Molecular, histologic, and clinical characterization of methylation class pleomorphic xanthoastrocytoma: An analysis of 469 tumors.

Background: Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM).

Methods: To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.

Two unique cases of eosinophilic granulomatosis with polyangiitis in childhood treated with anti-interleukin-5 therapy: infantile-onset and submandibular salivary gland involvement.

Background: ANCA-associated vasculitis is a systemic autoimmune disease involving small- and medium-sized blood vessels. Eosinophilic granulomatosis with polyangiitis (EGPA, previously Churg Strauss Syndrome) is the least common form in childhood with few cases reported. We present two unique pediatric cases, both of which were treated with anti-interleukin-5 therapy.

Sinonasal Teratocarcinosarcoma: A Case Report in a 13-Year-Old Male.

Teratocarcinosarcoma is rare malignant sinonasal neoplasm with immature and malignant endodermal, mesodermal, and neuroepithelial elements resembling immature teratoma, commonly with loss or activating mutation. The carcinoma component may be either squamous or adenocarcinoma and the mesenchymal component may be composed of spindle cells, cartilage, bone, smooth muscle, or skeletal muscle. Due to the uncommon nature of this malignancy, there are frequently diagnostic difficulties that result in management problems.

Spatial Profiling Reveals Equivalence-Derived Molecular Signatures of Brain Mimicry and Adaptation in Breast Cancer Brain Metastases.

Brain metastases (BrMets), common for advanced-stage breast cancer patients, are associated with poor median survival and accompanied by severe neurologic decline. Halting the progression of breast cancer brain metastases (BCBMs) may require modulation of the tumor microenvironment (TME), yet little is known about the impact of the primary breast TME on brain tropism, or how, once there, metastatic breast cancer cells coexist with brain-resident cells (e.g.

Are Dinucleotide Alterations Definitional for Myxoid Glioneuronal Tumor? Report of p. K385L Mutation in a Neonatal High-Grade Glioma.

Tumors are increasingly defined by molecular alterations but approach to cases with discordant histologic and molecular features is unclear. Myxoid glioneuronal tumor (MGNT), histologically similar to dysembryoplastic neuroepithelial tumor (DNET), is characterized by dinucleotide mutations in gene (K385L or K385I). Here, we report K385L mutation in a neonatal high-grade glioma.

Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus-Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study.

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer-HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus-associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies.

Perivascular Epithelioid Cell-Family Tumors in Children, Adolescents, and Young Adults: Clinicopathologic Features in 70 Cases.

Context.—: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors of uncertain histogenesis expressing smooth muscle and melanocytic markers. The clinicopathologic spectrum in young patients is not well documented.

ACAA2 is a novel molecular indicator for cancers with neuroendocrine phenotype.

Background: Neuroendocrine phenotype is commonly associated with therapy resistance and poor prognoses in small-cell neuroendocrine cancers (SCNCs), such as neuroendocrine prostate cancer (NEPC) and small-cell lung cancer (SCLC). Expression levels of current neuroendocrine markers exhibit high case-by-case variability, so multiple markers are used in combination to identify SCNCs. Here, we report that ACAA2 is elevated in SCNCs and is a potential molecular indicator for SCNCs.

Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.

Brain metastases represent an important clinical problem for patients with small-cell lung cancer (SCLC). However, the mechanisms underlying SCLC growth in the brain remain poorly understood. Here, using intracranial injections in mice and assembloids between SCLC aggregates and human cortical organoids in culture, we found that SCLC cells recruit reactive astrocytes to the tumour microenvironment.

When a dermatopathologist encounters the ultra-rare: A case series of superficial soft tissue/cutaneous myxopapillary ependymomas.

Myxopapillary ependymoma (MPE) is an uncommon variant of ependymoma, almost exclusively seen in conus medullaris or filum terminale. MPE can be diagnostically challenging, especially when arising extra-axially. Here we report 5 cases of superficial soft tissue/cutaneous MPE, identified across three tertiary institutions.

Vascular anomaly, lipoma, and polymicrogyria associated with schizencephaly: developmental and diagnostic insights. Illustrative case.

Background: Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain "tumors.

Purification and characterization of human neural stem and progenitor cells.

The human brain undergoes rapid development at mid-gestation from a pool of neural stem and progenitor cells (NSPCs) that give rise to the neurons, oligodendrocytes, and astrocytes of the mature brain. Functional study of these cell types has been hampered by a lack of precise purification methods. We describe a method for prospectively isolating ten distinct NSPC types from the developing human brain using cell-surface markers.

Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Progression.

Neural activity is increasingly recognized as a critical regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses, while perisynaptic neurotransmitter signaling drives breast cancer brain metastasis growth. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression.

Balamuthia mandrillaris brain infection: a rare cause of a ring-enhancing central nervous system lesion. Illustrative case.

Background: An 80-year-old man presented with subacute mental status change, dizziness, and left-sided vision loss. Magnetic resonance imaging demonstrated a ring-enhancing right parietooccipital lesion.

Observations: Biopsy and laboratory testing demonstrated an amoebic Balamuthia mandrillaris infection.

Trichodysplasia Spinulosa Polyomavirus Endothelial Infection, California, USA.

We describe 3 patients in California, USA, with trichodysplasia spinulosa polyomavirus (TSPyV) infection of endothelium after steroid administration. We detected TSPyV RNA in tissue specimens by in situ hybridization, which revealed localization to endothelial cells. These cases suggest that diseases associated with endothelial inflammation could be associated with TSPyV infection.

Preferentially Expressed Antigen in Melanoma Immunohistochemistry Labeling in Uveal Melanomas.

Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and despite treatment of the primary tumor, approximately 15%-50% of patients will develop metastatic disease. Based on gene expression profiling (GEPs), UM can be categorized as Class 1A (low metastatic risk), Class 1B (intermediate metastatic risk), or Class 2 (high metastatic risk). PReferentially expressed Antigen in MElanoma (PRAME) status is an independent prognostic UM biomarker and a potential target for immunotherapy in metastatic UM.

Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11.

GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics.

Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm that manifests histologically as a lobular proliferation of stellate to spindle-shaped cells in a myxoid background, exhibiting morphologic overlap with other cartilaginous and myxoid tumors of bone. CMF is characterized by recurrent genetic rearrangements that place the glutamate receptor gene GRM1 under the regulatory control of a constitutively active promoter, leading to increased gene expression. Here, we explore the diagnostic utility of GRM1 immunohistochemistry as a surrogate marker for GRM1 rearrangement using a commercially available monoclonal antibody in a study of 230 tumors, including 30 CMF cases represented by 35 specimens.

The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression.

Post-operative Stereotactic Radiosurgery of Malignant Melanotic Schwannoma.

Melanotic schwannoma is an extremely rare schwannoma variant with malignant potential, demonstrating high local and distant recurrence. Given the paucity of data, recommended treatment with localized disease is radical resection, with the unclear benefit of adjuvant therapy. We present a case of an 18-year-old female with no past medical history or genetic syndromes who underwent margin-positive resection of an S1 nerve root melanotic schwannoma followed by adjuvant stereotactic radiosurgery (SRS).

Initial experience with label-free stimulated Raman scattering microscopy for intraoperative assessment of peripheral nerves.

Background: During nerve repair, an intraoperative assessment of the quality of the nerve stump is critically important for achieving a good outcome. Frozen section analysis of osmium-hematoxylin stained sections has not been adopted at many centers, including ours. This has left us with bread-loafing the nerve and visually assessing for healthy fascicles.