Musculoskeletal Disease

Normal Skeletal SystemThe skeletal system is as vital to life as any organ system because it plays an essential role in:1) mineral homeostasis2) houses the hematopoietic elements3) provides mechanical support for movement4) protects & provides body size and shape

Normal Skeletal SystemBone is a type of connective tissueBiochemically, 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 bodys calcium

Normal Skeletal SystemBone also contains 85% of the bodys phosphorus and 65% of the sodium and magnesiumThe 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 SystemThe 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 System2) 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 SystemOSTEOCLASTS 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 SystemThe proteins of bone include type 1 collagen (90% of organic component) and a family of noncollagenous proteins that are derived mainly form osteoblastsOsteoblasts deposit collagen either in a random weave known as WOVEN BONE or in an orderly layered manner called LAMELLAR BONE

Normal Skeletal SystemThe presence of woven bone in the adult is always indicative of a pathologic stateLamellar 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 BoneCongenital ones are uncommon & include: 1) failure of development; e.g. rib absence2) formation of extra bones; e.g. extra digit3) fusion of bones; e.g. syndactylism(digits)4) development of long, spider-like digits; e.g. arachnodactylism5) craniorachischisis (failure of closure of skull and spinal column

AchondroplasiaIs the most common disease of the growth plate and is a major cause of dwarfismIs an autosomal dominant disorder with approx. 80% representing new mutationsPt. 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 MatrixOsteogenesis imperfecta

Osteogenesis imperfectaOsteogenesis imperfecta or brittle bone disease is a group of hereditary conditions characterized by abnormal development of type I collagenThis spectrum of disorders of varying severity are united by the common feature of abnormal collagen synthesis and the resulting bone fragility

Osteogenesis imperfectaMost variants are inherited as autosomal dominants Is characterized by multiple bone fractures which may occur in utero in the severe formsOther findings include: blue sclerae (caused by decreased collagen); hearing loss (ear bone abnormalities; dental imperfections

OsteoporosisIs a term that denotes increased porosity of the skeleton resulting from a reduction in bone massIt may be localized, e.g. disuse osteoporosis of a limb, or generalized as a manifestation of a metabolic bone disease

OsteoporosisWhen 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

OsteoporosisPeak bone mass is achieved during young adulthood and is largely determined by hereditary factors, especially the allele for the vitamin D receptor moleculePhysical activity, muscle strength, diet and hormonal state also contributeAge-related bone loss (approx. 0.7%/yr) is a normal biological phenomenon

OsteoporosisBoth sexes are affected equally and Whites more so than BlacksDifferences in the peak skeletal mass in men vs women and Blacks vs Whites may partially explain why certain populations are prone to develop the disorderMuch remains unknown; the following are related to the development of osteoporosis:

Osteoporosis1) Age-related changes; in older people bone-forming cells have diminished capacity to make bone2) Reduced physical activity; mechanical forces are important stimuli for normal bone remodeling3) Genetic factors; importance of vitamin D receptors

Osteoporosis4) Bodys calcium nutritional state; adolescent girls with insufficient calcium intake are later at greater risk of developing osteoporosis5) Hormonal influences; postmenopausal osteoporosis is characterized by a hormone-dependent acceleration of bone loss; estrogen replacement protects against bone loss

OsteoporosisClinical manifestations may include: vertebral fractures, lumbar lordosis and kyphoscoliosis; pulmonary embolism and pneumonia may result from overt fractures of the femoral neck, pelvis or spinePlain 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 sclerosisClinical 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 massPaget disease usually begins during middle adulthood and becomes progressively more common thereafter

Paget DiseaseAs 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 loss2) a phase of mixed osteoclastic and osteoblastic activity and3) a late, osteosclerotic phase

Paget DiseaseThe disease is usually asymptomatic but can frequently be diagnosed from radiographic findings; many patients manifest elevated serum alkaline phosphastase levelsPain 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 HomeostasisHyperparathyroidism

HyperparathyroidismHyperparathyroidism is classified into primary and secondary typesPrimary type results from autonomous hyperplasia or a tumor (usually an adenoma) of the parathyroid glandSecondary is commonly caused by prolonged states of hypocalcemia resulting in compensatory hypersecretion of PTH

HyperparathyroidismThe skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorptionThe entire skeleton is affected to more or lesser degreeAnatomic changes of severe hyperparathyroidism are known as osteitis fibrosa cystica

HyperparathyroidismSecondary hyperparathyroidism is usually not as severe or as prolonged as primary and hence skeletal changes are milderThe hallmark of PTH excess is increased osteoclastic activity with bone resorptionResorption may be generalized or localized, e.g. diffuse radiolucency, surface erosion or brown tumor

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

Renal OsteodystrophyThe term is used to describe collectively all of the skeletal changes of chronic renal diseaseThere are to major types:1) high-turnover osteodystrophy characterized by increased bone resorption and formation with the former predominating

Renal Osteodystrophy2) low-turnover (aplastic) characterized by a marked reduction in the rate of bone mineralization, formation and resorption

Renal OsteodystrophyThe skeletal changes include:1) increased osteoclastic bone resorption 2) delayed matrix mineralization (osteomalacia)3) osteosclerosis4) growth retardation5) osteoporosis

Infections of Bone-Osteomyelitis

OsteomyelitisOsteomyelitis denotes inflammation of bone and marrow and the common use of the term virtually always implies infectionAll 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 OsteomyelitisPyogenic osteomyelitis is almost always caused by bacteriaOrganism may reach bone by: 1) hematogenous spread (most common route); 2) extension from a contiguous site; or 3) direct implantationLong bones and vertebral bodies most commonly involved

Pyogenic OsteomyelitisS. aureus is responsible for 80-90% of casesE. coli, Pseudomonas and Klebsiella are more commonly isolated from pts. with UG tract infections or are drug usersMixed infections seen in cases of surgery or open fracturesNeonatal period: H. influenzae and group B strept.; Salmonella in pts. with sickle cell

Pyogenic OsteomyelitisLocation of lesions within specific bones is influenced by vascular circulation and varies with ageClinically hematogenous osteomyelitis may manifest as an acute systemic illness with malaise, fever, chills, leukocytosis and throbbing pain over affect siteX-rays, biopsy & cultures help with dx

Pyogenic OsteomyelitisThe combination of antibiotics and surgical drainage is usually curativeIn 5-25% of cases, acute osteomyelitis fails to resolve and persists as chronic infectionComplications may include: pathologic fracture, endocarditis, sepsis, etc.

Tuberculous Osteomyelitis1-3% of pts. with pulmonary or extrapulmonary T.B. have osseous infectionTypically, pts. present with pain on motion, localized tenderness, low-grade fevers, chills and weight lossSevere destruction of vertebrae (Potts disease) may cause skeletal deformities and neurologic deficits

Tumors of BoneBenign Bone-Forming Tumors

OsteomaOsteomas are benign lesions of bone that in many cases represent developmental or reactive growths rather than true neoplasmsThe most common locations are the facial bones and skullMost common in 40-50 yr. groupMost are exophytic growths attached to the bone surface

OsteomaHistologically they resemble normal boneMultiple osteomas are seen in GARDNER SYNDROMEThey are generally slow-growing tumors of little clinical significance except when they cause obstruction or produce cosmetic problemsThey do not undergo malignant change

Osteoid Osteoma and OsteoblastomaBenign 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 groupOsteoid osteomas are

Osteoid Osteoma and OsteoblastomaOsteoblastomas 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 siteBoth lesions are readily treated by conservative surgery but can recur if not completely excised; malignant transformation is rare unless irradiated

Tumors of BoneMalignant-Bone Forming

Osteosarcoma (Osteogenic Sarcoma)Osteosarcoma is defined as a malignant mesenchymal tumor in which the cancerous cells produce bone matrixIt is the most common primary malignant tumor of bone exclusive of myeloma and lymphoma75% of cases occur in pts. younger than 20 years (however, with jaw tumors pts. older)

OsteosarcomaMale predilection 1.6:1Tumors usually arise in metaphyseal region of long bones of extremities with almost 50% around the kneeMorphology: grow outward, lifting periosteum and inward to the medullary cavity; microscopically, malignant cells form osteoid; cartilage may be present also

OsteosarcomaTypically present as painful and progressively enlarging masses; occasionally pathologic fracture is first symptomApprox. 20% of pts. have pulmonary mets at time of dxAdvances in treatment have improved prognosis with 5yr survival now 60% overall

Tumors of BoneBenign Cartilaginous Tumors

OsteochondromaOsteochondroma, also known as an exostosis, is a benign cartilage-capped outgrowth that is attached to the underlying skeleton by a stalkThey may be solitary or multiple and hereditary (multiple hereditary exostosis which is autosomal dominant)

OsteochondromaMore commonly involve the metaphysis of long tubular bones in the 10-30 yr. age groupClinically, osteochondromas present as slow-growing masses which can be painful if they impinge on a nerveThey stop growing at the time of growth plate closure;

ChondromaChondromas are benign tumors of hyaline cartilageWhen they arise within the medullary cavity they are known as ENCHONDROMAS and on the surface of bone they are termed SUBPERIOSTEAL OR JUXTACORTICAL CHONDROMAS

ChondromaChondromas are most common in the small bones of the hands and feet of people in their twenties to fortiesThe syndrome of multiple enchondromas or enchondromatosis is known as OLLIER DISEASEThey are though to develop from rests of growth plate cartilage

ChondromaMost enchondromas are asymptomatic although occasionally they are painful or cause pathologic fractureOn x-ray they appear as unmineralized nodules of cartilage (well-circumscribed radiolucency) surrounded by a thin rim of radiodense bone (O ring sign)

ChondromaThe growth potential is limitedIf treatment is required, surgical excision is the choiceSolitary chondromas rarely undergo malignant change but the multiple enchondromatoses do so more frequently

Tumors of BoneMalignant Cartilaginous Tumors

ChondrosarcomaChondrosarcomas are malignant neoplasms populated by mesenchymal cells that produce a cartilaginous matrixThere are several subclassificationsChondrosarcomas are about half as frequent as osteosarcomasMost patients are in the 40-60 year range with a 2:1 male predilection

ChondrosarcomaThe bones of the shoulder, pelvis, proximal femur and ribs are most commonly involvedMicroscopically, range from well-differentiated cartilage-like to anaplastic tumorsIn contrast to enchondroma, chondrosarcoma rarely involves the distal extremities

ChondrosarcomaChondrosarcomas present most often as enlarging, painful masses; their growth rate and ultimate behavior is closely correlated with histologic gradeChondrosarcomas metastasize via the hematogenous route, most often to the lungs5-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 cellsMost arise in the epiphyses of long bonesPts. are in the 20-40 year age range with a slight female predilectionUsually present with pain and biopsy is necessary for dx

Giant Cell TumorSeveral different bone disorders have multinucleated giant cells so their presence along is not diagnosticThe behavior is somewhat unpredictableSarcomatous transformation is rare but may occur de novo or with irradiation of a benign tumor

Ewings SarcomaIs a primitive malignant neoplasm of bone that occurs predominantly in children in whom it is the second most common malignancy after osteosarcomaIt is a highly aggressive neoplasm which has been associated with a chromosomal translocation identical to that seen in primitive neuroectodermal tumors

Ewings SarcomaClassically presents with pain often accompanied by local inflammation; fever is fairly common along with elevated SED rate, anemia and leukocytosisX-rays show a destructive lytic tumor which may show a periosteal reaction producing layers of reactive bone (onion-skin appearance)

Ewings SarcomaTreatment includes chemotherapy and surgery with/without radiationThis treatment has increased the 5-year survival to approximately 75%

Fibrous DysplasiaIs 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 DysplasiaThere 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 caf-au-lait spots and endocrine abnormalities such as precocious puberty

Fibrous Dysplasia: MonostoticAccounts for approx. 70% of all casesOccurs about equally in boys & girls usually in early adolescenceOften stops growing at the time of growth plate closureRibs, femur, tibia, jaws, skull common sitesUsually asymptomatic; can cause marked enlargement and distortion of bone

Fibrous Dysplasia: Polyostotic without Endocrine Dysfunction27% of casesAppears at an earlier age and progresses into adulthood50% 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 & EndocrinopathyAlso known as McCune-Albright SyndromeCaf-au-lait spotsEndocrinopathies may include: sexual precocity, hyperthyroidism, pituitary adenomas producing GH and primary adrenal hyperplasiaGirls more frequently involved than boys

Fibrous DysplasiaPts. with monostotic disease have minimal symptomsLesions readily diagnosed by x-ray (ground-glass, etc.) and biopsyConservative surgery for symptoms or cosmeticsPolyostotic frequently associated with progressive disease; rare sarcomatous trans.

Diseases of the JointsOsteoarthritis

Osteoarthritis (Degenerative Joint Disease)Is the most common type of joint diseaseIs characterized by the progressive erosion of articular cartilageAlthough 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

OsteoarthritisMost 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

OsteoarthritisPrevalence increases exponentially beyond the age of 50 with about 80-90% of both sexes having osteoarthritis by age 65Age-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

OsteoarthritisChondrocytes play a primary role and constitute the cellular basis of the diseaseThey 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 FeaturesIs an insidious diseaseCharacteristic 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 FeaturesTypically, only one or a few joints are involvedJoints 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 FeaturesThere 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 worlds population with a female predilection of 3-5:1; peak incidence is between 20-40 yearsCause 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 CourseIs extremely variableBegins insidiously with malaise, fatigue and generalized musculoskeletal pain and then joint painSmall points are usually affected firstInvolved joints are swollen, warm, painful and stiff on arising or following inactivity

Rheumatoid Arthritis(RA): Clinical FeaturesDisease course may be slow or rapid and pts. may enjoy periods of partial or complete remissionX-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 FeaturesNo 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 FeaturesDx 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 FeaturesMost pts. have progressive disease and RA is said to reduce life expectancy by 3-7 yearsDeath 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

GoutIs the common end point of a group of disorders that produce hyperuricemiaCrystallization of urates within and around joints in gout create lesions known as TOPHITophi represent large aggregates of urate crystals and the surrounding inflammatory reaction

Classification of Gout: Primary Gout (90% of cases)Clinical Category1) Enzyme defects unknown

2) Known enzyme defects; e.g. partial HGPRT deficiency (rare)Metabolic Defect1) Overproduction or underexcretion of uric acid2) Overproduction of uric acid

Classification of Gout: Secondary Gout (10% of cases)Clinical CategoryAssoc. with increased nucleic acid turnover; e.g. leukemiasChronic renal diseaseInborn errors of metabolism; e.g. complete HGPRT defic. (Lesch-Nyhan)Metabolic DefectOverproduction & increased excretion of uric acidReduced excretionOverproduction of uric acid with increased urinary excretion

GoutFactors contributing to development of gout1) Age: increases with age2) Genetic predisposition: HGPRT defic.3) Alcohol: increased with heavy use4) Obesity: increased 5) Drugs: e.g. thiazides predispose to6) Lead toxicity: increases the tendency

GoutPatients with hyperuricemia do not necessarily have goutCentral to the pathogenesis of the arthritis is precipitation of monosodium urate crystals into the joints

Gout: Clinical FeaturesThe natural history of gout has 4 stages:1) asymptomatic hyperuricemia2) acute gouty arthritis3) intercritical gout (asymptomatic period)4) chronic tophaceous gout (disabling disease characterized by juxta-articular bone erosion and loss of joint space)

Gout: Clinical FeaturesHypertension is common in pts. with goutRenal problems are common also with renal colic, stone formation and finally chronic gouty nephropathy; 20% of those with chronic gout die of renal failureMany drugs are available to abort and prevent problems of gout; gout does not materially shorten life expectancy

Infectious Arthritis: Lyme DiseaseIs caused by the spirochete Borrelia burgdorferiIs 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 MuscleMuscle Atrophy

Neurogenic and Type II Myofiber AtrophySkeletal muscle fibers undergo progressive atrophy if deprived of their normal innervationType 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 GravisIs an acquired autoimmune disorder of neuromuscular transmission characterized by muscle weaknessHas been associated with other autoimmune diseases; e.g. SLE, RA and Sjogrens15-20% of pts. have have thymomas while 2/3 have hyperplasia of thymus

Myasthenia Gravis: Clinical FeaturesOnset of muscle weakness is typically insidious and often abruptInitial 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 dystrophinAs expected most pts. are maleThe cardinal manifestation is muscle weakness, which initially is most pronounced in the proximal muscles

DMDEarly 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 JointsGanglion

GanglionIs a small (1-2 cm) cyst that is almost always located near a joint capsule or tendon sheathMost common site is around the joints of the wrist where it appears as a firm, fluctuant, pea-sized translucent noduleIt arises as a result of cystic or myxoid degeneration of connective; not a true cyst

Soft Tissue Tumors and Tumor-Like Lesions

LipomaBenign tumors of fat are the most common soft tissue tumors (uncommon intraorally) of adulthoodThe are subclassified as: conventional, fibrolipoma, angiolipoma, spindle cell, myelolipoma and pleomorphic

LipomaSome variants have chromosomal abnormalities; e.g. spindle cell and pleomorphic have rearrangements of 16q and 13qLipomas are soft, mobile and painless and are usually cured by simple excision

LiposarcomaIs one of the most common sarcomas of adulthood and appear in the 40s to 60sThey usually arise in the deep soft tissues of the proximal extremities and retroperitoneum and are notorious for developing into large tumors

LiposarcomaThe 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 pseudosarcomasOccurs most often in adults on the forearm, chest or backPts. complain of a solitary, rapidly growing, sometimes painful mass10-15% of cases have a history of traumaSimple excision is usually curative

Fibromatoses

Superficial FibromatosisPalmar, plantar, and penile fibromatoses are more bothersome than seriousThey are characterized by nodular or poorly defined fascicles of mature-appearing fibroblasts surrounded by abundant dense collagen

Superficial FibromatosisIn 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 FibromatosisPenile fibromatosis (Peyronie disease) may cause curvature of the shaft or constriction of the urethra or bothAll forms are more common in malesSurgery 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 fibrosarcomasDesmoids are divided into extra-abdominal, abdominal and intra-abdominalIntra-abdominal often occur in patients with familial adenomatous polyposis (Gardner syndrome)

Deep-Seated Fibromatosis(Desmoid Tumors)Desmoid tumors may by disfiguring and may cause painAlthough curable by excision, they frequently recur locally; some cases have been treated successfully by chemotherapy or radiation therapy

FibrosarcomaAre rare malignant neoplasms composed of fibroblastsMost common sites are: deep tissues of the thigh, knee and trunkSome 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 HistiocytomaRelatively common lesion usually occurring in the dermis and subcutisTypically, slow-growing and painless lesion which presents as a firm, small, mobile noduleAdequate treatment is simple excision

Malignant Fibrous HistiocytomaOne of the most common sarcomas of adults (most pts. between 50-70 yrs. of age)It is the most common type of postirradiation sarcomaUsually arises in deep muscular tissues of extremities or in retroperitoneal areaMost are highly aggressive and often recur locally & metastasize in approx. 50% of pts.

Neoplasms of Skeletal Muscle

RhabdomyosarcomaIs the most common soft tissue sarcoma of childhood and adolescenceThey may arise anywhere but most common in head and neck or GU tractAggressive neoplasms that are treated with a combination of surgery & chemotherapy with/without radiation; histologic variant & location influence survival

Tumors of Smooth Muscle

LeiomyomaLeiomyomas are benign smooth muscle tumors which arise most commonly in the uterus, where they are often multipleThe lesions are well-circumscribed and slow growingSolitary lesions are easily cured by excision, while multiple lesions may be so numerous as to make surgical removal impractical

LeiomyosarcomaAccount for 10-20% of soft tissue sarcomasThey occur in adults and have a female predilectionMost develop in the skin & deep soft tissues of the extremities and retroperitoneumTreatment and prognosis depends on size, location and grade of tumor

Synovial SarcomaApprox. 10% of all soft tissue sarcomasDespite name do not arise from synovial cells but rather from mesenchymal cells about joints & occasionally elsewhereThey are treated aggressively with limb-sparing therapy; 5-yr survival rates range from 25-62%; common mets to regional lymph nodes, lung and skeleton