Brain Pathology

ALT Integrated molecular profiling reveals biological heterogeneity among primary meningeal melanocytic tumors, identifying intermediate-grade PMMT subgroups with distinct recurrence risk. Molecular alterations including SF3B1 mutations and chromosome 8q gains support prognostic stratification, while PRKAR1A alterations and chromosome 17/21q losses aid distinction from MMNSTs.

ALT (A) H&E-stained section (original magnification 400×) shows sheets of large, polygonal-to-round, moderately pleomorphic, epithelioid cells with prominent nucleoli, vesicular chromatin, increased nuclear-to-cytoplasmic ratio, distinct cell borders, brisk mitotic activity, and focal necrosis. Immunohistochemistry demonstrates patchy membranous positivity for EMA (B, 400×), focal positivity for CAM5.2 (C, 400×), and SMA (D, 400×), and complete loss of nuclear INI1/SMARCB1 expression (E, 400×).

ALT Aquaporin-4 antibody-positive neuromyelitis spectrum disorder is characterized by large tissue destructive lesions in medulla, spinal cord, and optic nerves, with only partial recovery from clinical symptoms, and by lesions with very little tissue destruction and mostly complete recovery from clinical symptoms, as seen in the area postrema. Immunohistochemical and spatial transcriptomic analysis revealed a dampened innate immune response in the area postrema, correlating with the strong expression of aldehyde dehydrogenase 1 family member a2 at this site.

ALT We describe a novel adult-onset myopathy with autophagic vacuoles and characteristic features of ceroid lipofuscinosis associated with biallelic CLN8 variants, seizures, and muscle weakness. Autophagosomal/lysosomal deposition of curvilinear, autofluorescent material containing the mitochondrial adenosine triphosphate (ATP) synthase membrane subunit c locus 3/subunit c of mitochondrial ATP synthase (ATP5MC3/SCMAS) protein and an increase of autophagic markers in muscle tissue is shown by combined diagnostic methods.

ALT How glioblastoma organoids are made shapes what they become. Fragment-based cultures preserve extracellular matrix networks, cellular diversity, and primary tumor identity, whereas dissociation-based cultures shift toward growth-adapted states and simplified microenvironments.

ALT A meaningful subset of IDH-mutant astrocytoma harbors ATRX missense variants that retain ATRX IHC immunoreactivity yet exhibit functional ALT activation, supporting the biologic relevance of these missense mutations.

ALT Sagittal T1-weighted post-contrast MRI scan of the spine showed a solid, intradural, extramedullary mass at the L1 level (white arrow). Inset: Axial PET-CT demonstrated increased tracer uptake in the spinal canal.

ALT Gross examination revealed a circumscribed, lobular mass with attached segment of filum terminale (A, scale bar: 5 mm). Smear preparation revealed markedly pleomorphic nuclei and fibrillary cellular processes (B). Histologic evaluation revealed a circumscribed glial neoplasm composed of cells arranged in lobules and vague fascicles (C). Tumor cells were markedly pleomorphic with enlarged nuclei, hyperchromatic chromatin, and nuclear pseudoinclusions (D). By immunohistochemistry, the tumor cells were diffusely positive for GFAP (E), while Olig2 labeled only occasional interspersed cells (E, inset). EMA highlighted rare perinuclear dot-like positivity (F) and tumor cells were strongly positive for HOXB13 (F, inset).