19 - Bone Tumors

Question 1

What is the most common type of primary tumor involving bone?

Answer 1

Hematopoietic (40%) tumors such as lymphomas and multiple myeloma.

Question 2

What are some nonspecific clinical presentations of bone tumors?

Answer 2

Usually nonspecific:

• Pain
• Mass
• Pathologic fracture
• Asymptomatic: usually found incidentally

Question 3

What aggressive bone tumors are associated with each age: children/adolescents, young adults, and elderly?

Answer 3

Children,adolescents: osteosarcoma, eqing’s sarcoma

Young adults: giant cell tumor

Elderly: chondrosarcoma

Question 4

What are some radiological patterns that indicate benign slow-growing neoplasms vs. malignant, rapidly-growing neoplasms?

Answer 4

Slow growing/benign: sclerotic margin because the bone has time to grow aruond the lesion. Well-circumscribed.

Rapidly growing/malignant: ill-defined margin, growth too rapid for sclerotic rim to form. Poorly defiend margins.

Question 5

What radiologic patterns are seen in malignant bone matrix-forming tumors and chondroid matrix-forming tumors?

Answer 5

Bone matrix-forming: solid ivory-like pattern

Chondroid matrix-forming: rings and arcs

Question 6

What are the two type of benign bone-forming tumors? How do they differ in their location, size, and pain?

Answer 6

Osteoid osteoma: long bones: femur and tibia. <2 cm with night pain but responds to aspirin.

Osteoblastoma: vertebrae or long bone metaphysis. >2 cm with pain that’s NOT responsive to aspirin.

Question 7

How do osteoid osteomas and osteoblastomas differ on radiograph? What type is pictured?

Answer 7

Osteoid osteomas: radiolucent lesion within sclerotic cortex

Osteoblastomas: expansile radio-lucency with mottling (no sclerotic rim)

Small well-circumscribed lesion pictured - ostoid osteoma.

Question 8

What does an osteoid osteoma look like on histology?

Answer 8

Bone forming lesion within bone with central area of immature bone formation.

All osteoblasts are making osteoid that’s becoming bone (but is not well formed) - osteoblasts are normal looking

Question 9

What does an osteoblastoma look like on histology?

Answer 9

Look like osteoid/osteoma

Area of immature bone being formed by osteoblasts

Question 10

How common are bone-forming (osteogenic) tumors?

Answer 10

Relatively rare group of tumors.

Malignant bone tumors comprise ~0.2% of all types of cancer.

Potentially curable.

Question 11

What is a an osteosarcoma? How common are they and why gets them?

Answer 11

Malignant mesenchymal tumor in which cells produce osteoid or bone; ~2000 new cases/yr in US.

Most comon sarcoma of the bone.

M>F, mean age 15 (60% ages 10-20), second peak from ages 55-80.

Question 12

Where in the body do osteosarcomas normally occur?

Answer 12

Metaphysis of long bones:

• 50% knee
• femur, tibia, humerus (56%)
• Flat bones
• spine
• mandible

May be polyostotic (more than one site at a time); Hematogenous spread to lungs common.

Question 13

What is the pathogenesis of osteosarcomas? Give examples of five things that can can cause them.

Answer 13

1. Inherited mutant alle of RB gene
2. Mutation of p53 suppressor gene
   
   • Li-fraumeni: bone tissue sarcoma causing easing onset breast cancer, brain tumor, and leukemia.
3. Overexpression of MDM2 (5-10%); INK4 and p16
4. Sites of bone growth/disease (Paget dz)
5. Prior irradiation

Question 14

What are characteristics of osteosarcoma on radiograph?

Answer 14

• Not well circumscribed/poorly delineated
• Bone destruction,
• Cortical disruption.
• Bone matrix
• Soft tissue extension: growing outside of the bone
• Codman’s triangle: trying to form cortex around expanding lesion to contain it

Question 15

Describe the pathology of osteosarcoma? How is it treated?

Answer 15

Infiltrative tumor that extends into soft tissue.

Malignant cells producing osteoid.

Treatment: neoadjuvant chemotherapy and surgical resection.

Question 16

What is the prognosis of osteosarcoma in metastatic and non-met disease?

Answer 16

60-70% 3-5 yr survival for patients with non-metastatic disease.

En-bloc resection following chemotherapy: >90% necrosis clearing is associated with 90% survival.

Question 17

What is the most common benign tumor of bone? Where does it occur? Does it metastasize?

Answer 17

Osteochondroma: occurs at the metaphysis of long bones.

Malignancy in <1%, but increase risk in hereditary multiple exotoses (when you have multiple osteochondromas)

• Aut dominant, secondary to mutations in EXT-1(8q24)

Question 18

Where do osteochondromas occur? What do they look like?

Answer 18

On the metaphysis of long bones.

• Both bone and cartilage in lesion
• Little growths occur off of cortex with bone in center and cartilage cap on top

Question 19

What do osteochondromas look like on histology?

Answer 19

Looks like normal cartilage maturation, similar to the epiphysis of growing bones.

Forms into bone with medullary spaces in the middle

Question 20

What is the name for a benign hyaline cartilage lesion?

Answer 20

Enchondroma: intramedullary chondroma (in the medullary space of bone)

Periosteal chondroma = juxtacortical chondroma (located on the cortical surface under the periosteum).

Question 21

What findings are seen on radiograph and histology for an enchondroma? Where are they found?

Answer 21

Usually asymptomatic and found incidentally; appendicular skeleton such as small bones of hands and feet.

On XRAY: lytic, lobulated, cortical thinning of bone

Histology: lobules of hyaline cart., minimal atypia.

Question 22

What is the treatment of an enchondroma?

Answer 22

None, unless lesion shows changes:

• Symptomatic - onset of acut pain is evidence that lesion is malig.
• Evidence of recent growth after skeletal maturity

Question 23

What do you see when you look at the cells in an enchondroma?

Answer 23

Lacuna with chondrocytes without mitotic activity, not very cellular, scattered chondrocytes in cartilage.

Looks very bland and beningn.

Question 24

What three diseases/genetic defects are associated with multiple chondromatosis?

Answer 24

1. Freq. point mutations in IDH1 or IDH2
2. Ollier disease
3. Maffucci syndrome

Question 25

What are characteristics of Ollier disease?

Answer 25

Multiple enchondromata that tend to be regionally distributed (ie in one hand) May or may not have skeletal malformation.

Question 26

What are characteristics of Maffucci syndrome?

Answer 26

* Multiple endochrondromata + angiomata (angiomas) * Severe skeletal malformation * Higher incicence of malignant transformation

Question 27

What type of malignant tymor has neoplastic cells that produce a purely cartilagenous matrix? How common are these, who gets them, and where?

Answer 27

**Chondrosarcoma:** second most common bone sarcoma (~26%) Mainly **older adults**, mostly above 40-50yos. Central skeleton: pelvis and ribs (45%), humerus, femur (metaphysis, diaphysis).

Question 28

How do chondrosarcomas look on imaging?

Answer 28

* Medullary location * Frequently contain calcifications which tend to be lost in grade 3 tumors * Cortical erosion or destriction * Occasional soft tissue extension

Question 29

What do chondrosarcomas look like on pathology? How due these differ from enchondromas histologically?

Answer 29

**Generally more cellular** (multiple nuclei in one lacunae) and **nuclei are more pleomorphic** than in enchondromas. _Binucleation is frequen_t but does NOT suffice for malig. diagnosis. Myxoid chance of chondroid matric.

Question 30

What correlates with the behavior of chondrosarcomas? How is this done?

Answer 30

Size (greater or less than 10cm) and grade correlate with behavior. Grading (1-3) is based on degree of cellularity and atypia.

Question 31

Describe the appearance of a grade 1 chondrosarcoma?

Answer 31

More cellular, but more matrix than cells still Cells look fairly normal, not much atypia

Question 32

Describe the appearance of a grade 2 chondrosarcoma?

Answer 32

More atypia - some focal areas that are dense with cellularity Areas of clear cut cartilage expression.

Question 33

Describe the appearane of a grade 3 chaondrosarcoma?

Answer 33

More severe atypia with mitotic figures Dense cellularity and tend to be more aggressive Fairly rare

Question 34

What is the 5yr survival for chondrosarcoma grades 1,2? What about grade 3?

Answer 34

Grades 1,2: 80-90% Grade 3: 29%, with pulmonary mets.

Question 35

What are variants of chondrosarcoma?

Answer 35

* De-differentiated * Myxoid * Clear cell * Mesenchymal * Juxtacortical

Question 36

What is the appearance of de-differentiated chondrosarcomas?

Answer 36

Loses terminal differntiation Have areas that look like carrtilage but then a lot of the tumor looks like non-specific mesenchymal tissue (looks almost like fetal development tissue).

Question 37

What is the most common space-occupying lesion of bone that occurs in 1 out of every 4 individuals? Where do they occur?

Answer 37

**Non-ossifying fibromas:** common developmental cortical defect. Multifocal in 25% of cases. _Occur in the tibia and femur metaphysis_ in the 1-3rd decades. Finding these is usually incidental or from pathologic fracture.

Question 38

Describe the lesion caused by non-ossifying fibromas?

Answer 38

These are slow growing benign lesions * eccentric, lytic, peripheral sclerosis (sclerotic rim)

Question 39

What histological pattern is seen with non-ossifying fibromas?

Answer 39

Storiform pattern: looks like van goughs starry night. Whirling pattern of fibroblasts. _No bone is being formed in this._

Question 40

What is fibrous dysplasia? What are the two types and what age/location are each found in?

Answer 40

Developmental arrest of bone. **Monostotic:** seen in adolescents in ribs, manidble, and femur **Polyostotic** (multiple cites): seen in infancy/childhood and causes crippling deformities; has craniofacial involvement.

Question 41

What is McCune-Albright syndrome? Who does it occur in and what are symtpoms?

Answer 41

**Polyostotic fibrous dysplasia with endocrinopathies** and café-au-lait spots. More common in females than males. * Sexual precocity (early puberty), acromegaly, and cushings syndrome

Question 42

What genetic mutation is associated with McCune-Albright syndrome?

Answer 42

Activating germline mutations of GNAS (GTP-binging protein) result in excess cAMP leading to endocrine gland hyperfuction.

Question 43

What do you see on radiology in fibrous dyspalsia?

Answer 43

* Expansile * Circumscribed * Thinned cortex * Ground glass appearance * May be multiple

Question 44

What does fibrous dysplasia look like on pathology? What is the treatment?

Answer 44

**Haphazard, curvilinear, randomly oriented woven bone trabeculae** (_"chinese characters"_) surrounded by fibroblastic stroma. No significant osteoblast rimming. **Treatment is conservative,** except in polyostotic form which tends to be more aggressive.

Question 45

What is the second most common malignant bone tumor in childhood? Who does it occur in? How does it present clinically?

Answer 45

**Ewing sarcoma/PNET** (Primitive Neuro Ectodermal Tumours) Occurs in _adolescents and young adults; M\>F_ Presents as painful, often enlarging mass that occurs on the **diaphysis** of long tubular bone, ribs, and pelvis.

Question 46

What does a ewing sarcoma/PNET look like on xray?

Answer 46

Destructive moth-eaten, permeative medullary lesion with large soft tissue mass. "onion-like" pattern of periosteal reaction in response to rapid growth (tried to grow around expanding lesion).

Question 47

What does an eqing sarcoma look like grossely? What is used to determine if the whole tumor was sucessfully resected?

Answer 47

Variable appearance - looks more like generic tumor with areas of hemmorrage. Yellow is necrosis. Ink used to determine resecetion margins.

Question 48

What does ewing sarcoma/PNET look like on pathology?

Answer 48

* Sheets of primitive small round blue cells with neural phenotype (rosettes) * Membranous CD99 (seen in brown) * Contain abundant glycogen (seen with PAS stain) * Hemorrhage and necrosis common

Question 49

What is the pathogenesis of ewings sarcoma?

Answer 49

EWS gene involved in \>95% of ES/PNET t(11;22) present in 85% of the tumors and is used to diagnose it. * EWS on 22q fused with FLI-1 transcription factor on 11q

Question 50

How is ewing sarcome treated? What is the five year survival associated with stage 1?

Answer 50

Chemotherapy and surgery; Radiation therapy might be added Stage 1: 5 year survival is 70% with chemo/RT

Question 51

Who gets giant cell tumors of bone and where do they occur?

Answer 51

Young adults (20-40), older adolescents (skeletally mature); Females \> males. **Epiphyseal location:** knee, proximal humerus, and radius

Question 52

Describe the behavior of giant cell tumors of the bone?

Answer 52

Most are benign, locally aggressive. May destroy the cortex of bone and extend into soft tissue.

Question 53

What do giant cell tumors look like on histology?

Answer 53

Tumor is composed of numerous giant cells that can have \>100 nuclei in one cell. Appearance similar to osteoCLASTS but MUCH larger. *If you have a locally expanding mass with this appearance its always a giant cell tumor.*

Question 54

How common are malignant bone tumors?

Answer 54

Most common malignant bone tumor, esp. in adults (20x more frequent than primary bone tumors) Mostly multiple.

Question 55

Solitary lesions of metastatic bone tumors may mimic what? What are characteristics of these lesions?

Answer 55

**Primary bone tumor and precede discovery of its source.** * **70% of primary tumors go to axial skeleton** (skull, ribs, vertebral column, sacrum) * _Mostly lytic_ * _May be blastic_ (bone forming): breast, prostate

Question 56

80% of metastatic bone tumors come from what sources?

Answer 56

**BLT-KP** Breast, lung, thyroid, prostate, and kidney.

Question 57

\_\_\_\_\_\_\_ is the most common sarcoma occuring in the bone, and it occurs prdominantly in \_\_\_\_\_\_\_.

Answer 57

Osteosarcoma is the most common sarcoma occuring in the bone and it occurs predominantly in children/adolescents.

Question 58

\_\_\_\_\_\_\_\_ is a painful bone lesion that is relieved by aspirin.

Answer 58

Osteoid osteoma is a painful bone lesion that is relieved by aspirin.

Question 59

What three syndromes are all associated with bone lesions?

Answer 59

* Li-fraumeni syndrome * Ollier disease * Maffucci syndrome

Question 60

A 25 yo presents with multiple enchondromas confirmed with biopsy, which in addition reveal frequent spindle cell hemangiomas. What is your diagnosis?

Answer 60

Maffucci syndrome. Associated with multiple enchondromas, angiomas, and severe skeletal malformations.

Question 61

An 8yo girl presents with signs and symptoms of precocious puberty, cutaneous cafe-au-lait sponts, and multiple ground class bony lesions on imaging. What is the most likely diagnosis?

Answer 61

McCune-Albright Syndrome.