Figure 5. Histopathologic patterns and different histologic severity in axial vs limb muscles.

The relative frequency of the different histopathologic patterns observed in this series (n = 78) is represented in the graph. Foci of sarcomere disorganization and mitochondria depletion, spanning only a few sarcomeres on the longitudinal axis of the fiber (minicores), were observed in 60% of the biopsies (A.c–A.e and B.b and B.c). (A) The most common pattern was typical of a congenital myopathy with minicores (multi-minicore disease), including mild or no endomysial fibrosis (A.a), type I fiber predominance and relative hypotrophy (dark fibers, A.b), and multiple lighter zones devoid of succinate dehydrogenase (SDH) or nicotinamide adenine dinucleotide (NADH) enzymatic activity (A.c) corresponding to mitochondria depletion and sarcomere disorganization on electron microscopy (EM) (minicores) (A.d and A.e). (B) Around 24% of biopsies showed a mild to moderate congenital muscular dystrophy pattern, associated with either abundant or scattered/inconspicuous minicores. Note prominent endomysial fibroadiposis but rare necrotic or regenerating fibers (B.a). (C) Eosinophilic inclusions compatible with Mallory body–like inclusions (arrows, C.a and C.b) or rimmed vacuoles (arrowheads, C.d and C.e) were identified in some samples but typically involved a small percentage of fibers. Thus they were easily overlooked unless specifically searched for. (D) Two muscle samples taken from the same patient at 12 years of age revealed that histopathologic changes were more severe in axial than in limb muscles, mirroring the clinical situation. Her deltoid muscle (D.a and D.b) showed minor myopathic changes, with mild fiber size variation and scattered internalized nuclei and minicores. In contrast, her abdominal muscles revealed major dystrophic changes with muscle fiber loss, fatty-adipose replacement, rimmed vacuoles (D.c), rod-like inclusions (D.e), multi-minicores (D.d), and also well-delimited cores with a hyperoxidative perilesional rim (similar to those observed in central core disease) (D.f). Transversal frozen sections stained with hematoxylin & eosin (A.a, B.a, C.b–C.d, D.a and D.c), reduced NADH (A.c, B.c, D.b and D.f), ATPase 4.6 (A.b), SDH (B.b and D.d), modified Gomori trichrome (C.a and C.e, D.e); longitudinal EM sections (A.d and A.e). Scale bars: 50 µm except for A.d and A.e: 2 µm.