The diagnostic value of routine muscle at autopsy: high prevalence and systematic under-detection of type 2 myofiber atrophy
In brief
Neuropathology review finds type 2 muscle atrophy fivefold more often
In a prospective autopsy series, fiber size variation on routine H&E staining accurately predicted type 2 myofiber atrophy (about 90% sensitivity and specificity). Yet a non-neuropathology-trained pathologist identified the lesion in only 10% of cases, revealing a five-fold detection gap. Wider muscle sampling and focused H&E review could close this under-diagnosis.
- Journal
- Neuromuscular disorders : NMD (Q1)
- Published
- 28 August 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Robert Hennis, Alex Rayo, Jody E Hooper, Hannes Vogel, Meagan Chambers
- PMID
- 42753429
- DOI
- 10.1016/j.nmd.2026.107415
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (paper of the day, 18 September 2026): Fiber size variation on H&E accurately predicts type 2 myofiber
Abstract
Type 2 myofiber atrophy is a clinically significant manifestation of muscle wasting. Its detection at autopsy depends on recognition of fiber size variation on routine hematoxylin and eosin (H&E) staining - a potentially subtle finding that may be missed without neuropathological training. Its prevalence is therefore likely to be under-reported, particularly in autopsy populations which are enriched for chronic illness, malignancy, and therapeutic high dose steroids. We conducted a prospective diagnostic accuracy study using a hospital autopsy cohort signed out by a board-certified neuropathologist, in which myosin fast immunohistochemistry was ordered prospectively as a reference standard. A non-neuropathology-trained pathologist's retrospective autopsy cohort, in which IHC was not ordered, served as a comparison. Diagnostic accuracy measures were calculated for fiber size variation as a predictor of type 2 atrophy. Logistic regression was performed to identify clinical predictors of type 2 atrophy. Diagnostic histopathological findings were present in 58.0% of prospective cases and included type 2 atrophy, necrosis and metastatic calcification. Type 2 fiber atrophy was identified in 52.2%. Fiber size variation as a predictor of type 2 atrophy had a sensitivity of 90.2%, specificity of 89.3%, positive predictive value of 92.5%, and negative predictive value of 86.2%. The non-neuropathology-trained pathologist identified type 2 atrophy in 10.5% of cases. Longer hospital stay was significantly associated with type 2 atrophy (median 19.0 vs. 4.0 days; p=0.0004; OR=6.37). In a hospitalized autopsy population, fiber size variation on H&E is a highly accurate proxy for clinically significant type 2 fiber atrophy. Type 2 atrophy may be substantially underdiagnosed at routine hospital autopsy, with a five-fold detection gap between neuropathology-trained and autopsy pathologists. Universal muscle sampling and targeted H&E evaluation for fiber size variation can achieve efficient and cost-effective detection of important diagnoses in the autopsy setting.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.