight opportunities to optimize steroid-sparing management in juvenile generalized MG.

Pemphigus is an autoimmune bullous disease. PNP/PAMS represents a rare subtype of autoimmune bullous disease, and typically associated with an underlying neoplasm, particularly lymphoproliferative disorders. Current management of PNP primarily involves glucocorticoids, immunosuppressants, and rituximab. This article reports a 67-year-old male who presented with generalized erythema, blisters, and oral erosions with pain for one month. Initially diagnosed with pemphigus, he received methylprednisolone treatment, which led to slight improvement in skin lesions but minimal resolution of oral ulcers. Based on the available clinical, histopathological, immunofluorescence, and serological findings, the patient was initially diagnosed with pemphigus vulgaris in the setting of CLL. However, the refractory oral mucositis, dual positivity for Dsg1 and Dsg3, and the underlying B-cell malignancy raised the concern for paraneoplastic pemphigus (PNP). Given that PNP-specific tests-including anti-plakin antibodies, indirect immunofluorescence on rat bladder, and immunoblotting-were not performed, a definitive diagnosis of PNP could not be established. Therefore, the condition was managed as "suspected CLL-associated PNP" Following the initiation of zanubrutinib in combination with ongoing corticosteroid therapy and CLL treatment, significant improvement of oral erosions was observed. In this case, the clinical improvement may be potentially related to zanubrutinib, but the concurrent corticosteroid therapy and the control of CLL likely contributed as well. If zanubrutinib did play a role, the mechanism might involve enhanced disease control or immune modulation. However, the current evidence is insufficient to draw a firm conclusion, and its true efficacy needs to be evaluated in further studies.

This study aimed to evaluate the prognostic value of absolute lymphocyte count (ALC) nadir and estimated dose of radiation to immune cells (EDRIC) in patients with limited-stage small cell lung cancer (LS-SCLC).

This study analyzed 288 patients with LS-SCLC treated with chemoradiotherapy (CRT) between 2019 and 2023. ALC nadir and EDRIC were evaluated for prognostic value across patients receiving twice-daily (BID) and once-daily (QD) radiotherapy. Survival outcomes included overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS).

Despite lower lymphocyte counts during early treatment in the BID group, the ALC nadir was significantly higher in the BID group compared with the QD group (median ALC nadir: 0.60 × 10⁹/L vs. 0.49 × 10⁹/L, P < 0.001). In the BID group, patients with ALC nadir > 0.55 × 10⁹/L showed significantly longer OS (median OS: NR vs. 46.7 months, P = 0.011), PFS (P = 0.022), and BMFS (P = 0.013) compared with those with ALC nadir ≤ 0.55 × 10⁹/L. Patients in the high EDRIC group had significantly shorter PFS (P = 0.001) and BMFS (P = 0.003), and a trend toward shorter OS (P = 0.179). In the QD group, no significant differences were observed when stratified by ALC nadir or EDRIC (P > 0.05).

ALC nadir and EDRIC demonstrated prognostic significance in the BID group but not in the QD group, suggesting potential differences in radiation-associated immune effects between fractionation schedules.