Muscle and Soft Tissue: Pathology

Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia may be inherited, acquired, or idiopathic. The diagnosis is made clinically, and genetic testing is recommended in individuals with a family history of dystonia. Management is with botulinum toxin or other drugs that target the various neurotransmitters involved in the pathogenesis of dystonia.

Uterine leiomyomas (or uterine fibroids) are benign tumors arising from smooth muscle cells in the uterine myometrium. Leiomyosarcomas, however, are malignant tumors, arising de novo (not from fibroids). With a lifetime risk of > 70% for both African American and Caucasian women, fibroids are common. Conversely, leiomyosarcomas are rare. Leiomyosarcomas may present similarly to uterine fibroids making preoperative diagnosis challenging. Both conditions present with abnormal bleeding, pelvic pain, and/or bulk symptoms. A fibroid is identified as a hypoechoic, well-circumscribed, round mass on pelvic ultrasound. A leiomyosarcoma is usually diagnosed on a postoperative specimen. Depending on patient symptoms and preference, treatment for leiomyoma may include surgical resection or medical options to reduce bleeding and/or bulk. Management of leiomyosarcoma, which carries a poor prognosis, may include adjuvant chemotherapy based on stage.

Becker muscular dystrophy (BMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. Abnormal, partially functional muscle dystrophin protein is produced, which leads to progressive muscle weakness and the eventual loss of ambulation. The clinical course is highly variable, but symptoms generally occur by adolescence. The diagnosis is based on muscle enzymes, genetic testing, and muscle biopsy (if necessary). Management of BMD is supportive and aimed at slowing disease progression and complications. Dilated cardiomyopathy is the leading cause of death.

Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). These misfolded proteins can become deposited in different tissues, interfere with normal organ functions, and cause tissue-specific diseases (e.g., renal amyloidosis causes proteinuria). Diagnosis is established clinically and confirmed with tissue biopsy. Treatment should be directed toward the underlying cause and the reduction of amyloid deposition.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction and has a strong association with small cell lung carcinoma. Lambert-Eaton myasthenic syndrome affects the voltage-gated calcium channels at the presynaptic membrane. Presentation includes proximal muscle weakness and symptoms of autonomic dysfunction such as dry mouth and sluggish pupillary reflexes. Diagnosis includes nerve conduction studies/electromyography (EMG) and serum detection of antibodies. Management is mainly symptomatic with the use of potassium channel blockers and immunosuppressants. Prognosis is good for nonparaneoplastic LEMS but usually poor for paraneoplastic LEMS secondary to underlying malignancy.

Muscle tissue is one of the basic tissue types. Histologically, the muscles of the body can be classified into 3 types: skeletal, smooth, and cardiac. The 3 types of muscle tissue are based on the morphologic and functional properties of the cells. One of the defining characteristics of muscle tissue is its contractility, which generates forces that move the musculoskeletal system as well as cause movement in the vasculature and multiple organ systems. This contractility is due to specialized proteins known as myofilaments, which create organized structures that have the ability to lengthen and contract.

Ion channel myopathies are a heterogeneous group of disorders that are caused by genetic defects in sodium, chloride, and calcium ion channels in the myocyte membranes resulting in myotonia. These myopathies present clinically with symptoms of muscle pain, weakness, stiffness, cramps, and spasm. Diagnosis is made on the basis of clinical presentation, lab testing, electromyography, and genetic testing. Management involves both prevention with diet and exercise modifications and treatment with diuretics in some cases.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. Myasthenia gravis presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Diagnosis is established based on clinical presentation, detection of antibodies, and electrophysiologic studies. Management is aimed at increasing the activity of acetylcholine at the neuromuscular junction and suppression of antibodies. This disease can be associated with thymomas and thymic hyperplasia, and thymectomy is sometimes indicated. Myasthenia gravis can progress to a life-threatening cholinergic crisis with respiratory failure, but this is preventable with appropriate management. Prognosis is generally good with treatment, and some patients can achieve a long-term remission.

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. The mutation leads to the production of abnormal dystrophin, resulting in muscle-fiber destruction and replacement with fatty or fibrous tissue. Affected individuals present with progressive proximal muscle weakness leading to the eventual loss of ambulation, as well as contractures, scoliosis, cardiomyopathy, and respiratory failure. A marked elevation in CK may be observed. Genetic testing is used to confirm the diagnosis. Management is supportive and aimed at slowing disease progression and complications. Duchenne muscular dystrophy is fatal with a life expectancy of about 20 years of age.

A lipoma is a benign neoplasm of fat cells (adipocytes) and the most common soft tissue tumor in adults. The etiology is unknown, but obesity is a predisposing factor; genetics also play a role, with multiple lipomas occurring in various inherited disorders. Lipomas can arise in any site with adipose tissue (including the gastrointestinal tract, chest cavity, retroperitoneum, and glands), but are most common in subcutaneous tissues of the trunk or proximal extremities. The treatment is not necessary for small asymptomatic lipomas. Surgical excision is the treatment if there is a cosmetic, functional, or diagnostic concern.