444 chapter 11 To advance the diagnostic workup and risk stratification of OCN, the development of a molecular test that is both accurate and feasible in everyday clinical practice is crucial. The methods previously used for CNA and LOH (CNA-LOH) analysis by Corver et al. and Ganly et al. are highly accurate and informative but time-consuming, costly, and thus not fit for everyday application [343, 649, 674, 682]. Corver et al. combined multiparameter DNA flow cytometry with whole-genome single nucleotide polymorphism (SNP) array analysis (using 6,000 to >200,000 SNPs) [649, 682]. The algorithm used is referred to as lesser-allele intensity-ratio (LAIR) analysis, which incorporates the DNA index of the G0G1 tumour cell fraction into the CNA-LOH analysis [682], validated by fluorescence in-situ hybridization (FISH) [343]. Ganly et al. combined [543, 674]. Doerfler et al. used the commercial ThyroSeq® v3, which is applied on a large scale in clinical practice in the USA [484, 579]. They distinguished two main types of CNA: a GH type characterized by widespread chromosomal losses and a focal chromosomal type characterized by random losses and gains of chromosomal regions. Unfortunately, full information regarding their interpretation of the CNA analysis, distinguished chromosomal patterns, and details on the underlying chromosomal alterations were not presented [484, 683]. The current study aimed to implement a clinically applicable test using a limited 1,500 SNP next generation sequencing (NGS) panel. We described the CNA patterns that we observed in benign and malignant OCN and assessed them in a clinical cohort of OCN, with certain focus on the methodological and bioinformatical aspects. We highlighted two cases to illustrate the added value of CNA-LOH analysis in clinical practice. Finally, we provided considerations for the structured interpretation of the CNA-LOH analysis results using this NGS panel. Materials and Methods Study design and case selection For the current retrospective study, pseudonymized pathology records were reviewed to identify cases with a OCN of the thyroid in which molecular analysis including CNA-LOH analysis was performed on the primary tumour at our tertiary care centre between 1 May 2020 and 31 December 2021. Patients were only eligible for inclusion if the diagnosis of a oncocytic cell lesion was confirmed by histopathology, including nodular hyperplasia with oncocytic cell metaplasia (NH-H), OA, and OCA. Prior to inclusion in the current study, all histopathological diagnosis were made or reviewed by an experienced thyroid pathologist (HM) in accordance with the WHO classification (5th edition), including a morphological assessment and immunohistochemistry of H&E sections [22]. Ethical study review was waived by the medical ethical review committee Leiden the Hague Delft (no. G21.167). No informed consent was required.
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