Breast cancer (BRCA) is a heterogeneous disease with a complex etiology. The prognostic value of genes related to migrasomes and the tumor microenvironment (MTMERGs) in BRCA is unclear.

A prognostic risk model was constructed using six core signature genes identified from MTMERGs via differential expression analysis and Cox regression. Its reliability was validated in an independent cohort using Kaplan-Meier and time-dependent ROC curves. A nomogram was developed and assessed via Decision Curve Analysis (DCA). Biological functions and immune infiltration were evaluated with GSEA, CIBERSORT, and ssGSEA. Immunotherapy sensitivity was predicted using TIDE/IPS scores and the IMvigor210 cohort. Tumor Mutation Burden (TMB) analysis and the pRRophetic algorithm were used for further clinical correlation and drug sensitivity prediction.

The six-MTMERG model effectively stratified patients into high- and low-risk groups with distinct survival outcomes. The high-risk group was associated with a predicted immunosuppressive microenvironment (estimated enrichment of M0/M2 macrophages), higher TMB, and poorer prognosis. In contrast, the low-risk group was estimated to possess an immunologically active profile and showed a better predicted response to immune checkpoint inhibitors. Predicted differential sensitivities to conventional chemotherapy were also computationally evaluated between the subgroups.

We developed a computationally derived and externally validated prognostic model for BRCA based on migrasome and tumor microenvironment features. It successfully stratifies patients into groups with divergent clinical outcomes, immune profiles, and therapeutic responses, providing insights into BRCA heterogeneity and prognosis. Further prospective and experimental validation is warranted before clinical application.

This study aimed to identify germline pathogenic/likely pathogenic variants in DNA damage repair genes associated with increased cancer risk in Korean patients with biliary tract cancer and characterize their population-specific patterns.

In this retrospective multicenter cohort study, we performed germline whole-exome sequencing in 172 Korean patients diagnosed with intrahepatic cholangiocarcinoma (n = 83) or gallbladder cancer (n = 89) between June 2001 and February 2022. Germline variants were analyzed in 210 hereditary cancer genes, and the germline landscape of this cohort was compared with that of global cohorts.

Pathogenic/likely pathogenic variants were identified in 24 of 172 (14.0%) patients, predominantly in DNA damage repair genes (18 of 24 [75.0%]). BRCA2 was among the most frequently altered genes, harboring two distinct pathogenic variants (2 of 24 [8.3%]; both cases of intrahepatic cholangiocarcinoma). Of the 24 carriers, five (20.8%) harbored Tier 1-2 variants of potential, tumor-confirmation-dependent therapeutic relevance. Notably, 15 of 24 (62.5%) carriers reported no family cancer history. In population-stratified comparisons across nine biliary tract cancer cohorts (n = 4,018), PMS2 showed a Korean-enriched signal after accounting for heterogeneous gene coverage, whereas TP53 showed only a directional, non-significant increase after multiple-testing correction.

The study findings provide reference data for genetic counseling in East Asian patients with biliary tract cancer and suggest that germline testing may warrant consideration regardless of family history.

The outcomes of different antidiarrheal strategies in HER2-positive breast cancer patients treated with pyrotinib plus trastuzumab and docetaxel are unknown.

97 eligible patients received pyrotinib once daily from Cycle 1 Day 7 onwards, combined with intravenous trastuzumab and docetaxel on Day 1 of each 21-day cycle. In the 400PYR cohort, patients were treated with 400 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the 320PYR+Pro-L and 400PYR+Pro-L cohorts, patients were given 320 or 400 mg pyrotinib and loperamide prophylaxis. In the 320PYR cohort, patients were treated with 320 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the PYR-DE+Pro-L cohort, patients were treated with escalating pyrotinib doses and loperamide prophylaxis.

The incidence of grade 3 diarrhea in cohorts with loperamide prophylaxis was lower than in the 400PYR cohort. In the 3 cohorts with loperamide prophylaxis, the dose escalation cohort had the lowest incidence of grade 3 diarrhea. The incidence of grade 3 diarrhea in 320PYR cohort was similar to the 3 cohorts with prophylactic antidiarrheal loperamide. No event of grade 4 or 5 diarrhea was reported.

Loperamide prophylaxis and pyrotinib dose escalation were associated with lower observed rates of grade 3 diarrhea in patients receiving pyrotinib plus trastuzumab and docetaxel. The lower rate observed in the 320PYR cohort should be interpreted cautiously and may reflect improved clinical management rather than a reproducible protocolized intervention.

To characterize short term clinical outcomes among pediatric patients with appendiceal neoplasms.

The National Cancer Database was queried for pediatric patients 0-17 years of age diagnosed with appendiceal tumors for 2004-2023. We analyzed demographic characteristics as well as short-term outcomes, tumor characteristics, and short-term outcomes. Patients were divided into AJCC stage, histology groups, and surgical approach for further subgroup analysis. All univariate statistical analysis was performed using GraphPad Prism 11 (GraphPad, La Jolla, CA, USA).

Pediatric appendiceal tumors are rare in the United States and often found incidentally on appendectomy, with an estimated annual incidence rate of 0.12% from 2004-2023. Patients with pediatric appendiceal neoplasms are more likely to be female, White, non-Hispanic, have private insurance, and live in high median household income areas. Most patients had neuroendocrine tumors that were well differentiated. Most patients underwent surgery, most commonly appendectomy followed by hemicolectomy. Advanced stage tumors, and more invasive surgery (hemicolectomy/partial colectomy) were all associated with prolonged hospital length of stay after surgery with very low overall mortality rates.

Pediatric appendiceal tumors are predominantly early-stage neuroendocrine neoplasms. Advanced stage, non-neuroendocrine histology, and more invasive surgery are associated with longer hospital length of stay and higher readmission rates, but no increased risk for mortality. Further studies are needed to optimize management and follow up for pediatric appendiceal neoplasms.

RECQL5 is a member of the RecQ helicase family involved in DNA replication, homologous recombination, and maintenance of genomic stability. While germline pathogenic variants in other RecQ helicases cause established cancer predisposition syndromes, the role of RECQL5 in human cancer susceptibility remains uncertain. We report monozygotic adolescent twins with distinct tumors: dysembryoplastic neuroepithelial tumor in one twin and Burkitt lymphoma in the other. Clinical genome sequencing was initially nondiagnostic, but reanalysis identified a rare heterozygous nonsense variant in RECQL5 (NM_004259.7:c.2698C>T, p.(Gln900Ter)), present in both twins and their unaffected mother. The variant is predicted to undergo nonsense-mediated mRNA decay or produce a truncated protein lacking the C-terminal SRI (Set2-Rpb1 interacting) domain, which mediates interaction with RNA polymerase II. However, tumor sequencing data were not available to evaluate loss of heterozygosity or second somatic events. Given the unaffected carrier parent, lack of tumor molecular confirmation, and the biological heterogeneity of the tumors, a causal relationship for this variant cannot be established. This case highlights the challenges of interpreting rare germline variants in genes with emerging but incompletely characterized disease associations. Although the available evidence is insufficient to establish a definitive causal relationship, the identification of a shared loss-of-function RECQL5 variant in monozygotic twins with distinct tumors is noteworthy and adds to the limited clinical evidence suggesting a potential role for RECQL5 in cancer susceptibility. Additional functional studies, tumor-based analyses and the accumulation of well-characterized clinical cases will be essential to determine whether RECQL5 contributes to hereditary cancer predisposition.

Clonal cytopenia of undetermined significance (CCUS) is defined by unexplained cytopenias with myeloid-associated somatic mutations not meeting diagnostic criteria for myelodysplastic syndromes/neoplasms (MDS) yet carries a highly risk-stratified probability of progression to myeloid neoplasms. The clinical distinction between CCUS and lower-risk MDS (LR-MDS) is challenging because current criteria rely heavily on semi-quantitative morphologic thresholds, despite substantial clinical and molecular overlap. In this prospective study of 409 patients with CCUS and 241 with LR-MDS, we applied harmonized diagnostic and progression criteria, rigorous centralized pathology review, and uniform genomic profiling to compare clinical, molecular, and outcome data. Risk stratification was performed using two independent models-the Clonal Hematopoiesis Risk Score (CHRS) and the Clonal Cytopenia Risk Score (CCRS). Patients with high-risk CCUS, as defined by CHRS or CCRS, exhibited clinical features and event rates comparable to those with LR-MDS. In contrast, patients with low- or intermediate-risk CCUS had markedly improved outcomes, supporting conservative management. These findings underscore that CHRS and CCRS are clinically informative tools that extend beyond morphology-based classification and enable a risk-adapted approach to the management of CCUS. Importantly, a subset of patients with high-risk CCUS demonstrated substantial clinical and genomic convergence with LR-MDS, supporting their consideration for enrollment in prospective clinical trials designed for LR-MDS. These observations highlight the need for further study of risk-adapted therapeutic approaches in this population and underscore the importance of prospective clinical evaluation.

Cushing's disease in pregnancy is rare and frequently underrecognized due to clinical overlap with physiologic gestational changes and hypertensive disorders of pregnancy, particularly preeclampsia. Delayed diagnosis may result in prolonged maternal morbidity and inappropriate management.

A 30-year-old gravida 2, para 1 woman delivered at 37 weeks' gestation via induced vaginal delivery for preeclampsia without severe features. Her immediate postpartum course was unremarkable. At 12 weeks postpartum, she developed persistent proteinuria with associated hypercalciuria and hyperuricosuria despite preserved renal function. Over the following weeks, she developed hypokalemia, leukocytosis, and progressive cushingoid features including facial rounding, dorsocervical fat pad, central obesity, proximal muscle weakness, hypertension, easy bruising, hirsutism, and frequent falls. Endocrine evaluation revealed markedly elevated serum and urinary cortisol levels with concomitant hyperandrogenism. Magnetic resonance imaging demonstrated a 9-mm pituitary adenoma with evidence of hemorrhage. She was diagnosed with cyclic Cushing's disease with intermittent adrenal insufficiency and initiated on glucocorticoid replacement therapy. Transsphenoidal resection of the adenoma was performed at 26 weeks postpartum, resulting in improvement in blood pressure and clinical symptoms. At one year postpartum, she remained clinically stable on glucocorticoid replacement therapy.

This case highlights the importance of maintaining a broad differential diagnosis in patients with hypertensive disorders of pregnancy. Persistent hypertension, proteinuria, and metabolic abnormalities should prompt evaluation for underlying endocrinopathies such as Cushing's disease. Early recognition and multidisciplinary management are critical to optimizing maternal outcomes and avoiding misattribution of symptoms to preeclampsia alone. Emerging biomarkers, including sFlt-1/PlGF ratios, may further aid in distinguishing preeclampsia from alternative pathologic processes.

Uterine fibroids affect an estimated 70% of women worldwide. Adenomyosis has an estimated prevalence ranging from 8.8% to 61.5% in hysterectomy cases over the past 50 years. Both conditions affect millions, yet remain underdiagnosed and poorly understood by patients. Transvaginal ultrasonography (TVUS) is the first line diagnostic imaging modality for detecting both uterine fibroids and adenomyosis. Despite advancements in diagnostic imaging, 50% of patients with uterine fibroids are unaware of their diagnosis even after TVUS detection, and one third of patients experience diagnostic delays of 5 or more years. Further, traditional 2D imaging such as MRI or ultrasound can be challenging for patients to interpret, potentially hindering understanding and affecting decision-making regarding treatment.

A multiparous woman with large uterine fibroids and two prior cesarean sections developed intermittent right lower quadrant pain along her c-section scar which persisted for nine years. Ultrasound and CT imaging repeatedly showed a markedly enlarged, fibroid uterus with no clear etiology. Hysterectomy was suggested as definitive treatment. Using CT data, the patient generated a 3D printed pelvic model of the uterus filling the pelvis, displacing intestines, compressing the bladder and pressing on the rectum. After visualization of this distortion, the patient elected to move forward with a hysterectomy which completely resolved her chronic pain and urinary symptoms.

This case underscores the importance of effective education and communication in managing gynecological conditions, especially when patients face complex decisions regarding treatment options such as undergoing a hysterectomy. Further the case emphasizes the possibility of enhancing patient education through 3D printing technology. As the American College of Obstetricians and Gynecologists (ACOG) notes, "Shared decision-making is a key component of patient-centered care, especially when multiple reasonable management options are available and the best choice depends on patient preferences and values."

Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive malignancy of the sinonasal cavity that can present with nonspecific symptoms such as nasal congestion and epistaxis. These are common primary care complaints and resemble several benign diseases, often leading to delayed diagnosis. We present an advanced case of SNUC in a patient with progressive nasal obstruction and new-onset vision changes to highlight concerning features that warrant urgent evaluation.

We present an 81-year-old male with a history of nasal polyps that presented with a two-year history of unilateral nasal congestion and intermittent left-side epistaxis. Symptoms progressively worsened and were accompanied by new-onset blurred vision in the left eye, headache, imbalance, and facial pressure. His physical exam was unremarkable on external inspection. CT and MRI were significant for an expansile mass in the left ethmoid air cells with erosion of the cribriform plate, extension into the anterior cranial fossa, and invasion of the extraconal orbital space. There were no concerns for distant metastases based on chest imaging. Endoscopic biopsy revealed poorly differentiated carcinoma consistent with SNUC. He was started on chemotherapy and follow up at one month showed significant clinical and radiographic response, including return of baseline vision.

Patients with SNUC can present with vague symptoms mimicking sinusitis, often leading to delayed diagnosis. High risk symptoms such as persistent unilateral nasal obstruction, recurrent epistaxis, new-onset visual changes, or neurological symptoms warrant early imaging and specialist referral. Sinonasal malignancies should be included in the differential when high risk symptoms are present or not responding to medical management. Despite its rarity, SNUC is highly aggressive and tends to invade nearby structures at presentation. Primary care clinicians serve a critical role in early recognition of alarming features to promote timely diagnosis and multidisciplinary management, which may improve patient outcomes.

Melanocytic matricoma is a rare biphasic cutaneous adnexal neoplasm composed of matrical epithelial cells admixed with dendritic melanocytes. First described in 1999, fewer than several dozen cases have been reported in the literature. These lesions most commonly arise on chronically sun-exposed skin of older adults and typically present as small, pigmented papules or nodules that may clinically mimic melanoma. Histopathologic evaluation is required for diagnosis and characteristically demonstrates matrical differentiation with shadow cell formation and admixed melanocytes. Atypical variants with increased cytologic atypia or mitotic activity can further complicate distinction from malignant melanocytic proliferations.

An 83-year-old Caucasian male presented for a general skin evaluation with concerns of an irregular papule on the dorsal hand that had been present for over one year. Physical examination revealed a 7 mm verrucous crusted papule. A shave biopsy demonstrated a dermal proliferation of basaloid matrical cells with scattered shadow cells and numerous pigmented dendritic melanocytes. Cytologic atypia and increased mitotic activity were noted. Immunohistochemical staining supported a biphasic epithelial and melanocytic population and helped exclude melanoma. These findings were most consistent with atypical melanocytic matricoma. The lesion was subsequently treated with complete surgical excision, and histopathology confirmed clear margins without residual tumor.

This case highlights the diagnostic challenges posed by atypical melanocytic matricoma, particularly its clinical and histologic overlap with melanoma and other pigmented adnexal tumors. Recognition of characteristic matrical differentiation and the use of immunohistochemical analysis are essential for accurate diagnosis. Complete surgical excision with negative margins appears to be curative in most cases, though the limited number of reported cases makes prognostic assessment difficult. This report adds to the growing literature describing the clinical and histopathologic features of this uncommon neoplasm and emphasizes the importance of clinicopathologic correlation in guiding management.