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Aims  Localised‐ and diffuse‐type tenosynovial giant cell tumours ( TGCT ) are regarded as different clinical and radiological  TGCT  types. However, genetically and histopathologically they seem indistinguishable. We aimed to correlate   CSF 1  expression and   CSF 1  rearrangement with the biological behaviour of different  TGCT ‐types with clinical outcome (recurrence).    Methods and results  Along a continuum of extremes, therapy‐naive knee  TGCT  patients with >3‐year follow‐up, mean age 43 (range = 6–71) years and 56% females were selected. Nine localised (two recurrences), 16 diffuse‐type (nine recurrences) and four synovitis as control were included. Rearrangement of the   CSF 1  locus was evaluated with split‐apart fluorescence  in‐situ  hybridisation ( FISH ) probes. Regions were selected to score after identifying   CSF 1 ‐expressing regions, using  mRNA ISH  with the help of digital correlative microscopy.   CSF 1  rearrangement was considered positive in samples containing >2 split signals/100 nuclei. Irrespective of  TGCT ‐subtype, all cases showed   CSF 1  expression and in 76%   CSF 1  rearrangement was detected. Quantification of   CSF 1 ‐expressing cells was not informative, due to the extensive intratumour heterogeneity. Of the four synovitis cases, two also showed   CSF 1  expression without   CSF 1  rearrangement. No correlation between   CSF 1  expression or rearrangement with clinical subtype and local recurrence was detected. Both localised and diffuse  TGCT  cases showed a scattered distribution in the tissue of   CSF 1 ‐expressing cells.    Conclusion  In diagnosing  TGCT ,   CSF 1   mRNA ‐ ISH , in combination with   CSF 1  split‐apart  FISH  using digital correlative microscopy, is an auxiliary diagnostic tool to identify rarely occurring neoplastic cells. This combined approach allowed us to detect   CSF 1  rearrangement in 76% of the  TGCT  cases. Neither   CSF 1  expression nor presence of   CSF 1  rearrangement could be associated with the difference in biological behaviour of  TGCT .

Does CSF 1 overexpression or rearrangement influence biological behaviour in tenosynovial giant cell tumours of the knee?