Abstract
PurposeScreening for paraneoplastic antibodies is often performed by means of indirect immunofluorescence on primate cerebellar slices. However, atypical immunofluorescence patterns, i.e. patterns that are not specifically related to paraneoplastic antibodies, are often reported. The clinical significance of these patterns is not clear. Therefore, the purpose of this study was to determine the significance and diagnostic value—in terms of a paraneoplastic neurological syndrome or other neurological disease being diagnosed in the patient—of such atypical immunofluorescence screening patterns on primate cerebellum.MethodsThis study is a retrospective single center study including atypical indirect immunofluorescence screening patterns of patients with a negative or absent typing assay for intraneuronal and anti-amphiphysin paraneoplastic antibodies. Patients with a positive typing assay or without final diagnosis were excluded. Included patients were grouped according to (i) reported immunofluorescence pattern and (ii) established diagnosis, after which contingency table analyses were performed to investigate an interrelation between reported pattern and diagnostic group.ResultsIn 3.7% of cases, patients with an atypical pattern obtained a final diagnosis of a paraneoplastic neurological syndrome. The presence of atypical patterns was more prominent in patients with epilepsy or peripheral neuropathies (pMonte Carlo simulation= 0.026), without, however, adding any diagnostic information.ConclusionsAn atypical indirect immunofluorescence pattern on primate cerebellum in the screening for paraneoplastic antibodies has only very minor relevance with respect to paraneoplastic neurological syndromes or any other neurological disease, recommending clinicians to interpret the results of positive screening assays for such antibodies with care.
Highlights
Paraneoplastic neurological syndromes (PNS) are remote effects of cancer not caused by tumor growth, infiltration, metastasis or chemotherapy [1, 2]
An atypical indirect immunofluorescence pattern on primate cerebellum in the screening for paraneoplastic antibodies has only very minor relevance with respect to paraneoplastic neurological syndromes or any other neurological disease, recommending clinicians to interpret the results of positive screening assays for such antibodies with care
Our study investigated the clinical significance of atypical indirect immunofluorescence (IIF) patterns on cerebellar slices, i.e. patterns that are not related to the presence of group I Ab and that are not followed by a positive line blot typing assay
Summary
Paraneoplastic neurological syndromes (PNS) are remote effects of cancer not caused by tumor growth, infiltration, metastasis or chemotherapy [1, 2] They are predominantly the result of an autoimmune process, mediated. Based upon targeted antigen location, AN Ab can be divided into two subgroups: intracellular (group I) or on the cell membrane (group II) (Fig. 1) [1, 12, 13] Their detection is classically performed by screening assays such as indirect immunofluorescence (IIF) screening on primate cerebellum, followed by typing assays such as line blots or cell-based assays [1, 13,14,15,16]. Intraneuronal and anti-Amphiphysin Ab (Fig. 1), the most often paraneoplastic (PN) Ab, show typical IIF patterns on primate cerebellum such as positive neuronal nuclei (anti-Hu) or coarse granular staining of cytoplasm of Purkinje cells (anti-Yo) [1, 12, 13, 17].
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