Bone Tumors

Question 1

How are bone tumors usually classified ?

Answer 1

By the Normal cell or matrix they produce

• if a lesion they are grouped by clinicopathologic features.

Question 2

Osteoid osteomalacia and osteoblastoma

Answer 2

Bending bone producing tumors that are similar histologically but located differently

• both appear round/oval masses of tan tissue w/ dilated and congested capillaries surrounding
• both usually dont involve malignancies

Osteoid osteoma: metaphysis of long bones

Osteoblastoma: Vertebral column

Question 3

Specifics of osteoid osteoma

Answer 3

Less than 2 cm diameters and are more common in men than women (1.6:1)

• usually occur in femur or Tibia diaphysis
• always marked with severe nocturnal pain that can be relieved by aspirin or NSAIDs
• almost always elicit a reactive bone formation
• pain is expected to be caused by prostaglandin E2 produced by osteoblasts*

Question 4

specifics of Osteoblastoma

Answer 4

Larger than 2 cms and is most frequently found in posterior components of vertebrae

• is marked by nocturnal pain that cannot be subdued via aspirin and NSAIDs
• Doesnot induce a marked bony reaction

Question 5

Osteosarcoma specifics

Answer 5

Malignant tumor that produces osteoid matrix

Common primary malignant tumor of bone

Contains a bimodal age distribution

Question 6

Bimodal age distribution of osteosarcoma

Answer 6

1 peak: 75% occur in persons younger than 20

2 peak: older adults with paget disease, bone infants or previous radiation

Question 7

Most common sites of osteosarcoma

Answer 7

Distal femur and proximal tibia in the metaphyseal regions.

Metaphyseal regions are common due to increased proliferation seen in these regions.

Question 8

Osteosarcoma pathogenesis

Answer 8

• 70% have acquired genetic abnormalities

Common mutated oncogenes (inactivated)
- RB (cell regulator)

• TP53 (initiation of apoptosis)
• CDKN2A (tumor suppressors)

Question 9

Osteosarcoma morphology

Answer 9

Bulky gray-white tumors

Frequently show destructions of surrounding tissues and spread into the medullary canal, replacing the marrow.

• most prevalent marked sign is increased formation of osteoid matrix or mineralized bone
• usually painful and can cause sudden fractures of bones.

Question 10

Osteosarcoma treatment

Answer 10

Neoadjuvant chemotherapy, surgery and additional chemotherapy.

• usually spread hematogenously to the lungs
• usually poor outcome

Question 11

Osteochondromas “exostosis” characteristics

Answer 11

Begin cartilage tumor that attaches to underlying Skeleton by a bony stalk.

85% are solitary and the rest are developed by multiple hereditary exostoses syndrome

Males are 3x more likely to be affected than females

Commonly diagnosed in late adolescence and early adulthood

Question 12

Multiple hereditary exostoses syndrome

Answer 12

Caused by germline loss of function in EXT1 or EXT2 genes

Encode enzymes that synthesize heparan sulfate glycosaminoglycans

Causes chondrocytes in growth plate to not differentiate properly.

Question 13

Osteochondroma sites of development

Answer 13

Only develop in bones of endochondrial origin growth and usually arise from the metaphysis of long bones.

Question 14

Osteochondroma morphology

Answer 14

Sessile: smooth tumor inline with bone

Pedunculated: raised tumor that “sprouts” out of bone

Both are comprised of a cap of begging hyaline cartilage and surrounded by perichondrium

Both have a stalk that are continuous with the medullary cavity of the bone.

Question 15

Clinical features of osteochondromas

Answer 15

Slow growing masses that can be painful due to nerveimpingement or stalk fractures

Can be cured by simple excisions

Question 16

Chondroma characteristics

Answer 16

Begin tumors of hyaline cartilage that only arise in bones of Endochondral origin.

• arise within medullary cavity
• usually diagnosed in people between 20-50 years of age
• typically arise in metaphyseal regions of tubular bones in hands and feet (phalanges)
• produce a C or O ring sign

Question 17

Ollie’s disease and Maffucci syndrome

Answer 17

Diseases caused by multiple enchondromas that are very prevalent in radiographs

Question 18

Chondroma morphology

Answer 18

Usually small gray-blue translucent nodules.

Outsides can appear calcified via spontaneous enchondral ossification

Question 19

Chondroma clinical features

Answer 19

Most are symptomatic, with only occasional pain

• only diagnosed through observation or accidental detection

Question 20

Chondrosarcoma characteristics

Answer 20

Malignant tumors that produce cartilage

• half as common as osteosarcomas
• usually men in their 40s or older
• sometimes arise secondary to osteochondromas

Almost always found in axial Skeleton bones

Question 21

Chondrosarcoma morphology

Answer 21

Large bulky tumors composed glistening gray-whites cartilage

Appear spotty calcifications and tumor spreads into muscle and fat surrounding it.

Assigned grade 1-3 depending on how differentiated it is (3= less differentiated)

Question 22

Clinical features of Chondrosarcoma

Answer 22

Very painful and grow quickly

Tumor grade predicts outcome
Grade 1: 80%
Grade 3: 43%

Grade 3 is usually the only one that metastasizes and does it hemarogenously, usually to the lungs.

Question 23

Ewing sarcoma

Answer 23

Malignant tumor composed of primitive round cells with varying degree of differentiation

• 2nd most common bone sarcoma Behind osteosarcoma
• usually present in children <20 age
• white males experience slightly more frequency

Question 24

Ewing Sarcoma Locations and pathogenesis

Answer 24

Arise in the diaphysis of long tubular bones.

Usually caused by a translocation that fuses the EWSR1 gene to the FLI1 gene

Question 25

Ewing sarcoma morphology

Answer 25

tumors appear soft tan-white, arising in the medullary cavity

Can appear small, round and blue single cell tumors in children

Usually contains areas of hemorrhage and necrosis

Tumors DONT produce bone or cartilage

Question 26

Homer-Wright rosettes

Answer 26

Round groupings of cells with central fibrillary core. Usually present in Ewing sarcomas

Question 27

Ewing sarcoma clinical features

Answer 27

Painful enlarged masses

Site is usually warm, tender and swollen

Layers of reactive bone appear deposited in onion-layered like fashion.

Treated with neoadjuvant chemo and surgical excision

50% mortality without chemo
25% mortality w/ chemo

Question 28

Giant cell tumor characteristics

Answer 28

Multinucleated osteoclast-type giant cell that dominate the histology slide they are presented in.

• almost exclusively affects adults
• usually occurs in epiphysis of long bones (specifically distal femur and proximal tibia)

Question 29

Giant cell pathogenesis

Answer 29

Osteoblast precursors that express high levels of RANKL causing increased proliferation and differentiation into osteoclasts.

Question 30

Giant-cell morphology

Answer 30

Red-brown masses that dominant the image and can sometimes appear to have a thin shell of reactive bone surrounding it.

Often destroy the overlying cortex of bone.

Microscopically appears to lack bone or cartilage and only contains mononuclear tumor cells.

Question 31

Giant-cell clinical features

Answer 31

Usually found in joints so often appear with similar symptoms to arthritis (pain/inflammation in joints)

40-60 % recurrence rate in local tissues after treatment

Treatment include curettage and RANKL inhibitor Denosumab.

Question 32

Aneurysmal Bone Cyst (ABC)

Answer 32

Benign tumor of bone that has multinucleate blood filled cystic spaces

Usually found in posterior elements of vertebrae and metaphysis of long bones (specifically proximal tibia and distal femur)

Affects males and females equally and occurs within 20 years of age.

Question 33

ABC morphology

Answer 33

Consists of blood-filled cystic spaces separated by thin tan-white septae

Septae are composed of fibroblasts, multinucleated giant cells and reactive woven bone.

NOT covered by endothelium

Question 34

ABC clinical features

Answer 34

Pain and swelling almost always appear

Appears as a metaphyseal lesion with all-defined margins on x-rays

May demonstrate internal septa and varying fluid levels on CT and MRIs

Treatment is surgical excision and curettage

Low risk of recurrence

Question 35

Non-ossifying Fibroma

Answer 35

Benign likely reactive mesenchymal proliferative cell

often present in children/young adults between ages 2-25 (occurrence rate is roughly 50%)

Form cellular lesions containing fibroblasts and macrophages

Most arise from the metaphysis of distal femur and proximal tibia

Most undergo spontaneous resolution without intervention within several years. (Only if small)

Question 36

Non-ossifying Fibroma morphology

Answer 36

Often appear in a pinwheel pattern w/ macrophages forming clusters and appearing like giant cells.

Radiographs show oval radiolucency with long axis parallel to the cortex of the bone

Question 37

Metastatic tumors in bones

Answer 37

The majority of cancer in bones are metastatic to the bone but do not originate in the bone.

In adults, more than 75% originate from prostate, breast kidney and lung cancers.

In children more than 75% originate from neuroblastoma, Wilms tumors and rhabdomyosarcoma

Question 38

Pathways for metastatic tumor spread to bone

Answer 38

Direct extension

Lymphatic/hematogenous dissemination

Intraspinal seeding

Question 39

Metastatic disease in bone morphology

Answer 39

Typically multifocal and involve the axial skeleton, especially the vertebral column.

Radiographs appear lyric (bone destroying) and/or blastic (bone forming)

Very poor prognosis