Malignant Tumors of Bone

Cartilage and Soft Tissue

Dr. Rachael Connington
Osteoma
Osteoma
• Benign, round, slow growing sessile
tumors that project from the
subperiosteal or endostea surfaces of
the cortex
• Subperiosteal osteomas  skull and
facial bones
• craniofacial bones  paranasal sinuses!
• pain, headache, facial distortion, proptosis,
visual changes, sinusitis, meningitis
• Solitary
• Middle aged adults
• Association with Gardner Syndrome!!!
Gardners Syndrome
• Subtype of FAP (Familial
Adenomatous Polyposis)
• Mutations of the APC gene
• Multiple adenomatous colon
polyps  increased risk of
colorectal carcinoma
• Multiple benign tumors, including:
• sebaceous cysts
• epidermoid cysts
• Fibromas
• desmoid tumors
• Osteomas!!!
Osteoma
Osteoma
Osteosarcoma
Osteosarcoma
• Malignant mesenchymal tumor
 Cancerous cells produce bone
matrix
• Most common primary
malignant tumor of bone
• Bimodal: 10-14 years and >65
• Associated with Paget disease!
• Arises in the Metaphyseal region
of long bones of extremities
• Around the Knee
Osteosarcoma
• Most common Osteosarcomas:
• Arise from the metaphysis of long
bones
• primary,
• solitary,
• intramedullary ad
• poorly differentiated and
• produces a bony matrix
• Formation of poorly formed
osteoid bone by tumor cells is
characteristic
• Stain positive for Alkaline
phosphatase!
Osteosarcoma
Osteosarcoma
Osteosarcoma Sunburst
Osteosarcoma Codman Triangle
Osteosarcoma
Osteosarcoma • Genetic mutations of:
• RB Gene
• Association with
Retinoblastoma!
• Cell cycle regulators
• p53
• CDK4
• p16
• INK4A
• CYCLIND1
• MDM2
Osteosarcoma
Osteosarcoma • Painful and progressively
enlarging
• Fracture of bone
• Radiographs:
• Large, destructive, mixed lytic
and blastic mass that has
permeative margins
• Breaks through cortex and
lifts periosteum  Codman
triangle
• Metastases to lungs
Paget Disease (Osteitis Deformans)
• Disordered Osteoclast and osteoblast
activity
• Furious osteoclastic bone resorption
followed by hectic bone formation
then bone cell activity becomes
diminished
• Repetitive and overlapping sequence
1. Osteolytic stage
2. Mixed osteoclastic-osteoblastic stage
3. Burnt-out quiescent osteosclerotic
stage
Paget Disease
• Mid-adulthood
• Common in whites in Europe
and United States
• Caused by paramyxovirus
• IL-6 and M-CSF
• Abnormal osteoclasts that are
hyper-responsive to RANKL and
vitamin D
• Linked to locus on Chromosome
18q
Paget Disease • Morphology:
• Hallmark = Mosaic pattern of lamellar
bone – Jigsaw puzzle
• Lytic phage  marked osteoclast
activity with numerous resorption pits
• Mixed phase  bone surfaces now
lined by osteoblasts
• Quiescent phase  fibrovascular tissue
recedes
• End product = Larger than normal
coarsely thicken trabeculae and cortices
that are soft and porous and lack
structural stability
Paget Disease
Paget Disease
• Clinical:
• Elevated serum alkaline
phosphatase
• Increased urinary excretion of
hydroxyproline
• Axial skeleton or proximal femur
involved in 80%
• Localized pain!
• Bone overgrowth of cranium and
craniofacial bones
• Severe secondary osteoarthritis
• At risk for developing
Osteosarcoma!
Paget Disease
Paget Disease
Chalk Stick Fracture
Chondroma
 • Benign tumor of hyaline
Chondroma cartilage
• When arising in the medullary
cavity = Enchondromas
• When arising on the surface =
subperiosteal or juxtacortical
chondromas
• Develop from rests of growth
plate cartilage
Enchondroma • Solitary and asymptomatic
• Located in the metaphysis
• Short tubular bones of hands and feet
• Ollier Disease
• Multiple Enchondromas
• Maffucci Syndrome
• Multiple enchondromas + soft tissue
angiomas
• Ovarian carcinomas and brain gliomas
• Radiographic findings:
• Unmineralized nodules of cartilage
surrounded by thin rim of bone  O
ring sign
Enchondroma
Enchondroma
Chondrosarcoma
Chondrosarcoma
• Tumors that produce neoplastic
cartilage
• Intramedullary and juxtacortical
• > 40 years
• Affects men twice as frequent
and women
• May arise from a pre-existing
enchondroma
 • Composed of malignant hyaline and
Chondrosarcoma myxoid cartilage
• Large bulky tumors gray white,
myxoid, translucent nodules
• Painful progressively enlarging
• Commonly arise in the central
portions of the skeleton including the
pelvis, shoulder, and ribs
• Radiographic findings: Endosteal
scalloping
• Tumors > 10 cm behave aggressively
and metastasize to lung and skeleton
• Resection and chemotherapy
Chondrosarcoma
Chondrosarcoma
Chondrosarcoma
Chondrosarcoma
Chondrosarcoma Endosteal Scalloping
Chondrosarcoma
Fibrosarcoma
Fibrosarcoma
• Fibroblastic collagen producing
sarcomas of bone
• Middle age and elderly
• Large, hemorrhagic, tan-white
masses that destroy the underlying
bone
• Metaphysis of long bones and
pelvic flat bones
• Histology: Malignant fibroblasts
arranged in a herring bone pattern
• Radiographic finding: permeative
and lytic lesions
Fibrosarcoma
Fibrosarcoma
Fibrosarcoma

Herringbone appearance
Fibrosarcoma
Ewing Sarcoma
Ewing Sarcoma
• Primary malignant small round cell
tumor of bone
• Second most common bone sarcomas
in children after osteosarcoma
• Sarcoma with the youngest average age
at presentation
• 10-15 years old
• Boys are affected more frequently in
girls
• Predilection for whites
• t(11;22) (q24;q12)
• Fusion of the EWS gene on 22q12 to
FLI1 (transcription factor) on t(11;22)
 • Arise in medullary cavity and invade the cortex
Ewing Sarcoma and periosteum
• Tan-white, soft tissue mass that frequently
contains areas of hemorrhage and necrosis
• Histology: Sheets of uniforms small, rounds blue
cells with Homer-Wright Rosettes
• Arise in the diaphysis of long tubular bones
• Femur and flat bones of pelvis
• Painful Enlarging masses which are tender warm
and swollen
• Radiography: Destructive lytic tumor with
permeative margins and extension into
surrounding soft tissues and Onion skin periosteal
reaction
• 75% 5-year survival and 50% cures!
Ewing Sarcoma
Ewing Sarcoma
Ewing Sarcoma
Liposarcoma
Liposarcoma
• One of the most common sarcomas of
adulthood
• 40-60 years of age
• Arise in the deep soft tissues of the
proximal extremities and
retroperitoneum
• Large Tumors
• Well differentiated liposarcomas are
indolent
• More poorly differentiated liposarcomas
have lipoblasts = mimic fetal fat cells and
contain round clear cytoplasmic vacuoles
of lips that scallop the nucleus
Liposarcoma
Liposarcoma
Liposarcoma

Lipoblast
Liposarcoma
Liposarcoma
Liposarcoma
Primary Bone Tumors Vs Metastatic Bone
Tumors
Primary Bone Tumors Vs Metastatic Bone
Tumors • Primary bone tumors are much less common
than Metastases in adults older than 45 years!
• The most common cancers that spread to
bone:
• Breast
• Lung
• Thyroid
• Kidney
• Prostate
• After lung and liver, the skeleton is the most
common site for metastasis
• Spine
• Pelvis
• Ribs
• Skull
• Upper arm
• Long bones of the leg
Primary Bone Tumors Vs Metastatic Bone
Tumors
• Metastatic tumor can completely
destroy the bone = osteolytic bone
destruction.
• Most common in lung, thyroid, kidney, and
colon cancers
• New bone can form in response to the
cancer spread = osteoblastic growth
• Grows abnormally and causes the bone to
be weak and deformed
• More common in prostate, bladder, and
stomach cancer
• Breast cancer often behaves in a mixed
osteolytic and osteoblastic manner
Primary Bone Tumors Vs Metastatic Bone
Tumors
• Pain
• Pathologic fractures
• Nerve damage or
paralysis with
vertebral bone
metastasis
• Anemia
Primary Bone Tumors Vs Metastatic Bone
Tumors
• The diagnosis of metastatic bone disease
should not be assumed unless a patient has
a known primary cancer that has previously
spread to bone
• A biopsy may be necessary
• Blood chemistries (i.e., electrolytes, calcium,
and alkaline phosphatase) may be abnormal
in patients with widespread disease.
• A urinalysis can detect blood  renal cell
carcinoma.
• Thyroid function tests, CEA, CA125, and PSA
may be abnormal in patients with specific
tumors.
• Serum and urine protein electrophoresis 
multiple myeloma.
Primary Bone Tumors Vs Metastatic Bone
Tumors
Primary Bone Tumors Vs Metastatic Bone
Tumors • PET Scan
Questions
• A 70-year old man complains of right hip and thigh pain of several months’
duration. On physical exam, he has reduced range of motion in both hips,
but there is no tenderness or swelling on palpation. Radiographs of the
pelvis and right leg show sclerotic thickened cortical bone with a narrowed
joint space near the acetabulum. Lab studies show a serum alkaline
phosphatase level of 173 U/L, calcium of 9.5 mg/dL and phosphorus 3.4
mg/dL. A bone biopsy is performed and the microscopic appearance of the
specimen is shown above. Which of the following conditions is most likely
to produce these findings?
A. Osteochondroma
B. Vitamin D deficiency
C. Degenerative Osteoarthritis
D. Hyperparathyroidism
E. Paget disease of bone
• A 79-year old man has had progressively worsening lower back, bilateral
hip and right shoulder pain for the past 6 years. He reports that he has had
to buy larger hats. On physical exam, there is no joint swelling, erythema,
warmth or tenderness, but the range of motion is reduced. Radiographs of
the affected joints show narrowing of the joint spaces with adjacent boney
sclerosis. A skull radiograph shows thickening of the skull bone. A bone
biopsy at the iliac crest shows a loss of normal trabeculae with a mosaic
pattern and increased numbers of osteoclasts and osteoblasts. Which of
the following complications is the patient most likely to suffer as a result of
this condition?
A. Ankylosing spondylitis
B. Osteoma
C. Fibrous dysplasia
D. Osteosarcoma
E. Enchondroma
• A 45-year-old man has experienced pain in the area of the left hip and
upper thigh for the past 7 months. On physical exam, there is
tenderness on deep palpation of the left side of the groin. There is a
reduction in the range of motion of the left hip. There is no swelling
or warmth to the tough. Pelvic and left leg radiographs show an
upper femoral mass lesion arising in the metaphyseal region and
eroding the surrounding bone cortex. The proximal femur is excised
and on sectioning has the gross appearance shown. Which of the
following cell types is most likely to be proliferating in this mass?
A. Osteoblasts
B. Chondroblasts
C. Osteoclasts
D. Primitive neuroectodermal cells
E. Plasma cells
• An 18 year-old-man sees the physician because he had pain around
the right knee for the past 3 months. There are no physical findings,
except for the local pain over the area of the distal right femur. A
radiograph of the right left shows an ill-defined mass involving the
metaphyseal area of the distal right femur and there is elevation of
the adjacent periosteum. A bone biopsy specimen shows large,
hyperchromatic pleomorphic spindle cells forming and osteoid matrix.
Which of the following is the most likely diagnosis?
A. Ewing Sarcoma
B. Chondrosarcoma
C. Giant cell tumor of bone
D. Fibrous dysplasia
E. Osteosarcoma
• A 75-year-old woman has experienced increasing pain in the back, right chest,
left shoulder and left upper thigh for the past 6 months. The pain is dull but
constant. She has no developed a sudden severe, sharp pain in the left thigh.
On physical exam, he is afebrile. She has intense pain on palpation of the upper
thigh, and the left leg is shorter than the right. A radiograph of the left leg
shows a fracture through the upper diaphyseal region of the femur in a 5-cm
lytic area that extends through the entire thickness of the bone. A bone scan
shows multiple areas of increased uptake in the left femur, pelvis, vertebrae,
right third and fourth ribs, upper left humerus and left scapula. Lab studies
how serum Na+ of 140 mmol/L, K+ 4.1 mmol/L, Cl- 99 mol/L, CO2 26 mmol/L,
glucose 78 mg/dL, total bilirubin 1.0 mg/dL, AST 28 U/L, ALT 22 U/L and
Alkaline phosphatase 202 U/L. Which of the following is the most likely
diagnosis?

A. Metastatic carcinoma
B. Multiple myeloma
C. Osteochondromatosis
D. Osteomyelitis
E. Paget Disease
END