Musculoskeletal Disease - MHE Research Foundation

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Musculoskeletal Disease
Normal Skeletal System
• The skeletal system is as vital to life as any
organ system because it plays an essential
role in:
• 1) mineral homeostasis
• 2) houses the hematopoietic elements
• 3) provides mechanical support for
movement
• 4) protects & provides body size and shape
Normal Skeletal System
• Bone is a type of connective tissue
• Biochemically, it is defined by its special
blend of organic matrix (35%) and
inorganic elements (65%)
• The inorganic component, calcium
hydroxyapatite is the mineral that give bone
strength and hardness and is the storehouse
for 99% of the body’s calcium
Normal Skeletal System
• Bone also contains 85% of the body’s
phosphorus and 65% of the sodium and
magnesium
• The rate of mineralization can vary but
normally there is a 12-15 day lag time
between the formation of the matrix and its
mineralization; bone that is unmineralized is
known as OSTEOID
Normal Skeletal System
• The organic component includes the cells of
bone and proteins of the matrix; the boneforming cells include:
• 1) OSTEOPROGENITOR cells are
pluripotential mesenchymal stem cells that
are located in the vicinity of all bony
surfaces; they can undergo cell division and
produce offspring that differentiate into
osteoblasts
Normal Skeletal System
• 2) OSTEOBLASTS are located on the
surface of bone & synthesize, transport, &
arrange the many proteins of the matrix;
they also initiate mineralization; once
surrounded by matrix they are called
• 3) OSTEOCYTES: these are the most
numerous bone-forming cells & although
encased in bone communicate via
CANALICULI
Normal Skeletal System
• OSTEOCLASTS are the cells responsible
for bone resorption and are derived from
hematopoietic progenitor cells that also give
rise to monocytes and macrophages; the
scalloped resorption pits they produce and
often reside in are known as HOWSHIP
LACUNAE; as bone is broken down to its
elemental units, substances are released that
initiate its renewal
Normal Skeletal System
• The proteins of bone include type 1
collagen (90% of organic component) and a
family of noncollagenous proteins that are
derived mainly form osteoblasts
• Osteoblasts deposit collagen either in a
random weave known as WOVEN BONE
or in an orderly layered manner called
LAMELLAR BONE
Normal Skeletal System
• The presence of woven bone in the adult is
always indicative of a pathologic state
• Lamellar bone, which gradually replaces the
woven bone of the fetal skeleton, is
deposited much more slowly and is stronger
than woven bone; there are 4 different types
of lamellar bone: circumferential,
concentric, interstitial (in cortex) &
trabecular lamellae
Diseases of Bone
Malformations of Bone
•
•
•
•
•
Congenital ones are uncommon & include:
1) failure of development; e.g. rib absence
2) formation of extra bones; e.g. extra digit
3) fusion of bones; e.g. syndactylism(digits)
4) development of long, spider-like digits;
e.g. arachnodactylism
• 5) craniorachischisis (failure of closure of
skull and spinal column
Achondroplasia
• Is the most common disease of the growth
plate and is a major cause of dwarfism
• Is an autosomal dominant disorder with
approx. 80% representing new mutations
• Pt. has shortened proximal extremities, a
trunk of relative normal length and an
enlarged head; not associated with changes
in longevity, intelligence or reproduction
Diseases Associated With
Abnormal Matrix
Osteogenesis imperfecta
Osteogenesis imperfecta
• Osteogenesis imperfecta or “brittle bone
disease” is a group of hereditary conditions
characterized by abnormal development of
type I collagen
• This spectrum of disorders of varying
severity are united by the common feature
of abnormal collagen synthesis and the
resulting bone fragility
Osteogenesis imperfecta
• Most variants are inherited as autosomal
dominants
• Is characterized by multiple bone fractures
which may occur in utero in the severe
forms
• Other findings include: blue sclerae (caused
by decreased collagen); hearing loss (ear
bone abnormalities; dental imperfections
Osteoporosis
• Is a term that denotes increased porosity of
the skeleton resulting from a reduction in
bone mass
• It may be localized, e.g. disuse osteoporosis
of a limb, or generalized as a manifestation
of a metabolic bone disease
Osteoporosis
• When used in an unqualified manner,
osteoporosis usually refers to the most
common forms, senile and postmenopausal
osteoporosis, in which the critical loss of
bone mass makes the skeleton vulnerable to
fractures
Osteoporosis
• Peak bone mass is achieved during young
adulthood and is largely determined by
hereditary factors, especially the allele for
the vitamin D receptor molecule
• Physical activity, muscle strength, diet and
hormonal state also contribute
• Age-related bone loss (approx. 0.7%/yr) is a
normal biological phenomenon
Osteoporosis
• Both sexes are affected equally and Whites
more so than Blacks
• Differences in the peak skeletal mass in
men vs women and Blacks vs Whites may
partially explain why certain populations
are prone to develop the disorder
• Much remains unknown; the following are
related to the development of osteoporosis:
Osteoporosis
• 1) Age-related changes; in older people
bone-forming cells have diminished
capacity to make bone
• 2) Reduced physical activity; mechanical
forces are important stimuli for normal bone
remodeling
• 3) Genetic factors; importance of vitamin D
receptors
Osteoporosis
• 4) Body’s calcium nutritional state;
adolescent girls with insufficient calcium
intake are later at greater risk of developing
osteoporosis
• 5) Hormonal influences; postmenopausal
osteoporosis is characterized by a hormonedependent acceleration of bone loss;
estrogen replacement protects against bone
loss
Osteoporosis
• Clinical manifestations may include:
vertebral fractures, lumbar lordosis and
kyphoscoliosis; pulmonary embolism and
pneumonia may result from overt fractures
of the femoral neck, pelvis or spine
• Plain radiographs cannot detect
osteoporosis until 30-40% of bone mass is
loss; thus specialized radiographic imaging
techniques and biopsy are helpful
Diseases Caused by Osteoclast
Dysfunction
Osteopetrosis (Marble Bone or
Albers-Schonberg Disease)
• Osteopetrosis refers to a group of rare
hereditary diseases characterized by
osteoclast dysfunction resulting in diffuse
symmetric skeletal sclerosis
• Clinical features: fractures, anemia, optic
atrophy, hydrocephaly, deafness, facial
paralysis & serious infections may occur;
manifestations depend on form of disease
Paget Disease (Osteitis
Deformans)
• Is a unique disorder characterized by
episodes of localized, frenzied osteoclastic
activity with bone resorption followed by
exuberant bone formation with a net effect
of a gain in bone mass
• Paget disease usually begins during middle
adulthood and becomes progressively more
common thereafter
Paget Disease
• As the result of the repetitive bone
destruction and formation 3 phases of Paget
can be identified:
• 1) an initial phase of osteoclastic activity,
hpervascularity and bone loss
• 2) a phase of mixed osteoclastic and
osteoblastic activity and
• 3) a late, osteosclerotic phase
Paget Disease
• The disease is usually asymptomatic but can
frequently be diagnosed from radiographic
findings; many patients manifest elevated
serum alkaline phosphastase levels
• Pain is most common problem; headache,
hearing & visual disturbances, enlargement
of the head (leontiasis ossea), bowing and
chalkstick-type fractures of legs, variety of
tumors/ tumor-like conditions occur
Diseases Associated With
Abnormal Mineral Homeostasis
Hyperparathyroidism
Hyperparathyroidism
• Hyperparathyroidism is classified into
primary and secondary types
• Primary type results from autonomous
hyperplasia or a tumor (usually an
adenoma) of the parathyroid gland
• Secondary is commonly caused by
prolonged states of hypocalcemia resulting
in compensatory hypersecretion of PTH
Hyperparathyroidism
• The skeletal manifestations of
hyperparathyroidism are caused by
unabated osteoclastic bone resorption
• The entire skeleton is affected to more or
lesser degree
• Anatomic changes of severe
hyperparathyroidism are known as osteitis
fibrosa cystica
Hyperparathyroidism
• Secondary hyperparathyroidism is usually
not as severe or as prolonged as primary
and hence skeletal changes are milder
• The hallmark of PTH excess is increased
osteoclastic activity with bone resorption
• Resorption may be generalized or localized,
e.g. diffuse radiolucency, surface erosion or
“brown tumor”
Hyperparathyroidism
• The decrease in bone mass predisposes to
fractures, deformities caused by the stress of
weight bearing and joint pain and
dysfunction
Renal Osteodystrophy
• The term is used to describe collectively all
of the skeletal changes of chronic renal
disease
• There are to major types:
• 1) high-turnover osteodystrophy
characterized by increased bone resorption
and formation with the former
predominating
Renal Osteodystrophy
• 2) low-turnover (aplastic) characterized by a
marked reduction in the rate of bone
mineralization, formation and resorption
Renal Osteodystrophy
• The skeletal changes include:
• 1) increased osteoclastic bone resorption
• 2) delayed matrix mineralization
(osteomalacia)
• 3) osteosclerosis
• 4) growth retardation
• 5) osteoporosis
Infections of Bone-Osteomyelitis
Osteomyelitis
• Osteomyelitis denotes inflammation of bone
and marrow and the common use of the
term virtually always implies infection
• All type of organisms including viruses,
parasites, bacteria, and fungi can produce
osteomyelitis but infections caused by
certain pyogenic bacteria and mycobacteria
are the most common
Pyogenic Osteomyelitis
• Pyogenic osteomyelitis is almost always
caused by bacteria
• Organism may reach bone by: 1)
hematogenous spread (most common
route); 2) extension from a contiguous site;
or 3) direct implantation
• Long bones and vertebral bodies most
commonly involved
Pyogenic Osteomyelitis
• S. aureus is responsible for 80-90% of cases
• E. coli, Pseudomonas and Klebsiella are
more commonly isolated from pts. with UG
tract infections or are drug users
• Mixed infections seen in cases of surgery or
open fractures
• Neonatal period: H. influenzae and group B
strept.; Salmonella in pts. with sickle cell
Pyogenic Osteomyelitis
• Location of lesions within specific bones is
influenced by vascular circulation and
varies with age
• Clinically hematogenous osteomyelitis may
manifest as an acute systemic illness with
malaise, fever, chills, leukocytosis and
throbbing pain over affect site
• X-rays, biopsy & cultures help with dx
Pyogenic Osteomyelitis
• The combination of antibiotics and surgical
drainage is usually curative
• In 5-25% of cases, acute osteomyelitis fails
to resolve and persists as chronic infection
• Complications may include: pathologic
fracture, endocarditis, sepsis, etc.
Tuberculous Osteomyelitis
• 1-3% of pts. with pulmonary or
extrapulmonary T.B. have osseous infection
• Typically, pts. present with pain on motion,
localized tenderness, low-grade fevers,
chills and weight loss
• Severe destruction of vertebrae (Pott’s
disease) may cause skeletal deformities and
neurologic deficits
Tumors of Bone
Benign Bone-Forming Tumors
Osteoma
• Osteomas are benign lesions of bone that in
many cases represent developmental or
reactive growths rather than true neoplasms
• The most common locations are the facial
bones and skull
• Most common in 40-50 yr. group
• Most are exophytic growths attached to the
bone surface
Osteoma
• Histologically they resemble normal bone
• Multiple osteomas are seen in GARDNER
SYNDROME
• They are generally slow-growing tumors of
little clinical significance except when they
cause obstruction or produce cosmetic
problems
• They do not undergo malignant change
Osteoid Osteoma and
Osteoblastoma
• Benign bone tumors that have identical
histologic features but that differ in size,
sites of origin and symptoms, however both
are more common in th 10-20 yr. age group
• Osteoid osteomas are <2 cm in greatest
dimension, more common in the metaphysis
of the femur and tibia and characterized by
severe pain (nocturnal and relieved by
aspirin)
Osteoid Osteoma and
Osteoblastoma
• Osteoblastomas are more common in the
spine; while painful, the pain is dull and
achy (not relieved by aspirin)and the
vertebral column is most common site
• Both lesions are readily treated by
conservative surgery but can recur if not
completely excised; malignant
transformation is rare unless irradiated
Tumors of Bone
Malignant-Bone Forming
Osteosarcoma (Osteogenic
Sarcoma)
• Osteosarcoma is defined as a malignant
mesenchymal tumor in which the cancerous
cells produce bone matrix
• It is the most common primary malignant
tumor of bone exclusive of myeloma and
lymphoma
• 75% of cases occur in pts. younger than 20
years (however, with jaw tumors pts. older)
Osteosarcoma
• Male predilection 1.6:1
• Tumors usually arise in metaphyseal region
of long bones of extremities with almost
50% around the knee
• Morphology: grow outward, lifting
periosteum and inward to the medullary
cavity; microscopically, malignant cells
form osteoid; cartilage may be present also
Osteosarcoma
• Typically present as painful and
progressively enlarging masses;
occasionally pathologic fracture is first
symptom
• Approx. 20% of pts. have pulmonary mets
at time of dx
• Advances in treatment have improved
prognosis with 5yr survival now 60%
overall
Tumors of Bone
Benign Cartilaginous Tumors
Osteochondroma
• Osteochondroma, also known as an
exostosis, is a benign cartilage-capped
outgrowth that is attached to the underlying
skeleton by a stalk
• They may be solitary or multiple and
hereditary (multiple hereditary exostosis
which is autosomal dominant)
Osteochondroma
• More commonly involve the metaphysis of
long tubular bones in the 10-30 yr. age
group
• Clinically, osteochondromas present as
slow-growing masses which can be painful
if they impinge on a nerve
• They stop growing at the time of growth
plate closure; <1% give rise to sarcoma
Chondroma
• Chondromas are benign tumors of hyaline
cartilage
• When they arise within the medullary cavity
they are known as ENCHONDROMAS and
on the surface of bone they are termed
SUBPERIOSTEAL OR JUXTACORTICAL
CHONDROMAS
Chondroma
• Chondromas are most common in the small
bones of the hands and feet of people in
their twenties to forties
• The syndrome of multiple enchondromas or
enchondromatosis is known as OLLIER
DISEASE
• They are though to develop from rests of
growth plate cartilage
Chondroma
• Most enchondromas are asymptomatic
although occasionally they are painful or
cause pathologic fracture
• On x-ray they appear as unmineralized
nodules of cartilage (well-circumscribed
radiolucency) surrounded by a thin rim of
radiodense bone (O ring sign)
Chondroma
• The growth potential is limited
• If treatment is required, surgical excision is
the choice
• Solitary chondromas rarely undergo
malignant change but the multiple
enchondromatoses do so more frequently
Tumors of Bone
Malignant Cartilaginous Tumors
Chondrosarcoma
• Chondrosarcomas are malignant neoplasms
populated by mesenchymal cells that
produce a cartilaginous matrix
• There are several subclassifications
• Chondrosarcomas are about half as frequent
as osteosarcomas
• Most patients are in the 40-60 year range
with a 2:1 male predilection
Chondrosarcoma
• The bones of the shoulder, pelvis, proximal
femur and ribs are most commonly involved
• Microscopically, range from welldifferentiated cartilage-like to anaplastic
tumors
• In contrast to enchondroma,
chondrosarcoma rarely involves the distal
extremities
Chondrosarcoma
• Chondrosarcomas present most often as
enlarging, painful masses; their growth rate
and ultimate behavior is closely correlated
with histologic grade
• Chondrosarcomas metastasize via the
hematogenous route, most often to the lungs
• 5-year survival rate was 90%, 81% and
43% in grades 1 through 3 in one study
Miscellaneous Tumors and
Tumor-Like Conditions of Bone
Giant Cell Tumor of Bone
(Osteoclastoma)
• Giant cell tumors are lesions that contain a
large number of osteoclast-like giant cells
admixed with mononuclear cells
• Most arise in the epiphyses of long bones
• Pts. are in the 20-40 year age range with a
slight female predilection
• Usually present with pain and biopsy is
necessary for dx
Giant Cell Tumor
• Several different bone disorders have
multinucleated giant cells so their presence
along is not diagnostic
• The behavior is somewhat unpredictable
• Sarcomatous transformation is rare but may
occur de novo or with irradiation of a
benign tumor
Ewing’s Sarcoma
• Is a primitive malignant neoplasm of bone
that occurs predominantly in children in
whom it is the second most common
malignancy after osteosarcoma
• It is a highly aggressive neoplasm which
has been associated with a chromosomal
translocation identical to that seen in
primitive neuroectodermal tumors
Ewing’s Sarcoma
• Classically presents with pain often
accompanied by local inflammation; fever
is fairly common along with elevated SED
rate, anemia and leukocytosis
• X-rays show a destructive lytic tumor which
may show a periosteal reaction producing
layers of reactive bone (onion-skin
appearance)
Ewing’s Sarcoma
• Treatment includes chemotherapy and
surgery with/without radiation
• This treatment has increased the 5-year
survival to approximately 75%
Fibrous Dysplasia
• Is a benign tumor-like lesion of bone that is
best characterized as a localized
developmental arrest; all the components
are present but they do not differentiate into
mature structures
Fibrous Dysplasia
• There are three clinical patterns:
• 1) involvement of a single bone
(monostotic)
• 2) involvement of multiple but not all bones
(polyostotic)
• 3) polyostotic disease associated with caféau-lait spots and endocrine abnormalities
such as precocious puberty
Fibrous Dysplasia: Monostotic
• Accounts for approx. 70% of all cases
• Occurs about equally in boys & girls
usually in early adolescence
• Often stops growing at the time of growth
plate closure
• Ribs, femur, tibia, jaws, skull common sites
• Usually asymptomatic; can cause marked
enlargement and distortion of bone
Fibrous Dysplasia: Polyostotic
without Endocrine Dysfunction
• 27% of cases
• Appears at an earlier age and progresses
into adulthood
• 50% have craniofacial involvement
• All forms have severe involvement of
shoulder and pelvic girdles resulting in
severe crippling deformities (shepherdcrook deformity) and often fractures
Polyostotic with Skin
Pigmentation & Endocrinopathy
• Also known as McCune-Albright Syndrome
• Café-au-lait spots
• Endocrinopathies may include: sexual
precocity, hyperthyroidism, pituitary
adenomas producing GH and primary
adrenal hyperplasia
• Girls more frequently involved than boys
Fibrous Dysplasia
• Pts. with monostotic disease have minimal
symptoms
• Lesions readily diagnosed by x-ray (groundglass, etc.) and biopsy
• Conservative surgery for symptoms or
cosmetics
• Polyostotic frequently associated with
progressive disease; rare sarcomatous trans.
Diseases of the Joints
Osteoarthritis
Osteoarthritis
(Degenerative Joint Disease)
• Is the most common type of joint disease
• Is characterized by the progressive erosion
of articular cartilage
• Although the term osteoarthritis implies an
inflammatory disease & inflammatory cells
may be present, it is considered an intrinsic
disease of cartilage in which biochemical &
metabolic alterations result in its breakdown
Osteoarthritis
• Most cases begin insidiously without an
apparent initiating cause as an aging
phenomenon (primary osteoarthritis)
• About 5% of cases appear in younger pts.
with predisposing conditions such as: joint
trauma, developmental deformity or a
systemic disease, e.g. diabetes or obesity; in
these cases is called secondary osteoarthritis
Osteoarthritis
• Prevalence increases exponentially beyond
the age of 50 with about 80-90% of both
sexes having osteoarthritis by age 65
• Age-related changes include: alterations in
proteoglycans & collagen, which decrease
tensile strength & shorten fatigue life but it
is not simply a disease of wear and tear
Osteoarthritis
• Chondrocytes play a primary role and
constitute the cellular basis of the disease
• They produce IL-1 & TNF-alpha, which are
known to stimulate the production of
catabolic metalloproteinases and inhibit the
synthesis of both type 2 collagen and
proteoglycans; other mediators also have a
role in matrix degradation
Osteoarthritis: Clinical Features
• Is an insidious disease
• Characteristic symptoms include: deep,
achy pain that worsens with use, morning
stiffness, crepitus, and limitation of range of
movement; impingement on spinal foramina
by osteophytes results in cervical & lumbar
nerve root compression with pain, muscle
spasms & atrophy & neurologic deficits
Osteoarthritis: Clinical Features
• Typically, only one or a few joints are
involved
• Joints commonly involved are: hips, knees,
lower lumbar & cervical vertebrae,
proximal & distal interphalangeal joints of
fingers, etc.; Heberden nodes: which
common in women, represent prominent
osteophytes in distal interphalangeal joints
Osteoarthritis: Clinical Features
• There is still no satisfactory means of
preventing primary osteoarthritis and no
methods of halting its progression
Rheumatoid Arthritis (RA)
• RA is a chronic systemic inflammatory
disorder that may affect many tissues and
organs (skin, blood vessels, heart, lungs and
muscles) but principally attacks the joints
producing a nonsuppurative proliferative
synovitis that often progresses to
destruction of the articular cartilage and
ankylosis of the joints
Rheumatoid Arthritis (RA)
• Affects 1% of world’s population with a
female predilection of 3-5:1; peak incidence
is between 20-40 years
• Cause remains unknown but autoimmunity
plays a pivotal role; currently believed RA
is triggered by exposure of an
immunogenetically susceptible host to an
arthritogenic microbial antigen
Rheumatoid Arthritis (RA):
Clinical Course
• Is extremely variable
• Begins insidiously with malaise, fatigue and
generalized musculoskeletal pain and then
joint pain
• Small points are usually affected first
• Involved joints are swollen, warm, painful
and stiff on arising or following inactivity
Rheumatoid Arthritis(RA):
Clinical Features
• Disease course may be slow or rapid and
pts. may enjoy periods of partial or
complete remission
• X-ray hallmarks are joint effusions and
juxtaarticular osteopenia with erosions and
narrowing of joint space with articular
cartilage loss; end result is deformed joints
that have no stability or range of motion
Rheumatoid Arthritis (RA):
Clinical Features
• No specific lab tests are diagnostic as pts.
may/may not have rheumatoid factor
(autoantibodies to Fc portion of autologous
IgG) and it may be seen in other diseases
Rheumatoid Arthritis (RA):
Clinical Features
• Dx is primarily made on clinical features of:
• 1) morning stiffness; 2) arthritis in 3 or
more joint areas; 3) arthritis of hand joints;
4)symmetric arthritis; 5) rheumatoid
nodules; 6) serum rheumatoid factor; and 7)
typical radiographic changes
Rheumatoid Arthritis (RA):
Clinical Features
• Most pts. have progressive disease and RA
is said to reduce life expectancy by 3-7
years
• Death is usually due to complications, e.g.
systemic amyloidosis & vasculitis or to
effects of therapy, e.g. GI bleeding related
to long-term use of anti-inflammatory drugs
& infections from steroid use
Gout
• Is the common end point of a group of
disorders that produce hyperuricemia
• Crystallization of urates within and around
joints in gout create lesions known as
TOPHI
• Tophi represent large aggregates of urate
crystals and the surrounding inflammatory
reaction
Classification of Gout: Primary
Gout (90% of cases)
• Clinical Category
• 1) Enzyme defects
unknown
• 2) Known enzyme
defects; e.g. partial
HGPRT deficiency
(rare)
• Metabolic Defect
• 1) Overproduction or
underexcretion of uric
acid
• 2) Overproduction of
uric acid
Classification of Gout: Secondary
Gout (10% of cases)
• Clinical Category
• Assoc. with increased
nucleic acid turnover;
e.g. leukemias
• Chronic renal disease
• Inborn errors of
metabolism; e.g.
complete HGPRT
defic. (Lesch-Nyhan)
• Metabolic Defect
• Overproduction &
increased excretion of
uric acid
• Reduced excretion
• Overproduction of uric
acid with increased
urinary excretion
Gout
•
•
•
•
•
•
•
Factors contributing to development of gout
1) Age: increases with age
2) Genetic predisposition: HGPRT defic.
3) Alcohol: increased with heavy use
4) Obesity: increased
5) Drugs: e.g. thiazides predispose to
6) Lead toxicity: increases the tendency
Gout
• Patients with hyperuricemia do not
necessarily have gout
• Central to the pathogenesis of the arthritis is
precipitation of monosodium urate crystals
into the joints
Gout: Clinical Features
•
•
•
•
•
The natural history of gout has 4 stages:
1) asymptomatic hyperuricemia
2) acute gouty arthritis
3) intercritical gout (asymptomatic period)
4) chronic tophaceous gout (disabling
disease characterized by juxta-articular
bone erosion and loss of joint space)
Gout: Clinical Features
• Hypertension is common in pts. with gout
• Renal problems are common also with renal
colic, stone formation and finally chronic
gouty nephropathy; 20% of those with
chronic gout die of renal failure
• Many drugs are available to abort and
prevent problems of gout; gout does not
materially shorten life expectancy
Infectious Arthritis: Lyme
Disease
• Is caused by the spirochete Borrelia
burgdorferi
• Is transmitted from rodents to people by
tiny, hard deer ticks (Ixodes dammini, I.
ricinus, etc.)
• Joint involvement is the most common
manifestation of disseminated infection and
develops in approx. 80% of patients
Diseases of Skeletal Muscle
Diseases of Skeletal Muscle
Muscle Atrophy
Neurogenic and Type II Myofiber
Atrophy
• Skeletal muscle fibers undergo progressive
atrophy if deprived of their normal
innervation
• Type II atrophy is seen in pts. who develop
disuse atrophy when bedridden or otherwise
immobilized; type II atrophy is also seen in
pts. receiving glucocorticoids or with
endogenous hypercortisolism
Myasthenia Gravis
• Is an acquired autoimmune disorder of
neuromuscular transmission characterized
by muscle weakness
• Has been associated with other autoimmune
diseases; e.g. SLE, RA and Sjogren’s
• 15-20% of pts. have have thymomas while
2/3 have hyperplasia of thymus
Myasthenia Gravis: Clinical
Features
• Onset of muscle weakness is typically
insidious and often abrupt
• Initial involvement is usually the muscles of
the eyelids and muscles controlling eye
movement (drooping of eyelid & double
vision); involvement of facial & neck
muscles makes chewing and holding the
head upright difficult; respiratory muscle
involvement may lead to respiratory failure
Muscular Dystrophies
Duchenne Muscular Dystrophy
(DMD)
• DMD is an X-linked hereditary disease
caused by the absence of a structural protein
termed dystrophin
• As expected most pts. are male
• The cardinal manifestation is muscle
weakness, which initially is most
pronounced in the proximal muscles
DMD
• Early manifestations include clumsiness,
followed by weakness in the pelvic and
shoulder girdles; calf muscles may enlarge
• Signs and symptoms begin about the age of
5 and progress to leave most pts.
wheelchair-bound by their teen years; most
pts. die in their 20s usually due to
respiratory failure or pneumonia; cardiac
abnormalities occur
Tumor or Tumor-Like Lesions of
the Joints
Ganglion
Ganglion
• Is a small (1-2 cm) cyst that is almost
always located near a joint capsule or
tendon sheath
• Most common site is around the joints of
the wrist where it appears as a firm,
fluctuant, pea-sized translucent nodule
• It arises as a result of cystic or myxoid
degeneration of connective; not a true cyst
Soft Tissue Tumors and TumorLike Lesions
Lipoma
• Benign tumors of fat are the most common
soft tissue tumors (uncommon intraorally)
of adulthood
• The are subclassified as: conventional,
fibrolipoma, angiolipoma, spindle cell,
myelolipoma and pleomorphic
Lipoma
• Some variants have chromosomal
abnormalities; e.g. spindle cell and
pleomorphic have rearrangements of 16q
and 13q
• Lipomas are soft, mobile and painless and
are usually cured by simple excision
Liposarcoma
• Is one of the most common sarcomas of
adulthood and appear in the 40s to 60s
• They usually arise in the deep soft tissues of
the proximal extremities and
retroperitoneum and are notorious for
developing into large tumors
Liposarcoma
• The well-differentiated variant is relatively
indolent, the myxoid is intermediate, while
the round cell and pleomorphic variants are
usually aggressive and frequently
metastasize; local recurrence is a common
problem with all types
Nodular Fasciitis (Infiltrative or
Pseudosarcomatous Fasciitis)
• Is the most common of the reactive
pseudosarcomas
• Occurs most often in adults on the forearm,
chest or back
• Pts. complain of a solitary, rapidly growing,
sometimes painful mass
• 10-15% of cases have a history of trauma
• Simple excision is usually curative
Fibromatoses
Superficial Fibromatosis
• Palmar, plantar, and penile fibromatoses are
more bothersome than serious
• They are characterized by nodular or poorly
defined fascicles of mature-appearing
fibroblasts surrounded by abundant dense
collagen
Superficial Fibromatosis
• In the palmar variant (Dupuytren
contracture) there is irregular or nodular
thickening of the palmar fascia either
unilaterally or bilaterally (50%)
• In plantar fibromatosis flexion contractures
are uncommon & involvement usually
unilateral
Superficial Fibromatosis
• Penile fibromatosis (Peyronie disease) may
cause curvature of the shaft or constriction
of the urethra or both
• All forms are more common in males
• Surgery is the treatment of choice and some
lesions recur
Deep-Seated Fibromatosis
(Desmoid Tumors)
• Biologically, these lesions lie between the
exuberant fibrous proliferations and lowgrade fibrosarcomas
• Desmoids are divided into extra-abdominal,
abdominal and intra-abdominal
• Intra-abdominal often occur in patients with
familial adenomatous polyposis (Gardner
syndrome)
Deep-Seated Fibromatosis
(Desmoid Tumors)
• Desmoid tumors may by disfiguring and
may cause pain
• Although curable by excision, they
frequently recur locally; some cases have
been treated successfully by chemotherapy
or radiation therapy
Fibrosarcoma
• Are rare malignant neoplasms composed of
fibroblasts
• Most common sites are: deep tissues of the
thigh, knee and trunk
• Some tumors grow slowly while others are
more aggressive and tend to recur locally
after excision (some more than once);
approx. 25% may metastasize
Fibrohistiocytic Tumors
Benign Fibrous Histiocytoma
• Relatively common lesion usually occurring
in the dermis and subcutis
• Typically, slow-growing and painless lesion
which presents as a firm, small, mobile
nodule
• Adequate treatment is simple excision
Malignant Fibrous Histiocytoma
• One of the most common sarcomas of
adults (most pts. between 50-70 yrs. of age)
• It is the most common type of
postirradiation sarcoma
• Usually arises in deep muscular tissues of
extremities or in retroperitoneal area
• Most are highly aggressive and often recur
locally & metastasize in approx. 50% of pts.
Neoplasms of Skeletal Muscle
Rhabdomyosarcoma
• Is the most common soft tissue sarcoma of
childhood and adolescence
• They may arise anywhere but most common
in head and neck or GU tract
• Aggressive neoplasms that are treated with
a combination of surgery & chemotherapy
with/without radiation; histologic variant &
location influence survival
Tumors of Smooth Muscle
Leiomyoma
• Leiomyomas are benign smooth muscle
tumors which arise most commonly in the
uterus, where they are often multiple
• The lesions are well-circumscribed and
slow growing
• Solitary lesions are easily cured by excision,
while multiple lesions may be so numerous
as to make surgical removal impractical
Leiomyosarcoma
• Account for 10-20% of soft tissue sarcomas
• They occur in adults and have a female
predilection
• Most develop in the skin & deep soft tissues
of the extremities and retroperitoneum
• Treatment and prognosis depends on size,
location and grade of tumor
Synovial Sarcoma
• Approx. 10% of all soft tissue sarcomas
• Despite name do not arise from synovial
cells but rather from mesenchymal cells
about joints & occasionally elsewhere
• They are treated aggressively with limbsparing therapy; 5-yr survival rates range
from 25-62%; common mets to regional
lymph nodes, lung and skeleton
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