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Biphenotypic sinonasal sarcoma (BSNS) is a rare, slow-growing soft tissue sarcoma of the sinonasal tract, typically presenting with nonspecific obstructive nasal symptoms. Although recurrences are common, no metastases have been reported, and only 1 patient has died of disease thus far. It characteristically demonstrates rearrangements of PAX3 with multiple fusion partners, the most common of which is MAML3. To highlight the most important diagnostic features, including morphologic, immunohistochemical, and molecular findings, and to provide comparisons to other entities in the differential diagnosis. We also aim to provide a summary of the clinical features and outcomes in cases reported to date. Recently published literature encompassing BSNS and its synonym, low-grade sinonasal sarcoma with neural and myogenic differentiation. BSNS is a sinonasal tumor that is important to recognize because its biologic behavior differs from most of the entities in the differential diagnosis. The diagnosis can typically be rendered through a combination of morphology, immunohistochemical stains, and ancillary testing for characteristic PAX3 rearrangements.

Learning about positive and negative outcomes of actions is crucial for survival and underpinned by conserved circuits including the striatum. How associations between actions and outcomes are formed is not fully understood, particularly when the outcomes have mixed positive and negative features. We developed a novel foraging (‘bandit’) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca ++ imaging, we monitored activity of visually identified anterodorsal striatal striosomal and matrix neurons. We found that action-outcome associations for reward and punishment were encoded in parallel in partially overlapping populations. Single neurons could, for one action, encode outcomes of opposing valence. Striosome compartments consistently exhibited stronger representations of reinforcement outcomes than matrix, especially for high reward or punishment prediction errors. These findings demonstrate multiplexing of action-outcome contingencies by single identified striatal neurons and suggest that striosomal neurons are particularly important in action-outcome learning. The role that the striatum plays in tracking the association between actions and combinations of rewarding and aversive outcomes remains unclear. Here, by using both calcium imaging in mice and reinforcement learning models, the authors find that individual striatal neurons can encode associations between actions and multiple, sometimes conflicting, outcomes.

Ossifying fibromyxoid tumor (OFMT) is a rare, slow-growing mesenchymal neoplasm of uncertain histogenesis with intermediate malignant potential. To highlight the most important diagnostic features, including morphologic, immunohistochemical, and molecular findings; to provide comparisons to other entities in the differential diagnosis; and to provide a summary of the clinical features and outcomes in cases reported to date. The data sources include recently published literature encompassing OFMT and tumors in the histologic differential diagnosis, and cases from institutional files. Ossifying fibromyxoid tumor is important to recognize because of its low-grade morphology but potential for recurrence and metastasis. Recent molecular analysis has expanded the morphologic spectrum of OFMT, with additional cases discovered that are enriched for aggressive behavior. The diagnosis can often be rendered through a combination of morphology and coexpression of S100 protein and desmin, although only a minority of cases described contain all of these primary features. In cases that do not have all of these features, a high index of suspicion guided by morphology and exclusion of other tumors in the histologic differential diagnosis can lead to the correct diagnosis. Growing access to molecular genetic testing will become increasingly important for correct diagnosis of tumors at the ends of the morphologic spectrum.

Cutaneous soft tissue tumors with epithelioid features present a diagnostic challenge given that many entities in this category are rare, and they show morphologic overlap with significantly more common cutaneous epithelial and melanocytic neoplasms. The challenge is compounded by overlapping expression of epithelial or melanocytic markers in some of these entities. A broad spectrum of primary cutaneous epithelioid soft tissue tumors exists, including benign and malignant counterparts of tumors with various differentiation including melanocytic, peripheral nerve sheath, angiomatous, fibrohistiocytic, and myoid or myoepithelial, in addition to translocation-associated tumors lacking a derivative tissue type. Given this spectrum, an initial targeted immunohistochemical panel for epithelioid dermal and subcutaneous neoplasms is recommended, covering a broad spectrum of differentiation. In diagnostically challenging cases, select molecular studies can be employed to make critical distinctions between entities sharing morphologic and immunohistochemical properties. Due to sometimes marked differences in prognosis and treatment, knowledge and familiarity with epithelioid soft tissue tumors is key for any surgical pathologist who evaluates skin and subcutaneous biopsies and excision specimens. This concise review provides brief descriptions, key diagnostic features, and important modern ancillary studies for the diagnosis of non-epithelial, non-melanocytic cutaneous tumors that can exhibit a prominent degree of epithelioid morphology.

The bactericidal function of neutrophils is dependent on a myriad of intrinsic and extrinsic stimuli. Using systems immunology approaches we identify microbiome- and infection-induced changes in neutrophils. We focus on investigating the Prenylcysteine oxidase 1 like (Pcyox1l) protein function. Murine and human Pcyox1l proteins share ninety four percent aminoacid homology revealing significant evolutionary conservation and implicating Pcyox1l in mediating important biological functions. Here we show that the loss of Pcyox1l protein results in significant reductions in the mevalonate pathway impacting autophagy and cellular viability under homeostatic conditions. Concurrently, Pcyox1l CRISPRed-out neutrophils exhibit deficient bactericidal properties. Pcyox1l knock-out mice demonstrate significant susceptibility to infection with the gram-negative pathogen Psuedomonas aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein in modulation of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality. Neutrophils play critical roles in the response to infection and their function relies on a range of intrinsic and extrinsic factors. Here the authors show a role for Pcyox1l and link this to metabolic pathways including prenylation and the neutrophil response to infection.

Cellular spindled histiocytic pseudotumor (CSHPT) is an exuberant, dense histiocytic proliferation seen in the setting of mammary fat necrosis. CSHPT has a broad histologic differential diagnosis, including benign, malignant, and inflammatory etiologies. To highlight the most important histologic and immunohistochemical findings of CSHPT and provide comparisons to entities within the broad differential diagnosis. Recently published literature regarding CSHPT and other diagnostic considerations. CSHPT is a benign histiocytic proliferation with a broad differential diagnosis, for which comprehensive ancillary studies may be required to exclude malignant and infectious entities.

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer.

Atypical ductal hyperplasia (ADH) is a challenging diagnosis defined by cytologic and architectural features that carries an increased risk of subsequent carcinoma when diagnosed in isolation. In addition, ADH may secondarily involve benign breast lesions, wherein it carries variable clinical significance. To review the diagnostic criteria and clinical significance of ADH in isolation and as it involves benign breast lesions, and to review the evolving literature on its molecular signature. Recently published studies that collectively examine ADH were reviewed. Atypical ductal hyperplasia carries an increased risk of subsequent carcinoma in isolation and when it involves most benign breast lesions. Identifying which cases of ADH will be upgraded to carcinoma has been challenging, and new laboratory developments, such as EZH2 overexpression, may have a future role.

Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences “heart rate” and “contractility,?” the key components of “palpitation.” While the prevalence of hypertension is 22.4% in 18–39‐year‐olds, the relationship between palpitations and hypertension remains unknown in this age group. In our study, we assessed the incidence and prevalence of hypertension over 5 years in 18–40‐year‐olds referred for palpitations who had no known arrhythmic cause for palpitations between January 1, 206 and December 31, 2017. We found that over a period of 2.2 (0.7–4.1) years, an additional 56% patients were diagnosed with stage 1 (65/130) and stage 2 (28/130) hypertension, increasing the prevalence from 16% at the start of the study period to 72% at the end of the study period (p < .0001). Hypertensive patients were obese (BMI: 29 [24–36] kg/m2 vs. 25 [22–31] kg/m2; p = .03), used nonsteroidal anti‐inflammatory drugs (NSAIDs) (62 vs. 35%; p = .04), had a stronger family history of hypertension (55 vs. 4%; p < .0001) and exhibited higher systolic (124[120–130] mmHg vs. 112[108–115] mmHg; p < .0001) and diastolic (80[76–83] mmHg vs. 72[69–75] mmHg; p < .0001) blood pressures. Hypertension is commonly diagnosed in 18–40‐year‐old predominantly white female patients referred for palpitations without a known arrhythmic cause. The possibility of untreated hypertension causing palpitations in this cohort needs further evaluation.

Lipoblastomas and liposarcomas are rare causes of soft tissue masses in paediatric patients. In this retrospective clinical case series we identified 11 patients from our paediatric database (10 with a lipoblastoma and one with a liposarcoma) who had attended our hospital between 1998 and 2019. The median age of patients with lipoblastoma was 29 months. All lipoblastoma cases were managed with surgical excision and histological examination. The 18-year old patient with liposarcoma presented with a metastatic and unresectable tumour that was unresponsive to chemotherapy and radiation. Our experience demonstrates the importance of differentiating the type of soft tissue mass in children.