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... Show moreAims 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 CSF1 expression and CSF1 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 CSF1 locus was evaluated with split-apart fluorescence in-situ hybridisation (FISH) probes. Regions were selected to score after identifying CSF1-expressing regions, using mRNA ISH with the help of digital correlative microscopy. CSF1 rearrangement was considered positive in samples containing >2 split signals/100 nuclei. Irrespective of TGCT-subtype, all cases showed CSF1 expression and in 76% CSF1 rearrangement was detected. Quantification of CSF1-expressing cells was not informative, due to the extensive intratumour heterogeneity. Of the four synovitis cases, two also showed CSF1 expression without CSF1 rearrangement. No correlation between CSF1 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 CSF1-expressing cells. Conclusion In diagnosing TGCT, CSF1 mRNA-ISH, in combination with CSF1 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 CSF1 rearrangement in 76% of the TGCT cases. Neither CSF1 expression nor presence of CSF1 rearrangement could be associated with the difference in biological behaviour of TGCT. Show less
Graaff, M.A. de; Jong, D. de; Briaire-De Bruijn, I.H.; Hogendoorn, P.C.W.; Bovee, J.V.M.G.; Szuhai, K. 2015
The purpose of this thesis was to obtain more insight into T-cell clonality in blood of mycosis fungoides (MF) patients. Investigation of the frequency of blood T-cell clonality clearly indicated... Show moreThe purpose of this thesis was to obtain more insight into T-cell clonality in blood of mycosis fungoides (MF) patients. Investigation of the frequency of blood T-cell clonality clearly indicated early dissemination of neoplastic T-cells into skin and blood as a sign of physiological recirculation. Nevertheless, circulating clonal T-cells not associated with a cutaneous clone were found in substantial numbers of MF patients and controls. This phenomenon remained obscure; we termed it T-cell Expansion of Undetermined Significance (TExUS). Qualitative investigation of T-cell clonality in blood samples at the initial diagnosis of MF could not predict the clinical course. Chromosomal analysis confirmed previous data demonstrating an early dissemination of the T-cell clone. Complex chromosomal aberrations were found exclusively in clonal T-lymphocytes. Characteristic combinations of chromosomal aberrations were found; some alterations seemed to be prognostically significant. Comparison of our in-house TCR_ assay with the Biomed-2 protocol verified our findings. Since detection of T-cell clonality by PCR assays fails in a substantial portion of CTCL samples, but succeeds in various benign conditions, accurate integration of clinical, histomorphological, immunohistochemical data still represents the golden diagnostic standard. Demonstration of a T-cell clone only supplements the diagnosis of CTCL. Show less
