{
  "passages": [
    {
      "id": "cns-astrocytoma-idh-mutant-grading-review",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:astrocytoma-idh-mutant"
      ],
      "topic": "grading",
      "he_observable": true,
      "text": "A 2026 review describes IDH-mutant astrocytoma as one entity spanning CNS WHO grades 2 to 4. Grade 2 shows diffuse infiltration with mild cellularity and nuclear atypia. Grade 3 shows increased cellularity, cytologic atypia and mitotic activity. Grade 4 is set by high-grade histology (microvascular proliferation and/or necrosis) or by homozygous CDKN2A/B deletion, which overrides the microscopic appearance, so a tumour that looks lower grade on H&E can still be grade 4. The review also notes that survival overlaps between grades 2 and 3, so the histologic grade is an imperfect separator.",
      "source_id": "pmc13042621",
      "locator": "Introduction; Histopathologic Features and Grading Criteria",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:astrocytoma-idh-mutant",
          "r": "grade_range",
          "o": "CNS WHO grade 2 to 4",
          "he_observable": true
        },
        {
          "s": "cns:astrocytoma-idh-mutant",
          "r": "has_feature",
          "o": "cns:cdkn2a-homozygous-deletion-grade-4",
          "he_observable": false
        }
      ]
    },
    {
      "id": "cns-gbm-histological-vs-molecular",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:gbm-idh-wt",
        "cns:anaplastic-astrocytoma-idh-wt-legacy"
      ],
      "topic": "definition",
      "he_observable": true,
      "text": "A real-world series using the 2021 WHO classification separates histological GBM, diagnosed by necrosis or microvascular proliferation, from molecular GBM. Molecular GBM is an IDH-wildtype diffuse astrocytic tumour that lacks these histologic features and would otherwise be grade 2 or 3, but is grade 4 because of TERT promoter mutation, EGFR amplification or combined chromosome 7 gain and 10 loss. On H&E a molecular GBM therefore looks like a lower-grade astrocytoma; the molecular criteria cannot be read from the slide. In the series molecular GBMs showed less contrast enhancement and less intratumoral necrosis on imaging, and a median survival of 15.6 versus 11.4 months for histological GBM, which was not statistically significant.",
      "source_id": "pmc10358772",
      "locator": "Introduction; Abstract",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:gbm-idh-wt",
          "r": "has_feature",
          "o": "cns:necrosis-or-microvascular-proliferation",
          "he_observable": true
        },
        {
          "s": "cns:gbm-idh-wt",
          "r": "has_feature",
          "o": "cns:tert-egfr-chr7-10-molecular-criteria",
          "he_observable": false
        },
        {
          "s": "cns:gbm-idh-wt",
          "r": "distinguished_from",
          "o": "cns:anaplastic-astrocytoma-idh-wt-legacy",
          "he_observable": false,
          "feature": "cns:molecular-grade-4-criteria-without-necrosis-or-vascular-proliferation"
        }
      ]
    },
    {
      "id": "cns-aa-idh-wt-histologic-grade-outcome",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:anaplastic-astrocytoma-idh-wt-legacy",
        "cns:gbm-idh-wt"
      ],
      "topic": "labeling_note",
      "he_observable": true,
      "text": "A multicentre series of 157 patients with histologically diagnosed grade 2 to 3 IDH-wildtype astrocytoma (78.3% anaplastic astrocytoma grade 3, 21.7% diffuse astrocytoma grade 2) titles these tumours as CNS WHO grade 4 glioma, which matches the 2021 molecular-GBM rule described in the other IDH-wildtype passage. Overall survival did not differ between histologic grades 2 and 3, and EGFR amplification and TERT promoter mutation were associated with shorter overall survival. So the legacy label anaplastic astrocytoma IDH-wildtype names a histologic pattern that carries glioblastoma-like behaviour when the molecular criteria are met, and the molecular result cannot be seen on H&E.",
      "source_id": "pmc10978634",
      "locator": "Abstract; Results",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:anaplastic-astrocytoma-idh-wt-legacy",
          "r": "distinguished_from",
          "o": "cns:gbm-idh-wt",
          "he_observable": true,
          "feature": "cns:no-necrosis-or-microvascular-proliferation-histology"
        }
      ]
    },
    {
      "id": "cns-medulloblastoma-histology-vs-molecular-group",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:medulloblastoma"
      ],
      "topic": "cytomorphology",
      "he_observable": true,
      "text": "A review of adult medulloblastoma lists four histological patterns (classic, desmoplastic/nodular, extensive nodularity, large cell/anaplastic) alongside four molecular types (WNT-activated, SHH-activated TP53-wildtype, SHH-activated TP53-mutant, non-WNT/non-SHH, which includes groups 3 and 4). Within non-WNT/non-SHH tumours classic morphology is the most common, and one subgroup has more large cell/anaplastic tumours; metastatic disease at presentation is relatively frequent in several subgroups. Histology does not by itself assign the molecular type, which in practice rests on immunophenotype and genetics (non-WNT/non-SHH is YAP1 and GAB1 negative in the review's table), so an H&E-only call between non-WNT/non-SHH and the other types is a limitation, not a rule.",
      "source_id": "pmc9367316",
      "locator": "Introduction; 2.5 Non-WNT/Non-SHH-MB; Table 1",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:medulloblastoma",
          "r": "has_feature",
          "o": "cns:classic-morphology-in-non-wnt-non-shh",
          "he_observable": true
        },
        {
          "s": "cns:medulloblastoma",
          "r": "has_feature",
          "o": "cns:yap1-gab1-negative-immunophenotype",
          "he_observable": false
        }
      ]
    },
    {
      "id": "cns-lch-he-limitation",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:lch"
      ],
      "topic": "differential",
      "he_observable": true,
      "text": "A 2025 review gives the H&E hallmark of Langerhans cell histiocytosis as Langerhans cells with nuclear grooves and abundant eosinophilic cytoplasm, often with eosinophils, lymphocytes and multinucleated giant cells, and defines it by CD1a, S100 and langerin staining. It lists Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, other non-Langerhans histiocytoses and histiocytic sarcoma as lesions with overlapping histology that make differential diagnosis a real challenge. None of these is a class in the EBRAINS label space, and no H&E-only rule against another EBRAINS class is given, so none is invented here.",
      "source_id": "pmc11861498",
      "locator": "Introduction; Langerhans Cell Histiocytosis",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:lch",
          "r": "has_feature",
          "o": "cns:nuclear-grooves-eosinophilic-cytoplasm",
          "he_observable": true
        },
        {
          "s": "cns:lch",
          "r": "has_feature",
          "o": "cns:cd1a-s100-langerin-positivity",
          "he_observable": false
        }
      ]
    },
    {
      "id": "cns-metastasis-infiltration-caveat",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:metastasis",
        "cns:gbm-idh-wt"
      ],
      "topic": "differential",
      "he_observable": true,
      "text": "A 2026 systematic review of intraoperative imaging at the brain-metastasis interface says brain metastases are traditionally viewed as well-demarcated, but histopathological evidence shows metastatic cells can infiltrate beyond the contrast-enhancing margin into brain parenchyma, and infiltrative growth patterns were reported as common in the MetInfilt trial. A sharp border is therefore a tendency that supports metastasis over a diffuse glioma, not an absolute rule, and an infiltrative edge does not exclude metastasis.",
      "source_id": "pmc13301885",
      "locator": "Abstract; 3.2 Intraoperative CLE Imaging and Tumor Margin Visualization",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:metastasis",
          "r": "has_feature",
          "o": "cns:infiltrative-edge-in-a-subset",
          "he_observable": true
        }
      ]
    },
    {
      "id": "cns-oligodendroglioma-like-pitfall",
      "datasets": [
        "ebr-coarse30"
      ],
      "entities": [
        "cns:oligodendroglioma",
        "cns:astrocytoma-idh-mutant",
        "cns:metastasis"
      ],
      "topic": "differential",
      "he_observable": true,
      "text": "A reappraisal of 23 non-oligodendroglial CNS tumours that were all read as oligodendroglioma-like found small monotonous round nuclei in all 23, perinuclear halos in 18, chicken-wire capillaries in 10, calcification in 9 and a microcystic background in 5. The final diagnoses were IDH-mutant astrocytoma (9), dysembryoplastic neuroepithelial tumour (3), central neurocytoma (3), metastatic renal cell carcinoma (2) and several others. The authors conclude that oligodendroglioma-like morphology is a pitfall pattern rather than a specific diagnosis, and that IDH and 1p/19q testing is what defines oligodendroglioma, so halos and chicken-wire vessels alone do not separate it from IDH-mutant astrocytoma.",
      "source_id": "pmc13564585",
      "locator": "Abstract; 3.2 Oligodendroglioma-like Histomorphological Features",
      "quote_type": "paraphrase",
      "facts": [
        {
          "s": "cns:oligodendroglioma",
          "r": "has_feature",
          "o": "cns:perinuclear-halo-nonspecific",
          "he_observable": true
        },
        {
          "s": "cns:oligodendroglioma",
          "r": "distinguished_from",
          "o": "cns:astrocytoma-idh-mutant",
          "he_observable": false,
          "feature": "cns:idh-mutation-with-1p-19q-codeletion"
        }
      ]
    }
  ]
}