Pathology of bone tumors

1. Bone tumors
Dr. Subhash Kumar Das
Resident
Department of Orthopaedics
SBH

3. Introduction
• Bone tumors are diverse in their gross and morphologic
features
• Innocuous to the rapidly fatal.
• Critical to diagnose these tumors correctly, stage them
accurately and treat them appropriately
• Affected patients should survive and maintain optimal
function of the affected body parts.
• Most bone tumors are classified according to the normal cell
or tissue type they arise from.

4. • Most frequent benign tumors - Osteochondroma
and fibrous cortical defect.
• Most common malignant tumor – Osteosarcoma
followed by chondrosarcoma and Ewing sarcoma
(excluding malignant neoplasms of marrow origin
such as myeloma, lymphoma and leukemia)

5. • Precise incidence of specific bone tumors is not
known
• Relatively infrequent
• Great diversity
• Occur at all ages / any part of body
• Certain tumors target particular age group and sites
• Diagnosis requires integration of
• Clinical history
• Radiographic appearance
• Histopathology

6. Age and location
• Most develop during the first several decades
of life and have a propensity to originate in the
long bones of the extremities.
• Location of a tumor provides important
diagnostic information.

7. Bone Tumours
Sites of Occurrence

8. Clinical presentation of Bone tumors
• Pain
• Slow-growing mass
• Sudden pathologic fracture
• Radiologic imaging studies - Important role in
diagnosing these lesions. In addition to
– Provides exact location
– Tumor extent
– Aggressiveness of the tumor

9. Classification of Bone tumors

10. Bone Tumours
Sites of Occurrence
Giant cell
tumour
Chondroblastom
a
Ewing’s
Osteosarcom
a

12. BONE-FORMING TUMORS
• Production of bone by the neoplastic cells.
• The tumor bone is usually deposited as woven
trabeculae and is variably mineralized.
• Benign – Osteoma, Osteoid Osteoma and
Osteoblastoma
• Malignant - Osteosarcoma

13. Osteoma
1. Benign, Often craniofacial in
location
2. Hamartomatous / reactive &
not true tumor.
3. Histologically dense
lamellar bone (closely
resemble normal bone).
4. Gardner Syndrome:
Autosomal Dominant
condition associated with
multiple, Osteoma,
Osteochondroma, GIT
polyps, skin tumors. Colon
Cancer may occur

14. Osteoid Osteoma
1. Osteoid osteoma are less than 2 cm in greatest dimension
and usually occur in patients in their teens and twenties. 90%
of patients are teens or in their 20’s.
2. Osteoid osteomas can arise in any bone but 50% of cases
involve the femur or tibia, affecting mainly the cortical bone
(diaphysis or metaphysis)
3. Osteoid osteomas are characteristically painful at night. The
pain is caused by excess prostaglandin E2 (due to
proliferating osteoblasts) and is relieved by aspirin.

15. Osteoid Osteoma
X-Ray: This is the central nidus of an
osteoid osteoma.
Radiographically, there is a small
round central lucent area in the
femoral cortex surrounded by
sclerotic bone.
Micro: the central nidus of an osteoid
osteoma is composed of irregular
reactive new woven bone
dispersed in a highly vascular
stroma
X-Ray & Microscopy

16. Central nidus – Actual tumor

17. Osteoblastoma
• Osteoblastoma is larger than 2 cm and
involves the spine more frequently
• The pain is dull, achy, and unresponsive to
salicylates
• Tumor usually does not induce a marked bony
reaction.

18. Osteosarcoma
• Osteosarcoma is a malignant mesenchymal tumor in
which the cancerous cells produce bone matrix.
• Most common primary malignant tumor of bone
• Occurs in all age groups but has a bimodal age
distribution
– 1st peak - 75% occur in persons younger than 20 years of
age
– 2nd peak occurs in the elderly – Predisposing conditions -
Pagets disease, bone infarcts and prior irradiation
• Men are more commonly affected than women

19. Major sites of origin of osteosarcoma
Usually arise in the metaphyseal region of the long bones of the extremities, and
almost 50% occur about the knee

20. Pathogenesis
• 70% of osteosarcomas have acquired genetic
abnormalities such as ploidy changes and
chromosomal aberrations
– RB, the retinoblastoma gene, a critical cell cycle
regulator
– p53, a gene whose product regulates DNA repair and
certain aspects of cellular metabolism. Li-Fraumeni
syndrome
• Abnormalities in INK4a, which encodes p16 (a cell
cycle regulator) and p14 (which aids and abets p53
function), also are seen in osteosarcoma

21. Morphology
• Site of origin (intramedullary, intracortical, or
surface)
• Degree of differentiation
• Multicentricity (synchronous, metachronous)
• Primary (underlying bone is unremarkable) or
secondary to preexisting disorders such as benign
tumors, Paget disease, bone infarcts, previous
irradiation
• Histologic features (osteoblastic, chondroblastic,
fibroblastic, telangiectatic, small cell, and giant
cell).

22. Classification of Osteosarcomas
Intramedullary osteosarcomas
• Conventional osteosarcoma
• Telangiectatic osteosarcoma
• Small cell osteosarcoma
• Osteosarcoma in Paget disease
• Post-irradiation osteosarcoma
Surface osteosarcomas
• Parosteal osteosarcoma
• Periosteal osteosarcoma

23. Osteosarcoma
• Typically present as painful and
progressively enlarging
masses. Sometimes a
sudden fracture of the bone is
the first symptom.
1. Classic X ray findings:
a) Codman’s triangle
(periosteal elevation)
b) Sunburst pattern
c) Bone destruction
Clinical & X-ray findings
Codman Triangle
Sunray
appearance
Sunray
appearance

24. Gross
• Big bulky tumors that are gritty, gray-white, and
often contain areas of hemorrhage and cystic
degeneration.
• Destroy the surrounding cortices and produce soft-
tissue masses. They spread extensively in the
medullary canal, infiltrating and replacing the
marrow surrounding the preexisting bone trabeculae.

25. Osteosarcoma of the upper end of the tibia. The tan-white tumor fills most of the medullary
cavity of the metaphysis and proximal diaphysis. It has infiltrated through the cortex, lifted the
periosteum, and formed soft-tissue masses on both sides of the bone.

26. Microscopy
• Tumor cells vary in size and shape and frequently
have large hyperchromatic nuclei.
• Bizarre tumor giant cells are common along with
mitoses.
• The formation of bone by the tumor cells is
characteristic.
• Neoplastic bone usually has a coarse, lace-like
architecture
• When malignant cartilage is abundant, the tumor is
called chondroblastic osteosarcoma.
• Vascular invasion and necrotic areas are present.

27. Coarse, lacelike pattern of neoplastic bone produced by osteiod deposition.
Note the mitotic figures

28. Metastasis, Treatment and Prognosis
• Highly aggressive neoplasms
• Hematogenous mode of spread
• 90% have metastases to the lungs, bones, brain and
elsewhere.
• Treated with a multimodality approach that includes
chemotherapy
• 5-year survival rate – 20%

29. CARTILAGE-FORMING TUMORS
• Characterized by the formation of hyaline or myxoid
cartilage
• Benign – Osteochondroma, Chondroma,
Chondroblastoma, Chondromyxoid fibroma
• Malignant - Chondrosarcoma

30. Osteochondroma
• Also known as an exostosis
• Benign cartilage-capped tumor that is attached to the
underlying skeleton by a bony stalk.
• Most common benign bone tumor; about 85% are
solitary
• Multiple hereditary exostosis syndrome, which is an
autosomal dominant hereditary disease. Hereditary
exostoses are caused by germline loss-of-function
mutations in either the EXT1 or EXT2 genes

31. • Solitary osteochondromas are usually first diagnosed
in late adolescence and early adulthood, but multiple
osteochondromas become apparent during
childhood.
• Men are affected three times more often than
women
• Develop only in bones of endochondral origin and
arise from the metaphysis near the growth plate of
long tubular bones, especially about the knee
• Incidental finding or presents as slow growing
masses

32. Osteochondroma
1. Hereditary (multiple) or sporadic (single)
2. Benign bone growths capped with
cartilage
3. affects children/ adolescent males; may
be asymptomatic or cause pain,
producing deformity
4. hereditary type can undergo malignant
transformation (Chondrosarcoma )
Exostosis

33. Morphology
• Sessile or mushroom shaped
• Range in size from 1 to 20 cm.
• The cap is composed of benign hyaline cartilage
varying in thickness and is covered peripherally by
perichondrium. The cartilage has the appearance of
disorganized growth plate and undergoes enchondral
ossification, with the newly made bone forming the
inner portion of the head and stalk.

35. Enchondroma
• Benign
• Single or multiple sites
• Often involves small bones of hands and
feet.
• Well demarcated, mature cartilage.
• Hereditary – multiple enchondromatosis.
Usually over one side of the body.
(Ollier’s disease).
• Maffucci's syndrome - multiple bone
chondromas and hemangiomas of soft
tissue
• Increased risk for chondrosarcoma

36. Enchondroma of the phalanx with a pathologic fracture. The radiolucent
nodules of hyaline cartilage scallop the endosteal surface.

37. Chondrosarcoma
• Production of neoplastic cartilage
• Subclassified according to site as central
(intramedullary) and peripheral (juxtacortical and
surface).
• Histologically, they include conventional (hyaline
and/or myxoid), clear cell, dedifferentiated, and
mesenchymal variants.
• Age > 40 years
• Men
• 15% of conventional chondrosarcomas arise from a
preexisting enchondroma or osteochondroma.

38. Morphology -
Gross
• Large bulky tumors are made up of nodules of
gray-white, somewhat translucent glistening
tissue

39. Microscopy
• Tumors vary in degree of cellularity, cytologic
atypia, and mitotic activity. Presence of anaplastic
chondrocytes
– Grade 1, 2 and 3

40. Metastasis and Prognosis
• Direct correlation between the grade and the
biologic behavior of the tumor
• 5-year survival rates were 90%, 81%, and 43%
for grades 1 through 3, respectively
• Spread preferentially to the lungs and skeleton
• Treatment of conventional chondrosarcoma is
wide surgical excision

41. Miscellaneous tumors of bone
• GIANT-CELLTUMOR
• EWING SARCOMA/PRIMITIVE
NEUROECTODERMAL
TUMOR
• ANEURYSMAL BONE CYST

42. Giant cell Tumour of Bone
• Known as osteoclastoma
• Common tumour – 20% of all benign
bone tumors
• Age - 20 -40 years
• Slight female preponderence
• Histogenesis – not known

43. • Epiphysis of long bones affected
• Radiolucent lesion involving end of long
bones
• Almost always solitary
• Grossly dark brown - due to
abundant vascularity
• Areas of necrosis and cystic change
present

44. Giant cell tumor

45. Magnetic resonance image of a giant-cell tumor that replaces
most of the femoral condyle and extends to the subchondral

46. Morphology
• HPE - 2 major population of cells
• Multinucleated giant cells - reactive
component
• Neoplastic component – round to spindle
shaped mononuclear cells
• Large number of osteoclast likes giant cells
with mononuclear cells.

47. Giant cell
tumor

48. • Clinical features
• Local pain – mistaken for arthritis
• Wide variety of bone disorder may
contain multinucleated giant cells
– Brown tumor
– Aneurysmal bone cyst
• Unpredictable behaviour
• Recurrence common after curettage

49. Ewing’s Sarcoma
• Most common form of bone tumour in children / adolescent
• Peak incidence 2nd decade
• Highly aggressive tumour
• Must be differentiated from other small blue cell tumours.
• Translocation involving the EWS gene on chromosome 22
and a gene encoding an ETS family transcription factor; the
most commonly involved ETS gene is FLI1

50. • Present as painful enlarging masses
• Tender, warm, and swollen.
• Plain radiograms show a destructive lytic tumor that
has permeative margins and extension into the
surrounding soft tissues.
• The characteristic periosteal reaction produces
layers of reactive bone deposited in an onion-skin
fashion.

51. Morphology
• Arise in medullary cavity
• Soft, expansive mass
• Site – femur, tibia, pelvis –
diaphysis commonly affected
• Extends beyond medullary cavity

53. • HPE
• Sheets of small round cells
• Small, fairly uniform nuclei
• Scant cytoplasm
• Cytoplasm contain glycogen (PAS stain)
• Produce reactive bone / not osteoid
• Presence of Homer-Wright rosettes
(tumor cells arranged in a circle about a
central fibrillary space) is indicative of
neural differentiation

54. Ewings tumour

55. • Immunohistochemical study
needed to distinguish from
• Neuroblastoma
• Rhabdomyosarcoma
• Lymphoma
• EWS express neural marker

56. Clinical features
• Pain and local inflammation
• Fever is common
• Biopsy needed for diagnosis
• Recent advances in treatment improved outlook
of patients
• 5 year survival rate is 75%

57. ANEURYSMAL BONE CYST
• Benign tumor of bone characterized by
multiloculated blood-filled cystic spaces that
may present as a rapidly growing expansile
tumor
• First 2 decades of life and has no sex predilection
• Metaphyses of long bones and the posterior
elements of vertebral bodies
• Most common signs and symptoms are pain and
swelling

58. Coronal computed axial tomography scan showing eccentric
aneurysmal
bone cyst of tibia

60. Aneurysmal bone cyst with blood-filled cystic space surrounded by wall
containing
proliferating fibroblasts, reactive woven bone, and osteoclast-type giant
cells.

61. Metastatic tumors to bone
• Pathways of spread
– Direct extension
– Lymphatic or hematogenous dissemination
– intraspinal seeding (via the Batson plexus of veins)
• Adults more than 75% of skeletal metastases
originate from cancers of the prostate, breast,
kidney, and lung.
• In children, metastases to bone originate from
neuroblastoma, Wilms tumor, osteosarcoma, Ewing
sarcoma, and rhabdomyosarcoma.

62. References
• Robbins and Cotran Pathological basis of disease 8th
edition
• Campbell Operative Orthopaedics 13th edition

63. Thank
You…