Transcript SURGICAL PATHOLOGY BONES

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
SKELETAL DEVELOPMENTAL AND
GENETIC DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND
GENETIC DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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 craniofacial 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 5. ASPHYXIATING THORACIC DYSPLASIA
• Jeune’s syndrome
• Narrowing of the chest and immobility
• Stippled epiphyses and chondroplasia punctata are
striking features on x-ray
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 7. PROGRESSIVE DIAPHYSEAL DYSPLASIA
• Camurati-Engelman disease
• Rare autosomal dominant disorder
• Formation of new bone at both the periosteal and
endosteal surfaces
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 9. OSTEOPOIKILOSIS
• Presence of numerous foci of sclerosis in
cancellous bone (“spotted bones”)
• Autosomal dominant disorder
• Bone changes are asymptomatic
• Found incidentally on radiographs
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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
SKELETAL DEVELOPMENTAL AND GENETIC
DISORDERS
• 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 nonexistent
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
METABOLIC BONE DISEASES
• 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
METABOLIC BONE DISEASES
• 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
METABOLIC BONE DISEASES
• 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
INFLAMMATORY BONE DISEASES
• 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
INFLAMMATORY BONE DISEASES
• 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
INFLAMMATORY BONE DISEASES
• 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%)
INFLAMMATORY BONE DISEASES
• 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
INFLAMMATORY BONE DISEASES
• 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
X-RAY OF TIBIA SHOWING BONE DESTRUCTION
AND BONE FORMATION
EARLY CHANGES SHOWING PROMINENT
OSTEOCLASTIC ACTIVITY
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
X-RAY
GROSS
MICROSCOPIC
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)
BONE-FORMING TUMORS
• OSTEOSARCOMA…..
• 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
BONE-FORMING TUMORS
• OSTEOSARCOMA…..
• 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
BONE-FORMING TUMORS
• 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
X-RAY
GROSS
MICROSCOPIC
CARTILAGE-FORMING TUMORS
• 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
CARTILAGE-FORMING TUMORS
• 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
CARTILAGE-FORMING TUMORS
• 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
CARTILAGE-FORMING TUMORS
• 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
CARTILAGE-FORMING TUMORS
• 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
CARTILAGE-FORMING TUMORS
• 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:
• 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:
1. 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
X-RAY
MICROSCOPIC APPEARANCE
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
• 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 TGFbeta, 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
X-RAY
GROSS APPEARANCE
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)
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SKELETAL MUSCLES
• 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
TUMORS OF SMOOTH MUSCLE
• 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
TUMORS OF SMOOTH MUSCLE
• 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
TUMORS OF SMOOTH MUSCLE
• 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