Bone Tumors

Question 1

What is the presentation, in general, of bone tumors?

Answer 1

1. Non specific.
2. Pain. A few nuances here to note
3. Mass (hard growing mass that may be palpable)
4. Pathologic fracture

Sometimes, ASYMPTOMATIC

Question 2

What is the metaphysis?

Answer 2

This is the area otherwise known as the growth plate in young patients… it is between the shaft/diaphysis and bone end/epiphysis

Question 3

What are the most common bone tumors of childhood and early adolesence?

Answer 3

Osteosarcoma and Ewing’s sarcoma

Question 4

What are the most common bone tumors of young adulthood?

Answer 4

Giant cell tumor

Question 5

What is the most common bone tumor of elderly?

Answer 5

Chondrosarcoma

Question 6

Signs of a benign or slow-growing neoplasm in bone?

Answer 6

Sclerotic margin, well circumscribed.

Malignant bone lytic lesions will be ill defined with no circumscription and no sclerotic border. Note that there are intermediates that may have well defined margins, but may grow too fast for a sclerotic ring to form.

Question 7

What to look for on X-ray for bone-forming malignancies (osteosarcomas)?

Answer 7

Solid, ivory-like pattern on X-ray (more brightly staining) is generally seen in malignant, bone-matrix forming tumors

Question 8

What is the radiological characteristics of bone-lytic cancers?

Answer 8

Rings and arcs, forming a popcorn? or web like appearance. This is classic for chondroid-matrix forming tumors (rather than bone-forming).

Question 9

What are the majority of tumors involving bones?

Answer 9

Hematopoietic tumors and Mets!

But there are some primary bone cancers as well.

Question 10

Osteoid Osteoma

Answer 10

Class: Benign Osteogenic Tumor

Location: Long bones, such as femur and tibia

Size: Expect larger than 2 cm

Pain History: Night pain that responds well to aspirin

Radiology: Sclerotic cortex, radiolucent lesion

Question 11

Osteoblastoma

Answer 11

Class: Benign Osteogenic Tumor

Location: Vertebrae, long bone metaphysis (growth plates)

Size: > 2 cm

Pain History: Painful, and will not respond to aspirin

Radiography: Expansile, radiolucent. With Mottling (irregular patches/smears of color)

Question 12

Osteosarcoma (class/epidemiology/location/mets)

Answer 12

Class: Malignant Osteogenic Lesion

Note: The most common sarcoma of bone

Epidemiology: Bimodal age distribution (peak at 15, and a second peak at 55-80). More common in men than women. Early peak is more common, but second peak is due to predispositions, such as Paget’s Disease.

Location: Metaphysis of long bones (femur, tibia, and humerus make up half)… also impacts flat bones and spine in older patients. Only rarely polyostotic

Spreads hematogenously to lungs (venous system)

Question 13

Pathogenesis of Osteosarcoma

Answer 13

1. Rb mutation inherited results in a 1000 fold higher risk
2. Li-Fraumeni Syndrome
3. Overexpression of MDM2, INK4, or p16
4. Bone disease (Paget’s Disease)
5. Prior irradiation

Question 14

Radiology of Osteosarcoma

Answer 14

1. Poor borders
2. Cortical disruption
3. Bone destruction; however it will be very radiodense and ivory-like on X-ray because it is also FORMING new bone
4. Medullary cavity becomes denser on X-ray
5. Codman’s triangle formation (X-ray showing radiodense periosteum being pulled away from the bone)… generally indicates infiltration

Question 15

Osteosarcoma pathology and treatment

Answer 15

Pathology: Infiltrative tumor that will enter soft tissue and produce osteoid

Treated with neoadjuvant chemotherapy and surgical resection

Question 16

Osteosarcoma histology

Answer 16

Tripolar mitotic figures in the speciman is a give away for malignancy

Question 17

Osteochondroma

Answer 17

Class: Chondrogenic

Location: Metaphysis of long bones

Prognosis: Rarely malignant; but if multiple osteochondromas (exostoses) are present, the risk is higher

Genetics: EXT-1 mutation predisposes a patient for malignancy, which is autosomal dominant

Outgrowth can become large and mushroom-like, with a shiny white multi-lobulated cap. They are made of cartilage

Question 18

Osteochondroma pathogenesis

Answer 18

Starts as an outgrowth in the growth plate, that contues to grow outward as the patient grows.

With time, this outgrowth will form a communication with the medullary cavity and produce marrow

Question 19

Enchondroma

Answer 19

Class: Benign Chondrogenic Tumor; in the Hyaline cartilage

The name suggests intramedullary chondroma

Location: Appendicular skeleton; small bones of the hand

Radiology: Lytic, lobulated, cortical thinning

Micro: Lobules of hyaline cartilage, with minimal atypical features

Findings: Usually asymptomic and found asymptomatically

Treatment: None, unless the lesion begins to change (symptoms appear.. such as onset of acute pain, that suggests malignancy or evidence of recent growth after skeleton is mature)

Note: Periosteal chondroma’s are juxtacortical chondromas (on the cortical surface)

Question 20

Grossly what does enchondroma look like?

Answer 20

Bluish white cartilagenous deposition. (Also, it may have calcium deposition on X-ray just to note)

Question 21

Ollier’s disease

Answer 21

Class: Chondrogenic… Multiple Chondromatosis

May or may not have skeletal malformations

Tend to be regionally distributed with multiple enchondromatas

Question 22

Maffucci’s syndrome

Answer 22

Class: Chondrogenic… Multiple Chondromatosis

Multiple enchondromatas… but also contains angiomata’s, unlike ollier’s disease

Sever skeletal malformation is classic

Higher incidence of malignant transformation

Question 23

What are the genetic factors for multiple chondromatosis… and name the two types, and which one is more likely to be malignant

Answer 23

IDH1 or IDH2 point mutations.

Maffuci’s syndrome and Ollier’s disease, with Maffuci’s more likely to become malignant

Question 24

Chondrosarcoma

Answer 24

Class: Malignant Chondrogenic Tumor

Produces a PURELY CARTILAGENOUS matrix

Age GRoup: Mostly older adults, above 60

Location: Central skeleton… pelvis and ribs… Also can affect humerus and fever at diaphysis and metaphysis. Location in the medulla, with many calcifications on imagin. At grade 3 tumor, the calcifications may disappear.

Pathogenesis: Cortical erosion and destruction, and extension into the soft tissue after the cortex is destroyed.

They will look nebulous rather than the thickened ivory like appearance of osteosarcoma.

Generally these will become pleomorphic unlike enchondromas, and chondrocytes will be binucleated with a myxoid change of the chondroid matrix

Question 25

What site correlates with chondrosarcoma grading?

Answer 25

Over 10 cm is worse behavior. 3 grades, with 3rd being most atypical and most cellular

Question 26

Where does chondrosarcoma metastasize at grade 3

Answer 26

Very poor prognosis with pulmonary metastasis

Question 27

Non-Ossifying Fibroma

Answer 27

Class: Fibrous Bone Tumor

25% of of space-occupying lesions are this

Multifocal

Location: Usually tibia femur

Age: 1-3rd decade

Lytic with peripheral sclerosis

Found incidentally or causes a pathologic fracture

Can eat at the cortex… it is not medullary. Ring like but with cortex penetration

Van Gogh on Histo

Question 28

Fibrous Dysplasia

Answer 28

Class: Fibrous Bone Tumor

Causes developmental arrest of the bone.

Monostotic form: Most common… seen in adolescents in ribs, mandible and femur

Polyostotic form: Rare… see in infants and children, with crippling deformities and craniofacial involvement

Question 29

McCune-Albright Syndrome

Answer 29

Class: Fibrous Bone Tumor

A special case of polyostotic fibrous displasia.

More common in females than plays.

Also presents with cafe-au-lait spots and endocrinopathies

Germline mutations in GNAS (GTP-binding protein) cause excess cAMP, which is why endocrine glands are hyperactive.

Have sexual precocity, acromegaly, and Cushing syndrome

Question 30

Fibrous Dysplasia on X-ray

Answer 30

Ground glass appearance, with multiple lesions often

They are well circumscripled, and the bone looks expansile and thinned out at the cortex

Question 31

Fibrous Dysplasia Pathology

Answer 31

Haphazard, curvilinear, randomly oriented woven bone trabeculae that resemble chinese characters

Surrounded by Fibroblastic Stroma

TREAT IT CONSERVATIVELY unless it is polyostotic

Question 32

Ewing Sarcoma

Answer 32

Second most common malignancy of childhood

Common in adolescents, more so in males

Painful, enlarged mass

Location: Diaphysis of long tubular bones, ribs and pelvis

Cell of origin unknown

X-ray: Moth-eaten permeated medullary lesion with large soft tissue mass. Onion skin pattern at the periosteum due to rapid growth

Pathology: Sheets of primitive small round blue cells with neural phenotype (resembling lymphocytes), with significant glycogen, CD99, and hemorrhage/necrosis

Question 33

Ewing Sarcoma Pathogenesis

Answer 33

EWS mutation or t(11;22) involved in most tumors

Treated with surgery, radiation

Question 34

Giant Cell Tumor of Bone

Answer 34

Also known as osteoblastoma

Young adults (20-40) with mature skeleton

More common in women

Location: Epihysis of knee, proximal humerus or radius

Usually benign, but locally aggressive with cortical and local soft tissue destruction

Question 35

Metastasis in bones

Answer 35

BLT-KP… Breast, lung, thyroid, prostate and kidney commonly met to bones.

Often multiple mets

Solitary lesions may seen to be primary bone tumor and precede the discovery of tumor source

70% are in axial skeleton, and they are usually osteolytic, but breast and prostate can be osteogenic