Assessment of Skin Biopsy as a Diagnostic Biomarker in CSF1R-Related Disorder.

Abstract

To validate a recently published study in which skin biopsy was reported as a valuable alternative to brain biopsy in diagnosing <i>CSF1R</i>-related disorder (<i>CSF1R</i>-RD). Blinded evaluation of skin samples was performed by independent reviewers using light and electron microscopy collected from a group of <i>CSF1R</i> variant carriers (n = 10) with various genotypes (mono and biallelic), different stages of the disease (asymptomatic and symptomatic), and exposed to different therapies (glucocorticoids, hematopoietic stem cell transplantation, and TREM2 agonist), and from a group of healthy controls (n = 5). Biopsies from patients with <i>CSF1R</i>-RD at various disease stages were indistinguishable from controls determined using light microscopy and electron microscopy. We found no distinctive axonal pathology in skin biopsies collected from <i>CSF1R</i> variant carriers at all stages of the disease. Our results are consistent with clinical and neurophysiologic features of the <i>CSF1R</i>-RD, in that peripheral nervous system involvement has not been reported. Studies aiming to discover new biomarkers are important, but the results must be validated with larger numbers of patients and healthy controls. Based on blinded light and electron microscopic studies of skin biopsies, there is no evidence that <i>CSF1R</i>-RD is associated with distinctive changes in cutaneous peripheral nerves. This suggests that skin biopsy is not useful in diagnosis of <i>CSF1R</i>-RD. This study provides Class III evidence that skin biopsy does not distinguish those with <i>CSF1R</i>-RD, or carriers, from normal controls.