BONES, Joints, Soft Tissues Part 2

Question 1

Bone Tumors:

Are most primary or metastatic?

What kinds of bones do we usually see them in?

When are they a/symptomatic?

What are the 3 most common (after hematopoietic)?

Answer 1

Almost always d/t hematopoietic or metastatic tumors (rarely primary)

Most often found in long bones

Benign tumors are often asx and found incidentally; possible pain or pathologic fracture

Most common: Osteosarcoma, chondrosarcoma, Ewing sarcoma

Question 2

What are 2 bone-forming tumors?

Answer 2

Osteoid osteoma & osteosarcoma

Question 3

What are 4 cartilage-forming tumors?

Answer 3

Osteochondroma, chondroma, enchondroma, chondrosarcoma

Question 4

What are 3 tumors of unknown origin?

Answer 4

Ewing sarcoma, giant cell tumor, aneurysmal bone cyst (ABC)

Question 5

What are 3 lesions simulating primary neoplasms?

Answer 5

Fibrous cortical defect, nonossifying fibroma, fibrous dysplasia

Question 6

Describe the pain pattern of an osteoid osteoma. Do medication will it respond to? What is this pain due to?

Where do they usually appear and how large are they?

Histo and tx?

Answer 6

Pain that is usually worse at night that responds to aspirin & NSAIDs; excess prostaglandin E2 production by osteoblasts

Seen in males in teens and 20s; 50% appear on femur or tibia
- Strictly <2cm

Central nidus surrounded by osteoblasts; thick rind of reactive cortical bone
- Tx w radiofreq ablation

Question 7

Compare osteoblastoma to an osteoid osteoma

Location, pain, medications, tx

Answer 7

Osteoblastoma is >2cm, so bigger than osteoma

Involves posterior spine

No bony reaction

Achy pain that does NOT respond to aspirin

Tx: Curetted or excised en bloc

Malignant transformation is rare

Question 8

What is an osteosarcoma? Are they typically malignant tor benign?

What age do we common see them in?

Answer 8

Malignant mesenchymal cells produce bone matrix; presents as painful enlarging mass
- Most common primary malignant tumor of bone

Bimodal age distribution

• First peak is in males <20yo
• Second peak is in older males w Pagets, bone infarcts, or prior radiation (secondary osteosarcoma)

Question 9

What do you see on x-ray and what do you see grossly in an osteosarcoma?

Answer 9

X-Ray: Mixed lytic and blastic mass w infiltrative margins
- Codman triangle (elevation of periosteum after bone breaks through cortex) demonstrates aggressive tumor

Gross: Bulky, gritty, grey-white tumors containing hemorrhage & cystic degeneration
- Destroys cortex, spreads to soft tissue, spreads extensively through medullary canal & replaces marrow

Question 10

What genetic abnormalities do you see with osteosarcomas?

Answer 10

• Rb gene inc risk of sporadic osteosarcoma by 70%
• TP53 Li-Farumani syndrome
• CDKN2A (aka INK4a)

Question 11

What do you see in microscopy in an osteosarcoma?

Answer 11

“Bizarre giant tumor cells”, large hyperchromic nuclei w abundant mitoses (abn tripolar forms)

• “Lace-like” bone
• May produce cartilage (chondroblastic osteosarcoma if abundant cartilage)

Question 12

What is an osteochondroma (aka exostiosis)?

What age is this normally seen? What gene abnormalities is this seen with?

Does this normally have a solitary or multiple tumors?

Answer 12

Most common benign bone tumor

Solitary and more common in men in early adulthood

• Younger ages see multiple hereditary exostoses
• EXT1 or EXT2

Multiple hereditary exostosis can progress to chondrosarcoma

Question 13

What does an osteochondroma (aka exostosis) look like grossly?

Where is it typically located?

Answer 13

Attached to skeleton by bony stalk capped by cartilage; pain if impinge on nerve or fracture

Cartilage is disorganized and undergoes endochondral ossification; medullary cavity of osteochondroma is continuous w bone of origin

Only in bones of endochondral origin
- Metaphysis near growth plate of long tubular bone (esp knee)

Question 14

What is a chondroma/enchondroma?

What genes are a/w them?

What is tx?

Answer 14

Benign hyaline cartilage, solitary metaphyseal lesion tubular bones of hands and feet

• If it’s within medullary cavity it is an enchondroma
• If it is on the surface it is a subperiosteal or juxtacortical chondroma
• IDH1 & IDH2

Tx: Observation or curettage

Question 15

What imaging do you see in an chondroma/enchondroma?

Answer 15

Well-circumscribed nodules of hyaline cartilage (lucency) w central irregular calcifications, a sclerotic rim, and an intact cortex

Question 16

What is Ollier syndrome?

What is Maffucci syndrome? What does this inc the risk for?

Answer 16

Ollier: Multiple chondroma/enchondromas, not hereditary

Maffucci: Multiple chondroma/enchondroma plus hemangiomas; inc risk of chondrosarcoma & other malignancies; not hereditary

Both have inc cellularity and atypia

Question 17

What is a chondrosarcoma? What patient population do we often see it in? Where in the body do we see it?

Answer 17

Second most common malignant matric producing tumor of bone (osteosarcoma is first)

• M:F=2:1; usually 40s or older
• Axial skeleton (pelvis, shoulders, ribs)
• 15% are secondary that arise from enchondromas or osteochondroms

Question 18

What are some characteristics of a chondrosarcoma? Genes?

Answer 18

Invade locally, painful enlarging mass, may metastasize

• Grade 3 often spread hematogenously esp to the lungs
• IDH1 & IDH2

Question 19

What does imaging show in a chondrosarcoma?

Answer 19

Calcified matrix appears as foci of flocculent densities

Question 20

What are the grades and types of chondrosarcomas and what is the correlation between histologic grade and behavior?

Answer 20

Direct correlation b/w grade and behavior; graded 1-3 based on cellularity, cytologic atypia, mitotic activity

• Conventional: Nodules of glistening grey-white, translucent cartilage
• Dedifferentiated: Low grade w a high grade component, no cartilage
• Clear cell: Numerous osteoclast-type giant cells & intralesional bone formation
• Mesenchymal: Islands of well-differentiated hyaline cartilage surrounded by sheets of primitive appearing small round cells

Question 21

What is tx for a chondrosarcoma?

Answer 21

Wide surgical excision for conventional. Mesenchymal & dedifferentiated require excision & adjuvant chemotx bc more aggressive

Question 22

What are Ewing Sarcoma Family Tumors?

• What are common ages and populations we see it in?
• What is the cell appearance?
• Where in the body do these present?
• Clinical sx?

Answer 22

• Often seen in Caucasian populations less than 20 years old
• Small blue round tumor or primitive round cells; neural differentiation (PNET)
• Reactive bone in “onion-skin” on xray
• Diaphysis of long bones esp femur and the flat bones of the pelvis
• Painful enlarging mass that is often tender, warm, and swollen; mimics infection

Question 23

• What genes do we see in Ewing Sarcoma Family Tumors?
• Histo?
• Gross appearance?
• Tx?
• Important prognostic finding?

Answer 23

• EWSR1 gene on chromosome 22 w partner of FLI1 on chromosome 11; fusion of these two leads to uncontrolled growth & abn differentiation
• Soft, tan-white, w areas of necrosis and hemorrhage
• Homer-wright rosettes
• These are aggressive malignancies best txx w chemo followed by surgical excision w or w/o radiation
• The amount of chemo-induced necrosis is an impt prognostic finding (the more necrosis the better, indicative of sensitivity to tx)

Question 24

Giant cell tumor:

What is an osteoclastoma? Benign or malignant? What is a ddx for this tumor?

What age do we normally see this?

Where in body do we see?

Answer 24

Multinucleated osteoclast-type giant cell; neoplastic cells are primitive osteoblast precursors expressing RANKL which promotes proliferation & differentiation of osteoclasts
- In ddx must consider brown tumor of hyperPTism

Common in 20-40yos; benign but locally aggressive

Arises in epiphyses
- Knee: Distal femur & proximal tibia gives arthritis-like sx

Question 25

Giant cell tumor:

Aneurysmal Bone Cyst: Benign or malignant?

What age do we normally see this?

Where in body do we see?

Imaging?

Answer 25

Benign but locally aggressive; reactive osteoblasts

Most cases in adolescence and occur in femur, tibia, vertebral body
- Localized pain and swelling that may cause limp, vertebral lesions, nerve compression

Imaging shows well-circumscribed lytic lesion; thin & sclerotic “eggshell” around periphery w “soap bubble” appearance

Question 26

Giant cell tumor:

Fibrous Cortical defect & nonossifying fibroma:
What is this and who does it happen in?

Where in the body do we see it? How large is it?

Imaging?

Tx?

Answer 26

Asx; 50% of children >2yo develop, found incidentally in adolescence

Ariise in metaphysis of distal femur and prox tibia; half are bilateral or have multiple lesions

Most <0.5cm, if >5-6cm then its nonossifying fibroma

Imaging shows small and sharply demarcated radiolucent mass w thin rim of sclerosis

Often spontaneously resolve over time but could need curettage and bone-grafting

Question 27

What is fibrous dysplasia and what are the main types?

Answer 27

Benign proliferation of fibrous tissue that do not mature

• Monostotic is a single bone, usually asx
• Polyostotic is multiple bones and has crippling deformities
• McCune-Albright disease is polyostic w unilateral bone lesion & cafe au lait spots on same side; precocious puberty in females
• Mazabraud syndrome is polyostotic that has soft tissue myxomas

Question 28

Where do we commonly see fibrous dysplasia in the body? Sx?

What do we see on imaging?

Answer 28

Craniofacial bones, femur or tibia, ribs, shoulder and pelvic girdle
- Can cause pain or pathologic fracture but often incidental findings; can be reactivated during pregnancy

Ground glass appearance w well-defined margins

Question 29

What gene mutations do we see in all fibrous dysplasias?

What does it look like?

Answer 29

Gain of fxn of GNAS1

• Phenotype depends on stage of embryogenesis when mutation occurred and fate of cell harboring mutation
• McCune-Albright is most extreme

Intramedullary lytic lesions that expand causing bowing and cortical thinning

• Nodules of hyaline cartilage and disorganized growth plates
• Curvilinear trabeculae of woven bone w prominent osteoblastic rimming

Question 30

Where do the majority of metastatic tumors to bone come from in adults?

Answer 30

• Prostate
• Breast
• Kidney
• Lung

Question 31

Where are the majority of metastatic tumors to bone come from in kids?

Answer 31

• Neuroblastoma
• Wilms
• Osteosarcoma
• Ewing
• Rhabdomyosarcoma

Question 32

Are most metastatic tumors to bone multifocal or solitary?

Answer 32

• Most are multifocal except kidney & thyroid

Question 33

In what metastatic tumors do we see lytic lesions on radiography?

Answer 33

Carcinomas of the kidney, lung, GIT, and melanoma

Question 34

In what metastatic tumors do we see blastic lesions on radiography?

Answer 34

Prostatic adenocarcinoma