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advanced stage, high FLIPI, high LDH, older age, high β2 microglobulin, but none of 1 these criteria, either alone or in risk models, can unequivocally predict transformation
(4-7,9).
Additionally gene expression- and immunohistochemical studies of FL have identified characteristicsofthemicro-environmentthatpredictFLprogressionandtransformation.
The presence, distribution pattern and molecular expression of the tumor infiltrating immune cells, such as T-lymphocytes, monocytes and dendritic cells, was found to be associated with outcome of FL (13-16) and transformation risk (17-19). However, results are not consistent enough to guide targeted treatment or actual treatment aimed at reducing transformation risk. This would require a more accurate prediction of transformation and further unraveling of molecular mechanisms responsible for transformation. Hopefully, integration of not only clinical data and biomarkers, but also other modalities like imaging will enable this in the future.
Diagnosis of transformation of follicular lymphoma
Transformation of FL is usually suspected on clinical and biochemical parameters, such as a sudden deterioration in performance status, development of B-symptoms, rapid discordant localized nodal growth or new extranodal disease, a rapid increase in LDH or hypercalcaemia. Biopsy of a lymph node (or other involved tissue) is imperative when suspicion of transformation arises (4,6,7), as histology is the gold standard for diagnosis of transformation. Histology will show aggressive NHL, mostly resembling DLBCL. Development of TFL does not generally occur in all lymph nodes simultaneously. As a result lymph nodes containing FL coexist with lymph nodes containing DLBCL in the same patient. This creates the potential for sampling errors (biopsy of a non- transformed lymph node) which often creates a significant diagnostic delay or even leads to missing the diagnosis of transformation. Diagnosis early in the course of the disease improves outcome of TFL, probably because of better outcome of limited stage disease (4,6,20). Therefore, there is a need for a non-invasive technique indicating the lymph node of interest (i.e. the transformed lymph node), to minimize the chance of sampling errors and time to diagnosis.
Positron emission tomography and diagnosis of transformation
PET-CT is such a non-invasive imaging technique of the whole body allowing quantitative assessment of biochemical and functional processes. It measures annihilated photons
Introduction and scope of this thesis
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