Muscle biopsy often contributes significantly to the evaluation of patients with neuromuscular disease. Knowledge of the fundamentals of muscle biopsy pathology is useful to promote understanding of the pathogenesis of many types of neuromuscular disorders and assists the non-pathologist clinician to understand reports that he or she receives for the muscle biopsies from his or her patients. Knowledge of the basic foundation of muscle biopsy also helps the clinician to understand in what situations a muscle biopsy would be expected to be helpful in assessment of the patient with neuromuscular disease and to be familiar with the types of information that it can provide.
This article is intended to provide an introduction to the pathology of skeletal muscle biopsy and present the pathological features characteristic of certain disorders; this will not present instruction on the subtleties of advanced muscle biopsy diagnosis. This article first presents and contrasts neurogenic and general myopathic features on muscle biopsy. The remainder of this article addresses the key clinical characteristics and pathologic findings on muscle biopsy of selected examples of disorders from 4 different categories of muscle disease: immune-mediated (inflammatory) myopathies, muscular dystrophies, metabolic myopathies, and congenital myopathies. There are occasional examples of the pathology of other disorders that are in the differential diagnosis of some of these entities in order to illustrate their contrasting pathologic features.
Two other articles are companions for this article. The article Skeletal Muscle – Structure and Histology provides a review of normal skeletal muscle histology and ultrastructure, including the histologic appearance of normal muscle with some of the various stains that are used for the processing of muscle biopsies. The article Muscle Biopsy and Clinical and Laboratory Features of Neuromuscular Disease provides information about the procedure of muscle biopsy and background about the general features of the clinical presentations of neuromuscular disorders.
Interpretation of a muscle biopsy can be a challenging task. This process can be difficult because few individual histologic findings are specifically diagnostic of a single disorder. Most muscle biopsies exhibit a constellation of pathologic findings that must be synthesized to arrive at a diagnosis. The muscle pathologist must analyze and interpret the histopathologic features within the individual clinical context to arrive at a diagnostic formulation that makes sense for a given patient.
Here is an example to illustrate the lack of specificity of histopathologic findings and the importance of clinical information for interpretation of a muscle biopsy: A biopsy might exhibit myofibers that contain clear vacuoles on hematoxylin and eosin (H&E) sections. Similar vacuoles can be observed in a variety of settings, including glycogen storage disease, colchicine toxic myopathy, critical care myopathy, the periodic paralyses, and technical artifact, among others. The pathologist uses a variety of strategies to decide which is the most likely cause of the vacuoles in a given case and to determine whether additional special studies are indicated. The simplest and most cost-effective first step is to know which disorders might be reasonable considerations for a specific patient.
Many biopsy samples show numerous pathological findings in varying degrees, each of which is consistent with an assortment of diagnoses. The pathologist must judge the clinical significance of each finding, decide if and how it fits with the other findings in the specimen, and determine what light to cast on the biopsy result to best fit the patient’s presentation. This means that the physicians who submit the biopsy must provide reasonably detailed clinical information. Simply writing, “R/O polymyositis” or “weakness”, or worse, “muscle weakness” (we would not be concerned about weakness of character here, so using the term muscle weakness in this context seems oddly redundant) does not provide the pathologist with any useful clinical information and is a disservice to the patient. The clinical information you provide is not just a bureaucratic requirement and it is not for the benefit of the pathologist; it is for the patient.
Here is the clinical information that must accompany a muscle biopsy to make it possible for the pathologist to fully interpret the histopathologic findings and to determine if special studies are indicated, and if so, which ones would be relevant to a specific individual. It can be stated concisely in a few short phrases or lists or can be submittted in the form of a preexisting clinical note that contains this information:
The clinical signs and symptoms (weakness, pain, fatiguability, numbness, tingling, other), their duration (years, months, weeks, days), distribution, rate of progression and severity
When relevant, lifelong activity level, exercise tolerance and relationship of signs and symptoms to activity
Concurrent medical problems and relevant past medical history
Relevant family history
Findings on physical examination- relevant systemic findings and strength, reflexes, sensory findings and gait
Results of relevant laboratory studies- particularly the creatine kinase level, rheumatologic serologies, electrodiagnostic studies