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  <head>
    <title>096-03 Specimens, diagnostic methods, and clinicopathological reasoning</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Specimens, methods, and clinicopathological reasoning">
      <outline text="Clinical question and pre-analytical phase">
        <outline text="Diagnosis begins before the laboratory"/>
        <outline text="Question sets site, speed, medium, handling">
          <outline text="Sterile, unfixed, frozen, or light-protected"/>
        </outline>
        <outline text="Right test on wrong specimen fails"/>
        <outline text="Integrate history, site, imaging, treatment"/>
        <outline text="Ischaemic time alters molecules and detail"/>
        <outline text="Crush, cautery, drying, contamination artefacts"/>
        <outline text="Small biopsy may miss a focal lesion">
          <outline text="May capture only necrosis or reactive tissue"/>
        </outline>
        <outline text="Auditable chain of identity and orientation"/>
        <outline text="Allocate scarce tissue in advance"/>
      </outline>
      <outline text="Gross examination">
        <outline text="Size, weight, colour, consistency, margins"/>
        <outline text="Ink margins, open, slice, map nodes"/>
        <outline text="Blocks from tumour, interface, deepest invasion"/>
        <outline text="Photographs preserve spatial relationships"/>
        <outline text="Sampling trade-off">
          <outline text="More blocks cost time and tissue"/>
          <outline text="Too few give false reassurance"/>
        </outline>
      </outline>
      <outline text="Fixation and processing">
        <outline text="Fixation limits autolysis and putrefaction"/>
        <outline text="Formalin cross-links proteins">
          <outline text="Delayed or excessive fixation alters assays"/>
        </outline>
        <outline text="Decalcification harms antigens and nucleic acids"/>
        <outline text="Paraffin processing and thin sections"/>
        <outline text="Frozen sections: rapid but less definitive">
          <outline text="Ice artefact and limited sampling"/>
        </outline>
      </outline>
      <outline text="Morphology on routine stains">
        <outline text="Haematoxylin: nuclei; eosin: cytoplasm, matrix"/>
        <outline text="Architecture, polarity, stroma, necrosis first"/>
        <outline text="Then nuclear and cytoplasmic detail"/>
        <outline text="Atypia is not malignancy">
          <outline text="Repair, infection, radiation, degeneration"/>
        </outline>
      </outline>
      <outline text="Special stains and immunohistochemistry">
        <outline text="Special stains answer narrow questions">
          <outline text="Organisms, mucin, iron, amyloid"/>
          <outline text="Sensitivity depends on burden and preservation"/>
        </outline>
        <outline text="Other modalities add artefacts and limits"/>
        <outline text="Immunohistochemistry localises proteins">
          <outline text="Lineage, origin, proliferation, receptors"/>
          <outline text="No marker is perfectly specific"/>
          <outline text="Staged panel beats broad unguided panel"/>
        </outline>
      </outline>
      <outline text="Specimen types">
        <outline text="Cytology: minimally invasive, little architecture">
          <outline text="Cell blocks add histology and immunostains"/>
        </outline>
        <outline text="Core biopsy preserves architecture and grade"/>
        <outline text="Excision shows boundaries and heterogeneity"/>
        <outline text="Resection permits pathological staging"/>
        <outline text="Least invasive is not always least costly"/>
      </outline>
      <outline text="Haematopathology and molecular tests">
        <outline text="Integrate counts, smears, marrow, genetics"/>
        <outline text="Flow cytometry detects subtle populations"/>
        <outline text="Chromosome analysis: large changes"/>
        <outline text="In situ hybridisation targets selected loci"/>
        <outline text="Polymerase chain reaction and sequencing"/>
        <outline text="Interpret against sensitivity and tumour fraction">
          <outline text="Clonal change without overt malignancy"/>
        </outline>
        <outline text="Marker roles must not be conflated">
          <outline text="Diagnostic names a disorder"/>
          <outline text="Prognostic estimates outcome"/>
          <outline text="Predictive estimates therapy response"/>
          <outline text="Monitoring tracks a known clone"/>
        </outline>
        <outline text="Negative result may reflect too few cells"/>
      </outline>
      <outline text="Tumour reporting">
        <outline text="Grade is differentiation, stage is extent"/>
        <outline text="Type, size, depth, invasion, margins, nodes"/>
        <outline text="Positive margin meaning depends on context"/>
        <outline text="Preoperative treatment causes regression changes"/>
      </outline>
      <outline text="Correlation, uncertainty, and quality">
        <outline text="Patterns have differentials, not final answers"/>
        <outline text="Discordance triggers review of identity and sampling"/>
        <outline text="State certainty explicitly in reports">
          <outline text="Definitive, favoured, indeterminate, inadequate"/>
        </outline>
        <outline text="Urgent findings need direct communication"/>
        <outline text="Predictive values depend on prevalence"/>
        <outline text="Selection and verification bias"/>
        <outline text="Consensus is more honest than false precision"/>
      </outline>
      <outline text="Autopsy and the diagnostic chain">
        <outline text="Autopsy audits cause, mechanism, treatment"/>
        <outline text="Cause of death as a causal sequence"/>
        <outline text="Sampling constrains morphology, morphology directs tests"/>
        <outline text="Confidence never exceeds specimen adequacy"/>
      </outline>
    </outline>
  </body>
</opml>
