1. Musculoskeletal DiseaseBy
S.S Eghbali APCP
Bushehr

2. 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

3. 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

5. 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 day lag time between the formation of the matrix and its mineralization; bone that is unmineralized is known as OSTEOID

6. Normal Skeletal System
The organic component includes the cells of bone and proteins of the matrix; the bone-forming 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

7. 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

8. 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

9. 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

10. Normal Skeletal System Woven vs Lamellar bone
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

11. Diseases of Bone

12. 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

13. 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

15. Diseases Associated With Abnormal Matrix
Osteogenesis imperfecta
&
Osteoporsis

16. 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

17. 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

19. 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

20. 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

21. 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

22. 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:

23. Osteoporosis Main risk factors
1) Age:Age-related changes; in older people bone-forming cells have diminished capacity to make bone
2) Physical activity:Reduced physical activity; mechanical forces are important stimuli for normal bone remodeling
3) Genetic factors:Genetic factors; importance of vitamin D receptors

24. 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 hormone-dependent acceleration of bone loss; estrogen replacement protects against bone loss
Race : whites are in more risk than blacks

27. 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

28. Osteoporosis Diagnosis is on the base of :
Plaine X-ray isnot fully effective specially when bone loss <30-40%
Bone densitometery
Bone biopsy is the most effective

29. Diseases Caused by Osteoclast Dysfunction
Osteopetrosis
&
Osteitis deformans (Paget dis.)

30. 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 and serious infections may occur; manifestations depend on form of disease

31. 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

32. 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
3) A late, osteosclerotic phase

34. Paget Disease
The disease is usually asymptomatic but can frequently be diagnosed from radiographic findings; many patients manifest elevated serum alkaline phosphatase 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

35. Diseases Associated With Abnormal Mineral Homeostasis
Hyperparathyroidism

36. 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

37. 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

38. 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”

39. Hyperparathyroidism
The decrease in bone mass predisposes to fractures, deformities caused by the stress of weight bearing and joint pain and dysfunction

40. Renal Osteodystrophy
The term is used to describe collectively all of the skeletal changes of chronic renal disease
There are two major types:
1) high-turnover osteodystrophy characterized by increased bone resorption and formation with the resorption predominating

41. Renal Osteodystrophy
2) low-turnover (aplastic) characterized by a marked reduction in the rate of bone mineralization, formation and resorption

42. Renal Osteodystrophy The skeletal changes include:
1) increased osteoclastic bone resorption
2) delayed matrix mineralization (osteomalacia)
3) osteosclerosis
4) growth retardation
5) osteoporosis

43. Infections of Bone
Osteomyelitis

44. 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

45. 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

46. Pyogenic Osteomyelitis
S. aureus is responsible for 80-90% of cases
E. coli, Pseudomonas and Klebsiella are more commonly isolated from pts. with GUT infections or are drug users
Mixed infections seen in cases of surgery or open fractures
Neonatal period: H. influenzae and group B strept.; Salmonella ( sickle cell Anemia)

47. 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
Diagnosis is on the base of: X-rays, biopsy & cultures

48. 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, multiple small abcess (brian,lung,liver) and etc.

49. 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

50. Benign Bone-Forming Tumors
Tumors of Bone
Benign Bone-Forming Tumors

52. 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 yr. group
Most are exophytic growths attached to the bone surface

53. 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

54. 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 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),ESR(High)

55. 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

56. Malignant-Bone Forming
Tumors of Bone
Malignant-Bone Forming

57. 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)

58. Osteosarcoma Male predilection 1.6:1
Tumors usually arise in metaphyseal region of long bones of extremities with almost 50% around the knee
Gross morphology: grow outward, lifting periosteum(codman triangle) and inward to the medullary cavity;Upward&downward with skipt tumors,
Microscopically: malignant cells form osteoid; cartilage may be present also

59. Osteosarcoma
Typically present as painful and progressively enlarging masses; occasionally pathologic fracture is first symptom
Approx. 20% of pts. have pulmonary metastasis at time of diagnosis
Outcome:Advances in treatment (surgery,radiotherapy , chemotherapy)have improved prognosis with 5yr survival now 60% overall

61. Benign Cartilaginous Tumors
Tumors of Bone
Benign Cartilaginous Tumors

62. 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)

63. Osteochondroma
More commonly involve the metaphysis of long tubular bones in the yr. age group
Clinically, osteochondromas present as slow-growing masses which can be painful if they impinge on a nerve or traumatized
They stop growing at the time of growth plate closure;
<1% give rise to sarcoma

65. 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

66. Chondroma
Chondromas are most common in the small bones of the hands and feet of people in their years old of age
The syndrome of multiple enchondromas or enchondromatosis is known as OLLIER syn
The synd. Of ench. With soft tissue hemangioma is known as Maffcci syn.
They are though to develop from rests of growth plate cartilage

67. 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)

68. 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

69. Malignant Cartilaginous Tumors
Tumors of Bone
Malignant Cartilaginous Tumors

70. 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 year range with a 2:1 male predilection

71. Chondrosarcoma
The bones of the shoulder, pelvis, proximal femur and ribs are most commonly involved
Microscopically, range from well-differentiated cartilage-like to anaplastic tumors
In contrast to enchondroma, chondrosarcoma rarely involves the distal extremities

72. 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

73. Miscellaneous Tumors and Tumor-Like Conditions of Bone

74. 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 year age range with a slight female predilection
Usually present with pain and painfull mass
Biopsy is necessary for dx

75. 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

76. 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
t 11:22(extra skletal tumors),t 21:22(PNET),t7;22

77. 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)

78. Ewing’s Sarcoma
Treatment includes chemotherapy and surgery with/without radiation
This treatment has increased the 5-year survival to approximately 75%

79. 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

80. 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 café-au-lait spots and endocrine abnormalities such as precocious puberty

81. 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

82. 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 (shepherd-crook deformity) and often fractures

83. 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

84. Fibrous Dysplasia Pts. with monostotic disease have minimal symptoms
Lesions readily diagnosed by x-ray (ground-glass, etc.) and biopsy
Conservative surgery for symptoms or cosmetics
Polyostotic frequently associated with progressive disease; rare sarcomatous trans.

85. Diseases of the Joints
Osteoarthritis

86. 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

87. 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

88. 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

89. Osteoarthritis
Chondrocytes play a primary role and constitute the cellular basis of the disease
They produce IL-1 & TNF-a, which are known to stimulate the production of catabolic metalloproteinases and inhibit the synthesis of both collagen II and proteoglycans
other mediators also have a role in matrix degradation

90. Osteoarthritis: Clinical Features
DJD is an insidious disease
Characteristic symptoms include: deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement; pressure on spinal foramina by osteophytes results in cervical & lumbar nerve root compression with pain, muscle spasms & atrophy & neurologic deficits
Continued…..

91. 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

92. Osteoarthritis: Treatment&outcome
Conservative therapy with anti-inflammatory drugs and rest is the chioce
There is still no satisfactory means of preventing primary osteoarthritis and no methods of halting its progression

93. 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

95. Rheumatoid Arthritis (RA)
Affects 1% of world’s population with a female predilection of 3-5:1; peak incidence is between 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

97. 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

98. 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

99. 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

100. 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

101. 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

102. 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

103. 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

104. 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

106. 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

107. 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

109. 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)

110. 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

111. 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

112. Diseases of Skeletal Muscle

113. Diseases of Skeletal Muscle
Muscle Atrophy

114. 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

115. 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

116. 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

117. Muscular Dystrophies

118. 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

119. 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

121. Tumor or Tumor-Like Lesions of the Joints
Ganglion

122. 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

123. Soft Tissue Tumors and Tumor-Like Lesions

124. 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

125. 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

126. 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

127. 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

128. 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

129. Fibromatoses

130. 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

131. 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

132. 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

133. Deep-Seated Fibromatosis (Desmoid Tumors)
Biologically, these lesions lie between the exuberant fibrous proliferations and low-grade fibrosarcomas
Desmoids are divided into extra-abdominal, abdominal and intra-abdominal
Intra-abdominal often occur in patients with familial adenomatous polyposis (Gardner syndrome)

134. 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

135. 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

136. Fibrohistiocytic Tumors

137. 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

138. Malignant Fibrous Histiocytoma
One of the most common sarcomas of adults (most pts. between 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.

139. Neoplasms of Skeletal Muscle

140. 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

141. Tumors of Smooth Muscle

142. 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

143. 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

144. 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 limb-sparing therapy; 5-yr survival rates range from 25-62%; common mets to regional lymph nodes, lung and skeleton

145. Thank you for your attention
Any question?