Pathology Review Ch 27

(C) This patient has a paraneoplastic syndrome called Lambert-Eaton myasthenic syndrome. Similar to many
paraneoplastic syndromes, it is most often associated with small-cell carcinoma of the lung. Patients with chronic viral
hepatitis may have generalized malaise and weakness that is not related to specific muscle disease. Duchenne muscular
dystrophy is an X-linked disease that manifests early in childhood. Lead poisoning leads to peripheral neuropathy.
Diabetes mellitus also may produce peripheral neuropathy.
BP7 780BP8 830PBD7 1344–1345PBD8 1276

(C) The biopsy specimen shows reduced amounts of dystrophin, suggesting Becker muscular dystrophy. In Duchenne
muscular dystrophy, dystrophin is absent because of gene deletion. In keeping with the diagnosis of Becker muscular
dystrophy, the patient is older and not severely affected. Both dystrophies are X-linked conditions. Werdnig-Hoffmann
disease is a form of spinal muscular atrophy. Onset is at birth, and it results from a genetically determined loss of anterior
horn cells. Polymyositis is an autoimmune disease that results from a T cell–mediated attack on muscle fibers, causing
muscle fiber degeneration with inflammation. Amyotrophic lateral sclerosis is a denervation atrophy seen in adults, with
loss of anterior horn cells in the spinal cord and cranial nerve nuclei. Myasthenia gravis results from acetylcholine-receptor
antibody, and there is minimal structural change to the muscle. Myotonic dystrophy is characterized by facial and upper
body weakness, cataracts, gonadal atrophy, cardiomyopathy, and dementia.
BP7 780–782BP8 827–828PBD7 1336–1338PBD8 1268–1269

(F) After infection with chickenpox the varicella-zoster virus (VZV) becomes dormant in dorsal root ganglia, only to
reactivate later when the immune system no longer contains it. Such containment failures are more likely with age and with
immunocompromised states, and this produces the classic appearances of shingles in a dermatomal distribution. She also
has postherpetic neuralgia, a disabling condition of chronic pain that is difficult to manage. Aging alone does not explain
disease, but older individuals are more likely to have disease conditions. Diabetes mellitus leads to neuropathies that can
have loss of sensation or even pain, but there are no associated skin lesions. Multiple sclerosis can involve the spinal cord
white matter with variable neurologic findings, but there are no skin lesions, and the onset of MS is at a younger age. Pain out of proportion to the pathologic findings suggests a somatoform pain disorder, but she does have significant pathologic
findings that explain her continued pain. Pernicious anemia with subacute combined degeneration of the spinal cord can
lead to paresthesias and loss of function, but not to skin lesions.
BP8 877PBD7 1332PBD6 1262–1263

(B) The onset of muscle weakness in childhood suggests an inherited muscular dystrophy. The biopsy specimen shows
variation in muscle fiber size and increased connective tissue between the fibers. This morphologic finding in a boy
strongly suggests X-linked muscular dystrophy. Immunohistochemical staining for dystrophin would show an absence of
dystrophin, confirming the diagnosis of Duchenne muscular dystrophy. Antibodies to the acetylcholine receptor are found
in myasthenia gravis, which is characterized by weakness in muscles after repetitive use. Eosinophilia may be present in
allergic or parasitic disorders, including trichinosis. Oligoclonal immunoglobulin bands in the cerebrospinal fluid are a
feature of multiple sclerosis. Expansion of CGG repeats on Xq27.3 is diagnostic of familial mental retardation.
BP7 780–782BP8 827–828PBD7 1336–1338PBD8 1268–1269

(A) The patient's history is typical of Guillain-Barré syndrome. This uncommon disorder most often follows a viral or
mycoplasmal infection. It is believed to be caused by generation of myelin-reactive T cells, somehow triggered by viral
infection. The paralysis of respiratory muscles may be life-threatening, although many patients recover after weeks of
ventilatory support. Various presentations are possible in multiple sclerosis, but the plaques of demyelination are generally
not large or diffuse enough to cause paralysis of the respiratory muscles. Amyotrophic lateral sclerosis is associated with
slowly progressive muscle weakness. Mechanical ventilation may be necessary eventually. Varicella-zoster virus infection
most often involves the skin in a dermatomal distribution from a spinal nerve root. Vitamin B12 deficiency results in subacute progressive degeneration of the spinal cord plus sensorimotor disturbances in the extremities.
BP7 848BP8 899PBD7 1331PBD8 1261–1262

(B) This patient has myasthenia gravis, with muscle weakness resulting from loss of motor end plate function. This
disorder is caused by an antibody-mediated loss of acetylcholine receptors at neuromuscular junctions. Myopathic
diseases such as muscular dystrophies are accompanied by increased levels of serum creatine kinase. Parasitic infection
with Trichinella spiralis can lead to eosinophilia. Generalized muscle weakness with type II muscle fiber atrophy occurs in
glucocorticoid excess. The anti-Jo-1 antibody is present in polymyositis. Sjögren syndrome does not cause muscle
weakness with use.
BP7 115, 779–780BP8 125, 830PBD7 1344PBD8 1275–1276

(A) This patient has malignant hyperthermia, a rare but life-threatening disorder seen in only 1 in 20,000 adults, but
with millions of surgical procedures under anesthesia being performed, it must be considered when the patient's
temperature increases rapidly. There is impaired reuptake of calcium into the sarcoplasmic reticulum with increased
intracellular calcium leading to hypermetabolism. Motor end plates include acetylcholine and acetylcholine receptors that
are involved with myasthenia gravis. The mitochondrial DNA genes are mainly involved in oxidative phosphorylation, and
there is a maternal inheritance pattern, with possible muscular weakness, but not hyperthermia. The sarcoglycan complex
includes many proteins such as dystrophin that can be involved with muscular dystrophies, but not hyperthermia. Thick
filaments include the myosin contractile protein; β-myosin mutations are found in some cases of hypertrophic
cardiomyopathy.
BP8 829PBD7 1340PBD8 1270

(B) Amyotrophic lateral sclerosis is also known as Lou Gehrig disease, named for the famous New York Yankee first
baseman affected with the disorder. Lower and upper motor neurons can be affected, resulting in a denervation-type
pattern of muscular atrophy. This occurs because an individual neuron innervates a group of muscle fibers. Bulbar
involvement denotes a more rapid course. Werdnig-Hoffman disease also is a neuropathic disease with grouped atrophy,
but onset is in infancy. The other listed options are not associated with denervation.
BP7 778–779BP8 827, 896PBD7 1335, 1396–1397PBD8 1324–1325

(E) Oxidative phosphorylation in mitochondria can be affected by mitochondrial genes, which are separate from those
on chromosomes in the cell nucleus. These abnormal genes can lead to mitochondrial myopathies, encephalopathies, and
deafness. In this case, there is mitochondrial encephalopathy with lactic acidosis and strokelike episodes (MELAS).
Mitochondrial genes have a maternal pattern of inheritance. An abnormal voltage-gated calcium channel is seen in one of
the channelopathies; it causes hypokalemic periodic paralysis. Channelopathies are typically inherited in an autosomal
dominant fashion. Antibodies to acetylcholine receptor cause myasthenia gravis; its sole manifestation is muscle
weakness. Cytotoxic CD8+ cells mediate the muscle injury in polymyositis. Decreased sarcolemmal dystrophin is present
in Becker muscular dystrophy; dystrophin is absent in Duchenne muscular dystrophy. The dystrophin gene is located on
the X chromosome. Increased CTG repeats occur in myotonic dystrophy.
BP7 15, 235–236BP8 829PBD7 1341–1342PBD8 1271–1273

(E) The axons distal to the point of injury or transection degenerate. The Schwann cells that remain can guide the
regrowing nerves. Macrophages help to remove myelin-derived debris from the area of nerve injury, but acute
inflammation is not a typical feature of diseases involving peripheral nerves. Traumatic neuromas may occur after
transection. The purpose of the graft is to guide orderly regrowth. A tumor is unlikely to follow a nerve, although a feature
of a malignant tumor is a tendency to invade nerves. Grouped atrophy occurs later with progression of disease when
denervation is followed by reinnervation.
BP7 847BP8 898PBD7 1329–1330PBD8 1258–1260

(A) She has a statin-induced myopathy, with a creatine kinase level more than 10 times normal from rhabdomyolysis
(myoglobin causing renal tubular damage and detected by the dipstick). Statins are HMG CoA reductase inhibitors that
reduce endogenous cholesterol synthesis in liver. Cholestyramine binds bile acids in the intestine and disrupts
enterohepatic bile acid circulation to increase conversion of cholesterol to bile acids in the liver. Clofibrate enhances
uptake and oxidation of free fatty acids in muscle. Ezetimibe interferes with intestinal lipid absorption. Nicotinic acid inhibits
mobilization of peripheral free fatty acids to reduce hepatic triglyceride synthesis and secretion of VLDL.
PBD8 1275

(D) Muscle pain with fever and eosinophilia suggests a parasitic infestation of the skeletal muscles, most likely
trichinosis; this results from ingesting poorly cooked infected meat. Duchenne muscular dystrophy is a noninflammatory
myopathy that begins in early childhood. Polymyositis is an autoimmune condition characterized by muscle inflammation,
but no eosinophilia. Poliomyelitis can lead to muscle weakness, but is noninflammatory. Diabetes mellitus can lead to
peripheral vascular disease and gangrene, but this complication would be rare at age 17.
BP7 312, 780BP8 327PBD7 407–408PBD8 393

(B) She has nemaline rod myopathy, one form of congenital myopathy. The congenital myopathies may present in
infancy or childhood and may be non-progressive or slowly progressive. They are often named for their characteristic
histologic features. Channelopathies typically present as periodic paralysis with abnormalities in serum potassium. The
two glycogen storage diseases most often affecting striated muscle include Pompe disease (type II) and McArdle disease
(type V). There are increased glycogen deposits seen with periodic acid-Schiff (PAS) stain. Neuropathies affect muscle
through denervation, leading to groups of atrophic muscle fibers. Polymyositis and dermatomyositis are inflammatory
myopathies that are accompanied by myalgia and fiber degeneration with increased serum creatine kinase. Mitochondrial
myopathies may appear in childhood but are usually progressive, and often other organs such as heart or brain are
involved. Dystrophic muscle diseases lead to fiber degeneration with atrophy and fibrosis, with elevation in creatine
kinase; the most common muscular dystrophies involve dystrophin gene mutations that are X-linked.
BP8 829PBD7 1340PBD8 1271–1272

(D) Laceration of the femoral nerve results in wallerian degeneration distal to the injury. Realignment of the nerve is
accompanied by axonal sprouting. The new axons find the residual myelin sheaths and grow down at the rate of about 2
mm/day, taking 1 year for the distance of a lower extremity. There can be reinnervation of the muscle, but there is type
grouping of the muscle fascicles that are reinnervated.
BP7 847BP8 898PBD7 1329–1330PBD8 1259–1260

(C) The clinical features and histologic findings are typical of dermatomyositis, an immunologically mediated form of
inflammatory myopathy. In these patients, antibodies and complement damage small capillaries, resulting in a
characteristic perifascicular myofiber atrophy. The CD8+ T cells are believed to be important in the pathogenesis of
polymyositis. T cell–mediated myelin injury is seen with Guillain-Barré syndrome, causing an acute ascending paralysis.
Mutations in ion channel genes give rise to various channelopathies, including hypokalemic periodic paralysis and
malignant hyperthermia. Expansion of CTG repeats is seen with myotonic dystrophy.
BP7 143–144BP8 151PBD7 1342–1343PBD8 1273–1275

(A) This patient has carpal tunnel syndrome, a form of compression neuropathy, which results from entrapment of the
median nerve beneath the flexor retinaculum at the wrist. Women are more commonly affected than men, and the problem
is often bilateral. The most common cause is excessive repetitive use of the wrist. Conditions such as hypothyroidism,
amyloidosis, and edema with pregnancy also diminish the space in the carpal tunnel. Diabetes mellitus leads to a
symmetric distal sensorimotor neuropathy. Amyotrophic lateral sclerosis results in progressive symmetric weakness from
loss of motor neurons. Acute intermittent porphyria can lead to a hereditary form of motor and sensory neuropathy.
Infection with varicella-zoster virus produces a painful neuropathy in a dermatomal distribution pattern.
BP7 847PBD7 1335PBD8 1266–1267

(D) The most common cause of a predominantly sensory peripheral neuropathy is diabetes mellitus. Long-standing
diabetes mellitus also gives rise to renal failure. Guillain-Barré syndrome produces a rapidly ascending paralysis.
Sensorimotor disturbances are typically not seen with intracranial mass lesions such as astrocytomas. A cerebral infarction
could lead to decreased motor activity and sometimes to sensory loss, although not in a symmetric pattern. The
demyelinating lesions of multiple sclerosis can produce many signs and symptoms, but symmetric lesions should suggest
another disease process.
BP7 847BP8 784–785, 898PBD7 1334PBD8 1265–1266

(F) This infant has Werdnig-Hoffman disease, a form of spinal muscular atrophy resulting from loss of motor neurons in
infancy, so the biopsy specimen shows group atrophy of myofibers. Death is inevitable by age 3 years. Amyotrophic lateral
sclerosis is a progressive disease with a neurogenic form of muscle atrophy resulting from loss of motor neurons.
Duchenne muscular dystrophy has an X-linked pattern of inheritance and onset in childhood, and there is a mutation in the
dystrophin gene. McArdle disease is an autosomal recessive condition resulting from a deficiency in muscle
phosphorylase and does not produce progressive weakness. Myasthenia gravis results from acetylcholine receptor
antibody and leads to progressive weakness. Myotonic dystrophy is characterized by facial and upper body weakness,
cataracts, gonadal atrophy, cardiomyopathy, and dementia.
BP7 216BP8 827, 897PBD7 1336PBD8 1267

(C) Fashion may have a price. The patient has a Morton neuroma, a form of compressive neuropathy in which a
plantar nerve is trapped between metatarsal heads. Chronic injury leads to growth of a tangled mass of axons, fibroblasts,
and perineural cells. The toxic disorder (lead poisoning) and metabolic disorders (beriberi with thiamine deficiency or
subacute combined degeneration with cobalamin deficiency) are not as focal. Diabetic neuropathy, which occurs in either
type 1 or type 2 disease, is bilateral. It is characterized by loss of sensation, which may be a predisposing factor for foot
trauma. Wallerian degeneration is a dying-back neuropathy associated with severing of a nerve; a neuroma may form at
the site of injury.
BP7 847PBD7 1335PBD8 1267

(A) Type II atrophy can occur with glucocorticoid excess and after prolonged immobilization. Routine light microscopy
may not allow the physician to distinguish type II atrophy from denervation atrophy. Histochemical staining for ATPase
must be done. There is a deficiency of myophosphorylase enzyme in McArdle disease, leading to muscle pain and
cramping with vigorous exercise. Duchenne muscular dystrophy is an X-linked condition and is rare in females. Onset is in
early childhood. Antibodies to the acetylcholine receptor cause the muscular weakness in myasthenia gravis. Polymyositis
is an inflammatory condition affecting all fiber types.
BP7 779BP8 826PBD7 1209, 1344PBD8 1260

(E) The features described are consistent with a peripheral neuropathy associated with diabetes mellitus. Motor and
sensory nerves are involved, and there may be an autonomic neuropathy. Histologic examination shows an axonal
neuropathy with segmental demyelination. Difficulty in emptying the urinary bladder and impotence are results of
autonomic neuropathy. Longer nerves are affected first; this explains the lower leg involvement and accounts for many
cases of diabetic foot, with trauma and subsequent ulceration. Wallerian degeneration typically occurs with traumatic
transection of a nerve. Acute inflammation is not generally seen in neuropathies. Onion bulb formation is a feature of the
hereditary neuropathy known as Refsum disease. Lymphocytic infiltrates may be seen in Guillain-Barré syndrome.
BP7 847BP8 784–785, 898PBD7 1334PBD8 1265–1266