Chapter 26: Bone Tumors and Tumor-Like Lesions Flashcards
1
Q
How does osteoid osteoma differ from osteoblastoma in terms of size and bone predilection?
A
- Osteoid osteoma: <2cm in diameter; predilection for appendicular skeleton (50% involve femur or tibia) arising in cortex
- Osteoblastoma: are >2cm and involve posterior spine (laminae and pedicles); no bony reaction
2
Q
How does the pain and responsiveness to aspirin/NSAIDs differ between osteoid osteoma and osteoblastoma?
A
- Both are painful, and the pain is typically worse at night for osteoid osteomas
- Osteoid osteoma DOES respond to aspirin/NSAIDs
- Osteoblastoma DOES NOT respond!
3
Q
What is a radiographic clue for osteoid osteoma?
A
- Thick rind of reactive cortical bone; surrounding a nidus
- Osteoid osteomas elicit formaion of a tremendous amount of reactive bone
4
Q
Describe the characteristic morphology of osteoid osteoma?
A
Haphazardly interconnecting trabeculae of woven bone that are rimmed by prominent osteoblasts
5
Q
Which histologic features of osteoid osteomas and osteoblastomas help to distinguish them from osteosarcomas?
A
Relatively small size, well-defined margins, and benign cytologic features of the neoplastic osteoblasts
6
Q
How is osteoid osteoma vs. osteoblastoma treated?
A
- Osteoid osteoma is frequently treated w/ radiofrequency ablation
- Osteoblastoma is usually curetted or excised en bloc
7
Q
What is the bimodal age of distribution seen with osteosarcoma; which sex is most affected?
A
- 75% occur in pt’s <20 y/o
- 2nd peak in older adults (>65 y/o), frequently in assoc. w/ Paget disease, bone infarcts, and prior radiation
- Men more commonly affected
8
Q
Which part of bones do osteosarcomas arise in and which bones are most often affected?
A
- Arise in metaphyseal region of long bones of extremities
- Almost 50% occur about the knee (i.e., distal femur or prox. tibia)
9
Q
How do osteosarcomas typically present?
A
- Painful, progressively enlarging mass
- Sometimes sudden fracture is the 1st sx
10
Q
What are the characteristic X-ray findings with osteosarcoma?
A
- Large destructive, mixed lytic and blastic mass w/ infiltrative margins
- Frequently breaks thru periosteum, resulting in reactive periosteal bone formation –> Codman triangle = elevated periosteum
11
Q
Germline mutations in what gene are associated with a 1000-fold increased risk for osteosarcoma; occurrence in sporadic tumors?
A
- Germline mutation in RB = 1000-fold ↑ risk
- This mutation is present in up to 70% of sporadic tumors
12
Q
Li-Fraumeni syndrome is associated with what germline mutation; have an increased risk for what MSK pathology?
A
- Germline TP53 mutations
- Greatly ↑ risk of osteosarcoma
13
Q
Besides RB and tP53, what is another gene associated with increased risk of osteosarcoma?
What is the function of this gene?
A
CDKN2A (inactivated in many osteosarcomas)
-encodes two tumor suppressors, p16 and p14
14
Q
Why do osteosarcomas peak in incidence around the time of the adolescent growth spurt and how does this relate to their location?
A
- Occur most frequently in the region of the growth plate in bones with the fastest growth
- The ↑ proliferation at these sites may predispose to mutations
15
Q
What is the gross appearance of osteosarcomas?
A
bulky, gritty, gray-white tumors containing hemorrhage and cystic degeneration
-destroys cortex, spreads to soft tissue → ST mass, spreads through medullary canal & replaces marrow
16
Q
Which morphological feature of osteosarcomas is diagnostic; what is the appearance of the neoplastic bone?
A
- Formation of bone by the tumor cells = diagnostic
- Neoplastic bone usually has fine, lace-like architecture but also may be deposited in broad sheets of primitive trabeculae
17
Q
What is the histologic appearance (micro) of osteosarcoma?
A
pleomorphic, large hyperchromatic nuclei, bizarre giant tumor cells, abundant mitoses (including abnormal tripolar forms)
18
Q
When malignant cartilage is abundant in osteosarcomas they are referred to as what?
A
Chondroblastic osteosarcoma
19
Q
Osteosarcomas frequently metastasize via which route and to where?
A
Hematogenously to the lungs, bone, and brain
20
Q
What is the multi-modality approach to tx of osteosarcomas?
A
- Neoadjuvant chemotherapy, which is given under the assumption that all pt’s have occult metastases at time of dx
- Followed by surgery & postop adjuvant chemotherapy
21
Q
What is the most common benign bone tumor?
A
Osteochondroma (aka exostosis)
22
Q
What is another name for osteochondroma?
A
exostosis
23
Q
Majority (85%) of osteochondroma arise how and the remainder are associated with what hereditary disease?
A
- 85% are solitary; arise in early adulthood w/ men 3x > women
- Remainder assoc. w/ multiple hereditary exostosis syndrome, an autosomal dominant hereditary disease
24
Q
Where in bone do osteochondromas arise and which bones most often affected?
A
- Only bones of endochondral origin and arise from the metaphysis near the growth plate
- Long tubular bones, especially near knee
- Occasionally seen in bones of pelvis, scapula, and ribs (but less common)
25
Hereditary osteochondroma (exostoses) and some sporadic types are assoc. w/ what mutations?
What do these genes encode?
- **Hereditary** = germline loss-of-function ***EXT1*** or ***EXT2***
- **Sporadic** = ↓ expression of **EXT1** or **EXT2**
- These genes encode enzymes that synthesize **heparin sulfate gylcosaminoglycans**
26
What is the characteristic morphology and growth pattern of osteochondromas?
- Are **_sessile**_ or _**pedunculated_** w/ _cap_ composed of **benign hyaline cartilage** varying in thickness; bluish-white cartilaginous cap overlies the bony cortex
- **Cortex** of newly formed stalk **_merges_** w/ cortex of the host bone, so that **medullary cavity** of the osteochondroma and bone from which it arises are in **continuity**
27
What is a complication of osteochondroma that is more often seen in those assoc. w/ multiple hereditary exostosis?
Progression to **_chondrosarcoma_**
28
What are chondromas and what are they known as if they arise in the medullary cavity vs. surface of bone?
- **Benign** tumors of **hyaline cartilage**
- In **medullary cavity** = **enchondromas**
- **Surface of bone** = **juxtacortical** or **subperiosteal** chondromas
29
Which age group are enchondromas most often seen in and which bones most often affected?
- **20-50 y/o**
- Appear as **solitary metaphyseal lesions** of **tubular bones** of the **hands** and **feet**
30
Which 2 non-hereditary disorders are characterized by multiple enchondromas; characteristics of each?
- **Ollier syndrome** = multiple enchondromas (not hereditary)
- **Mafucci syndrome** = multiple enchondromas + **angiomas** --\> ↑ risk of chondro**sarcoma** and other malignancies
31
Which mutations have been identified in the chondrocytes of syndromic and solitary enchondromas?
**Heterozygous** mutations in the ***IDH1*** and ***IDH2*** genes
32
What is the size and characteristic morphology of enchondromas; how does this differ in the non-hereditary disorders Ollier and Maffucci syndrome?
- Usually **\<3cm** and are **gray-blue** and **translucent**
- **Well-circumscribed** nodules of **hyaline cartilage** containing **benign chondrocytes**
- Periphery may **ossify** and _center_ can **calcify** and **infarct**
- **Ollier** and **Maffucci**: ↑ cellularity and atypia
33
Which malignancies are those with Mafucci Syndrome at increased risk of developing?
Chondro**sarcoma** + **ovarian carcinomas** and **brain gliomas**
34
Which age group is Chondrosarcoma most often seen in and it commonly arises in which bones?
- **Usually 40 y/o +** with **Men 2x \> female**
- **Axial skeleton**: pelvis, shoulder, and ribs
35
A majority of chondrosarcomas arise de novo, but some arise from which 2 pre-existing tumors?
**Osteochondroma** or **enchondromas**
36
Chondrosarcomas arising in associated with syndromes such as multiple osteochondroma syndrome or those that are chondromatosis-related have which mutations?
- **Multiple osteochondroma syndrome**: mutations in ***EXT*** genes
- **Chondromatosis-related**: ***IDH1*** and ***IDH2***
37
Sporadic chondrosarcomas may have what mutations?
- ***IDH1*** and ***IDH2*** mutations
38
Which variant of chondrosarcoma is characterized as being composed of islands of well-differentiated hyaline cartilage surrounded by sheets of small round cells, which can mimic Ewing Sarcoma?
**Mesenchymal** chondrosarcoma
39
Which variant of chondrosarcoma has nodules of glistening gray-white, translucent cartilage; matrix is often gelatinous or myxoid and can ooze from cut surface; spotty calcifications and central necrosis may create cystic spaces?
conventional
40
Which variant of chondrosarcoma is considered low-grade with a high-grade component; no cartilage?
dedifferentiated
41
What is characteristically seen on radiographic imaging of chondrosarcoma?
Calcified matrix appears as foci of **flocculent densities**
42
What is the gross morphology of chondrosarcomas?
**Large bulky tumors** made up of **_nodules_** of **glistening gray-white**, _translucent_ cartilage but matrix is often gelatinous or myxoid
43
How are chondrosarcomas graded and what is unique about this grading?
- Assigned a **grade** from **1 to 3**
- **_Direct_** correlation between **grade** and **behavior**
44
What is the behavior of chondrosarcomas and how may they metastasize and to where?
- Invade **locally**, _painful_ enlarging mass.
- 70% of **grade 3** spread _hematogenously_, especially to **lungs**
45
What is the 5-year survival for grade 1 vs. grade 3 chondrosarcomas and how are they tx?
- **Grade 1** have **5-year** of **80-90%**; drops to **43%** for **grade 3**
- **Tx** is by **wide surgical excision**
46
Ewing Sarcoma is a malignant bone tumor characterized by what? Aka what is the histology of ewing sarcoma
Primitive **round cells** _without_ obvious differentiation
47
Ewing sarcoma is most often seen in which age group and has a predilection for which ethnicity?
- **80%** arise in pt's **\<20 y/o** with slightly more **males** affected
- **Striking** predilection for **_whites_**, while **blacks/asians** _rarely_ affected
48
Where in bones does Ewing Sarcoma arise and which bones are most often affected?
- Arise in the **_diaphysis_** of **long tubular bones**; in the **medullary cavity**
- Especially the **femur** and **flat bones** of the **pelvis**
49
How does Ewing Sarcoma typically present?
- **Painful** enlargin mass; frequently **tender, warm**, and **swollen**
- Some have **systemic findings** that _mimic_ **infection** --\> including fever, ↑ ESR, anemia, and leukocytosis!
50
Plain radiographs of Ewing Sarcoma will show what; what is characteristic of the periosteal rxn of these tumors?
- **Destructive lytic tumor** w/ permeative margins that **extends** into surrounding soft tissues
- Produces layers of reactive bone deposited in an **_onion-skin_** like fashion
51
Which translocation and fusion gene product is characteristic of Ewing Sarcoma?
**t(11;22)** --\> ***EWS-FL11*** gene
52
What does the presence of Homer-Wright rosettes in Ewing Sarcomas indicate?
A **greater degree** of **neuroectodermal differentiation**
53
What is the treatment and 5-year survival with Ewing Sarcomas?
- Tx w/ **neoadjuvant chemotherapy** followed by **surgical excision** with or without **radiation**
- **5-year survival** of **75%** and **long-term** cure in **50%**
54
What is an important prognostic finding associated with tx of Ewing Sarcoma?
Amount of **_chemotherapy-induced necrosis_**
55
Which bone tumor composed of multinucleated osteoclast-type giant cells is benign, but locally aggressive?
**Giant Cell Tumor**
56
The neoplastic cells of Giant Cell Tumors express high levels of what?
**RANKL** --\> promoting proliferation and differentiation of osteo**clasts**
57
Where do Giant Cell Tumors most often arise?
- **Epiphyses**, may _extend_ into **metaphysis**
- **Majority** around **knee** (**distal femur** and **prox. tibia**)
58
Why are giant cell tumors so highly destructive?
↑ **RANKL** from neoplastic cells with _**loss** of **feedback**_ btw osteo**blasts** and osteo**clasts** that normally **regulates** process of **bone remodeling**
59
What is the treatment, recurrence rate and prognosis for Giant Cell Tumors?
- Tx with **curettage** ---\> **40-60%** will **recur locally**
- **4%** will **metastasize** to lung, may **regress** and **seldom fatal**
60
Aneurysmal bone cyst (ABC) frequenlty arises in which bones?
- **Metaphysis** of **long bones**
- **Posterior** elements of **vertebral bodies**
61
Signs and sx's of Aneurysmal bone cyst (ABC)?
- **Most common** = pain + swelling
- If involves vertebrae, can **compress nerves** --\> **neurologic sx's**
62
How do aneurysmal bone cyst (ABC) appear radiographically?
- **Eccentric**, _expansile lesion_ w/ **well-defined** margins
- Most being **completely lytic**, often w/ **thin shell** of **reactive bone** at the **periphery**
63
CT and MRI of aneurysmal bone cyst (ABC) may demonstrate what?
**Internal septa** and _characteristic_ air**-fluid levels**
64
The spindle cells of aneurysmal bone cyst (ABC) frequently demonstrate which mutations?
**Chr 17p13 _rearrangement_** ---\> **USP6 overexpression**
65
Unusually dense calcified matrix called "blue bone" is seen in some cases of what bone tumor?
Aneurysmal bone cyst (ABC)
66
Morphology of aneurysmal bone cyst (ABC)?
- **Multiple** _blood_-filled **cystic** spaces separatd by **thin, tan-white septa**
- **Septa** are composed of **plump, uniform fibroblasts**, multinucleated osteo**lcast**-like **giant cells**, and _reactive_ **woven bone**
67
What are fibrous cortical defects (aka metaphyseal fibrous defects); where and in whom do they arise; defining characteristics?
- **_Extemely common_** arising in **30-50%** of _children_ **\>2 y/o**
- Arise **eccentrically** in **metaphysis** of **distal femur** and **prox. tibia**
- Almost **1/2** are **_bilateral**_ or _**multiple_**
68
How does fibrous cortical defect differ from nonossifying fibroma?
- **Fibrous cortical defects**: typically **small**, about **0.5cm** in diameter
- **Nonossifying fibroma**: larger, up to **5-6cm** in size; usually not detected until **adolescence** or **adulthood**
69
What is the characteristic morphology of the fibroblasts and macrophages seen in both fibrous cortical defect and nonossifying fibroma; what other finding is commonly present?
- Cytologically _bland_ fibroblasts arranged in **storiform (pin-wheel) pattern\*\*\***
- Macrophages may take form of **clustered cells** w/ **foamy cytoplasm** or **multinucleated giant cells**
- **Hemosiderin** is **_commonly_** present
70
What are the characteristic findings on radiograph of fibrous cortical defects and nonossifying fibromas?
**Eccentric lobulated** radiolucency surrounded by **thin rim** of **sclerosis**
71
What is the typical behavior and prognosis of fibrous cortical defects?
- Most have **_limited_** growth potential and undergo **spontaneous** **resolution** within several years
- Few progressively enlarge --\> **nonossifying fibroma** may present w/ **pathologic fracture** or require biopsy and curettage to exclude other tumor types
72
What is fibrous dysplasia and what has it been likened to?
- **Benign** tumor likened to **localized developmental arrest**
- **_ALL_** components of **normal bone present**, but they **_do not_** differentiate into **mature structures**
73
Which 2 syndromes are associated with fibrous dysplasia and what is seen in each?
- **Mazabraund syndrome**: fibrous dysplasia (usually **polyostotic**) + **soft tissue myxomas**
- **McCune-Albright disease**: _unilateral_ bone lesions w/ **café-au-lait skin pigmentations** + **endocrine** abnormalities; esp. **_precocious puberty_**
74
Fibrous dysplasia is due to mutations in what; what other pathology is this gene mutated in?
- **Somatic gain-of-function** mutation during development in ***GNAS1***
- Leads to constitutively active **GS-protein**
- This gene is also mutated in **_pituitary adenomas_**
75
Characteristic morphology of fibrous dysplasia includes what?
**Curvilinear shapes** of the **trabeculae** of **woven bone** _mimic_ **Chinese characters** and bone _lacks_ prominent osteoblastic **rimming**
76
Monostotic fibrous dysplasia most often occur when and affects which bone; presenting sx's?
- **Early adolescence** and **_equally_** in **boys** and **girls**; typically **asymptomatic**
- The **femur, tibia, ribs, jawbones**, **calvarium**, and **humerus** = **most commonly** affected
77
fibrous dysplasia is seen on radiographic imaging as what?
**Ground glass** appearance and **well-defined** margins
78
Polyostotic fibrous dysplasia appears when, affects which bones, and produces what problems?
- Slightly **earlier** than the _monostotic_ form
- **Femur \> skull \> tibia \> humerus \> ribs \> fibula \> radius \> ulna \> mandible \> vertebrae**
- Propensity to involve **shoudler** and **pelvic girdles** --\> _severe_, progressive disease w/ _crippling deformities_ and _fractures_
79
What is a rare complication of polyostotic fibrous dysplasia?
**Malignant** transformation ---\> **sarcoma**
80
Which cancers in adult most frequently metastasize to the bone?
**Prostate** + **breast** + **kidney** + **lung**
81
Which cancers in children most frequently metastasize to the bone?
**Neuroblastoma** + **Wilms tumor** + **Osteosarcoma** + **Ewing sarcoma** + **Rhabdomyosarcoma**
82
Skeletal metastases are typically multifocal, but carcinomas from which 2 sites may present with solitary lesions?
**Kidney** and **thyroid** carcinomas
83
Metastases from which site produces a blastic (bone forming) pattern?
**Prostatic adenocarcinoma**
