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NON-NEOPLASTIC BONE DISEASES - Coggle Diagram
NON-NEOPLASTIC BONE DISEASES
BONE
a special type of connective tissue with 35% organic and 65% inorganic components
storage of 98% of body Ca2+, 80% P, 65% Na+ and Mg
non-mineralized form: OSTEOID
cell types
osteoblasts, osteocytes and osteoclasts
genetic developmental abnormalities
Marfan syndrome
loss of development of bone segments, supernumerary segments, syndactyly, arachnodactily
achondroplasia
FGFR3 mutation
osteogenesis imperfecta
COL1A1 and COL1A2 genes mutation
osteopetrosis
hereditary
autosomal dominant/recessive
defective osteoclasts increase in number
inefficient bone resorption
"marble" bones
shrinkage of foramina and nerves compression
decrease in size of medullary canal in long bones
deformation of extremities
fractures
fibrous dysplasia
benign lesion (predisposition to osteosarcoma)
monostotic (70-85%) --> jaw, ribs, skull and long bones
polyostotic (15%): earlier, associated with extra-osseous diseases in syndromic forms (endocrinopathies, cafe au lait spots)
GNAS1
(20q13, coding for Galpha subunit)
rise in cAMP levels
this mutation occurs in post-zygotic phase in somatic cells
the earlier the stage of embryogenesis, the more severe th phenotype
microscopic pathology
spindle cell proliferation
scarcely mineralized bone component
thin sheets
chinese letters
no osteoclasts
low mitotic index
osteopenic diseases
osteoporosis
bone mass loss
diffuse
localized
primary (menopause and old age)
secondary (neoplasia, endocrinopathies, malnutrition, drugs)
tissue damage: unbalanced bone deposition and resorption; reduced trabecular thickness, easy fractures
osteomalacia
decreased mineralization of bone with increase of osteoid border
secondary to endogenous or exogenous deficit of Vit D or deficit od phosphates (malabsorption, urine loss)
rickets
typical of children
endogenous or exogenous deficit of Vit D
lack of calcification of cartilages with bone enlargement
increase in osteoid component with osteophytes (periostal ossification
bone deformities
fibrous cystic osteitis (HPT)
PTH or PTH-related peptides
primary or secondary
increased resorption (osteoclasts) and deposition (osteoblasts(
increased turnover preventing adequate maturation of newly formed bone (irregular trabeculae)
brown pseudocysts
renal osteodystrophy
paget disease
old age
mono-/polyostotic
pain as dominant symptom
pathogenesis: probably post-infective, viral (paramyxoviridae?), increased IL6 and M-CSF, increased osteoclasts number and activity
location: skull, spine, long bones
deformities
evolution: secondary OS
microscopic pathology
different phases
osteolytic
mixed
osteosclerotic
quiescence
mosaic features of lamellar bone
osteomyelitis
bone and bone marrow involvement
hematogenous spread or contiguity
pyogenic type
90% S. aureus
dissemination of bacteria in the bone
acute inflammation with increased pressure and cell death
intracanalar dissemination through havers channels
subperiostal abscesses
isolation of non-vital bone
bone sequestration + fistulae
TBC type
hematogenous in 1-3% TBC patients
spine (thoracic and lumbar), knee and hip
destructive lesions with extraosseous involvement
Pott's abscesses in the spine
cystic lesions
solitary simple cyst
age: children and adolescents
asymptomatic
location: metaphysis of long bones, central
macroscopic pathology
complications and involutive changes in case of fracture
watery or serous-hematic content
thin walls
ossification defects
aneurysmatic cyst
primary (de novo)
secondary (benign or malignant lesions)
also found in soft tissues
pathogenesis
primary
increased vein pressure
hemorrhage
osteolysis
hemorrage
vascular damage causes are unknown
eccentric expansive lesion
epidemiology:
age: 20-30
location: long bones and spine
pathology
macroscopic
multiple cystic spaces with variable sizes
microscopic
no endothelial lining
one content + osteoid + giant cells (atypia)
DD:
giant cell tumor of bone
giant cell granuloma
telangectatic osteosarcoma
benign (hemangioma( and malignant lesions with hemorrhagic cystic component
tumors
bone-forming tumors
malignant
OSTEOSARCOMA
osteoid production
rare occurrence of extra-skeletal osteosarcoma
age <20 y (second peak in elderly)
M>F
increasing incidence
etiology
unknown
genetic predisposition
Li-Fraumeni
retinoblastoma
secondary
Paget disease
prosthesis
poliostotic fibrous dysplasia
site: metaphysis (knee, humerus, femur)
classification
central
(intra-medullary)
clinical variants: jaw/maxilla, post-RT, multicentric, secondary
histological variants: classic, small cell, telangectatic, low grade central
CLASSIC
solitary and intramedullary
whitish/brown with periosteal lift (codman sign)
microscopy
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histology
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subtypes
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superficial
periosteal/parosteal, parosteal dedifferentiated, superficial, of high grade
PAROSTEAL
site: femur
RX: juxta-cortical dense lesion
micro: usually well differentiated
better outcome than classic
based on:
grading, site and histology
prognosis
highly malignant
hematogenous spread
lungs
factors
extent of disease
grading
size
site
primary vs secondary
molecular pathology
TP53
RB1
PTEN
DLG2
MYC
NF1
benign
OSTEOID OSTEOMA / OSTEOBLASTOMA
2nd-3rd decade
M:F = 2:1
long bones (proximal and distal femur and proximal tibia), spine, jaw (cementoblastoma), sacrum
size: 2 cm cut off
microscopic pathology
interconnected trabeculae with numerous osteoblasts at the periphery
loose stroma with capillaries
reactive peritumoral reaction embedding the tumor
central transparent NIDUS and peripheral sclerotic reaction, more typical of osteoblastoma
symptoms
osteoid osteoma
generalized pain
increased PGE2
osteoblastoma
rare systemic symptoms
weight loss
fever
generalized periostitis
OSTEOMA
benign
compact or lamellar mature bone at the periostal surface or endosteal
hamartomatous
in case of multiple lesions --> association with hereditary syndromes (e.g. Gardner)
histology:
mineralized bone with irregular deposition
cartilage-forming tumors
benign
OSTEOCHONDROMA
developmental abnormality, growth arrest at the end of skeletal development
mature bone extrusion covered by cartilage, variable thickness
more evident in children
variable size (up to 20 cm)
usually asymptomatic or pain due to irritation of surrounding tissues
thickness >2 cm
likely malignant transformation
pain
enlargement
<1% of solitary exostoses
OSTEOCHONDROMATOSIS
multiple osteochondromas, bilateral, symmetric
autosomal dominant
diagnosis after 5 years of age
germ-line mutations (EXT1 and EXT2)
M>F
developmental disorders of long bones
risk of malignant transformations
accurate follow up and wxcision if symptomatic or suspected malignant transformation
CHONDROMA
solitary (en)chondroma
localization
short bones
fractures
pain
long bones
asymptomatic
microscopy
proliferation of chondrocytes with aboundant chondroid mature matrix
no atypia
DD: well-diferentiated chondrosarcoma
in hands/feet: hypercellularity
multiple chondromas
Ollier disease
unilateral
localization at hand or at metaphysis of long bones or flat bones
microscopy
overlapping with solitary chondroma, more frequent hypercellularity and mild atypia
malignant transformation in 25-30% of cases
Maffucci syndrome
very rare
chondromas + soft tissue hemangiomas
IDH1 mutation
= gliomas
malignant
CHONDROSARCOMA
4th decade
location: central (75%) or peripheral
central: intra-medullary
peripheral: juxtacortical (periosteal)
likely to arise from a previous osteochondroma
macroscopy
translucent
grey
cortical erosion, protruding
RX: radiopaque with calcifications
grading
cellular grading: nuclear size, nuclear hyperchromasy, cellularity
10% of cases are de-differentiated
stroma: chondroid (G1), myxoid (G2)
necrosis: present (G3)
prognosis
Grade 1: 90% survival
Grade 2: 60-70%
Grade 3: 30-50%
Dedifferentiated: 10%
treatment: surgery + CT/RT
there are no molecular targets for therapeutic purposes
genetics: differential genomic alterations in central vs peripheral, but no relevant molecular biomarkers
two main groups from the genetic point of view
central: IDH1 and IDH2 mutations
secondary: EXT1 and EXT2 mutations
EWING SARCOMA
6-10% of bone tumors
children (<20 y)
highly malignant
site: diaphysis of long bones
from medullary cavity to cortex and periosteum
microscopy
sheets of small cells
monotonous
small nucleoli
glycogen content (PAS+)
pseudo-rosettes
CD99 +
neuroendocrine differentiation
"blue tumors of infancy"
MULTIPLE MYELOMA
most frequent malignant primary bone tumor
age: >40
site: more frequent on bones with more aboundant marrow content
RX: multiple lytic lesions
diagnosis: serum proteins, hypercalcemia, hypocalciuria
BONE HEMANGIOMA (vascular hamartoma)
site: spine and skull
asymptomatic
RX: lytic (alveolar) lesions
rare fractures or extra-osseous growth
histology of benign vascular tumors
METASTASES
osteolytic or increased density (i.e. prostate cancer)
more frequent tumors in the bone