Musculoskeletal Disease

By S.S Eghbali APCP Bushehr 2008

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 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

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 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

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 & Osteoporsis

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 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

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

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

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

Diseases Caused by Osteoclast Dysfunction

Osteopetrosis & Osteitis deformans (Paget dis.)

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

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 • 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 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

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 two major types: • 1) high-turnover osteodystrophy characterized by increased bone resorption and formation with the resorption 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 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)

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

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.

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 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),ESR(High)

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 • 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

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

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 or traumatized • 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 20-40 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

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 well differentiated 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 painfull mass • 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 • t 11:22(extra skletal tumors),t 21:22(PNET),t7;22

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 café au-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 (shepherd crook 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 (ground glass, 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-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

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…..

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: 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

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 Tumor Like 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 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)

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

Thank you for your attention

Any question?