465 A clinically applicable molecular classification of oncocytic cell thyroid nodules 11 Table 3. Consideration points for CNA-LOH analysis in daily clinical practice · All assessments should be performed by an experienced thyroid pathologist. · Confirm the presence of true oncocytic cells in the cytological or histopathological sample by microscopic assessment [20]. · Consider the tumour cell percentage of the tested sample. In case of a suboptimal tumour cell percentage, i.e., 30-50% in the case of testing on cytology, assessing the possible presence of endoreduplication may be more difficult. · Four main CNA patterns are distinguished: o GH type alterations with (suspected) endoreduplication, consistent with genotype AA or a multiple thereof in the affected chromosomes, associated with OCA, progression of disease and worse prognosis; initial total thyroidectomy may be considered instead of diagnostic hemithyroidectomy depended on the clinical patient context. o GH type alterations without (suspected) endoreduplication, consistent with genotype A0 in the affected chromosomes. Observed in both OA and OCA, the number of affected chromosomes and presence of heterogenicity define the molecular diagnosis (Figure 2); diagnostic hemithyroidectomy is recommended to obtain a definitive diagnosis. o RCI type with chromosomal copy number gains, genotype AAB, foremost associated with benign, biologically indolent disease. Hemithyroidectomy may be considered. o No CNA, normal heterozygous pattern. · The presence of widespread GH type alterations with suspected endoreduplication likely indicates a biologically more aggressive tumour, even in OCN without signs of capsular or vascular invasion (i.e., morphological OA). (Re-)consideration of a malignant molecular diagnosis is warranted. · The results of the CNA-LOH analysis should be interpreted alongside the results of somatic mutation and fusion analysis. No CNA are found in nodular hyperplasia with oncocytic cell metaplasia and part of the OA. The absence of CNA alone does not exclude malignancy and does not justify withholding diagnostic surgery for a Bethesda III or IV nodule with cytology suspicious for OCN. If no CNA and no somatic mutations or fusions are detected, however, withholding diagnostic surgery may be considered oncologically safe. · The results of the CNA-LOH analysis should be interpreted in context of other clinicopathological characteristics, including nodule size.
RkJQdWJsaXNoZXIy MTk4NDMw