Primary Bone tumor are less common

1. BONE TUMORS
Dr. Manoj Prajapati

2. Parts of bones
1. Epiphysis : ends of bone
2. Diaphysis : shaft
3. Metaphysis : epiphysial end of diaphysis
Macroscopically the architecture of bone may
be
1. Compact
2. cancellous/spongy/trabeculae
NORMAL BONE

3. On longitudinal
section the bone is
composed of :
1. Periosteum
2. Cortex
3. Endosteum
4. Medullary cavity

4. Introduction
• Primary bone tumors are rare;
• Non-neoplastic conditions, metastatic disease, and
lymphohematologic malignancies, which may simulate
primary bone tumors, by far outnumber genuine bone tumors.

5. Predominant tissue Benign Malignant
Bone forming Osteoma
Osteoid osteoma and
osteoblastoma
Osteosarcoma
-central
-peripheral
-parosteal
Cartilage forming Chondroma
Osteochondroma
Chondroblastoma
Chondromyxoid
fibroma
Chondrosarcoma
-Juxtacortical chondrosarcoma
-Mesenchymal chondrosarcoma
-Dedifferentiated chondrosarcoma
-Clear cell chondrosarcoma
-Malignant chondroblastoma
Marrow tumors -Ewing sarcoma
-Primitive neuroectodermal tumor of
bone (PNET)
-Malignant lymphoma of bone
-Myeloma
WHO Histologic Classification of Bone Tumors

6. Osteoma
• Osteoma is
proliferation
a benign neoplasm characterized by a
of either compact or cancellous bone,
usually in an endosteal or periosteal location.
• Exclusively in the flat bones of skull and face
• May protrude inside paranasal sinus( particulary
frontal & ethmoidal) & block normal drainage of
sinus.

7. Clinical features
• Age: 40- 50 years
• males> female (2:1)
• c/p: slow growing tumor.
• Periosteal origin → circumscribed swelling → obvious asymmetry.
• Endosteal origin → expansion of the cortical plates.
• Multiple osteomas of the jaws, as well as of long bones and skull,
are a characteristic manifestation of Gardner syndrome.

8. GARDNER SYNDROME
• It is an autosomal dominant disorder.
• Mutation in APC gene
• characterized by the triad of colonic polyposis, multiple
osteomas and mesenchymal tumors of the skin and soft tissues
including epidermal inclusion cyst, lipoma, fibroma, and
fibromatosis

9. Histologic Features.
• Composed of extremely dense, mature lamellar bone.
• Bone formed appears normal
• Well circumscribed.
• Myxomatous tissue also may be intermingled on rare
occasions.

11. Compact and trabecular bone is present beneath intact mucosa at the left of the field.
B, Compact cortical-type bone of the osteoma shown in A contains haversiansystems

12. Treatment and Prognosis
• Symptomatic lesions→ local
excision.
• No recurrence after surgical removal.

13. Osteoid osteoma
• Benign tumor of bone.
Clinical Features.
• Age:10-30 years
• Sex: males:female - 2:1.
• Site: Frequently in the femur or in the tibia; may also be
seen in humerus, bones of hand and feet , vertebrae and
fibula.

14. .
• Most of them are centred in cortex (85%)
• Chief symptoms → intense pain → sharply localized, worse at
night , classically, relieved by NSAIDs
• Unaccompanied by clinical or laboratory evidence of infection

15. • Radiographically tumor
contains radiolucent central
nidus that is seldom larger
than 1.5 cm and that may or
may not contain a dense
centre.
• Peripheral sclerotic reaction
may be seen in cortical
tumors.

16. Pathologic Features
• In its active growth phase
• Grossly appears as a discrete, round to
oval lesion marked by a cherry-red or
reddish-brown color. Friable ,easily
distinguished from the adjacent bone.
• In its mature phase → more
calcification and bone production, the
lesion is hard and gritty and blends with
the bone around it.

17. Histologic Features
• Characteristic and consists of a central nidus , which is sharply
delineated composed of compact osteoid tissue, varying in degree
of calcification and woven bone lined by plump osteoblasts
• growing within highly vascularized connective tissue.
• Osteoclasts and foci of bone resorption are also usually evident.

18. A, Nidus of osteoid osteoma abuts thickened mature bone. B, Osteoid trabeculae, some
partially calcified, within the nidus of an osteoid osteoma. The trabeculae are rimmed with
plump osteoblasts with occasional osteoclasts. The stroma is hemorrhagic.

19. • May be due to presence of entrapped and proliferating nerves
within and around the nidus.
• ↑Levels of prostaglandin E2 produced by osteoblasts in the
nidus; this is presumably the cause of pain and vasodilatation.
• Pain is completely eliminated by removal of nidus.
Causes of pain in osteoid osteoma

21. Treatment
• NSAIDS- Aspirin relieves the pain
• Surgical curettage
• Lasers

22. Osteoblastoma
• Osteoblastoma accounts →1% of primary bone tumors.
• It is typically a slow-growing, benign bone tumor.
• Osteoblastoma frequently lacks the characteristic pain and the
halo of sclerotic bone associated with osteoid osteoma.

23. Clinical Features
• Age: in young persons, 10-30 years.
• Sex: Males>Females.
• C/P: characterized clinically by pain and swelling.
pain → more generalized and less likely relieved by salicylates.
• Most common site → vertebral column. Other sites include
tibia, femur , humerus , pelvis and ribs.
• Occurs mostly in medullary cavity.

24. • Well defined radiolucent lesions
with haphazardly distributed foci
of mineralization.
• Size is often > 2cm
• Perilesional reactive bone is
typically less pronounced.

25. Pathologic Features.
On gross examination,
• Well delineated.
• Hemorrhagic
• Gritty or granular consistency with
cystic regions.

26. Histologic Features
 Sharply circumscribed
 Anastomosing trabeculae of woven bone lined by actively
proliferating osteoblasts
 The moderate numbers of multinucleated giant cells
scattered throughout the tissue
 Loose fibrovascular stroma

27. • In the less mature lesion → abundance of connective tissue
stroma in which osteoclast-type giant cells and small foci of
osteoid are present, some in a lacelike pattern.
• With maturation → progressive mineralization of the osteoid
with conversion to trabeculae of coarse woven bone, rimmed by
plump osteoblasts. The trabeculae may fuse to form an
anastomosing, netlike pattern.
• The osteoblasts usually lack any significant atypia, having
round to oval regular nuclei, often with prominent nucleoli.
Mitotic activity is infrequent.

28. A, Nidus of osteoblastoma shows active production of osteoid trabeculae, some in the early stage
of bone formation. The trabeculae are lined with enlarged osteoblasts with occasional osteoclasts.
Numerous dilated capillaries are present in the stroma. B, Large epithelioid osteoblasts, in
osteoblastoma, have abundant cytoplasm and large nuclei containing prominent nucleoli.
Formation of lacelike osteoid is seen.

29. Aggressive Osteoblastoma
It is primarily defined by epithelioid osteoblasts,
cells with abundant eosinophilic cytoplasm twice
the size of conventional osteoblasts. These cells
are frequently arranged in sheets with little or no
intervening osteoid
Cytologically, the neoplastic osteoblasts have
abundant basophilic, finely granular cytoplasm
with a perinuclear holo of less dense cytoplasm
and an eccentric vesicular nucleus with a solitary
prominent nucleolus

30. Differential Diagnosis
• Osteoid osteoma
• Aneurysmal bone cyst
• Osteoblastoma like Osteosarcoma

31. Treatment and Prognosis:
• Conservative surgical excision
• Recurrence is rare.

32. OSTEOSARCOMA / OSTEOGENIC SARCOMA
• Osteosarcoma is the third most common
adolescence, occurring less frequently
cancer in
than only
lymphomas and brain tumors.
• Most common primary malignant tumour of bone
• It is a malignant neoplasm in which the neoplastic cells
produce bone.

33. Etiology
• Radiation exposure : 2% of osteosarcomas.
• Paget disease
• pre-existing benign bone disorders –
bone infarct, fibrous dysplasia, osteogenesis
imperfecta
• Chemotherapy
• Foreign bodies

34. • Environmental factors:
 Ultraviolet and ionising radiation
 Viral origin: simian virus 40 (SV40)
• Transcription Factors
 Excess MDM2 amplification, Hypermethylation of P14/ARF
 Overexpression of Myc & PRIM1 gene
• Growth Factor
 Dysregulated expression of growth factors such as TGF, IGF, and
CTGF leads to the accelerated proliferation of cells.

35. • Genetic predisposition
Alterations in genetic pathways including Rb, p53, SAS (sarcoma
amplified sequence)
Protein expression of the defective/amplified genes results in loss of
control of cell proliferation and differentiation
• Syndromes – Li-Fraumeni syndrome
- Rothmund-Thompson syndrome

36. Clinical features
• Sex- M>F (3:2)
• Age – Bimodal distribution ;
10 to 25 years of age ; 2nd peak seen after 40 years
• Site - metaphysial growth plates of extremities of long bones
distal femur>proximal tibia>proximal humerus>skull or jaw
> pelvis
• Painful, progressively increasing mass
• Sudden fracture of bone is first symptom

37. Radiographically – large
destructive , mixed lytic and
blastic mass with infiltrative
margins
Codman triangle- triangular
shell of reactive bone
CODMAN TRIANGLE

38. Histological subtypes of osteosarcoma
 Osteoblastic (50%)
 Chondroblastic (25%)
 Fibroblastic (25%)
Less common subtypes :
 Osteoblastoma-like
 Chondroblastoma-like
 Giant cell rich
 Epitheloid
 Clear cell

39. Gross pathology
• Osteoblastic - white-tan, yellow in color, bony hard to firm
in consistency
• Chondroblastic - translucent lobules
• Fibroblastic - tan colored with soft or firm in consistency
 Contain areas of hemorrhage and cystic degenration
 Surrounding cortex frequently destroyed producing soft
tissue mass,
 Spreads extensively in medullary canal, infiltrating and
replacing the marrow.

40. • Periosteal reaction in
form of codman
triangle or sunburst
appearance can be
seen grossly
• Infrequently penetrate
epiphyseal plate and
enter the joint
• Distant metastasis to
lungs, other bones,
pleura through blood

41. Histological features
• Presence of osteoid formation by malignant osteoblasts
• Stromal cells are spindle shaped and atypical with
irregularly shaped nuclei
• The amount of matrix material produced in the tumor
varies considerably.
• Mitotic activity with frequent abnormal forms
• Destroy pre-existing bony trabeculae or grow around them in an
appositional fashion

42. • Osteoid produced by tumor cells is
eosinophilic, glassy, irregular border and
presence of osteoblasts
• In some ; thin , tubular , anastomosing
highly basophilic microtrabeculae
present
• Morphological variation- osteoid sparse
or dense, surrounded by bizzare cells or
acellular, or rosette like,
• tumor cells grow diffusely , nested or
pseudopapillary arrangement,
• vessels scanty or numerous, tumor cells
may be spindle or oval or round and may
be multinucleate. Cartilage may be
immature, mineralized or highly myxoid.

43. OSTEOBLASTIC OSTEOSARCOMA CHONDROBLASTIC OSTEOSARCOMA

44. Lacelike streamers of pink osteoid
produced by malignant stromal cells
(osteoblasts).
Area in a conventional
osteosarcoma shows a combination
of osteoid, malignant cartilage, and
spindle cell fibrous zones

45. Other Variants :
Telangiectatic osteosarcoma- large cavernous, dilated vascular
channels, Aggressive course, detected by presence of numerous
blood filled spaces separated by septa containing highly pleomorphic
mononuclear and multinucleated giant cells accompanied by
abundant mitotic activity.
Small cell osteosarcoma- small , uniform , round or spindeloid cells
, look like ewings but osteogenesis by the tumour cell is
distinguishing.
Low grade central osteosarcoma- very bland looking, resemble
fibrous dysplasia. GNAS1 gene mutation consistently found in
fibrous dysplasia is generally absent in low grade central
osteosarcoma.

46. Telangiectatic osteosarcoma resemble an
aneurysmal bone cyst. Blood filled cystic
spaces are separated by delicate septa.
Benign giant cells resembling osteoclasts
are seen in about 25% of osteosarcomas.

47. Small round cell osteosarcoma

48. • 1) juxtacortical osteosarcoma
(parosteal)
• Slightly older age group
• Grows very slowly
• Forms large lobulated mass
with tendency to encircle
bone
• Microscopicallly there is
disorderely pattern of well
formed bone, osteoid,
occasional cartilage and a
highly fibrous bland stroma.
• d/d-myositis ossificans(
orderly pattern of maturation)
• Prognosis very good Chromosomal study : 12q 13-15
corresponding to CDK4 & MDM2

49. 2) periostel osteosarcoma-:
Located in upper tibial shaft or femur and have presented as
small lucent lesions on the bone surface, bony spicules
arranged perpendicular to shaft
The lesions are limited to the cortex and only rarely invade
the medullary cavity. Prognosis good.
Microscopically the tumors are relatively high grade
osteosarcomas with a prominent cartilagenous component.
3) osteosarcoma of jaw-:
Patients affected are slightly older(34yrs)
Most lesions show a prominent chondroblastic component.
Prognosis good.

51. 1)presence of paget disease- highly malignant
2)specific bone involved- osteosarcoma of jaw and
distal extremities have better prognosis
Osteosarcoma of other cranial facial bones and
vertebrae have very poor prognosis.
3) multifocal osteosarcoma- almost uniformly fatal
4)osteoblasic, chondroblastic, fibroblastic types-
chondroblastic type is less responsive to
chemotherapy.
5) microscopic variants-telangiectatic osteosarcoma
has worse prognosis while well differentiated has
better prognosis.
PROGNOSTIC FACTORS

52. 6) serum elevation of ALP- have an increased metastaic rate.
7) aneuploidy- most osteosarcomas are hyperploid or
aneuploid whereas vast majority of benign bone tumours are
diploid, however periosteal and well differentiated
osteosarcomas are usually diploid.
8) heat shock protein- heat shock protein 72 correlates with
good response to neoadjuvant chemotherapy
9) RB gene expression- loss of heterozygosity of RB gene is
a poor prognostic factor.
10)HER2/neu expression-correlate with poor prognosis.
11)p-glycoprotein-a/w increased rate of systemic relapse.

53. IHC-:
• strong alkaline phosphatase activity
• Consistently express actin,vimentin,
• positive for SMA & desmin, keratin, s-100
• Osteonectin,osteocalcin & osteopontin
positivity, BMA, Bone GLA protein

54. CHONDROMA-:
 Benign tumours of hyaline cartilage most
frequently in small bones of hand and feet
particularly proximal phalanges that usually
occur in bones of enchondral origin.
 When arise within medullary cavity k/a
enchondromas and when on the surface of
bone k/a juxtacortical chondromas.
 Diagnosed in 20-50 yrs of age
 Appear as solitary metaphyseal lesions of
tubular bones of hand and feet.

55.  Radiographically , radiolucent nodule
of cartilage with central calcification
thins but doesn’t penetrate the cortex.
 u/l multiple enchondromas referred as
ollier disease
 Multiple enchondrma+ soft tissue
hemangioma= maffuci syndrome.
 Pathogenesis-:
 Heterozygous mutation in IDH1 and
IDH2 genes leads to synthesis of 2-
hydroxyglutarate which diffuses into
neighbouring cells with normal IDH
genes, thereby causing oncogenic
epigenetic changes in genetically
normal neighbours.

56. m/e-:
composed of well circumscribed
nodules of hyaline cartilage
containing cytomorphologically
benign chondrocytes, foci of
myxoid changes, calcification,
enchondral ossification.
Juxtacortical are more cellular
t/t-:
Observation and curettage
Maffuci sydrome also associated
with risk of developing ovarian
cacinoma and brain gliomas.

57. A, Chondroma. Strands of epithelium-like cells with abundant eosinophilic cytoplasm
reside in a blue-gray mucinous stroma. B, Area of chondroma with tumor cells showing
cytoplasmic vacuolation with the formation of multivacuolated physaliferous cells.

58.  OSTEOCHONDROMA-:
 Also k/a exostosis
 Most frequent benign bone tumor.
 Benign cartilage capped tumor that is attached to
underlying skeleton by bony stalk.
 Solitary lesion usuallly first diagnosed in late adolscents
and early adulthood but multiple exostosis during
childhood.
 Usually asymptomatic but may lead to deformity or
interfere with fxn of adjacent structures.

59.  Men are affected more
 Arise from metaphysis near the growth plate of
long tubular bones , especially near the knee.
 Present as slow growing masses, which c/b painful
if they impinge on a nerve or if the stalk is #.
 Average greatest dia is approx 4 cm but may reach
sizes of 10 cm or more.
 Characterstically , there is a cap of cartilage
covered by fibrous membrane, which is continuous
with the periosteum of the adjacent bone.
 Its average thickness is about 0.6 cm , rare for it to
exceed 1 cm.

60. Total bulk of lesion is made up of mature bone trabeculae
located beneath the cartilagnous cap and containing normal
bone marrow.
Pathogenesis-:
Loss of function mutations in either the EXT1 or the EXT2
gene which l/t reduce synthesis of heparan sulfate
glycosaminoglycans. Hence disruption of chondrocyte
differentiation and local skeletal development.
Clinical course-:
Stop growing at the time of growth plate closure
Symptomatic tumors are cured by simple excision

62.  CHONDROBLASTOMA-:
 Males under 20 years of age
 Quite painful
 Epiphyseal and may extend upto
metaphysis
 Distal end of femur, proximal end of
tibia, proximal end of humerus
 Radiographically , sharply delineated
lytic appearance
 m/e-:
 Small tumours of round shapes are
accompanied by scattered osteoclast l/t
erroneous diagnosis of giant cell tumour.
 Limited capacity for the production of
cartilagenous matrix

63.  Shape of the cell is usually polyhederal or spindle
limited capacity for production of cartilaginous
matrix with cell membrane thick nuclei vary in
shape from round to indented and lobulated(
resemble Langerhan cells).
 Small zones of focal calcification which range from
network of thin lines(chicken wire ) to obivous
deposits surrounded by giant cells.
 Immunohistochemical positivity for s-100 & sox-9

64. M/E of chondroblastoma small
tumor cell of round shape are
accompanied by scatterd
osteoclasts

65.  CHONDROMYXOID FIBROMA-:
 Usually occurs in long bone of a young adult
 Radiographically, sharply defined and may attain a large
size.
 Usually located in the medullary portion of the bone, but a
juxtacortical variant arising on bone surface has been
described.
 GROSS- solid and yellowish white or tan , replaces bone,
thins the cortex
 m/e- hypocellular lobules with a myxochondroid appearance
, seperated by intersecting bands of highly cellular tissue
composed of fibroblast like spindle cell and osteoclasts

66. Large pleomorphic cells may result
in erroneous diagnosis of
chondrosarcoma.
Mitotic figures are exceptional
Reactivity for s-100 protein is the
rule.
Immunoreactivity for sox9 and type
2 collagen positivity.
t/t- en bloc excision
Soft tissue extension or
implantation may occur but no
distant mets.

67.  CHONDROSARCOMA-:
 Two major categories on the basis of
microscopic criteria-:
 1) conventional chondrosarcoma
 2) chondrosarcoma variants
 Conventional chondrosarcoma-:
 b/w 30-60 years of age
 Second most common malignant matrix
producing tumour of bone.
 Further subdivided as central, peripheral and
juxtacortical.

68.  Central-
 Located in medullary cavity
 Radiographically, osteolytic lesion with splotchy calcification
 Ill defined margins, fusiform thickening & perforation of the
cortex- 3 imp diagnostic signs
 Pelvic bones, shoulder girdles and ribs are most common
locations.
 Peripheral-
 Arise de novo or from cartilagenous cap of a preexsisting
osteochondroma.
 Signs of malignancy in osteochondroma- inc growth during
adolscence, a diameter over 8 cm and cartilagenous cap that is
irregular and thicker than 3 cm.
 Radiograph- large, heavily calcified center surrounded by lesser
denser periphery with splotchy calcification

69.  Juxtacortical -:
 Involves shaft of long bones, ch by cartilagenous lobular
pattern with areas of spotty calcification and enchondral
ossification.
 well differentiated
 Moderately differentiated
 Poorly differentiated
 In well differntiated chondrosarcoma, the nuclei are
plump and hyperchromatic; there may be two or more
nuclei per cell and two or more cells per lacunae.
 Chondrosarcoma distinguished from osteosarcoma by
lack of direct bone formation by the tumor cells.

71. gross appearance of a secondary peripheral chondrosarcoma
arising from an osteochondroma of the scapula. The cartilage
cap is thick and highly irregular, and the lesion

72.  IHC-:
 S-100, ER, Sox9 positivity
 BCL2 is positive in over half of the cases whereas
it is negative in 95% of osteochondromas.
 Also show positivity for MCM6 and CXCR4
 Overexpression of TP53 is seen in high grade
tumors.
 Soft tissue implantation following biopsy is a well
known complication of chondrosarcoma.
 Recurrence often of a higher microscopic grade
than the original tumor.
 High grade chondrosarcoma metastatize early
particularly to the lungs .

74.  CHONDROSARCOMA VARIANTS
1) CLEAR CELL-
 Contains sheets of large, malignant chondrocytes that
have abundant clear cytoplasm , numerous osteoclast type
giant cells and intralesional reactive bone formation,
S100
 Radio- lytic, expansile and well marginated
2) MYXOID (CHORDOID SARCOMA)
 Can occur in bone but more common in soft tissue.
 Morphologically reminiscent of chordoma b/c rows of
cuboidal cells seperated by myxoid background.
 S-100 and vimentin positivity but negative for
keratin(chordoma positive

75. 3.DEDIFFERENTIATED
Edge of an island of well differentiated cartilage is surrounded
by highly pleomorphic sarcoma containing tumor giant cells
Antichymotrypsin, actin, desmin, myoglobin, myogenin
Anaplasia due to P53 or HRAS mutation
4. MESENCHYMAL
Composed of islands of well differentiated hyaline cartilage
s/b sheets of small round cells which can mimic ewing
sarcoma.
C/F-:
Painful, progressively enlarging masses.
Grade 1 chondrosarcoma rarely metastatize whereas 70% of
grade 3 tumors spread hematogenously, especially to lungs.

76. On low magnification, clear cell chondrosarcomas often contain large areas of
woven bone and numerous multinucleated giant cells. The defining cells are large
and contain either eosinophilic or clear cytoplasm, large nuclei, and a prominent
central

77. Microscopic features of dedifferentiated
chondrosarcoma. The low-grade chondroid
component can be seen in the medullary cavity,
and the high-grade component is present in the
soft tissue.

79.  Highly malignant small round cell tumour
 b/w 5-20 years
 2nd most common group of bone sarcomas in
children
 Predilection for occurrence in boys.
 ES includes 3 variants-
 1) classic ewing sarcoma
 2)Soft tissue ewing sarcoma
 3) PNET
Ewing sarcoma

80.  Common neuroectodermal
origin
 Common cytogenetic
translocation t(11;22)
(q24;12)
 CD 99 cosistently expressed
by cells of ES/PNET.
 Morphology -:
 Arise in medullary cavity
 Invade the cortex,
periosteum and soft tissue
 Soft, tan-white and
frequently contain area of
hmg and necrosis.
Gross
appearance
of Ewing
sarcoma.It
has typical ill
defined
quality

81.  m/e –
 Uniform, small, round cells
that are slightly larger than
lymphocytes
 Have scant cytoplasm, which
may be clear because it is rich
in glycogen.
 Homer-wright rosett indicative
of neural differentiation
 Necrosis may be prominent
 Relatively few mitotic figures
in relation to dense cellularity
of the tumour.

82.  IHC-
 Consistent positivity for vimentin
 Frequent reactivity for LMWK
 NSE, protein gene product 9.5, Leu 7(CD57),
secretogranin II, neurofilament positivity.
 Molecular genetics-
 95% of cases of ES/PNET shows reciprocal translocation
t(11;22) (q24;q12) or t(21;22) (q22;q12) which results in
fusion of the EWS with FLI 1.
 Inactivation of INK4A in upto one third of cases which
stablizes chimeric oncoprotein EWS/FLI1 and a/w worse
prognosis.

83.  Clinical feature-:
 usually arise in diaphysis of long tubular bones.
 Femur and flat pelvis bone
 Painful enlarging mass, affected site tender, warm
and swollen.
 Fever, inc ESR, anaemia and leukocytosis
 Radiographically, periosteal rxn produces layers of
reactive bones deposited in onion skin fashion

84.  t/t-:
 Chemotherapy and surgical excision with or without
irradiation.
 Prognostic factor
 1)Osseous versus extraosseous-
 ES of bone has better prognosis
 2)soft tissue extension,metastses-poor prognosis
 3)neural differentiation-poor
 4)type of gene fusion transcript- EWS-FLI1 fusion
has better prognosis.
 5) overexpression of TP53, MYC amplification,
INK4A deletion- poor prognosis.

85.  Uncommon benign but locally aggressive neoplasm
 20-40 years
 > common in women
 Epiphysis of long bone is classic location
 Lower end of femur, upper end of tibia and lower end of
radius is common location.
 Radiographically, entirely lytic , expansile lesion in
the epiphysis, usually without peripheral bone sclerosis
or periosteal reaction.
GCT( osteoclastoma)

86.  PATHOGENESIS-
 Neoplastic cells express high level of
RANKL, which promotes prolifertaion
of osteoclast precursor and their
differentiation into mature osteoclast
via RANK expressed by these cells.

87.  Gross-
 Cut surface is solid and tan or light
brown, traversed by fibrous
trabeculae, and often contains
hemorrhagic areas
 M/E
 2 main component – stromal cells
and giant cells
 Giant cells are usually large and
have over 20 or 30 nuclei , most of
them arranged towards the centre
 Neoplastic stromal cells share
features of mesenchymal cells. At
ultrastructural level resemble
fibroblast or osteoblast.

90.  Most true giant cell tumors express TP63
whereas this is true for only a small minority of
the lesions that simulate it.
 Main microscopic differences between true
giant cell tumor and so called variants in the
spatial relationship between the giant and
stromal cells.
 Former tends to be distributed regularly and
uniformly in giant cell tumor whereas in the
lesion that simulate it , foci contining numerous
clumped giant cells alternate with larger areas
completely lacking this component.

91.  Upper portion of shaft of humerus or
femur
 M>F, <20yrs
 Metaphyseal, cortex thin
 Cyst contains clear or yellow fluid lined
by smooth fibrous membrane
 M/E- well-vascularized connective
tissue, hemosiderin and cholesterol
clefts, bone surrounding cyst dense with
irregular cement line.
Solitary bone cyst

93.  10-20 years of age
 > common in females
 Mainly in vertebrae and flat bones
 Shaft of long bone
 Soft tissue location & wall of major artey
 Radiographically , eccentric expansion of the
bone, with erosion and destruction of the
cortex and a small peripheral area of periosteal
new bone formation.
Aneurysmal bone cyst

94.  Grossly – spongy haemorrhagic mass
covered by a thin shell of reactive bone,
which may extend into the soft tissue.
 M/E- large spaces filled with blood are
seen. Don’t have endothelial lining but
are rather delimited by cells with the
morphologic, ultrastructural and
immunohistochemical features of
fibroblast, myofibroblast and histiocytes.
 A row of osteoclast immediately beneath
the surface.

95. Gross appearance
of an aneurysmal
bone cyst, which
contains multiple
blood-filled cystic
structures.

96.  d/d-
 Solitary bone cyst
 Giant cell tumor
 Hemangioma
 Teangiectatic osteosarcoma
 Giant cell reparative granuloma( lesions located in jaw)
 Chondroblastoma
 Pathogenesis -:
 IGF-1 may play role in its pathogenesis
 Chromosomal translocation, USP6 (ubiquitin specific
protease gene on chromosome 17p13 can be fused with
number of partner gene- CDH1, TRAP 150, ZNF9

97.  T/T-
 En bloc resection or curettage with
bone grafting
 Lesions containing fibromyxoid areas
and immatre osteoid are more likely to
reccur.

98.  Adolescent, long tubular bones, eccentric,
sharply delimited, near epiphysis
 When loose and associated with intramedullary
components known as nonossifying or
nonosteogenic fibromas.
 Gross- Granular, brown or dark red
 M/E- cellular masses of fibrous tissue arranged
in storiform pattern, scattered osteoclasts and
collection of foamy and hemosiderin laden
macrophages
Metaphyseal fibrous
defect(nonossifying fibroma)

100.  Two forms-
 1) monostotic variety- seen in older children and young
adults, most commonly affects rib, femur and tibia.
 2) polyostotic type- u/l distribution a/w endocrine
dysfunction, precocious puberty in female individuals and
areas of cutaneous hyperpigmentation(McCune-Albright
syndrome).
 All c/b activating mutation in GNAS1 gene .
 Mutation during embryonic life likely to result in Mc-
Cune Albright while mutation in postnatal life likely to
cause monostotic disease.
Fibrous dysplasia

101.  Radiographs-fusiform, expanded mass with
thinning of the cortex.
 Grossly-ts cuts with a gritty consistency and is
grayish white, cortical bone often is thinned and
expanded.
 M/E-
 Narrow, curved and misshaped bone trabeculae,
often having a characterstic fishhook configuration,
are interspersed with fibrous tissue of variable
cellularity. The coarse fiber (woven) bone present in
this condition doesn’t transform into lamellar bone,
suggesting that fibrous dysplasia represent a
maturation defect .

102. Fibrous dysplasia

104.  Infiltration by a cell of accessory immune
system known as langerhans cell, accompanied
by admixture of eosinophils, giant cells,
neutophils, foamy cells and areas of fibrosis.
 Langerhans cells- nuclei often lobulated or
indented, sometimes with a longitudnal groove,
acidophilic cytoplasm, intracytoplasmic birbeck
granules.
 Diagnostic IHC marker-s-100 protein, CD1a
and langerin(CD 207)
Langerhans cell
histiocytosis

105.  Divided in 3 main categories on basis of type and
extent of organ involvement-
 1) solitary bone involvement
 2) multiple bone involvement
 3) multiple organ invovement
 Solitary bone invovement( eosinophilic
granuloma)-:
 Young adults mc affected
 Any bone c/b involved except hand and feet
 Mc sites are cranial vault, jaw, humerus, rib and
femur.
 Radiographically, osteolytic lesion often in
metaphyseal area of long bones, sometime a/w
periosteal bone proliferation.

106.  Radiologically c/b confused with metstaic
carcinoma or ewing sarcoma.
 After # or trauma may extend into adjacent soft
tissue.
 Extremely radiosensitive
 Long term prognosis excellent
 multiple bone involvement/ polyostotic
eosinophilic granuloma-:
 Depending on location bony infiltration may result
in proptosis, diabetes insipidus, chronic otitis
media or combination
 Hand-Schuller-Christian disease has been applied
to this variety.

107. Histologic features of Langerhans cell
histiocytosis include large, ovoid Langerhans
cells with surrounding inflammation rich in
eosinophils.

108.  Involve tibia, femur, ulna, fibula
 In shaft or metaphysis
 R/D- single or multiple lytic areas surrounded by
marked sclerosis
 GROSS- poorly defined may extend to soft tissue
 M/E- solid nests of basloid cells with palisading at
periphery
 Keratin 14 & 19 +ve, In contrast to synovial
sarcoma, chordoma and epitheloid sarcoma –ve for
CK8 & 18
ADAMANTINOMA OF
LONG BONE

110. Thankyou