19 - Bone Tumors Flashcards
What is the most common type of primary tumor involving bone?
Hematopoietic (40%) tumors such as lymphomas and multiple myeloma.
What are some nonspecific clinical presentations of bone tumors?
Usually nonspecific:
- Pain
- Mass
- Pathologic fracture
- Asymptomatic: usually found incidentally
What aggressive bone tumors are associated with each age: children/adolescents, young adults, and elderly?
Children,adolescents: osteosarcoma, eqing’s sarcoma
Young adults: giant cell tumor
Elderly: chondrosarcoma
What are some radiological patterns that indicate benign slow-growing neoplasms vs. malignant, rapidly-growing neoplasms?
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.
What radiologic patterns are seen in malignant bone matrix-forming tumors and chondroid matrix-forming tumors?
Bone matrix-forming: solid ivory-like pattern
Chondroid matrix-forming: rings and arcs
What are the two type of benign bone-forming tumors? How do they differ in their location, size, and pain?
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.
How do osteoid osteomas and osteoblastomas differ on radiograph? What type is pictured?
Osteoid osteomas: radiolucent lesion within sclerotic cortex
Osteoblastomas: expansile radio-lucency with mottling (no sclerotic rim)
Small well-circumscribed lesion pictured - ostoid osteoma.
What does an osteoid osteoma look like on histology?
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
What does an osteoblastoma look like on histology?
Look like osteoid/osteoma
Area of immature bone being formed by osteoblasts
How common are bone-forming (osteogenic) tumors?
Relatively rare group of tumors.
Malignant bone tumors comprise ~0.2% of all types of cancer.
Potentially curable.
What is a an osteosarcoma? How common are they and why gets them?
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.
Where in the body do osteosarcomas normally occur?
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.
What is the pathogenesis of osteosarcomas? Give examples of five things that can can cause them.
- Inherited mutant alle of RB gene
- Mutation of p53 suppressor gene
- Li-fraumeni: bone tissue sarcoma causing easing onset breast cancer, brain tumor, and leukemia.
- Overexpression of MDM2 (5-10%); INK4 and p16
- Sites of bone growth/disease (Paget dz)
- Prior irradiation
What are characteristics of osteosarcoma on radiograph?
- 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
Describe the pathology of osteosarcoma? How is it treated?
Infiltrative tumor that extends into soft tissue.
Malignant cells producing osteoid.
Treatment: neoadjuvant chemotherapy and surgical resection.
What is the prognosis of osteosarcoma in metastatic and non-met disease?
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.
What is the most common benign tumor of bone? Where does it occur? Does it metastasize?
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)
Where do osteochondromas occur? What do they look like?
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
What do osteochondromas look like on histology?
Looks like normal cartilage maturation, similar to the epiphysis of growing bones.
Forms into bone with medullary spaces in the middle
What is the name for a benign hyaline cartilage lesion?
Enchondroma: intramedullary chondroma (in the medullary space of bone)
Periosteal chondroma = juxtacortical chondroma (located on the cortical surface under the periosteum).
What findings are seen on radiograph and histology for an enchondroma? Where are they found?
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.
What is the treatment of an enchondroma?
None, unless lesion shows changes:
- Symptomatic - onset of acut pain is evidence that lesion is malig.
- Evidence of recent growth after skeletal maturity
What do you see when you look at the cells in an enchondroma?
Lacuna with chondrocytes without mitotic activity, not very cellular, scattered chondrocytes in cartilage.
Looks very bland and beningn.
What three diseases/genetic defects are associated with multiple chondromatosis?
- Freq. point mutations in IDH1 or IDH2
- Ollier disease
- Maffucci syndrome
What are characteristics of Ollier disease?
Multiple enchondromata that tend to be regionally distributed (ie in one hand)
May or may not have skeletal malformation.
What are characteristics of Maffucci syndrome?
- Multiple endochrondromata + angiomata (angiomas)
- Severe skeletal malformation
- Higher incicence of malignant transformation
What type of malignant tymor has neoplastic cells that produce a purely cartilagenous matrix? How common are these, who gets them, and where?
Chondrosarcoma: second most common bone sarcoma (~26%)
Mainly older adults, mostly above 40-50yos.
Central skeleton: pelvis and ribs (45%), humerus, femur (metaphysis, diaphysis).
How do chondrosarcomas look on imaging?
- Medullary location
- Frequently contain calcifications which tend to be lost in grade 3 tumors
- Cortical erosion or destriction
- Occasional soft tissue extension
What do chondrosarcomas look like on pathology? How due these differ from enchondromas histologically?
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.
What correlates with the behavior of chondrosarcomas? How is this done?
Size (greater or less than 10cm) and grade correlate with behavior.
Grading (1-3) is based on degree of cellularity and atypia.
Describe the appearance of a grade 1 chondrosarcoma?
More cellular, but more matrix than cells still
Cells look fairly normal, not much atypia
Describe the appearance of a grade 2 chondrosarcoma?
More atypia - some focal areas that are dense with cellularity
Areas of clear cut cartilage expression.
Describe the appearane of a grade 3 chaondrosarcoma?
More severe atypia with mitotic figures
Dense cellularity and tend to be more aggressive
Fairly rare
What is the 5yr survival for chondrosarcoma grades 1,2? What about grade 3?
Grades 1,2: 80-90%
Grade 3: 29%, with pulmonary mets.
What are variants of chondrosarcoma?
- De-differentiated
- Myxoid
- Clear cell
- Mesenchymal
- Juxtacortical
What is the appearance of de-differentiated chondrosarcomas?
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).
What is the most common space-occupying lesion of bone that occurs in 1 out of every 4 individuals? Where do they occur?
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.
Describe the lesion caused by non-ossifying fibromas?
These are slow growing benign lesions
- eccentric, lytic, peripheral sclerosis (sclerotic rim)
What histological pattern is seen with non-ossifying fibromas?
Storiform pattern: looks like van goughs starry night.
Whirling pattern of fibroblasts.
No bone is being formed in this.
What is fibrous dysplasia? What are the two types and what age/location are each found in?
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.
What is McCune-Albright syndrome? Who does it occur in and what are symtpoms?
Polyostotic fibrous dysplasia with endocrinopathies and café-au-lait spots. More common in females than males.
- Sexual precocity (early puberty), acromegaly, and cushings syndrome
What genetic mutation is associated with McCune-Albright syndrome?
Activating germline mutations of GNAS (GTP-binging protein) result in excess cAMP leading to endocrine gland hyperfuction.
What do you see on radiology in fibrous dyspalsia?
- Expansile
- Circumscribed
- Thinned cortex
- Ground glass appearance
- May be multiple
What does fibrous dysplasia look like on pathology? What is the treatment?
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.
What is the second most common malignant bone tumor in childhood? Who does it occur in? How does it present clinically?
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.
What does a ewing sarcoma/PNET look like on xray?
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).
What does an eqing sarcoma look like grossely? What is used to determine if the whole tumor was sucessfully resected?
Variable appearance - looks more like generic tumor with areas of hemmorrage.
Yellow is necrosis.
Ink used to determine resecetion margins.
What does ewing sarcoma/PNET look like on pathology?
- 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
What is the pathogenesis of ewings sarcoma?
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
How is ewing sarcome treated? What is the five year survival associated with stage 1?
Chemotherapy and surgery; Radiation therapy might be added
Stage 1: 5 year survival is 70% with chemo/RT
Who gets giant cell tumors of bone and where do they occur?
Young adults (20-40), older adolescents (skeletally mature);
Females > males.
Epiphyseal location: knee, proximal humerus, and radius
Describe the behavior of giant cell tumors of the bone?
Most are benign, locally aggressive.
May destroy the cortex of bone and extend into soft tissue.
What do giant cell tumors look like on histology?
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.
How common are malignant bone tumors?
Most common malignant bone tumor, esp. in adults (20x more frequent than primary bone tumors)
Mostly multiple.
Solitary lesions of metastatic bone tumors may mimic what? What are characteristics of these lesions?
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
80% of metastatic bone tumors come from what sources?
BLT-KP
Breast, lung, thyroid, prostate, and kidney.
_______ is the most common sarcoma occuring in the bone, and it occurs prdominantly in _______.
Osteosarcoma is the most common sarcoma occuring in the bone and it occurs predominantly in children/adolescents.
________ is a painful bone lesion that is relieved by aspirin.
Osteoid osteoma is a painful bone lesion that is relieved by aspirin.
What three syndromes are all associated with bone lesions?
- Li-fraumeni syndrome
- Ollier disease
- Maffucci syndrome
A 25 yo presents with multiple enchondromas confirmed with biopsy, which in addition reveal frequent spindle cell hemangiomas. What is your diagnosis?
Maffucci syndrome.
Associated with multiple enchondromas, angiomas, and severe skeletal malformations.
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?
McCune-Albright Syndrome.
