Muscle and nerve biopsies can be extremely useful in the evaluation of patients with myopathies and neuropathies. That said, not everyone suspected of having a muscle or nerve disorder needs a biopsy. In this chapter, we discuss the indications and limitations for muscle and nerve biopsies, how specific muscle or nerves are selected for biopsy, and various aspects of specimen handling. Further, we review the routine stains that are performed on muscle and nerve tissue, other stains or studies that can be performed on the tissue, and when to order them. We also mention the role of skin biopsy to assess epidermal nerve fibers in the evaluation of patients with peripheral neuropathy. This chapter is not designed to make the reader a neuropathologist. However, clinicians who take care of patients with neuromuscular disease and order biopsies should have at least a working knowledge of muscle and nerve histopathology.
Muscle biopsies are studied through a combination of various histochemistry stains on frozen sections and paraffin-embedded tissue, electron microscopy (EM), and molecular studies (e.g., enzyme assay, protein analysis by Western blot, mitochondrial DNA mutations).1–5 It is important to correlate the histopathologic findings with clinical history, neuromuscular examination, and electrodiagnostic findings.
INDICATIONS FOR MUSCLE BIOPSY
A muscle biopsy may be helpful when the patient has objective muscle weakness, abnormal muscle enzymes (e.g., elevated serum creatine kinase [CK] levels), abnormal skeletal muscle magnetic resonance imaging, or myopathic electromyography (EMG) findings. These findings may point to a myopathy but not the exact etiology, and therefore a muscle biopsy may be indicated. That said, if the diagnosis is suspected on the basis of the phenotype and can be made by less invasive means, we generally opt for this first. For example, in a young boy with proximal weakness and large calves, we would first do genetic testing for a dystrophinopathy. Muscle biopsies are less helpful in evaluating patients with only myalgias, subjective weakness, or just slight elevations of CK in the absence of objective abnormalities.6
Muscle tissue can be obtained through an open (minor surgical procedure) or needle biopsy. A larger sample of tissue can be biopsied by the open surgery technique, and we prefer this method in patients who may have patchy pathology (e.g., inflammatory myopathies) or myopathies that require metabolic analysis (e.g., mitochondrial disorders or glycogen storage diseases), molecular studies (e.g., Western blotting and direct genetic analysis), or EM. Needle biopsy can also be technically difficult in patients with substantial subcutaneous tissue or whose muscles are atrophic and/or fibrotic. However, the yield of a needle biopsy can be quite high in laboratories that are experienced in handling the small amount of tissue obtained by this technique.7–10 The advantage of a needle biopsy is that it allows for the examination of multiple sites within the muscle ...