Muscle biopsy in genomic era: real-world diagnostic and clinical implications over 10 years

The diagnostic role of muscle biopsy has evolved with the increasing availability of next-generation sequencing (NGS). However, real-world data on its clinical impact in contemporary neuromuscular practice remain limited.

To evaluate the diagnostic yield of muscle biopsy in a 10 year consecutive cohort, assessing concordance across clinical suspicion, histopathological findings, and final clinical diagnosis, and exploring demographic predictors of biopsy outcome.

A retrospective cohort study of all consecutive muscle biopsies performed at a single tertiary neuromuscular center (2015-2025). Concordance analysis was performed at two levels: clinical suspicion vs. biopsy conclusion, and biopsy conclusion vs. final diagnosis at the last follow-up. Sex- and age-related differences across biopsy categories were evaluated using chi-square and Kruskal-Wallis tests.

Among 401 consecutive biopsies (56.9% male; median age 49 years), overall concordance between clinical suspicion and biopsy conclusion was 42.3%. Concordance with final clinical diagnosis was substantially higher, reaching 94.0% for idiopathic inflammatory myopathies (IIMs) among evaluable cases. Non-specific myopathic findings and normal biopsies accounted for 36.0% of cases; however, patients with non-specific myopathic findings were significantly more likely to receive a conclusive diagnosis at follow-up than those with normal biopsies (43.8% vs. 23.4%; OR 2.54, 95% CI 1.23-5.26, p = 0.011). Sex distribution differed significantly across biopsy categories (p < 0.001), with IIMs showing marked female predominance (69.1%).

Muscle biopsy retains high diagnostic value in contemporary neuromuscular practice when applied to clinically selected patients. Beyond establishing specific diagnoses, biopsy findings carry prognostic significance and provide demographic signatures that reinforce their clinical validity.