Sarcoma can originate from bone or vascular tissues. The most common type is osteosarcoma, which often affects the distal femur or proximal tibia in two peak age groups - adolescents ages 10-20 and older adults over 50. Osteosarcoma is diagnosed based on symptoms like pain and swelling, elevated alkaline phosphatase levels, and imaging findings. Treatment and prognosis depend on factors like tumor grade, location, and presence of metastases.

1. Sarcoma
Bone and vascular origin
Dr. Subas Maharjan

2. Dr. Subas Maharjan

4. )

5. • 2nd most common primary malignant tumor
of bone
• Most common primary cancer of bone in
children and adolescents

6. • Mild Pain and swelling for weeks-months
• High serum alkaline phosphatase
• Two peak age groups (rare <6y or >60y)
• 10-20 years: Most common
• Over 50 years of age
• Usually secondary to an underlying predisposing condition
• Radiation, Pagets disease, prosthetics

7. • Sites:
• Distal Femur: most common site
• Proximal Tibia: Second most common site
• Proximal Humerus: Third most common site
• Metaphysis (90%); Diaphysis (10%)

10. MRI: Osteosarcoma of Distal Femur with Skip Metastasis
to Proximal Femur
Osteosarcoma
of Distal Femur
Skip Metastasis
to Proximal
Femur/Femoral
Neck

12. Codman’s
Triangle
Ossification
in Soft Tissue
Component

14. Pink Lace-like
Osteoid
Large
Hyperchromatic
Spindle Cells with
Large Nuclei
Nuclear
Pleomorphism
Cells are Crowded
No trabeculae; the
osteoid is layed
down in between
cells

15. Commonly increase alkaline phosphate
osteocalcin,osteonectin, S100 protein, actin,
SMA
NSE, and CD99
Importantly, as it is a diagnostic pitfall, these
tumours may also express keratin and EMA

16. • Telangiectatic osteosarcoma is a variant of an intramedullary
high grade osteosarcoma.
• Accounts for 3% of osteosarcomas
• Extremely lytic on X-rays
• Very little osteoid production.
• Cystic spaces filled with blood that are separated by thin septa.
• Fluid-Fluid Levels on MRI: Cystic spaces filled with
hemorrhagic material
• ABC- like changes can sometimes lead to a misdiagnosis on X-
rays and the tumor may be misinterpreted as being a benign
ABC.

17. Codman’s
Triangle
Lesion
Permeative
Margin

19. Cystic Cavity Cystic Cavity with
Hemorrhage/Blood Clot

20. Septae
Blood Filled Cystic Cavity

21. Cystic Blood Filled Cavity Malignant Spindle Cells
Osteoid

22. Microscopic Pathology:
Telangiectatic Osteosarcoma
Malignant Spindle Cells

24. Sharp Margin
Egg Shell
Calcification
Fluid-Fluid Levels

26. Microscopic Pathology ABC
Osteoid
Benign
appearing cells
Benign
appearing cells
line up along
Osteoid

27. Low Grade Intramedullary
Osteosarcoma

28. General Information
• Low-grade fibroblastic osteoid producing lesion
arising within the medullary space of the bone
• Usually well-differentiated cells
• 1% of all
osteosarcomas

29. Clinical Presentation
• Signs: Pain in affected region for months to
years
• Age: Peak in 20s (50% of cases)
• Individual cases in 2nd decade and 50s
• Sites: Metaphysis offemur and tibia most
common

30. • Meta-epiphyseal
• Central
ossification/sclerosis
with expansile
remodeling
• Ground glass density and
internal trabeculation
(simulates fibrous
dysplasia)
• Usually no soft tissue
mass and not as
aggressive appearing
• Usually no periosteal
reaction

31. • Fibroblastic tumor
producing bone
(osteoid/immature
bone)

32. Osteoid
Production

35. • Parosteal osteosarcoma is a low grade, well
differentiated fibroblastic tumor that produces
bone/osteoid (immature woven bone)
• Outer layer ofthe periosteum.
• Slow growing and slow to metastasize.
• Most common type of
juxtacortical/surface osteosarcoma
• 5% of all types of osteosarcomas

37. Clinical Presentation
• Signs/Symptoms: Painless slowly enlarging
firm immobile mass in an extremity
• Prevalence: Female>Male 2:1
• Age: 20-40 yrs
• Sites:
• Posterior distal femur metaphysis (65%)
• Presents as a mass in popliteal fossa
• Proximal humerus (15%); Tibia (10%); Fibula (3%)

38. • X-Rays:
• Lobulated and ossified exophytic
mass (cauliflower like)
• Radiodense Centrally
• Radiolucies Peripherally
represent low grade cartilaginous
lobules, fibrous tissue or fat
• No periosteal reaction.
• String Sign: Cleft between
exophytic base and cortex at
periphery (Cleft is often only
identifiable on CT scan)

40. • Firm, exophytic bony
mass fixed to cortex by
means of a broad base
• If it has grown
through the cortex
there may be an
intramedullary
component
• May encircle bone or
invade medullary canal

43. Prognosis
• 80-90% cure rate for low grade parosteal
osteosarcomas treated with surgery alone
• Metastases more common with medullary
invasion, high grade components (grade 3) and
dedifferentiation (grade 3 tumors)

47. • <2% of all osteosarcomas
• Inner layer of the periosteum and therefore
elevates the periosteum and produces a periosteal
reaction
• Chondroblastic tumor that produces osteoid or
bone
• Diaphysis of the tibia
• Intermediate grade tumors as compared to
conventional (most common type) osteosarcomas
that are high grade.
• Better prognosis than conventional osteosarcomas.

48. • Age: 10-20 yrs
• Sites: Tibia or Femur (>85%); Humerus, Radius,
Ulna

51. Osteoid
Production
Identified in
Various Areas
of Tumor

52. Cartilaginous Cells in
Lacunae
Osteoid Production
Pink and Lace-like

53. radiologic presentation is important in the distinction
as well as the fact that in periosteal chondrosarcoma,
the cartilage is usually more lobular and well
differentiated, whereas osteoid depositionby spindle
cells is absent.
Chondro blastic vs chondrosarcoma

54. • 15-25% metastatic rate to lungs

57. • Sites: Femur (45%); Humerus (26%); Fibula
(10%)
• Diaphysis or metadiaphysis of the bone
most common

58. Ossification
in Tumor Subtle Cortical
Erosion

59. Necrotic Cystic Cavity
Areas of
Cortical
Erosion
Fleshy Area
Tumor is
arising from
Surface of
Distal Tibia

60. • The lack of medullary
involvement distinguishes
this tumor from a
conventional
intramedullary
osteosarcoma
• It consists of high grade,
anaplastic, pleomorphic
spindle cells producing
osteoid, and immature
bone that is deposited in a
lace-like manner
Osteoid
Production
High Grade
Anaplastic
Spindle Cells with
Large
Hyperchromatic
Nuclei

61. Osteoblastoma vs. Osteosarcoma

62. Callus

63. IRRELEVANT OR GOOD PROGNOSIS BAD PROGNOSIS
•Age, sex, and pregnancy.
•Osteoblastic, chondroblastic, and
fibroblastic types
•Microscopic grading
•Parosteal and periosteal
osteosarcoma
•well-differentiated
•intramedullary osteosarcoma
•Postchemotherapy tumor necrosis
•Heat shock protein
•Presence of Paget
disease
•Specific bone involved
•Telangiectatic
osteosarcoma and small
cell
•Serum elevation of
alkaline phosphatase
•HER2/neu expression
•P-glycoprotein

64. Chondrosarcoma
Primary (90%)
Arising de novo in
normal bone
Secondary (10%)
Arising from pre
existing conditions of
bone
Enchondroma
Osteochondroma
Ollier’s, Maffucci’s
Fibrous Dysplasia
Paget’s
Chondroblastoma
Radiation induced
Central Intramedullary (99%)
Conventional (85-90%)
Grade 1 (30%)
Grade 2 (40%)
Grade 3 (30%)
Dedifferentiated (8%)
Clear Cell (4%)
Mesenchymal (1%)
Peripheral (1%)
Periosteal C.S

65. Conventional Chondrosarcoma Clinical Presentation
•Signs/Symptoms:
•Pain, with or without mass
•Pathological fracture is rare
•Prevalence:
•2 to 1 male predilection
•Most common bone sarcoma in adult population
•Second most common primary sarcoma of bone
•20% of all primary malignant bone sarcomas
•Age:
•Peak incidence between 50-70 years of age
•Uncommon before the age of 40
•Sites:
•Most common sites: Proximal femur, Distal femur, Proximal
Humerus, Pelvis, Scapula, Ribs
•Spine and craniofacial bones are rare sites

66. •Metaphysis or diaphysis
•Rarely, they arise in the epiphysis
•Calcifications have a distinctive
“Ring and Arc”-like pattern
•Low-grade chondrosarcomas
•Uniformly calcified
•Well-defined margins
•High-grade chondrosarcomas
•Large non-calcified areas
•Irregular, ill-defined margins
•Often extend into soft tissues

67. Bone contour in the affected area may be expanded
•Cortical thickening
•Endosteal scalloping
•New areas of lysis adjacent to
calcified areas
•Cortical destruction and soft
tissue extension in higher grade
lesions; extension into soft
tissues is definitive

68. Plain X-ray: Chondrosarcoma of Proximal Femur
Periosteal Reaction
Cortical Thickening
Deep endosteal
Erosion
Cortical
Destruction
Calcifications
Lysis next to Well
Calcified Area
Calcified Area
Permeative
Lesion

69. •Enchondroma
•Common in hand/foot
•Common in long bones
•Rare in axial skeleton
•Rare in pelvis
•Never has an associated
soft tissue component
Chondrosarcoma
•Common in axial skeleton
•Common in long bones
•Rare in hand/foot
•May or may not have an associated soft
tissue mass
•Low grade chondrosarcomas do not
often have an associated soft tissue
mass and are most difficult to
differentiate from an enchondroma
Diagnostic Dilemma Long Bone:Enchondroma
vs. Chondrosarcoma

80. Secondary Chondrosarcoma
•Secondary Chondrosarcomasarise from a pre-existing
lesion such as an osteochondroma or enchondroma
•Most arise from osteochondromas
•Scapula, ribs, pelvis and proximal femur
•Most are low grade and cured by wide excision
•Dedifferentiation possible

81. Microscopic Pathology
•Broad spectrum of microscopic appearances
that depends on Grade
•Entrapment of pre-existing trabeculaeby
chondrosarcoma is important for distinguishing
low grade chondrosarcoma from
enchondroma(The chondrosarcoma surrounds
pre-existing trabeculae)

82. Microscopic Pathology
•Three Grade System
•I, II, III
•Cellularity, myxoid change, nuclear pleomorphism,
multinucleated lacunae and mitoses increase as go
from Grade I to III

83. Conventional Chondrosarcoma
Grade I (Low Grade Chondrosarcoma)
•Similar microscopic features to
Enchondroma
•Relatively low cellularity
•Mitotic figures not typically present
•Bone Entrapment of pre-existing
trabeculaeis important
•More than occasional double nuclei

84. Entrapment of Trabeculae by Chondrosarcoma
Chondrosarcoma surrounds the trabeculae
This is a feature of malignancy

85. Microscopic Pathology: Grade I Chondrosarcoma

86. Microscopic Pathology: Grade I Chondrosarcoma
Entrapment of Pre-existing
Trabeculae of Bone

87. Microscopic Pathology: Grade I Chondrosarcoma

88. Conventional Chondrosarcoma
Grade II (Intermediate Grade Chondrosarcoma)
•Increased cellularity evenly distributed in a
cartilaginous matrix
•Plump cartilage cells with enlarged nuclei and
distinct nucleoli
•Greater nuclear pleomorphism
•Frequent binucleated, trinucleatedcells
•Occasional mitotic figures

89. Microscopic Pathology: Grade II Chondrosarcoma
Hypercellular
Cells are crowded
Binucleated cells
common

90. Microscopic Pathology: Grade II Chondrosarcoma

91. Microscopic Pathology: Grade II Chondrosarcoma

92. Microscopic Pathology: Grade II
Bony Trabeculae

93. Conventional Chondrosarcoma
Grade III (High Grade Chondrosarcoma)
•Higher cellularity and greater degree of
cellular pleomorphism
•Hyaline cartilage matrix is sparse
•Cells may have stellate/spindle appearance
with myxoid chondroid matrix
•Presence of mitotic figures

94. Microscopic Pathology: Grade III Chondrosarcoma
Chondroid Area
Hypercellular

95. Microscopic Pathology: Grade III Chondrosarcoma
Mitotic Figure
Spindle/Stellate
Appearance to
Cells in Areas
Cell in Lacunae
Signet Ring
Configuration
Pleomorphism

96. General Information
•Dedifferetiatedchondrosarcomaconsists of a low grade
malignant hyaline cartilage tumor associated with a high-
grade nonchondroidspindle sarcoma. The two components
are juxtaposed with abrupt clear demarcation line
•Sarcoma is most commonly an MFH, osteosarcoma or
fibrosarcoma
•Extremely aggressive tumor with a high metastatic rate and
dismal prognosis
•50% arise from a secondary chondrosarcoma

97. Clinical Presentation
•Age:
•Most patients are older than 50
•Sites:
•Pelvis, proximal femur, proximal humerus, distal
femur, ribs

98. Low Grade Cartilaginous
Area
Heavily Calcified
Aggressive Lytic Area (Dedifferentiated
Sarcomatous Component)
Cortical Destruction
Soft Tissue Mass without Calcification

99. Microscopic Pathology
•Chondrosarcomacomponent is often grade I
(Low Grade Hyaline Type Cartilage)
•Dedifferentiated component: high grade spindle
cell sarcoma
•Sharp and distinct junction. There are no
dedifferentiated areas admixed in the middle of
the cartilaginous areas

100. Microscopic Pathology: Dedifferentiated Chondrosarcoma
Low Grade Cartilage
Component
Dedifferentiated Component

102. Dedifferentiated Chondrosarcoma: High Power View of Dedifferentiated High
Grade Pleomorphic Spindle Cell Component
Malignant Fibrous Histiocytoma with Storiform Pattern

103. General Information
•Malignant low to intermediate grade tumor
•Comprised of neoplastic chondrocytes
•Abundant, clear cytoplasm
•Little intervening matrix
•Foci of conventional chondrosarcomamay be
present
•Approximately 15% rate of metastases primarily to
the lungs

104. Clinical Presentation
•Age:
•20 years to 40 years of age
•Sites:
•Epiphyses of long bones (rarely metaphysis or diaphysis)
•Proximal femur, proximal humerus, distal femur,
proximal tibia

105. Microscopic Pathology
•Large clear cells with abundant
cytoplasm, sharp cell border
•Nuclei are more pleomorphic
than chondroblastoma(less
uniform compared to
chondroblastoma)
•Special stains-S-100-positive,
P.A.S-positive collagen ll and x
•Heavy glycogen production
accounts for the clear appearance
of the cytoplasm
•May have small deposits of
uncalcifiedor calcified osteoid

106. Giant Cells
Clear Cytoplasm

108. General Information
•High grade malignant, cartilage-forming tumor
•Noncartilaginoussmall, round, oval, or spindle shaped cells
with islands of malignant cartilage dispersed throughout
noncartilaginouscomponent of tumor
•Tumor frequently has a hemangiopericytoma-like
appearance
•Metastasizes to the lungs and lymph nodes
•May have chondroidmatrix calcification

109. Clinical Presentation
•Age:
•10 to 40
•Sites:
•Arises in bone and soft tissue (1/3 of cases arise
from soft tissue)
•Femur, ribs, spine, maxilla, mandible, and pelvis

110. Plain X-ray: Mesenchymal Chondrosarcoma of Fibula Shaft
Permeative Lesion
Indistinct Border
Cortical destruction
Soft Tissue Extension
Stippled Calcifications

111. Microscopic Pathology
•Neoplastic cells may be small, round, oval, or spindle
shaped
•Undifferentiated mesenchymal cells similar to Ewing
sarcoma
•Low grade islands of cartilage scattered throughout
the mesenchymal cells
•Usually only a small part of lesion
•Lesions are vascular and often have large,
anastomosing vessels that impart
hemangiopericytoma-like pattern
•Similar chromosomal translocation as Ewing
sarcoma t(11;22)

112. Mesenchymal
Small Round
Blue Cell
Component
Cartilaginous
Component
Microscopic Pathology: Mesenchymal Chondrosarcoma

119. • ALWAYS CHECK FOR HYPERPARATHYROIDISM
especially if the
GCT is occurring in an unusual location
• Brown tumors of
hyperparathyroidism can look similar
histologically as a GCT

122. Thin Sclerotic Rim
Lesion
Internal
Trabeculation

125. Multiple
Multinucleated
Giant Cells in a Sea
of Mononuclear
Cells

127. Giant Cell of Giant CellTumor
Mononuclear Cells in
between Giant Cells
Mitotic Figure

128. • Osseous recurrence – new bone destruction;
area of lysis adjacent to the cement
• Soft tissue recurrence – mass and may calcify
• Metastatic rate – 3%
• Lungs—most common site
• Controversy: are mets really retrospectively from a
malignant GCT; Do GCTs metastasize from surgical
procedure forcing tumor emboli into venous system?
• Malignant GCT –rare entity (more common
after radiation)

129. • normal osteoclasts, expressing the
vitronectin receptor (CD51) and a restricted
range of macrophage markers, including
CD45, CD33 and CD68, but not CD14,
CD163 or HLA-DR
The giantcells also strongly express tartrate-
resistant acid phosphatase and cathepsin K.

135. Microscopic Pathology: Ewing
Sarcoma

136. Microscopic Pathology: Ewing
Sarcoma

138. Hemorrhagic zone.
Extensive zones of necrosis in

144. Kaposi sarcoma (KS)
• Definition
• Kaposi sarcoma (KS) is a locally aggressive,
• endothelial tumour or a tumour-like lesion that
usually presents with cutaneous lesions in the form
of multiple
• patches, plaques or nodules, but may
• also involve different mucosal sites, lymph
• nodes and visceral organs.
• human herpesvirus (HHV8) infection

145. Four different clinical and epidemiological
(i) classic indolent KS, which occurs predominantly
in elderly men of Mediterranean/
East European or Ashkenazi descent;
(ii) endemic African KS, which occurs
in middle-aged adults and children in
equatorial Africa who are not infected with
HIV
(iii) iatrogenic KS
(iv) AIDS-associated the most aggressive HIV-1,

146. Clinical features
• the appearance of purplish, reddish blue or dark
brown macules, plaques and nodules that may
ulcerate.
• disease is usually indolent; lymph-node and visceral
involvement occurs only rarely.

147. Macroscopy
• The lesions in the skin (patches, plaques, nodules)
• range in size from very small to several centimetres
in diameter.
• Involvement of the mucosa, soft tissues, lymph
nodes and visceral organs presents as haemorrhagic
nodules of various sizes that may coalesce.

148. In the patch stage,
• vascular spaces are increased in number, and dissect
collagen fibres in the upper reticular dermis.
• Lining endothelial cells are flattened or more oval, with
no or little atypia.
• Pre-existing blood vessels may protrude into the lumen
of new vessels. Promontry sign
• In addition a proliferation of oval to spindle-shaped
endothelial cells surrounding pre-existing blood vessels is
noted.
• Extravasated erythrocytes and haemosiderin deposits is
seen.
• The papillary dermis is not involved in early stages.

149. Diffuse dermal angiomatosis

152. In the plaque stage
• all characteristics of the patch stage are
exaggerated, angioproliferation is extensive with
vascular
• spaces showing jagged outlines.
• erythrocytes and siderophages
• Hyaline globules

153. The nodular stage
• well-circumscribed, cellular nodules of intersecting
fascicles of spindle cells with no or little cytological atypia
and
• numerous slit-like spaces containing erythrocytes.
• Peripherally, there are ectatic blood vessels.
• Hyaline droplets are present inside and outside the
spindle cells.

156. Busy dermis surrounding adnexal structures

157. • Rare histological variants include
• anaplastic Kaposi sarcoma
characterized by an aggressive clinical course and
increased metastatic potential.
• In lymph nodes, the infiltrate may be uni or
multifocal and lymph nodes may be entirely effaced
by the tumour.

159. • pan-endothelial markers including CD31,
• CD34 and ERG,
• as well as lymphatic markers such as podoplanin (D2-
40),
• HHV8 .
• In rare negative cases, PCR

161. Angiosarcoma
Definition
Angiosarcoma is a malignant tumour that
recapitulates the morphological and functional
features of endothelium to a variable degree.

162. Epidemiology
• Angiosarcoma. Many cases in soft tissue have
predominantly epithelioid cytomorphology with
variably solid or vasoformative architecture
• Angiosarcoma of soft tissue of all ages and have a
peak incidence in the seventh decade of life.
• More cases occur in males than in females
• Angiosarcomas of deep soft tissue
in children are extremely rare

163. Etiology
• unknown in most cases
• radiation.
• A smaller subset occur adjacent to synthetic (graft)
or foreign material,
• in the vicinity of arteriovenous fistulas
• in certain syndromes (neurofibromatosis,
Maffucci syndrome) and,
• rarely, within other tumours.

164. Sites of involvement
• Angiosarcomas of soft tissue arise most commonly in
the deep muscles of the lower extremities
• followed by the retroperitoneum, and mesentery
Macroscopy
• Multinodular haemorrhagic masses often with
secondary cystic degeneration and necrosis.

165. Histopathology
• well-formed, anastomosing vessels to solid sheets of
high-grade epithelioid or spindled cells without clear
vasoformation In pool of blood
• Crack-like spaces between collagen bundles
• • Spaces lined by hyperchromatic endothelial cells
• • Nodular areas commonly epithelioid with more
pronounced atypia

169. • Solid areas lacking vasoformation are composed of high-grade
spindled and epithelioid cells with abundant amphophilic
to lightly eosinophilic cytoplasm,
• large vesicular nucleli and prominent nucleoli.
• Tumours in which these epithelioid cells predominate are
classified as “epithelioid angiosarcomas.” They are commonly
confused with carcinomas because of morphological and
immunophenotypical similarities
• This is high-grade neoplasms with brisk mitotic
• activity, coagulative necrosis and significant
• nuclear atypia.

170. marked spindling of the cells Highly pleomorphic tumor with rudimentary lumen
formation

171. • Markers of angiosarcoma:
• • Factor VIII (unreliable)
• • CD34 (clean stain, little background, not specific)
• • CD31 (very specific, but background staining
common)
• • D2-40+
• • MYC is amplified in post-radiation angiosarcoma,

175. • Intracortical osteosarcoma is an extremely rare
type of high grade osteosarcoma that arises
within and is usually confined to the cortex of
the bone
• Differential: osteoid osteoma, osteoblastoma

176. Intracortical Tumor
with Surrounding
Edema
Periosteal Reaction

177. Intracortical
Tumor
Expanded Cortex and
Periosteal Reaction
Necrosis and
Hemorrhage
Permeation
through Bone

178. • Malignant spindle cell tumor producing
osteoid
• Malignant cells have large nuclei, minimal
cytoplasm,
Malignant Spindle Cells
Osteoid

179. Staging

180. • x