2025 – Case 8

by | Sep 25, 2025 | 2025 Diagnostic Case Studies

Presenter

John Rossiter

Bio
John Rossiter is a neuropathologist at Kingston Health Sciences Centre and a professor in the Department of Pathology and
Molecular Medicine, Queen’s University, Kingston, Ontario, Canada.

Authors

John P. Rossiter1, Paula Adler2, Kevin Y. M. Ren1, Michel Melanson2

1Department of Pathology & Molecular Medicine and 2Division of Neurology, Queen’s University, Kingston, ON, Canada.

Conflict of Interest

I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose.

Clinical Summary

An 86 year old woman presented with an 8 month history of rapidly progressive proximal muscle weakness in association with weight loss, but without myalgia, oculobulbar, respiratory, sensory or autonomic symptoms. On examination there was severe proximal limb weakness, hyporeflexia and significant diffuse muscle atrophy. EMG showed myopathic motor units with widespread fibrillation potentials and nerve conduction studies suggested mild peripheral neuropathy. Initial laboratory investigations showed mildly elevated creatinine kinase (280, normal range 40-230 U/L), while serum myositis and paraneoplastic antibody panels were negative. MR imaging showed diffuse edema throughout muscles of the chest wall, shoulder and upper arm, along with muscle atrophy. Additional investigations included serum protein electrophoresis, bone marrow analysis and left deltoid muscle biopsy. The integrated findings directed further patient management.

Discussion points

  1. What are the most significant histopathological findings?
  2. What additional stains/investigations of the biopsy are likely to be most informative?
  3. What is the most likely diagnosis?
Deltoid muscle biopsy: scanned H&E frozen section
Deltoid muscle biopsy: scanned toluidine blue stained resin section (high resolution 3rd from left)
Reveal Diagnosis

Amyloid myopathy: myopathic changes, including ‘ringed’ fibers with prominent sarcolemmal folding, in association with
extensive endomysial and microvascular kappa immunoglobulin light chain amyloid (AL) accumulation.

Additional relevant investigations and comment:
Serum protein electrophoresis identified IgG kappa monoclonal protein, with quantitative serum free light chains showing markedly elevated kappa (637, normal range 3.3 -19.4 mg/L), kappa/lambda ratio 62; and bone marrow aspirate and trephine biopsy showed a plasma cell dyscrasia with 12% cellularity. Additional investigations were negative for osteolytic lesions or cardiac amyloidosis. Treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone was initiated, but without clinical improvement in weakness.
Congo Red staining of the muscle biopsy showed multifocal microvascular and endomysial amyloid accumulation. Immunofluorescent microscopy showed abundant kappa immunoglobulin light chain deposition in microvessels and throughout the endomysium, with accentuation around many muscle fibers.
Electron microscopy showed amyloid fibrils in/around the walls of many microvessels and extensively in the endomysium, including in extracellular clefts of muscle fibers with prominent sarcoplasmic folding.

References
1. Chapin JE, Kornfeld M, Harris A. Amyloid myopathy: characteristic features of a still underdiagnosed disease. Muscle Nerve.
2005; 31(2):266-272.
https://doi.org/10.1002/mus.20169
2. Ostrow, LW, Corse AM, Morrison BM, Huff CA, Carrino JA, Hoke A, Mammen AL. Expanding the spectrum of monoclonal light chain deposition disease in muscle. Muscle Nerve. 2012; 45(5):755-761. https://doi.org/10.1002/mus.23287
3. Tonin P, Pancheri E, Orlandi R, Gajofatto A, Rinaldi R, D’Angelo R, Papa V, Vattemi G, Cenacchi G. Amyloid myopathy: an intriguing diagnosis. Clin Neurol Neurosurg. 2020; 195:105848. doi: 10.1016/j.clineuro.2020.105848
4. Pinto MV, Dyck PJB, Liewluck T. Neuromuscular amyloidosis: unmasking the master of disguise. Muscle Nerve. 2021; 64(1):23-36. doi: 10.1002/mus.27150.
https://doi.org/10.1002/mus.27150
5. Xu J, Zhou X, Wang Y, Liu W, Shan Y, Zhang D, Lv H, Zhao D, Dai T, Zhao Y, Li W, Liu F, Yan C. Skeletal muscle involvement in systemic amyloidosis is often overlooked. Neuropathol Appl Neurobiol 2024; 50(4):e12996.
doi: 10.1111/nan.12996. https://doi.org/10.1111/nan.12996
6. Grafham GK, Mak, G, Grant S, Murphy A, Baker SK, Tarnopolsky M, Lu JQ. Intracellular amyloidosis in peripheral nerve and skeletal muscle. Journal of Neuropathology & Experimental Neurology, 2025 Jul 23:nlaf088.
doi: 10.1093/jnen/nlaf088. https://doi.org/10.1093/jnen/nlaf088

0 Comments