Contributed by Tomoya Kawazoe, MD, PhD1, Akinori Uruha, MD, PhD2, 3, 4, Madoka Mori-Yoshimura, MD, PhD1, Yuko Saito, MD, PhD5,
Shu-ichi Ikeda, MD, PhD6, Mike Saji, MD7, Akira Tanimura, MD, PhD8, Tomofumi Amano, MD, PhD9,
Tomoko Okamoto, MD, PhD1, Yasushi Oya, MD1, Miho Murata, MD, PhD1, Ichizo Nishino, MD, PhD2, 3, Yuji Takahashi, MD, PhD1
1Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Japan.
2Department of Genome Medicine Development, Medical Genome Center, NCNP, Japan.
3Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Japan.
4Pierre and Marie Curie University - Paris VI, National Institute of Health and Medical Research (INSERM),
Mixed Research Unit 974, Center of Research in Myology, Institute of Myology, Pitié-Salpêtrière University Hospital, France.
5Department of Neuropathology, National Center Hospital, NCNP, Japan.
6Intractable Disease Care Center, Shinshu University Hospital, Japan.
7Department of Cardiology, Sakakibara Heart Institute, Japan.
8Division of Hematology, Department of Internal Medicine, National Center for Global Health and Medicine, Japan.
9Hiratsuka Gastroenterological Hospital, Japan.
A 67-year-old man presented with a two-year history of dyspnea on exertion and lower limb weakness. He had undergone endoscopic early gastric cancer treatment twice, at ages 64 and 67. He had no family history of neuromuscular diseases. Hyper-creatine kinase-emia (300 to 1000 IU/L) was noted during annual medical check-ups since age 62. Dyspnea on exertion occurred at age 65, and lower proximal limb weakness occurred at age 66, for which he used a cane at age 67. Neurological examination at age 67 revealed proximal lower limb weakness (Medical Research Council grade 2) with decreased deep tendon reflexes, and constipation/diarrhea with marked intestinal gas accumulation. Blood tests showed hypoproteinemia [total protein (g/dL)/albumin (g/dL) = 5.9/3.8 (1.5)] and hypogammaglobulinemia [IgG 357 mg/dL (870-1700), IgA 17 mg/dL (110-410), and IgM 7 mg/dL (33-190)]. Electrocardiography revealed complete right bundle-branch block, not detected during routine screening until age 64. Echocardiography revealed hypertrophic cardiomyopathy with moderate mitral valve regurgitation. His respiratory function was normal. No dysphagia was observed on video fluoroscopic examination. Results of nerve conduction study were normal. EMG indicated a myogenic pattern with abundant fibrillation potentials and positive sharp waves in the affected/weak muscles. CT revealed bilaterally positioned mass-like lesions in the adductor magnus. 18F-FDG PET demonstrated low diffuse uptake throughout the skeletal muscles and subcutaneous tissues.
Myopathic changes were noted in the vastus medialis. H&E stains showed moderate to severe fiber size variation with scattered necrotic and regenerating fibers. Inflammatory cells were absent. NADH-TR staining revealed disorganized myofibrillar networks (Figure1A). There were myofibers with marked cytoplasmic bodies (CBs) and spheroid bodies (SBs) (Figure 1B). Immunostains showed sarcoplasmic and sarcolemmal expression of HLA-ABC, but not of HLA-DR. C5b-9 deposits were observed partly on the sarcolemma. Genetic testing for myofibrillar myopathy (MFM) was negative. The muscle stained strongly for lambda-light chain (Figure 1C). What is your diagnosis? What additional studies would be confirmatory?