Transcript BONE PATHOLOGY - Technion moodle

BONE PATHOLOGY
Eugene Vlodavsky MD
Pathology Institute RAMBAM Medical Center
MICROSCOPIC STRUCTURE OF BONE
• Osteoprogenitor cells – pluripotential mesenchymal cells. Under
appropriate stimulation can differentiate into osteoblasts
• Osteoblasts – located on the surface of bone, “build” the bone and
initiate process of mineralization. Have receptors for PTH, vit D and
estrogen. Osteoblasts surrounded by bone matrix – osteocytes.
• Osteocytes are less active than osteoblasts but play important role
in control of the fluctuations in serum Ca and Ph levels.
• Osteoclasts – responsible for bone resorption, multinucleated giant
cell,derivate of granulocyte-monocyte precursor cell from bone
marrow
MICROSCOPIC STRUCTURE OF BONE
• Osteoblasts produce proteins of bone,pred. collagen type 1 (90%of
organic component - matrix)
• Woven bone – irregular nonmineralized bone, normally seen only in
fetus. In adult is always sign of pathologic process
• Lamellar bone – gradually replaces woven bone during growth and
is stronger than woven bone
• Osteoblasts and osteoclasts act in coordination as “basic
multicellular unit” performing bone formation and resorption during
skeletal growth (modeling) and maintenance of mature skeleton
(remodeling)
NON-TUMOROUS DISEASES OF
BONE
PAGET’S DISEASE
• Is characterized by regions of “furious” bone resorption by
osteoclasts, followed by a periods of irregular and disordered bone
formation
• Chronic disease, divided into 1. osteolytic stage: 2. mixed
osteoclastic- osteoblastic; 3. burnt-out osteosclerotic stage
• Pathogenesis – viral intranuclear inclusions in the nuclei of
osteoclasts; bone marrow of the patients contains paramyxovirus
nucleocapsid transcripts
• Axial skeleton and prox.femur involved in 80% of cases. Mostly
polyostotic(pelvis,spine,scull), in 15% - monostotic (tibia,
ilium,scull,femur,humerus)
PAGET’S DISEASE - MICROSCOPY
PAGET’S DISEASE - COURSE
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Pain
Bone deformations with various complications
Fractures
Hypervascularity may cause heart failure
Benign tumors – giant cell tumor
Sarcoma (5-10% of polyostotic PD) –
osteosarcoma,chondrosarcoma,MFH
• Most patients have mild symptoms,treated by calcitonin
and diphosphonates
AVASCULAR NECROSIS OF BONE
• Infarction of bone and marrow – relatively common event
• The cause is ischemia, the mechanisms are varied: mechanical
rupture of blood vessels(fracture); thrombosis and embolism;
vasculitis,radiation damage, increased intraosseous pressure due to
steroid therapy and many others.
AVASCULAR NECROSIS
• In medullary necrosis cortical bone is preserved(collateral blood
supply). Subchondral epiphyseal necrosis has triangular shape,
cartilage is preserved, but will collapse later and will cause
secondary osteoarthritis.
• Clinical picture depends on location and size, usually pain
• About 50000 joint replacements annualy in US – due to
complications of avascular necrosis
BONE INFECTIONS - OSTEOMYELITIS
• Inflammation(infection) of bone and marrow
• Pyogenic Os – caused by bacteria: 80-90% Staph.
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Aureus; E.coli, Pseudomonas, Klebsiella – in
genitourinary infections and IV drug users; H.influenzae
and grour B streptococci – in neonates
Bacteria may reach the bone by (1) hematogenous
spread (2) extension from contiguous site (3) direct
implantation
Location – in children – metaphysis and epiphysis, in
adults – epiphysis, vertebra
PATHOLOGY OF OSTEOMYELITIS
• Acute, subacute and chronic
• Cause formation of necrotic bone area (“sequestrum”)
• Inflammation may reach the periost and rupture to the soft tissue
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with formation of draining sinus
In children (rarely in adults) inflammation can involve joints and
produce septic arthritis
In vertebra infection destroys the hyaline cartilage and involve
intervertebral discs(“discitis-osteomyelitis”)
Over time – resorbtion of bone,reactive bone formation and fibrosis
New bone around sequestrum – “involucrum”
Brodie abscess – small intraosseous (often – cortical) abscess
Os of Garre – in the jaw with extensive new bone formation
OSTEOMYELITIS – CLINICAL COURSE
• Acute systemic ilness with
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malaise,fever,leukocytosis,pain
Symptoms may be mild (only pain,esp. infants)
Culture is often negative due to antibiotic treatment
Chronicity may develop when: delay in
diagnosis;ineffective treatment; large area of
necrosis;weakened host defence
Complications of chronic Os: pathologic fracture,
secondary amyloidosis,endocarditis,sepsis, squamous
cell carcinoma in sinus tract, sarcoma of bone
TUBERCULOUS OSTEOMYELITIS
• Increased incidence in western countries due to influx of
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immigrants and growing No of immunosupressed people
Usually blood borne infection
TB Os is more destructive and resistant to treatment
than pyogenic Os
In the spine involves several vertebra and soft
tissue(Pott’s disease), often with compression fractures
and scoliotic or kiphotic deformations
Complications - TB artrithis, sinus tract
formation,amyloidosis
BONE TUMORS
BONE TUMORS MAY BE PRIMARY OR
SECONDARY.MOST COMMON
MALIGNANCIES,PRODUCING BONE METASTASES:
ADULTS. More than 75% of skeletal metastases originate
from Ca of the prostate,breast,kidney, lung,thyroid and
colon. DO NOT FORGET MELANOMA!
CHILDREN. Neuroblastoma,rhabdomyosarcoma and
retinoblastoma
RADIOGRAPHIC APPEARANCE OF
METASTATIC TUMORS
• Purely lytic – kidney,lung,colon,melanoma
• Purely blastic – prostate and breast
• Mixed lytic and blastic (most common)
PRIMARY BONE TUMORS
• More common in first 3 decades of life (skeletal growth activity)
• The commonest sites for both benign and malignant – distal femur
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and proximal tibia – the bones with the highest growth rate
Relatively specific radiologic presentation
Benign tumors are by far more common than malignant
Some are difficult to classify as benign or malignant(giant cell
tumor)
Among malignant tumors osteosarcoma is most common,followed
by chondrosarcoma and Ewing sarcoma
BONE TUMORS
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RELEVANT CLINICAL
INFORMATION
• Age – may be the most important clinical clue: primary
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osteoSa and Ewing Sa are tumors of children and young
adults. After 40 – bone metastases and chondrosarcoma
are most common.
Pain. Benign lesions tend to be asymptomatic.Pain may
be symptom of a)growing lesion b)pathologic fracture
c)significant local tissue reaction to the tumor. Pain can
help in diagnosis of osteoid-osteoma and differential
diagnosis between enchondroma and chondrosarcoma
grade I
Radiological correlation
• Plain radiograph – the first imaging technique for suspected bone
lesion
• Computer tomography – method of choice when plain film is not
sufficient. The best for assesment of mineralization, cortical detail,
cystic and fatty lesions
• MRI is good for local staging – spread of tumor and its relation to
critical neurovascular structures. MRI appearance of most bone
tumors is non-specific
• Bone scintigraphy – highly sensitive but relatively nonspecific
method
RADIOLOGICAL EXAMINATION SHOULD ANSWER THE
FOLLOWING QUESTIONS:
• The exact location of the lesion
• Evidence of any underlying bone abnormality(bone infarct,Paget’s
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disease
Is the lesion multifocal?
Does the tumor have a well defined margin?The rim of sclerotic
bone?(signs of benign lesions).
Is there evidence of cortical destruction or expansion?(signs of
aggressive behavior).
Does the tumor produce mineralized matrix(osteoid or cartilage)?
Is there a soft tissue mass?
OTHER IMPORTANT DIAGNOSTIC FEATURES
• Skeletal location
• Site of long bone involvement
BENIGN BONE TUMORS
OSTEOMA
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Slowly growing tumors of low clinical significance
Predominantly located in scull and facial bones
Microscopically – coarse lamellar and trabecular bone
Multiple osteomas are the part of Gardner
syndrome(fibromatosis, familial intestinal polyposis)
• Resected when cause cosmetic problems,impinge on the
brain or eye etc.
• Do not transform to osreosarcomas
OSTEOID-OSTEOMA AND OSTEOBLASTOMA
• Have identical histological features; differs in size, sites
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of origin and symptoms.
Osteoid-osteoma(OO): less than 2 cm in diameter. 75%
of patients are younger than 25 years old. 50% involves
femur and tibia(but every bone may be involved).
OO is painful lesion(excess production of prostaglandin
E2). The pain is rather severe, nocturnal and relieved by
aspirin
Osteoblastoma is larger than OO, the same age,more
frequent in spine, the pain if present,is different –not so
severe and not so responsive to salicilates
OSTEOID-OSTEOMA
OSTEOBLASTOMA
OSTEOID OSTEOMA AND OSTEOBLASTOMA
TREATMENT AND PROGNOSIS
• Both are treated by conservative surgery
• Incomplete excision – may recur
• Malignant transformation is very rare,usually
after irradiation
OSTEOGENIC SARCOMA
(OSTEOSARCOMA)
OSTEOSARCOMA – MALIGNANT MESENCHYMAL TUMOR IN WHICH
MALIGNANT CELLS PRODUCE BONE MATRIX
• Most common primary malignant tumor of bone(exc. myeloma and
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lymphoma) – 20% of primary bone cancers
About 75% of patients younger than 20 years old (primary OSa)
In older patients – secondary OSa – in conditions associated with
risk of OSa development – Paget’s disease,bone infarcts,prior
irradiation
Usual location – metaphysial region of bone, 60% about the knee:
distal femur,proximal tibia,proximal humerus,proximal femur.
Mutations are very important in development of OSa: Rb-gene
(hereditary cases) and esp. p53 mutations in sporadic OSa
CLASSIFICATION OF OSTEOSARCOMA
• Acc. to anatomic origin:
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intramedullary,intracortical,surface
Grade of malignancy(low and high grade)
Primary or secondary
Histologic variants:
osteoblastic,chondroblastic,fibroblastic,telangioectatic
etc.
Most common type is intramedullary high grade primary
OSa, which arises in metaphysis of the long bones in
young patients
OSTEOSARCOMA – TREATMENT AND PROGNOSIS
• Appr. 20% of patients have lung metastases at the time
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of diagnosis
In the past with surgery alone(amputation) 5-years
survival did not exceed 20%.
To-day – chemotherapy and limb-sparing surgery – up
to 60%
Resection of solitary lung metastases prolong survival
CARTILAGE-PRODUCING TUMORS
SOLITARY CHONDROMA – ENCHONDROMA – IS A BENIGN
INTRAOSSEOUS TUMOR COMPOSED OF WELL
DIFFERENTIATED HYALINE CARTILAGE
• Most common location – metacarpals and phalanges of
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the hands and feet ,may be in other tubular bones
Radiologically – radiolucent,well delineated,with
calcifications
May be also on the surface of bone
• May be multiple (Ollier’s and Maffucci’ syndromes)
• Treatment – curretage,rarely recur if incompletely
excised
CHONDROSARCOMA – GROUP OF
SARCOMAS,PRODUCING NEOPLASTIC CARTILAGE
• Second most frequent matrix producing sarcoma of
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bone(after OSa)
Commonly located in the central part of the skeleton –
pelvis,shoulders,ribs
Patients usually are older than 30 years
May arise in association with pre-exiting enchondroma
Radiologically – calcifications,destructive growth
CHONDROSARCOMA - GRADING
• There is direct correlation between the grade and
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biologic behavior of the tumor
Five-year survival for grade I – 90%; grade II – 81%;
grade III – 43%
Most conventional chondrosarcomas are grade I-II and
have relatively indolent course
Tumor’s size is also significant prognostic feature –
tumors >10cm behave more agressively, than those
<10cm
GRADE I
GRADE II
GRADE III
Pathological differential diagnosis of
chondrosarcoma – with enchondroma and
chondroblastic osteosarcoma
• Microscopically enchondroma and chondrosarcoma may
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be practically indistinguishable
Diagnosis is based on clinical data – age,location,pain(in
chondrosarcoma); radiological features are extremely
important – the presence of destructive growth favor
chondrosarcoma
Chondroblastic osteosarcoma – younger patients,typical
location(metaphysis of long bone), high microscopic
grade,presence of osteoid
Treatment of chondrosarcoma – surgery
only(wide excision),resistant to
chemotherapy!
GIANT CELL TUMOR OF BONE(GCT)
• GCT is relatively uncommon benign but locally
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aggressive neoplasm
The patients are usually in their 20-40-ies
Located in epiphysis and metaphysis,pred. around the
knee,but every bone may be involved
Usually cause pain,arthritic symptoms or pathological
fracture
The main cell of GCT is mononuclear cell of
macrophage-monocyte lineage,the fusion(or incomplete
division) of these cells produce giant cells
TREATMENT AND PROGNOSIS
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GCT is biologically unpredictible
Conservative surgery – up to 60% recurrence
5-10% metastasize to the lungs
Treatment usually – thorough curretage and grafting
In some cases “en block” resection or even amputation
may be nesessary