Musculoskeletal system

1. Neoplastic bone tumors
Lec 5&6

2. CLASSIFICATION OF PRIMARY BONE TUMORS
Histological Types Benign Malignant
Hematopoietic (40%) Myeloma
Malignant lymphoma
Chondrogenic (22%) Osteochondroma
Chondroma
Chondroblastoma
Chondromyxoid fibroma
Chondrosarcoma
Dedifferentiated
chondrosarcoma
Osteogenic (19%) Osteoid osteoma,Osteoma
Osteoblastoma
Osteosarcoma
Unknown origin (10%) Giant cell tumour Ewing tumor
Giant cell tumor
Histiocytic origin
Fibrogenic
Notochordal
Vascular, Cystic, lipogenic
neurogenic
Fibrous histiocytoma
Fibroma
MFH
Fibrosarcoma

4. BONE TUMORS
• Benign lesions are more common than malignant.
• The most common benign tumour of bone is
osteochondroma.
• All bone forming tumors occur between the ages
of 10-20yrs except osteoma which occurs in
older age group (40-50ys).
• Metastatic bone tumors > Primary bone T.
• Common tumor sites giving bone metastasis are:
prostate and breast .

5. BONE TUMORS cont…..
• Malignant bone tumors, the most common are
osteosarcoma followed by chondrosarcoma, and
Ewing’s sarcoma.
• Osteosarcoma occur in adolescence and affect bone
around the knee in ½ of cases.
• Chondrosarcoma develop in the mid to late adulthood
involve the trunk, limb girdles, proximal long bones.
• Chondroblastoma and giant cell tumor occur in the
epiphysis of long bone.
• Ewing’s sarcoma arise in diaphysis.
• Diagnosis of bone tumors requires clinical history, X-
ray, gross and microscopic examination.

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

9. OSTEOMA
• Osteoma are benign lesions of bone, developmental
or reactive growths rather than true neoplasms.
• Common in head, neck, paranasal sinuses, and facial
bone.
• Osteomas are localized, usually solitary, hard
exophytic growths attached to the surface of the
bone.
• More common in males, any age, middle age.

10. Osteoma
Gross
Osteoma most
commonly present as
localized, usually
solitary, hard,
exophytic growth
attached to the
surface of bone.

11. OSTEOMA cont…..
• Histologically, are composed of a
mixture of woven and lamellar bone,
similar to normal bone, might have
bone marrow elements.
• Do not undergo malignant
transformation.
• When multiple + intestinal polyposis
+ soft tissue tumors (Gardner’s
syndrome)
DDX: Reactive bone induced by
infection, trauma, or hemangioma
simulate osteoma.

12. OSTEOID OSTEOMA AND
OSTEOBLASTOMA
• Osteoid osteomas and osteoblastomas are benign
neoplasms
• Have very similar histologic features.
• Different in size, and site of origin and symptoms.

13. OSTEOID OSTEOMA AND
OSTEOBLASTOMA
Osteoid Osteomas
• Arise in proximal femur and tibia, on the cortex.
• Second to third decades of life.
• Males > females, 2:1 ratio.
• Cause pain, severe at night, relieved by aspirin.
• Measure less than 2 cm in greatest dimension.
• Treatment with local excision.

14. OSTEOID OSTEOMA AND
OSTEOBLASTOMA
Osteoblastoma
• Are larger.
• Cause dull achy pain, not relived by aspirin.
• Occur in vertebral column,& long bone.
• Affect 20-30 y, M>F.
• Treatment local excision , may recur.

15. Osteoid osteoma & Osteoblastoma
• Radiographically:
Are well-circumscribed lesions, involve cortex.
The central area called the nidus, radiolucent
surrounded by rim of sclerotic bone in both types.
• Gross:
round oval mass of hemorrhagic gritty tan tissue.
• Microscopically:
both are well circumscribed and composed of
trabeculae woven bone surrounded by
Osteoblast. The stoma is made up of loose,
vascular connective tissue, and contains number
of giant cells.

16. This is the central nidus of an osteoid osteoma.
Radiographically, there is a small round central lucent area
variably mineralized in the metatarsal bone cortex
surrounded by sclerotic bone.

17. This is the central nidus of
an osteoid osteoma
composed of irregular
reactive new bone.
Osteoid osteomas usually
occur in the axial skeleton
(especially tibia and
femur) in bone cortex of
young males in the second
decade of life. An
osteoblastoma is just a big
osteoid osteoma in the
vertebra&rarely have well
formed nidus .

19. OSTEOSARCOMA
(OSTEOGENIC SARCOMA)
• Osteosarcomas are malignant mesenchymal
neoplasms in which the cancerous cells produce
bone matrix.
• Osteosarcoma 20% of all primary bone tumors.
• It is the most common malignant primary bone
tumor.

20. Osteosarcoma cont….
Occur:
in 10-20 years of age.
Affect:
Male > female.
Second peak in elderly who have had Pagets disease
or bone infarction.
Site
in metaphysis (60-70% around the knee, distal femur
and proximal tibia). Any bone can be involved. Flat
bone (jaws and pelvis) and long bone are involved
equally after age 25 years.

22. Osteosarcoma cont…..
Morphology:
Several subtypes are described, and grouped according to:
1.The anatomic location in the bone (intramedullary,
intracortical or surface).
2.Degree of differentiation.
3.Multicentrecity (synchronous, metachronous).
4.Primary or secondary (arising on preexisting disease such
benign tumors, Paget’s disease, infarcts…….)
5.Histological variants (osteoblastic, chrondroblastic,
fibroblastic, telangiectatic, small cell, and giant cell).

23. Osteosarcoma cont……..
• The most common type is osteosarcoma arising in the
metaphysis of long bone.
• It is solitary.
• Poorly differentiated and produce large bony matrix.

24. Osteosarcoma cont…….
Grossly:
• are large, fleshy ill-defined, in medullary cavity of
metaphyseal end of the bone
• areas of necrosis and haemorrhage.
• areas of bone and cartilage formation present.
• The tumor destroys the cortex and frequently the
T.extends inwards in marrow cavity and outwards
into soft tissues.
• Invasion of epiphyseal plate uncommon.

26. Osteosarcoma cont…..
Microscopically:
• The hallmark of osteosarcoma is the formation of
osteoid by malignant osteoblast.
• Island of bony trabeculae hugged by a rim of
malignant osteoblasts.
• Cartilage also be present.
• Neoplastic mesenchymal cells between osteoid are
spindle or pleomorphic, with frequent mitotic figures.
• Giant cells, either many or few.

28. Osteosarcoma cont….
X-ray:
Tumor is destructive breaks the cortex, elevates the
periosteum result in reactive new bone deposition.
Give the so-called Codman’s triangle on radiographs.

30. 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

31. Osteosarcoma cont……
• Clinical Features
• Early
give progressively enlarging, painful masses with
limited joint movement.
• Late
cause weight loss, anaemia and fracture of the
involved bone.
Fracture can be the presenting symptom.

32. Osteosarcoma cont…..
Spread of osteosarcomas:
• Metastasize via the bloodstream to the lung.
• 20% of pt. have pulmonary spread at diagnosis.
• Direct spread to the soft tissue.
Prognosis:
• 5 years survival rate is 5-20%.
• Improved prognosis, advanced surgical techniques,
combined with radiation and chemotherapy.

34. Assessment
-The most common primary malignant
neoplasm of bones under the age of 20 years is:
a. Osteosarcoma
b. Giant cell tumor of bone
c. Chondrosarcoma
d. Metastasis

35. Lecture 6

36. CARTILAGE FORMING TUMORS
• OSTEOCHONDROMA (EXOSTOSIS)
• CHONDROMA
• CHONDROBLASTOMA
• CHONDROSARCOMA

38. Osteochondroma
• Osteochondromas, exostoses are benign,&
common.
• Are malformation rather than neoplasm.
• Most common benign bone tumors under age 21
(10-30).
• M:F is 3:1.
• Occur as solitary lesion, sporadic can be multiple in
familial exostosis which have the risk of rare (1%)
sarcomatous transformation .
• Are outgrowth attached to the skeleton by bony
stalk & covered by cartilage cap.

39. Osteochondroma cont……
• Clinically : are asymptomatic, cause deformities.
• Site : arise from the metaphysis near the growth
plate of long tubular bones (about the knee) rare
in short tubular bone of hands and feet.
• Gross : Mushroom shaped with broad-base,
anchored to the cortex of the adjacent bone, the
outer layer of the head is composed of benign
hyaline cartilage and from 1-20 cm in size .
• Microscopically : are proliferations composed of
mature bone and cartilaginous cap. They stop
growing once the normal growth of the skeleton is
completed.

40. This is an osteochondroma cut into three sections. A bluish-
white cartilagenous cap overlies the bony cortex. These are
probably not true neoplasms, but they are a mass lesion
that extends outward from the metaphyseal region of a long
bone.

41. The microscopic appearance of an osteochondroma displays
the benign cartilagenous cap at the left and the bony cortex at
the right. This bone growth, though benign, can sometimes
cause problems of pain and irritation that leads to removal
surgically.

42. CHONDROMA
(ENCHONDROMA)
*Chrondromas are benign lesions composed of
mature hyaline cartilage.
Site: small bones of hands and feet.
Age: 20-40y, occur at any age.
Clinical: solitary or multiple, well-circumscribed.
Occur in metaphysis of tubular short bone of the
hand and feets.
if within the medullary cavity of the bone (called
enchondroma).
if on surface of the bone (called subperiosteal
chondromas).

43. CHONDROMA cont……
Ollier’s disease is multiple chondromas involving
one side of the body.
Maffucci’s syndrome is multiple chondromas
associated with benign vascular tumors (angiomas)
and brain gliomas.
Pathogenesis : Develop in enchondral bone.
arising from rests of growth plate cartilage.
X-ray : give O ring sign, unmineralized nodule
surrounded by rim of radiodense bone.

45. CHONDROMA cont……
Gross : are usually smaller than 3 cm , gray-blue
translucent with nodular configuration.
Microscopically : are composed of mature,
hypocellular benign hyaline cartilage .
Clinically : can be painful or cause pathological
fracture.
If multiple result in deformities and recur if
incompletely excised.
Prognosis : solitary are benign.
Chondrosarcomas may develop in patients with
multiple chondromas.

46. CHONDROMA

47. CHONDROBLASTOMA
 Rare benign neoplasm
 affected age is 10-20 years
 male > female.
Site : Epiphyseal region of long bone, femur,
humerous, tibia (around the knee).
less common in pelvis, ribs, skull, small bone of
feets and in vertebrae.
Gross : Round oval soft gray pink, with
calcification, hemorrhage, necrosis and cystic
changes.

48. CHONDROBLASTOMA cont…..
Micro : Uniform small round chondroblasts.
calcification (chicken wire pattern),
multinucleated giant cells,
mitosis and necrosis present.
Clinically : are painful, cause effusion in joint and
motion restriction.
Recurrence is common after excision or curettage.
Metastasis occur if the lesions fracture or after
repeated curettage.
X-ray : well-defined lucency with spotty calcification
DDX : giant cell tumor.

51. CHONDROSARCOMA
**Chondrosarcomas are malignant neoplasms.
**Second to osteosarcoma in frequency.
Incidence : Males 2x > females.
Age : older patients, with a peak incidence in the
60y
Site : Central portions of skeleton, shoulder area,
pelvis, proximal femur, and ribs, around the
knee, these tumors may occur anywhere.
*Most primary chondrosarcomas arise de novo.
*Secondary occur in patients with multiple
enchondromas or osteochondromas.

52. CHONDROSARCOMA cont…
MORPHOLOGY:
*Cells in chondrosarcomas do not form osteoid.
*Chondrosarcoma arises centrally within the
medullary cavity of the bone
*Rarely on the surface of the bone (peripheral,
subperiosteal).
Gross: large, gray-white glistening mass, with
spotty calcification;
central necrosis and cyst formation.
erodes the cortex and extend into soft
tissue.

53. A chondrosarcoma
arising in the pelvis.
Note the extensive
nodules of white to
bluish-white
cartilagenous tumor
tissue eroding and
extending outward
from the bone at the
lower right. Many of
them are slow
growing .

54. CONDROSARCOMA cont…
Histology
• Malignant cells infiltrates the marrow and surrounds
bony trabeculae.
• Well differentiated T. have little atypia.
• Poorly differentiated T. have pleomorphic cells with
many mitosis. Two or more chondroblasts in one
lacuna.
• 10% of low grade chondrosarcoma transform into
high grade sarcoma and called dedifferentiated
chondrosarcoma.

55. This high power microscopic appearance of a chondrosarcoma
demonstrates pleomorphic chondrocytes that are piled together
in a haphazard arrangement.

56. CHONDROSARCOMA cont…
Clinical Features
*Most of chondrosarcomas are indolent
(grade1&2).
*progressively enlarging mass.
*painful masses involving the central portions
of the skeleton.
*poorly differentiated T. behaves in a more
aggressive fashion (grade 3 ).
*Large chondrosarcoma (>10 cm ) are more
aggressive.
*Chondrosarcomas metastasize via blood, to
lungs and skeleton.

58. MISC. TUMORS of BONE
• EWING sarcoma
• GIANT CELL TUMOR
• METASTASES

59. EWING’S SARCOMA
 Ewing’s sarcoma is a primitive malignant small
round cell tumor of bone and soft tissues.
 Accounts for 6-10% of primary malignant bone
tumors.
 Is a common malignancy of bone in children,
second to osteosarcoma.
 It is the third most common malignant bone
tumor, exceeded only by osteosarcoma and
chondrosarcoma.

60. EWING’S SARCOMA cont…
Age: Children and adolescents.
Peak incidence younger than 20 years.
M > F more in whites.
Site of origin:
Can be skeletal or extra skeletal in the soft tissues

61. EWING’S SARCOMA cont…
Gross
Soft, tan-white expansile mass with areas of necrosis
and hemorrhage.
Site Diaphysis region in the medullary cavity of long
tubular bone as femur, tibia, and pelvis are favored sites of
origin
Extends to the cortex and periosteum & produce soft
tissue mass.
X-ray:
Destructive lytic tumor.
Give periosteal reaction with lamellae of reactive bone
deposited in an onion-skin pattern.

62. EWING’S SARCOMA cont…..
Microscopy
*Ewing’s sarcoma is composed of sheets of
primitive small round blue cells .
*Have uniform nuclei and little cytoplasm.
*The cytoplasm contains glycogen( seen with
periodic acid-Schiff (PAS) stains or by electron
microscopy ).

64. EWING’S SARCOMA cont….
CLINICAL FEATURES
*Presents with pain as local inflammation with
fever.
*The diagnosis requires biopsy.
Prognosis: is bad but recent advances in treatment,
the 5-year survival rate close to 75%.
Spread: Via blood.

65. Giant Cell Tumor of Bone
*Giant cell tumor of bone, known as
osteoclastoma.
*neoplasm that contains large numbers of
osteoclast-like giant cells admixed with
mononuclear cells.
Incidence relatively uncommon tumors and locally
aggressive, 20% of all benign tumors of the bone.

66. Giant Cell Tumor of Bone
Site:
*In adult involve the epiphyses and metaphysis
*in adolescent are confined to growth plate.
*55% around the knee, the distal femur, proximal
tibia, proximal humerus, and distal radius, sacrum,
pelvis, and small bones of hand and feets.
Age: 20 and 40, female > male.
Histogenesis
Is incompletely understood.
The giant cells are reactive ( are macrophages).
The accompanying mononuclear cells are neoplastic.

67. Giant Cell Tumor of Bone
Grossly
Are dark brown due to abundant vascularity.
Areas of necrosis, hemorrhage and cystic
change.
The cortex either thinned or eroded due to
tumor expansion.

68. Here is a giant
cell tumor of
bone. The
proximal
femur has
been
amputated and
cut in half to
reveal an
irregular dark
red-black
hemorrhagic
mass in the
epiphyseal
region. Giant
cell tumors are
lytic on

69. Giant Cell Tumor of Bone
Histologically are composed of two major cell populations:
• Large multinucleated giant cells ,resemble
osteoclasts, have 100 nuclei identical to the
mononuclear cells.
• Neoplastic component is made up of round to
spindle-shaped mononuclear cells, contains a
number of mitotic figures.
• Rare occasions malignancy may develop.
• Necrosis, hemorrhage, hemosiderin and reactive
bone formation are common.

70. GCT (Giant Cell Tumor), BONE

72. METASTASES
• Metastatic bone tumors are more common
than primary malignant bone tumors
• Common tumor sites giving bone metastasis
are: prostate and breast .
• Some metastatic deposits are osteolytic ,
others are osteoblastic and most of them
induce a mixed lytic and blastic reactions

73. Here is a closer view of bone metastases. Virtually all bone
metastases are from carcinomas. The primary sites of
carcinomas that commonly go to bone are: breast, prostate,
kidney, thyroid, lung. Renal cell carcinomas tend to be
osteolytic (they destroy the bone) whereas prostatic
adenocarcinomas tend to be osteoblastic (they initiate new
bone formation).

74. At high magnification, metastatic infiltrating ductal carcinoma of
breast is seen within bone and filling the marrow cavity. There is
reactive new bone with pale pink osteoid being laid down next to a
bony spicule at the upper left.

75. Assessment
• A 37 year old lady with a known history of
breast carcinoma presents with a fracture of
the neck of femur. The most likely cause is :
a. Trauma
b. Osteoporosis
c. Osteomyelitis
d. Pathological fracture due to metastasis