Blame for docs/rubric.v2.json

{
 "_meta": {
  "built": "2026-10-01",
  "version": "v2",
  "claims": "CONSISTENCY WITH CITED FREE SOURCES ONLY. Not pathological correctness; no pathologist reviewed anything. A feature is listed only if a verbatim quote was re-found in a local source snapshot.",
  "usable_rule": "usable = status verified = >=2 independent source groups (bracs-paper and bracs-paper-arxiv count as one) with re-found quotes, or one T1 (guideline) source. single-source and weak items are never usable; weak = hedged, inferred or sources disagree.",
  "label_status": "verified if >=2 usable expected features, single-source if >=1 non-weak expected feature, else weak",
  "tiers": "tier per source from merged-v2/source-tiers.json (T1 guideline, T2 peer reviewed, T3 community)",
  "patches_vs_v1": [
   "Secretory meningioma: expected psammoma removed (sources describe pseudopsammoma bodies, a different structure)",
   "Secretory meningioma: excluded pleomorphism_nonmild downgraded to single-source (case report only)",
   "Fibrous meningioma: excluded whorls made weak",
   "FEA: columnar_cells second quote (paper title only) dropped -> single-source"
  ],
  "independence_note": "Independence = distinct source ids except the BRACS journal/arXiv pair. Two Libre Pathology pages count as two sources (both T3): flagged by the tier field on each evidence row."
 },
 "concept_terms": {
  "necrosis": [
   "\\bnecro(?:sis|tic)\\b",
   "comedonecrosis"
  ],
  "vascular_invasion": [
   "(?:lympho)?vascular invasion",
   "lymphatic invasion",
   "angioinvasion",
   "invasion of (?:the )?(?:blood )?vessels",
   "tumou?r cells? (?:are )?(?:seen )?(?:within|in) (?:the )?(?:blood )?vessels"
  ],
  "calcification": [
   "calcif"
  ],
  "desmoplasia": [
   "desmoplas"
  ],
  "pleomorphism_any": [
   "pleomorph",
   "\\batypi",
   "anaplas"
  ],
  "pleomorphism_marked": [
   "(?:marked|severe|significant|high[- ]grade|prominent|pronounced|bizarre|extreme|highly)\\s+(?:nuclear\\s+)?(?:pleomorph|atypi|anaplas)",
   "(?:highly|markedly|severely)\\s+(?:pleomorphic|atypical)",
   "(?:pleomorph|atypi)\\w*\\s+(?:is|are)\\s+(?:marked|severe|prominent)"
  ],
  "mitoses_any": [
   "mitos",
   "mitotic",
   "cell division"
  ],
  "mitoses_high": [
   "(?:brisk|high|frequent|numerous|marked|increased|elevated|abundant)\\s+(?:rate of\\s+)?(?:mitotic|mitoses|mitosis|cell division)",
   "(?:mitotic|mitoses)\\s+(?:activity|figures|count|rate)?\\s*(?:is|are)\\s+(?:brisk|high|frequent|numerous|marked|increased|elevated)"
  ],
  "stromal_invasion": [
   "infiltrat\\w*\\s+(?:into\\s+)?(?:the\\s+)?(?:surrounding\\s+|adjacent\\s+)?(?:breast\\s+)?stroma",
   "invad\\w*\\s+(?:into\\s+)?(?:the\\s+)?(?:surrounding\\s+|adjacent\\s+)?(?:breast\\s+)?stroma",
   "stromal (?:invasion|infiltration)",
   "invasion (?:of|into) (?:the )?(?:surrounding )?stroma",
   "epithelial cells infiltrat\\w+",
   "tumou?r cells (?:are )?infiltrat\\w+",
   "invasive (?:growth|pattern|carcinoma|front)",
   "infiltrative (?:growth|pattern)"
  ],
  "glandular": [
   "gland",
   "\\bacin(?:ar|i|us)",
   "tubul",
   "lepidic"
  ],
  "mucin": [
   "mucin",
   "mucinous"
  ],
  "prominent_nucleoli": [
   "(?:prominent|conspicuous) nucleol"
  ],
  "lepidic_papillary_pattern": [
   "lepidic",
   "micropapillary",
   "papillary (?:pattern|architecture|growth)"
  ],
  "keratinization": [
   "keratiniz",
   "keratin\\b",
   "keratinis"
  ],
  "keratin_pearls": [
   "keratin pearl",
   "squamous pearl"
  ],
  "intercellular_bridges": [
   "intercellular bridge",
   "intercellular junction"
  ],
  "nests": [
   "\\bnests?\\b",
   "nest-like"
  ],
  "solid_sheets": [
   "solid (?:growth|pattern|sheets?|areas)",
   "\\bsheets? of\\b",
   "in sheets",
   "and sheets"
  ],
  "cribriform": [
   "cribriform"
  ],
  "papillary": [
   "papillary",
   "papillae"
  ],
  "in_situ": [
   "\\bin situ\\b",
   "\\bdcis\\b",
   "confined to (?:the )?(?:duct|basement)"
  ],
  "normal_breast": [
   "\\bnormal (?:breast|mammary|glandular|ductal|lobular|duct|lobule|epithelium)\\b",
   "\\bunremarkable\\b",
   "\\bbenign (?:breast|glandular|ductal)\\b"
  ],
  "benign_lesion_terms": [
   "\\bcyst",
   "apocrine",
   "fibrocystic",
   "ectasia",
   "sclerosing adenosis",
   "papilloma",
   "fibroadenoma",
   "squamous metaplasia",
   "radial scar",
   "mastitis"
  ],
  "epithelial_hyperplasia": [
   "hyperplasi",
   "multilayer",
   "streaming",
   "stratif",
   "slit-like"
  ],
  "columnar_cells": [
   "columnar"
  ],
  "apical_snouts": [
   "apical snout",
   "snouting"
  ],
  "monomorphic_cells": [
   "monomorph",
   "monotonous",
   "uniform (?:cells|nuclei)",
   "evenly spaced"
  ],
  "partial_duct_involvement": [
   "partial(?:ly)? (?:fill|involv)",
   "only partially"
  ],
  "fills_entire_duct": [
   "(?:fill|filling|distend)\\w* (?:the )?(?:entire|whole|complete) (?:duct|lumen)",
   "multiple (?:adjacent )?(?:duct|ductal)"
  ],
  "microvascular_prolif": [
   "microvascular",
   "vascular proliferation",
   "endothelial proliferation",
   "glomeruloid"
  ],
  "fibrillary_background": [
   "fibrillary",
   "fibrillar"
  ],
  "diffuse_infiltration": [
   "diffuse(?:ly)? infiltrat",
   "infiltrat\\w+ (?:the )?(?:adjacent|surrounding)? ?(?:brain|parenchyma|neuropil)"
  ],
  "circumscribed": [
   "circumscribed",
   "well[- ]demarcated",
   "sharply (?:demarcated|defined)",
   "well[- ]defined (?:border|margin)",
   "sharp border"
  ],
  "perinuclear_halo": [
   "perinuclear (?:halo|clearing)",
   "\\bhalos?\\b",
   "\\bhaloes\\b",
   "fried[- ]egg"
  ],
  "chicken_wire": [
   "chicken[- ]wire",
   "delicate (?:capillary|vascular)",
   "capillary network"
  ],
  "rosenthal": [
   "rosenthal"
  ],
  "eosinophilic_granular_bodies": [
   "eosinophilic granular"
  ],
  "biphasic": [
   "biphasic",
   "sarcomatous",
   "mesenchymal component"
  ],
  "spindle_cells": [
   "spindle"
  ],
  "whorls": [
   "whorl",
   "onion[- ]bulb"
  ],
  "psammoma": [
   "psammoma"
  ],
  "antoni_verocay": [
   "antoni",
   "verocay"
  ],
  "rosettes": [
   "rosette"
  ],
  "small_round_cells": [
   "small round",
   "small,? round",
   "round blue"
  ],
  "dysplastic_neurons": [
   "dysplastic neuron",
   "ganglion cell",
   "neuronal component"
  ],
  "lymphoid_perivascular": [
   "lymphoid",
   "lymphoma",
   "angiocentric",
   "perivascular cuff"
  ],
  "clear_cells": [
   "clear cell",
   "clear cytoplasm",
   "vacuolated"
  ],
  "vascular_network": [
   "capillary network",
   "vascular network",
   "prominent vessels",
   "rich vascular",
   "hyalini[sz]ed vessels",
   "thick-walled",
   "staghorn",
   "dense capillary"
  ],
  "staghorn_collagen": [
   "staghorn",
   "hemangiopericytoma-like",
   "patternless",
   "keloid"
  ],
  "adipocytes": [
   "adipo",
   "fat cells",
   "mature fat"
  ],
  "wet_keratin_reticulum": [
   "wet keratin",
   "stellate reticulum",
   "palisading columnar"
  ],
  "langerhans_grooves": [
   "nuclear groove",
   "coffee[- ]bean",
   "langerhans",
   "reniform"
  ],
  "eosinophils": [
   "eosinophil(?:s|ic infiltrate)"
  ],
  "glial_processes": [
   "cytoplasmic processes",
   "glial processes"
  ],
  "sheeting": [
   "sheeting",
   "loss of lobular"
  ],
  "vascular_channels": [
   "vascular channels",
   "ectatic",
   "endothelium",
   "back-to-back"
  ],
  "pseudoinclusions": [
   "pseudoinclusion",
   "nuclear clearing",
   "syncytial"
  ]
 },
 "derived_concepts": {
  "pleomorphism_nonmild": {
   "base": "pleomorphism_any",
   "downgrade_regex_excluded": "\\b(?:mild|minimal|slight|minor|little|low[- ]grade|bland|uniform|no significant)\\b"
  },
  "mitoses_nonlow": {
   "base": "mitoses_any",
   "downgrade_regex_excluded": "\\b(?:infrequent|rare|rarely|few|low|scant|sparse|inconspicuous|minimal|occasional|uncommon|not significant|slow)\\b"
  }
 },
 "datasets": {
  "tcga-nsclc": {
   "labels": {
    "LUAD": {
     "entity": "lung:LUAD",
     "expected_features": [
      {
       "concept": "glandular",
       "description": "glandular / acinar architecture",
       "evidence": [
        {
         "source_id": "librepath-luad",
         "tier": "T3",
         "quote": "Acinar - berry-shaped glands, smaller than lung acini",
         "context": "Acinar - berry-shaped glands, smaller than lung acini."
        },
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "cases exhibited a combination of acinar (77.1%) and solid (85.7%) arrangements",
         "context": "95 Adenocarcinoma Morphologically, most adenocarcinoma cases exhibited a combination of acinar (77.1%) and solid (85.7%) arrangements in varying proportions."
        },
        {
         "source_id": "pmc12153718",
         "tier": "T2",
         "quote": "The acinar pattern is the most prevalent architectural pattern",
         "context": "The acinar pattern is the most prevalent architectural pattern and consists of round-to-oval-shaped malignant glands invading the fibrous stroma [3,8]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "lepidic_papillary_pattern",
       "description": "lepidic / papillary / micropapillary growth patterns",
       "evidence": [
        {
         "source_id": "pmc11729388",
         "tier": "T2",
         "quote": "six major growth patterns of nonmucinous lung adenocarcinoma: lepidic, acinar, papill",
         "context": "The 2021 WHO classification of lung cancer recognizes six major growth patterns of nonmucinous lung adenocarcinoma: lepidic, acinar, papillary, micropapillary, solid, and complex glandular [4]."
        },
        {
         "source_id": "librepath-luad",
         "tier": "T3",
         "quote": "Micropapillary - nipple shaped projections without fibrovascular cores",
         "context": "Micropapillary - nipple shaped projections without fibrovascular cores."
        },
        {
         "source_id": "pmc12153718",
         "tier": "T2",
         "quote": "lepidic, acinar, papillary, micropapillary, solid, and complex glandular patterns",
         "context": "In 2011, a new classification based on six major architectural patterns was introduced for invasive and non-mucinous-LUAD (NM-LUAD), including lepidic, acinar, papillary, micropapillary, solid, and complex glandular patterns (CGPs; cribriform and fused gland) [3,4]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mucin",
       "description": "mucin vacuoles in cytoplasm",
       "evidence": [
        {
         "source_id": "librepath-luad",
         "tier": "T3",
         "quote": "Abundant cytoplasm - classically with mucin vacuoles",
         "context": "Abundant cytoplasm - classically with mucin vacuoles."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "prominent_nucleoli",
       "description": "prominent / conspicuous nucleoli",
       "evidence": [
        {
         "source_id": "librepath-luad",
         "tier": "T3",
         "quote": "often conspicuous nucleoli",
         "context": "abundant cytoplasm (classically with mucin vacuoles), often conspicuous nucleoli, +/-nuclear pseudoinclusions"
        },
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "prominent nucleoli in 82.9%",
         "context": "The tumor cells displayed vacuolated to eosinophilic cytoplasm in 51.4% of cases, vesicular nuclei in 51.4%, and prominent nucleoli in 82.9%, all of which were statistically significant (p < 0.0001) (Fig."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "intercellular_bridges",
       "description": "intercellular bridges (squamous feature)",
       "evidence": [
        {
         "source_id": "librepath-luad",
         "tier": "T3",
         "quote": "Lack of intercellular bridges",
         "context": "Negatives: Lack of intercellular bridges."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "explicit absence statement in one source only; pmc13116887 and pmc13368955 define SCC by bridges (supporting inference, not an absence statement)"
      },
      {
       "concept": "keratinization",
       "description": "keratinization / keratin pearls (squamous feature)",
       "evidence": [
        {
         "source_id": "pmc13116887",
         "tier": "T2",
         "quote": "evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges",
         "context": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation, evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges."
        },
        {
         "source_id": "pmc13368955",
         "tier": "T2",
         "quote": "characterized by keratinization, intercellular bridges, or squamous differentiation",
         "context": ": Squamous cell carcinoma, Subepithelial, Lung carcinoma, Subsolid tumour Introduction Squamous cell carcinoma (SCC) is a malignant epithelial tumour characterized by keratinization, intercellular bridges, or squamous differentiation at immunohistochemistry (IHC) [1]. SCC, the second most common subtype of lung cancer, account for 20% of all lung carcinomas [2] and 30% of non-small cell lung cancers [3]. At CT-scan, lung SCC usua"
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "absence in adenocarcinoma is inferred from SCC-defining statements; no snapshot says adenocarcinoma lacks keratin; adenosquamous tumours exist",
       "note": null
      },
      {
       "concept": "keratin_pearls",
       "description": "keratin pearls (squamous feature)",
       "evidence": [
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "keratin pearls (78.94%)",
         "context": "Among the 56 SCC cases, classic histopathologic features were noted, including keratin pearls (78.94%), intercellular bridges (75.43%), and individual cell keratinization (76.68%), all statistically significant (p < 0.005), consistent with SCC morphology (34)."
        },
        {
         "source_id": "pmc13116887",
         "tier": "T2",
         "quote": "formation of keratin pearls",
         "context": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation, evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "same inference as keratinization",
       "note": null
      }
     ],
     "source_ids": [
      "librepath-luad",
      "pmc11729388",
      "pmc12153718",
      "pmc12308192",
      "pmc13116887",
      "pmc13368955"
     ],
     "status": "verified",
     "compat_dx": [
      "adeno",
      "nsclc_nos",
      "carcinoma_unspec"
     ],
     "ambiguous_dx": [
      "papillary_carcinoma",
      "adenosquamous"
     ],
     "dx_basis": [
      {
       "source_id": "librepath-luad",
       "quote": "Adenocarcinoma is the non-smoker tumour"
      }
     ]
    },
    "LUSC": {
     "entity": "lung:LUSC",
     "expected_features": [
      {
       "concept": "keratinization",
       "description": "keratinization",
       "evidence": [
        {
         "source_id": "pmc13116887",
         "tier": "T2",
         "quote": "evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges",
         "context": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation, evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges."
        },
        {
         "source_id": "pmc13368955",
         "tier": "T2",
         "quote": "malignant epithelial tumour characterized by keratinization, intercellular bridges",
         "context": "/s00428-026-04524-z.Keywords: Squamous cell carcinoma, Subepithelial, Lung carcinoma, Subsolid tumour Introduction Squamous cell carcinoma (SCC) is a malignant epithelial tumour characterized by keratinization, intercellular bridges, or squamous differentiation at immunohistochemistry (IHC) [1]. SCC, the second most common subtype of lung cancer, account for 20% of all lung carcinomas [2] and 30% of non-small cell lung cancers ["
        },
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "individual cell keratinization (76.68%)",
         "context": "Among the 56 SCC cases, classic histopathologic features were noted, including keratin pearls (78.94%), intercellular bridges (75.43%), and individual cell keratinization (76.68%), all statistically significant (p < 0.005), consistent with SCC morphology (34)."
        },
        {
         "source_id": "librepath-lung-scc",
         "tier": "T3",
         "quote": "Grade 1 (well differentiated) - extensive keratinization",
         "context": "PMID = 7092385 }}</ref> The grading system loosely defined by the CAP protocol (version 3.4.0.0):<ref name=cap_protocol_v3400/> Grade 1 (well differentiated) - extensive keratinization."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "non-keratinizing SCC exists (wp-lung-scc), so absence of keratin is not contradictory"
      },
      {
       "concept": "keratin_pearls",
       "description": "keratin pearls",
       "evidence": [
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "keratin pearls (78.94%)",
         "context": "Among the 56 SCC cases, classic histopathologic features were noted, including keratin pearls (78.94%), intercellular bridges (75.43%), and individual cell keratinization (76.68%), all statistically significant (p < 0.005), consistent with SCC morphology (34)."
        },
        {
         "source_id": "pmc13116887",
         "tier": "T2",
         "quote": "formation of keratin pearls",
         "context": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation, evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges."
        },
        {
         "source_id": "wp-lung-scc",
         "tier": "T3",
         "quote": "showing keratin pearls and cell junctions",
         "context": "On such exams, these tumors range from well differentiated, showing keratin pearls and cell junctions, to anaplastic, with only minimal residual squamous-cell features."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "intercellular_bridges",
       "description": "intercellular bridges",
       "evidence": [
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "Intercellular bridges were present in 75.4%",
         "context": "Intercellular bridges were present in 75.4%, and hyperchromatic nuclei were identified in 92.9% of cases, all demonstrating high statistical significance (p < 0.0001)."
        },
        {
         "source_id": "pmc13116887",
         "tier": "T2",
         "quote": "identifiable intercellular bridges",
         "context": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation, evidenced by keratinization, formation of keratin pearls, and identifiable intercellular bridges."
        },
        {
         "source_id": "pmc13368955",
         "tier": "T2",
         "quote": "keratinization, intercellular bridges",
         "context": "arcinoma, Subepithelial, Lung carcinoma, Subsolid tumour Introduction Squamous cell carcinoma (SCC) is a malignant epithelial tumour characterized by keratinization, intercellular bridges, or squamous differentiation at immunohistochemistry (IHC) [1]. SCC, the second most common subtype of lung cancer, account for 20% of all lung carcinomas [2] and 30% of non-small cell lung cancers ["
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "nests",
       "description": "nest-like / nested growth",
       "evidence": [
        {
         "source_id": "pmc12308192",
         "tier": "T2",
         "quote": "nest-like arrangement of tumor cells (100%)",
         "context": "25% Squamous Cell Carcinoma Most squamous cell carcinoma cases showed a nest-like arrangement of tumor cells (100%), with eosinophilic cytoplasm suggestive of individual cell keratinization observed in 76.6% of cases."
        },
        {
         "source_id": "pmc11505874",
         "tier": "T2",
         "quote": "categorization into large nests",
         "context": "The assessment of tumor cell arrangement included the categorization into large nests (≥5 tumor cells), small nests (2-4 tumor cells), and single-cell invasion."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-lung-scc",
      "pmc11505874",
      "pmc12308192",
      "pmc13116887",
      "pmc13368955",
      "wp-lung-scc"
     ],
     "status": "verified",
     "note_excluded": "No snapshot states that squamous carcinoma lacks glandular or mucin features, so no excluded H&E feature is listed; only diagnosis-level incompatibility (adenocarcinoma) applies.",
     "compat_dx": [
      "scc",
      "nsclc_nos",
      "carcinoma_unspec"
     ],
     "ambiguous_dx": [
      "papillary_carcinoma",
      "adenosquamous"
     ],
     "dx_basis": [
      {
       "source_id": "pmc13116887",
       "quote": "Squamous cell carcinomas are characterized by unequivocal squamous differentiation"
      }
     ]
    }
   }
  },
  "bracs": {
   "labels": {
    "N": {
     "entity": "breast:N",
     "expected_features": [
      {
       "concept": "normal_breast",
       "description": "normal mammary gland: luminal + myoepithelial layers, preserved epithelium:stroma ratio",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "there are two types of epithelial cells (the luminal layer and the basal myoepithelial layer)",
         "context": "Normal Tissue (N) In normal mammary glandular tissue, there are two types of epithelial cells (the luminal layer and the basal myoepithelial layer) and two types of stromal cells (interlobular stroma and intralobular stroma)."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "the ratio between epytelial component and stroma is preserved",
         "context": "Differently from PB, the ratio between epytelial component and stroma is preserved."
        },
        {
         "source_id": "librepath-breast-pathology",
         "tier": "T3",
         "quote": "A benign gland has two cell layers",
         "context": "A benign gland has two cell layers - myoepithelial and epithelial."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion (invasive-carcinoma feature); WSI label = most severe annotated lesion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "derived the WSI-level label as the most severe cancerous lesion detected within the slide",
         "context": "To address the aforementioned challenges, we started by extracting and annotating RoIs in WSIs, and subsequently derived the WSI-level label as the most severe cancerous lesion detected within the slide."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "rule: a slide labelled below IC cannot carry annotated invasive carcinoma; both quotes are one paper (single-source)"
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-breast-pathology"
     ],
     "status": "single-source",
     "severity": 0
    },
    "PB": {
     "entity": "breast:PB",
     "expected_features": [
      {
       "concept": "benign_lesion_terms",
       "description": "non-malignant benign lesions (cyst, apocrine metaplasia, sclerosing adenosis, papilloma, fibroadenoma, ...)",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "metaplasia, atrophy, stromal fibrosis, mastitis, sclerosing adenosis, papilloma, radial scar, simple and complex fibroadenoma",
         "context": "Therefore, PB includes cyst, apocrine metaplasia, ductal ectasia, squamous metaplasia, atrophy, stromal fibrosis, mastitis, sclerosing adenosis, papilloma, radial scar, simple and complex fibroadenoma."
        },
        {
         "source_id": "librepath-fibrocystic-breast-changes",
         "tier": "T3",
         "quote": "Dilated glands",
         "context": "==Microscopic== Features: Dilated glands - key change."
        },
        {
         "source_id": "librepath-intraductal-papilloma-breast",
         "tier": "T3",
         "quote": "true papillae (nipple-shaped structures with fibrovascular cores)",
         "context": "Micro = true papillae (nipple-shaped structures with fibrovascular cores), intraductal proliferation of epithelial and myoepithelial elements, +/-hyalinization"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion (invasive-carcinoma feature); WSI label = most severe annotated lesion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "derived the WSI-level label as the most severe cancerous lesion detected within the slide",
         "context": "To address the aforementioned challenges, we started by extracting and annotating RoIs in WSIs, and subsequently derived the WSI-level label as the most severe cancerous lesion detected within the slide."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "rule: a slide labelled below IC cannot carry annotated invasive carcinoma; both quotes are one paper (single-source)"
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-fibrocystic-breast-changes",
      "librepath-intraductal-papilloma-breast"
     ],
     "status": "single-source",
     "severity": 1
    },
    "UDH": {
     "entity": "breast:UDH",
     "expected_features": [
      {
       "concept": "epithelial_hyperplasia",
       "description": "multilayered, cohesive, haphazard / streaming epithelial proliferation",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "It is a cohesive proliferation of disorderly distributed but oriented cells",
         "context": "It is a cohesive proliferation of disorderly distributed but oriented cells."
        },
        {
         "source_id": "librepath-florid-epithelial-hyperplasia",
         "tier": "T3",
         "quote": "breast glands with more than four cell layers above the basement membrane",
         "context": "Micro = breast glands with more than four cell layers above the basement membrane with irregular cell spacing (e.g."
        },
        {
         "source_id": "wp-udh",
         "tier": "T3",
         "quote": "haphazard, jumbled cell arrangement or streaming growth pattern",
         "context": "== Histopathology == Usual ductal hyperplasia is typically a cohesive proliferation with haphazard, jumbled cell arrangement or streaming growth pattern."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "cytologic atypia",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "it does not show atypia",
         "context": "Even if UDH shares some architectural features with ADH and DCIS, it does not show atypia."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; BRACS describes UDH as not atypical. Stock text asserting generic \"nuclear pleomorphism\" would be flagged by this."
      },
      {
       "concept": "necrosis",
       "description": "necrosis",
       "evidence": [
        {
         "source_id": "pmc3357964",
         "tier": "T2",
         "quote": "and absence of necrosis",
         "context": "In epitheliosis, there is little distension of TDLU, few calcifications (not in granular form in necrotic debris), and absence of necrosis."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "sentence is about epitheliosis (= usual ductal hyperplasia per the same paper)"
      },
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion (invasive-carcinoma feature); WSI label = most severe annotated lesion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "derived the WSI-level label as the most severe cancerous lesion detected within the slide",
         "context": "To address the aforementioned challenges, we started by extracting and annotating RoIs in WSIs, and subsequently derived the WSI-level label as the most severe cancerous lesion detected within the slide."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "rule: a slide labelled below IC cannot carry annotated invasive carcinoma; both quotes are one paper (single-source)"
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-florid-epithelial-hyperplasia",
      "pmc3357964",
      "wp-udh"
     ],
     "status": "single-source",
     "severity": 2
    },
    "FEA": {
     "entity": "breast:FEA",
     "expected_features": [
      {
       "concept": "columnar_cells",
       "description": "columnar cell morphology",
       "evidence": [
        {
         "source_id": "librepath-flat-epithelial-atypia",
         "tier": "T3",
         "quote": "Columnar cell morphology",
         "context": "Columnar cell morphology."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "apical_snouts",
       "description": "apical snouts",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "presence of apical snout, endoluminal secretion and frequent calcifications",
         "context": "Flat Epithelial Atypia (FEA) FEA is a proliferative lesion characterized by low grade cytological atypia, cell monomorphism, loss of polarity and orientation with respect to the basement membrane, presence of apical snout, endoluminal secretion and frequent calcifications."
        },
        {
         "source_id": "librepath-flat-epithelial-atypia",
         "tier": "T3",
         "quote": "Apical snouts",
         "context": "+/-Apical snouts."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "monomorphic_cells",
       "description": "low-grade monomorphic cytologic atypia",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "FEA is a proliferative lesion characterized by low grade cytological atypia, cell monomorphism, loss of polarity",
         "context": "Flat Epithelial Atypia (FEA) FEA is a proliferative lesion characterized by low grade cytological atypia, cell monomorphism, loss of polarity and orientation with respect to the basement membrane, presence of apical snout, endoluminal secretion and frequent calcifications."
        },
        {
         "source_id": "pmc9406596",
         "tier": "T2",
         "quote": "flat epithelial atypia (FEA) exhibits low-grade (monomorphic) cytologic atypia",
         "context": "While CCLs have historically been described using a variety of terms, the World Health Organization currently classifies CCLs without atypia as columnar cell change (CCC) and columnar cell hyperplasia (CCH), whereas flat epithelial atypia (FEA) exhibits low-grade (monomorphic) cytologic atypia and may be used as a unifying term encompassing both CCC and CCH with atypia [1]."
        },
        {
         "source_id": "pmc11964577",
         "tier": "T2",
         "quote": "uniform low-grade monotonous rounded nuclei with loss of polarity",
         "context": "In contrast, in case 6, the most significant features of FEA/AIDEP were the uniform low-grade monotonous rounded nuclei with loss of polarity and occasional micronucleoli (Figure 2D-F)."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "calcification",
       "description": "frequent calcifications",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "presence of apical snout, endoluminal secretion and frequent calcifications",
         "context": "Flat Epithelial Atypia (FEA) FEA is a proliferative lesion characterized by low grade cytological atypia, cell monomorphism, loss of polarity and orientation with respect to the basement membrane, presence of apical snout, endoluminal secretion and frequent calcifications."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion (invasive-carcinoma feature); WSI label = most severe annotated lesion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "derived the WSI-level label as the most severe cancerous lesion detected within the slide",
         "context": "To address the aforementioned challenges, we started by extracting and annotating RoIs in WSIs, and subsequently derived the WSI-level label as the most severe cancerous lesion detected within the slide."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "rule: a slide labelled below IC cannot carry annotated invasive carcinoma; both quotes are one paper (single-source)"
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-flat-epithelial-atypia",
      "pmc11964577",
      "pmc9406596"
     ],
     "status": "verified",
     "severity": 3
    },
    "ADH": {
     "entity": "breast:ADH",
     "expected_features": [
      {
       "concept": "monomorphic_cells",
       "description": "monomorphic, evenly spaced cells",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "ADH is a proliferation of monomorphic cells, which only partially fill the ductal spaces",
         "context": "Atypical Ductal Hyperplasia (ADH) ADH is a proliferation of monomorphic cells, which only partially fill the ductal spaces."
        },
        {
         "source_id": "pmc5932853",
         "tier": "T2",
         "quote": "ducts partially filled with abnormally uniform evenly spaced cells",
         "context": "In ADH there are ducts partially filled with abnormally uniform evenly spaced cells with polarization [20] (Fig."
        },
        {
         "source_id": "librepath-adh",
         "tier": "T3",
         "quote": "equal cell spacing",
         "context": "Micro = cytologic and architectural features of low-grade DCIS (equal cell spacing, lumina round, variable architecture (classically cribriform or solid - may be micropapillary or papillary), small nuclei, small indistinct nucleoli); limited extent - either (1) two or less complete ducts, (2) <2 mm in size"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "partial_duct_involvement",
       "description": "partial duct involvement / limited extent",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "which only partially fill the ductal spaces",
         "context": "Atypical Ductal Hyperplasia (ADH) ADH is a proliferation of monomorphic cells, which only partially fill the ductal spaces."
        },
        {
         "source_id": "pmc5932853",
         "tier": "T2",
         "quote": "partial involvement of the ducts",
         "context": "Definition of ADH ADH resembles low nuclear grade ductal carcinoma in situ (DCIS) with cytonuclear and architectural atypia but with either partial involvement of the ducts and/or small size for a diagnosis of DCIS."
        },
        {
         "source_id": "librepath-adh",
         "tier": "T3",
         "quote": "limited extent",
         "context": "Micro = cytologic and architectural features of low-grade DCIS (equal cell spacing, lumina round, variable architecture (classically cribriform or solid - may be micropapillary or papillary), small nuclei, small indistinct nucleoli); limited extent - either (1) two or less complete ducts, (2) <2 mm in size"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "cribriform",
       "description": "cribriform / solid / papillary architecture",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "a solid pattern, a cribriform pattern and a papillary pattern",
         "context": "Architectural aspects include a solid pattern, a cribriform pattern and a papillary pattern."
        },
        {
         "source_id": "librepath-adh",
         "tier": "T3",
         "quote": "classically cribriform or solid - may be micropapillary or papillary",
         "context": "Micro = cytologic and architectural features of low-grade DCIS (equal cell spacing, lumina round, variable architecture (classically cribriform or solid - may be micropapillary or papillary), small nuclei, small indistinct nucleoli); limited extent - either (1) two or less complete ducts, (2) <2 mm in size"
        },
        {
         "source_id": "pmc5932853",
         "tier": "T2",
         "quote": "cribriform-like and/or micro-papillary formation",
         "context": "ADH has been defined as having \"some but not all the requisite features of DCIS\" with an involvement of ducts by an architecturally complex proliferation of monotonous cells forming cribriform-like and/or micro-papillary formation with a maximum of two separate spaces [20, 22]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "necrosis",
       "description": "central necrosis",
       "evidence": [
        {
         "source_id": "pmc5932853",
         "tier": "T2",
         "quote": "ADH typically lacks central necrosis and significant nuclear atypia",
         "context": "Unlike intermediate and high grade DCIS, ADH typically lacks central necrosis and significant nuclear atypia [1].Fig."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; \"typically\" hedge"
      },
      {
       "concept": "pleomorphism_marked",
       "description": "significant / marked nuclear atypia",
       "evidence": [
        {
         "source_id": "pmc5932853",
         "tier": "T2",
         "quote": "ADH typically lacks central necrosis and significant nuclear atypia",
         "context": "Unlike intermediate and high grade DCIS, ADH typically lacks central necrosis and significant nuclear atypia [1].Fig."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; \"typically\" hedge"
      },
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion (invasive-carcinoma feature); WSI label = most severe annotated lesion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "derived the WSI-level label as the most severe cancerous lesion detected within the slide",
         "context": "To address the aforementioned challenges, we started by extracting and annotating RoIs in WSIs, and subsequently derived the WSI-level label as the most severe cancerous lesion detected within the slide."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "rule: a slide labelled below IC cannot carry annotated invasive carcinoma; both quotes are one paper (single-source)"
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-adh",
      "pmc5932853"
     ],
     "status": "verified",
     "severity": 4
    },
    "DCIS": {
     "entity": "breast:DCIS",
     "expected_features": [
      {
       "concept": "fills_entire_duct",
       "description": "proliferation fills the entire duct / several adjacent ducts",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "fills the entire duct, without evidence of stroma invasion",
         "context": "Ductal Carcinoma in Situ (DCIS) In situ carcinoma is a malignant proliferation of epithelial cells that fills the entire duct, without evidence of stroma invasion."
        },
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "Typically it involves multiple adjacent ductal spaces",
         "context": "Typically it involves multiple adjacent ductal spaces."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "both quotes from one paper"
      },
      {
       "concept": "cribriform",
       "description": "cribriform / solid / papillary / micropapillary architecture",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "It can have cribriform, solid, papillary and micropapillary patterns",
         "context": "It can have cribriform, solid, papillary and micropapillary patterns."
        },
        {
         "source_id": "pmc3357964",
         "tier": "T2",
         "quote": "solid, papillary, or cribriform growth patterns",
         "context": "IG-DCIS has solid, papillary, or cribriform growth patterns, cytologically similar to those of LG-DCIS but with intraluminal necrosis (Figure 4(a)) or with intermediate cytological grade (Figure 4(b)), with or without necrosis."
        },
        {
         "source_id": "pmc8833401",
         "tier": "T2",
         "quote": "micropapillary (club-shaped)",
         "context": "The architecture could be cribriform (with fenestrations) (Figure 4A), solid (Figure 4B), micropapillary (club-shaped) (Figure 4C), papillary (Figure 4D), comedo (Figure 4E), or clinging (single layer), (Figure 4F)."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "in_situ",
       "description": "in situ (intraductal, non-invasive) growth",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "without evidence of stroma invasion",
         "context": "Ductal Carcinoma in Situ (DCIS) In situ carcinoma is a malignant proliferation of epithelial cells that fills the entire duct, without evidence of stroma invasion."
        },
        {
         "source_id": "wp-dcis",
         "tier": "T3",
         "quote": "not yet crossed the basement membrane",
         "context": "potentially malignant) condition, because the biologically abnormal cells have not yet crossed the basement membrane to invade the surrounding tissue."
        },
        {
         "source_id": "pmc8833401",
         "tier": "T2",
         "quote": "noninvasive form of ductal carcinoma",
         "context": "Ductal carcinoma in situ (DCIS) is a noninvasive form of ductal carcinoma."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "stromal_invasion",
       "description": "stromal invasion",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "without evidence of stroma invasion",
         "context": "Ductal Carcinoma in Situ (DCIS) In situ carcinoma is a malignant proliferation of epithelial cells that fills the entire duct, without evidence of stroma invasion."
        },
        {
         "source_id": "wp-dcis",
         "tier": "T3",
         "quote": "not yet crossed the basement membrane to invade the surrounding tissue",
         "context": "potentially malignant) condition, because the biologically abnormal cells have not yet crossed the basement membrane to invade the surrounding tissue."
        },
        {
         "source_id": "pmc8833401",
         "tier": "T2",
         "quote": "intraepithelial ductal neoplastic proliferation confined to the basement membrane",
         "context": "Both ADH and DCIS are characterized by intraepithelial ductal neoplastic proliferation confined to the basement membrane."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "source_ids": [
      "bracs-paper-arxiv",
      "pmc3357964",
      "pmc8833401",
      "wp-dcis"
     ],
     "status": "verified",
     "severity": 5
    },
    "IC": {
     "entity": "breast:IC",
     "expected_features": [
      {
       "concept": "stromal_invasion",
       "description": "tumour cells infiltrating breast stroma",
       "evidence": [
        {
         "source_id": "bracs-paper-arxiv",
         "tier": "T2",
         "quote": "IC is characterized by the invasion of tumor cells infiltrating the breast stroma",
         "context": "Invasive Carcinoma (IC) IC is characterized by the invasion of tumor cells infiltrating the breast stroma with loss of peripheral myoepithelial cells."
        },
        {
         "source_id": "librepath-idc-breast",
         "tier": "T3",
         "quote": "Small glands of variable size within desmoplastic stroma",
         "context": "\"Infiltrative\" pattern: Small glands of variable size within desmoplastic stroma."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "desmoplasia",
       "description": "desmoplastic stroma",
       "evidence": [
        {
         "source_id": "librepath-idc-breast",
         "tier": "T3",
         "quote": "within desmoplastic stroma",
         "context": "\"Infiltrative\" pattern: Small glands of variable size within desmoplastic stroma."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "mimicked by benign sclerosing adenosis",
       "note": "one source; desmoplasia also occurs as a mimic in benign sclerosing adenosis (Libre)"
      },
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia / nucleoli",
       "evidence": [
        {
         "source_id": "librepath-idc-breast",
         "tier": "T3",
         "quote": "Atypical nucleus adjacent to adipocyte",
         "context": "Evidence of invasion: Atypical nucleus adjacent to adipocyte - diagnostic."
        },
        {
         "source_id": "librepath-idc-breast",
         "tier": "T3",
         "quote": "Nucleoli common",
         "context": "Atypical cells: Usually >2x RBC diameter, but may be bland, especially in tubular carcinomas Nucleoli common."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "bracs-paper-arxiv",
      "librepath-idc-breast"
     ],
     "status": "single-source",
     "severity": 6
    }
   },
   "coarse": {
    "benign": {
     "members": [
      "N",
      "PB",
      "UDH"
     ],
     "severity": 2,
     "status": "single-source",
     "source_ids": [
      "bracs-paper-arxiv"
     ],
     "rule": "coarse flag uses the fine severity ordering; threshold = most severe member"
    },
    "atypical": {
     "members": [
      "FEA",
      "ADH"
     ],
     "severity": 4,
     "status": "single-source",
     "source_ids": [
      "bracs-paper-arxiv"
     ],
     "rule": "coarse flag uses the fine severity ordering; threshold = most severe member"
    },
    "malignant": {
     "members": [
      "DCIS",
      "IC"
     ],
     "severity": 6,
     "status": "single-source",
     "source_ids": [
      "bracs-paper-arxiv"
     ],
     "rule": "coarse flag uses the fine severity ordering; threshold = most severe member"
    }
   }
  },
  "ebr-coarse30": {
   "labels": {
    "Glioblastoma, IDH-wildtype": {
     "entity": "cns:gbm-idh-wt",
     "expected_features": [
      {
       "concept": "necrosis",
       "description": "necrosis",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "areas of necrosis and microvascular proliferation are r",
         "context": "Mitotic activity is brisk and areas of necrosis and microvascular proliferation are readily encountered (Figure 4A,B)."
        },
        {
         "source_id": "pmc10358772",
         "tier": "T2",
         "quote": "central pseudo-palisading necrosis",
         "context": "The traditional hallmarks of GBM were astrocytomas with the features of central pseudo-palisading necrosis and abnormal microvascular proliferation under the microscope (6)."
        },
        {
         "source_id": "pmc11722003",
         "tier": "T2",
         "quote": "microvascular proliferation (glomeruloid vasculature), and/or necrosis",
         "context": "On the other hand, glioblastomas are classically described as hypercellular lesions with nuclear atypia, cellular pleomorphism, increased mitotic activity, microvascular proliferation (glomeruloid vasculature), and/or necrosis [16]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "molecular GBM (pmc10358772) lacks necrosis/MVP on H&E, so absence is NOT contradictory"
      },
      {
       "concept": "microvascular_prolif",
       "description": "microvascular proliferation",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "areas of necrosis and microvascular proliferation are r",
         "context": "Mitotic activity is brisk and areas of necrosis and microvascular proliferation are readily encountered (Figure 4A,B)."
        },
        {
         "source_id": "pmc10358772",
         "tier": "T2",
         "quote": "abnormal microvascular proliferation",
         "context": "The traditional hallmarks of GBM were astrocytomas with the features of central pseudo-palisading necrosis and abnormal microvascular proliferation under the microscope (6)."
        },
        {
         "source_id": "pmc11722003",
         "tier": "T2",
         "quote": "microvascular proliferation (glomeruloid vasculature)",
         "context": "On the other hand, glioblastomas are classically described as hypercellular lesions with nuclear atypia, cellular pleomorphism, increased mitotic activity, microvascular proliferation (glomeruloid vasculature), and/or necrosis [16]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mitoses_high",
       "description": "brisk mitotic activity",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "Mitotic activity is brisk",
         "context": "Mitotic activity is brisk and areas of necrosis and microvascular proliferation are readily encountered (Figure 4A,B)."
        },
        {
         "source_id": "pmc11722003",
         "tier": "T2",
         "quote": "increased mitotic activity",
         "context": "On the other hand, glioblastomas are classically described as hypercellular lesions with nuclear atypia, cellular pleomorphism, increased mitotic activity, microvascular proliferation (glomeruloid vasculature), and/or necrosis [16]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "pleomorphism_marked",
       "description": "pleomorphic hyperchromatic nuclei",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "hyperchromatic and pleomorphic nuclei",
         "context": "The conventional glioblastoma is a densely cellular and infiltrative tumour characterized by fibrillary astrocytic cells with highly hyperchromatic and pleomorphic nuclei."
        },
        {
         "source_id": "pmc11722003",
         "tier": "T2",
         "quote": "nuclear atypia, cellular pleomorphism",
         "context": "On the other hand, glioblastomas are classically described as hypercellular lesions with nuclear atypia, cellular pleomorphism, increased mitotic activity, microvascular proliferation (glomeruloid vasculature), and/or necrosis [16]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "pmc10216527",
      "pmc10358772",
      "pmc11722003"
     ],
     "status": "verified",
     "compat_dx": [
      "glioblastoma",
      "gliosarcoma"
     ],
     "ambiguous_dx": [
      "anaplastic_astrocytoma",
      "diffuse_astrocytoma",
      "astrocytoma"
     ],
     "dx_note": "ambiguous: pmc10358772/pmc10978634 say IDH-wt grade 2-3 histology can be glioblastoma by molecular criteria"
    },
    "Gliosarcoma": {
     "entity": "cns:gliosarcoma",
     "expected_features": [
      {
       "concept": "biphasic",
       "description": "biphasic glial + sarcomatous pattern",
       "evidence": [
        {
         "source_id": "pmc7170742",
         "tier": "T2",
         "quote": "biphasic configuration",
         "context": "Its characteristic features are biphasic configuration, constituting a definite, separate glial and sarcomatous differentiation, on histological evaluation."
        },
        {
         "source_id": "librepath-astrocytoma",
         "tier": "T3",
         "quote": "gliosarcoma = glioblastoma + sarcomatous component",
         "context": "|volume=96 |issue=3 |pages=313-20 |year=2010 |month=February |pmid=19618114 |pmc=2808523 |doi=10.1007/s11060-009-9973-6 |url=}}</ref> Rare ~ 200 cases reported in the literature.<ref name=pmid19618114/> Definition: gliosarcoma = glioblastoma + sarcomatous component.<ref name=pmid20415184>{{cite journal |author=Ayadi L, Charfi S, Khabir A, et al."
        },
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "a sarcomatous subtype that is termed",
         "context": "(Figure 4A,B). Histologic variants of glioblastomas include the following: a giant cell subtype characterized by bizarre multinucleated giant cells, a sarcomatous subtype that is termed \"gliosarcoma\" (Figure 4D), an epithelioid subtype with abundant eosinophilic cytoplasm and distinct cell borders (Figure 4E), a granular cell subtype characterized by a PAS-positive granular cytoplas"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-astrocytoma",
      "pmc10216527",
      "pmc7170742"
     ],
     "status": "single-source",
     "compat_dx": [
      "gliosarcoma",
      "glioblastoma"
     ],
     "ambiguous_dx": [
      "astrocytoma",
      "sarcoma_other"
     ],
     "dx_note": "variant of glioblastoma (pmc10216527, librepath-astrocytoma)"
    },
    "Oligodendroglioma, IDH-mutant and 1p/19q codeleted": {
     "entity": "cns:oligodendroglioma",
     "expected_features": [
      {
       "concept": "perinuclear_halo",
       "description": "perinuclear haloes (\"fried-egg\")",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "giving rise to the described",
         "context": "Individual tumour cells are characterized by relatively monomorphic ovoid-to-round nuclei containing stippled chromatin surrounded by perinuclear haloes, giving rise to the described \"fried-egg\" appearance."
        },
        {
         "source_id": "pmc13564585",
         "tier": "T2",
         "quote": "monotonous round nuclei, perinuclear halos, and calcification",
         "context": "Circumscribed MAPK pathway-altered gliomas, including pilocytic astrocytoma, may occasionally show focal oligodendroglioma-like areas with monotonous round nuclei, perinuclear halos, and calcification, especially when classic biphasic architecture, Rosenthal fibers, and eosinophilic granular bodies are limited or underrepresented in small tissue samples [11,12,13,14,15]."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "pmc13564585: halos seen in 18/23 non-oligodendroglial tumours, nonspecific",
       "note": null
      },
      {
       "concept": "chicken_wire",
       "description": "delicate capillary network (\"chicken-wire\")",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "There is often a delicate capillary backgr",
         "context": "There is often a delicate capillary background in a characteristic \"chicken-wire\" pattern (Figure 3A)."
        },
        {
         "source_id": "pmc13564585",
         "tier": "T2",
         "quote": "delicate branching or chicken-wire-like capillary vasculature",
         "context": "rphology was defined by the presence of one or more of the following features: small monotonous round nuclei, perinuclear clearing or halo formation, delicate branching or chicken-wire-like capillary vasculature, calcification, microcystic background, and/or a histological pattern raising the differential diagnosis of oligodendroglioma during routine microscopic evaluation. Cases were eligible for inclusion"
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "nonspecific (10/23 mimics)",
       "note": null
      },
      {
       "concept": "calcification",
       "description": "microcalcification",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "Areas showing microcalcification",
         "context": "Areas showing microcalcification, hemorrhage, and cystic degeneration with myxoid material can also be observed."
        },
        {
         "source_id": "pmc13564585",
         "tier": "T2",
         "quote": "perinuclear halos, and calcification",
         "context": "Circumscribed MAPK pathway-altered gliomas, including pilocytic astrocytoma, may occasionally show focal oligodendroglioma-like areas with monotonous round nuclei, perinuclear halos, and calcification, especially when classic biphasic architecture, Rosenthal fibers, and eosinophilic granular bodies are limited or underrepresented in small tissue samples [11,12,13,14,15]."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "nonspecific (9/23 mimics)",
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "pmc10216527",
      "pmc13564585"
     ],
     "status": "weak",
     "compat_dx": [
      "oligodendroglioma",
      "anaplastic_oligodendroglioma"
     ],
     "ambiguous_dx": []
    },
    "Anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeleted": {
     "entity": "cns:oligodendroglioma",
     "expected_features": [
      {
       "concept": "perinuclear_halo",
       "description": "perinuclear haloes (\"fried-egg\")",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "giving rise to the described",
         "context": "Individual tumour cells are characterized by relatively monomorphic ovoid-to-round nuclei containing stippled chromatin surrounded by perinuclear haloes, giving rise to the described \"fried-egg\" appearance."
        },
        {
         "source_id": "pmc13564585",
         "tier": "T2",
         "quote": "monotonous round nuclei, perinuclear halos, and calcification",
         "context": "Circumscribed MAPK pathway-altered gliomas, including pilocytic astrocytoma, may occasionally show focal oligodendroglioma-like areas with monotonous round nuclei, perinuclear halos, and calcification, especially when classic biphasic architecture, Rosenthal fibers, and eosinophilic granular bodies are limited or underrepresented in small tissue samples [11,12,13,14,15]."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "nonspecific",
       "note": null
      },
      {
       "concept": "chicken_wire",
       "description": "delicate capillary network (\"chicken-wire\")",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "There is often a delicate capillary backgr",
         "context": "There is often a delicate capillary background in a characteristic \"chicken-wire\" pattern (Figure 3A)."
        },
        {
         "source_id": "pmc13564585",
         "tier": "T2",
         "quote": "delicate branching or chicken-wire-like capillary vasculature",
         "context": "rphology was defined by the presence of one or more of the following features: small monotonous round nuclei, perinuclear clearing or halo formation, delicate branching or chicken-wire-like capillary vasculature, calcification, microcystic background, and/or a histological pattern raising the differential diagnosis of oligodendroglioma during routine microscopic evaluation. Cases were eligible for inclusion"
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "nonspecific",
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "pmc10216527",
      "pmc13564585"
     ],
     "status": "weak",
     "compat_dx": [
      "oligodendroglioma",
      "anaplastic_oligodendroglioma"
     ],
     "ambiguous_dx": []
    },
    "Diffuse astrocytoma, IDH-mutant": {
     "entity": "cns:astrocytoma-idh-mutant",
     "expected_features": [
      {
       "concept": "diffuse_infiltration",
       "description": "diffuse infiltration within fibrillary background",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "within a fibrillary neuropil background",
         "context": "Histology and Diagnostic Workup IDH-mutant astrocytomas are characterized by diffuse infiltration of neoplastic astrocytic tumour cells into surrounding normal brain parenchyma within a fibrillary neuropil background."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "show diffuse infiltration with mild cellularity and nuclear atypia",
         "context": "Grade 2 tumors show diffuse infiltration with mild cellularity and nuclear atypia, achieving median survivals approaching a decade [3]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "fibrillary_background",
       "description": "fibrillary background",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "within a fibrillary neuropil background",
         "context": "Histology and Diagnostic Workup IDH-mutant astrocytomas are characterized by diffuse infiltration of neoplastic astrocytic tumour cells into surrounding normal brain parenchyma within a fibrillary neuropil background."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      }
     ],
     "excluded_features": [
      {
       "concept": "necrosis",
       "description": "necrosis (absent in grade 2)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "necrosis are absent",
         "context": "Mitotic activity is uncommon, and microvascular proliferation and necrosis are absent."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "microvascular_prolif",
       "description": "microvascular proliferation (absent in grade 2)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "necrosis are absent",
         "context": "Mitotic activity is uncommon, and microvascular proliferation and necrosis are absent."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "source_ids": [
      "pmc10216527",
      "pmc13042621"
     ],
     "status": "single-source",
     "compat_dx": [
      "diffuse_astrocytoma",
      "astrocytoma"
     ],
     "ambiguous_dx": [
      "anaplastic_astrocytoma"
     ],
     "dx_note": "pmc13042621: survival overlaps between grades 2 and 3"
    },
    "Anaplastic astrocytoma, IDH-mutant": {
     "entity": "cns:astrocytoma-idh-mutant",
     "expected_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "increased nuclear pleomorphism / atypia",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "a more densely cellular pattern with increased nuclear pleomorphism",
         "context": "Grade 3 tumours show a more densely cellular pattern with increased nuclear pleomorphism; however, the presence of increased mitoses is the definitive criterion that upgrades a grade 2 neoplasm to a grade 3 neoplasm."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "Grade 3 tumors exhibit increased cellularity, cytologic atypia, and mitotic activity",
         "context": "Grade 3 tumors exhibit increased cellularity, cytologic atypia, and mitotic activity."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mitoses_nonlow",
       "description": "increased mitoses (defining grade 3)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "the presence of increased mitoses is the definitive criterion",
         "context": "Grade 3 tumours show a more densely cellular pattern with increased nuclear pleomorphism; however, the presence of increased mitoses is the definitive criterion that upgrades a grade 2 neoplasm to a grade 3 neoplasm."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "mitotic activity",
         "context": "Grade 3 tumors exhibit increased cellularity, cytologic atypia, and mitotic activity."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "necrosis",
       "description": "necrosis (grade 4 criterion)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4",
         "context": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "microvascular_prolif",
       "description": "microvascular proliferation (grade 4 criterion)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4",
         "context": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "source_ids": [
      "pmc10216527",
      "pmc13042621"
     ],
     "status": "verified",
     "compat_dx": [
      "anaplastic_astrocytoma",
      "astrocytoma"
     ],
     "ambiguous_dx": [
      "diffuse_astrocytoma",
      "glioblastoma"
     ]
    },
    "Glioblastoma, IDH-mutant": {
     "entity": "cns:astrocytoma-idh-mutant",
     "expected_features": [
      {
       "concept": "necrosis",
       "description": "necrosis or microvascular proliferation (grade 4 histology)",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4",
         "context": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "CDKN2A/B deletion also gives grade 4 without these features, so absence is not contradictory"
      },
      {
       "concept": "microvascular_prolif",
       "description": "microvascular proliferation",
       "evidence": [
        {
         "source_id": "pmc10216527",
         "tier": "T2",
         "quote": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4",
         "context": "If microvascular proliferation or necrosis are present, this designates the tumour as grade 4."
        },
        {
         "source_id": "pmc13042621",
         "tier": "T2",
         "quote": "microvascular proliferation and/or necrosis defining Grade 4",
         "context": "t microscopy remains the foundation of initial classification, and historical grading was anchored in anaplasia-mitotic activity defining Grade 3 and microvascular proliferation and/or necrosis defining Grade 4-within the context of classic astrocytic versus oligodendroglial cytomorphology [1, 2]. In the integrated era, molecular alterations can supersede histology in specific contexts. Most notably, CDKN2A"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "pmc10216527",
      "pmc13042621"
     ],
     "status": "verified",
     "compat_dx": [
      "glioblastoma",
      "astrocytoma"
     ],
     "ambiguous_dx": [
      "anaplastic_astrocytoma",
      "diffuse_astrocytoma"
     ],
     "dx_note": "legacy name; CNS5 calls grade 4 IDH-mutant tumour an astrocytoma (pmc10216527)"
    },
    "Anaplastic astrocytoma, IDH-wildtype": {
     "entity": "cns:anaplastic-astrocytoma-idh-wt-legacy",
     "expected_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia and pleomorphism",
       "evidence": [
        {
         "source_id": "librepath-anaplastic-astrocytoma",
         "tier": "T3",
         "quote": "Distinct nuclear atypia",
         "context": "Distinct nuclear atypia and pleomorphism."
        },
        {
         "source_id": "librepath-anaplastic-astrocytoma",
         "tier": "T3",
         "quote": "pleomorphism",
         "context": "Distinct nuclear atypia and pleomorphism."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      },
      {
       "concept": "mitoses_nonlow",
       "description": "mitoses",
       "evidence": [
        {
         "source_id": "librepath-anaplastic-astrocytoma",
         "tier": "T3",
         "quote": "mitoses",
         "context": "Specimens with low cellularity but plenty mitoses are also considered anaplastic."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "necrosis",
       "description": "necrosis (absent, except radiation necrosis after pretreatment)",
       "evidence": [
        {
         "source_id": "librepath-anaplastic-astrocytoma",
         "tier": "T3",
         "quote": "No necrosis, no vascular proliferations",
         "context": "No necrosis, no vascular proliferations."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; older WHO 2016 revision; pmc10978634 shows molecular-GBM overlap"
      },
      {
       "concept": "microvascular_prolif",
       "description": "vascular proliferation (absent)",
       "evidence": [
        {
         "source_id": "librepath-anaplastic-astrocytoma",
         "tier": "T3",
         "quote": "No necrosis, no vascular proliferations",
         "context": "No necrosis, no vascular proliferations."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      }
     ],
     "source_ids": [
      "librepath-anaplastic-astrocytoma"
     ],
     "status": "single-source",
     "compat_dx": [
      "anaplastic_astrocytoma",
      "astrocytoma"
     ],
     "ambiguous_dx": [
      "glioblastoma",
      "diffuse_astrocytoma"
     ],
     "dx_note": "pmc10978634: histologic grade 2-3 IDH-wt astrocytoma titled grade 4 glioma"
    },
    "Pilocytic astrocytoma": {
     "entity": "cns:pilocytic-astrocytoma",
     "expected_features": [
      {
       "concept": "biphasic",
       "description": "biphasic (compact fibrillar + loose microcystic) architecture",
       "evidence": [
        {
         "source_id": "librepath-pilocytic",
         "tier": "T3",
         "quote": "Classically biphasic",
         "context": "==Microscopic== Features:<ref name=Ref_PSNP82-4>{{Ref PSNP|82-4}}</ref> Classically biphasic (though either may be absent): Fibrillar."
        },
        {
         "source_id": "pmc11511714",
         "tier": "T2",
         "quote": "The tumour is often biphasic",
         "context": "The tumour is often biphasic with a mixture of bipolar cells with thin (hair-like or 'piloid') cell processes and stellate cells, along with various mixtures of other characteristic features (e.g."
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "conventional biphasic architecture with Rosenthal fibers and eosinophilic granular bodies",
         "context": "Although pilocytic astrocytoma (PA) classically demonstrates a conventional biphasic architecture with Rosenthal fibers and eosinophilic granular bodies, rare cases may exhibit extensive oligodendroglioma-like morphology [17]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "rosenthal",
       "description": "Rosenthal fibres",
       "evidence": [
        {
         "source_id": "librepath-pilocytic",
         "tier": "T3",
         "quote": "Rosenthal fibres - key feature",
         "context": "Rosenthal fibres - key feature."
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "Rosenthal fibers",
         "context": "Although pilocytic astrocytoma (PA) classically demonstrates a conventional biphasic architecture with Rosenthal fibers and eosinophilic granular bodies, rare cases may exhibit extensive oligodendroglioma-like morphology [17]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "may be rare, not pathognomonic (Libre)"
      },
      {
       "concept": "eosinophilic_granular_bodies",
       "description": "eosinophilic granular bodies",
       "evidence": [
        {
         "source_id": "librepath-pilocytic",
         "tier": "T3",
         "quote": "PAS-D +ve (eosinophilic granular bodies)",
         "context": "Stains = PAS-D +ve (eosinophilic granular bodies)"
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "eosinophilic granular bodies",
         "context": "Although pilocytic astrocytoma (PA) classically demonstrates a conventional biphasic architecture with Rosenthal fibers and eosinophilic granular bodies, rare cases may exhibit extensive oligodendroglioma-like morphology [17]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "circumscribed",
       "description": "circumscribed growth",
       "evidence": [
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "circumscribed growth pattern",
         "context": "In such cases, the distinction from \"true\" oligodendroglioma may be challenging, particularly in limited biopsy samples, and must be based on a careful evaluation of additional histological features (i.e., circumscribed growth pattern, biphasic architecture with Rosenthal fibers, and eosinophilic granular bodies), together with immunohistochemical and molecular studies."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      }
     ],
     "excluded_features": [
      {
       "concept": "mitoses_high",
       "description": "brisk / frequent mitoses",
       "evidence": [
        {
         "source_id": "pmc11511714",
         "tier": "T2",
         "quote": "monomorphic with inconspicuous mitotic activity",
         "context": "The cells typically are monomorphic with inconspicuous mitotic activity."
        },
        {
         "source_id": "librepath-pilocytic",
         "tier": "T3",
         "quote": "Mitoses - not significant",
         "context": "+/-Mitoses - not significant in the context of the Dx."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "source_ids": [
      "librepath-pilocytic",
      "pmc11511714",
      "pmc13513445"
     ],
     "status": "verified",
     "compat_dx": [
      "pilocytic_astrocytoma"
     ],
     "ambiguous_dx": [
      "astrocytoma"
     ],
     "dx_note": "astrocytic lineage"
    },
    "Ganglioglioma": {
     "entity": "cns:ganglioglioma",
     "expected_features": [
      {
       "concept": "dysplastic_neurons",
       "description": "dysplastic neurons",
       "evidence": [
        {
         "source_id": "pmc11511714",
         "tier": "T2",
         "quote": "composed of a mixture of dysplastic neurons and neoplastic glial cells",
         "context": "Ganglioglioma Definition Gangliogliomas are low-grade tumours composed of a mixture of dysplastic neurons and neoplastic glial cells."
        },
        {
         "source_id": "librepath-ganglioglioma",
         "tier": "T3",
         "quote": "Dysplastic neurons",
         "context": "==Microscopic== ====Microscopic==== Features: Dysplastic neurons."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "eosinophilic_granular_bodies",
       "description": "eosinophilic granular bodies",
       "evidence": [
        {
         "source_id": "librepath-ganglioglioma",
         "tier": "T3",
         "quote": "PAS-D +ve (eosinophilic granular bodies)",
         "context": "Stains = PAS-D +ve (eosinophilic granular bodies)"
        },
        {
         "source_id": "pmc11511714",
         "tier": "T2",
         "quote": "eosinophilic granular bodies",
         "context": "Rosenthal fibres, eosinophilic granular bodies)."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "calcification",
       "description": "calcification",
       "evidence": [
        {
         "source_id": "librepath-ganglioglioma",
         "tier": "T3",
         "quote": "Dystrophic calcification",
         "context": "Dystrophic calcification."
        },
        {
         "source_id": "pmc11511714",
         "tier": "T2",
         "quote": "These include calcification, inflammation, Rosenthal fibres",
         "context": "These include calcification, inflammation, Rosenthal fibres and eosinophilic granular bodies."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "as \"dystrophic calcification\" / \"sometimes\""
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-ganglioglioma",
      "pmc11511714"
     ],
     "status": "verified",
     "compat_dx": [
      "ganglioglioma"
     ],
     "ambiguous_dx": [
      "astrocytoma",
      "pilocytic_astrocytoma",
      "oligodendroglioma"
     ],
     "dx_note": "Libre: glial part can resemble fibrillary astrocytoma, oligodendroglioma or pilocytic astrocytoma"
    },
    "Ependymoma": {
     "entity": "cns:ependymoma",
     "expected_features": [
      {
       "concept": "rosettes",
       "description": "perivascular pseudorosettes / ependymal rosettes",
       "evidence": [
        {
         "source_id": "librepath-ependymoma",
         "tier": "T3",
         "quote": "Perivascular pseudorosettes, ependymal rosettes",
         "context": "Micro = Perivascular pseudorosettes, ependymal rosettes"
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "pseudorosettes",
         "context": "Ependymomas with clear-cell (oligodendroglioma-like) morphology may show compact growth, uniform polygonal cells, and only subtle or absent perivascular pseudorosettes [14]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "circumscribed",
       "description": "sharp demarcation from brain",
       "evidence": [
        {
         "source_id": "librepath-ependymoma",
         "tier": "T3",
         "quote": "Usu. sharply demarcated from surrounding brain parenchyma",
         "context": "Usu. sharply demarcated from surrounding brain parenchyma."
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "partially circumscribed growth-pattern",
         "context": "In a supratentorial glioma with partially circumscribed growth-pattern and perivascular arrangement with pseudorosettes, OLIG-2 negativity, along with EMA dot-like or ring-like positivity, supports ependymal differentiation."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-ependymoma",
      "pmc13513445"
     ],
     "status": "verified",
     "compat_dx": [
      "ependymoma"
     ],
     "ambiguous_dx": [
      "oligodendroglioma"
     ],
     "dx_note": "pmc13513445: clear-cell ependymoma simulates oligodendroglioma"
    },
    "Anaplastic ependymoma": {
     "entity": "cns:ependymoma",
     "expected_features": [
      {
       "concept": "rosettes",
       "description": "perivascular pseudorosettes / ependymal rosettes",
       "evidence": [
        {
         "source_id": "librepath-ependymoma",
         "tier": "T3",
         "quote": "Perivascular pseudorosettes, ependymal rosettes",
         "context": "Micro = Perivascular pseudorosettes, ependymal rosettes"
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "pseudorosettes",
         "context": "Ependymomas with clear-cell (oligodendroglioma-like) morphology may show compact growth, uniform polygonal cells, and only subtle or absent perivascular pseudorosettes [14]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mitoses_nonlow",
       "description": "mitoses / microvascular proliferation / necrosis (grade 3 criteria)",
       "evidence": [
        {
         "source_id": "librepath-ependymoma",
         "tier": "T3",
         "quote": "Cellular density",
         "context": "Grade 3 depends on: Cellular density."
        },
        {
         "source_id": "pmc11089008",
         "tier": "T2",
         "quote": "nuclear pleomorphism, microvascular proliferation, and mitotic figures",
         "context": "Tumor tissue was available from cases 1-4, all of which displayed anaplastic features by histology, including nuclear pleomorphism, microvascular proliferation, and mitotic figures (Fig."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "grade-3 criteria only from Libre; pmc11089008 is a 4-case spinal series",
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-ependymoma",
      "pmc11089008",
      "pmc13513445"
     ],
     "status": "single-source",
     "compat_dx": [
      "ependymoma"
     ],
     "ambiguous_dx": [
      "oligodendroglioma"
     ]
    },
    "Meningothelial meningioma": {
     "entity": "cns:meningioma-meningothelial",
     "expected_features": [
      {
       "concept": "whorls",
       "description": "whorls / onion-bulb formations",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Whorls, Onion bulb formations",
         "context": "Whorls, Onion bulb formations."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "pmc7536112 reports whorls are not common in this subtype (sources disagree)",
       "note": null
      },
      {
       "concept": "pseudoinclusions",
       "description": "syncytial growth, nuclear pseudoinclusions",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Syncytial, nuclear clearing",
         "context": "Microscopic: Syncytial, nuclear clearing (pseudoinclusions)."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      },
      {
       "concept": "psammoma",
       "description": "few psammoma bodies",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Few psammoma bodies",
         "context": "Few psammoma bodies."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "\"few\"; classic meningioma lists psammoma bodies as a key feature",
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia / pleomorphism (classic grade 1 meningioma)",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "less then 4 mit/10 HPF and no atypia",
         "context": "less then 4 mit/10 HPF and no atypia"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source (Libre overview table, classic WHO I)"
      }
     ],
     "source_ids": [
      "librepath-meningioma"
     ],
     "status": "single-source",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma"
     ]
    },
    "Fibrous meningioma": {
     "entity": "cns:meningioma-fibrous",
     "expected_features": [
      {
       "concept": "spindle_cells",
       "description": "spindle cells in parallel bundles",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Spindle cells in parallel bundles",
         "context": "Spindle cells in parallel bundles."
        },
        {
         "source_id": "pmc12777031",
         "tier": "T2",
         "quote": "fascicular spindle-cell proliferation lacking whorls or psammoma bodies",
         "context": "In contrast, the extraforaminal specimen from the second-stage surgery demonstrated fibrous meningioma (WHO grade I), composed of densely collagenous stroma with fascicular spindle-cell proliferation lacking whorls or psammoma bodies, confirming two histological subtypes within the same lesion (Fig."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "whorls",
       "description": "prominent whorls (few or none)",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Few to none whorl formations",
         "context": "Few to none whorl formations."
        },
        {
         "source_id": "pmc12777031",
         "tier": "T2",
         "quote": "fascicular spindle-cell proliferation lacking whorls or psammoma bodies",
         "context": "In contrast, the extraforaminal specimen from the second-stage surgery demonstrated fibrous meningioma (WHO grade I), composed of densely collagenous stroma with fascicular spindle-cell proliferation lacking whorls or psammoma bodies, confirming two histological subtypes within the same lesion (Fig."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "Libre says \"few to none\": occasional whorls do not exclude the subtype; second source is one case report",
       "note": null
      },
      {
       "concept": "psammoma",
       "description": "psammoma bodies",
       "evidence": [
        {
         "source_id": "pmc12777031",
         "tier": "T2",
         "quote": "fascicular spindle-cell proliferation lacking whorls or psammoma bodies",
         "context": "In contrast, the extraforaminal specimen from the second-stage surgery demonstrated fibrous meningioma (WHO grade I), composed of densely collagenous stroma with fascicular spindle-cell proliferation lacking whorls or psammoma bodies, confirming two histological subtypes within the same lesion (Fig."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; one case report"
      },
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia / pleomorphism (classic grade 1 meningioma)",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "less then 4 mit/10 HPF and no atypia",
         "context": "less then 4 mit/10 HPF and no atypia"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source (Libre overview table, classic WHO I)"
      }
     ],
     "source_ids": [
      "librepath-meningioma",
      "pmc12777031"
     ],
     "status": "single-source",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma"
     ]
    },
    "Transitional meningioma": {
     "entity": "cns:meningioma-transitional",
     "expected_features": [
      {
       "concept": "whorls",
       "description": "whorls (prominent in the transitional component)",
       "evidence": [
        {
         "source_id": "pmc12777031",
         "tier": "T2",
         "quote": "prominent whorl formation and psammoma bodies",
         "context": "The intradural specimen obtained during the first-stage surgery was diagnosed as transitional meningioma (WHO grade I), exhibiting mixed meningothelial and fibrous areas with prominent whorl formation and psammoma bodies."
        },
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Lobular and fasicular growth patterns coexist",
         "context": "Lobular and fasicular growth patterns coexist."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "first quote is one case report",
       "note": null
      },
      {
       "concept": "psammoma",
       "description": "psammoma bodies",
       "evidence": [
        {
         "source_id": "pmc12777031",
         "tier": "T2",
         "quote": "prominent whorl formation and psammoma bodies",
         "context": "The intradural specimen obtained during the first-stage surgery was diagnosed as transitional meningioma (WHO grade I), exhibiting mixed meningothelial and fibrous areas with prominent whorl formation and psammoma bodies."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "one case report",
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia / pleomorphism (classic grade 1 meningioma)",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "less then 4 mit/10 HPF and no atypia",
         "context": "less then 4 mit/10 HPF and no atypia"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source (Libre overview table, classic WHO I)"
      }
     ],
     "source_ids": [
      "librepath-meningioma",
      "pmc12777031"
     ],
     "status": "weak",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma"
     ]
    },
    "Angiomatous meningioma": {
     "entity": "cns:meningioma-angiomatous",
     "expected_features": [
      {
       "concept": "vascular_network",
       "description": "blood vessels dominate (>half of tumour volume), hyalinised vessels",
       "evidence": [
        {
         "source_id": "pmc12724472",
         "tier": "T2",
         "quote": "more than half of the tumor volume consists of blood vessels",
         "context": "Among these, angiomatous meningioma (AM) is a rare subtype, accounting for approximately 2.1% of all meningiomas, and is characterized by a highly vascular composition in which more than half of the tumor volume consists of blood vessels [1]."
        },
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "Hyalinized vessels dominate over tumor cells",
         "context": "Hyalinized vessels dominate over tumor cells."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pleomorphism_marked",
       "description": "anaplasia / marked atypia",
       "evidence": [
        {
         "source_id": "pmc12724472",
         "tier": "T2",
         "quote": "Nuclear atypia and anaplasia are absent",
         "context": "Nuclear atypia and anaplasia are absent, and the proliferative index (Ki-67) is typically low (~2.4%), further supporting their indolent nature [7]."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; Libre lists \"degenerative nuclear atypia\" so only marked/anaplastic features are excluded"
      }
     ],
     "source_ids": [
      "librepath-meningioma",
      "pmc12724472"
     ],
     "status": "single-source",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma",
      "haemangioblastoma",
      "haemangioma"
     ]
    },
    "Secretory meningioma": {
     "entity": "cns:meningioma-secretory",
     "expected_features": [],
     "excluded_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia",
       "evidence": [
        {
         "source_id": "pmc11226565",
         "tier": "T2",
         "quote": "with the absence of cellular atypia",
         "context": "The tumor cells exhibit predominantly oval or round nuclei, eosinophilic cytoplasm, and indistinct cell borders, with the absence of cellular atypia."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single case description; not a stand-alone exclusion rule"
      }
     ],
     "source_ids": [
      "pmc11226565"
     ],
     "status": "weak",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma",
      "metastatic_tumour",
      "pituitary_adenoma"
     ]
    },
    "Atypical meningioma": {
     "entity": "cns:meningioma-atypical",
     "expected_features": [
      {
       "concept": "sheeting",
       "description": "sheeting / loss of lobular architecture, hypercellularity",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "loss of lobular architecture (\"sheeting\") and hypercellularity",
         "context": "Histological examination shows a neoplasm with loss of lobular architecture (\"sheeting\") and hypercellularity (hematoxylin-eosin staining, original magnification 100×) (C)."
        },
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "nucleoli, sheeting",
         "context": "brain invasion, 4 or more mit/10 HPF, or 3 of the following: necrosis, increased cellularity, high nuc:cyto ratio, nucleoli, sheeting"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "necrosis",
       "description": "necrosis (one of the grade 2 criteria)",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "3 of the following: necrosis",
         "context": "brain invasion, 4 or more mit/10 HPF, or 3 of the following: necrosis, increased cellularity, high nuc:cyto ratio, nucleoli, sheeting"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "optional criterion; absence not contradictory"
      },
      {
       "concept": "mitoses_nonlow",
       "description": ">=4 mitoses per 10 HPF",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "4 or more mit/10 HPF",
         "context": "brain invasion, 4 or more mit/10 HPF, or 3 of the following: necrosis, increased cellularity, high nuc:cyto ratio, nucleoli, sheeting"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "threshold from Libre only (also in REPORT.md as single-source)"
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-meningioma",
      "pmc10033642"
     ],
     "status": "single-source",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma"
     ]
    },
    "Anaplastic meningioma": {
     "entity": "cns:meningioma-anaplastic",
     "expected_features": [
      {
       "concept": "pleomorphism_marked",
       "description": "frank anaplasia / marked nuclear atypia",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "\"Frank anaplasia\"; marked nuclear atypia",
         "context": "Grade 3 (either of the following): High mitotic rate (>=20 mitoses/10 HPF - for whatever HPF means, see HPFitis.) \"Frank anaplasia\"; marked nuclear atypia."
        },
        {
         "source_id": "pmc12103695",
         "tier": "T2",
         "quote": "frank anaplasia",
         "context": "More than 20 mitoses in 10 consecutive fields, frank anaplasia, TERT mutation, or homozygous deletion of CDKN2A and/or CDKN2B The frequency of high-grade meningiomas is higher in children [9,10]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mitoses_high",
       "description": ">=20 mitoses per 10 HPF",
       "evidence": [
        {
         "source_id": "librepath-meningioma",
         "tier": "T3",
         "quote": "20 or more mit",
         "context": "20 or more mitoses/10 HPF, morphologiy similiar to carcinoma or sarcoma"
        },
        {
         "source_id": "pmc12103695",
         "tier": "T2",
         "quote": "More than 20 mitoses in 10 consecutive fields",
         "context": "More than 20 mitoses in 10 consecutive fields, frank anaplasia, TERT mutation, or homozygous deletion of CDKN2A and/or CDKN2B The frequency of high-grade meningiomas is higher in children [9,10]."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-meningioma",
      "pmc12103695"
     ],
     "status": "verified",
     "compat_dx": [
      "meningioma"
     ],
     "ambiguous_dx": [
      "schwannoma",
      "haemangiopericytoma",
      "sarcoma_other"
     ]
    },
    "Schwannoma": {
     "entity": "cns:schwannoma",
     "expected_features": [
      {
       "concept": "antoni_verocay",
       "description": "Antoni A / B areas, Verocay bodies",
       "evidence": [
        {
         "source_id": "librepath-schwannoma",
         "tier": "T3",
         "quote": "Antoni B area (pauci-cellular, loose microcystic tissue), Verocay bodies",
         "context": "Micro = Antoni A areas (cellular, fibrillary, polar, elongated), Antoni B area (pauci-cellular, loose microcystic tissue), Verocay bodies (paucinuclear area surrounded by nuclei), hyaline thickened blood vessels, thick capsule."
        },
        {
         "source_id": "pmc13605746",
         "tier": "T2",
         "quote": "alternating Antoni A and Antoni B areas",
         "context": "Histopathological Findings Histological evaluation revealed a biphasic spindle cell neoplasm composed of alternating Antoni A and Antoni B areas."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": "cellular schwannoma lacks Verocay bodies (Libre)"
      },
      {
       "concept": "vascular_network",
       "description": "thick-walled hyalinised vessels",
       "evidence": [
        {
         "source_id": "pmc13605746",
         "tier": "T2",
         "quote": "Thick-walled hyalinized vessels and siderophages were observed",
         "context": "Thick-walled hyalinized vessels and siderophages were observed."
        },
        {
         "source_id": "librepath-schwannoma",
         "tier": "T3",
         "quote": "hyaline th",
         "context": "Micro = Antoni A areas (cellular, fibrillary, polar, elongated), Antoni B area (pauci-cellular, loose microcystic tissue), Verocay bodies (paucinuclear area surrounded by nuclei), hyaline thickened blood vessels, thick capsule."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-schwannoma",
      "pmc13605746"
     ],
     "status": "verified",
     "compat_dx": [
      "schwannoma"
     ],
     "ambiguous_dx": [
      "meningioma",
      "mpnst"
     ]
    },
    "Pituitary adenoma": {
     "entity": "cns:pituitary-adenoma",
     "expected_features": [
      {
       "concept": "solid_sheets",
       "description": "solid growth pattern",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "Histological examination shows a tumor with solid growth pattern",
         "context": "Histological examination shows a tumor with solid growth pattern, that in some areas is composed of elongated cells arranged in a perivascular fashion (hematoxylin-eosin staining, original magnification 200×) (E)."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      }
     ],
     "excluded_features": [
      {
       "concept": "mitoses_nonlow",
       "description": "mitotic activity (rare in adenoma)",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "mitotic activity and cellular pleomorphism are nearly always hallmarks of a metastatic neoplasm",
         "context": "On the other hand, the differential diagnosis between a PA and a metastatic cancer is only rarely a concern, given that mitotic activity and cellular pleomorphism are nearly always hallmarks of a metastatic neoplasm while being extremely rare in PAs."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; \"extremely rare\" in adenoma"
      },
      {
       "concept": "pleomorphism_nonmild",
       "description": "cellular pleomorphism (rare in adenoma)",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "mitotic activity and cellular pleomorphism are nearly always hallmarks of a metastatic neoplasm",
         "context": "On the other hand, the differential diagnosis between a PA and a metastatic cancer is only rarely a concern, given that mitotic activity and cellular pleomorphism are nearly always hallmarks of a metastatic neoplasm while being extremely rare in PAs."
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source"
      }
     ],
     "source_ids": [
      "pmc10033642"
     ],
     "status": "single-source",
     "compat_dx": [
      "pituitary_adenoma"
     ],
     "ambiguous_dx": [
      "craniopharyngioma",
      "haemangioblastoma"
     ]
    },
    "Adamantinomatous craniopharyngioma": {
     "entity": "cns:craniopharyngioma-adamantinomatous",
     "expected_features": [
      {
       "concept": "wet_keratin_reticulum",
       "description": "wet keratin, stellate reticulum, palisading columnar epithelium",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "the so-called wet keratin",
         "context": "Microscopic examination (E) reveals keratin deposits, the so-called wet keratin (1), surrounded by loose textured cells, known as \"stellate reticulum\" (2)."
        },
        {
         "source_id": "librepath-craniopharyngioma",
         "tier": "T3",
         "quote": "Lobules with loosely distributed epithelia (\"stellate reticulum\")",
         "context": "Lobules with loosely distributed epithelia (\"stellate reticulum\")."
        },
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "surrounded by palisading columnar epithelium",
         "context": "reticulum\" (2). Reticulum is thought to derive from degeneration of internal cells. The cords and islands of well differentiated squamous epithelium surrounded by palisading columnar epithelium (3) are distinctive and diagnostic features of adamantinomatous craniopharyngioma (hematoxylin-eosin staining, original magnification 100×) On histology, the hallmarks of ACP are keratin deposits (th"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "keratinization",
       "description": "keratin deposits",
       "evidence": [
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "keratin deposits",
         "context": "Microscopic examination (E) reveals keratin deposits, the so-called wet keratin (1), surrounded by loose textured cells, known as \"stellate reticulum\" (2)."
        },
        {
         "source_id": "librepath-craniopharyngioma",
         "tier": "T3",
         "quote": "nests of whorled keratin",
         "context": "small nucleoli), \"wet\" keratin (nests of whorled keratin), calcifications"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "calcification",
       "description": "calcifications",
       "evidence": [
        {
         "source_id": "librepath-craniopharyngioma",
         "tier": "T3",
         "quote": "calcifications",
         "context": "small nucleoli), \"wet\" keratin (nests of whorled keratin), calcifications"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; pmc10033642 lists partly calcified mass on imaging (cns-acp-vs-papillary)"
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-craniopharyngioma",
      "pmc10033642"
     ],
     "status": "verified",
     "compat_dx": [
      "craniopharyngioma"
     ],
     "ambiguous_dx": [
      "astrocytoma",
      "pilocytic_astrocytoma"
     ]
    },
    "Haemangioblastoma": {
     "entity": "cns:haemangioblastoma",
     "expected_features": [
      {
       "concept": "vascular_network",
       "description": "dense capillary / prominent vascular network",
       "evidence": [
        {
         "source_id": "pmc13056813",
         "tier": "T2",
         "quote": "embedded within a dense capillary network",
         "context": "Microscopy revealed sheets of short spindle-shaped tumor cells with lipid-rich cytoplasm, embedded within a dense capillary network and abundant stromal reticulin fibers (Figure 1F)."
        },
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "stromal clear cells with a prominent vascular network",
         "context": "Hemangioblastoma combines stromal clear cells with a prominent vascular network (Figure 7A) and may be confused with metastatic renal cell carcinoma or other clear-cell lesions."
        },
        {
         "source_id": "librepath-hemangioblastoma",
         "tier": "T3",
         "quote": "vascular tumour with large polygonal stromal cells",
         "context": "Micro = vascular tumour with large polygonal stromal cells with hyperchromatic nuclei and vacuolar cytoplasm"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "clear_cells",
       "description": "stromal clear / vacuolated cells",
       "evidence": [
        {
         "source_id": "pmc13513445",
         "tier": "T2",
         "quote": "stromal clear cells",
         "context": "Hemangioblastoma combines stromal clear cells with a prominent vascular network (Figure 7A) and may be confused with metastatic renal cell carcinoma or other clear-cell lesions."
        },
        {
         "source_id": "librepath-hemangioblastoma",
         "tier": "T3",
         "quote": "vacuolar cytoplasm",
         "context": "Micro = vascular tumour with large polygonal stromal cells with hyperchromatic nuclei and vacuolar cytoplasm"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-hemangioblastoma",
      "pmc13056813",
      "pmc13513445"
     ],
     "status": "verified",
     "compat_dx": [
      "haemangioblastoma"
     ],
     "ambiguous_dx": [
      "metastatic_tumour",
      "haemangioma",
      "meningioma"
     ]
    },
    "Haemangioma": {
     "entity": "cns:haemangioma",
     "expected_features": [
      {
       "concept": "vascular_channels",
       "description": "endothelium-lined vascular channels",
       "evidence": [
        {
         "source_id": "librepath-hemangioma",
         "tier": "T3",
         "quote": "channels lined by benign endothelium containing RBCs",
         "context": "Micro = channels lined by benign endothelium containing RBCs"
        },
        {
         "source_id": "pmc10033642",
         "tier": "T2",
         "quote": "different sized, ectasic, vascular channels, often back-to-back arranged",
         "context": "On microscopy, different sized, ectasic, vascular channels, often back-to-back arranged and densely-packed, are evident."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "sources describe soft-tissue / cavernous-sinus venous malformation; EBRAINS class identity assumed (final-ebr REPORT)",
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-hemangioma",
      "pmc10033642"
     ],
     "status": "weak",
     "compat_dx": [
      "haemangioma"
     ],
     "ambiguous_dx": [
      "meningioma",
      "haemangioblastoma"
     ]
    },
    "Haemangiopericytoma": {
     "entity": "cns:haemangiopericytoma",
     "expected_features": [
      {
       "concept": "staghorn_collagen",
       "description": "staghorn vessels, patternless growth, keloid-like collagen",
       "evidence": [
        {
         "source_id": "pmc10791336",
         "tier": "T2",
         "quote": "prominent gaping thin-walled (staghorn) vessels",
         "context": "Histopathological Findings In case 1, the tumor showed bland-appearing spindle cells, a collagenous background stroma, and prominent gaping thin-walled (staghorn) vessels."
        },
        {
         "source_id": "librepath-sft",
         "tier": "T3",
         "quote": "keloid-like collagen bundles",
         "context": "Micro = spindle cells in a patternless pattern, hemangiopericytoma-like areas (staghorn vessels), keloid-like collagen bundles, +/-well-circumscribed (common)"
        },
        {
         "source_id": "librepath-sft",
         "tier": "T3",
         "quote": "spindle cells in a patternless pattern",
         "context": "Micro = spindle cells in a patternless pattern, hemangiopericytoma-like areas (staghorn vessels), keloid-like collagen bundles, +/-well-circumscribed (common)"
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pseudoinclusions",
       "description": "meningioma-type nuclear pseudoinclusions",
       "evidence": [
        {
         "source_id": "pmc10791336",
         "tier": "T2",
         "quote": "Nuclear pseudoinclusions or psammomatous calcification was not evident",
         "context": "Nuclear pseudoinclusions or psammomatous calcification was not evident."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "case-report statement about individual cases",
       "note": "case report (first case) only; matches pseudoinclusion terms only"
      }
     ],
     "source_ids": [
      "librepath-sft",
      "pmc10791336"
     ],
     "status": "single-source",
     "compat_dx": [
      "haemangiopericytoma"
     ],
     "ambiguous_dx": [
      "meningioma"
     ]
    },
    "Lipoma": {
     "entity": "cns:lipoma",
     "expected_features": [
      {
       "concept": "adipocytes",
       "description": "mature adipocytes",
       "evidence": [
        {
         "source_id": "pmc9422988",
         "tier": "T2",
         "quote": "formation composed by mature adipocytes",
         "context": "On the other hand, histopathological investigations of the viscera and the cerebellopontine neoformation showed a formation composed by mature adipocytes, allowing to define it as an intracranial lipoma (Figure 3)."
        },
        {
         "source_id": "librepath-lipoma",
         "tier": "T3",
         "quote": "Mature adipose tissue (lipoma)",
         "context": "Caption = Mature adipose tissue (lipoma)."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "pleomorphism_nonmild",
       "description": "cellular atypia",
       "evidence": [
        {
         "source_id": "pmc9422988",
         "tier": "T2",
         "quote": "Lacking cellular atypia, dysplasia, and other malignancy indices",
         "context": "ords: Brain Neoplasm, Autopsy, Forensic pathology INTRODUCTION Intracranial lipomas are rare benign lesions with an incidence at autopsy of 0.08%.1,2 Lacking cellular atypia, dysplasia, and other malignancy indices, these lipomas are considered embryonic developmental disorders rather than neoplasms.3,4-5 Frequently, intracranial lipomas are localized on the midline above the corpus callosum or near the cerebel"
        }
       ],
       "status": "single-source",
       "usable": false,
       "weak_reason": null,
       "note": "single source; Libre names cytologic atypia as a risk marker"
      }
     ],
     "source_ids": [
      "librepath-lipoma",
      "pmc9422988"
     ],
     "status": "single-source",
     "compat_dx": [
      "lipoma"
     ],
     "ambiguous_dx": []
    },
    "Diffuse large B-cell lymphoma of the CNS": {
     "entity": "cns:cns-dlbcl",
     "expected_features": [
      {
       "concept": "lymphoid_perivascular",
       "description": "large lymphoid cells, perivascular / angiocentric growth",
       "evidence": [
        {
         "source_id": "librepath-neuropath-tumours",
         "tier": "T3",
         "quote": "Lesion predominantly perivascular",
         "context": "Lesion predominantly perivascular."
        },
        {
         "source_id": "pmc11722003",
         "tier": "T2",
         "quote": "perivascular growth pattern referred to as angiotropism",
         "context": "Histological examination frequently reveals a perivascular growth pattern referred to as angiotropism [22]."
        },
        {
         "source_id": "pmc13260794",
         "tier": "T2",
         "quote": "angiocentric growth patterns",
         "context": "Typical histopathological characteristics of PCNSL include diffuse infiltrative and highly proliferating lymphoma cells with angiocentric growth patterns (31), and EBV-positive PCNSL often exhibits larger areas of necrosis (48)."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-neuropath-tumours",
      "pmc11722003",
      "pmc13260794"
     ],
     "status": "single-source",
     "compat_dx": [
      "lymphoma"
     ],
     "ambiguous_dx": []
    },
    "Langerhans cell histiocytosis": {
     "entity": "cns:lch",
     "expected_features": [
      {
       "concept": "langerhans_grooves",
       "description": "nuclear grooves / reniform (coffee-bean) nuclei",
       "evidence": [
        {
         "source_id": "librepath-lch",
         "tier": "T3",
         "quote": "nuclear grooves",
         "context": "have nuclear grooves (similar to those in papillary thyroid carcinoma) -- appearance dependent on the rotation of the nucleus.<ref>BN."
        },
        {
         "source_id": "pmc11227055",
         "tier": "T2",
         "quote": "frequent nuclear grooves",
         "context": "The histiocytes had indented and convoluted nuclei with frequent nuclear grooves (Fig."
        },
        {
         "source_id": "pmc11861498",
         "tier": "T2",
         "quote": "Langerhans cells with nuclear grooves",
         "context": "The histopathologic hallmark of LCH is the presence of Langerhans cells with nuclear grooves and abundant eosinophilic cytoplasm, often accompanied by eosinophils, lymphocytes, and multinucleated giant cells."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "eosinophils",
       "description": "eosinophil-rich infiltrate",
       "evidence": [
        {
         "source_id": "librepath-lch",
         "tier": "T3",
         "quote": "Eosinophils - often prominent",
         "context": "+/-Eosinophils - often prominent."
        },
        {
         "source_id": "pmc11227055",
         "tier": "T2",
         "quote": "an inflammatory background rich in eosinophils",
         "context": "Alcohol-fixed smears with Papanicolaou stain, as routinely performed in our department, showed discohesive and loose clusters of large histiocytes in an inflammatory background rich in eosinophils."
        },
        {
         "source_id": "pmc11861498",
         "tier": "T2",
         "quote": "inflammatory infiltrate rich in eosinophils",
         "context": "These lesions are frequently accompanied by an inflammatory infiltrate rich in eosinophils."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-lch",
      "pmc11227055",
      "pmc11861498"
     ],
     "status": "verified",
     "compat_dx": [
      "lch"
     ],
     "ambiguous_dx": []
    },
    "Metastatic tumours": {
     "entity": "cns:metastasis",
     "expected_features": [
      {
       "concept": "circumscribed",
       "description": "well-demarcated border against brain",
       "evidence": [
        {
         "source_id": "librepath-brain-metastasis",
         "tier": "T3",
         "quote": "usu. well-demarcated border between brain and lesion",
         "context": "Micro = usu. well-demarcated border between brain and lesion, no cytoplasmic processes (seen in glial tumours), usu."
        },
        {
         "source_id": "librepath-neuropath-tumours",
         "tier": "T3",
         "quote": "Well-demarcated border between brain and lesion",
         "context": "====Secondary==== Carcinomas: Well-demarcated border between brain and lesion - key feature."
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "pmc13301885: infiltrative edge in a subset; the two Libre pages are one wiki",
       "note": null
      },
      {
       "concept": "pleomorphism_nonmild",
       "description": "nuclear atypia of malignancy",
       "evidence": [
        {
         "source_id": "librepath-brain-metastasis",
         "tier": "T3",
         "quote": "nuclear atypia of malignancy",
         "context": "have nuclear atypia of malignancy, +/-glandular architecture, +/-nucleoli seen"
        },
        {
         "source_id": "librepath-neuropath-tumours",
         "tier": "T3",
         "quote": "Usu. have nuclear atypia of malignancy",
         "context": "Usu. have nuclear atypia of malignancy."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "glandular",
       "description": "glandular architecture (sometimes)",
       "evidence": [
        {
         "source_id": "librepath-brain-metastasis",
         "tier": "T3",
         "quote": "+/-glandular architecture",
         "context": "have nuclear atypia of malignancy, +/-glandular architecture, +/-nucleoli seen"
        },
        {
         "source_id": "librepath-neuropath-tumours",
         "tier": "T3",
         "quote": "+/-Glandular arrangement",
         "context": "+/-Glandular arrangement."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [
      {
       "concept": "glial_processes",
       "description": "glial cytoplasmic processes",
       "evidence": [
        {
         "source_id": "librepath-brain-metastasis",
         "tier": "T3",
         "quote": "no cytoplasmic processes (seen in glial tumours)",
         "context": "well-demarcated border between brain and lesion, no cytoplasmic processes (seen in glial tumours), usu."
        },
        {
         "source_id": "librepath-neuropath-tumours",
         "tier": "T3",
         "quote": "No cytoplasmic processes",
         "context": "No cytoplasmic processes."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "source_ids": [
      "librepath-brain-metastasis",
      "librepath-neuropath-tumours"
     ],
     "status": "verified",
     "compat_dx": [
      "metastatic_tumour",
      "adeno",
      "scc",
      "idc",
      "ilc",
      "carcinoma_unspec",
      "nsclc_nos",
      "melanoma",
      "gastric_adeno",
      "dcis"
     ],
     "ambiguous_dx": [
      "papillary_carcinoma",
      "serous",
      "endometrioid",
      "cholangiocarcinoma",
      "mesothelioma",
      "sarcoma_other",
      "leiomyosarcoma",
      "mmmt",
      "germ_cell",
      "thymoma",
      "adenosquamous",
      "mpnst"
     ],
     "dx_note": "Libre lists lung, breast, kidney, GI and melanoma primaries; other tumour types can metastasise but no snapshot says so"
    },
    "Medulloblastoma, non-WNT/non-SHH": {
     "entity": "cns:medulloblastoma",
     "expected_features": [
      {
       "concept": "small_round_cells",
       "description": "small round cell tumour",
       "evidence": [
        {
         "source_id": "librepath-medulloblastoma",
         "tier": "T3",
         "quote": "malignant small round cell tumour",
         "context": "Tx = }} Medulloblastoma is a malignant small round cell tumour that is found in the cerebellum or dorsal brainstem."
        },
        {
         "source_id": "pmc9367316",
         "tier": "T2",
         "quote": "classic",
         "context": "pe (WNT)-activated, Sonic Hedgehog (SHH) activated TP53-wildtype, SHH-activated and TP53-mutant, and non-WNT/non-SHH) and four histological patterns (classic, desmoplastic/nodular, MB with extensive nodularity, and large cell/anaplastic). The diverse molecular types show significantly different age, molecular and clinical profiles [17,18,19,20,21,22,23,24"
        }
       ],
       "status": "weak",
       "usable": false,
       "weak_reason": "second quote only supports classic histology, not the term \"small round\"",
       "note": null
      },
      {
       "concept": "rosettes",
       "description": "Homer-Wright rosettes",
       "evidence": [
        {
         "source_id": "librepath-medulloblastoma",
         "tier": "T3",
         "quote": "Homer-Wright rosettes",
         "context": "Homer-Wright rosettes: Rosette with a meshwork of fibers (neuropil) at the centre.<ref>{{cite journal |author=Wippold FJ, Perry A |title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes |journal=AJNR Am J Neuroradiol |volume=27 |issue=3 |pages=488-92 |year=2006 |month=March |pmid=16551982 |doi= |url=}}</ref> ==IHC== MAP2 usu."
        },
        {
         "source_id": "pmc9367316",
         "tier": "T2",
         "quote": "frequent presence of Homer-Wright rosettes",
         "context": "Classic MB is a blue cell tumor without distinctive architectural features composed of cells with high NC ratio, a variable degree of nuclear anaplasia from slight to moderate and the frequent presence of Homer-Wright rosettes."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      },
      {
       "concept": "mitoses_high",
       "description": "high mitotic count",
       "evidence": [
        {
         "source_id": "librepath-medulloblastoma",
         "tier": "T3",
         "quote": "High mitotic count",
         "context": "High mitotic count."
        },
        {
         "source_id": "pmc9367316",
         "tier": "T2",
         "quote": "Mitotic activity is variable but generally high",
         "context": "Mitotic activity is variable but generally high in the poorly differentiated components of the tumor."
        }
       ],
       "status": "verified",
       "usable": true,
       "weak_reason": null,
       "note": null
      }
     ],
     "excluded_features": [],
     "source_ids": [
      "librepath-medulloblastoma",
      "pmc9367316"
     ],
     "status": "verified",
     "compat_dx": [
      "medulloblastoma"
     ],
     "ambiguous_dx": []
    }
   }
  }
 }
}