Subcellular spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory arthritis of childhood, yet the spatial organization in the synovium remains poorly understood. Here, we perform subcellular-resolution spatial transcriptomic profiling of synovial tissue from patients with active JIA. We identify diverse immune and stromal cell populations and reconstruct spatially defined cellular niches.

Reappraisal of soft tissue myoepithelial tumors by DNA methylation profiling reveals an epigenetically distinct group of mostly fusion-driven neoplasms.

Soft tissue myoepithelial tumors (METs) are diagnostically challenging tumors that require careful histologic and immunohistochemical characterization for accurate classification. Nearly half of METs show recurrent EWSR1 or FUS gene rearrangements with a diverse set of fusion partners. The diversity of fusion partners and lack of known driver abnormalities in many cases raises the question of whether METs represent a uniformly distinct tumor entity.

Pediatric Adrenocortical Carcinoma: The Nuts and Bolts of Diagnosis and Treatment and Avenues for Future Discovery.

Adrenocortical tumors (ACTs) are infrequent neoplasms in children and adolescents and are typically associated with clinical symptoms reflective of androgen overproduction. Pediatric ACTs typically occur in the context of a germline mutation, can be cured when diagnosed at an early stage, but are difficult to treat when advanced or associated with concurrent and alterations. Recent work has demonstrated DNA methylation patterns suggestive of prognostic significance.

Decay-Accelerating Factor Differentially Associates With Complement-Mediated Damage in Synovium After Meniscus Tear as Compared to Anterior Cruciate Ligament Injury.

We have reported that anterior cruciate ligament (ACL) injury leads to the differential dysregulation of the complement system in the synovium as compared to meniscus tear (MT) and proposed this as a mechanism for a greater post-injury prevalence of post traumatic osteoarthritis (PTOA). To explore additional roles of complement proteins and regulators, we determined the presence of decay-accelerating factor (DAF), C5b, and membrane attack complexes (MACs, C5b-9) in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy, osteoarthritis (OA)-related knee replacement surgery and normal controls. Multiplexed immunohistochemistry was used to detect and quantify complement proteins.

Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases.

Aims: Classification of renal neoplasms on small tissue biopsies is in increasing demand, and maintaining broad differential diagnostic considerations in this setting is necessary. When evaluating a renal or perirenal tumour biopsy with sarcomatoid morphology, together with sarcomatoid renal cell carcinoma and sarcomatoid urothelial carcinoma as top diagnostic considerations, it is vital to additionally consider the possibility of well-differentiated and de-differentiated liposarcoma.

Methods And Results: This study reports a series of 30 biopsy samples from sites in or around the kidney collected from four institutions in which the correct diagnosis was either well-differentiated or de-differentiated liposarcoma.

Adamantinoma of the Ulnar Shaft Reconstructed With a Vascularized Free Fibula.

We describe a 36-year-old man with a long-standing diagnosis of ulnar fibrous dysplasia with associated fracture of the ulna. He presented with a growing and increasingly tender forearm mass and was diagnosed with adamantinoma of the ulna, for which he underwent wide resection of the ulnar diaphysis followed by reconstruction with a vascularized fibula autograft. This case serves to emphasize the importance of performing a stepwise workup for the diagnosis of osseous neoplasms even in cases with long-standing diagnoses.

Current therapies and future prospective for locally aggressive mesenchymal tumors.

Locally aggressive mesenchymal tumors comprise a heterogeneous group of soft tissue and bone tumors with intermediate histology, incompletely understood biology, and highly variable natural history. Despite having a limited to absent ability to metastasize and excellent survival prognosis, locally aggressive mesenchymal tumors can be symptomatic, require prolonged and repeat treatments including surgery and chemotherapy, and can severely impact patients' quality of life. The management of locally aggressive tumors has evolved over the years with a focus on minimizing morbid treatments.

Senescence-induced immune remodeling facilitates metastatic adrenal cancer in a sex-dimorphic manner.

Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy.

Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear.

Anterior cruciate ligament (ACL) injury and meniscal tear (MT) are major causal factors for developing post-traumatic osteoarthritis (PTOA), but the biological mechanism(s) are uncertain. After these structural damages, the synovium could be affected by complement activation that normally occurs in response to tissue injury. We explored the presence of complement proteins, activation products, and immune cells, in discarded surgical synovial tissue (DSST) collected during arthroscopic ACL reconstructive surgery, MT-related meniscectomy and from patients with OA.

Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway.

Unlabelled: Liposarcoma is the most commonly occurring soft-tissue sarcoma and is frequently characterized by amplification of chromosome region 12q13-15 harboring the oncogenes MDM2 and CDK4. This unique genetic profile makes liposarcoma an attractive candidate for targeted therapeutics. While CDK4/6 inhibitors are currently employed for treatment of several cancers, MDM2 inhibitors have yet to attain clinical approval.

The Genetic and Epigenetic Features of Bilateral Wilms Tumor Predisposition: A Report from the Children's Oncology Group AREN18B5-Q Study.

This study comprehensively evaluated the landscape of genetic and epigenetic events that predispose to synchronous bilateral Wilms tumor (BWT). We performed whole exome or whole genome sequencing, total-strand RNA-seq, and DNA methylation analysis using germline and/or tumor samples from 68 patients with BWT from St. Jude Children's Research Hospital and the Children's Oncology Group.

Spontaneous carotid blowout of the common carotid artery in a chronically immunosuppressed transplant patient.

Carotid blowout (CB) is a life-threatening surgical emergency with a mortality rate of up to 60%. CB is commonly seen in head and neck cancer patients after surgical and radiation therapy; other causes include iatrogenic, traumatic, or infectious etiologies. We report an unusual case of spontaneous CB presumed to be caused by cytomegalovirus (CMV) in a chronically immunosuppressed transplant recipient.

Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of .

The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for mucosal immune responses in the initiation or perpetuation of the systemic autoimmunity that occurs with disease. However, the connection between the mucosa and systemic autoimmunity in RA remains unclear. Using dual immunoglobulin A (IgA) and IgG family plasmablast-derived monoclonal autoantibodies obtained from peripheral blood of individuals at risk for RA, we identified cross-reactivity between RA-relevant autoantigens and bacterial taxa in the closely related families and .

Intra-articular Osteoid Osteoma of the Olecranon Fossa.

Osteoid osteomas are benign primary bone lesions characterized by a central nidus with surrounding reactive sclerosis, classically presenting as worsening nocturnal pain relieved by non-steroidal anti-inflammatory medications (NSAIDs). These most commonly occur in intracortical bone and the diaphysis of long bones. As a rare entity, intra-articular osteoid osteomas present unusually, often resulting in a delayed or incorrect diagnosis.

Lipoma and Its Doppelganger: The Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma.

Lipomatous tumors are among the most common soft tissue lesions encountered by the general surgeon. Shared history and clinical presentation make differentiation between benign lipomas and low-grade liposarcomas a diagnostic dilemma. This article reviews the epidemiology, clinical history, diagnostic workup, management, natural history, and surveillance of benign lipomas and atypical lipomatous tumors/well-differentiated liposarcomas.

The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a pediatric cancer with features of skeletal muscle; patients with unresectable or metastatic RMS fare poorly due to high rates of disease recurrence. Here, we use single-cell and single-nucleus RNA sequencing to show that RMS tumors recapitulate the spectrum of embryonal myogenesis. Using matched patient samples from a clinical trial and orthotopic patient-derived xenografts (O-PDXs), we show that chemotherapy eliminates the most proliferative component with features of myoblasts within embryonal RMS; after treatment, the immature population with features of paraxial mesoderm expands to reconstitute the developmental hierarchy of the original tumor.

Expression in Wilms Tumor Is Regulated by Promoter Mutation or Hypermethylation, WT1, and N-MYC.

Increased mRNA is associated with disease relapse in favorable histology Wilms tumor (WT). This study sought to understand the mechanism of increased expression by determining the association between and WT1 and N-MYC, two proteins important in Wilms tumor pathogenesis that have been shown to regulate expression. Three out of 45 (6.

Pathological and Genetic Stratification for Management of Adrenocortical Carcinoma.

Context: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers.

Evidence Acquisition: This review is based on the evidence collected from primary research studies, expert reviews, and published guidelines.

Methylation profiling reveals novel molecular classes of rhabdomyosarcoma.

Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS.

Clinical and Functional Significance of TP53 Exon 4-Intron 4 Splice Junction Variants.

Germline splicing variants are uncommon, and their clinical relevance is unknown. However, splice-altering variants at exon 4-intron 4 junctions are relatively enriched in pediatric adrenocortical tumors (ACT). Nevertheless, family histories of cancer compatible with classic Li-Fraumeni syndrome are rarely seen in these patients.