For medical students

1. Bone Tumours
DR. USMAN SHAMS

3. CELLS of BONE
 OSTEOPROGENITOR (“STEM”)
 OSTEOBLASTS (surface of spicule), under control of
calcitonin to take blood calcium and put it into bone.
 OSTEOCYTES (are osteoblasts which are now
completely surrounded by bone)
 OSTEOCLASTS (macrophage lineage), under control of
PTH to chew up the calcium of bone and put it into
blood

6. While not very common, bone sarcomas are lethal in 50%
of cases.
Metastases and hematopoietic tumors far outnumber
primary bone neoplasms.
Most bone neoplasms develop during the first several
decades of life and have a propensity for the long bones of
the extremities.
Bone tumors may present in a number of ways :
asymptomatic, pain, a slow-growing mass or a fracture

7. Excluding neoplasms originating from hematopoietic cells
(myeloma, lymphoma, and leukemia), osteosarcoma is the
most common primary cancer of bone, followed by
chondrosarcoma and Ewing sarcoma.
Insults that induce chronic injury and inflammation, such as
bone infarcts, chronic osteomyelitis, Paget disease,
radiation, and metal prostheses, increase the risk of bone
neoplasia.

8. PRECURSOR OF MALIGNANCY IN BONE
A) High Risk
• Ollier disease (enchondromatosis) and Maffucci syndrome
• Familial retinoblastoma syndrome
• Rothmund-Thomson syndrome (RTS)
B) Moderate Risk
• Multiple osteochondromas (osteochondromatosis)
• Polyostotic Paget disease
• Radiation osteitis
C) Low Risk
• Fibrous dysplasia/Osteofibrous dysplasia
• Bone infarct
• Chronic osteomyelitis
• Metallic and polyethylene implants
• Osteogenesis imperfecta
• Giant cell tumor
• Osteoblastoma and chondroblastoma

12. BONE FORMING
TUMORS
OSTEOMA
OSTEOID OSTEOMA
OSTEOBLASTOMA
OSTEOSARCOMA (OSTEOGENIC SARCOMA)

13. OSTEOMA
SOLITARY
MIDDLE AGE
FROM SUBPERIOSTEAL or ENDOSTEAL surfaces
SKULL, FACE, most common
Totally BENIGN
To be distinguished from REACTIVE BONE (can be
difficult)

14. Why am I not showing you HISTOLOGY?

15. OSTEOID OSTEOMA
Less than 2 cm in diameter
Teens & Twenties
APPENDICULAR skeleton … arise in CORTEX
M>>F
PAINFUL (nocturnal)
Has a NIDUS
Responds to NSAIDs like aspirin
Induces a MARKED bony reaction
Treated by radiofrequency ablation

18. OSTEOBLASTOMA
LARGER than 2 cm in diameter
AXIAL skeleton … posterior spine
No nidus
NO response to NSAIDs like aspirin
NO a MARKED bony reaction
Treated by curettage or en bloc excision

20. OSTEOSARCOMA
(OSTEOGENIC SARCOMA)
LATE TEENS
KNEES
METAPHYSES
PAINFUL!!!

21. Age:
Bimodal
Majority below 20 year
Rest of cases at more then 40 year
Location:
Metaphyses of long bones
With in medullary cavity*
*Can also arise from cortex and bone surface

22. Clinical features:
Painful enlarging mass
Fracture of bones
Radiology (X-ray):
Codman triangle
Destructive lytic and blastic mass
Malignant Osteoid

23. Gross :
Gray white tumor
Gritty cut surface (Bone)
Hemorrhage

24. Microscopic :
Neoplastic Bone which is (lace like)
is directly formed by tumor cells
Tumor cells have pleomorphic, large
hyperchromatic nuclei.
Tumor giant cells
Mitosis

26. Several subtypes of osteosarcoma are recognized and
are grouped according to:
Site of origin (intramedullary, intracortical, or surface)
Histologic grade (low, high)
Primary (underlying bone is unremarkable) or
Secondary to preexisting disorders (benign tumors,
Paget disease, bone infarcts, previous radiation)
Histologic features (osteoblastic, chondroblastic,
fibroblastic, telangiectatic, small cell, and giant cell)

27. The most common subtype is osteosarcoma that arises in the
metaphysis of long bones; is primary, solitary, intramedullary, and
poorly differentiated; and produces a predominantly bony matrix

28. CARTILAGE FORMING
TUMORS
OSTEOCHONDROMA
(EXOSTOSIS)
CHONDROMA
CHONDROBLASTOMA
CHONDROMYXOID FIBROMA
CHONDROSARCOMA

29. OSTEOCHONDROMA
(EXOSTOSIS)
Common, Cartilage AND Bone present
Often MULTIPLE as a hereditary syndrome
M>>>F
PELVIS, SCAPULAE, RIBS

31. Osteochondromas are sessile or pedunculated, and
range in size from 1 to 20 cm.
The cap is composed of benign hyaline cartilage varying
in thickness.
The cartilage undergoes enchondral ossification, with
the newly made bone forming the inner portion of the
head and stalk.
The cortex of the stalk merges with the cortex of the
host bone, so that the medullary cavity of the
osteochondroma and bone from which it arises are in
continuity.

33. CHONDROMA
Chondroma (juxtacorical/surface of bone) vs. EN-
chondroma (within medullary cavity)
20 to 50 years of age.
Typically appear as solitary metaphyseal lesions of
tubular bones of the hands and feet
MULTIPLE enchondromas = Ollier’s disease
MULTIPLE enchondromas + Hemangiomas = Maffucci
Syndrome

34. Heterozygous mutations in the IDH1 and IDH2 genes …
2 hydroxyglutarate (oncometabolite)
Usually smaller than 3 cm
Gross: gray-blue and translucent.
Microscopy: Well-circumscribed nodules of hyaline
cartilage containing cytomorphologically benign
chondrocytes.
In Ollier disease and Maffucci syndrome … more
cellular and exhibit cytologic atypia

36. CHONDROBLASTOMA
RARE, in teenagers
M>>F
KNEES, usually
Epiphyses
MUCH LESS matrix than a chondroma
PERICELLULAR calcifications

38. CHONDROMYXOID
FIBROMA
RAREST of all
TEENS, MALES
“MYXOID” concept
“ATYPIA”
Collagenous to myxoid matrix, stellate cells

40. Chondrosarcoma (CS)
Age: 40s or older
Site of origin: Axial skeleton
(pelvis, shoulder, ribs)
Clinically: Painful enlarging mass
Radiology: Osteolytic lesion with calcification.

41. SITE
Central/intramedullary
Juxtacortical
Surface
HISTOLOGY
Conventional CS
Clear cell CS
De-differentiated CS
Mesenchymal CS

42. Gross:
Nodule of gray white glistening
tissue
Spotty calcifications
Microscopy:
[Grade I to III]
*Hypercellularity
Lacuna with two or more cells
Cells with binucleation
*Pleomorphism
*Mitosis

43. Dedifferentiated chondrosarcoma:
Low grade chondrosarcoma + second high-grade component that
does not produce cartilage.
Clear cell chondrosarcoma:
Large, malignant chondrocytes that have abundant clear
cytoplasm, numerous osteoclast-type giant cells, and intralesional
reactive bone formation
Mesenchymal chondrosarcoma:
Islands of well-differentiated hyaline cartilage surrounded by
sheets of small round cells.

46. FIBROUS TUMORS
(Lesions silmulating primary
neoplasms)
FIBROUS CORTICAL DEFECT/NON-OSSIFYING FIBROMA
FIBROUS DYSPLASIA

47. FIBROUS CORTICAL
DEFECT
COMMON, usually LESS THAN 1 CM
CHILDREN >2
Undergo SPONTANEOUS RESOLUTION
IF MORE THAN 5-6 CM, they are then called
NON-OSSIFYING FIBROMA

48. FIBROUS “DYSPLASIA”
BENIGN TUMOR
THREE TYPES
◦SINGLE BONE (70%)
◦POLY-OSTOTIC (27%)
◦POLY-OSTOTIC (3%) with café-au-lait and
endocrine disorders, especially precocious
puberty

49. 1) CURVED thin spicules
2) LACK of osteoblastic “rimming”

50. Feature Fibrous dysplasia Osteofibrous dysplasia
Age Children & adults (Most <30yrs) Commonly seen in 1st
2 decades
Sex Equal sex distribution More common in males
Sites Jaw bones most common. The proximal or middle-third of the
tibia is most frequent site.
Imaging Intramedullary non-aggressive Intracortical eccentric expansile
process
Gross Tan grey & firm- to-gritty. Solid with a whitish, yellowish or
reddish color & soft or gritty texture
blending into the surrounding host
bone.
Histopath
ology
a) Thin, wavy spicules of woven
bone ("chinese characters"); b)
lack of osteoblastic rimming or
osteoclastic activity; c)
moderately cellular bland fibrous
background.
Irregular fragments of woven bone
often rimmed by lamellar layers of
bone laid down by osteoblasts. The
fibrous component consists of bland
spindle cells with collagen production
& a variable matrix (myxoid to
fibrous).

52. TUMORS of UNKNOWN
ORIGIN
EWING sarcoma/PNET (Primitive
NeuroEctodermal Tumor)
GIANT CELL TUMOR
METASTASES

53. EWING/PNET
SAME TUMOR
SMALL ROUND BLUE CELL TUMOR
NEUROENDOCRINE CELL ORIGIN
SECOND most COMMON bone malignancy in CHILDREN
LOOK LIKE LYMPHOMA

54. Age: Young 10-15years
Common sites of origin: {Bone, soft tissue}
Medullary cavity of shaft of long bones (femur), flat
bones of pelvis.
Chromosomal abnormality: EWS-FLI1 t(11;22)(q24;q12)
Symptoms: Painful enlarging mass

55. Signs: Warm, tender, swollen, Fever
Radialogically: Destructive lytic tumor
“ONION-SKIN”
(Periosteal reactive bone)

57. Periosteal reactions:
1. Ewing sarcoma,
osteosarcoma,
langerhans cell
histiocytosis,acute
osteomyelitis.
2. Osteosarcoma, seen
in Ewing sarcoma,
osteomyelitis
3. Slow, benign
processes: osteoid
osteoma + stress
fracture, osseous
pathologies
4. Rapidly progressive:
Ewing sarcoma,
osteosarcoma,
metatstatic

59. Gross: Tan-white
Soft cut surface (Necrosis & hemorrhage)
Microscopically:
Sheets
Uniform small round cells
Scanty cytoplasm with
Clear areas due to glycogen
Necrosis
Mitosis

61. Homer-Wright rosettes - central fibrillary space surrounded by tumor
cells arranged in circle

63. Osteosarcoma Chondrosarcoma Ewing’s sarcoma
Age Bi modal
(Below 20 &
above 40)
40s or older Young 10-15years
Location Long bones
metaphyses
Pelvis, shoulder, ribs Shaft of long bones
Flat bones of pelvis
Radiology Codman triangle
Lytic
Lytic lesion with
calcification
Lytic tumor
Gross Gray white
Gritty cut surface
Gray white nodules
Calcifications
Tan-white, necrosis
&
hemorrhage
Microscopic Osteoid directly
formed by
malignant cells
Pleomorphism
Hypercellular,
Lacuna with two or
more cells
Cells with
Sheets of uniform
small round cells
Homer-Wright
rosettes

64. GIANT CELL TUMOR
Adults with female predominance
Involve epiphyses and metaphyses
Lower end of femur & upper end of tibia are
common sites
The neoplastic cells express high levels of RANKL,
which promotes the proliferation of osteoclast
precursors and their differentiation into mature
osteoclasts … DENOSUMAB

65. Gross
Red-brown with cystic areas
Microscopy:
Sheets of uniform oval mono-nuclear cells and numerous
osteoclast-type giant cells with 100 or more nuclei
The nuclei of the mononuclear cells and the osteoclasts
are similar, ovoid with prominent nucleoli.

67. ANEURYSMAL BONE
CYST
(a close relative of GCT)
ABCs have large numbers of benign giant cells, and
this may lead to a mistaken diagnosis of giant cell
tumor. However,
- the background cells in ABCs are more fibrogenic
- they occur in the metaphysis of long bones in young
people.

69. METASTASES
MALE: PROSTATE
FEMALE: BREAST
RENAL, THYROID, LUNG
also seek bone early also
LYTIC?
BLASTIC?

70. Most metastases involve the axial skeleton
(vertebral column, pelvis, ribs, skull, and sternum).
In children, metastases to bone originate from
neuroblastoma, Wilms tumor, osteosarcoma,
Ewing sarcoma, and rhabdomyosarcoma.
Skeletal metastases are typically multifocal.

71. Colon cancer

75. Summary