Skeletal muscle pathology is the study of diseases and disorders that effect skeletal muscle.

In this section we highlight non neoplastic entities that effect skeletal muscle, which include:

Dermatomyositis
Polymyositis
Muscular dystrophy (Duchenne muscular dystrophy & Becker muscular dystrophy)
Neuromuscular junction disorders (Myasthenia gravis & Lambert-Eaton syndrome)

For neoplastic lesions that may affect skeletal muscle please refer to Soft Tissue Tumors Pathology Study Guide.

Dermatomyositis

Dermatomyositis is an inflammatory disorder of the skin and skeletal muscle.

Dermatomyositis is characterized by muscle weakness and Gottron’s papules which is a pathognomonic distinctive skin rash.

The exact cause of dermatomyositis is unknown.

Some cases of dermatomyositis are associated with carcinoma, for example, gastric carcinoma.

Clinical features of dermatomyositis include:

Bilateral proximal muscle weakness (distal involvement can develop late in disease)
Rash of the upper eyelids (heliotrope rash)
Grotton’s papules which are red papules on the knuckles, elbows, and knees
Malar rash

Laboratory findings of dermatomyositis include:

Increased creatinine kinase
Positive antinuclear antibody (ANA)
Positive anti-Jo-1 antibody

Histology of dermatomyositis will show perimysial inflammation (CD4+ T-cells) with perifascicular atrophy.

Corticosteroids are used for the treatment of dermatomyositis.

Dermatomyositis. Gottron's papules on finger joints Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider - Not altered. CC BY-SA 3.0
Dermatomyositis. Micrograph of dermatomyositis, muscle biopsy, H&E stain Nephron - Not altered.CC BY-SA 3.0
Dermatomyositis. Gottron's papules Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider - Not altered. CC BY-SA 3.0
Dermatomyositis. Gottron's papules on the elbows of a person with juvenile DM Elizabeth M. Dugan, Adam M. Huber, Frederick W. Miller, Lisa G. Rider - Not altered. CC BY-SA 3.0
Dermatomyositis. X-Ray of the knee in a person with dermatomyositis. M Rich. Not altered. CC BY-SA 1.0
Dermatomyositis. Calcification from dermatomyositis James Heilman, MD - Not altered. CC BY-SA 4.0
Dermatomyositis. A hematoxylin-eosin stain of skin biopsy showing perivascular and interface lymphocytes and dermis edema and mucin that are characteristic of dermatomyositis. (×100 magnification). b Alcian Blue stain of skin of the skin biopsy highlighting the increased dermal mucin in the superficial dermis that is characteristic of dermatomyositis. (×40 magnification). Paraneoplastic cerebellar degeneration and dermatomyositis as first manifestations of underlying breast malignancy: a report of two cases and a brief review of the subject. Ng YR, Ho CD, Ng WL, Tan SM - Surgical case reports (2015). Not Altered. CC.

Polymyositis

Polymyositis is an inflammatory disorder of skeletal muscle.

Polymyositis is a rare condition that weakens the muscles on both sides of the body.

Clinically, polymyositis resembles dermatomyositis but the skin is not involved.

Histology of polymyositis will show endomysium inflammation (CD8+ T cells) with necrotic muscle fibers.

Polymyositis. Inflammatory infiltrates in a muscle biopsy. Holes in the muscle cell vacuoles, deposits of abnormal proteins within the cells and in filamentous inclusions (hence the name inclusion body myositis} are clearly visible in the cellular interstitial space. Jensflorian -Not altered. CC BY-SA 3.0
Immunohistochemical staining (brown) for (A, B) microsomal prostaglandin E synthase (mPGES)-1, (C, D) cyclooxygenase (COX)-1 and (E, F) COX-2 in representative muscle tissue sections counterstained with haematoxylin (A, C, E) from patients with polymyositis and (B, D, F) from healthy individuals (original magnification ×500).Effects of immunosuppressive treatment on microsomal prostaglandin E synthase 1 and cyclooxygenases expression in muscle tissue of patients with polymyositis or dermatomyositis. Korotkova M, Helmers SB, Loell I, Alexanderson H, Grundtman C, Dorph C, Lundberg IE, Jakobsson PJ - Annals of the rheumatic diseases (2007). Not Altered. CC.

Muscular Dystrophy

Muscular dystrophy is a degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue.

The main types of muscular dystrophy to be aware of are:

Duchenne muscular dystrophy (Duchenne is disastrous = worse prognosis)
Becker muscular dystrophy (Becker is better = better prognosis)

Muscular dystrophy is caused by abnormal dystrophin.

The attachment of the muscle cytoskeleton to the extracellular matrix is made possible by dystrophin.

Mutations in dystrophin often occur spontaneously, and a high rate of mutation is predisposed by a large gene size.

Duchenne muscular dystrophy is due to deletion of dystrophin.

At around the age of 1-year-old, patients with Duchenne muscular dystrophy may have proximal muscular weakness that progresses to involve distal muscles.

Calf pseudohypertrophy is a characteristic finding of Duchenne muscular dystrophy.

Lab findings of Duchenne muscular dystrophy may show:

Elevated lactic acid
Elevated serum creatinine kinase is elevated

The heart is typically involved in Duchenne muscular dystrophy.

In Duchenne muscular dystrophy death typically results from cardiac or respiratory failure.

Becker muscular dystrophy is due to mutated dystrophin.

Becker muscular dystrophy clinically results in milder disease compared to Duchenne muscular dystrophy.

Muscular Dystrophy. Muscular dystrophy is a genetic disorder where the muscle tissue wastes away and loses function. In the affected muscle (right), the tissue has become disorganized and the concentration of dystrophin (green), an important protein in normal muscle functioning, is greatly reduced. Cbenner - Not altered. CC BY-SA 3.0

Neuromuscular Junction Disorders

Myasthenia Gravis

Myasthenia gravis is a chronic autoimmune disorder due to autoantibodies against the postsynaptic acetylcholine receptor at the neuromuscular junction.

Myasthenia gravis is more commonly seen in women than men.

Clinical manifestations of Myasthenia gravis include:

Muscle weakness that worsens with use
Muscle weakness improves rest
Ptosis (lid lag)
Diplopia

Myasthenia gravis is associated with thymic hyperplasia and thymomas.

Thymectomy may improves symptoms.

Treatment of myasthenia gravis are anti-cholinesterase agents which help alleviate symptoms.

Mysathenia Gravis. Strabismus in a person with myasthenia gravis trying to open their eyes. James Heilman, MD - Not altered. CC BY-SA 3.0
Mysathenia Gravis. Photograph of a person showing right partial ptosis (left picture), the left lid shows compensatory pseudo lid retraction because of equal innervation of the m. levator palpabrae superioris (Hering's law of equal innervation): Right picture: after an edrophonium test, note the improvement in ptosis. Mohankumar Kurukumbi, Roger L Weir, Janaki Kalyanam, Mansoor Nasim, Annapurni Jayam-Trouth. - Not altered. CC BY 2.0
Mysathenia Gravis. A chest CT-scan showing a thymoma (red circle) Tdvorak - Not altered CC BY-SA 4.0

Lambert-Eaton Syndrome

Lambert-Eaton syndrome is due to antibodies directed against presynaptic calcium channels of the neuromuscular junction.

Lambert-Eaton syndrome may arise due to a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lung.

Lambert-Eaton syndrome is associated with impaired acetylcholine release.

Firing of presynaptic calcium channels is required for acetylcholine release.

Clinical features of Lambert-Eaton syndrome include:

Proximal muscle weakness that improves with use

Anticholinesterase agents do not cause any improvement of the symptoms due to Lambert-Eaton syndrome.

Lambert-Eaton syndrome may resolves with resection of the cancer if the cancer is the underlying cause.

Lambert-Eaton Syndrome. Not altered. CC BY-SA 3.0
Lambert-Eaton Syndrome. Chest X-ray showing a tumor in the left lung (right side of the image) Lange. Not altered. CC BY-SA 3.0
Pathological and cytological findings in an SCLC patient with LEMS. Specimens were obtained by cervical lymph node biopsy on February 14, 2002. Paraffin-embedded sections were stained with antibody using the polymer method (The Dako Envision™ FLEX, Dako Japan, Tokyo, Japan) and signal was developed with diaminobenzidine (DAB). Sections were counterstained with hematoxylin. Positive staining for markers in cytoplasm and on cell membrane was indicated in brown. a There are dense sheets of small cells with nuclear molding and necrosis (hematoxylin–eosin staining). b CD56 was diffusely and strongly positive on cell membrane. c Chromogranin A was diffusely and moderately expressed in cytoplasm. d Synaptophysin was focally and weakly expressed in cytoplasmRelapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period. Asano F, Watanabe K, Shinkai M, Tei Y, Mishina K, Tanabe M, Ishii H, Shinoda M, Shimokawaji T, Kudo M, Kaneko T - Chinese journal of cancer (2016). Not Altered. CC.