Clinicopathological collaboration in adult muscle disease: a pragmatic pathway to approach diagnostic dilemmas

Abstract

The role of muscle biopsy in the investigation of neuromuscular disease remains firmly established but has evolved. Expertise in diagnostic myopathology remains relevant and supports clinical practice. Neuromuscular disease is rare; thus clinicopathological correlation, or better, collaboration is important. The process starts in the clinic with the identification of patients for whom muscle biopsy will be beneficial for diagnosis and management in a multidisciplinary neuromuscular care setting. In this review article, we describe the current use of muscle biopsy in our adult practice and discuss several carefully selected real cases [e.g., asymmetric hand weakness, dysphagia and proximal weakness, subacute weakness with raised creatine kinase (CK), non-specific presentation], where biopsy and collaboration have been instrumental in achieving the correct diagnosis for the patient. We discuss areas of diagnostic difficulty, such as fairly common starting scenarios leading to unusual entities, atypical presentations of common diseases and novel pathological findings. We will focus on the idiopathic inflammatory myopathies (IIMs), the most common indication for adult muscle biopsies in many diagnostic settings, whereby the use of an integrated clinical–serological–pathological classification is now firmly established. We will also explore the evolving role for and continuing need of muscle biopsy in the genomic era, particularly with assessing the potential pathogenicity of reported genetic variants of uncertain significance (VUS). We describe a pragmatic approach to detecting the more common disorders, which also enables us to distinguish ‘the horses from the zebras’ and manage diagnostic uncertainty.