Histopathology of Skeletal Muscle Degeneration: A Review, Study notes of Pathology

An in-depth analysis of skeletal muscle degeneration, including its various microscopic changes, causes, and diagnostic challenges. figures illustrating different stages of degeneration in rats and references to relevant literature.

Typology: Study notes

2021/2022

Uploaded on 09/12/2022

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Skeletal Muscle Degeneration
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Figure Legend: Figure 1 Skeletal muscle - Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. A central myofiber is swollen and hypereosinophilic (arrows), and a fragmented segment of another fiber (arrowhead) demonstrates segmental degeneration. Figure 2 Skeletal muscle

  • Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. An enlarged, hypereosinophilic muscle fiber with subtle vacuolation is present in an otherwise normal muscle bundle. Figure 3 Skeletal muscle - Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. A rounded fiber contains multiple peripheral nuclei, a single internal nucleus, and abundant cytoplasmic vacuoles. Figure 4 Skeletal muscle - Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. Multiple macrophages and interstitial cells have phagocytized degenerative portions of an enlarged muscle fiber. Figure 5 Skeletal muscle - Degeneration in a male F344/N rat from a chronic study. In this cross section of muscle, several adjacent muscle fibers exhibit multiple features of degeneration; increased sarcolemmal nuclei are indicative of an early regenerative response. Figure 6 Skeletal muscle - Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. Degeneration is represented by a swollen, hyalinized, and partly fragmented muscle fiber. Figure 7 Skeletal muscle - Degeneration in a male Harlan Sprague-Dawley rat from a subchronic study. A fragmented and partly hyalinized muscle fiber has lost its striations and is accompanied by early infiltration of macrophages.

Comment: Degenerated muscle can grossly appear either pale or dark. Histologically, degenerating myofibers can exhibit a variety of microscopic changes, including cell swelling, hypereosinophilia,

inflammation and hemorrhage, should not be diagnosed separately unless warranted by severity but should be described in the narrative.

References: Berridge BR, Van Vleet JF, Herman E. 2013. Cardiac, vascular, and skeletal muscle systems. In: Haschek and Rousseaux’s Handbook of Toxicologic Pathology, 3rd ed (Haschek WM, Rousseaux CG, Wallig MA, Bolon B, Ochoa R, Mahler MW, eds). Elsevier, Amsterdam, 1635-1665.

Greaves P. 2007. Musculoskeletal system. In: Histopathology of Preclinical Toxicity Studies, 3rd ed. Elsevier, Oxford, 160-214.

Greaves P, Seely JC. 1996. Non-proliferative lesions of soft tissues and skeletal muscle in rats, MST-1. In: Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC.

Greaves P, Chouinard L, Ernst H, Mecklenburg L, Pruimboom-Brees IM, Rinke M, Rittinghausen S, Thibault S, von Erichsen J, Yoshida T. 2013. Proliferative and non-proliferative lesions of the rat and mouse soft tissue, skeletal muscle, and mesothelium. J Toxicol Pathol 26(3 suppl):1S-26S. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/

Haschek WM, Rousseaux CG, Wallig MA. 2010. Cardiovascular and skeletal muscle systems. In: Fundamentals of Toxicologic Pathology, 2nd ed. Academic Press, San Diego, 319-376.

Leninger JR. 1999. Skeletal muscle. In: Pathology of the Mouse (Maronpot R, Boorman G, Gaul BW, eds). Cache River Press, St Louis, 637-643.

McDonald MM, Hamilton BF. 1990. Bones, joints, and synovia. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman G, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 193-207.

Vahle JL, Leininger JR, Long PH, Hall DG, Ernst H. 2013. Bone, muscle, and tooth. In: Toxicologic Pathology Nonclinical Safety Assessment (Sahota PS, Popp JA, Hardisty JF, Gopinath C, eds). CRC Press, Boca Raton, FL, 561-587.

Van Vleet JF, Valentine BA. 2007. Muscle and tendon. In: Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, 5th ed, Vol 1 (Grant MG, ed). Elsevier, Edinburgh, 185-280.

Weller AH, Magliato SA, Bell KP, Rodenberg NL. 1997. Spontaneous myopathy in the SJL/J mouse: Pathology and strength loss. Muscle Nerve 20:72-82. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/

Author:

Torrie A. Crabbs, DVM, DACVP Pathologist Experimental Pathology Laboratories, Inc. Research Triangle Park, NC