How to Read a Biopsy

When the pathologist is asked to evaluate a muscle biopsy, much of the interpretation is based on his or her previous experience and the recognition of similarities between the biopsy and muscle from known diseases. In some instances, such as an advanced dystrophy or a spinal muscular atrophy, the changes may be striking and unequivocal. In others, the changes may be more subtle and a systematic approach is required in the evaluation and interpretation. Once the pathology is defined, correlation with clinical features is essential and the pathology must be interpreted in the light of this. A muscle biopsy is only one piece of the jigsaw and has to be considered together with the family history, the clinical history and presentation and the results of any other investigations. Knowledge of serum creatine kinase (CK) levels, for example, is a useful indicator; no case of Duchenne muscular dystrophy has a normal CK, whereas levels are usually normal in congenital myopathies and neurogenic disorders. Knowledge of the distribution of muscle weakness, cardiac involvement, respiratory difficulties, abnormalities in brain and muscle magnetic resonance imaging (MRI), contractures and joint laxity are also valuable. Clinical spectra are widening with molecular advances and the increasing application of whole genome and exome sequencing, which has led to a wider appreciation of pathological features seen in muscle biopsies. There is frequently a lack of concordance between the severity of the pathological change and the degree of clinical disability, which places a constraint on the pathologist in giving a prognostication for a particular disease process. It is safer to define the type of pathological change and leave the assessment of clinical severity and prognosis to the clinician. Relating the pathology to the clinical picture is paramount to diagnosis. For example, an overtly dystrophic picture in a 6-month-old infant with hypotonia from birth may suggest the diagnosis of congenital muscular dystrophy, whereas a similar picture in a 14-year-old boy who was ambulant until the age of 10 would be characteristic of Duchenne muscular dystrophy. Similarly, an identical pathological picture is seen in a severely affected infant with Werdnig–Hoffmann disease (spinal muscular atrophy; SMA I) as in a milder case with later onset and better motor function and prognosis (SMA II).

There are considerable advantages if the clinician assessing the patient can also view and discuss the biopsy with the pathologist, and then provide a comprehensive diagnosis of the patient. This has always been our policy and gives continuity between the clinical diagnosis and other investigations. Regular multidisciplinary meetings between the clinicians, pathologists and other personnel involved in the diagnosis and care of a patient therefore have an important role.

During the preparation of the first edition of this book, a chapter was added, almost as an afterthought, which reflected many discussions on various aspects of interpretation of muscle pathology. It represented a synthesis of the approach to the interpretation of changes in a biopsy which we thought might be helpful, particularly to the novice in muscle pathology.

While retaining the same basic format as before, we have revised and extended the content of this chapter, updated each section, including the section on clinical features that may alert the pathologist to consider a possible diagnosis. Our aim is to summarize the main pathological features and to give a synopsis of their relevance. Subsequent chapters will give more detail on individual disorders. Part I attempts to place the biopsy into a normal or abnormal category and, if abnormal, to try and characterize the abnormality as myopathic/dystrophic or neurogenic, or some other pathological change. Part II attempts to provide a more specific diagnosis, based on comparison with the classical changes found in individual disorders. The sequence of features is expressed in the form of a flow sheet and is based primarily on the routine histological stains, haematoxylin and eosin (H&E), and Gomori trichrome, and the histochemical reactions for oxidative enzymes and adenosine triphosphatase (ATPase) and the additional techniques mentioned in Chapter 2 . Parts III and IV provide a similar approach to immunohistochemistry and electron microscopy, respectively. Part V lists some useful clinical features that are relevant to differential diagnosis and can alert the pathologist towards a possible diagnosis. It is not intended as a comprehensive or exclusive list of clinical features associated with particular disorders and should be read in conjunction with the chapters in Section B.