Bone and Cartilage Tumors Flashcards
What are the 4 pieces of information needed to diagnose a mass in a bone?
[1] the age of the patient
[2] the sex of the patient
[3] the location of the lesion
[4] the radiographic appearance of the lesion
Malignant tumors occurring in the diaphysis are?
Ewing’s sarcoma and chondrosarcoma
Benign tumors occurring in the diaphysis are?
enchondroma
fibrous dysplasia
Metaphyseal lesions that are malignant are?
osteosarcoma and juxtacortical osteosarcomas
Metaphyseal lesions that are benign are?
osteoblastoma, osteochondroma non-ossifying fibroma osteoid osteoma chondromyxoid fibroma giant cell tumors
What is more common, primary malignant or benign lesions?
Primary benign lesions are more common (malignant primary bone neoplasms account for fever than 1% of all malignant tumors)
How big are osteoid osteomas? How big are osteoblastomas?
OO: < 2cm
OB: >2cm
Where do osteoid osteomas most likely form? Where do osteoblastomas usually form?
OO: femur or tibia
OB: posterior spine (laminae and pedicles)
What are the symptoms of osteoid osteoma v. osteoblastoma?
OO: nocturnal pain that is relieved with aspirin
OB: less frequently assoicated with pain (but pain is not relieved with aspirin)
Which produces a marked bony reaction: osteoid osteoma or osteoblastoma?
osteoid osteoma (forms a tremendous amount of reactive bone that encircles the lesion)
How do you differ a benign primary osteogenic bone tumor from osteosarcoma?
small size, well-defined margins, and benign cytologic features of the neoplastic osteoblasts
How do you treat osteoid osteoma v. osteoblastoma?
Osteoid osteoma is frequently treated by radiofrequency ablation, whereas osteoblastoma is usually curetted or excised en bloc.
True or false: the neoplastic cells in giant cell tumors do not actually cause the destruction.
TRUE! The bulk of the tumor consists of non-neoplastic osteoclasts and their precursors (stimulated by RANKL expressed by neoplastic cells) that have abnormal communication with osteoblasts–so localized but highly destructive resorption of bone matrix occurs
Where do giant cell tumors occur?
arise in the epiphysis but may extend into the metaphysis: usually near joints (knee and wrist)
What is the name of the RANKL inhibitor that has shown promise in the adjuvant treatment of giant cell tumors?
denosumab
True or false: Benign cartilage tumors are much more common than malignant ones.
TRUE
What is a benign cartilage-capped tumor that is attached to the underlying skeleton by a bony stalk?
osteochondroma
What is multiple hereditary exostosis syndrome?
autosomal dominant hereditary disease with germline loss-of-function mutations in either the EXT1 gene or EXT2 gene (enzymes that synthesize heparan sulfate glycosaminoglycans)
Why is loss of heparin sulfate glycosaminoglycans pathologic in osteochondroma?
reduced or abnormal glycosaminoglycans may prevent normal diffusion of the factor Indian hedgehog (Ihh), a local regulator of cartilage growth, thereby disrupting chondrocyte differentiation and local skeletal development
Where are osteochondromas most likely found?
bones of endochondral origin and arise from the metaphysis near the growth plate of long tubular bones, especially near the knee
What is the name of a a nonhereditary syndrome of multiple enchondromas or enchondromatosis?
Ollier disease
What are benign tumors of hyaline cartilage?
chondromas
Where do enchondromas arise?
medullary bone, typically in tubular bones of the hand or feet
Where do Juxtacortical chondromas arise?
surface of bones
What is a nonhereditary syndrome combining multiple enchondromas with multiple soft tissue hemangiomas?
Maffucci syndrome
What is the underlying cause of most enchondromas?
Heterozygous mutations in the IDH1 and IDH2 genes
What is the result of heterozygous mutations in the IDH1 and IDH2 genes?
acquisition of new enzymatic activity in two isoforms of the enzyme isocitrate dehydrogenase to be able to synthesize 2-hydroxyglutarate. (interferes with regulation of DNA methylation)
How do enchondromas cause transformation by association?
2-hydroxyglutarate can diffuse into neighboring cells with normal IDH genes, causing oncogenic epigenetic changes in genetically normal neighbors
Do most enchondromas undergo sarcomatous transformation?
NOT sporadic ones–mainly just those associated with syndromes
What additional complications do individuals with Maffucci syndrome have?
also at risk of developing other types of malignancies, including ovarian carcinomas and brain gliomas
What is the name of the malignant tumor in which the cancerous cells produce osteoid matrix or mineralized bone?
osteosarcoma
Where is the most common site of osteosarcomas?
tumors usually arise in the metaphyseal region of the long bones of the extremities, and almost 50% occur around the knee in distal femur or proximal tibia.
What is the triangular shadow located between the bone cortex and raised ends of the periosteum (due to osteosarcoma breaking through the cortex and lifting the periosteum, called?
Codman triangle
What are the well-known mutations of osteosarcomas?
RB, TP53, INK4a, and MDM2/CDK4
When do osteosarcomas peak in incidence?
around the time of the adolescent growth spurt and occur most frequently in the region of the growth plate in bones with the fastest growth
What is the most common subtype of osteosarcoma?
arises in the metaphysis of long bones and is primary, intramedullary, osteoblastic, and high grade
What is the DIAGNOSTIC microscopic finding of osteosarcoma?
formation of bone by the tumor cells
What is the most common site of metastasis in osteosarcomas?
lungs
What are malignant tumors that produce cartilage?
chondrosarcomas
What are the 4 classification of chrondrosarcomas?
1) conventional (hyaline cartilage producing)
2) clear cell
3) dedifferentiated
4) mesenchymal variants
What are the subdivisions of convential chondrosarcomas?
central (intramedullary) and peripheral (juxtacortical)
What is the most common type of chondrosarcoma?
Conventional central tumors
Where do chondrosarcomas commonly arise?
axial skeleton, especially the pelvis, shoulder, and ribs.
What is a common genetic finding seen in sporadic chondrocarcinomas?
Silencing of the CDKN2A tumor suppressor gene by DNA methylation
May also have IDH1 and IDH2 mutations.
What is the genetic finding seen in multiple osteochondroma syndrome?
exhibit mutations in the EXT genes
may have IDH1 and IDH2 mutations.
What is the matrix like in conventional chondrosarcomas?
matrix is often gelatinous or myxoid and can ooze from the cut surface.
Can conventional chondrosarcomas spread?
YES: spreads through the cortex into surrounding muscle or fat
What is dedifferentiated chondrosarcoma?
low-grade chondrosarcoma with a second, high-grade component that does not produce cartilage
What are characteristics of clear cell chondrosarcoma?
contains sheets of large, malignant chondrocytes that have abundant clear cytoplasm, numerous osteoclast-type giant cells, and intralesional reactive bone formation
What is clear cell chondrosarcoma often confused with?
osteosarcoma
What are the characteristics of mesenchymal chondrosarcoma?
composed of islands of well-differentiated hyaline cartilage surrounded by sheets of small round cells
What is mesenchymal chondrosarcoma commonly confused with?
Ewing Sarcoma
What determines the prognosis of chondrosarcomas?
tumor grade
How do you treat chondrosarcoma?
wide surgical excision and chemotherapy (in mesenchymal and dedifferentiated tumors)
What are Ewing sarcoma family tumors (ESFT)?
Ewing sarcoma and primitive neuro-ectodermal tumor (PNET)
What is Ewing sarcoma?
malignant bone tumor composed of primitive small round blue cells without obvious differentiation.
Where are ESFTs most commonly found?
medulla of the diaphysis of long tubular bones, especially the femur, or in the flat bones of the pelvis
The characteristic periosteal reaction produces layers of reactive bone deposited in what fashion?
onion skin
What mutation is found in most ESFTs?
(11;22) (q24;q12) translocation generating in-frame fusion of the EWS gene on chromosome 22 to the FLI1 gene
What does the presence of Homer-Wright rosettes (round groupings of cells with a central fibrillary core) indicate ?
greater degree of neuroectodermal differentiation
True or flase: Malignant bone tumors are much commonly metastatic than primary.
TRUE
Where are the most popular origins for bone metastasis in adults?
prostate, breast, lung and kidney
Where are the most popular origins for bone metastasis in children?
neuroblastoma, Wilms’ tumor, osteosarcoma, Ewing sarcoma (extraosseous) and rhabdomyosarcoma
List the pathways of spread of metastases into bone?
(1) direct extension
(2) lymphatic drainage
(3) hematogenous dissemination
(4) intraspinal seeding (via the Batson plexus of veins).
True or false: skeletal mets are usually single.
FALSE: typically multifocal unless carcinomas of the kidney and thyroid (may present with solitary lesions)
Most skeletal metastasis involve what bones?
axial skeleton (vertebral column, pelvis, ribs, skull, and sternum)
Why is the axial skeleton a popular site of metastasis?
red marrow in these areas, with its rich capillary network and slow blood flow, facilitates implantation and growth of the tumor cells
What types of cancers metastasize to small bones of hands and feet (very rare occurrence)?
lung, kidney, colon
What is the pathogenesis behind bone mets?
Cross-talk between metastatic cancer cells (prostaglandins, cytokines and PTHrP, which upregulate RANKL on osteoblasts and stromal cells thereby stimulating osteoclast activity) and native bone cells leads to changes in the bone matrix.
Sclerotic metastases may be produced by tumor cells secreting what proteins?
WNT proteins that stimulate osteoblastic bone formation
What type of metastasis is typically “blastic”–forms bone?
prostate adenocarcinoma
Carcinomas of the kidney, lung, and gastrointestinal tract and malignant melanoma produce what types of lesions?
Lytic (bone destroying)
