BONES AND MUSCLES ROBERTO D. PADUA JR., MD, DPSP

BONES AND MUSCLES ROBERTO D. PADUA JR., MD, DPSP
DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE

SKELETAL DEVELOPMENTAL AND GENETIC DISORDERS
CHONDRODYSPLASIAS Abnormalities in the size and shape of bones Disproportionate shortness in stature Named after the part of the bone affected Other names refer to the appearance of the bone Diastrophic (twisted) Thanatophoric (death-bearing) Metatropic (changing) Family history of disease is obligatory Radiologic appearance can be confused with other metabolic bone diseases Serum levels of biochemical markers are normal Bone is well mineralized

1. ACHONDROPLASIA Most common cause of disproportionately short stature 1 of 40,000 live births, autosomal dominant Head is large, frontal region is protuberant, nasal bridge is depressed Lordosis and lumbar kyphosis are present Anteroposterior flattening of the pelvic inlet Failure of normal endochondral ossification at the level of the proliferating and maturing cartilage

2. ACHONDROGENESIS Affected infants are either stillborn or do not survive the immediate neonatal period 2 syndromes a) Achondrogenesis I (Parenti-Fraccaro) Associated with congenital heart defects No ossification in the skull & vertebral bodies b) Achondrogenesis II (Langer-Saldino) Shortened limbs & disproportionately large head Underdeveloped ossification centers in the vertebral bodies and pelvis Epiphyseal cartilage is lobulated with increased vascularity Completely disorganized endochondral ossification of the growth plate and there is no column formation

3. THANATOPHORIC DYSPLASIA Infants are either stillborn or die of respiratory distress during the neonatal period Pattern of inheritance is unknown Length of trunk is normal but the head is large with cranio-facial disproportion Common CVS and CNS anomalies Pronounced platyspondyly of the lumbar vertebrae with an inverted U appearance Curvature of femurs with medial and lateral spikes at their lower ends; short, flared ribs Endochondral ossification is disrupted at the growth plate, no regular column formation

4. CHONDROECTODERMAL DYSPLASIA Also known as Ellis-van Creveld syndrome Short limb dwarfism Consanguity is an important factor in the etiology of the disease Clinical presentation: Narrowing of rib cage Congenital heart disease Ectodermal abnormalities Acromegalic micromelia (shortening of the distal segment of the limb

5. ASPHYXIATING THORACIC DYSPLASIA Jeune’s syndrome Narrowing of the chest and immobility Stippled epiphyses and chondroplasia punctata are striking features on x-ray

6. OSTEOPETROSIS Marble bone disease Defective osteoclast function that impairs skeletal resorption Primary spongiosa persists during adult life Increased incidence of parental consanguity Early symptom is malformation of mastoid and paranasal sinuses Pathognomonic histologic finding is the failure of osteoclast to resorb skeletal tissue

7. PROGRESSIVE DIAPHYSEAL DYSPLASIA Camurati-Engelman disease Rare autosomal dominant disorder Formation of new bone at both the periosteal and endosteal surfaces

8. ENDOSTEAL HYPEROSTOSIS Van Buchem disease Autosomal dominant/recessive disorder Progressive enlargement of mandible during puberty Radiographic feature: dense and homogenous diaphyseal cortex with narrowing of the medullary canal

9. OSTEOPOIKILOSIS Presence of numerous foci of sclerosis in cancellous bone (“spotted bones”) Autosomal dominant disorder Bone changes are asymptomatic Found incidentally on radiographs

10. OSTEOPATHIA STRIATA Characterized by linear striations at the ends of long bones and in the ilium X-ray shows gracile linear striations in the cancellous region of the skeleton Autosomal dominant trait

11. MELORHEOSTOSIS Characterized by hyperostosis of the limb bones X-ray : likened to appearance of melted wax that is dripped down the side of the candle Typical histologic finding is endosteal thickening

12. PACHYDERMOPERIOSTOSIS Hypertrophic osteoarthropathy Characterized by clubbing of digits, hyperhidrosis, thickening of skin around the face and forehead and periosteal new bone formation in the distal limbs Inherited as autosomal dominant trait Men>women X-ray shows thickening and sclerosis of the distal portions of the tubular bones

13. OSTEOGENESIS IMPERFECTA “Brittle bone disease” Hereditary disorder involving defects in the synthesis or structure of collagen type I Cardinal features : osteopenia associated with recurrent fracture and skeletal deformity Biochemical findings : increased AP, increased level of hydroxyproline, hypercalciuria Histology : abnormal skeletal matrix; cartilaginous bars formed by vascular invasion of the metaphyses do not become envelop by bones; cortical bone is almost non-existent

METABOLIC BONE DISEASES
1. OSTEOPOROSIS Loss of normally minerralized bone Diagnosed clinically with non-invasive radiographic techniques that measures bone density Changes in the bone : Structurally weak Loss of trabecular bone Enlargement of the medullary space Cortical porosity Reduction in cortical thickness

2. RENAL OSTEODYSTROPHY Seen in patients with advanced renal failure Clinical presentations : Bone pain (most common), spontaneous fractures, aseptic necrosis of hip, myopathy Laboratory findings : Low levels of 1;25(OH)2D3, hyperphosphatemia, hypocalcemia, alterations in the secretion or activity of PTH X-ray : Subperiosteal erosions, patchy osteosclerosis (“rugger jersey” appearance of thoracic vertebral spine on lateral views, “salt and pepper” appearance of skull, slipped epiphyses

3. OSTEOMALACIA Defective mineralization of the trabecular and cortical bone matrix Associated with decreased serum calcium phosphate product A common complication of chronic renal failure in adults Secondary to Vitamin D deficiency Histologically characterized by excessive quantities of osteoid because of the failed matrix calcification despite continued matrix synthesis by the osteoblasts

4. RICKETS Defective mineralization of the epiphyseal growth plate cartilage Clinical features : craniotabes, frontal bossing, rachitic rosary, pectus excavatum, “Harrison’s groove”, thoracic kyphosis, rachitic potbelly, genu varum/genu valgum Histologic appearance : Rachitic growth plate is wide and irregular Columnar rearrangement of the hypertrophic chondrocyts is lost Zone of provisional calcification disappears Cartilage extends deep into the metaphyses

TRAUMA FRACTURE REPAIR Blastema  wound closure  scar formation
Initial repair tissue formed is called a CALLUS which is composed of fibrous tissue, woven bone and cartilage 3 phases of fracture healing : A) inflammatory phase B) reparative phase = orderly removal and replacement of immature woven bone by cartilage differentiation C) modeling phase = realignment & mechanical shaping of the bone and callus; restoration of the medullary cavity and bone marrow Complications of fracture healing : A) nonunions B) fibrous union

INFLAMMATORY BONE DISORDERS
OSTEOMYELITIS Classified according to several factors 1. its duration = acute, subacute or chronic 2. nature of the exudate = hemorrhagic, purulent, or nonsuppurative 3. its location = bone, periosteum, or epiphyses 4. etiologic agent = Staphylococcus, Tb, etc. Histologically, inflammatory cells are seen Loss of normal marrow architecture Hematopoietic elements and fat are replaced by leukocytic infiltrates

INFLAMMATORY BONE DISEASES
OSTEOMYELITIS….. “Chronic sclerosing osteomyelitis of Garre” A chronic form of osteomyelitis with findings of dense, scarred bone and few clinical symptoms without any abscess formation. “Brodies abscess” Osteomyelitis sharply limited to one side with formation of abscess cavity surrounded by a rim of sclerotic bone. Causes: Coagulase (+) Staph. Aureus (60-90%) Strep, Pneumococcus, E. coli, Klebsiella, Salmonella, Bacteroides

OSTEOMYELITIS….. Causes : Tuberculosis Spread hematogenously Characteristic lesion : Chronic caseating granulomatous inflammation which often involves the subchondral part of the joint. Sequestrum forms in the subchondral bone and articular cartilage resulting in a “kissing sequestrum”. Pott’s disease – Tb of the spine

OSTEOMYELITIS X-RAY GROSS : UPPER FEMUR

SARCOIDOSIS Noncaseating granulomatous process Manifest as small lytic and sclerotic foci in the bones of the hand Large areas of destruction are not typically found

PAGET’S DISEASE OF BONE (OSTEITIS DEFORMANS) A chronic osteolytic and osteosclerotic disease of uncertain cause May involve one or more bones Presents with pain, skeletal deformities, and occasionally sarcomatous transformation Usually affects 3% of white population over 40 y/o Incidence increases with age; men>women Most patients are asymptomatic (80-90%)

PAGET’S DISEASE OF BONE….. Common skeletal sites of involvement are the sacrum, spine, pelvis, skull, femur, clavicle, tibia, ribs, and humerus Histopathology: Normal marrow is replaced by a richly vascular, loose fibrous connective tissue Isolated clusters of inflammatory cells may be seen Osteoclasts aggregate on the existing bone trabeculae and within the cortex Innumerable small, irregularly shaped bone fragments (mosaic pattern) Grossly resembles the gritty but brittle texture of pumice or lava rock

PAGET’S DISEASE OF BONE…. X-RAY : flocculant, radiopaque deposit likened to cotton wool. Pelvis is the most common site of involvement. Elevated AP and osteocalcin level Elevated urinary excretion of hydroxyproline, pyridinoline and deoxypyridinoline Malignant transformation are also observed Osteosarcomas Fibrosarcomas Giant cell malignant fibrous histiocytoma

PAGET’S DISEASE OF BONE
EARLY CHANGES SHOWING PROMINENT OSTEOCLASTIC ACTIVITY X-RAY OF TIBIA SHOWING BONE DESTRUCTION AND BONE FORMATION

DEGENERATIVE DISEASES OF BONE
OSTEONECROSIS Infarction of bone typically involving the femoral head 3 generic categories = postfracture, idiopathic, and renal transplant associated Also known as “avascular necrosis of bone” Earliest histologic changes are death of the bone and the surrounding hematopoietic & fatty marrow X-ray : “Crescent sign” , a separation of fracture cleft forms between the impacted fragments and the overlying subchondral plate. Increased density within the necrotic bone.

BONE TUMORS Most malignant tumors arise de novo
Benign bone lesions that predispose to the development of skeletal malignancies Paget’s disease, chondromatosis, osteochondromatosis, fibrous dysplasia, and osteofibrous dysplasia Five basic parameters in the diagnosis of bone tumors Age of the patient Bone involved Specific area within the bone Radiographic appearance Microscopic appearance

BONE FORMING TUMORS 1. OSTEOMA
Seen almost exclusively in the flat bones of skull and face Microscopically: composed of dense, mature, predominantly lamellar bone Benign Associated with Gardner’s syndrome

BONE-FORMING TUMORS 2. OSTEOID OSTEOMA
Benign neoplasm seen in patients between 10 and 30 y/o 2:1 male-female ratio Intense pain is the most prominent symptom Reported in practically every bone, most are centered in the cortex (85%), spongiosa (13%), or subperiosteal region (2%) X-ray: typical finding is a radiolucent nidus that is seldom larger than 1.5 cm and may or may not contain a dense center. This nidus is surrounded by a peripheral sclerotic reaction. Microscopic: sharply delineated central nidus composed of more or less calcified osteoid lined by plump osteoblast and growing within vascularized connective tissue, without evidence of inflammation.

OSTEOID OSTEOMA MICROSCOPIC GROSS X-RAY

BONE-FORMING TUMORS 2. OSTEOBLASTOMA
Benign osteoblastoma, giant osteoid osteoma Closely related to osteoid osteoma both microscopically and ultrastructurally It has a larger size of the nidus, absence of surrounding area of reactive bone formation, and the lack of intense pain A cartilaginous matrix is present in some cases Most cases arise in the spongiosa of the bone involving the spine or major bones of the lower extremity Osteomalacia can be seen as a complication

BONE-FORMING TUMORS 3. OSTEOSARCOMA
The most frequent primary malignant tumor, exclusive of hematopoietic malignancy Usually occurs in patients between 10 and 25 years of age and is rare in pre-school children Another peak age incidence occurs after the age of 40, in association with other disorders Most osteosarcomas arise de novo, but others arise within the context of a preexisting condition Paget’s disease, radiation exposure, chemotherapy, preexisting benign bone lesions, foreign bodies, trauma

BONE-FORMING TUMORS OSTEOSARCOMA…..
Located in the metaphyseal area of long bones, particularly the lower end of femur, upper end of the tibia, and the upper end of the humerus Large majority arise within the medullary cavity from which they extend into the cortex Gross appearance varies depending on the relative amounts of bone, cartilage, cellular stroma and vessels  bony hard to cystic, friable, and hemorrhagic From its usual origin in the metaphysis of a long bone, the tumor may spread along the marrow cavity, invade the adjacent cortex, or elevate or perforate the periosteum (Codman’s triangle)

Extend into the soft tissues, extend into the epiphysis, extend into the joint space, form satellite nodules independent from the main tumor mass proximal to the primary lesion (“skip metastases”), metastasize through the blood stream to distant sites particularly the lung.

BONE-FORMING TUMORS OSTEOSARCOMA….. Microscopic features
May destroy preexisting bone trabeculae or grow around them in an appositional fashion Key feature is the presence of osteoid and or bone produced directly by tumor cells without interposition of cartilage Osteoblastic areas are often mixed with fibroblastic and chondroblastic foci Tumor cells may grow in diffuse, nesting or pseudopapillary arrangements

OS cells usually exhibit strong AP activity, regardless of their appearance Ultrastructurally, tumor cells resemble normal osteoblasts Consistently expresses Vimentin In some cases, they are positive for smooth muscle actin, desmin, EMA, S-100 protein Osteonectin, osteocalcin, osteopontin bone morphogenetic protein and bone GLA protein have been identified immunohistochemically

BONE-FORMING TUMORS OSTEOSARCOMA….. Microscopic variants
Telangiectatic Small cell Fibrohistiocytic Anaplastic Well-differentiated intramedullary Others = parosteal (juxtacortical), periosteal

OSTEOSARCOMA GROSS SHOWING SKIP METASTASIS MICROSCOPIC APPEARANCE

OSTEOSARCOMA TELANGIECTATIC VARIANT OF OSTEOSARCOMA

OSTEOSARCOMA JUXTACORTICAL OSTEOSARCOMA

Diagnosis: characteristic radiographic appearance, open biopsy, needle biopsy, FNAB, frozen section. Therapy: amputation or disarticulation. At present, limb-sparing procedures coupled with other therapeutic modalities. Prognosis: Poor : presence of Paget’s disease, multifocal OS, chondroblastic type, Telangiectatic variant, elevated AP, low postchemotherapy tumor necrosis, loss of heterozygosity of the RB gene, HER2/neu expression, expression of P-glycoprotein

CARTILAGE-FORMING TUMORS
1. CHONDROMA A common benign cartilaginous tumor that occurs most frequently in the small bones of the hands and feet, particularly the proximal phalanges 30% are multiple Microscopically, they are composed of mature hyaline cartilage. Foci of myxoid degeneration, calcification, and endochondral ossification are common Enchondromas begins in the spongiosa of the diaphysis from which they expand and thin out the cortex Lesions with predominantly unilateral distribution are referred to as Ollier’s disease Its association with soft tissue hemangiomas is known as Maffucci’s syndrome

CHONDROMA MICROSCOPIC X-RAY GROSS

2. OSTEOCHONDROMA Most frequent benign tumor Usually asymptomatic, but may lead to deformity or interfere with the function of adjacent structures such as tendons and blood vessels Most common locations are metaphyses of the lower femur, upper tibia, upper humerus and pelvis Average age of onset is 10 y/o, majority appears before the age of 20 Average greatest diameter is 4 cm but may reach 10 cm or more A cap of cartilage covered by fibrous membrane continous with the periosteum of the adjacent bone Microscopically, the cells resemble those of normal hyaline cartilage. Eosinophilic, PAS-(+) inclusions may be seen in the cytoplasm. The bulk of the lesion is composed of mature bone trabeculae located beneath the cartilaginous cap and containing normal bone marrow.

OSTEOCHONDROMA GROSS, CUT SECTION MICROSCOPIC

3. CHONDROBLASTOMA Occurs predominantly in males under 20 y/o Usually arises in the epiphyseal end of long bones before the epiphyseal cartilage has disappeared, particularly in the distal end of femur, proximal end of humerus, and proximal end of tibia X-ray: tumor is fairly well delimited and contains areas of rarefaction Microscopic: the basic tumor cell is an embryonic chondroblast with only a limited capacity for the production of cartilaginous matrix. Presence of occasional scattered giant cells

CHONDROBLASTOMA….. Microscopic: Cells are usually polyhedral with round to indented nuclei. Reticulin fibers surround each individual cell. Presence of small zones of focal calcification (“chicken wire”) Diagnosis can be made by fine needle aspiration which will show neoplastic chondroblast, multinucleated osteoclast-like giant cells, and chondroid myxoid fragments Treatment is by curettement with bone grafting

CHONDROBLASTOMA X-RAY GROSS

CHONDROBLASTOMA MICROSCOPIC

4. CHONDROMYXOID FIBROMA An unusual benign tumor Usually occurs in long bones of young adults Radiographically, it is sharply defined and may attain a large size Grossly, it is solid and yellowish white or tan, replaces bone and thins the cortex. Microscopically, shows hypocellular lobules with a chondromyxoid appearance separated by intersecting bands of fibroblast-like spindle cells and osteoclasts Strong positivity to S-100 protein Treatment is by curettage with a recurrence rate of 25%

CHONDROMYXOID FIBROMA
X-RAY GROSS MICROSCOPIC

5. CHONDROSARCOMA A malignant tumor of cartilage-forming tissues Divided into conventional and variants Conventional chondrosarcoma can be Central = located in the medullary cavity, usually of flat or long bone. X-ray show osteolytic lesion with splotchy calcification with ill-defined margins, fusiform thickening of the shaft, and perforation of the cortex Peripheral = may arise de novo or from the cartilaginous cap of a preexisting osteochondroma Juxtacortical (periosteal) = involves the shaft of a long bone characterized by a cartilaginous lobular pattern with areas of splotchy calcification and endochondral ossification

CHONDROSARCOMA….. Microscopically, there is production of cartilaginous matrix and the lack of direct bone formation by the tumor cells Soft tissue implantation following biopsy is a well known complication Chondrosarcoma variants Clear cell chondrosarcoma Myxoid chondrosarcoma Dedifferentiated chondrosarcoma Mesenchymal chondrosarcoma

CHONDROSARCOMA GROSS APPEARANCES OF CHONDROSARCOMA

CHONDROSARCOMA X-RAY, FEMUR

CHONDROSARCOMA WELL-DIFFERENTIATED CLEAR CELL VARIANT

GIANT CELL TUMOR Osteoclastoma Patients are over 20 years of age
More common in women then men More frequently in Oriental than Western countries Classic location is epiphysis of long bone Affects more commonly the lower end of femur, upper end of tibia, and lower end of the radius. It also occurs in the humerus, fibula, and skull particularly the sphenoid bone. Multicentricity has been reported particularly in young patients and in the small bones of hands and feet

GIANT CELL TUMOR X-ray: Gross:
The typical appearance is that of an entirely lytic, expansile lesion in the epiphysis, usually without peripheral bone sclerosis, or periosteal reaction Gross: The size of the tumor varies; when large, it may be associated with a pathologic fracture The cut surface is solid and tan or light brown, traversed by fibrous trabeculae, and often contains hemorrhagic areas The cortex is thinned, but periosteal new bone formation is rare

GIANT CELL TUMOR Microscopic:
Two main components are stromal cells and giant cells The giant cells are usually large and have over twenty or thirty nuclei, most of then are arranged toward the center. They resemble osteoclasts at all levels: ultrastructurally, enzyme histochemically and immunohistochemical Result of fusion of circulating monocytes that have been recruited into the lesion Possible mechanisms: Autocrine or paracrine loop mediated by transforming growth factor beta

GIANT CELL TUMOR Microscopic….. Possible mechanisms….
2. Production of osteoprotegerin ligand (a factor essential for osteoclastogenesis) 3. Expression of the ligand for RANK (receptor activator of nuclear factor Kappa B) Mononuclear stromal cells is the only proliferating element in the lesion and the one exhibiting atypia in the rare cytologically malignant examples of this tumor These changes may be focal, hence a thorough sampling is required Produces type I & III collagen and has receptors for PTH

GIANT CELL TUMOR X-RAY GROSS APPEARANCE

GIANT CELL TUMOR MICROSCOPIC APPEARANCE

GIANT CELL TUMOR Frequent positivity for S-100 protein
Many benign lesions with giant cells have been diagnosed as giant cell tumor in the past A diagnosis of a lesion other than GCT should be favored if: 1. patient is a child 2. lesion is located in the metaphysis or diaphysis of a long bone 3. lesion is multiple 4. lesion is located in the vertebrae, jaw, or bones of the hands or feet

GIANT CELL TUMOR Treatment :
Surgical = consists of curettage with bone grafting or en bloc resection with allograft or artificial material Use of radiation therapy should be reserved only for cases in which surgical removal is impossible

MARROW TUMORS 1. EWING’S SARCOMA/PRIMITIVE NEUROECTODERMAL TUMOR (PNET) Undifferentiated type of bone sarcoma in children Related to the neoplasm originally described in the soft tissues as primitive (peripheral) neuroectodermal tumor Usually seen in patients between the ages of 5 and 20 years Clinically, the tumor may simulate OM because of pain, fever, and leukocytosis

EWING’S/PNET Occurs most often in long bones (femur, tibia, humerus, and fibula) and in the bones of the pelvis, rib, vertebrae, mandible and clavicle It generally arises in the medullary canal of the shaft, from which it permeates the cortex and invade the tissues Can present clinically as a soft tissue neoplasm with a normal appearance of the underlying bone on plain x-ray films X-ray : cortical thickening and widening of the medullary canal. With progression of the lesion, reactive periosteal bone may be deposited in layers parallel to the cortex (“onion-skin” appearance) or at right angle to it (“sun-ray” appearance)

EWING’S SARCOMA/PNET Microscopic :
Consists of solid sheets of cells divided into irregular masses by fibrous bands Individual cells are small and uniform The cells outline are indistinct, resulting in a “syncitial” appearance The nuclei are round, with frequent indentations, small nucleoli and variable but usually brisk mitotic activity There is well developed vascular network Pseudorosettes and rosettes arrangement of cells may be seen

EWING’S SARCOMA/PNET X-RAY GROSS APPEARANCE

EWING’S SARCOMA/PNET MICROSCOPIC APPEARANCE

EWING’S SARCOMA/PNET Cells contains large amounts of cytoplasmic glycogen --- (+) PAS Ultrastructurally, a few dense core granules will be found either in the cell cytoplasm or in cell prolongations Immunohistochemically, positive for vimentin, LMW keratin, NSE, protein gene product 9.5, Leu7, and neurofilaments Over 95% of cases show a reciprocal translocation 11;22 (q24;q12), which results in the fusion of EWS gene with FLI or ERG genes

EWING’S SARCOMA/PNET Metastatic spread is to the lungs and pleura, other bones (particularly the skull), CNS, and (rarely) regional LN About 25% of the patients have multiple bone and/or visceral lesions at the time of presentation Treatment: Combination of high-dose irradiation and multidrug chemotherapy– sometimes combined with limited surgery

MARROW TUMORS 2. MALIGNANT LYMPHOMA
Can involve the skeletal system primarily or as a manifestation of a systemic disease LARGE CELL LYMPHOMA More common in adults than in children 60% of cases occurring in patients over 30 y/o No sex predilection Most cases involve the diaphysis or metaphysis og long bones or vertebrae producing patchy cortical and medullary destruction associated with minimal to moderate periosteal reaction The tumor is pinkish gray and granular, frequently extends into the soft tissues and invades the muscle

MALIGNANT LYMPHOMA LARGE CELL LYMPHOMA…..
Radiographically, a combination of bone production and bone destruction often involves a wide area of a long bone Microscopically, the appearance is similar to that of the large cell lymphoma in nodal and other extranodal sites, some cases are accompanied by prominent fibrosis The 5-year survival rate for localized B-cell lymphoma of bone has ranged from 30-60% The stage of the disease is the single most important prognostic determinator

MALIGNANT LYMPHOMA MICROSCOPIC APPEARANCE X-RAY

MALIGNANT LYMPHOMA HODGKIN’S LYMPHOMA
Produces radiographically detectable bone lesions in approximately 15% of the patients Involvement is multifocal in about 60% of cases, most frequent sites being vertebrae, pelvis, ribs, sternum, and femur Osseous lesions are often asymptomatic and in half of the cases are not demonstrable radiographically

MALIGNANT LYMPHOMA Anaplastic large cell lymphoma Burkitt’s lymphoma
Lymphoblastic lymphoma

ACUTE LEUKEMIA Associated with radiographic abnormalities in the skeletal system in 70-90% of cases Destructive bone lesions are extremely rare in the chronic leukemias

VASCULAR TUMORS 1. HEMANGIOMA
Often seen in the vertebrae as an incidental post-mortem finding The most common locations are the skull, vertebrae, and jaw Cut section has a currant jelly appearnce Microscopically, there is a thick-walled lattice-like pattern of endothelial lined cavernous spaces filled with blood Multiple hemangiomas are mainly seen in children and are associated in about half of the cases with cutaneous, soft tissue, or visceral hemangiomas

VASCULAR TUMORS 2. MASSIVE OSTEOLYSIS Gorham’s disease
Not a vascular neoplasm Has microscopic similarities with skeletal angiomatosis It has a destructive character It results in reabsorption of a whole bone or several bones and the filling of the residual spaces by a heavy vascularized fibrous tissue

VASCULAR TUMORS 3. LYMPHANGIOMAS 4. GLOMUS TUMOR 5. HEMANGIOPERICYTOMA
Most cases are multiple and associated with soft tissue tumors of similar appearance 4. GLOMUS TUMOR May erode the underlying bone 5. HEMANGIOPERICYTOMA Can present as a primary bone lesion, most common location is the pelvis

VASCULAR TUMORS 6. EPITHELIOID HEMANGIOENDOTHELIOMA
A borderline type of vascular neoplasm characterized microscopically by the presence epithelial- or histiocyte-like endothelial cells with abundant acidophilic and often vacuolated cytoplasm, large vesicular nucleus, modest atypia, scanty mitotic activity, inconspicous or absent anastomosing channels, recent and old hemorrhage and an inconstant but sometimes prominent inflammatory component rich in eosinophils

VASCULAR TUMORS 7. ANGIOSARCOMA
Malignant hemangioendothelioma, hemangioendothelial sarcoma Exhibits obvious atypia of the tumor cells, formation of solid areas alternating with others with anastomosing vascular channels, and foci of necrosis and hemorrhage Multicentricity is common Distant metastasis are common, particularly lungs

VASCULAR TUMORS CAVRNOUS HEMANGIOMA OF BONE

VASCULAR TUMORS EPITHELIOID HEMANGIOENDOTHELIOMA

METASTATIC TUMORS In most cases the lesions are multiple
More than 80% arises from the breast, lung, prostate, thyroid, or kidney These metastases can be accompanied by visceral deposits or represent the only apparent site of dissemination Soft tissue sarcomas rarely metastasize to the bones except embryonal rhabdomyosarcoma in children They are usually osteolytic but maybe osteoblastic or mixed

Metastatic tumors The mechanism is thought to be the production of bone growth factors by tumor cells, such as TGF-beta, fibroblast growth factor, and bone morphogenetic proteins Symptoms is usually pain Treatment is relief of pain and to prevent fracture of weight-bearing bones

TUMORLIKE LESIONS 1. SOLITARY BONE CYST Unicameral bone cyst
Usually occur in long bones, most often in the upper portion of the shaft of the humerus and femur Also seen in the short bones, calcaneus Mostly affects males and are seen in patients under 20 years Usually are advanced when first seen, most are centered in the metaphysis and they migrate away from the epiphyseal line

TUMORLIKE LESIONS SOLITARY BONE CYST….
The cysts contains a clear or yellow fluid that is lined by a smooth fibrous membrane Maybe hemorrhagic if previous fracture occurred Microscopic: well-vascularized connective tissue, hemosiderin and cholesterol clefts are frequent Treatment of choice is curettement and replacement of the cyst with bone chips

SOLITARY BONE CYST X-RAY GROSS APPEARANCE

TUMORLIKE LESIONS 2. ANEURYSMAL BONE CYST
Usually seen in patients between 10 and 20 years of age More common in females Occurs mainly in the vertebrae and flat bones but can also arise in the shaft of long bones Multiple involvement is common in the vertebral lesions X-ray: shows eccentric expansion of the bone with erosion and destruction of the cortex and a small area of periosteal new bone formation

TUMORLIKE LESIONS ANEURYSMAL BONE CYST….
GROSS: it forms a spongy hemorrhagic mass covered by a thin shell of reactive bone, which may extend into the soft tissue Microscopic: show large spaces filled with blood They do not contain endothelial lining but are rather delimited by cells with similar features to fibroblast, myofibroblasts, and histiocytes A row of osteoclasts is often seen immediately beneath the surface There is significant deposition of generated calcifying fibromyxoid tissue.

TUMORLIKE LESIONS ANEURYSMAL BONE CYST…. Pathogenesis is still unknown
In a few cases, the lesion is preceded by trauma with fracture or subperiosteal hematoma It may also arise in some preexisting bone lesion as a result of changed hemodynamics Insulin-like growth factor-I may play in its pathogenesis Ddx: chondroblastoma, GCT, fibrous dysplasia, nonossifying fibroma, osteoblastoma, chondrosarcoma Treatment : en bloc resection or curettage with bone grafting

ANEURYSMAL BONE CYST GROSS APPEARANCE X-RAY

ANEURYSMAL BONE CYST MICROSCOPIC APPEARANCE

TUMORS OF SKELETAL MUSCLES
RHABDOMYOSARCOMA Most common soft tissue sarcoma of childhood and adolescence Usually appears before the age of 20 Commonly occurs in the head and neck or genitourinary tract, extremities Cytogenic abnormalities t(2;13)(q35;q14) t(1;13)(q36;14)

RHABDOMYOSARCOMA In the more common translocation, t(2;13), the PAX3 gene on chromosome 2 fuses with the FKHR gene on chromosome 13 PAX3 gene functions upstream of genes that control muscle differentiation Pathogenesis of tumor involves dysregulation of muscle differentiation by the chimeric PAX3-FKHR protein

RHABDOMYOSARCOMA – MORPHOLOGY EMBRYONAL ALVEOLAR PLEOMORPHIC *** Diagnostic cell is the RHABDOMYOBLAST = contains eccentric eosinophilic granular cytoplasm rich in thick and thin filaments = may be round or elongated (tadpole or strap cells = Ultrastructurally, contain sarcomeres = Immunohistochemically, they stain with antibodies to the myogenic markers desmin, MYOD1 and myogenin

RHABDOMYOSARCOMA – MORPHOLOGY EMBRYONAL RHABDOMYOSARCOMA Most common type, accounting to 60% Includes Sarcoma Botryoides Occurs in children under 10 years of age Typically arises in the nasal cavity, orbit, middle ear, prostate and paratesticular region Allelic loss of chromosome 11p15.5 as its major genomic abnormality

RHABDOMYOSARCOMA – MORPHOLOGY EMBRYONAL RHABDOMYOSARCOMA Grossly,they present as a soft gray infiltrative mass Microscopically, the tumor cells mimic skeletal muscle cells at various stages of embryogenesis and consist of sheets of both malignant round and spindled cells in a variably myxoid stroma Sarcoma botryoides grows in a polypoid fashion, producing the appearance of a cluster of grapes protruding into a hollow structure such as the bladder or vagina

RHABDOMYOSARCOMA – MORPHOLOGY ALVEOLAR RHABDOMYOSARCOMA Most common in the early and mid-adolescence and usually arises in the deep musculature of the extremities Histologically, the tumor is traversed by a network of fibrous septae that divide the cells into clusters or aggregates; as the central cells degenerate and drop out, resembles pulmonary alveolae Tumor cells are moderate in size and have little cytoplasm

RHABDOMYOSARCOMA – MORPHOLOGY ALVEOLAR RHABDOMYOSARCOMA Cells with cross-striations are identified in about 25% of cases Cytogenetic studies show a t(2;13) or t(1;13) chromosomal translocations

RHABDOMYOSARCOMA – MORPHOLOGY PLEOMORPHIC RHABDOMYOSARCOMA Characterized by numerous large, sometimes multinucleated, bizarre eosinophilic tumor cells This variant is rare Arises in the deep soft tissue of adults Resemble malignant fibrous histiocytoma histologically

RHABDOMYOSARCOMA Usually treated with a combination of surgey and chemotherapy with or without radiation Histologic variant and location of the tumor influence survival Sarcoma botryoides have the best prognosis, followed by embryonal, pleomorphic, and alveolar variants Overall prognosis for children is good = 65%; less for adults

TUMORS OF SMOOTH MUSCLE
LEIOMYOMA Benign smooth muscle tumor, commonly arises in the uterus May also arise in the erector pili muscles found in the skin, nipples, scrotum and labia and less in the deep soft tissues Multiple lesions is thought to be hereditary and transmitted as an autosomal dominant trait Occur in adolescence and early adult life

LEIOMYOMA Tumors are usually not larger than 1 to 2 cm in greatest dimension Composed of fascicles of spindle cells that tend to intersect each other at right angles Tumor cells have blunt-ended, elongated nuclei and show minimal atypia and few mitotic figures Treatment is surgical

LEIOMYOSARCOMA Account for 10 to 20% of soft tissue sarcomas Occurs in adults, women>men Most develop in the skin and deep soft tissues of the extremities and retroperitoneum Present as painful, firm masses Retroperitoneal tumors may be large and bulky and cause abdominal symptoms

LEIOMYOSARCOMA Histologically, characterized by malignant spindle cells that have cigar-shaped nuclei arranged in interweaving fascicles Immunologically, they stain with antibodies to vimentin, actin, smooth muscle actin and desmin Treatment depends on the size, location and grade of the tumor

Thank You

BONES AND MUSCLES ROBERTO D. PADUA JR., MD, DPSP

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BONES AND MUSCLES ROBERTO D. PADUA JR., MD, DPSP

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Presentation on theme: "BONES AND MUSCLES ROBERTO D. PADUA JR., MD, DPSP"— Presentation transcript:

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