Presentor- Dr Lachhima Bhandari
Moderator- Dr Heena
1
Normal bone
 Parts of bone-1) epiphysis
2)metaphysis
3)diaphysis
 Macroscopic architecture of bone
may be1)Compact bone
2)cancellous/spongy/trabecular bone
2
Microscopic arrangement of bone1)Woven bone- random deposition of collagen
2)Lamellar bone- collagen deposited in orderly manner.
3
osteoid
 Unmineralised matrix produced by osteoblasts
 Type I collagen with a minor component of non-
collagenous proteins & growth factors
 On H&E-dense,pink,amorphous intercellular material
 D/d-collagen, fibrin, chondroid
4
WHO classification of bone tumors
 Osteogenic Tumours
a) Osteoid osteoma
b)Osteoblastoma
c)Osteosarcoma- conventional
- chondroblastic
- fibroblastic
- osteoblastic
d) Telangiectatic
e) Small cell
f) Low grade central
g) Secondary
h) Parosteal
i) Periosteal
j) High grade surface
5
Contd...
 Catilage tumors
a) Osteochondroma
b) Chondroma- enchondroma
- periosteal chondroma
-multiple chondromatosis
c) Chondroblastoma
d) Chondromyxoid fibroma
e) Chondrosarcoma- central, primary and secondary
- peripheral
- dedifferentiated
- mesenchymal
- clear cell
6
Contd…..
 Fibrogenic tumours
a)Desmoplastic fibroma
b) Fibrosarcoma
 Fibrohistiocytic tumours
a) Benign
b) malignant
 Ewing sarcoma/ primitive neuroectodermal
tumour- ewing sarcoma
 Giant cell tumour
 Haematopoietic tumours- plasma cell myeloma
- malignant lymphoma, NOS
Notochordal tumours- chordoma

 Vascular tumour- hemangioma
- angiosarcoma
7
Contd….
 Smooth muscle tumour- leiomyoma





- leiomyosarcoma
Lipogenic tumours- lipoma
- liposarcoma
Neural tumours- neurilemmoma
Miscellaneous tumours- adamantinoma
- metastatic malignancy
Miscellaneous lesions- aneurysmal bone cyst
- simple cyst
- fibrous dysplasia
- osteofibrous dysplasia
- langerhans cell histiocytosis
- erdheim chester disease
- chest wall hamartoma
Joint lesions- synovial chondromatosis
8
Precursor lesions of bone tumours
 High risk- ollier disease( enchondromatosis)
- maffucci syndrome
- familial retinoblastoma syndrome
- rothmund-thomson syndrome
 Moderate risk- multiple osteochondromas
- polyostotic paget disease
- radiation osteitis
 Low risk- fibrous dysplasia
- bone infarct
- chronic osteomyelitis
- osteogenesis imperfecta
- giant cell tumour
- osteoblastoma and chondroblastoma
- implants
9
Osteogenic tumoursThese are bone forming tumours.
1.OSTEOMA
2.OSTEOID OSTEOMA
benign
3.OSTEOBLASTOMA
4.OSTEOSARCOMA
malignant
10
OSTEOID OSTEOMA
 Age-10-30 yrs
 Sex- male predominance
 Site –majority seen in metaphysis long bones esp.
femur & tibia
 Clinical features – Painful, Worse at night
Relieved by NSAIDs
 Radiological featuresRadioluscent central nidus(<1.5 cm) surrounded
by a peripheral sclerotic reaction.
11
 Gross well circumscribed,size <2 cm
 nidus-small ,red and
granular area;
 periphery- white sclerotic
bone
 M/E
 Interlacing network of osteoid
trabeculae that are variably
mineralised
 Lined by prominent,
plump osteoblasts
 Hypervascular sclerotic bone
around tumour
12
 Immunophenotype- strong nuclear staining for
Runx 2 and Osterix
 Differential diagnosis
1.Osteomyelitis(Radiological)-Brodie’s abscess
2.Osteoblastoma
- indistinguishable histologically
- Size main distinguishing factor>2cms
13
OSTEOBLASTOMA
 Age- mainly between 10-30 yrs
 Sex-Male predominace(M:F 2.5:1)
 Site-prediliction for posterior elements of spine
and sacrum. Also metaphysis of long bones
 Clinically-back pain,scoliosis,nerve root
compression;pain not relieved by aspirin
 Radiology- radiolucent lesion with haphazard foci
of mineralization with perilesional reactive bone
14
 Gross well demarcated scalloped
edges ,periosteal reactive bone
 rich vascular supply( redbrown color), gritty sensation
 M/E Anastomosing trabeculae of
woven bone rimmed by a
single layer of osteoblasts
 Intertrabecular space-loose
fibrovascular stroma and
multinucleate giant cells
 Well circumscribed, no
permeation of pre-existing
bone
15
Cytology- osteoblast like cells, singly or in groups or row
-multinucleated osteoclast like cells
- clusters of spindle cells
Aggressive /epitheloid osteoblastomasAtypical radiographic & architectural features, tendency of
local recurrence
m/e- presence of large, epithelioid like osteoblasts with low
mitotic activity and absence of permeation of surrounding
bone.
Differential diagnosis
1.
Osteoid osteoma-on basis of size(<2 cm)
2. Osteosarcoma- permeation of surrounding
intertrabecular spaces
16
OSTEOID OSTEOMA
OSTEOBLASTOMA
Trabeculae of woven bone are randomly arranged
and interconnect haphazardly. Large osteoblasts
rim the woven bone surfaces, and intertrabecular
spaces contain loose fibrovascular tissue.
17
OSTEOSARCOMAS


-
Most common non-hemopoeitic primary malignant tumors of bone
Predisposing factors- paget disease
radiation exposure
chemotherapy(alkylating agents)
preexisting benign bone lesion(fibrous dysplasia, bone infarct
Genetics- association with Li-Fraumani syndrome(TP53), hereditary
retinoblastoma(RB1 gene0, Rothmund Thomson syndrome, Werner
syndrome.
 Osteosarcomas are classified into- conventional
- telangiectatic
- small cell
- parosteal
- periosteal
- high grade surface
18
a)Conventional osteosarcoma
 Age- bimodal; first bigger peak 10-14 yrs and 2nd
smaller peak >40 yrs.
 Sex-male predominance( M:F 1.35:1)
 Site-metaphysis of long bones, distal femur>proximal
tibia >proximal humerus
 Symptoms- enlarging painful mass with warm,
erythemtous overlying skin; restricted movement,
fracture
 Radiology- destruction of medullary cavity and
cortical bone, resulting in periosteal reaction like
codman triangle or sunburst appearance.
19
Gross Large, intramedullay tan-grey-
white, gritty mass
 Reactive periosteal boneformation with lifting off
periosteum-codman triangle
Cytology Pleomorphic pattern of cells
 Epithelioid tumour cellsosteoblastic or chondroblastic
type
 Multinucleated tumor cells
 Mitotic figures(often atypical)
 Intercellular tumour matrix of
osteoid within clusters
 Cytoplasmic ALPase positive
20
M/E-highly anaplastic tumor,
tumor cells may be
epithelioid,fusiform,ovoid,
clear cells or spindle cells
 Permeative pattern of
growth
 Accurate identification of
osteoidEosinophilic,dense,homoge
nous
 Osteoblastic areas mixed
with chondroblastic &
fibroblastic areas
 Predominant matrix-decides
the name
21
 Conventional osteosarcoma is further subclassified
into- osteoblastic
- chondroblastic
- fibroblastic
- giant cell rich
- clear cell
- epithelioid
- osteoblastoma like
- chondroblastoma like
22
23
HISTOLOGIC VARIANTS OF
OSTEOSARCOMA
TYPES
CHARACTERISTICS
DIFFERENTIAL
DIAGNOSIS
TELANGIECTATIC
OSTEOSARCOMA
Blood filled or empty
ANEURYSMAL BONE
cystic spaces separated by CYST
thin septa
SMALL CELL
OSTEOSARCOMA
Small cells with scanty
EWING’S SARCOMA
cytoplasm associated with
osteoid production
LOW-GRADE
INTRAOSSEOUS/
CENTRAL
OSTEOSARCOMA
Bland spindle cell
background arranged in
irregular bundles
Low grade fibro-osseous
lesions like FIBROUS
DYSPLASIA, desmoplastic
fibroma
24
Telangiectatic osteosarcoma
Blood
clot
Blood filled cystic spaces
25
s
Small cell osteosarcoma- small cells Intraosseous osteosarcomawith scant cytoplasm
Fibroblastic stroma with
variable
26
amount of osteoid
Surface based osteosarcoma
DIAGNOSIS
LOCATION
RADIOLOGICAL
FEATURES
HISTOLOGICAL
FEATURES
BEHAVIOUR
Parosteal
osteosarcoma
Distal femur
(70%); proximal
tibia
Arises from bone
cortex and
surrounding bone;
“PASTED-ON”
appearance
Very bland
spindle cell
stroma with wellformed trabecular
osteoid and bone
Low-grade
lesion; adequate
surgical excision is
usually curative
D/dosteochondroma
Periosteal
osteosarcoma
Diaphysis of long
bones: tibia and
femur
Thickened cortex
with parallel lines
of calcified matrix;
also frequently lytic
Chondroblastic in
appearance with
focal osteoid
formation
Intermediategrade lesion; will
recur and
metastasize in a
subset of patients
d/dosteochondroma,
chondroblastic
osteosarcoma
High-grade
surface
osteosarcoma
Metaphysis or
diaphysis of long
bones
Arises from cortex;
poorly delineated;
may involve the
bone medullary
cavity
Similar to
conventional
osteosarcoma
High grade
lesion; aggressive
behaviour
27
e)Parosteal osteosarcoma
 most common osteosarcoma of surface of bone
 Sex- female predominance
 Age- third decade
 Site-distal posterior femur(metaphyseal surface)
 Symptom-painless swelling, inability to flex knee
 Radiology- heavily mineralized mass attached to
cortex with broad base
28
Gross-hard lobulated mass
attached to the
cortex;encircling the bone
m/e- spindle cells with
minimum atypia, forming
parallely arranged bony
trabeculae
- Intertrabecular stroma is
hypocellular
D/D- osteochondromapresence of cartilaginous cap
29
f)PERIOSTEAL OSTEOSARCOMA
 Age-second & third decade
 Sex-male predominance
 Site-diaphysis or diaphyseal-metaphyseal region of
long bones,esp. tibia and femur
 Symptom- limb swelling, mass, pain
 Radiological- cortical thickening, extrinsic cortical
scalloping, periosteal reaction perpendicular to bone’s
long axis(hair on end appearance)
30
 Gross-a broad based with
cortical thickening
 M/E-prominent cartilaginous
component showing varying
degrees of cytological atypia

D/D
1.Osteochondroma,
2.Conventional chondroblastic
osteosarcoma
3.Chondrosarcoma
(juxtacortical)
31
g)High grade surface osteosarcoma




Age- second decade
Sex-male predominance
Site- femur>tibia>humerus
Gross-situated on the cortical surface of bone,varying
in consistency depending on predominant matrix
 M/E-Same spectrum as conventional osteosarcoma
32
Osteosarcoma arising in special
clinical settings
a)osteosarcoma in paget’s disease- most cases arise
in polyostotic paget disease
b)Osteosarcoma of jaw
 Age-average age 34 yrs.
 Site-body of the mandible &alveolar ridge of maxilla
 Relative good prognosis
c)Postradiation osteosarcoma
 Most common location-pelvis and the shoulder region
 Radiation doses of usually greater than 20Gy
 High grade osteosarcomas
33
d)Osteosarcomas in course of various benign diseases
Three important associations
 Bone infarct
 Prosthetic joint
 Fibrous dysplasia
34
BONE TUMOURS
IHC
DIFFERENTIAL DIAGNOSIS
OSTEOMA
NOT USEFUL
1.
2.
3.
4.
PAROSTEAL OSTEOSARCOMA
JUXTACORTICAL MYOSITIS OSSIFICANS
MELORHESTOSIS
OSTEOCHONDROMA
OSTEOID OSTEOMA
NOT USEFUL
1.
2.
OSTEOBLASTOMA
INTRAOSSEOUS ABSCESS(BRODIE
ABSCESS)
STRESS FRACTURE
3.
OSTEOBLASTOMA
NOT USEFUL
1.
2.
3.
OSTEOID OSTEOMA
ANEURYSMAL BONE CYST
OSTEOBLASTOMA LIKE
OSTEOSARCOMA
OSTEOSARCOMA
Not specific, but different
markers are:
CD99
VIMENTIN
S-100
OSTEONECTIN
OSTEOCALCIN
1.
2.
3.
OSTEOBLASTOMA
CHONDROSARCOMA
DEDIFFERENTIATED
CHONDROSARCOMA
MYOSITIS OSSIFICANS
GIANT CELL TUMOUR
EWING’S SARCOMA
ANEURYSML BONE CYST
4.
5.
6.
7.
35
Cartilaginous tumors
ENCHONDROMA
OSTEOCHONDROMA
benign
CHONDROBLASTOMA
CHONDROMYXOID FIBROMA
CHONDROSARCOMA
malignant
36
tumour
Age and sex
site
symptoms
radiology
enchondroma
Wide range
(5 to 80 yrs)
M=F
Small bones of
hand and feet
Asymptomatic,
incidental
finding
Well defined,
radiolucent to
variable
calcification
osteochondroma
10-20 yrs age;
M>F
Metaphysis of
long bones
Asymptomatic,
incidental
Exophytic
osteocartilaginou
s lesion,
sessile/pedunclat
ed; cartilage cap
on MRI
chondroblastoma 10-25 yrs;
M>F
Chondromyxoid
fibroma
2nd -3rd
decade; M>F
Epiphysis of
Localised pain
long bones,
immature bone
Well defined,
multiloculated,
lytic lesion
Metaphysis of
pain
long
bones,Proximal
tibia, distal femur
Well defined,
with
surrounding
reactive bone
37
a)Enchondroma
Gross- <5cm in size, well defined margins
- gritty, yellow( calcification) or red( ossification)
foci
M/E- lobules of hyaline cartilage separated by
normal cancellous bone or marrow
- Endochondral calcification seen
- Mostly hypocellular with pyknotic nuclei of
chondrocytes
Genetics- heterozygous IDH1/IDH2 somatic
mutations, aberration in chr 6-
38
b)Osteochondroma
Gross- tumour has thin layer of fibrous tissue
- cartilage cap with variable thickness
M/E- cap has hyaline cartilage
- Stalk has cortical-cancellous
- endochondral calcification at junction of cap and
stalk.
Genetics- mutation in EXT1(8q22-24.1) or
EXT2(11p11-12) gene
39
Variants
of
osteochondroma
1)Multiple hereditary exostosis- multiple
osteochondromas with modeling defects at ends of
bones
2) Subungual exostosis(dupuytren exostosis)osteochondroma like lesion involving distal phalanx.
Genetics- t(X;6)
3)Bizarre parosteal osteochondromatous proliferation(Nora lesion)- involves surface of small bones of hand
and feet.
40
ENCHONDROMA
OSTEOCHONDROMA
BONE
ENCHONDRAL
OSSIFICATION
FIBROUS PERICHONDRIUM
CARTILAGE CAP
The well circumscribed nodules encased
by a thin rim of reactive bone.
Portions of the neoplastic cartilage have
undergone ENCHONDRAL
OSSIFICATION & remain in the
centers of some trabeculae.
CARTILAGE CAP undergoing
endochondral ossification with orderly
arrangement of chondrocytes.
CANCELLOUS BONE seen beneath the
cartilage cap.
Intertrabecular spaces filled by fat and
hematopoietic marrow.
41
c)Chondroblastoma
Gross-pinkish-tan with ares of haemorrhage,
calcification or cystic change.
M/E- highly cellular
- Sheets of chondroblasts having well defined
cytoplasm, round to ovoid nuclei with longitudinal
groove and inconspicuous nucleoli.
- Osteoclastic type giant cell.
- Fine network of pericellular “chicken wire”
calcification.
Immunophenotype- vimentin, S100, SOX9,cytokeratin
8,18,19 and p63
Genetics- mutations in H3F3B gene
42
Chondroblastoma displaying all three key
histologic elements:
1.Numerous small chondroblasts
2. Rare osteoclast-type giant cells, and
3. Ill defined matrix material.
Histologic hallmark of
chondroblastoma:
“CHICKEN WIRE” type of
calcification pattern.
43
d)Chondromyxoid fibroma
Gross- solid, yellowish-white or tan, well defined
margins, replacing bone and thinned cortex.
M/E- lobular pattern with stellate or spindle shaped
cells in myxochondroid background
- Lobules have hypocellular centres with hypercellular
periphery
Immunophenotype- S100, SOX9. negative for keratin
Genetics- rearrangement of 6q13 and 6q25
44
Lobulated architecture with foci of myxoid
material separated by incomplete fibrous
septae as well as rare multinucleate giant
cells.
Intramedullary margin of a CMF shows a well
demarcated border with the adjacent marrow
fat .The tumor has a lobular architecture and
varies in the degree of cellularity.
45
e)Chondrosarcoma
 3rd m.c primary malignancy of bone
 Age- older group (>50 yrs)
 Sex- M>F
 Site- bones from enchondral ossification,
(pelvis;ileum> proximal femur and humerus)
 Clinical- local swelling, pain,
 Radiology- radiolucent with variable mineralization,
cortical erosion seen
 Depending on location chondrosarcoma is further
divided into-central, peripheral, periosteal
46
Gross- c/s is translucent, lobular, blue-grey or white
areas of hyaline cartilage
M/E- production of irregulaer lobules of cartilaginous
matrix, absent direct bone formation
Chondrosarcomas are graded as I,II,III
grade
Nuclear size
hyperchromasia
cellularity
mitoses
I
Plump,Uniform
size
+
moderate
absent
II
Nuclear atypia
+
hypercellular
+
III
Nuclear
pleomophism
more than GdII
+
More than gdII
++
47
Cytology- low grade(grade1,2)- predominantly tissue
fragments
high grade(grade3)- predominantly single cells
- abundant eosinophilic, vacoulated cytoplasm
- chondromyxoid material
48
CHONDROSARCOMA VARIANTS
CLEAR CELL
CHONDROSARCOMA
DEDIFFERENTIATED
CHONDROSARCOMA
MESENCHYMAL
CHONDROSARCOMA
DEFINITION
Low grade malignant
neoplasm of cartilage with
characteristic large cells and
clear cells.
Malignant tumor of cartilage
with second, high grade, non
cartilaginous component.
High grade malignant
biphasic neoplasm of
benign cartilage and
primitive small round blue
cells.
MICROSCOPIC
APPEARANCES
Large clear cells with
2 main components:
prominent cytoplasmic
• Central area of
borders, round to oval nuclei
conventional
with vesicular chromatin,
chondrosarcoma(grade 1)
prominent nucleoli
• High grade component of
Matrix include woven bone
osteosarcoma,
and hyaline cartilage.
fibrosarcoma, MFH
Osteoclast like giant cells
also seen.
Biphasic population of
cells:
• Well differentiated
hyaline cartilage.
• Small round to oval to
spindle cells with scant
cytoplasm
DIFFERENTIAL
DIAGNOSIS
1.
1.
2.
IMMUNOPHE
NOTYPE
Chondroblastic
osteosarcoma
Osteoblastoma
S100, type II and type X
collagen positive
1.
2.
3.
4.
Chondroblastic
osteosarcoma
Chondrosarcoma
MFH
Fibrosarcoma
Weak IDH 1/2 positive, TP53
over expression , HRAS
mutation
2.
3.
Chondroblastic
osteosarcoma
Ewing’s sarcoma
Dedifferentiated
chondrosarcoma
SOX9, CD99 positive
49
Clear cell
dedifferentiated
50
TUMORS
ANCILLARY TESTS
ENCHONDROMA
VIMENTIN
S100
IDH1/IDH2 mutations
OSTEOCHONDROM
A
S100
Inactivating mutations of 1.
EXT1 and EXT2 genes on 2.
3.
Ch-8q24 and 11p11-12
MUTATIONS
CHONDROBLASTOM S100,SOX9, RANKL,
A
H3F3 K36M protein
Mutation in chromatin
histone gene,H3F3A
CHONDROMYXOID
FIBROMA
SOX9
S100
CHORDOMA
CYTOKERATIN 8, 18,19
EMA
Loss of INI 1
BRACHYURY, S100
Clonal rearrangement of
ch-6 involving bands q13
and q25.
Involvement of GRM1
gene
CHONDROSARCOMA S100
IDH1 and IDH2
mutations
DIFFERENTIAL
DIAGNOSIS
1.
2.
Low grade chondrosarcomas
Chondroblastic osteosarcoma
Chondrosarcoma
Parosteal osteosarcoma
Bizarre parostel
osteochondromatous
proliferation
1.
2.
3.
Giant cell tumor
Aneurysmal bone cyst
Chondromyxoid fibroma
1.
2.
3.
4.
Chondroblastoma
Enchondroma
Chondroblastic osteosarcoma
Chondrosarcoma
1.
2.
3.
4.
Chondrosarcoma
Metastatic adenocarcinoma
Giant notochordal rest
Extraskeletal myxoid
chondrosarcoma
1.
2.
3.
Enchondroma
Chondromyxoid fibroma
Chondroblastic osteosarcoma
51
Ewing sarcoma
 Small round cell sarcoma of bone
 2nd m.c bone sarcoma in children
 Age- 5-20 yrs
 Site- metaphysis or diaphysis of long bones
 Symptoms- pain, fever, leukocytosis( simulates
osteomyelitis)
 Immunophenotype- CD99, anti FLI1 and ERG
antibodies
 Genetics- t(11;22)(q24;q12), t(21;22)(q22;q12).
52
Gross- tan-grey in colour, destructive borders with
invasive margins with areas of necrosis and
haemorrhage.
M/Ea)Classical Ewing- uniform, small round cells with PASpositive, scant clear or eosinophilic cytoplasm.
b) Atypical Ewing- large cells, prominent nucleoli and
irregular contour
Cytology- dissociated cells and clusters of loosely
cohesive cells
- Two cell types-large pale cells and small dark cells
-Abundant cytoplasmic glycogen
-Occasionally rosette-like structures
53
Typical ONION PEEL
multilayered appearance of
periosteal new bone formation
along the cortices. The tumor is
poorly defined and invades into
the soft tissues, forming a subtle
mass
Typical thin, linear, HAIR ON END /
SUNBURST PERIOSTEAL
REACTION around a highly
permeative, aggressive tumor. A
CODMAN TRIANGLE is present
along the medial proximal cortex
54
Cytology-mixture of cells with
Large pale staining nuclei and
Cells with small, dark nuclei;
Note cytoplasmc vacoules and clear
spaces in large cell cytoplasm
Individual cells have round nuclei with
indentation, finely dispersed chromatin,
small nucleoli, variable mitotic activity
and clear cytoplasm caused by
intracytoplasmic glycogen.
55
Ewing sarcoma arising in the medullary
cavity permeates the cortex and extends to
the surface .
Prominent HOMER WRIGHT ROSETTE
formations
56
TUMOR
IHC
GENETIC
DIFFERENTIAL
DIAGNOSIS
EWING’S
SARCOMA
•
•
•
1.
•
CD99(0-13, HBA-74)
FLI-1, ERG antibodies
sensitive not specific
CD3,20,34,45 and
TDT negative
•
•
LYMPHOMA
•
•
•
Reciprocal
translocation
between Ch11 &22
and between 21 &22
Translocations of
Ch 7 & 22, 17 & 22, 2
& 22
Inversion of Ch22
DLBCL:CD45 &
CD20, CD79a, PAX5+
ALCL:CD30+, EMA,
CD3, CD4, ALK1 +
lymphoblastic
lymphoma:CD99+,
TdT, PAX5, CD34,
CD79a
S100(cartilage
MESENCHYMAL
CHONDROSARCO component)
CD99(small cells)
MA
SOX9, osteocalcin +
Translocation not seen
2.
3.
4.
5.
6.
Lymphoblastic
Lymphoma
Osteomyelitis
Metastatic neuroblastoma
Mesenchymal
chondrosarcoma
Small cell osteosarcoma
Embryonal
rhabdomyosarcoma
1.
2.
3.
4.
Ewings sarcoma
Metastatic carcinoma
Myeloma
Sarcoma in tumours with
extensive fibrosis
1.
Chondroblastic
osteosarcoma
Ewing sarcoma
Dedifferentiated
chondrosarcoma
2.
3.
57
GIANT CELL
RICH
TUMOURS
GIANT CELL RICH
LESION OF SMALL
BONE
GIANT CELL TUMOUR
OF BONE
58
Giant cell tumour
 age- >20 yrs, F>M
 Site- epiphysis and metaphysis of long bones
 Symptoms- pain, swelling
 Radiology- well defined, expansile, eccentric ,
osteolytic lesion
 Immunophenotype- vitronectin receptor(CD51), weak
positivity for CD45,CD33, CD 68
 Genetics- IDH2-R172S mutation, H3F3A gene
mutation
59
Gross- c/s solid or friable, variegated red-brown and yellow
appearence; hemorrhage and necrosis; thin cortex with
reactive bone
M/E- 2 main component-Stromal cells- mononuclear, round to oval to spindle shaped
-Giant cells- large number of osteoclast like giant cells (>20
nuclei)uniformly scattered in stromal cells
- Secondary changes- hemorrhage, necrosis, fibrohistiocytic
change, aneurysmal bone cyst, hemosiderin deposition
Cytology- cellular smear,
-dual population of osteoclast giant cells and mononuclear
spindle cells,
-giant cells attached to periphery of cluster of spindle cells
60
The tumor is radiolucent
and destroys the lateral
cortex.
Cytology- showing cluster of
spindle cells with giant cell at
periphery
61
GCT of bone has destroyed the cortex and
displaced the periosteum, which has
produced a thin shell of reactive woven bone
rimmed by osteoblasts .
GCT is composed of many large
multinucleated osteoclast-type giant cells.
The giant cells contain numerous nuclei that
are similar in appearance to the nuclei in the
neoplastic mononuclear cells.
62
TUMORS
IHC
S100, CD1a
LANGERHANS
Langerin+
CELL
HISTIOCYTOSIS CD68+
Negative
CD45,AE1/3, CD15
and CD30
GIANT CELL
LESION OF
BONE
P63+
GIANT CELL
TUMOR OF
BONE
RANK
P63
GENETIC
STUDIES
Recurrent abn
of
chromosomal
loci 9p and 22q
DIFFERENTIAL
DIAGNOSIS
1.
2.
3.
4.
5.
Osteomyelitis
Granulomatous inflammation
HL
NHL
Fibrohistiocytic lesions of bone
1.
USP6
rearrangement 2.
Giant cell tumor of bone
Aneurysmal bone cyst
Nonossifying fibroma
Ossifying fibroma
1.
Mutation in
H3F3A histone 2.
3.
gene
Aneurysmal bone cyst
Benign fibrous histiocytoma
Chondroblastoma
Giant cell rich osteosarcoma
3.
4.
4.
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Notochordal tumours-CHORDOMA
• Primary low grade malignant tumor of bone showing
notochordal differentiation
• Site: Axial skeleton, base of skull, sacrococcyx
• Gross- expansile, lobulated structure, c/s is slate-grey,
gelatinous matrix
• M/E- a) chordoma,NOS- large cells with clear to
eosinophilic cytoplasm, separated by fibrous sepate
into lobules.
b) chondroid chordoma- Tumor with areas of
conventional chordoma and regions resembling lowgrade, hyaline-type chondrosarcoma
c) Dedifferentiated chordoma- biphasic tumour with
features of chordoma, NOS and high grade
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undifferentiated spindle cell tumour
TUMOR
CELLS
lobular growth pattern separated by fibrous
septa. The stroma is usually prominent,
basophilic, and myxoid in appearance and
contains abundant glycosaminoglycans. The
tumor cells are arranged in cords and
aggregates, variable in size.
Classic chordoma cells are large,
polyhedral, contain abundant
eosinophilic cytoplasm , and have oval to
round nuclei with fine chromatin.
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NUCLEI WITH
PROMINENT
NUCLEOLI
VACUOLES
HYALINE
CARTILAGE
TUMOR CELLS
Characteristic of chordoma is the
PHYSALIPHOROUS CELL.The cell
contains intracytoplasmic, sharp, clear
vacuoles , which cause it to have a bubbly
appearance . The cell nuclei may contain
prominent nucleoli.
The tumor is composed of conventional
chordoma with areas that closely
resemble neoplastic hyaline cartilage. In
the chondroid regions, the cells are
distributed singly and reside in lacunar
spaces
66
ANEURYSMAL BONE CYST
CYSTIC
LESIONS
SIMPLE BONE CYST
FIBROUS DYSPLASIA
67
ANEURYSMAL BONE CYST
 Age and sex- 10-20 yrs; F>M
 Site- vertebrae and flat bones
 Radiology- radiolucent lesion, thin cortex, covered by thin shell of
reactive bone
 Gross- hemorrhagic mass covered by thin shell of reactive bone
 M/E- large blood filled spaces, separated by cellular septa containing
inflammatory cells, fibrovascular tisssue, giant cells, foci of osteoid and
bone
D/D-Giant cell tumour
 Simple bone cyst
 hemangioma
 Telangiectatic Osteosarcoma
Genetics- USP6 gene on chr 17
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ABC shows a cellular neoplasm with
multiple bloodfilled cystic spaces. The
tumor is arising in the medullary cavity of
the bone and scallops the inner surface of
the cortex. Note the solid portion of the
tumor
The wall of an ABC displays reactive woven bone
that is blue-purple in color (so called BLUE
BONE). The bone has osteoblastic rimming and
the wall contains bland, spindle-shaped cells and
scattered osteoclast-type giant cells.
69
SIMPLE BONE CYST / UNICAMERAL BONE CYST
Benign, intraosseous, fluid-filled, fibrous walled cyst.
FIBROBLASTS
FIBROBLASTS
CEMENTUM
The cyst wall is composed of spindled fibroblasts and
collagen. Note that fibroblasts line the surface st of
the cyst wall, mimicking a true epithelial cyst lining.
The underlying endosteal surface of the cortex has an
undulating contour.
The wall of a UBC is distorted by abundant intramural
fibrin. Fibrin is commonly seen in the walls of UBC
and can histologically mimic cementum and neoplastic
bone. The luminal portion is lined by a thin layer of
fibroblasts
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Fibrous dysplsia
 Benign, fibro-osseous lesion
 Age- children and adults
 Sex- M=F
 Site- craniofacial and femur
 Gross- bone is expanded, tan-grey in colour, firm to
gritty in consistency
 M/E- a)Fibrous component- bland, fibroblastic cells
b)Osseous component- irregular, curvilinear,
trabeculae of woven bone
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Bland fibrous background with curvilinear
fragments of trabecular bone, no
osteoblastic rimming
72
CYSTIC LESIONS
IHC/ genetic
studies
SIMPLE BONE CYST
DIFFERENTIAL
DIAGNOSIS
1. ABC
2. Intraosseous
ganglion
ANEURYSMAL
BONE CYST
• CDH11-USP6
fusion genes
+(detected by
FISH)
• Spindle
fibroblasts: SMA+
• Osteoclast: CD68+
FIBROUS
DYSPLASIA
Missense mutation
in GNAS gene(20q13)
1. Telangiectatic
osteosarcoma
2. Giant cell tumor
3. Chondroblastoma
4. Osteoblastoma
5. Simple bone cyst
6. Giant cell
reparative
granuloma
73
Thank you
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